Role of Vitamin E in Pregnancy

*Mohd Aftab Siddiqui, Usama Ahmad, Asad Ali, Farogh Ahsan and Md. Faheem Haider*

#### **Abstract**

Vitamins play important roles in female health. They are essential for many functions, including menstruation and ovulation, oocyte (egg) quality and maturation. Vitamin E was first discovered in 1922 as a substance necessary for reproduction. It has become widely known as a powerful lipid-soluble antioxidant. There are various reports on the benefits of vitamin E on health in general. Vitamin E helps your body create and maintain red blood cells, healthy skin, eyes and strengthens your natural immune system. However, despite it being initially discovered as a vitamin necessary for reproduction, to date studies relating to its effects in this area are lacking. Vitamin E supplementation may help reduce the risk of pregnancy complications involving oxidative stress, such as pre-eclampsia. This chapter is written to provide a review of the known roles of vitamin E in pregnancy.

**Keywords:** Vitamin E, Pregnancy, Oxidative stress, Tocopherol

#### **1. Introduction**

Vitamin E is an important micronutrient in the human body. Vitamin E maintains various body functions. It plays a very important role in maternal health and child development [1]. Vitamin E is an essential fat-soluble micronutrient for higher mammals and functions as an antioxidant for lipids [2]. American scientists Herbert McLean Evans and Katherine Scott Bishop discovered vitamin E in 1922. Vitamin E is an essential lipid-soluble vitamin. It was initially denoted as an "antisterility factor X" that was necessary for reproduction. The vital role of vitamin E in reproduction was first investigated 80 years ago [3]. It was named according to a consecutive alphabetical order preceded by the discovery of vitamins A to D. Later vitamin E was called alpha-tocopherol, according to the Greek term "tokos" childbirth, "phero" to bear, and -ol indicating alcohol. Vitamin E is also called the "protecting vitamin" [4]. The amount of vitamin E is determined by age. For adults, the safest dose of vitamin E supplements is 1,500 IU/day for natural forms and 1,000 IU/day for man-made (synthetic) forms. **Table 1** shows the average daily prescribed doses as determined by the Food and Nutrition Board of the Institute of Medicine [5–7].

Some vitamin E containing foods include wheat, rice bran, barley, oat, coconut, palm, and annatto [8–9]. Other sources include rye, amaranth, walnut, hazelnut, poppy, sunflower, maize and the seeds of grape and pumpkins [10]. The richest sources are nuts, spinach, whole grains, olive oil, and sunflower oil [11]. Vitamin E now refers to eight different isoforms that belong to two categories, four saturated analogues (α, β, γ, and δ) called tocopherols and four unsaturated analogues


**Table 1.**

*Recommended Dietary Allowances (RDAs) for Vitamin E.*

(α, β, γ, and δ) referred to as tocotrienols [12]. α-, β-, γ- and δ-homologues contain three, two, two and one methyl groups, respectively. These structural differences and isomerism determine the biological activity [13]. Tocotrienols differ in the presence of 3 double bonds in their side chain from tocopherols. The position of the methyl groups on the chromanol ring varies between the tocopherol and tocotrienol isomers. Tocopherols can form 8 stereoisomers due to the presence of 3 asymmetrical carbons in their side chains (RRR, RRS, RSR, RSS, SRR, SRS, SSR, SSS) [14]. Among these isomers, α-tocopherol (**Figure 1**) has the highest biologically active form [15]. α-tocopherol is the most abundant in plasma, cell membranes, other human tissues, and nutritional supplements, whereas γ-tocopherol is the primary form found in the human diet [16]. Tocopherols and tocotrienols, collectively known as tocols, are phenolic compounds. Although phenolic and polyphenolic compounds such as phenolic acids, flavonoids, anthocyanins, proanthocyanidins, and ellagitannins have received much attention due to their antioxidant activities and potential health benefits [17, 18].

Natural and synthetic forms of the tocopherols and tocotrienols are equally absorbed from the intestinal lumen in the form of mixed micelles. After the passage of the micelles into the intestinal mucosa, chylomicrons are synthesized to transport vitamin E from the intestinal mucosa through the lymphatic system to the circulatory system [19]. In plasma, alpha-tocopherol is found in all lipoprotein fractions but mostly is associated with apo B-containing lipoproteins. Via the action of lipoprotein lipase (LPL), extrahepatic tissues pick up parts of the tocopherols transported in chylomicrons, and the remaining chylomicrons transport the remaining tocopherols to the liver. Here, a large proportion of alpha-tocopherol is incorporated into nascent very-low-density lipoproteins by the operation of the "alpha-tocopherol transfer protein" (VLDL), whereas the excess of alpha-tocopherol plus the other forms of vitamin E is excreted in bile. When VLDL is secreted into circulation, the action of LPL transforms VLDL into IDL and LDL, and the excess surface components, including alpha-tocopherol, are transferred to HDL. In addition to the LPL action, alpha-tocopherol is transmitted to tissues via the absorption of lipoproteins by different tissues through their corresponding receptors [20–24].

Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation and forms the water-soluble end-product carboxyethyl hydroxy chroman. α-Tocopherol can be oxidized to the tocopheroxyl radical. Further oxidation of the tocopheroxyl radical forms tocopheryl quinone. Other Metabolites of vitamin E include

**97**

**2.1 Infertility**

*Role of Vitamin E in Pregnancy*

**Figure 1.**

intestinal absorption [25, 26].

*Chemical Structure of alpha-Tocopherol.*

**2. Role of vitamin E in pregnancy**

*DOI: http://dx.doi.org/10.5772/intechopen.97268*

2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman (α-CEHC) derived from α-tocopherol and 2,7,8-trimethyl-2- (2′-carboxyethyl)-6-hydroxychroman (γ-CEHC) derived from γ-tocopherol. There are two primary pathways for the excretion of vitamin E. Bile, which is then excreted in the urine, is the primary path of excretion. The second path is in the urine to make it more water-soluble after vitamin E is chain-shortened in a process similar to beta-oxidation. The major route of excretion of ingested vitamin E is fecal elimination because of its relatively low

Because of its antioxidant function, it has several significant functions within the body. Numerous potential complications and disorders, including cancer, diabetes, arthritis and cataracts, have been related to oxidation; vitamin E is beneficial against these conditions. Vitamin E may also prevent platelet hyper aggregation, which can lead to atherosclerosis; it also helps to reduce the development of prosta-

Vitamin E supplementation may help reduce the risk of pregnancy complications involving oxidative stress. There is a need to evaluate the efficacy and safety of vitamin E supplementation in pregnancy [28]. A lack of vitamin E can lead to female infertility, miscarriage, premature delivery, eclampsia, fetal intrauterine growth restriction and other diseases associated with pregnancy [29–31]. Here some

Due to excessive production of ROS and/or insufficient consumption of antioxidants, oxidative stress arises. When the generation of reactive oxygen species (ROS) and other radical species exceeds then scavenging ability of antioxidants fail, injury to cells can occur. The mitochondrial respiratory chain produces the majority of ROS, although they may also be generated through exogenous exposures such as alcohol, cigarette smoke, and environmental pollutants. Antioxidants (such as vitamins C and E) and antioxidant cofactors (such as selenium, zinc, and copper) can dispose of, scavenge, or suppress the formation of reactive oxygen species (ROS). Reduced sperm motility, sperm number, and sperm–oocyte fusion have all been linked to oxidative stress in male infertility. In women, several animal and in-vitro studies suggest that oxidative stress may affect female fertility. Adequate intake of

According to Cooper et al., vitamin E deficiency impaired both male and female rats' germ cells. Vitamin E deficiency has a significant impact on secondary spermatocytes and spermatids [33]. According to several studies, vitamin E deficiency has been linked to reduced fertility in both humans and lab animals. Rengaraj et al.

glandins, such as thromboxane, that cause platelet clumping [27].

conditions in which vitamin E role are being described:

vitamin E protects from free radical generation [32].

*Role of Vitamin E in Pregnancy DOI: http://dx.doi.org/10.5772/intechopen.97268*

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

(α, β, γ, and δ) referred to as tocotrienols [12]. α-, β-, γ- and δ-homologues contain three, two, two and one methyl groups, respectively. These structural differences and isomerism determine the biological activity [13]. Tocotrienols differ in the presence of 3 double bonds in their side chain from tocopherols. The position of the methyl groups on the chromanol ring varies between the tocopherol and tocotrienol isomers. Tocopherols can form 8 stereoisomers due to the presence of 3 asymmetrical carbons in their side chains (RRR, RRS, RSR, RSS, SRR, SRS, SSR, SSS) [14]. Among these isomers, α-tocopherol (**Figure 1**) has the highest biologically active form [15]. α-tocopherol is the most abundant in plasma, cell membranes, other human tissues, and nutritional supplements, whereas γ-tocopherol is the primary form found in the human diet [16]. Tocopherols and tocotrienols, collectively known as tocols, are phenolic compounds. Although phenolic and polyphenolic compounds such as phenolic acids, flavonoids, anthocyanins, proanthocyanidins, and ellagitannins have received much attention due to their antioxidant activities

**Life stage Recommended Amount** Birth to 6 months 4 mg/day Infants 7 to 12 months 5 mg/day Children 1 to 3 years 6 mg/day Children 4 to 8 years 7 mg/day Children 9 to 13 years 11 mg/day Teens 14–18 years 15 mg/day Adults 15 mg/day Pregnant women 15 mg/day Breastfeeding women 19 mg/day

Natural and synthetic forms of the tocopherols and tocotrienols are equally absorbed from the intestinal lumen in the form of mixed micelles. After the passage of the micelles into the intestinal mucosa, chylomicrons are synthesized to transport vitamin E from the intestinal mucosa through the lymphatic system to the circulatory system [19]. In plasma, alpha-tocopherol is found in all lipoprotein fractions but mostly is associated with apo B-containing lipoproteins. Via the action of lipoprotein lipase (LPL), extrahepatic tissues pick up parts of the tocopherols transported in chylomicrons, and the remaining chylomicrons transport the remaining tocopherols to the liver. Here, a large proportion of alpha-tocopherol is incorporated into nascent very-low-density lipoproteins by the operation of the "alpha-tocopherol transfer protein" (VLDL), whereas the excess of alpha-tocopherol plus the other forms of vitamin E is excreted in bile. When VLDL is secreted into circulation, the action of LPL transforms VLDL into IDL and LDL, and the excess surface components, including alpha-tocopherol, are transferred to HDL. In addition to the LPL action, alpha-tocopherol is transmitted to tissues via the absorption of lipopro-

teins by different tissues through their corresponding receptors [20–24].

ω-hydroxylation followed by five cycles of subsequent β-oxidation and forms the water-soluble end-product carboxyethyl hydroxy chroman. α-Tocopherol can be oxidized to the tocopheroxyl radical. Further oxidation of the tocopheroxyl radical forms tocopheryl quinone. Other Metabolites of vitamin E include

Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent

**96**

and potential health benefits [17, 18].

*Recommended Dietary Allowances (RDAs) for Vitamin E.*

**Table 1.**

**Figure 1.** *Chemical Structure of alpha-Tocopherol.*

2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman (α-CEHC) derived from α-tocopherol and 2,7,8-trimethyl-2- (2′-carboxyethyl)-6-hydroxychroman (γ-CEHC) derived from γ-tocopherol. There are two primary pathways for the excretion of vitamin E. Bile, which is then excreted in the urine, is the primary path of excretion. The second path is in the urine to make it more water-soluble after vitamin E is chain-shortened in a process similar to beta-oxidation. The major route of excretion of ingested vitamin E is fecal elimination because of its relatively low intestinal absorption [25, 26].

Because of its antioxidant function, it has several significant functions within the body. Numerous potential complications and disorders, including cancer, diabetes, arthritis and cataracts, have been related to oxidation; vitamin E is beneficial against these conditions. Vitamin E may also prevent platelet hyper aggregation, which can lead to atherosclerosis; it also helps to reduce the development of prostaglandins, such as thromboxane, that cause platelet clumping [27].

#### **2. Role of vitamin E in pregnancy**

Vitamin E supplementation may help reduce the risk of pregnancy complications involving oxidative stress. There is a need to evaluate the efficacy and safety of vitamin E supplementation in pregnancy [28]. A lack of vitamin E can lead to female infertility, miscarriage, premature delivery, eclampsia, fetal intrauterine growth restriction and other diseases associated with pregnancy [29–31]. Here some conditions in which vitamin E role are being described:

#### **2.1 Infertility**

Due to excessive production of ROS and/or insufficient consumption of antioxidants, oxidative stress arises. When the generation of reactive oxygen species (ROS) and other radical species exceeds then scavenging ability of antioxidants fail, injury to cells can occur. The mitochondrial respiratory chain produces the majority of ROS, although they may also be generated through exogenous exposures such as alcohol, cigarette smoke, and environmental pollutants. Antioxidants (such as vitamins C and E) and antioxidant cofactors (such as selenium, zinc, and copper) can dispose of, scavenge, or suppress the formation of reactive oxygen species (ROS). Reduced sperm motility, sperm number, and sperm–oocyte fusion have all been linked to oxidative stress in male infertility. In women, several animal and in-vitro studies suggest that oxidative stress may affect female fertility. Adequate intake of vitamin E protects from free radical generation [32].

According to Cooper et al., vitamin E deficiency impaired both male and female rats' germ cells. Vitamin E deficiency has a significant impact on secondary spermatocytes and spermatids [33]. According to several studies, vitamin E deficiency has been linked to reduced fertility in both humans and lab animals. Rengaraj et al.

discovered that a moderate amount of vitamin E in poultry diet preserves semen/ sperm quality in male birds and egg quality in female birds by reducing lipid peroxidation in semen/sperms and eggs [34]. The effects of vitamin E on sperm motility were studied by Suleiman et al. A total of 11 out of 52 treated patients (21%) were pregnant, and 31 subjects experienced increased sperm motility [35]. In a systematic review of the effect of oral antioxidants (vitamins C and E, zinc, Se, carnitine) on male infertility by Ross et al., 17 randomized trials, including a total of 1665 men, were identified. Of the 17 trials, 14(82%) showed an improvement in either sperm quality or pregnancy rate after antioxidant therapy [36]. Cicek et al., studied the impact of vitamin E on the treatment results of women who were going through intrauterine insemination and controlled ovarian stimulation and had an unknown cause of infertility. Two groups A and B had 53 and 50 volunteers respectively. Group A received 400 IU/day of vitamin E and clomiphene citrate. This combination was used for producing controlled ovarian stimulations. Group B (control) also received controlled ovarian stimulation but without vitamin E. Outcome of the study demonstrated that both the groups had a significant difference in the thickness of endometrium on the day which human chorionic gonadotropin (hCG) was administered. Nevertheless, implantation and pregnancy rates had no connection with the administration of vitamin E. Based on the study it can be concluded that vitamin E possesses antioxidant effect and its administration could enhance the response of endometrium in females with unknown cause of infertility [37]. Das et al. performed a study in which female rats (30 days age) were maintained on a vitamin E-deficient diet for 70 days. At 100 days of age, the vitamin E-deficient and control animals were sacrificed. A group of animals was supplemented with a normal diet for the last 25 days following a 45-day deficient diet, or vice versa. The most notable findings were (i) a significant decrease in uterine weight in the deficient group, (ii) a significant decrease in estrogen, LH, and estrogen-induced uterine enzymes alkaline phosphatase and peroxidase, and (iii) ovarian dysfunction as shown by degenerating graffian follicles [38].

#### **2.2 Endometriosis**

Endometriosis is a condition characterized by the presence of endometrial tissue outside the uterine cavity [39]. Endometriosis is a condition that affects mostly women of reproductive age. The peak incidence is between 35 and 45 years old [40]. Endometriosis is found in 25 to 40% of women with infertility and 40–87% of women with chronic pelvic pain have endometriosis [41–43]. Endometriosis is associated with oxidative stress, even though the pathogenesis of the condition is currently unknown. Patient with endometriosis have an altered balance of prooxidant and antioxidant molecules [44–46].

Santanam et al. performed a randomized, placebo-controlled trial of antioxidant vitamins (vitamin E and C) in women with pelvic pain and endometriosis. This study included 59 women between the ages of 19 and 41 who had pelvic pain and had a history of endometriosis or infertility. Before surgery, patients were randomly assigned to one of two groups: vitamin E (1200 IU) and vitamin C (1000 mg) or placebo for eight weeks. Results indicated that after treatment with antioxidants, chronic pain ("everyday pain") improved in 43 percent of patients in the antioxidant treatment group (P = 0.0055) compared with the placebo group. The results of this clinical trial show that administration of antioxidants reduces chronic pelvic pain in women with endometriosis and inflammatory markers [47]. East-Powell et al. performed a randomized, placebo-controlled trial of antioxidant vitamins (vitamin E and C) in women with pelvic pain and endometriosis and/or infertility. A total of 59 women were included in the trial. Patients were randomly assigned to

**99**

*Role of Vitamin E in Pregnancy*

**2.3 Miscarriage**

in pregnant women by around 50% [52].

condensation in recurrent miscarriage male partners [56].

*DOI: http://dx.doi.org/10.5772/intechopen.97268*

2 groups: vitamin E 1200 IU (3 capsules of 400 mg each) and vitamin C 1000 mg (2 tablets of 500 mg each) daily for eight weeks before surgery. The results of this clinical trial show that administration of antioxidants (vitamin E and C) reduces chronic pelvic pain in women with endometriosis and inflammatory markers [48]. Hashemi et al. performed a randomized clinical trial in 40 women with implantation failure aged 18–37 years old. Participants were randomly divided into two groups: group A received 400-IU vitamin E supplements and group B received a placebo for 12 weeks. Vitamin E supplements were shown to dramatically improve serum vitamin E levels and endometrial thickness in women with implantation failure [49]. Kavtaradze et al. performed a clinical trial in 59 patients age 19–41 years with pelvic pain and history of endometriosis and/or infertility. Patients were randomly assigned to 2 groups: vitamin E (1200 IU) and vitamin C (1000 mg) combination or placebo daily for two months before surgery. This clinical trial's preliminary findings indicate that antioxidants (vitamins E and C) improve pelvic pain in women with endometriosis. According to this report, antioxidant vitamins are effective in reducing chronic pelvic pain in women with endometriosis. This research supports the development of a new class of medicines for the treatment of endometriosis-related pelvic pain. This information further supports our overall conclusion that endometriosis is an oxidative stress-related condition [50].

Miscarriage is a serious pregnancy complication that can be brought about by a variety of causes. Vitamin deficiency has been linked to an increased risk of miscarriage, so supplementing women with vitamins before or during pregnancy can help prevent miscarriage [51]. Vitamin E deficiency's effects on human health have yet to be thoroughly reported and investigated. Low plasma vitamin E, on the other hand, has been linked to miscarriage in the first trimester of a woman's pregnancy. Furthermore, vitamin E supplementation in the diet reduced the rate of miscarriage

Pregnant women have quicker metabolism, increased production of free radicals, and increased lipid peroxidation. Thus, low levels of vitamin E can lead to the production of excessive free radicals, leading to placental aging, endothelial vascular damage, which increases the incidence of high-risk infections in pregnancy [53, 54]. It can also damage the lining of the fetal cell membranes, increasing the risk of premature rupture of the embryo [55]. Increased reactive oxygen species and decreased antioxidant levels in men are associated with recurrent miscarriage (RM). Antioxidant therapy has recently been recognized as a way to improve sperm parameters. Pourmasumi et al. evaluate the effect of paternal factor and antioxidant therapy on sperm parameters in couples with RM. Sixty samples with RM patients were analyzed before and after 3 months of vitamin E and selenium therapy. Results of this study show that antioxidants can improve sperm parameters and chromatin

Vitamin E has anticoagulant activity; excessive vitamin E can have an impact on blood clotting in the fetus, increasing the risks of high levels of bilirubin and nuclear jaundice for newborn babies. Also, excessive vitamin E has an antagonistic effect on other fat-soluble vitamins in the blood of pregnant women, preventing the absorption and functions of other vitamins. As a result, clinicians should pay careful attention to changes in vitamin E levels during pregnancy and offer appropriate dietary advice, with an emphasis on reasonable vitamin E supplementation [57]. Kurmacheva et al. conduct a pharmacoeconomic analysis of two schemes of vitamin-mineral drugs in the peri-gestation period in women. In two classes of women, the cost-effectiveness of vitamin-mineral formulations was calculated. Patients in

#### *Role of Vitamin E in Pregnancy DOI: http://dx.doi.org/10.5772/intechopen.97268*

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

as shown by degenerating graffian follicles [38].

dant and antioxidant molecules [44–46].

**2.2 Endometriosis**

discovered that a moderate amount of vitamin E in poultry diet preserves semen/ sperm quality in male birds and egg quality in female birds by reducing lipid peroxidation in semen/sperms and eggs [34]. The effects of vitamin E on sperm motility were studied by Suleiman et al. A total of 11 out of 52 treated patients (21%) were pregnant, and 31 subjects experienced increased sperm motility [35]. In a systematic review of the effect of oral antioxidants (vitamins C and E, zinc, Se, carnitine) on male infertility by Ross et al., 17 randomized trials, including a total of 1665 men, were identified. Of the 17 trials, 14(82%) showed an improvement in either sperm quality or pregnancy rate after antioxidant therapy [36]. Cicek et al., studied the impact of vitamin E on the treatment results of women who were going through intrauterine insemination and controlled ovarian stimulation and had an unknown cause of infertility. Two groups A and B had 53 and 50 volunteers respectively. Group A received 400 IU/day of vitamin E and clomiphene citrate. This combination was used for producing controlled ovarian stimulations. Group B (control) also received controlled ovarian stimulation but without vitamin E. Outcome of the study demonstrated that both the groups had a significant difference in the thickness of endometrium on the day which human chorionic gonadotropin (hCG) was administered. Nevertheless, implantation and pregnancy rates had no connection with the administration of vitamin E. Based on the study it can be concluded that vitamin E possesses antioxidant effect and its administration could enhance the response of endometrium in females with unknown cause of infertility [37]. Das et al. performed a study in which female rats (30 days age) were maintained on a vitamin E-deficient diet for 70 days. At 100 days of age, the vitamin E-deficient and control animals were sacrificed. A group of animals was supplemented with a normal diet for the last 25 days following a 45-day deficient diet, or vice versa. The most notable findings were (i) a significant decrease in uterine weight in the deficient group, (ii) a significant decrease in estrogen, LH, and estrogen-induced uterine enzymes alkaline phosphatase and peroxidase, and (iii) ovarian dysfunction

Endometriosis is a condition characterized by the presence of endometrial tissue

Santanam et al. performed a randomized, placebo-controlled trial of antioxidant

vitamins (vitamin E and C) in women with pelvic pain and endometriosis. This study included 59 women between the ages of 19 and 41 who had pelvic pain and had a history of endometriosis or infertility. Before surgery, patients were randomly assigned to one of two groups: vitamin E (1200 IU) and vitamin C (1000 mg) or placebo for eight weeks. Results indicated that after treatment with antioxidants, chronic pain ("everyday pain") improved in 43 percent of patients in the antioxidant treatment group (P = 0.0055) compared with the placebo group. The results of this clinical trial show that administration of antioxidants reduces chronic pelvic pain in women with endometriosis and inflammatory markers [47]. East-Powell et al. performed a randomized, placebo-controlled trial of antioxidant vitamins (vitamin E and C) in women with pelvic pain and endometriosis and/or infertility. A total of 59 women were included in the trial. Patients were randomly assigned to

outside the uterine cavity [39]. Endometriosis is a condition that affects mostly women of reproductive age. The peak incidence is between 35 and 45 years old [40]. Endometriosis is found in 25 to 40% of women with infertility and 40–87% of women with chronic pelvic pain have endometriosis [41–43]. Endometriosis is associated with oxidative stress, even though the pathogenesis of the condition is currently unknown. Patient with endometriosis have an altered balance of prooxi-

**98**

2 groups: vitamin E 1200 IU (3 capsules of 400 mg each) and vitamin C 1000 mg (2 tablets of 500 mg each) daily for eight weeks before surgery. The results of this clinical trial show that administration of antioxidants (vitamin E and C) reduces chronic pelvic pain in women with endometriosis and inflammatory markers [48]. Hashemi et al. performed a randomized clinical trial in 40 women with implantation failure aged 18–37 years old. Participants were randomly divided into two groups: group A received 400-IU vitamin E supplements and group B received a placebo for 12 weeks. Vitamin E supplements were shown to dramatically improve serum vitamin E levels and endometrial thickness in women with implantation failure [49]. Kavtaradze et al. performed a clinical trial in 59 patients age 19–41 years with pelvic pain and history of endometriosis and/or infertility. Patients were randomly assigned to 2 groups: vitamin E (1200 IU) and vitamin C (1000 mg) combination or placebo daily for two months before surgery. This clinical trial's preliminary findings indicate that antioxidants (vitamins E and C) improve pelvic pain in women with endometriosis. According to this report, antioxidant vitamins are effective in reducing chronic pelvic pain in women with endometriosis. This research supports the development of a new class of medicines for the treatment of endometriosis-related pelvic pain. This information further supports our overall conclusion that endometriosis is an oxidative stress-related condition [50].

#### **2.3 Miscarriage**

Miscarriage is a serious pregnancy complication that can be brought about by a variety of causes. Vitamin deficiency has been linked to an increased risk of miscarriage, so supplementing women with vitamins before or during pregnancy can help prevent miscarriage [51]. Vitamin E deficiency's effects on human health have yet to be thoroughly reported and investigated. Low plasma vitamin E, on the other hand, has been linked to miscarriage in the first trimester of a woman's pregnancy. Furthermore, vitamin E supplementation in the diet reduced the rate of miscarriage in pregnant women by around 50% [52].

Pregnant women have quicker metabolism, increased production of free radicals, and increased lipid peroxidation. Thus, low levels of vitamin E can lead to the production of excessive free radicals, leading to placental aging, endothelial vascular damage, which increases the incidence of high-risk infections in pregnancy [53, 54]. It can also damage the lining of the fetal cell membranes, increasing the risk of premature rupture of the embryo [55]. Increased reactive oxygen species and decreased antioxidant levels in men are associated with recurrent miscarriage (RM). Antioxidant therapy has recently been recognized as a way to improve sperm parameters. Pourmasumi et al. evaluate the effect of paternal factor and antioxidant therapy on sperm parameters in couples with RM. Sixty samples with RM patients were analyzed before and after 3 months of vitamin E and selenium therapy. Results of this study show that antioxidants can improve sperm parameters and chromatin condensation in recurrent miscarriage male partners [56].

Vitamin E has anticoagulant activity; excessive vitamin E can have an impact on blood clotting in the fetus, increasing the risks of high levels of bilirubin and nuclear jaundice for newborn babies. Also, excessive vitamin E has an antagonistic effect on other fat-soluble vitamins in the blood of pregnant women, preventing the absorption and functions of other vitamins. As a result, clinicians should pay careful attention to changes in vitamin E levels during pregnancy and offer appropriate dietary advice, with an emphasis on reasonable vitamin E supplementation [57].

Kurmacheva et al. conduct a pharmacoeconomic analysis of two schemes of vitamin-mineral drugs in the peri-gestation period in women. In two classes of women, the cost-effectiveness of vitamin-mineral formulations was calculated. Patients in

the first group (n = 60) were given a vitamin-mineral complex before and during pregnancy that included metafolin, other B vitamins, vitamins C, E, PP, and iodine (150 mcg) in physiological doses, as well as 200 mg of docosahexaenoic acid in a capsule intended for use from the 13th week until the end of pregnancy. During pregravid preparation and the gestational period, women in the second group (n = 54) took high doses of synthetic folic acid, vitamins B6 and B12 as part of two vitamin and mineral preparations. The use of vitamin-mineral complex containing physiological dosages of vitamins of group B, vitamins C, E, PP and iodine in the peri-gestation period in women with habitual miscarriages has tangible clinical and economic advantages in comparison with the administration of high doses of synthetic folic acid, vitamins B6 and B12 [58].

Shamim et al. studied the contribution of deficiencies of vitamin E to human pregnancy loss (pregnancy losses <24 wk. of gestation) in rural Bangladesh. A trial was done in 1605 pregnant Bangladeshi women, gestational age: 8–13 weeks. Of the 1,605 women in the study, 141, or 8.8%, miscarried. About 5.2% of women with adequate alpha-tocopherol miscarried in the first or second trimester, compared with 10.2 percent of women with low levels. It was found that low plasma α-tocopherol was associated with an increased risk of miscarriage. Maternal vitamin E status in the first trimester may influence the risk of early pregnancy loss [59].

Junovich et al. investigate the fertility properties of Vitamin E. Pregnant females from CBA/J × DBA/2 miscarriage model (creates an immune type miscarriage) were orally supplemented with Vitamin E (15 mg/day). It was found that Vitamin E has able to decrease the miscarriage rate [60]. Şimşek et al. investigated plasma levels of vitamin E in 40 women with habitual abortion (HA) at the Department of Obstetrics and Gynaecology, Medical Faculty of Firat University, ElazigÏ, Turkey. The mean age of the patients was 28.5 years (21 ± 38 years). The levels of vitamin E were significantly lower in women with HA than in controls. According to the results of this study, it was found that a level of vitamin E was significantly decreased (P < 0.01) in HA. The decrease of this antioxidant may play a significant role in women with habitual abortion [61]. Vural et al. performed a clinical trial to determine the relationship between changes in some parameters of the antioxidant system like vitamin E and recurrent abortion. For the study 120 women with recurrent abortions, 25 non-pregnant healthy women in the productive era and 25 normotensive pregnant women within their first trimester were taken into the study in Istanbul Medical Faculty, Gynecology and Obstetric Department. According to the etiology, women with chronic miscarriage were classified into four subgroups: autoimmune, luteal phase defect, anatomical disease, and unexplained. Vitamin E levels in the autoimmune, unexplained, and luteal phase defect subgroups were slightly lower than in the two control groups and the anatomical defect group. It was found that decreased concentrations of plasma vitamin E reflect the increased oxidative stress. In a conclusion, recurrent miscarriages may also result in oxidative stress and depletion and weakness of antioxidant defence [62].

Von Mandach et al. studied that whether there is an association between reduced vitamin E levels and abnormal pregnancy. Abnormal pregnancies were compared with normals. In normal pregnancies, mean vitamin E levels rose from 12.9 +/− 1.1 micrograms/ml in early pregnancy to 22.5 +/− 1.5 micrograms/ml at term (p < 0.05, n = 11). In pregnancies with fetal complications or maternal risks, vitamin E levels were lower than in normal at corresponding gestational age. The results show lower maternal levels of vitamin E in abnormal pregnancies [63].

Oladimeji et al. performed a clinical trial to examine the relationship between serum vitamin E levels and unexplained infertility and recurrent miscarriages. Eighty-two healthy Nigerian Women volunteers were recruited for this study.

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*Role of Vitamin E in Pregnancy*

treatment options [66].

*DOI: http://dx.doi.org/10.5772/intechopen.97268*

The mean serum vitamin E concentration in pregnant women was found to be insignificantly higher (10.36 ± 3.52 mg/ml) than the reported values in women with unexplained infertility and persistent miscarriage (8.97 ± 3.56 mg/ml). It was concluded from this study that there is no relationship between recurrent miscar-

Miscarriage risk is significantly reduced by taking supplementary vitamin E (at least 200 IU and perhaps 400 IU daily). There were already results of medical

Polycystic ovary syndrome is a common birth defect in women during childbearing age. According to the Endocrine Society released training strategies for PCOS, in adolescents with PCOS, metformin and hormonal contraceptives are the

Vitamin E is not a hormone but acts as a hormone. It works by impersonating the effects of progesterone on the body, as well as by reducing the side effects of high levels of androgens (testosterone and estrogen). In a study after 12 weeks, the amount of serum testosterone decreased which provides evidence against it. The study also found that lifestyle changes and the use of supplements including omega-3 and/or Vitamin E will improve inflammation and insulin sensitivity thus remaining an effective treatment approach for PCOS subjects. Vitamin E may serve as a necessary supplement included in the current treatment guide to improve PCOS parameters, which will also improve the quality of life in PCOS and reduce overall medical costs, often unaffordable for most people with PCOS in India [67]. Vitamin E reacts often with lipid peroxyl radicals which leads to the elimination of peroxidation chain reactions and thus reduces oxidative damage. The serum concentration of vitamin E in the study was significantly lower in PCOS patients compared with controls. Similar reports of reduced vitamin E concentration in PCOS patients were stated in various studies [68]. The prospect of a fast response of vitamin E to cellular oxygen and free radicals may be the cause of a significant decrease in vitamin E concentration. Therefore, it is proposed that vitamin E through its natural scavenging method protects polyunsaturated fatty acids from peroxidation reactions [69]. Mohan et al. 2009 estimated plasma vitamin E level in fifty-six Polycystic Ovary Syndrome patients. It was observed that there was a significant decrease in plasma vitamin E levels in patients with polycystic ovary syndrome when compared to controls [70]. Hamad et al. studied the effect of vitamin E and selenium on ovulation in PCOS patients. The participants in this sample included 25 PCOS patients who were untreated and 26 PCOS patients who were treated, as well as 42 healthy controls. From the results of this study, it was found that vitamin E has a significant role in the ovulation of PCOS patients [71]. Angiogenesis disturbances are common in women with polycystic ovary syndrome (PCOS). Shirazi et al. performed a randomized, double-blind, placebo-controlled trial on 43 women, ages 20–40 years, with PCOS to evaluate antiangiogenic properties of Vitamin E. Patients were randomly assigned into two groups: group A received vitamin E 400 IU/day and group B received placebo for 8 weeks. At the start and end of the analysis, anthropometric and angiogenic parameters such as body weight, fat mass, and fat-free mass, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) were calculated using standard methods. Vitamin E supplementation for eight weeks had beneficial effects on body weight, Ang-1, Ang-1/Ang-2 ratio, and VEGF level in PCOS women [72]. Carotid intima-media thickness (CIMT) artery in women with PCOS was significantly higher than healthy women. CIMT has been widely

riages and unexplained infertility and vitamin E levels [64].

reports confirming this by the end of WW II [65].

**2.4 Polycystic ovary syndrome (PCOS)**

#### *Role of Vitamin E in Pregnancy DOI: http://dx.doi.org/10.5772/intechopen.97268*

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

synthetic folic acid, vitamins B6 and B12 [58].

tion and weakness of antioxidant defence [62].

maternal levels of vitamin E in abnormal pregnancies [63].

the first group (n = 60) were given a vitamin-mineral complex before and during pregnancy that included metafolin, other B vitamins, vitamins C, E, PP, and iodine (150 mcg) in physiological doses, as well as 200 mg of docosahexaenoic acid in a capsule intended for use from the 13th week until the end of pregnancy. During pregravid preparation and the gestational period, women in the second group (n = 54) took high doses of synthetic folic acid, vitamins B6 and B12 as part of two vitamin and mineral preparations. The use of vitamin-mineral complex containing physiological dosages of vitamins of group B, vitamins C, E, PP and iodine in the peri-gestation period in women with habitual miscarriages has tangible clinical and economic advantages in comparison with the administration of high doses of

Shamim et al. studied the contribution of deficiencies of vitamin E to human pregnancy loss (pregnancy losses <24 wk. of gestation) in rural Bangladesh. A trial was done in 1605 pregnant Bangladeshi women, gestational age: 8–13 weeks. Of the 1,605 women in the study, 141, or 8.8%, miscarried. About 5.2% of women with adequate alpha-tocopherol miscarried in the first or second trimester, compared with 10.2 percent of women with low levels. It was found that low plasma α-tocopherol was associated with an increased risk of miscarriage. Maternal vitamin E status in

Junovich et al. investigate the fertility properties of Vitamin E. Pregnant females from CBA/J × DBA/2 miscarriage model (creates an immune type miscarriage) were orally supplemented with Vitamin E (15 mg/day). It was found that Vitamin E has able to decrease the miscarriage rate [60]. Şimşek et al. investigated plasma levels of vitamin E in 40 women with habitual abortion (HA) at the Department of Obstetrics and Gynaecology, Medical Faculty of Firat University, ElazigÏ, Turkey. The mean age of the patients was 28.5 years (21 ± 38 years). The levels of vitamin E were significantly lower in women with HA than in controls. According to the results of this study, it was found that a level of vitamin E was significantly decreased (P < 0.01) in HA. The decrease of this antioxidant may play a significant role in women with habitual abortion [61]. Vural et al. performed a clinical trial to determine the relationship between changes in some parameters of the antioxidant system like vitamin E and recurrent abortion. For the study 120 women with recurrent abortions, 25 non-pregnant healthy women in the productive era and 25 normotensive pregnant women within their first trimester were taken into the study in Istanbul Medical Faculty, Gynecology and Obstetric Department. According to the etiology, women with chronic miscarriage were classified into four subgroups: autoimmune, luteal phase defect, anatomical disease, and unexplained. Vitamin E levels in the autoimmune, unexplained, and luteal phase defect subgroups were slightly lower than in the two control groups and the anatomical defect group. It was found that decreased concentrations of plasma vitamin E reflect the increased oxidative stress. In a conclusion, recurrent miscarriages may also result in oxidative stress and deple-

Von Mandach et al. studied that whether there is an association between reduced vitamin E levels and abnormal pregnancy. Abnormal pregnancies were compared with normals. In normal pregnancies, mean vitamin E levels rose from 12.9 +/− 1.1 micrograms/ml in early pregnancy to 22.5 +/− 1.5 micrograms/ml at term (p < 0.05, n = 11). In pregnancies with fetal complications or maternal risks, vitamin E levels were lower than in normal at corresponding gestational age. The results show lower

Oladimeji et al. performed a clinical trial to examine the relationship between serum vitamin E levels and unexplained infertility and recurrent miscarriages. Eighty-two healthy Nigerian Women volunteers were recruited for this study.

the first trimester may influence the risk of early pregnancy loss [59].

**100**

The mean serum vitamin E concentration in pregnant women was found to be insignificantly higher (10.36 ± 3.52 mg/ml) than the reported values in women with unexplained infertility and persistent miscarriage (8.97 ± 3.56 mg/ml). It was concluded from this study that there is no relationship between recurrent miscarriages and unexplained infertility and vitamin E levels [64].

Miscarriage risk is significantly reduced by taking supplementary vitamin E (at least 200 IU and perhaps 400 IU daily). There were already results of medical reports confirming this by the end of WW II [65].

#### **2.4 Polycystic ovary syndrome (PCOS)**

Polycystic ovary syndrome is a common birth defect in women during childbearing age. According to the Endocrine Society released training strategies for PCOS, in adolescents with PCOS, metformin and hormonal contraceptives are the treatment options [66].

Vitamin E is not a hormone but acts as a hormone. It works by impersonating the effects of progesterone on the body, as well as by reducing the side effects of high levels of androgens (testosterone and estrogen). In a study after 12 weeks, the amount of serum testosterone decreased which provides evidence against it. The study also found that lifestyle changes and the use of supplements including omega-3 and/or Vitamin E will improve inflammation and insulin sensitivity thus remaining an effective treatment approach for PCOS subjects. Vitamin E may serve as a necessary supplement included in the current treatment guide to improve PCOS parameters, which will also improve the quality of life in PCOS and reduce overall medical costs, often unaffordable for most people with PCOS in India [67]. Vitamin E reacts often with lipid peroxyl radicals which leads to the elimination of peroxidation chain reactions and thus reduces oxidative damage. The serum concentration of vitamin E in the study was significantly lower in PCOS patients compared with controls. Similar reports of reduced vitamin E concentration in PCOS patients were stated in various studies [68]. The prospect of a fast response of vitamin E to cellular oxygen and free radicals may be the cause of a significant decrease in vitamin E concentration. Therefore, it is proposed that vitamin E through its natural scavenging method protects polyunsaturated fatty acids from peroxidation reactions [69]. Mohan et al. 2009 estimated plasma vitamin E level in fifty-six Polycystic Ovary Syndrome patients. It was observed that there was a significant decrease in plasma vitamin E levels in patients with polycystic ovary syndrome when compared to controls [70]. Hamad et al. studied the effect of vitamin E and selenium on ovulation in PCOS patients. The participants in this sample included 25 PCOS patients who were untreated and 26 PCOS patients who were treated, as well as 42 healthy controls. From the results of this study, it was found that vitamin E has a significant role in the ovulation of PCOS patients [71]. Angiogenesis disturbances are common in women with polycystic ovary syndrome (PCOS). Shirazi et al. performed a randomized, double-blind, placebo-controlled trial on 43 women, ages 20–40 years, with PCOS to evaluate antiangiogenic properties of Vitamin E. Patients were randomly assigned into two groups: group A received vitamin E 400 IU/day and group B received placebo for 8 weeks. At the start and end of the analysis, anthropometric and angiogenic parameters such as body weight, fat mass, and fat-free mass, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) were calculated using standard methods. Vitamin E supplementation for eight weeks had beneficial effects on body weight, Ang-1, Ang-1/Ang-2 ratio, and VEGF level in PCOS women [72]. Carotid intima-media thickness (CIMT) artery in women with PCOS was significantly higher than healthy women. CIMT has been widely

used as a surrogate index of atherosclerosis and CVD events. Talari et al. performed a randomized, double-blind, placebo-controlled trial in 60 women with PCOS to evaluate the beneficial effects of omega-3 and vitamin E co-supplementation on carotid intima-media thickness (CIMT). Participants were randomly assigned into two groups and assigned to take either 1000 mg omega-3 plus 400 IU vitamin E supplements or a placebo for 12 weeks. It was found a significant reduction in maximum and mean levels of the left and right CIMT in patients with PCOS compared with placebo. Antioxidant and anti-inflammatory effects of Vitamin E may improve CIMT [73].

PCOS is a heterogeneous syndrome characterized by hyperandrogenism symptoms. Izadi et al. performed a randomized, double-blind, placebo-controlled clinical trial to evaluate the effects of CoQ10 and/or vitamin E on glucose homeostasis parameters and reproductive hormones in women with PCOS. In this study, it was found that CoQ10 with or without vitamin E supplementation for 8 weeks among patients with PCOS significantly decreased serum total testosterone levels (*P* < 0.001) compared with those of the placebo group. CoQ10 supplementation in combination with vitamin E significantly improved sex hormone-binding globulin (SHBG) levels compared with other groups (*P* = 0.008) [74].

#### **2.5 Embryonic development**

Human embryonic development refers to the development and formation of the human embryo. It is characterized by the processes of cell division and cellular differentiation of the embryo that occurs during the early stages of development [75].

ROS are highly reactive molecules, their accumulation can lead to damage and breakage of DNA strands. Many pieces of evidence have been found that ROS compromises embryo development in many species [76–78].

Selenium and Vitamin E are the important antioxidants that protect mammalian cells against lipid peroxidation. Tsujii et al. conducted a study to investigate whether Selenium or Vitamin E and Selenium + Vitamin E overcome the undesirable oxidative stress produced by hydrogen peroxide (H2O2) and enhance the development of pre implanted mice embryo. Co-incubating the embryos with 60 nM Selenium and/or 100 nM Vitamin E were increased (P < 0.05) the blastocyst development rate. The addition of H2O2 reduced the development of mouse embryos, but the addition of Vitamin E, Se and Selenium+Vitamin E reduced the detrimental effect of H2O2 and influenced the higher rate of development to blastocysts, compared to CZB alone (P < 0.05). The incorporation and oxidation of 14C-glucose in the blastocysts developed by the medium supplemented with Se and/or Vitamin E in the presence or absence of H2O2 were significantly higher (P < 0.05) than that of the control. Moreover, Vitamin E is more effective than Selenium and Selenium + Vitamin E in reversing ROS-induced mouse embryotoxicity [79]. McDougall et al. studied the long-term effects of Vitamin E deficiency on embryonic development and improvement effect after feeding Vitamin E-adequate diets by using a zebrafish model. Adult zebrafish maintained on Vitamin E-deficient (E-) or sufficient (E+) diets up to 12 days post-fertilization (dpf) to obtained E- and E+ embryos. The E- group suffered significantly increased morbidity and mortality as well as altered DNA methylation status through 5 dpf when compared to E+ larvae, but upon feeding with a Vitamin E -adequate diet from 5 to 12 dpf both the E- and E+ groups survived and grew normally; the DNA methylation profile also was similar between groups by 12 dpf. However, 12 dpf E- larvae still had behavioral defects. Outcomes suggest that embryonic Vitamin E deficiency causes behavioral impairments due to persistent lipid peroxidation and metabolic perturbations that are not resolved via later dietary vitamin E supplementation [80].

**103**

**2.7 Uterine fibroids**

impairing gamete transport [87].

*Role of Vitamin E in Pregnancy*

**2.6 Pre-mature delivery**

South Asia [81].

*DOI: http://dx.doi.org/10.5772/intechopen.97268*

Every year, about 15 million babies (1 in 10) are delivered prematurely around the world. Prematurity is the second leading cause of death among newborns after pneumonia. Pre-mature babies struggle with visual, auditory and learning disabilities. Over 60% of pre-mature delivery worldwide occurs in Sub-Saharan Africa and

Cruz et al. studied the effect of vitamin E supplementation on mothers with threatened premature delivery and premature infants. It was found that maternal vitamin E treatment did not prevent either erythrocyte hemolysis or lipid peroxide formation in premature infants after birth. On the other hand, intramuscular vitamins E to infants after birth prevent erythrocyte hemolysis and low lipid peroxide formation when serum vitamin E increased above 2 mg/100 ml [82]. Hittner et al. performed a double-blind study in 101 preterm infants to evaluate the efficacy of oral vitamin E in preventing the development of retrolental fibroplasia. 50 infants received vitamin E 100 mg/Kg/ day and 51 infants received 5 mg mg/Kg/ day (controls). The severity of retrolental fibroplasia was found to be significantly reduced in infants given 100 mg of vitamin E (P = 0.012) [83]. The link between vitamin E deficiency and hemolytic anemia in small premature infants prompted researchers to look into vitamin E absorption in infants of different gestational and developmental ages. Premature infants' capacity to sustain vitamin E sufficiency during the first three months of life was shown to be directly related to their gestational age; infants with the lowest gestational age were the least likely to attain vitamin E sufficiency, even when given a vitamin E supplement. In infants with a gestational age of fewer than 32 weeks, there was a gradual increase in vitamin absorption in the intestine. Oral iron administration has been linked to a reduction in vitamin E absorption in the intestine. Since maintenance of vitamin E sufficiency appears to be nutritionally important in the premature infant, the efficacy of other routes of administration of the vitamin should be explored [84]. Vitamin E has been linked to several positive outcomes in premature newborn infants. Vitamin E deficiency is believed to be at least partially responsible for the anemia that happens often 4 to 6 weeks after premature birth, and regular vitamin E supplementation is often recommended. However, a review of published controlled trials of vitamin E supplementation shows that the extent, if any, of this preventive effect against anemia is debated. According to research, the dietary ratio of alpha-tocopherol to polyunsaturated fatty acids is normally sufficient to avoid symptoms of vitamin E deficiency without the use of supplements. Premature infants exposed to oxygenrich conditions and artificial ventilation are protected from the risks of retrolental fibroplasia and bronchopulmonary dysplasia by receiving large parenteral doses of vitamin E. However, subsequent research has yet to verify these positive early findings of preventive effects. At this time, there does not seem to be any clear evidence that supplementing a premature infant's usual vitamin E intake is essential [85].

Uterine fibroids or myomas are benign tumours of the human uterus. The main symptoms are prolonged or heavy menstrual bleeding, pelvic pressure or pain, and reproductive dysfunction [86]. Fibroids have an effect on a woman's pregnancy as well as her quality of life. Fibroids affect approximately 35–77% of reproductiveage women. Fibroids may cause infertility by obstructing the fallopian tubes and

A total of 49 patients were enrolled in a double-blind, randomized, placebo-controlled trial conducted by Harrison et al. in 2003. For six months, all patients were

#### **2.6 Pre-mature delivery**

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

(SHBG) levels compared with other groups (*P* = 0.008) [74].

compromises embryo development in many species [76–78].

later dietary vitamin E supplementation [80].

used as a surrogate index of atherosclerosis and CVD events. Talari et al. performed a randomized, double-blind, placebo-controlled trial in 60 women with PCOS to evaluate the beneficial effects of omega-3 and vitamin E co-supplementation on carotid intima-media thickness (CIMT). Participants were randomly assigned into two groups and assigned to take either 1000 mg omega-3 plus 400 IU vitamin E supplements or a placebo for 12 weeks. It was found a significant reduction in maximum and mean levels of the left and right CIMT in patients with PCOS compared with placebo. Antioxidant and anti-inflammatory effects of Vitamin E may improve

PCOS is a heterogeneous syndrome characterized by hyperandrogenism symptoms. Izadi et al. performed a randomized, double-blind, placebo-controlled clinical trial to evaluate the effects of CoQ10 and/or vitamin E on glucose homeostasis parameters and reproductive hormones in women with PCOS. In this study, it was found that CoQ10 with or without vitamin E supplementation for 8 weeks among patients with PCOS significantly decreased serum total testosterone levels (*P* < 0.001) compared with those of the placebo group. CoQ10 supplementation in combination with vitamin E significantly improved sex hormone-binding globulin

Human embryonic development refers to the development and formation of the human embryo. It is characterized by the processes of cell division and cellular differentiation of the embryo that occurs during the early stages of development [75]. ROS are highly reactive molecules, their accumulation can lead to damage and breakage of DNA strands. Many pieces of evidence have been found that ROS

Selenium and Vitamin E are the important antioxidants that protect mammalian cells against lipid peroxidation. Tsujii et al. conducted a study to investigate whether Selenium or Vitamin E and Selenium + Vitamin E overcome the undesirable oxidative stress produced by hydrogen peroxide (H2O2) and enhance the development of pre implanted mice embryo. Co-incubating the embryos with 60 nM Selenium and/or 100 nM Vitamin E were increased (P < 0.05) the blastocyst development rate. The addition of H2O2 reduced the development of mouse embryos, but the addition of Vitamin E, Se and Selenium+Vitamin E reduced the detrimental effect of H2O2 and influenced the higher rate of development to blastocysts, compared to CZB alone (P < 0.05). The incorporation and oxidation of 14C-glucose in the blastocysts developed by the medium supplemented with Se and/or Vitamin E in the presence or absence of H2O2 were significantly higher (P < 0.05) than that of the control. Moreover, Vitamin E is more effective than Selenium and Selenium + Vitamin E in reversing ROS-induced mouse embryotoxicity [79]. McDougall et al. studied the long-term effects of Vitamin E deficiency on embryonic development and improvement effect after feeding Vitamin E-adequate diets by using a zebrafish model. Adult zebrafish maintained on Vitamin E-deficient (E-) or sufficient (E+) diets up to 12 days post-fertilization (dpf) to obtained E- and E+ embryos. The E- group suffered significantly increased morbidity and mortality as well as altered DNA methylation status through 5 dpf when compared to E+ larvae, but upon feeding with a Vitamin E -adequate diet from 5 to 12 dpf both the E- and E+ groups survived and grew normally; the DNA methylation profile also was similar between groups by 12 dpf. However, 12 dpf E- larvae still had behavioral defects. Outcomes suggest that embryonic Vitamin E deficiency causes behavioral impairments due to persistent lipid peroxidation and metabolic perturbations that are not resolved via

**102**

CIMT [73].

**2.5 Embryonic development**

Every year, about 15 million babies (1 in 10) are delivered prematurely around the world. Prematurity is the second leading cause of death among newborns after pneumonia. Pre-mature babies struggle with visual, auditory and learning disabilities. Over 60% of pre-mature delivery worldwide occurs in Sub-Saharan Africa and South Asia [81].

Cruz et al. studied the effect of vitamin E supplementation on mothers with threatened premature delivery and premature infants. It was found that maternal vitamin E treatment did not prevent either erythrocyte hemolysis or lipid peroxide formation in premature infants after birth. On the other hand, intramuscular vitamins E to infants after birth prevent erythrocyte hemolysis and low lipid peroxide formation when serum vitamin E increased above 2 mg/100 ml [82]. Hittner et al. performed a double-blind study in 101 preterm infants to evaluate the efficacy of oral vitamin E in preventing the development of retrolental fibroplasia. 50 infants received vitamin E 100 mg/Kg/ day and 51 infants received 5 mg mg/Kg/ day (controls). The severity of retrolental fibroplasia was found to be significantly reduced in infants given 100 mg of vitamin E (P = 0.012) [83]. The link between vitamin E deficiency and hemolytic anemia in small premature infants prompted researchers to look into vitamin E absorption in infants of different gestational and developmental ages. Premature infants' capacity to sustain vitamin E sufficiency during the first three months of life was shown to be directly related to their gestational age; infants with the lowest gestational age were the least likely to attain vitamin E sufficiency, even when given a vitamin E supplement. In infants with a gestational age of fewer than 32 weeks, there was a gradual increase in vitamin absorption in the intestine. Oral iron administration has been linked to a reduction in vitamin E absorption in the intestine. Since maintenance of vitamin E sufficiency appears to be nutritionally important in the premature infant, the efficacy of other routes of administration of the vitamin should be explored [84]. Vitamin E has been linked to several positive outcomes in premature newborn infants. Vitamin E deficiency is believed to be at least partially responsible for the anemia that happens often 4 to 6 weeks after premature birth, and regular vitamin E supplementation is often recommended. However, a review of published controlled trials of vitamin E supplementation shows that the extent, if any, of this preventive effect against anemia is debated. According to research, the dietary ratio of alpha-tocopherol to polyunsaturated fatty acids is normally sufficient to avoid symptoms of vitamin E deficiency without the use of supplements. Premature infants exposed to oxygenrich conditions and artificial ventilation are protected from the risks of retrolental fibroplasia and bronchopulmonary dysplasia by receiving large parenteral doses of vitamin E. However, subsequent research has yet to verify these positive early findings of preventive effects. At this time, there does not seem to be any clear evidence that supplementing a premature infant's usual vitamin E intake is essential [85].

#### **2.7 Uterine fibroids**

Uterine fibroids or myomas are benign tumours of the human uterus. The main symptoms are prolonged or heavy menstrual bleeding, pelvic pressure or pain, and reproductive dysfunction [86]. Fibroids have an effect on a woman's pregnancy as well as her quality of life. Fibroids affect approximately 35–77% of reproductiveage women. Fibroids may cause infertility by obstructing the fallopian tubes and impairing gamete transport [87].

A total of 49 patients were enrolled in a double-blind, randomized, placebo-controlled trial conducted by Harrison et al. in 2003. For six months, all patients were

given either vitamins E (1000 IU) and C (1000 mg) or a placebo. Results show that a statistically significant improvement in fibrosis score (p = 0.002) [88]. Fruscella et al. studied the effect of vitamin E (300 mg per day) in a group of 25 women, aged between 25 and 41 years old, suffering from uterine myomas in pregnancy. All the pregnancies continued to term. The neonatal outcome was satisfactory in all cases and no collateral effects were observed in either mothers or fetuses [89]. Tocopherol can stop cancer cells from growing in culture by trapping free radicals and other mechanisms [90]. Young et al. discovered that vitamin E succinate (a vitamin E analogue) decreased the number of UF cells and caused cell death [91]. In addition, Zhang et al. discovered that vitamin E succinate ester could suppress steroid hormone signalling [92].

#### **2.8 Preeclampsia**

Preeclampsia is a major cause of both maternal and fetal neonatal morbidity. Endothelial damage in the arteries is believed to play a role. The simple clinical definition [gestational hypertension (>90 mmHg diastolic) occurring after the 20th week of gestation with superimposed proteinuria (>300 mg/day) belies the complexity of preeclampsia, which is often accompanied by multi-organ dysfunction. Free radical-mediated lipid peroxidation may be involved in endothelial damage in preeclampsia. Complications such as endothelial cell dysfunction of blood vessels in women with preeclampsia and other hypertensive conditions are linked with oxidative stress and lipid peroxidation.

Antioxidants may be essential for lipid peroxidation prevention and, hypothetically, pre-eclampsia prevention. Vitamin E, which is a free radical scavenger and thus inhibits the development of lipid peroxides, opposes the toxic acts of lipid peroxides. It acts as in-vivo antioxidant that protects tissue lipids from free radical attack and thus stabilizes cell membranes. Compared to non-pregnancy, maternal levels of vitamin E are elevated in pregnancy, which is consistent with previous studies. In women with preeclampsia, the antioxidant function is decreased relative to women who have normal pregnancies. Antioxidant activity increases throughout normal gestation, but not with preeclampsia. It has been suggested that evidence of vitamin E consumption is an alerting mechanism for the development of preeclampsia [93, 94]. Some preclinical studies show that vitamin E plays a role in preeclampsia [95]. But some clinical studies suggest that there is no role of vitamin E in preeclampsia [96, 97]. A study has found that level of vitamin E in preeclampsia was low, but no preventive role was found in preeclampsia [98].

#### **2.9 Intrauterine growth restriction**

Intrauterine growth restriction (IUGR) is the inability of fetuses to achieve their genetically defined growth rate resulting in offspring with low birth weight (LBW) and is a problem for both human and veterinary medicine. IUGR has significant consequences for the mortality and morbidity of LBW newborns and has long-term effects on their development and health. The presence of IUGR is directly linked to an insufficient supply of nutrients and oxygen to the fetus due to maternal malnutrition and/or placental insufficiency [99, 100].

In the study, Sales et al. found that combined maternal administration of vitamin C and E in sheep was associated with increased levels of both vitamins in the fetal cord, enhanced antioxidant status, and increased fetal development in singleton and twin pregnancies, but with a greater impact on twin pregnancies. These findings demonstrate the ability of supplementation of vitamin C and E to reduce the effects of IUGRR [101]. Since the transplacental transmission of

**105**

*Role of Vitamin E in Pregnancy*

*DOI: http://dx.doi.org/10.5772/intechopen.97268*

**2.10 Premature rupture of membranes**

in their neonates [106].

**3. Discussion**

restriction on the intrauterine growth of fetuses [102].

alpha-tocopherol is minimal, newborns are considered an at-risk category for vitamin E deficiency. Low serum levels of alpha-tocopherol are associated with the development of edemas, thrombocytosis, and hemolytic anemia, which can result in cardiomyopathy and the possible consequence of this vitamin deficiency is its

Atherosclerosis is one of the main factor of intrauterine growth restriction. Busso et al. [103] studied LDL KO mice diet-induced maternal hypercholesterolemia and atherosclerosis during pregnancy can negatively impact fetal growth. Vitamin E dietary supplementation has a beneficial effect, preventing growth restriction in a significant proportion of fetuses from HC-fed mice [103].

Preterm, premature rupture of the membranes (PPROM) is defined as mem-

deliveries with the regular mortality rate in neonates [104]. Infection, cigarette smoke, and inflammation have all been linked to preterm premature rupture of fetal membranes. Since hypochlorous acid (a reactive oxygen species) is essential to the body's reaction to infection, it may cause tissue damage when destroying pathogens. Plessinger et al. found that antioxidant therapy (vitamins C and E) has a

Preterm infants have a higher risk of oxidative stress and free-radicalmediated diseases, which is partially due to their low antioxidant levels. Bolisetty et al. studied the effect of maternal supplementation of antioxidant vitamins before delivery to reduce the oxidative stress in the mothers and their infants. Five mothers between the ages of 30 and 36 weeks who were at risk of preterm delivery were given a daily oral dosage of betacarotene 20 mg, vitamin E 167.8 mg, and vitamin C 1000 mg until delivery. There was a trend of lower plasma MDA and higher vitamin E at birth in infants born to supplemented mothers. Finally, it has been concluded that short supplementation of antioxidant vitamins to preterm pregnant women reduced the oxidative stress at delivery in mothers and probably

The fetal membranes (amnion and chorion) derive their strength principally from collagen. Collagen provides fetal membranes with both tensile strength and elasticity. Reactive oxygen species (ROS) generated by the body's response to infection, cigarette smoking, bleeding, or cocaine use can activate collagen lytic enzymes and impair fetal membrane integrity. Vitamin E, a lipid-soluble antioxidant, inhibits membrane-damaging effects of reactive oxygen species induced lipid peroxidation [107]. Hauth et al., studied that maternal supplementation with vitamin C and

Several risk factors contributing to reproductive- and pregnancy-related disorders have been reported. Environmental and lifestyle factors are the two main types factors. Examples of major environmental pollutants include hazardous man-made chemicals, industrial discharge, agricultural run-off, human and animal waste, municipal and domestic effluents, and spillage of vessels and oil spills [109]. Lifestyle factors represent another category of major risk factors for reproductive and pregnancy-related disorders. Unhealthy lifestyle behaviors, including cigarette smoking, alcohol consumption, and/or drug abuse,

PPROM occurs in 1–2% of all deliveries and results in a major portion of preterm

brane rupture before 37 weeks' gestation in the absence of labour.

protective effect against hypochlorous acid-induced damage [105].

E did not reduce the occurrence of spontaneous preterm birth [108].

#### *Role of Vitamin E in Pregnancy DOI: http://dx.doi.org/10.5772/intechopen.97268*

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

hormone signalling [92].

oxidative stress and lipid peroxidation.

**2.9 Intrauterine growth restriction**

trition and/or placental insufficiency [99, 100].

**2.8 Preeclampsia**

given either vitamins E (1000 IU) and C (1000 mg) or a placebo. Results show that a statistically significant improvement in fibrosis score (p = 0.002) [88]. Fruscella et al. studied the effect of vitamin E (300 mg per day) in a group of 25 women, aged between 25 and 41 years old, suffering from uterine myomas in pregnancy. All the pregnancies continued to term. The neonatal outcome was satisfactory in all cases and no collateral effects were observed in either mothers or fetuses [89]. Tocopherol can stop cancer cells from growing in culture by trapping free radicals and other mechanisms [90]. Young et al. discovered that vitamin E succinate (a vitamin E analogue) decreased the number of UF cells and caused cell death [91]. In addition, Zhang et al. discovered that vitamin E succinate ester could suppress steroid

Preeclampsia is a major cause of both maternal and fetal neonatal morbidity. Endothelial damage in the arteries is believed to play a role. The simple clinical definition [gestational hypertension (>90 mmHg diastolic) occurring after the 20th week of gestation with superimposed proteinuria (>300 mg/day) belies the complexity of preeclampsia, which is often accompanied by multi-organ dysfunction. Free radical-mediated lipid peroxidation may be involved in endothelial damage in preeclampsia. Complications such as endothelial cell dysfunction of blood vessels in women with preeclampsia and other hypertensive conditions are linked with

Antioxidants may be essential for lipid peroxidation prevention and, hypothetically, pre-eclampsia prevention. Vitamin E, which is a free radical scavenger and thus inhibits the development of lipid peroxides, opposes the toxic acts of lipid peroxides. It acts as in-vivo antioxidant that protects tissue lipids from free radical attack and thus stabilizes cell membranes. Compared to non-pregnancy, maternal levels of vitamin E are elevated in pregnancy, which is consistent with previous studies. In women with preeclampsia, the antioxidant function is decreased relative to women who have normal pregnancies. Antioxidant activity increases throughout normal gestation, but not with preeclampsia. It has been suggested that evidence of vitamin E consumption is an alerting mechanism for the development of preeclampsia [93, 94]. Some preclinical studies show that vitamin E plays a role in preeclampsia [95]. But some clinical studies suggest that there is no role of vitamin E in preeclampsia [96, 97]. A study has found that level of vitamin E in preeclamp-

Intrauterine growth restriction (IUGR) is the inability of fetuses to achieve their genetically defined growth rate resulting in offspring with low birth weight (LBW) and is a problem for both human and veterinary medicine. IUGR has significant consequences for the mortality and morbidity of LBW newborns and has long-term effects on their development and health. The presence of IUGR is directly linked to an insufficient supply of nutrients and oxygen to the fetus due to maternal malnu-

In the study, Sales et al. found that combined maternal administration of vitamin C and E in sheep was associated with increased levels of both vitamins in the fetal cord, enhanced antioxidant status, and increased fetal development in singleton and twin pregnancies, but with a greater impact on twin pregnancies. These findings demonstrate the ability of supplementation of vitamin C and E to reduce the effects of IUGRR [101]. Since the transplacental transmission of

sia was low, but no preventive role was found in preeclampsia [98].

**104**

alpha-tocopherol is minimal, newborns are considered an at-risk category for vitamin E deficiency. Low serum levels of alpha-tocopherol are associated with the development of edemas, thrombocytosis, and hemolytic anemia, which can result in cardiomyopathy and the possible consequence of this vitamin deficiency is its restriction on the intrauterine growth of fetuses [102].

Atherosclerosis is one of the main factor of intrauterine growth restriction. Busso et al. [103] studied LDL KO mice diet-induced maternal hypercholesterolemia and atherosclerosis during pregnancy can negatively impact fetal growth. Vitamin E dietary supplementation has a beneficial effect, preventing growth restriction in a significant proportion of fetuses from HC-fed mice [103].

#### **2.10 Premature rupture of membranes**

Preterm, premature rupture of the membranes (PPROM) is defined as membrane rupture before 37 weeks' gestation in the absence of labour.

PPROM occurs in 1–2% of all deliveries and results in a major portion of preterm deliveries with the regular mortality rate in neonates [104]. Infection, cigarette smoke, and inflammation have all been linked to preterm premature rupture of fetal membranes. Since hypochlorous acid (a reactive oxygen species) is essential to the body's reaction to infection, it may cause tissue damage when destroying pathogens. Plessinger et al. found that antioxidant therapy (vitamins C and E) has a protective effect against hypochlorous acid-induced damage [105].

Preterm infants have a higher risk of oxidative stress and free-radicalmediated diseases, which is partially due to their low antioxidant levels. Bolisetty et al. studied the effect of maternal supplementation of antioxidant vitamins before delivery to reduce the oxidative stress in the mothers and their infants. Five mothers between the ages of 30 and 36 weeks who were at risk of preterm delivery were given a daily oral dosage of betacarotene 20 mg, vitamin E 167.8 mg, and vitamin C 1000 mg until delivery. There was a trend of lower plasma MDA and higher vitamin E at birth in infants born to supplemented mothers. Finally, it has been concluded that short supplementation of antioxidant vitamins to preterm pregnant women reduced the oxidative stress at delivery in mothers and probably in their neonates [106].

The fetal membranes (amnion and chorion) derive their strength principally from collagen. Collagen provides fetal membranes with both tensile strength and elasticity. Reactive oxygen species (ROS) generated by the body's response to infection, cigarette smoking, bleeding, or cocaine use can activate collagen lytic enzymes and impair fetal membrane integrity. Vitamin E, a lipid-soluble antioxidant, inhibits membrane-damaging effects of reactive oxygen species induced lipid peroxidation [107]. Hauth et al., studied that maternal supplementation with vitamin C and E did not reduce the occurrence of spontaneous preterm birth [108].

#### **3. Discussion**

Several risk factors contributing to reproductive- and pregnancy-related disorders have been reported. Environmental and lifestyle factors are the two main types factors. Examples of major environmental pollutants include hazardous man-made chemicals, industrial discharge, agricultural run-off, human and animal waste, municipal and domestic effluents, and spillage of vessels and oil spills [109]. Lifestyle factors represent another category of major risk factors for reproductive and pregnancy-related disorders. Unhealthy lifestyle behaviors, including cigarette smoking, alcohol consumption, and/or drug abuse, have negative impacts, particularly on female fertility [110, 111]. Furthermore, exposure to multiple environmental pollutants may also result in reactive oxygen species (ROS)-induced oxidative stress (OS). High levels of OS can be linked to a variety of pregnancy-related issues, including embryonic death, early spontaneous abortion, IUGR, fetal death, preterm births, and low birth weight [112, 113]. ROS are highly reactive and unstable. They acquire electrons from nucleic acids, lipids, proteins, carbohydrates, or any other nearby molecule causing a string of chain reactions to become stable. These chain reactions result in cellular damage and diseases [114]. The human body produces reactive compounds known as free radicals which exert a positive as well as a negative impact on the body. To minimize the harmful effect, a complex protection system is required which is known as the antioxidant system. When there is an imbalance between the production of free radicals and the defense mechanism of the antioxidant system it leads to a condition known as oxidative stress [115]. Oxidative stress affects the interaction of gametes and their quality. Spermatozoa, embryos, and oocyte and their environment are affected by free radicals such as reactive oxygen species (ROS). The quality of sperm-mediated oocyte activation, early embryo development, implantation, sperm oocyte interaction is dependent on the microenvironment associated with peritoneal fluid, follicular fluid, and hydrosalpingeal fluid. Implantation and early embryo development are adversely affected by oxidative stress leading to a negative effect on the rate of pregnancy. One of the causative factors for infertility and endometriosis is oxidative stress [116]. ROS or prooxidant or free radicals production have a connection with aerobic metabolism [117, 118], and also the hormones, cytokines, and other stressors are associated with its production. Hydroxyl radical, superoxide anion and hydrogen peroxide are examples of reactive oxygen species (ROS) and they act by modulating the gene expression and transcription factor. A broad range of antioxidants is available which hold the capability to repair cell damage caused by ROS and can neutralize them as well [119, 120].

Some studies suggested that there is a direct relationship between the outcome of the pregnancy and the level of ROS. The placental mitochondrion is the place that has been identified for the production of superoxide in a great amount [121, 122]. Antioxidants such as vitamin C and vitamin E have been reported to be efficient, and their uses in reproductive- and pregnancy-related disorders have been the subject of significant clinical trials [123]. Vitamin E is a chain-breaking antioxidant that helps to inhibit lipid peroxidation [124, 125].

All of these studies show that vitamin E is essential for a natural and stable pregnancy and that vitamin E supplementation has no negative effects on pregnancy outcomes. As discussed above, vitamin E has been proven to be beneficial in pregnancy and neonatal health.

#### **4. Conclusion**

Vitamin E has antioxidant properties that may support pregnancy, but more research is needed to determine its effectiveness. There is a need to evaluate the efficacy and safety of vitamin E supplementation in pregnancy. More research is needed to accurately quantify antioxidant-like vitamin E levels in pregnancy and how they change throughout the pregnancy. It is necessary to investigate the effects of antioxidants on maternal, fetal, and placental health. Prenatal advice should be clear to ensure that women and physicians understand the dietary conditions during pregnancy and how a balanced diet contains antioxidant micronutrients like vitamin E will help avoid pregnancy-related diseases.

**107**

**Author details**

and Md. Faheem Haider

Mohd Aftab Siddiqui\*, Usama Ahmad, Asad Ali, Farogh Ahsan

Faculty of Pharmacy, Integral University, Lucknow, U.P., India

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: aftab.uzaiz@gmail.com

provided the original work is properly cited.

*Role of Vitamin E in Pregnancy*

**Conflict of interest**

*DOI: http://dx.doi.org/10.5772/intechopen.97268*

The authors declare no conflict of interest.

### **Conflict of interest**

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

have negative impacts, particularly on female fertility [110, 111]. Furthermore, exposure to multiple environmental pollutants may also result in reactive oxygen species (ROS)-induced oxidative stress (OS). High levels of OS can be linked to a variety of pregnancy-related issues, including embryonic death, early spontaneous abortion, IUGR, fetal death, preterm births, and low birth weight [112, 113]. ROS are highly reactive and unstable. They acquire electrons from nucleic acids, lipids, proteins, carbohydrates, or any other nearby molecule causing a string of chain reactions to become stable. These chain reactions result in cellular damage and diseases [114]. The human body produces reactive compounds known as free radicals which exert a positive as well as a negative impact on the body. To minimize the harmful effect, a complex protection system is required which is known as the antioxidant system. When there is an imbalance between the production of free radicals and the defense mechanism of the antioxidant system it leads to a condition known as oxidative stress [115]. Oxidative stress affects the interaction of gametes and their quality. Spermatozoa, embryos, and oocyte and their environment are affected by free radicals such as reactive oxygen species (ROS). The quality of sperm-mediated oocyte activation, early embryo development, implantation, sperm oocyte interaction is dependent on the microenvironment associated with peritoneal fluid, follicular fluid, and hydrosalpingeal fluid. Implantation and early embryo development are adversely affected by oxidative stress leading to a negative effect on the rate of pregnancy. One of the causative factors for infertility and endometriosis is oxidative stress [116]. ROS or prooxidant or free radicals production have a connection with aerobic metabolism [117, 118], and also the hormones, cytokines, and other stressors are associated with its production. Hydroxyl radical, superoxide anion and hydrogen peroxide are examples of reactive oxygen species (ROS) and they act by modulating the gene expression and transcription factor. A broad range of antioxidants is available which hold the capability to repair cell damage caused by ROS and can

Some studies suggested that there is a direct relationship between the outcome of the pregnancy and the level of ROS. The placental mitochondrion is the place that has been identified for the production of superoxide in a great amount [121, 122]. Antioxidants such as vitamin C and vitamin E have been reported to be efficient, and their uses in reproductive- and pregnancy-related disorders have been the subject of significant clinical trials [123]. Vitamin E is a chain-breaking antioxi-

All of these studies show that vitamin E is essential for a natural and stable pregnancy and that vitamin E supplementation has no negative effects on pregnancy outcomes. As discussed above, vitamin E has been proven to be beneficial in

Vitamin E has antioxidant properties that may support pregnancy, but more research is needed to determine its effectiveness. There is a need to evaluate the efficacy and safety of vitamin E supplementation in pregnancy. More research is needed to accurately quantify antioxidant-like vitamin E levels in pregnancy and how they change throughout the pregnancy. It is necessary to investigate the effects of antioxidants on maternal, fetal, and placental health. Prenatal advice should be clear to ensure that women and physicians understand the dietary conditions during pregnancy and how a balanced diet contains antioxidant micronutrients like

**106**

neutralize them as well [119, 120].

pregnancy and neonatal health.

**4. Conclusion**

dant that helps to inhibit lipid peroxidation [124, 125].

vitamin E will help avoid pregnancy-related diseases.

The authors declare no conflict of interest.

### **Author details**

Mohd Aftab Siddiqui\*, Usama Ahmad, Asad Ali, Farogh Ahsan and Md. Faheem Haider Faculty of Pharmacy, Integral University, Lucknow, U.P., India

\*Address all correspondence to: aftab.uzaiz@gmail.com

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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teratogenicity following simultaneous administration of folic acid and vitamin E with antiepileptic, antihypertensive and anti-allergic drugs. J Pharm Bioallied Sci. 2014;6(3):185-91

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common and emerging dietary sources: Occurrence, applications, and health benefits. International journal of molecular sciences. 2016 Oct;17(10):1745.

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[21] Meier R, Tomizaki T, Schulze-Briese C, Baumann U, Stocker A. The molecular basis of vitamin E retention: structure of human α-tocopherol transfer protein. Journal of molecular biology. 2003 Aug 15; 331(3):725-34.

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[23] Rizvi S, Raza ST, Faizal Ahmed AA, Abbas S, Mahdi F. The role of vitamin E in human health and some diseases. Sultan Qaboos University Medical Journal. 2014 May;14(2):e157

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7, 43-52.

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

alpha-, beta-, gamma-, and deltatocopherols and their contents in human milk. Biochim. Biophys. Acta 1975, 380,

[12] Aggarwal BB, Sundaram C, Prasad S, Kannappan R. Tocotrienols, the vitamin E of the 21st century: it's potential against cancer and other chronic diseases. Biochemical pharmacology. 2010 Dec

[13] Mohd Mutalip SS, Ab-Rahim S, Rajikin MH. Vitamin E as an antioxidant

Desmarchelier C. Bioavailability of vitamin E in humans: an update. Nutrition reviews. 2013 Jun 1;

[15] Gagné A, Wei SQ, Fraser WD, Julien P. Absorption, transport, and bioavailability of vitamin e and its role

in pregnant women. Journal of Obstetrics and Gynaecology Canada.

[16] Scholl TO, Chen X, Sims M, Stein TP. Vitamin E: maternal

[17] Shahidi F, Ambigaipalan P. Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects–A review. Journal of functional foods. 2015 Oct

[18] Shahidi F, De Camargo AC. Tocopherols and tocotrienols in

concentrations are associated with fetal growth. The American journal of clinical nutrition. 2006 Dec 1;

2009 Mar 1;31(3):210-7

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[11] Bunnel RH, Keating J, Quaresimo A, Parman GK. Alpha-tocopherol content of foods. Am J Clin Nutr. 1965; 17:1-10.

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1;80(11):1613-31

71(6):319-31.

84(6):1442-8.

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Navali N. Effects of vitamin E supplementation on some pregnancy health indices: A randomized clinical trial. International journal of general

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[3] Evans, H.M.; Bishop, K.S. On the existence of a hitherto unrecognized dietary factor essential for reproduction.

[4] Ute C. Obermuller-Jevic, Lester Packer. Vitamin E. Encyclopedia of

[5] Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids.

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[6] https://ods.od.nih.gov/pdf/ factsheets/VitaminE-Consumer.pdf

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[10] Kobayashi, H.; Kanno, C.;

Yamauchi, K.; Tsugo, T. Identification of

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Press, 2000.

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a mouse model of gestational hypercholesterolemia and atherosclerosis. BioMed research international. 2014 Jan 1; 2014.

[104] Shubert PJ, Diss E, Iams JD. Etiology of preterm premature rupture

[105] Plessinger MA, Woods Jr JR, Miller RK. Pretreatment of human amnion-chorion with vitamins C and E prevents hypochlorous acid–induced damage. American journal of obstetrics

[106] Bolisetty S, Naidoo D, Lui K, Koh TH, Watson D, Whitehall J. Antenatal supplementation of antioxidant vitamins to reduce the oxidative stress at delivery—a pilot study. Early human development. 2002

[107] Woods Jr JR, Plessinger MA, Miller RK. Vitamins C and E: missing

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1992 Jun 1; 19(2):251-63.

and gynecology. 2000 Oct

1;183(4):979-85

Apr 1;67(1-2):47-53

Mar; 8(3):59.

2019 Sep; 37(3):291-6.

[92] Zhang Y, Ni J, Messing EM, Chang E, Yang CR, Yeh S. Vitamin E succinate inhibits the function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells. Proceedings of the National

Academy of Sciences. 2002 May

[93] Akyol D, Mungan T, Görkemli H, Nuhoglu G. Maternal levels of vitamin E in normal and preeclamptic pregnancy. Archives of gynecology and obstetrics.

[94] Brown MA, Lindheimer MD, de Swiet M, Assche AV, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in

[95] Poston L, Raijmakers M, Kelly F. Vitamin E in preeclampsia. Annals of the New York Academy of Sciences.

[96] Shennan AH, Duckworth S. Use of

preeclampsia. Obstetric medicine. 2010

[97] Salles AM, Galvao TF, Silva MT, Motta LC, Pereira MG. Antioxidants for preventing preeclampsia: a systematic review. The Scientific World Journal.

[98] Kharb S. Vitamin E and C in preeclampsia. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2000 Nov 1;

[99] Brodsky D, Christou H. Current concepts in intrauterine growth restriction. Journal of intensive care medicine. 2004 Nov; 19(6):307-19.

[100] Nardozza LM, Júnior EA, Barbosa MM, Caetano AC, Lee DJ, Moron AF. Fetal growth restriction: current knowledge to the general Obs/

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Pregnancy (ISSHP).

2004 Dec; 1031(1):242-8.

vitamin C and E to prevent

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2012 Apr 19; 2012.

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links in preventing preterm premature rupture of membranes? American journal of obstetrics and gynecology. 2001 Jul 1; 185(1):5-10.

[108] Hauth JC, Clifton RG, Roberts JM, Spong CY, Myatt L, Leveno KJ, Pearson GD, Varner MW, Thorp Jr JM, Mercer BM, Peaceman AM. Vitamin C and E supplementation to prevent spontaneous preterm birth. Obstetrics and gynecology. 2010 Sep;116(3):653.

[109] Al-Gubory KH. Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development. Reproductive BioMedicine Online. 2014 Jul 1; 29(1):17-31.

[110] Anderson K, Nisenblat V, Norman R. Lifestyle factors in people seeking infertility treatment–a review. Australian and New Zealand journal of obstetrics and gynaecology. 2010 Feb; 50(1):8-20.

[111] Sharma R, Biedenharn KR, Fedor JM, Agarwal A. Lifestyle factors and reproductive health: taking control of your fertility. Reproductive biology and endocrinology. 2013 Dec; 11(1):1-5.

[112] Al-Gubory KH, Fowler PA, Garrel C. The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. The international journal of biochemistry & cell biology. 2010 Oct 1; 42(10):1634-50.

[113] Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reproductive biology and endocrinology. 2012 Dec; 10(1):1-31.

[114] Evans MD, Dizdaroglu M, Cooke MS. Oxidative DNA damage and disease: induction, repair and significance. Mutation Research/

Reviews in Mutation Research. 2004 Sep 1; 567(1):1-61.

[115] Finaud J, Lac G, Filaire E. Oxidative stress. Sports medicine. 2006 Apr 1; 36(4):327-58.

[116] Agarwal A, Gupta S, Sharma R. Oxidative stress and its implications in female infertility–a clinician's perspective. Reproductive biomedicine online. 2005 Jan 1; 11(5):641-50.

[117] Agarwal A, Allamaneni SS, Said TM. Chemiluminescence technique for measuring reactive oxygen species. Reproductive BioMedicine Online. 2004 Jan 1; 9(4):466-8.

[118] Agarwal A, Nallella KP, Allamaneni SS, Said TM. Role of antioxidants in treatment of male infertility: an overview of the literature. Reproductive biomedicine online. 2004 Jan 1; 8(6):616-27.

[119] Harvey AJ, Kind KL, Thompson JG. REDOX regulation of early embryo development. Reproduction-Cambridge-. 2002 Apr 1; 123(4):479-86.

[120] Dennery PA. Role of redox in fetal development and neonatal diseases. Antioxidants and Redox Signaling. 2004 Feb 1; 6(1):147-53.

[121] Myatt L, Cui X. Oxidative stress in the placenta. Histochemistry and cell biology. 2004 Oct 1; 122(4):369-82.

[122] Sikkema JM, van Rijn BB, Franx A, Bruinse HW, de Roos R, Stroes ES, et al. Placental superoxide is increased in pre-eclampsia. Placenta. 2001; 22: 304-308.

[123] Fraser WD, Audibert F, Bujold E, Leduc L, Xu H, Boulvain M, Julien P. The vitamin E debate: implications for ongoing trials of pre-eclampsia prevention. BJOG: an international journal of obstetrics and gynaecology. 2005 Jun 1; 112(6):684-8.

#### *Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

[124] Poston L, Chappell L, Seed P, Shennan A. Biomarkers of oxidative stress in pre-eclampsia. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 2011 Jan 1; 1(1):22-7.

[125] Burton GW, Foster DO, Perly B, Slater TF, Smith IC, Ingold KU. Biological antioxidants. Philosophical Transactions of the Royal Society of London. B, Biological Sciences. 1985 Dec 17; 311(1152):565-78.

**117**

**Chapter 7**

**Abstract**

medicinal plants

**1. Introduction**

*1.1.1 Definition*

**1.1 Urinary stones - kidney stones**

on Vitamin E

Impact of Vitamins and Minerals

Enriched Flora in the Management

of Calciphytoliths: A Special Focus

Calciphytoliths (calcium oxalate calculi) have a great influence on human health and are a disease with a high likelihood of recurrence at a rate of more than 10% within a year. Plant flavonoids, saponins, and tannins are reported to be Litholytic by inhibiting calcium oxalate crystals or by their calcium channel blocking activity. Vitamins and minerals containing flora completely prevent deposition of oxalate by preventing pre-oxidation injury and restoring renal tissue antioxidants. So vitamin therapy also might protect against oxalate calculi deposition in the human kidneys. The present chapter discusses the impact of vitamins especially vitamin E, calcium, and low oxalate-containing plants for the

**Keywords:** calciphytoliths, prevention, vitamin E, vitamin C, calcium supplement,

Urinary stones are solid masses composed of a collection of small crystals which are formed and present in the urinary tract, due to the agglomeration of some components in the urine under certain physicochemical conditions. The urinary stone disease has a great influence on human health and is a disease with a high likelihood

Most urinary stones are formed in kidneys (80%), then migrate in the urine stream to other places of the urinary tract. When a stone appears at any part of the urinary system, it means a urinary stone disease. Thus, urinary stones include

of recurrence (or recurrent at a rate of more than 10% within a year).

kidney stones, ureteral stones, bladder stones, and urethral stones.

*Ramu Govindan, Tilak Meenakshisundaram,* 

*Duraiswamy Basavan and Dhanabal Palanisamy*

*Navanita Sivaramakumar, Podila Naresh,* 

management of various urinary or kidney disorders.

#### **Chapter 7**

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

[124] Poston L, Chappell L, Seed P, Shennan A. Biomarkers of oxidative stress in pre-eclampsia. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 2011

[125] Burton GW, Foster DO, Perly B, Slater TF, Smith IC, Ingold KU. Biological antioxidants. Philosophical Transactions of the Royal Society of London. B, Biological Sciences. 1985

Dec 17; 311(1152):565-78.

Jan 1; 1(1):22-7.

**116**

## Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths: A Special Focus on Vitamin E

*Ramu Govindan, Tilak Meenakshisundaram, Navanita Sivaramakumar, Podila Naresh, Duraiswamy Basavan and Dhanabal Palanisamy*

#### **Abstract**

Calciphytoliths (calcium oxalate calculi) have a great influence on human health and are a disease with a high likelihood of recurrence at a rate of more than 10% within a year. Plant flavonoids, saponins, and tannins are reported to be Litholytic by inhibiting calcium oxalate crystals or by their calcium channel blocking activity. Vitamins and minerals containing flora completely prevent deposition of oxalate by preventing pre-oxidation injury and restoring renal tissue antioxidants. So vitamin therapy also might protect against oxalate calculi deposition in the human kidneys. The present chapter discusses the impact of vitamins especially vitamin E, calcium, and low oxalate-containing plants for the management of various urinary or kidney disorders.

**Keywords:** calciphytoliths, prevention, vitamin E, vitamin C, calcium supplement, medicinal plants

#### **1. Introduction**

#### **1.1 Urinary stones - kidney stones**

#### *1.1.1 Definition*

Urinary stones are solid masses composed of a collection of small crystals which are formed and present in the urinary tract, due to the agglomeration of some components in the urine under certain physicochemical conditions. The urinary stone disease has a great influence on human health and is a disease with a high likelihood of recurrence (or recurrent at a rate of more than 10% within a year).

Most urinary stones are formed in kidneys (80%), then migrate in the urine stream to other places of the urinary tract. When a stone appears at any part of the urinary system, it means a urinary stone disease. Thus, urinary stones include kidney stones, ureteral stones, bladder stones, and urethral stones.

#### *Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

According to research, among cases of urinary stones on average, kidney stones (**Figure 1**) account for the highest proportion (40%), ureteral stones account for 28%, bladder stones account for 26% and urethral stones account for 4% (**Figure 2**).

#### *1.1.2 Epidemiological characteristics*

Urinary stone is a common disease in the world. The Urolithiasis prevalence in countries varies from 2–12% of the population, particularly with higher data as in the study of Albuquerque (Brazil), the rate of urinary stones is up to 14% and in 2014, nearly 4–15% of the population has urinary stone problems globally.

The incidence of urinary stones is related to age, gender, race, geographical environment, and eating habits [1].

Regarding gender, epidemiological studies showed that kidney stones are less common in women (6%) than in men (12%). The sex ratio ranges from 5: 1 in Japan to 15: 1 in Iran, but the likelihood of developing kidney stones is increasing in both

**Figure 1.** *Kidney stones.*

**119**

with 2–10%.

12.8% [8].

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

are at higher risk of urinary stones than other ethnic groups.

such as urinary tract infections or kidney failure.

found in the South [4].

drivers of this trend [6].

cal components.

*1.1.3 Classification of urinary stones*

genders [2]. The risk of kidney stones increases in men in their 40s and continues to increase until the age of 60s. Several studies show that white-skin people and men

The incidence of Urolithiasis is usually low among black-skin Americans but higher in Asian countries, typically in Thailand and India [3]. The regions with the highest percentage of kidney stones are called the "Stone Belt" in Humberger and Higgins maps. Vietnam is a country located in the "Stone Belt" of the world with a high incidence (40–60% of the total number of patients treated in the Urology department and has its special characteristics of stone disease including coming late to the hospital when the stones have enlarged; there are many serious complications

In India, about 12% of the population has Urolithiasis, of which 50% may suffer

People who live in rocky areas, where the climate is hot and dry, are more likely

Based on the composition of stones, kidney stones are classified into 2 groups with 6 common types including inorganic stones (Calcium, Oxalate, Phosphate) and organic stones (Cystine, Struvite, and Uric acid). Each type has different causes as well as different methods of treatment. Stones often exist as a mixture of chemi-

A collaborative study in France involving 51,747 stones, in mid-January 2001 and December 2004 by many laboratories showed that Calcium oxalate (CaOx) is the most common ingredient accounting for 71.8% of stones. Calcium phosphate

Among the types of kidney stones, CaOx is the most common type. Calcium oxalate stones have two types including calcium oxalate monohydrate (whewellite) and calcium oxalate dehydrates (weddellite). The incidence of whewellite is 78% while that of weddellite is 43% [7]. Whewellite is highly capable of agglomerating, tightly binds to renal tubular epithelial cells, and retained forming stones. Whewellite accounts for 39% in men and 37.4% in women. Weddellite does not agglomerate into stable masses, does not attach to renal tubular epithelial cells and

In Vietnam, all stone samples analyzed have two or more components, of which the most common component is calcium oxalate (90.7% of incidence), followed by

It was observed that urinary stones in England, Scotland, and Sudan are mainly composed of a mixture of calcium oxalate and calcium phosphate. Meanwhile, uric acid stones in the upper urinary tract are quite common in Israel. In Saudi Arabia, calcium stones make up the majority (84.6%), uric acid stones account for

In India, calcium oxalate stones are found to be the most important component of Urolithiasis. Calcium oxalate stones make up 80% of the analyzed stones. Calcium phosphate stones account for 15–25%, while 10–15% is mixed stones. The others are struvite with 15–30%, cystine with 6–10%, and uric acid stones

accounts for 13.6% and Uric acid accounts for 10.8% of the total stones.

is easily swept with urine, and difficult to form urinary stones.

calcium phosphate, struvite, ammonium urate, and cysteine.

kidney loss or kidney damage. The incidence of Urolithiasis is prevalent in the North of India (nearly 15% of the population), while this disease is less commonly

to get urinary stones [5]. The incidence of urinary stones has been increasing globally. Dietary changes, as well as the effects of global warming, can be the major

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

**Figure 2.** *Kidney stone position.*

#### *Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths… DOI: http://dx.doi.org/10.5772/intechopen.97777*

genders [2]. The risk of kidney stones increases in men in their 40s and continues to increase until the age of 60s. Several studies show that white-skin people and men are at higher risk of urinary stones than other ethnic groups.

The incidence of Urolithiasis is usually low among black-skin Americans but higher in Asian countries, typically in Thailand and India [3]. The regions with the highest percentage of kidney stones are called the "Stone Belt" in Humberger and Higgins maps. Vietnam is a country located in the "Stone Belt" of the world with a high incidence (40–60% of the total number of patients treated in the Urology department and has its special characteristics of stone disease including coming late to the hospital when the stones have enlarged; there are many serious complications such as urinary tract infections or kidney failure.

In India, about 12% of the population has Urolithiasis, of which 50% may suffer kidney loss or kidney damage. The incidence of Urolithiasis is prevalent in the North of India (nearly 15% of the population), while this disease is less commonly found in the South [4].

People who live in rocky areas, where the climate is hot and dry, are more likely to get urinary stones [5]. The incidence of urinary stones has been increasing globally. Dietary changes, as well as the effects of global warming, can be the major drivers of this trend [6].

#### *1.1.3 Classification of urinary stones*

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

4% (**Figure 2**).

*1.1.2 Epidemiological characteristics*

environment, and eating habits [1].

According to research, among cases of urinary stones on average, kidney stones (**Figure 1**) account for the highest proportion (40%), ureteral stones account for 28%, bladder stones account for 26% and urethral stones account for

Urinary stone is a common disease in the world. The Urolithiasis prevalence in countries varies from 2–12% of the population, particularly with higher data as in the study of Albuquerque (Brazil), the rate of urinary stones is up to 14% and in

The incidence of urinary stones is related to age, gender, race, geographical

Regarding gender, epidemiological studies showed that kidney stones are less common in women (6%) than in men (12%). The sex ratio ranges from 5: 1 in Japan to 15: 1 in Iran, but the likelihood of developing kidney stones is increasing in both

2014, nearly 4–15% of the population has urinary stone problems globally.

**118**

**Figure 2.**

**Figure 1.** *Kidney stones.*

*Kidney stone position.*

Based on the composition of stones, kidney stones are classified into 2 groups with 6 common types including inorganic stones (Calcium, Oxalate, Phosphate) and organic stones (Cystine, Struvite, and Uric acid). Each type has different causes as well as different methods of treatment. Stones often exist as a mixture of chemical components.

A collaborative study in France involving 51,747 stones, in mid-January 2001 and December 2004 by many laboratories showed that Calcium oxalate (CaOx) is the most common ingredient accounting for 71.8% of stones. Calcium phosphate accounts for 13.6% and Uric acid accounts for 10.8% of the total stones.

Among the types of kidney stones, CaOx is the most common type. Calcium oxalate stones have two types including calcium oxalate monohydrate (whewellite) and calcium oxalate dehydrates (weddellite). The incidence of whewellite is 78% while that of weddellite is 43% [7]. Whewellite is highly capable of agglomerating, tightly binds to renal tubular epithelial cells, and retained forming stones. Whewellite accounts for 39% in men and 37.4% in women. Weddellite does not agglomerate into stable masses, does not attach to renal tubular epithelial cells and is easily swept with urine, and difficult to form urinary stones.

In Vietnam, all stone samples analyzed have two or more components, of which the most common component is calcium oxalate (90.7% of incidence), followed by calcium phosphate, struvite, ammonium urate, and cysteine.

In India, calcium oxalate stones are found to be the most important component of Urolithiasis. Calcium oxalate stones make up 80% of the analyzed stones. Calcium phosphate stones account for 15–25%, while 10–15% is mixed stones. The others are struvite with 15–30%, cystine with 6–10%, and uric acid stones with 2–10%.

It was observed that urinary stones in England, Scotland, and Sudan are mainly composed of a mixture of calcium oxalate and calcium phosphate. Meanwhile, uric acid stones in the upper urinary tract are quite common in Israel. In Saudi Arabia, calcium stones make up the majority (84.6%), uric acid stones account for 12.8% [8].

#### *1.1.4 Causes and mechanism of formation of kidney stones*

#### *1.1.4.1 Causes*

The generation and formation of urinary stones come from different sources that are not only caused by any group of reasons but due to a combination of factors including diet, diseases in the body, and genetic factors which together form urinary stones. Factors leading to the risk of kidney stones include

1.**Not drinking enough water** (<1,200 ml/day) makes the urine more concentrated with minerals such as calcium and phosphorus leading to the risk of kidney stones.

#### 2.**Eating more animal protein in the diet**

High animal protein in food causes acidosis of urine, creating conditions for crystals as uric acid to crystallize to stones. Eating a lot of sodium (salty foods) causes an increase in the renal tubular sodium and this will reduce the reabsorption of calcium there. Also, studies by scientists from Ahvaz University of Medical Sciences, Iran showed that there is an intimate relationship between the consumption of purines, calcium oxalate foods, and the formation of stones [9].

#### 3.**Genetics**

Families with a regular incidence of developing stones (an abnormal amount of calcium filtered into the urinary tract) are at higher risk of kidney stones than other families.


#### 6.**Improper calcium supplementation**

Pregnant women often need a supplement with a lot of vitamins and minerals, including calcium. However, calcium excess causes kidney stones. Moreover, calcium content is usually absorbed better during pregnancy. Therefore, both of these factors increase the risks. Pregnant women with urinary tract infections should discuss with their doctor for appropriate examination and treatment.

#### 7.**Occupation**

Urinary stones are closely related to the profession of the patients. People who work in a hot environment like metallurgists, construction workers, sailors, stressed-minded workers like doctors, officers, etc. are more likely to be in the disease than those who are unskilled laborers.

8.Another reason causing kidney stones is long-term treatment with certain medication. It is believed that 1–2% of kidney stones are drug-induced. Certain medications including the antiviral drug Indinavir, Triamterene (diuretic), Sulfadiazine (an antibiotic) as well as Ephedrine and Guaifenesin are known as a cause of kidney stones [10].

**121**

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

Also, different reasons for stone formation purely depend on stone type such as

The main reason is due to the state of oversaturated urine with calcium salts causing by the increase of calcium absorption in the intestine or the increase of calcium reabsorption in the renal tubular region. Causes that increase the concentration of calcium in the urine are hyperparathyroidism, major bone fractures, and immobilization for a long time, taking lots of Vitamin D and Corticoid, metastases of cancer through the bone, causing bone destruction. However in many cases not able to find the reason for calcium increase in urine. High level

is not a determinant of urinary stone formation but a favorable factor.

This type of stone account for a high proportion in tropical countries like Vietnam and India. Oxalate is often combined with calcium to form calcium oxalate stones and 2/3 of stones in oxalate stone are due to the insoluble calcium oxalate salt. When the urine is saturated with oxalate, by eating foods and vegetables which are high in oxalate and poor in calcium, these molecules will pass through the digestive tract and be excreted as waste. When passing through the intestine, oxalate can combine with calcium to form calcium oxalate and be excreted in the waste. Having too much oxalate in the kidneys can lead to kidney stones. According to Prien, lack of vitamin B6 in the body is a cause of oxalate stones. Experiments in rats showed that vitamin B6-deficient foods produce in the renal tubule and thorn the Randalllike lesions in kidneys and oxalates are crystallized. In contrast, vitamin B6 will

A common type of phosphate stone is ammonium-magnate-phosphate (struvite stone), accounting for 5–15% of the number of stones. This type of stone has a large

Stones are formed as a result of a bacterial infection, especially proteus bacteria in the urinary system. This bacterium releases the urease enzyme, which breaks down urea into ammonia, making urine alkaline, resulting in a reduction in

With the increase of uric acid concentration in blood, in addition to deposition in cartilage, mucous membranes, muscle skin, the concentration of uric acid in the kidneys also increase. Uric acid deposition in kidneys is a major cause of uric acid stones, which is more common in gout patients (the result of nucleic acid metabolism disorders). Possible causes of purine metabolism increase include the intake of purine-rich foods such as pig intestine, dried fish, meat, and mushrooms. It is noted that uric acid is soluble in an alkaline environment and crystallizes in an acidic environment when urine pH is below 6. Accordingly, acidified urine is a

Stones are formed when cystine is excreted to the kidneys but less soluble making it easily be deposited. The stone is often congenital with the disorders of cystine reuptake transport and some other amino acids such as lysine and arginine in the

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

reduce the excretion of oxalate in urine.

size, coral shape, and is in contrast.

good environment for forming stones.

struvite solubility which facilitates stone formation.

1.**Calcium stones**

2.**Oxalate stone**

3.**Phosphate stones**

4.**Uric acid stones**

5.**Cystine stones**

Also, different reasons for stone formation purely depend on stone type such as

### 1.**Calcium stones**

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

urinary stones. Factors leading to the risk of kidney stones include

The generation and formation of urinary stones come from different sources that are not only caused by any group of reasons but due to a combination of factors including diet, diseases in the body, and genetic factors which together form

1.**Not drinking enough water** (<1,200 ml/day) makes the urine more concentrated with minerals such as calcium and phosphorus leading to the risk of

High animal protein in food causes acidosis of urine, creating conditions for crystals as uric acid to crystallize to stones. Eating a lot of sodium (salty foods) causes an increase in the renal tubular sodium and this will reduce the reabsorption of calcium there. Also, studies by scientists from Ahvaz University of Medical Sciences, Iran showed that there is an intimate relationship between the consumption of purines, calcium oxalate foods, and the formation of

Families with a regular incidence of developing stones (an abnormal amount of calcium filtered into the urinary tract) are at higher risk of kidney stones than

4.Chronic enterocolitis leads to kidney stone formation during pregnancy.

5.The increase in parathyroid activity is another reason. Hyperparathyroidism can be either a primary or secondary method, increasing calcium reabsorption

Pregnant women often need a supplement with a lot of vitamins and minerals, including calcium. However, calcium excess causes kidney stones. Moreover, calcium content is usually absorbed better during pregnancy. Therefore, both of these factors increase the risks. Pregnant women with urinary tract infections should discuss with their doctor for appropriate examination and treatment.

Urinary stones are closely related to the profession of the patients. People who work in a hot environment like metallurgists, construction workers, sailors, stressed-minded workers like doctors, officers, etc. are more likely to be in the

8.Another reason causing kidney stones is long-term treatment with certain

medication. It is believed that 1–2% of kidney stones are drug-induced. Certain medications including the antiviral drug Indinavir, Triamterene (diuretic), Sulfadiazine (an antibiotic) as well as Ephedrine and Guaifenesin are known as

*1.1.4 Causes and mechanism of formation of kidney stones*

2.**Eating more animal protein in the diet**

from bone and leading to hypercalciuria.

disease than those who are unskilled laborers.

a cause of kidney stones [10].

6.**Improper calcium supplementation**

*1.1.4.1 Causes*

kidney stones.

stones [9].

3.**Genetics**

other families.

7.**Occupation**

**120**

The main reason is due to the state of oversaturated urine with calcium salts causing by the increase of calcium absorption in the intestine or the increase of calcium reabsorption in the renal tubular region. Causes that increase the concentration of calcium in the urine are hyperparathyroidism, major bone fractures, and immobilization for a long time, taking lots of Vitamin D and Corticoid, metastases of cancer through the bone, causing bone destruction. However in many cases not able to find the reason for calcium increase in urine. High level is not a determinant of urinary stone formation but a favorable factor.

#### 2.**Oxalate stone**

This type of stone account for a high proportion in tropical countries like Vietnam and India. Oxalate is often combined with calcium to form calcium oxalate stones and 2/3 of stones in oxalate stone are due to the insoluble calcium oxalate salt. When the urine is saturated with oxalate, by eating foods and vegetables which are high in oxalate and poor in calcium, these molecules will pass through the digestive tract and be excreted as waste. When passing through the intestine, oxalate can combine with calcium to form calcium oxalate and be excreted in the waste. Having too much oxalate in the kidneys can lead to kidney stones. According to Prien, lack of vitamin B6 in the body is a cause of oxalate stones. Experiments in rats showed that vitamin B6-deficient foods produce in the renal tubule and thorn the Randalllike lesions in kidneys and oxalates are crystallized. In contrast, vitamin B6 will reduce the excretion of oxalate in urine.

#### 3.**Phosphate stones**

A common type of phosphate stone is ammonium-magnate-phosphate (struvite stone), accounting for 5–15% of the number of stones. This type of stone has a large size, coral shape, and is in contrast.

Stones are formed as a result of a bacterial infection, especially proteus bacteria in the urinary system. This bacterium releases the urease enzyme, which breaks down urea into ammonia, making urine alkaline, resulting in a reduction in struvite solubility which facilitates stone formation.

#### 4.**Uric acid stones**

With the increase of uric acid concentration in blood, in addition to deposition in cartilage, mucous membranes, muscle skin, the concentration of uric acid in the kidneys also increase. Uric acid deposition in kidneys is a major cause of uric acid stones, which is more common in gout patients (the result of nucleic acid metabolism disorders). Possible causes of purine metabolism increase include the intake of purine-rich foods such as pig intestine, dried fish, meat, and mushrooms. It is noted that uric acid is soluble in an alkaline environment and crystallizes in an acidic environment when urine pH is below 6. Accordingly, acidified urine is a good environment for forming stones.

#### 5.**Cystine stones**

Stones are formed when cystine is excreted to the kidneys but less soluble making it easily be deposited. The stone is often congenital with the disorders of cystine reuptake transport and some other amino acids such as lysine and arginine in the

renal tubules and intestinal mucosa. Cystine stones are usually simple and rarely combine with other stones [11].

#### *1.1.4.2 Mechanism and development of stones*

The formation of stones in the body is a complex process, which is a result of a series of physicochemical processes including five main stages: (i) oversaturation of substances dissolved in urine (ii) nuclear formation (iii) nuclear proliferation (iv) crystallization and (v) crystals attachment to epithelial cells of renal tubules [12].

Oversaturation of substances that are capable to crystallize in urine is a phenomenon of concentration of a substance being able to crystallize in urine exceeds its solubility. There are many causes of urine oversaturation, including a change in urine pH, decrease in urine volume or metabolic disorder that increases the elimination of one or several substances through kidneys, imbalances in urine calcium excretion, hypercalciuria which is familiar or idiopathic, imbalance in oxalate excretion, reduction in urinary citrate and hyperuricemia due to purine-rich foods. It not only depends on the concentration of the stone formation substances but also depends on other factors such as urine pH, the ions representing inhibitors of the stone formation process such as citrate, pyrophosphate, magnesium, ribonucleic acid, and glycosaminoglycan.

#### *1.1.4.2.1 Crystal nucleus formation*

In oversaturated urine, free ions tend to coalesce into very small particles. The result of this process is the formation of a crystal nucleus which may be singlecomponent or multi-component. In urine, a crystal nucleus can be formed on the structure of cellular debris and urinary crystals. The majority of urinary stones is a mixture of more than two substances. When there is a saturation of calcium or oxalate by urine when passing through the renal tubules, it will form a nucleus making COD form (which is common in the urine of healthy people) and COM form (mostly common in urinary stones).

#### *1.1.4.2.2 Nuclear proliferation*

It is the process of a nucleus which is made up of very small size continues to grow during the movement in the urinary tract, through the transferring of free ions in the solution into the crystals. This process does not cause any problems if the crystals are easily removed (as stones that are less than 5 mm in diameter). Larger stones are difficult to be excreted causing the blockage, pain, injury, and bleeding during urinary tract movement. However, this process takes a long time. Therefore in the process of moving through the nephron (5–7 minutes), the growth of crystals will not reach a large size which is enough to obstruct the renal tubules. The growth of the crystal is then explained by the aggregation of small crystals or the creation of secondary nuclei on the initial crystal surface.

#### *1.1.4.2.3 Crystal aggregation*

It is the process of linking small crystals together by chemical or electrostatic forces to form large crystals. For oxalate stones, the formation of urinary stones from COD crystals is difficult because COD crystals do not coalesce into stable masses, do not attach to the tubular epithelial cells and so they have easily swept away with urine. COM crystals are highly agglomerated and can bind tightly to tubular epithelial cells and be trapped facilitating the formation of stones.

**123**

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

The mechanism of this process is still unclear and explained by many different theories. The first theory is that stone crystals are formed in the kidney's lumen, where they aggregate, grow to a size large enough to block the renal tubules, and be trapped there. The second theory also states that stone crystals are formed in the renal tubules but suggests that crystals are formed by the development of apatite plaques and attached to a certain location at the surface of the tubular epithelial cells and structures present in the renal papillae also known as Randall's plaque. Various studies have confirmed the role of microscopic lesions in kidneys in the formation of kidney stones. These lesions were detected in causing urinary stones

After forming, if the stone is small, it usually passes through the urine and is expelled. But if the stone is trapped somewhere in the urinary tract, it will grow larger obstructing the flow of urine, leading to stagnation and swelling above the blockage and causing many symptoms such as obstruction, infection, additional

If urolithiasis is not monitored and treated promptly, it can lead to many serious

If ureters are completely obstructed, the renal pelvis dilates, and after 6 weeks

It may be occurred due to a severe obstruction (completely or near completely) on both sides of the ureters. Kidney failure occurs in the case of ureteral stones on one side but creating vasoconstriction on both sides causing anuria. Clinical manifestations are anuria, urea test, creatinine, a rapid increase of potassium (K+)

Chronic pyelonephritis is the most severe consequence of kidney and urinary

Symptoms of kidney stones can range from asymptomatic to the frequency of mild and uncomfortable urination, then severe colic in the abdomen, hips, and lower back. When a stone passes through the ureter, it can cause hematuria, severe pain, nausea, vomiting, diarrhea, sweating, and a fast heartbeat. In severe cases, kidney stones can obstruct the urinary tract, scar, kidney infections, and

stones because it is no longer able to recover due to gradual renal fibrosis.

the renal parenchyma may not recover. The consequence of water retention is

complications such as urinary tract infections, kidney failure even death.

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

*1.1.4.2.4 Crystal attachment to kidney cells*

by a model that causes an increase of urinary oxalate.

stones, and gradual destruction of kidney structure.

*1.1.5.1 Common and dangerous complications*

*1.1.5.1.1 Obstruction is a severe acute complication*

structural damage leading to functional damage.

*1.1.5.1.2 Acute renal failure*

in blood, and metabolic acidosis.

*1.1.5.1.3 Chronic renal failure*

*1.1.6 Symptoms*

kidney damage.

*1.1.5 Harmful effects*

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths… DOI: http://dx.doi.org/10.5772/intechopen.97777*

#### *1.1.4.2.4 Crystal attachment to kidney cells*

The mechanism of this process is still unclear and explained by many different theories. The first theory is that stone crystals are formed in the kidney's lumen, where they aggregate, grow to a size large enough to block the renal tubules, and be trapped there. The second theory also states that stone crystals are formed in the renal tubules but suggests that crystals are formed by the development of apatite plaques and attached to a certain location at the surface of the tubular epithelial cells and structures present in the renal papillae also known as Randall's plaque. Various studies have confirmed the role of microscopic lesions in kidneys in the formation of kidney stones. These lesions were detected in causing urinary stones by a model that causes an increase of urinary oxalate.

#### *1.1.5 Harmful effects*

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

combine with other stones [11].

acid, and glycosaminoglycan.

*1.1.4.2.1 Crystal nucleus formation*

(mostly common in urinary stones).

of secondary nuclei on the initial crystal surface.

*1.1.4.2.2 Nuclear proliferation*

*1.1.4.2.3 Crystal aggregation*

*1.1.4.2 Mechanism and development of stones*

renal tubules and intestinal mucosa. Cystine stones are usually simple and rarely

The formation of stones in the body is a complex process, which is a result of a series of physicochemical processes including five main stages: (i) oversaturation of substances dissolved in urine (ii) nuclear formation (iii) nuclear proliferation (iv) crystallization and (v) crystals attachment to epithelial cells of renal tubules [12]. Oversaturation of substances that are capable to crystallize in urine is a phenomenon of concentration of a substance being able to crystallize in urine exceeds its solubility. There are many causes of urine oversaturation, including a change in urine pH, decrease in urine volume or metabolic disorder that increases the elimination of one or several substances through kidneys, imbalances in urine calcium excretion, hypercalciuria which is familiar or idiopathic, imbalance in oxalate excretion, reduction in urinary citrate and hyperuricemia due to purine-rich foods. It not only depends on the concentration of the stone formation substances but also depends on other factors such as urine pH, the ions representing inhibitors of the stone formation process such as citrate, pyrophosphate, magnesium, ribonucleic

In oversaturated urine, free ions tend to coalesce into very small particles. The result of this process is the formation of a crystal nucleus which may be singlecomponent or multi-component. In urine, a crystal nucleus can be formed on the structure of cellular debris and urinary crystals. The majority of urinary stones is a mixture of more than two substances. When there is a saturation of calcium or oxalate by urine when passing through the renal tubules, it will form a nucleus making COD form (which is common in the urine of healthy people) and COM form

It is the process of a nucleus which is made up of very small size continues to grow during the movement in the urinary tract, through the transferring of free ions in the solution into the crystals. This process does not cause any problems if the crystals are easily removed (as stones that are less than 5 mm in diameter). Larger stones are difficult to be excreted causing the blockage, pain, injury, and bleeding during urinary tract movement. However, this process takes a long time. Therefore in the process of moving through the nephron (5–7 minutes), the growth of crystals will not reach a large size which is enough to obstruct the renal tubules. The growth of the crystal is then explained by the aggregation of small crystals or the creation

It is the process of linking small crystals together by chemical or electrostatic forces to form large crystals. For oxalate stones, the formation of urinary stones from COD crystals is difficult because COD crystals do not coalesce into stable masses, do not attach to the tubular epithelial cells and so they have easily swept away with urine. COM crystals are highly agglomerated and can bind tightly to tubular epithelial cells and be trapped facilitating the formation of stones.

**122**

After forming, if the stone is small, it usually passes through the urine and is expelled. But if the stone is trapped somewhere in the urinary tract, it will grow larger obstructing the flow of urine, leading to stagnation and swelling above the blockage and causing many symptoms such as obstruction, infection, additional stones, and gradual destruction of kidney structure.

If urolithiasis is not monitored and treated promptly, it can lead to many serious complications such as urinary tract infections, kidney failure even death.

#### *1.1.5.1 Common and dangerous complications*

#### *1.1.5.1.1 Obstruction is a severe acute complication*

If ureters are completely obstructed, the renal pelvis dilates, and after 6 weeks the renal parenchyma may not recover. The consequence of water retention is structural damage leading to functional damage.

#### *1.1.5.1.2 Acute renal failure*

It may be occurred due to a severe obstruction (completely or near completely) on both sides of the ureters. Kidney failure occurs in the case of ureteral stones on one side but creating vasoconstriction on both sides causing anuria. Clinical manifestations are anuria, urea test, creatinine, a rapid increase of potassium (K+) in blood, and metabolic acidosis.

#### *1.1.5.1.3 Chronic renal failure*

Chronic pyelonephritis is the most severe consequence of kidney and urinary stones because it is no longer able to recover due to gradual renal fibrosis.

#### *1.1.6 Symptoms*

Symptoms of kidney stones can range from asymptomatic to the frequency of mild and uncomfortable urination, then severe colic in the abdomen, hips, and lower back. When a stone passes through the ureter, it can cause hematuria, severe pain, nausea, vomiting, diarrhea, sweating, and a fast heartbeat. In severe cases, kidney stones can obstruct the urinary tract, scar, kidney infections, and kidney damage.

It was identified that pain in the lumbar region is the main symptom of ureteral stones; renal colic occurs when stones move and cause edematous inflammation and acute ureteral obstruction.

#### *1.1.7 Treatments*

The choice of treatment method depends on many factors such as the size of stones, the severity of symptoms, the degree of obstruction, kidney function, the location of stones, and whether or not the infection is present.

### **2. Applications of medicinal plants in the management of kidney stones**

#### **2.1 Some effects of natural medicines in the treatment of kidney stones**

The use of drugs which are from herbal plants in the treatment of kidney stones is increasingly common but its majority comes from folk remedies. In recent years, there have been many studies of scientists on the treatment effects of medicinal plants for kidney stones.

Proven studies have shown the action mechanism of herbal extracts on the treatment and the relapse prevention of kidney stones, including


The antioxidant activity of medicinal plants also helps to prevent urinary cell damage. Some promising plants containing vitamin E, vitamin C, and calcium showing their antioxidant and anti-urolithic activity demonstrated through *in vivo* and *in vitro* studies are discussed below.

#### *2.1.1 Flax*

Flax (*Linum usitatissimum* L) in the genus Linum, which belongs to the Linaceae family, is an annual herb with green flowers, produces different small flat seeds

**125**

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

ranging from yellow to reddish-brown color. The plant is 40–70 cm tall, smooth, with only branches in the upper part. Leaves are staggered, spear-shaped, 1–3 cm long, and 0.3 cm wide with three ribs. Flowers often grow individually with 5 blue petals; petals are three times longer than sepals. The capsule has smooth walls, divided into 10 cells containing one grain in each. The grain is oval, long, pointed,

Since ancient times, flax has been grown for fiber or seeds using for medicinal purposes and as nutritional products [13]. Currently, flax is grown in more than 50 countries, mainly in the Northern Hemisphere. Canada is the world's largest producer and exporter of flaxseeds [14]. Important developing countries for flaxseed include India, China, United States, and Ethiopia [15, 16]. India ranks first among the top flaxseed producing countries in terms of area, accounting for 23.8% of total production and third in production, contributing to 10.2% of world production [16]. In India, flaxseeds are mainly grown in Madhya Pradesh, Maharashtra, Chattisgarh, and Bihar. The bark of the plant has good fiber quality and high

Flaxseeds, also known as Linseed, have a crunchy texture and chestnut flavor [17, 18]. Seeds with oil after refining are used for edible purposes [16]. People have been consuming flaxseeds since ancient times. In India, flaxseeds are still being consumed as food and also for medicinal purposes [19]. It has an important position among oilseeds because of its versatility. It is considered an attractive nutritional food because of its exceptionally high content of alpha-linolenic acid (ALA), high-quality fiber and protein, lignans, vitamin E, phenolic compounds, and

Flaxseeds contain about 55% of alpha-linolenic acid (ALA), 30% of protein and 35% of fiber [18, 20, 21]. Flaxseed oil has alpha-linolenic fatty acid, which is an essential acid (ALA). From these facts, the body will convert to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Flaxseeds are increasingly considered by nutritionists and medical researchers due to their potential health benefits associated with bioactive components, lignan-secoisolariciresinol glycoside (SDG), and dietary fiber [22]. The composition of flaxseeds is presented in **Figure 3** [17, 23, 24]. Flaxseed oil has alpha-linolenic fatty acid, which is an essential acid (ALA). From these facts, the body will convert to eicosapentaenoic

The chemical composition of flaxseed depends on its growing environment, genetics, and processing conditions [17]. The lipid content of flaxseeds varies from 37 to 45 g/100 g of seeds as reported by various scientists [17, 20, 24]. Cotyledons

Flaxseed oil makes up 98% of triacylglycerol, phospholipids, and 0.1% of free fatty acids [26]. On average it contains 21% protein. The majority of protein is concentrated in cotyledons [21]. The main protein segments are globulin (26–58%) and albumin (20–42%). The nutritional value and amino acid content of flaxseeds

Flaxseed protein is rich in arginine, aspartic acid, and glutamic acid, while lysine is restricted [16, 25, 29]. A high content of cysteine and methionine improves antioxidant content, thereby reducing the risk of cancer [14]. Treatment, de-heat, and defatting conditions affect protein content. Defatted and de-heat meals are high in protein [15, 30]. Flaxseed protein exhibits antifungal properties against *Alternaria* 

are the main oil storage tissues containing 75% of seed oil [16, 18, 25].

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

durability, so it is used to weave cloth.

glossy, and brown.

phytoestrogen.

*2.1.1.1 Chemical composition*

acid (EPA) and docosahexaenoic acid (DHA).

are equivalent to that of soy-bean protein [27, 28].

*solani, Candida albicans,* and *Aspergillus flavus* [31, 32].

#### *Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths… DOI: http://dx.doi.org/10.5772/intechopen.97777*

ranging from yellow to reddish-brown color. The plant is 40–70 cm tall, smooth, with only branches in the upper part. Leaves are staggered, spear-shaped, 1–3 cm long, and 0.3 cm wide with three ribs. Flowers often grow individually with 5 blue petals; petals are three times longer than sepals. The capsule has smooth walls, divided into 10 cells containing one grain in each. The grain is oval, long, pointed, glossy, and brown.

Since ancient times, flax has been grown for fiber or seeds using for medicinal purposes and as nutritional products [13]. Currently, flax is grown in more than 50 countries, mainly in the Northern Hemisphere. Canada is the world's largest producer and exporter of flaxseeds [14]. Important developing countries for flaxseed include India, China, United States, and Ethiopia [15, 16]. India ranks first among the top flaxseed producing countries in terms of area, accounting for 23.8% of total production and third in production, contributing to 10.2% of world production [16]. In India, flaxseeds are mainly grown in Madhya Pradesh, Maharashtra, Chattisgarh, and Bihar. The bark of the plant has good fiber quality and high durability, so it is used to weave cloth.

Flaxseeds, also known as Linseed, have a crunchy texture and chestnut flavor [17, 18]. Seeds with oil after refining are used for edible purposes [16]. People have been consuming flaxseeds since ancient times. In India, flaxseeds are still being consumed as food and also for medicinal purposes [19]. It has an important position among oilseeds because of its versatility. It is considered an attractive nutritional food because of its exceptionally high content of alpha-linolenic acid (ALA), high-quality fiber and protein, lignans, vitamin E, phenolic compounds, and phytoestrogen.

#### *2.1.1.1 Chemical composition*

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

location of stones, and whether or not the infection is present.

acute ureteral obstruction.

plants for kidney stones.

urinary tract.

saturation.

*1.1.7 Treatments*

It was identified that pain in the lumbar region is the main symptom of ureteral stones; renal colic occurs when stones move and cause edematous inflammation and

The choice of treatment method depends on many factors such as the size of stones, the severity of symptoms, the degree of obstruction, kidney function, the

**2. Applications of medicinal plants in the management of kidney stones**

The use of drugs which are from herbal plants in the treatment of kidney stones is increasingly common but its majority comes from folk remedies. In recent years, there have been many studies of scientists on the treatment effects of medicinal

Proven studies have shown the action mechanism of herbal extracts on the

2.An alkaline urine and inhibit the process of crystallization of stones on the

4.Reduce the deposition of crystals on tissue and in the lumen of kidneys.

7.Support diuretic, analgesic, and anti-inflammatory activities.

reduce the recurrence of kidney stones.

and *in vitro* studies are discussed below.

5.Enhance the concentration of inhibitors of stone formation in the kidneys to increase urine citrate excretion, reduce calcium and oxalate excretion in urine.

6.Reduce the concentration of calcium in kidney tissue and improve the state of

8.Balance electrolytes and minerals and regulate oxalate metabolism helping to

The antioxidant activity of medicinal plants also helps to prevent urinary cell damage. Some promising plants containing vitamin E, vitamin C, and calcium showing their antioxidant and anti-urolithic activity demonstrated through *in vivo*

Flax (*Linum usitatissimum* L) in the genus Linum, which belongs to the Linaceae

family, is an annual herb with green flowers, produces different small flat seeds

3.Inhibit stone formation by preventing calcium oxalate nucleation and the growth of calcium oxalate crystals, inhibiting synthesis and accumulation of the crystals.

**2.1 Some effects of natural medicines in the treatment of kidney stones**

treatment and the relapse prevention of kidney stones, including

1.Help to erode and reduce stone size naturally.

**124**

*2.1.1 Flax*

Flaxseeds contain about 55% of alpha-linolenic acid (ALA), 30% of protein and 35% of fiber [18, 20, 21]. Flaxseed oil has alpha-linolenic fatty acid, which is an essential acid (ALA). From these facts, the body will convert to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Flaxseeds are increasingly considered by nutritionists and medical researchers due to their potential health benefits associated with bioactive components, lignan-secoisolariciresinol glycoside (SDG), and dietary fiber [22]. The composition of flaxseeds is presented in **Figure 3** [17, 23, 24]. Flaxseed oil has alpha-linolenic fatty acid, which is an essential acid (ALA). From these facts, the body will convert to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

The chemical composition of flaxseed depends on its growing environment, genetics, and processing conditions [17]. The lipid content of flaxseeds varies from 37 to 45 g/100 g of seeds as reported by various scientists [17, 20, 24]. Cotyledons are the main oil storage tissues containing 75% of seed oil [16, 18, 25].

Flaxseed oil makes up 98% of triacylglycerol, phospholipids, and 0.1% of free fatty acids [26]. On average it contains 21% protein. The majority of protein is concentrated in cotyledons [21]. The main protein segments are globulin (26–58%) and albumin (20–42%). The nutritional value and amino acid content of flaxseeds are equivalent to that of soy-bean protein [27, 28].

Flaxseed protein is rich in arginine, aspartic acid, and glutamic acid, while lysine is restricted [16, 25, 29]. A high content of cysteine and methionine improves antioxidant content, thereby reducing the risk of cancer [14]. Treatment, de-heat, and defatting conditions affect protein content. Defatted and de-heat meals are high in protein [15, 30]. Flaxseed protein exhibits antifungal properties against *Alternaria solani, Candida albicans,* and *Aspergillus flavus* [31, 32].

#### *Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

#### *2.1.1.2 Pharmacological effects and uses*

Scientists are interested in flaxseed for its health benefits due to its high content of α-linolenic acid and lignans. Natural treatment agents which have the effects on lipid-lowering, antioxidant, anti-inflammatory, and antihypertensive are expected to have a protective effect on the kidneys.

**127**

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

For kidney stones, flaxseeds may help reduce the amount of calcium in the urine. Daily intake of organic, unrefined, and cold-pressed flaxseed oil has been shown to

William F. Clark, Anwar Parbtani (1995) studied the impact of flaxseed on immune and renal damage models. ALA in flax constituents has been shown to have anti-inflammatory and anti-thrombotic properties, while flaxseed lignans have been reported as platelet-activating factor receptor antagonists (PAF). PAF contributes to the inflammatory response in progressive glomerulonephritis. The authors conclude that results from animal and human studies indicated that flaxseeds provide significant benefits in kidney function as well as important atherogenic and inflammatory mechanisms in the pathogenesis of lupus nephritis. Thereby, the authors recommend long-term studies with flaxseeds as a potential treatment for

lupus nephritis and other forms of progressive kidney diseases [33].

According to research by the University of Manitoba and the Manitoba Children's Health Institute, Winnipeg, Man., Canada (2007), late intervention with soy protein and flaxseed oil in the diet has reduced the number of diseases related to multipurpose kidney diseases which were present in the rat. The potential benefits of antioxidant and anti-inflammatory effects on kidney disease results are

According to the report on "medical and dietary therapies for the prevention of kidney stones" by Zeyneplrul and Manoj Monga (2014), the main source of polyunsaturated fats in the Western diet is arachidonic acid (AA) an n-6 fatty acid found in vegetable oils and animal fats. N-6 fatty acids are involved in stone formation. The breakdown of AA leads to the formation of precursors including prostaglandin E2

PGE2 causes hypercalciuria because it increases intestinal calcium absorp-

Eicosapentaenoic acid (EPA) is an n-3 fatty acid and is a component of fish oil, as well as is found in flaxseeds. EPA undergoes the metabolism similar to n-6 fatty acids. Therefore, increasing EPA and reducing n-6 fatty acid metabolites, especially PGE2. Lower PGE2 concentration not only reduces calcium excretion through urine but also leads to the activation of nephron Na/K/2Ca transporters, leading to the increase of renal calcium reabsorption. The clinical experiment showed that consuming 1,200 mg/day of flax oil is associated with a significant decrease of calcium

tion, reduces renal tubular reabsorption, and increases bone resorption.

and oxalate concentration and an increase of citrate concentration in urine.

promising for further research on the treatment of kidney stones [36].

India (2015) conducted a study to assess *in vitro* anti-inflammatory activity of flax. Ethanolic extract showed its maximum effectiveness in dissolving calcium oxalate crystals, thereby clearly showing that ethanolic extract of flaxseed was quite

Research Institute for Pharmaceutical Education, Narsapur, Medak, Telangana,

Several clinical studies have realized the great potential of n-3 polyunsaturated fatty acids (eicosapentaenoic acid - EPA) found in flaxseeds, which not only work against inflammatory mediators (such as prostate E2, leukotriene B4, TNF-α, interleukin, and cytokine) but are also very helpful in reducing the risk of calcium stone formation for kidney stones. According to a study by the authors of the Department of Urology, Nagoya City University of Medicine, Japan, to determine the effect of EPA on Urolithiasis, the authors conducted a clinical study in which a high-purity EPA product is provided (at a dose of 1,800 mg/day) for 88 patients with urinary stones for 3 months (short term) and 18 months (long term). The results suggest that EPA has reduced the amount of calcium in the urine which well affects the urine composition in a way that can reduce the risk of calcium stone formation. The Japanese authors when doing clinical research "Preventive effects for the recurrence of kidney stones", implemented high-purity EPA preparation at

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

continuing to be studied [34].

(PGE2) [35].

have good results for patients with kidney stones.

#### *Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths… DOI: http://dx.doi.org/10.5772/intechopen.97777*

For kidney stones, flaxseeds may help reduce the amount of calcium in the urine. Daily intake of organic, unrefined, and cold-pressed flaxseed oil has been shown to have good results for patients with kidney stones.

William F. Clark, Anwar Parbtani (1995) studied the impact of flaxseed on immune and renal damage models. ALA in flax constituents has been shown to have anti-inflammatory and anti-thrombotic properties, while flaxseed lignans have been reported as platelet-activating factor receptor antagonists (PAF). PAF contributes to the inflammatory response in progressive glomerulonephritis. The authors conclude that results from animal and human studies indicated that flaxseeds provide significant benefits in kidney function as well as important atherogenic and inflammatory mechanisms in the pathogenesis of lupus nephritis. Thereby, the authors recommend long-term studies with flaxseeds as a potential treatment for lupus nephritis and other forms of progressive kidney diseases [33].

According to research by the University of Manitoba and the Manitoba Children's Health Institute, Winnipeg, Man., Canada (2007), late intervention with soy protein and flaxseed oil in the diet has reduced the number of diseases related to multipurpose kidney diseases which were present in the rat. The potential benefits of antioxidant and anti-inflammatory effects on kidney disease results are continuing to be studied [34].

According to the report on "medical and dietary therapies for the prevention of kidney stones" by Zeyneplrul and Manoj Monga (2014), the main source of polyunsaturated fats in the Western diet is arachidonic acid (AA) an n-6 fatty acid found in vegetable oils and animal fats. N-6 fatty acids are involved in stone formation. The breakdown of AA leads to the formation of precursors including prostaglandin E2 (PGE2) [35].

PGE2 causes hypercalciuria because it increases intestinal calcium absorption, reduces renal tubular reabsorption, and increases bone resorption. Eicosapentaenoic acid (EPA) is an n-3 fatty acid and is a component of fish oil, as well as is found in flaxseeds. EPA undergoes the metabolism similar to n-6 fatty acids. Therefore, increasing EPA and reducing n-6 fatty acid metabolites, especially PGE2. Lower PGE2 concentration not only reduces calcium excretion through urine but also leads to the activation of nephron Na/K/2Ca transporters, leading to the increase of renal calcium reabsorption. The clinical experiment showed that consuming 1,200 mg/day of flax oil is associated with a significant decrease of calcium and oxalate concentration and an increase of citrate concentration in urine.

Research Institute for Pharmaceutical Education, Narsapur, Medak, Telangana, India (2015) conducted a study to assess *in vitro* anti-inflammatory activity of flax. Ethanolic extract showed its maximum effectiveness in dissolving calcium oxalate crystals, thereby clearly showing that ethanolic extract of flaxseed was quite promising for further research on the treatment of kidney stones [36].

Several clinical studies have realized the great potential of n-3 polyunsaturated fatty acids (eicosapentaenoic acid - EPA) found in flaxseeds, which not only work against inflammatory mediators (such as prostate E2, leukotriene B4, TNF-α, interleukin, and cytokine) but are also very helpful in reducing the risk of calcium stone formation for kidney stones. According to a study by the authors of the Department of Urology, Nagoya City University of Medicine, Japan, to determine the effect of EPA on Urolithiasis, the authors conducted a clinical study in which a high-purity EPA product is provided (at a dose of 1,800 mg/day) for 88 patients with urinary stones for 3 months (short term) and 18 months (long term). The results suggest that EPA has reduced the amount of calcium in the urine which well affects the urine composition in a way that can reduce the risk of calcium stone formation.

The Japanese authors when doing clinical research "Preventive effects for the recurrence of kidney stones", implemented high-purity EPA preparation at

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

**126**

**Figure 3.**

*2.1.1.2 Pharmacological effects and uses*

*Nutrient composition of flaxseed.*

to have a protective effect on the kidneys.

Scientists are interested in flaxseed for its health benefits due to its high content of α-linolenic acid and lignans. Natural treatment agents which have the effects on lipid-lowering, antioxidant, anti-inflammatory, and antihypertensive are expected 1,800 mg EPA/day for 29 patients in 36.4 ± 22.0 months after treatment of kidney stones. By observing the recurrence of Urolithiasis in these patients during 8 years (before, during, and after taking the drug) and studying the preventive effects for the recurrence of kidney stones, the study results showed that prevalence of nephrolithiasis (times/year) before, during and after taking EPA are respectively 0.22283, 0.0693 and 0.11742. The incidence of Nephrolithiasis while taking EPA was significantly lower than the findings before and after using (p < 0.05). Thus, the results suggest that EPA may reduce the risk of calcium stone formation.

#### *2.1.2 Plantago major*

*Plantago major* is also known as broadleaf plantain, white man's foot, or greater plantain, which belongs to the Plantaginaceae family. It is a kind of plant that is used both as food and as a medicinal plant. *Plantago major* is native to most of Europe and northern and central Asia. It is one of the most abundant and widely distributed medicinal crops in the world.

*Plantago major* is a herbaceous perennial plant with a rosette of leaves. Each leaf is oval-shaped. The leaf blade is 12 cm long and 8 cm broad. There are five to seven parallel veins that diverge in the wider part of the leaf. The inflorescences are borne on stalks. Flowers are always bisexual. They are small, greenish-brown with purple stamens, produced in a dense spike 5–15 cm long on top of a stem, 13–15 cm tall, and rarely to 70 cm tall. *Plantago major* propagates primarily by seeds, which are held on the long, narrow spikes which rise well above the foliage. *Plantago major* fruits are canned fruits, containing many glossy dark brown seeds. Each fruit has 8–13 seeds. The outer shell of the seed becomes mucous in water. Each plant part of *Plantago major* has been used in many traditional medicines for the treatment of cough, diarrhea, dysentery, urinary stones. The seeds of *Plantago major* have long been used in the treatment of urinary retention and urination.

#### *2.1.2.1 Chemical composition*

*Plantago major* leaves contain iridoid, aucubosid, catalpol), phenolic acid, and phenylpropanoid esters of glycosides, majorosides. Leaves also contain mucus with a content of 20%. *Plantago* contains mucus which is rich in D-galactose, L-arabinose, and has about 40% uronic acid, fatty oils including 9-hydroxy-cis-11 octadecenoic acid. Besides, *Plantago major* is also rich in flavonoids including apigenin, quercetin, scutellarin, baicalein, hispidulin (5,7,4′-trihydroxy-6-methoxyflavon), luteolin −7-glucoside, luteolin-7-glucuronide, homoplantaginin (= 7- O-Dglucopyranosyl-5,6,3', 4'-trihydroxyflavon). Besides, *Plantago major* contains many other substances such as coumaric acid, ferulic acid, caffeic acid, chlorogenic acid, carotene, vitamin K and vitamin C.

#### *2.1.2.2 Pharmacological effects and uses*

In the document of medicinal plants, Prof. Dr. Do Tat Loi also mentioned the effect of increased excretion of urea, uric acid, and salt (the components that make up urinary stones in urine) of *Plantago major* seeds. This activity was confirmed again by research done at Vietnam - Sweden hospital. The scientists found that the extract of *Plantago major* seed contains the active ingredient aucubin - 1 iridoid glycoside that works to increase the amount of urine, thereby stimulating more urine excretion, helping to enhance bacterial excretion and stones out of the urinary tract for people who have a urinary tract infection or have urinary stones.

**129**

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

*Plantago major* is used to treating nerve stutter and eye pain.

oxidative stress in cisplatin-induced kidney toxicity in rats.

There are 3 varieties of Malabar spinach. They are

1.White Malabar spinach (also known as Green Malabar spinach)

small leaf blade and slender stems. Its stems and leaf are pale green.

Leaf-blade is small with a slender stem. Malabar spinach stems and leaves are pale green. The most commonly grown species is white Malabar spinach with a

tory mediators such as leukotrienes, nitric oxide, prostaglandins, etc.

In Japanese traditional medicine, the decoction of *Plantago major* helps to treat cough, urinary tract infection, and inflammation. In Thailand, whole plants or leaves are used for the effects of diuretic, antipyretic, laxative, anti-inflammatory, and flatulence. In Korea, *Plantago major* is used to treating liver diseases. In Haiti,

Scientists at Malaysia Kebangsaan University (2003) also found that ethanol extract of whole *Plantago major* plant significantly reduces the size of calcium oxalate crystals better than allopurinol and potassium citrate drugs, at the same time inhibits newly formed stones. Malaysian scientists (2012) conducted a study to determine the inhibitory effect of *Plantago major*'s terpenoid extract on *in vitro* crystalline calcium oxalate and compared the effects of *Plantago major* with drugs which are clinically used as zyloric and potassium. The results showed that terpenoid extract of *Plantago major* inhibited the size of calcium oxalate crystals much better than zyloric and potassium citrate in the treatment of urinary stones.

According to research by Istanbul University and Kafkas University (Turkey), *Plantago major* seed extract works against most bacteria such as *Bacillus cereus*, *Staphylococcus aureus,* and especially *Escherichia coli* (E.coli)-the main agent of most

Research by scientists from Mashhad University of Medical Sciences, Mashhad, Iran showed that *Plantago major* extract can improve kidney function as well as

Spinach has the scientific name of *Basella alba* L. (*Basella rubra* L.), belongs to the family of Spinach - *Basellaceae*, also known as Malabar spinach, is an ancient tropical species, often grown as a vegetable. This plant is native to South Asian countries, spreads and grows wildly in many tropical Asian countries. It is grown in Asia, Africa, South America, and also in temperate regions of Asia and Europe. Its common distribution is in Africa, the Angels, Brazil, and Asia, Japan, China, Thailand, Laos, Cambodia, and Vietnam. In Vietnam, Malabar spinach grows

Malabar spinach is a herbaceous climbing plant with wrapped, fat and viscous, and reddish stems. Plants live annually or for two years. Leaves are staggered with raw and succulent leaf-blade. Flowers are arranged in flower form and are light purple. Fruits are oval-shaped or egg-shaped. Clump roots grow deep in the soil and are suitable for loose soil. Inflorescence in flower-shape growing in spaces between leaves which are white or pale reddish-purple. Berries of Malabar spinach are small, sphereshaped, or egg-shaped, about 5–6 mm long. They are green and turn dark purple when being ripe. Malabar spinach grows fast. Its stem can grow up to 10 m long.

In the study of *Plantago major* activity for urinary tract-related infectious diseases, scientists from Kaohsiung Medical Institute, Taiwan found that *Plantago major* extract is in high concentration (> 50 micrograms/ml) can inhibit inflamma-

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

urinary infections.

*2.1.3 Spinach*

wildly and is planted everywhere.

*2.1.3.1 Varieties of spinach*

#### *Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths… DOI: http://dx.doi.org/10.5772/intechopen.97777*

In Japanese traditional medicine, the decoction of *Plantago major* helps to treat cough, urinary tract infection, and inflammation. In Thailand, whole plants or leaves are used for the effects of diuretic, antipyretic, laxative, anti-inflammatory, and flatulence. In Korea, *Plantago major* is used to treating liver diseases. In Haiti, *Plantago major* is used to treating nerve stutter and eye pain.

Scientists at Malaysia Kebangsaan University (2003) also found that ethanol extract of whole *Plantago major* plant significantly reduces the size of calcium oxalate crystals better than allopurinol and potassium citrate drugs, at the same time inhibits newly formed stones. Malaysian scientists (2012) conducted a study to determine the inhibitory effect of *Plantago major*'s terpenoid extract on *in vitro* crystalline calcium oxalate and compared the effects of *Plantago major* with drugs which are clinically used as zyloric and potassium. The results showed that terpenoid extract of *Plantago major* inhibited the size of calcium oxalate crystals much better than zyloric and potassium citrate in the treatment of urinary stones.

According to research by Istanbul University and Kafkas University (Turkey), *Plantago major* seed extract works against most bacteria such as *Bacillus cereus*, *Staphylococcus aureus,* and especially *Escherichia coli* (E.coli)-the main agent of most urinary infections.

Research by scientists from Mashhad University of Medical Sciences, Mashhad, Iran showed that *Plantago major* extract can improve kidney function as well as oxidative stress in cisplatin-induced kidney toxicity in rats.

In the study of *Plantago major* activity for urinary tract-related infectious diseases, scientists from Kaohsiung Medical Institute, Taiwan found that *Plantago major* extract is in high concentration (> 50 micrograms/ml) can inhibit inflammatory mediators such as leukotrienes, nitric oxide, prostaglandins, etc.

#### *2.1.3 Spinach*

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

1,800 mg EPA/day for 29 patients in 36.4 ± 22.0 months after treatment of kidney stones. By observing the recurrence of Urolithiasis in these patients during 8 years (before, during, and after taking the drug) and studying the preventive effects for the recurrence of kidney stones, the study results showed that prevalence of nephrolithiasis (times/year) before, during and after taking EPA are respectively 0.22283, 0.0693 and 0.11742. The incidence of Nephrolithiasis while taking EPA was significantly lower than the findings before and after using (p < 0.05). Thus, the

*Plantago major* is also known as broadleaf plantain, white man's foot, or greater plantain, which belongs to the Plantaginaceae family. It is a kind of plant that is used both as food and as a medicinal plant. *Plantago major* is native to most of Europe and northern and central Asia. It is one of the most abundant and widely

*Plantago major* is a herbaceous perennial plant with a rosette of leaves. Each leaf is oval-shaped. The leaf blade is 12 cm long and 8 cm broad. There are five to seven parallel veins that diverge in the wider part of the leaf. The inflorescences are borne on stalks. Flowers are always bisexual. They are small, greenish-brown with purple stamens, produced in a dense spike 5–15 cm long on top of a stem, 13–15 cm tall, and rarely to 70 cm tall. *Plantago major* propagates primarily by seeds, which are held on the long, narrow spikes which rise well above the foliage. *Plantago major* fruits are canned fruits, containing many glossy dark brown seeds. Each fruit has 8–13 seeds. The outer shell of the seed becomes mucous in water. Each plant part of *Plantago major* has been used in many traditional medicines for the treatment of cough, diarrhea, dysentery, urinary stones. The seeds of *Plantago major* have long

*Plantago major* leaves contain iridoid, aucubosid, catalpol), phenolic acid, and phenylpropanoid esters of glycosides, majorosides. Leaves also contain mucus with a content of 20%. *Plantago* contains mucus which is rich in D-galactose, L-arabinose, and has about 40% uronic acid, fatty oils including 9-hydroxy-cis-11 octadecenoic acid. Besides, *Plantago major* is also rich in flavonoids including apigenin, quercetin, scutellarin, baicalein, hispidulin (5,7,4′-trihydroxy-6-methoxyflavon), luteolin −7-glucoside, luteolin-7-glucuronide, homoplantaginin (= 7- O-Dglucopyranosyl-5,6,3', 4'-trihydroxyflavon). Besides, *Plantago major* contains many other substances such as coumaric acid, ferulic acid, caffeic acid, chlorogenic acid,

In the document of medicinal plants, Prof. Dr. Do Tat Loi also mentioned the effect of increased excretion of urea, uric acid, and salt (the components that make up urinary stones in urine) of *Plantago major* seeds. This activity was confirmed again by research done at Vietnam - Sweden hospital. The scientists found that the extract of *Plantago major* seed contains the active ingredient aucubin - 1 iridoid glycoside that works to increase the amount of urine, thereby stimulating more urine excretion, helping to enhance bacterial excretion and stones out of the urinary tract for people who have a urinary tract infection or

results suggest that EPA may reduce the risk of calcium stone formation.

been used in the treatment of urinary retention and urination.

*2.1.2 Plantago major*

distributed medicinal crops in the world.

*2.1.2.1 Chemical composition*

carotene, vitamin K and vitamin C.

*2.1.2.2 Pharmacological effects and uses*

**128**

have urinary stones.

Spinach has the scientific name of *Basella alba* L. (*Basella rubra* L.), belongs to the family of Spinach - *Basellaceae*, also known as Malabar spinach, is an ancient tropical species, often grown as a vegetable. This plant is native to South Asian countries, spreads and grows wildly in many tropical Asian countries. It is grown in Asia, Africa, South America, and also in temperate regions of Asia and Europe. Its common distribution is in Africa, the Angels, Brazil, and Asia, Japan, China, Thailand, Laos, Cambodia, and Vietnam. In Vietnam, Malabar spinach grows wildly and is planted everywhere.

Malabar spinach is a herbaceous climbing plant with wrapped, fat and viscous, and reddish stems. Plants live annually or for two years. Leaves are staggered with raw and succulent leaf-blade. Flowers are arranged in flower form and are light purple. Fruits are oval-shaped or egg-shaped. Clump roots grow deep in the soil and are suitable for loose soil. Inflorescence in flower-shape growing in spaces between leaves which are white or pale reddish-purple. Berries of Malabar spinach are small, sphereshaped, or egg-shaped, about 5–6 mm long. They are green and turn dark purple when being ripe. Malabar spinach grows fast. Its stem can grow up to 10 m long.

#### *2.1.3.1 Varieties of spinach*

There are 3 varieties of Malabar spinach. They are

1.White Malabar spinach (also known as Green Malabar spinach)

Leaf-blade is small with a slender stem. Malabar spinach stems and leaves are pale green. The most commonly grown species is white Malabar spinach with a small leaf blade and slender stems. Its stems and leaf are pale green.

#### 2.Purple Malabar spinach

Purple Malabar spinach has small leaves, reddish-purple stems, and veins. This is a wrapped climbing plant. The stem is fat and viscous with a 2–3 year lifespan. Leaves of purple Malabar spinach are thick, heart-shaped, and intertwined. The inflorescence is flower-shaped and white or pale reddish-purple. Berries of purple Malabar spinach are small, sphere-shaped, or egg-shaped, about 5–6 mm long. They are green and turn dark purple when being ripe. According to some Chinese medicine documents, the whole stem of Malabar spinach has a light sweet taste, a cold property which has the effects of heat dissipation, cool blood, diuretic, detoxification, and pain relief. Leaves and young stem buds of Malabar spinach are often used to stir-fry, boil, or cook soup as a cool and laxative food.

#### 3.Large leaf Malabar spinach

Large leaf Malabar spinach is very similar to the green Malabar spinach but has different characteristics, with a larger leaf blade, the leaves are thicker, the color is darker green and the stems are fatter.

Spinach contains high amounts of vitamin A3, vitamin B3, vitamin E, saponin, and iron which are essential for general health and well-being Spinach is a wildgrowing variety so it is not picky, easy to grow and take care of and grow fast with an over 10 m length of the stem.

#### *2.1.3.2 Chemical composition*

According to the documents of the United States Department of Agriculture (USDA, 2016), 100 g of edible Malabar spinach portion contains 93 g of water; 79 kJ (19 kcal) of energy; 1.4% glucid; 2.5% fiber; 0.9% ash; 1.8 g of protein; 0.3 g of fat; 109 mg Ca; 52 mg of P; 1.2 mg of Fe; 8000 IU of vitamin A; 0.05 mg of thiamin, 0.16 mg of riboflavin; 0.50 mg of niacin; 140 mg of folate; 102 mg of ascorbic acid. Besides, spinach leaves also contain aminoglycosides, several oleanane triterpenes, including *basella* saponins, betavulgaroside I, spinacoside C, and momordins. The spinach seeds contain 2 antifungal peptides and ribosome-inactivated proteins, with antiviral activity isolated from seeds.

Spinach contains many bioactive compounds such as carbohydrates, proteins, enzymes, fats and oils, vitamins, alkaloids, quinine, terpenoids, flavonoids, carotenoids, sterols, simple phenol glycosides, tannins, saponins, polyphenols, etc. It also contains Vitamin A, Vitamin E, Vitamin K, flavonoids, saponins, and β Carotene [37].

#### *2.1.3.3 Pharmacological effects and uses*

The whole plant of Malabar spinach is used to treat dysentery, esoteric defecation, cystitis, and appendicitis. Externally used for bone fractures, injuries (outside of the body), outside hemorrhage, burns. In India, people use leaves in the treatment of gonorrhea and glansitis. Leaf fluid is used to treat urticaria and constipation, especially in children and pregnant women. In Thailand, the leaves are used to treat round spots, flowers used to treat tinea diseases, roots used for laxative effect, and externally used to treat discoloration of the skin of hands, feet, and dandruff; berries used as food dyes. In Vietnam, Malabar spinach is recorded as having cold property, sour taste, heat dissipation, blood cooling, diuretic, urinary retention, dysuria, detoxification, and pain relief.

Many scientific reports indicate that sponges can be used to treat laxatives, inflammation, rubefacient, skin diseases, burns, ulcers, diarrhea, diuretics, and cancer.

**131**

ringworm, and laboring.

causing gout or kidney stones.

*2.1.4 Fenugreek*

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

Spinach leaves contain several active ingredients including flavonoids with antioxidant and anti-inflammatory properties. Spinach extract has been shown to have numerous effects such as chemotherapy, protection of the central nervous system,

For kidney stones, the Indian Institute of Pharmaceutical Sciences and Research (2020) conducted a study to evaluate the diuretic [38] and anti-diuretic activities of ethanolic extract of Malabar spinach leaves in rats that had been induced to cause kidney stones. The study results showed that ethanolic extract from Malabar spinach leaves has a significant diuretic activity by increasing the total amount of urine and the excretion of sodium, potassium, chloride, and bicarbonate, and also has significant anti-thrombotic activity by reducing high concentrations of oxalate, calcium, and phosphate in the urine and adding calcium, creatinine and uric acid in the serum. The extract of the seed's peel of Malabar spinach has properties that enhance the reducing properties of the calcium oxalate crystals. The results obtained from the studies show the potential benefits of the extract of Malabar

In Ayurveda, used for hemorrhages, skin diseases, sexual weakness, ulcers, and as a laxative in children. Leaves are applied to the head for half an hour before bathing to help bring about good refreshing sleep. The sap is applied to acne eruptions to reduce inflammation. Decoction of leaves used for a mild laxative effect. Pulped leaves applied to boils and ulcers to hasten suppuration. Leaf juice mixed with butter applied to burns and scalds for a soothing and cooling effect. Leaves and stems have been used as anticancer for melanoma, leukemia, and oral cancer. Roots and leaves are used for stomach pains and increase milk production. Used orally for anal prolapse and hernia. In Nigeria, used for hypertension and also used for fertility enhancement in women. In Nepal, leaf juice is used to treat dysentery, catarrh, and applied externally to boils. In Thai traditional medicine, mucilage is used as an application for bruises, ringworm, and laboring. Stem and leaves are used as a mild laxative, diuretic and antipyretic. In Cameroon, used for malaria. Herbal healers use plant extracts to enhance libido and as a remedy for infertility. In the Antilles, leaves are considered good maturative as a cataplasm. In Thai traditional medicine, mucilage is used as a topical medicine for skin irritation, bruises,

A study of leaves extract of *Basella alba* showed an admirable dissolving capacity of calcium oxalate crystals in both *in vitro* and *in vivo* studies. Although Malabar spinach has a rich nutrient (1/2 cup of spinach after cooking provides 190% of vitamin A and 20% of iron which the body needs), it should not be abused. Eating too much spinach makes the body absorb less because it contains a high content of oxalic acid. This is a chemical that binds calcium and iron, making it difficult for the body to absorb other important nutrients. Therefore, when eating spinach, it is better to eat with foods that are rich in vitamin C such as oranges, lemons, tomatoes, star fruit, or consuming oxalate removed spinach is much safer and useful for preventing kidney stones. Especially eating spinach cooked with star fruit will be very good for the body. Because of the content of oxalic acid and purine, eating lots of spinach converting to uric acid will increase the concentration of calcium oxalate in urine and accumulate in the body, easily

Fenugreek, also known as *Trigonella foenum-graecum* L., belongs to the family Fabaceae. The plant is about 60–90 cm tall and green. The flowers are small and white. Its seed is small and yellow-brown. Because of its preventive and curative

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

anti-cancer, anti-aging functions, and hypoglycemia.

spinach in treating and preventing the recurrence of kidney stones.

#### *Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths… DOI: http://dx.doi.org/10.5772/intechopen.97777*

Spinach leaves contain several active ingredients including flavonoids with antioxidant and anti-inflammatory properties. Spinach extract has been shown to have numerous effects such as chemotherapy, protection of the central nervous system, anti-cancer, anti-aging functions, and hypoglycemia.

For kidney stones, the Indian Institute of Pharmaceutical Sciences and Research (2020) conducted a study to evaluate the diuretic [38] and anti-diuretic activities of ethanolic extract of Malabar spinach leaves in rats that had been induced to cause kidney stones. The study results showed that ethanolic extract from Malabar spinach leaves has a significant diuretic activity by increasing the total amount of urine and the excretion of sodium, potassium, chloride, and bicarbonate, and also has significant anti-thrombotic activity by reducing high concentrations of oxalate, calcium, and phosphate in the urine and adding calcium, creatinine and uric acid in the serum. The extract of the seed's peel of Malabar spinach has properties that enhance the reducing properties of the calcium oxalate crystals. The results obtained from the studies show the potential benefits of the extract of Malabar spinach in treating and preventing the recurrence of kidney stones.

In Ayurveda, used for hemorrhages, skin diseases, sexual weakness, ulcers, and as a laxative in children. Leaves are applied to the head for half an hour before bathing to help bring about good refreshing sleep. The sap is applied to acne eruptions to reduce inflammation. Decoction of leaves used for a mild laxative effect. Pulped leaves applied to boils and ulcers to hasten suppuration. Leaf juice mixed with butter applied to burns and scalds for a soothing and cooling effect. Leaves and stems have been used as anticancer for melanoma, leukemia, and oral cancer. Roots and leaves are used for stomach pains and increase milk production. Used orally for anal prolapse and hernia. In Nigeria, used for hypertension and also used for fertility enhancement in women. In Nepal, leaf juice is used to treat dysentery, catarrh, and applied externally to boils. In Thai traditional medicine, mucilage is used as an application for bruises, ringworm, and laboring. Stem and leaves are used as a mild laxative, diuretic and antipyretic. In Cameroon, used for malaria. Herbal healers use plant extracts to enhance libido and as a remedy for infertility. In the Antilles, leaves are considered good maturative as a cataplasm. In Thai traditional medicine, mucilage is used as a topical medicine for skin irritation, bruises, ringworm, and laboring.

A study of leaves extract of *Basella alba* showed an admirable dissolving capacity of calcium oxalate crystals in both *in vitro* and *in vivo* studies. Although Malabar spinach has a rich nutrient (1/2 cup of spinach after cooking provides 190% of vitamin A and 20% of iron which the body needs), it should not be abused. Eating too much spinach makes the body absorb less because it contains a high content of oxalic acid. This is a chemical that binds calcium and iron, making it difficult for the body to absorb other important nutrients. Therefore, when eating spinach, it is better to eat with foods that are rich in vitamin C such as oranges, lemons, tomatoes, star fruit, or consuming oxalate removed spinach is much safer and useful for preventing kidney stones. Especially eating spinach cooked with star fruit will be very good for the body. Because of the content of oxalic acid and purine, eating lots of spinach converting to uric acid will increase the concentration of calcium oxalate in urine and accumulate in the body, easily causing gout or kidney stones.

#### *2.1.4 Fenugreek*

Fenugreek, also known as *Trigonella foenum-graecum* L., belongs to the family Fabaceae. The plant is about 60–90 cm tall and green. The flowers are small and white. Its seed is small and yellow-brown. Because of its preventive and curative

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

Purple Malabar spinach has small leaves, reddish-purple stems, and veins. This is a wrapped climbing plant. The stem is fat and viscous with a 2–3 year lifespan. Leaves of purple Malabar spinach are thick, heart-shaped, and intertwined. The inflorescence is flower-shaped and white or pale reddish-purple. Berries of purple Malabar spinach are small, sphere-shaped, or egg-shaped, about 5–6 mm long. They are green and turn dark purple when being ripe. According to some Chinese medicine documents, the whole stem of Malabar spinach has a light sweet taste, a cold property which has the effects of heat dissipation, cool blood, diuretic, detoxification, and pain relief. Leaves and young stem buds of Malabar spinach are often used to stir-fry, boil, or cook soup as a cool and laxative food.

Large leaf Malabar spinach is very similar to the green Malabar spinach but has different characteristics, with a larger leaf blade, the leaves are thicker, the color

Spinach contains high amounts of vitamin A3, vitamin B3, vitamin E, saponin, and iron which are essential for general health and well-being Spinach is a wildgrowing variety so it is not picky, easy to grow and take care of and grow fast with

According to the documents of the United States Department of Agriculture (USDA, 2016), 100 g of edible Malabar spinach portion contains 93 g of water; 79 kJ (19 kcal) of energy; 1.4% glucid; 2.5% fiber; 0.9% ash; 1.8 g of protein; 0.3 g of fat; 109 mg Ca; 52 mg of P; 1.2 mg of Fe; 8000 IU of vitamin A; 0.05 mg of thiamin, 0.16 mg of riboflavin; 0.50 mg of niacin; 140 mg of folate; 102 mg of ascorbic acid. Besides, spinach leaves also contain aminoglycosides, several oleanane triterpenes, including *basella* saponins, betavulgaroside I, spinacoside C, and momordins. The spinach seeds contain 2 antifungal peptides and ribosome-inactivated proteins,

Spinach contains many bioactive compounds such as carbohydrates, proteins, enzymes, fats and oils, vitamins, alkaloids, quinine, terpenoids, flavonoids, carotenoids, sterols, simple phenol glycosides, tannins, saponins, polyphenols, etc. It also contains Vitamin A, Vitamin E, Vitamin K, flavonoids, saponins, and β Carotene [37].

The whole plant of Malabar spinach is used to treat dysentery, esoteric defecation, cystitis, and appendicitis. Externally used for bone fractures, injuries (outside of the body), outside hemorrhage, burns. In India, people use leaves in the treatment of gonorrhea and glansitis. Leaf fluid is used to treat urticaria and constipation, especially in children and pregnant women. In Thailand, the leaves are used to treat round spots, flowers used to treat tinea diseases, roots used for laxative effect, and externally used to treat discoloration of the skin of hands, feet, and dandruff; berries used as food dyes. In Vietnam, Malabar spinach is recorded as having cold property, sour taste, heat dissipation, blood cooling, diuretic, urinary retention,

Many scientific reports indicate that sponges can be used to treat laxatives, inflammation, rubefacient, skin diseases, burns, ulcers, diarrhea, diuretics,

2.Purple Malabar spinach

3.Large leaf Malabar spinach

an over 10 m length of the stem.

*2.1.3.2 Chemical composition*

is darker green and the stems are fatter.

with antiviral activity isolated from seeds.

*2.1.3.3 Pharmacological effects and uses*

dysuria, detoxification, and pain relief.

**130**

and cancer.

properties, fenugreek is used as a herb. It is native to the Middle and Near East and is widely used in the Indian subcontinent. There is even evidence that ancient Egyptians understood the benefits of Fenugreek because its seeds were found in tombs, especially Tutankhamen. The plant is grown in countries across the globe as a semi-arid crop, but most are grown and consumed in India.

Fenugreek is used as a medicinal plant (leaves) as well as a spice (seeds). Parts that are used as a medicine of Fenugreek include stems, leaves, and seeds. Fenugreek seeds are yellow or amber and generally used for dipping food, dried and pasty curry powders, commonly found in Indian cuisine. Young leaves and buds of fenugreek are also used as a vegetable, while fresh or dried leaves are used to flavor other dishes.

#### *2.1.4.1 Chemical composition*

According to the study documents, fenugreek seeds contain 26.2% of protein, 5.8% of lipids, 3% of minerals including iron, calcium, phosphorus, magnesium, potassium, sodium, zinc, copper, manganese, vitamin C, folic acid, vitamins E, B1, B2, B3, 3% of fiber and 44.2% of powdered sugar. Besides, fenugreek seeds contain saponins, oil substances, flavonoids and mucus, 4-hydroxy isoleucine (amino acids that stimulate insulin secretion), and galactomannan that slow down the absorption of blood glucose.

According to a study in 2014 published in the Journal of Nutrition, fenugreek contains soluble fiber, which can reduce the glucose absorption of cells, helping to low down blood sugar. Besides, it also contains trigonelline a compound that increases insulin sensitivity, and 4-hydroxy isoleucine -an amino acid that helps stimulate insulin release in pancreatic cells, helping to control blood sugar levels automatically.

Fenugreek contains polyphenols and flavonoids that have antioxidant effects, which reduce the amount of cholesterol and triglycerides in the body. The galactomannan forms a layer of mucus in the intestines limiting the absorption of lipids and glucose.

#### *2.1.4.2 Pharmacological effects and uses*

Fenugreek seeds are commonly used in Northern Africa to prevent and treat kidney stones. In a study on an animal, it was found that fenugreek seeds significantly reduce kidney calcification and the total calcium content of kidney tissue in rats, helping to prevent kidney stones.

According to a study of King Saud University, Riyadh, Saudi Arabia on the effects of fenugreek seeds and *Ammi majus* [39] on calcium oxalate urinary stones in rats, when treated daily by oral route with fenugreek extract, it significantly reduced the amount of calcium oxalate deposited in the kidneys while the inhibitory effects obtained from *Ammi majus* grass were negligible.

In 2014, the Science University of Salahaddin, Kurdistan - Iraq region conducted a study on the effects of fenugreek in preventing the formation of kidney stones. The study result has proven its potential effects of antioxidants and Urolithiasis prevention, thus making a beneficial effect to prevent the formation of kidney stones and related free-radical complications in kidney tissues.

According to a study result on the effects of some medicinal plants used in the treatment of urinary stones of Abulcocation-Rabat University, Morocco, the extract of fenugreek seed has a good effect on dissolving cystine and carbapatite stones, probably due to the complex formation between stones and polyphenols or flavonoids in the extract [40].

**133**

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

**3. Role of vitamins and minerals in the management of calciphytoliths**

Calcium oxalate deposits in numerous plants and animal cells. Neither it excretes in urine nor retained in the form of urinary calculi. Calcium oxalate in plant sources was first described by "Leeuwenhoek" using a Simple microscope. Oxalate ranges in plants from 3 to 80%. Non-accumulating oxalate plants have less oxalic acid in them. In plants, oxalic acid is obtained from glycolate conversion. Oxidation takes place where glycolic acid is oxidase and glyoxylic acid is intermediate. Glyoxylic acid as intermediate is obtained by cleavage of isocitric acid and oxaloacetate

It is present in numerous parts of plants and is considered the strongest acid present in plants. Oxalic acid as a chelating agent reacts with cations and results in the end product being oxalates. Oxalic acid is considered as the end product but in some cases, it converts to oxalate by several conditions as the alternate change in oxalate concentration. Oxalic acid acts as an "ionic balance" in plants and the formation of soluble or insoluble compounds. Oxalate in plants promotes antioxidant property. Content of oxalate more in plants results in attaining uncomfort taste but promotes plant protection from insects and animals and oxalic acid content fruits have high superoxide dismutase activity. This plays a major role in systematic resistance, programmed cell death, redox homeostasis, and anti-senescence effect

Calcium oxalate crystals form by oxalic acid interiorly present in plants and calcium obtained from the environment. Calcium oxalate occurs in many plant regions except pollen. The highest oxalic acid concentration commonly occurs in leaves and it is lowest in all other parts. It exerts its effects by binding calcium, magnesium, and other trace minerals like iron making them unavailable for assimilation. The calcium ions bind with free oxalic acid or oxalate and precipitates as insoluble crystals of calcium oxalate which may lead to hypocalcemia and urolithiasis. In the human being, <0.5% soluble oxalate in a diet may be acceptable. Plants accumulate oxalate in high proportion only during the young stage of growth and the content decreases with maturity and drying of the plant. Matured plant organs of the selected plants were discussed here which contain considerable calcium and very low amounts of

Generally oxalic acid is present in many plant families but commonly occurs in Amaranthaceae, Polygonaceae, Chenopodiaceae, Oxiladaceae, Convolvulaceae, etc. General natural products that contain oxalic acids are Sugarbeet, Spinach, Saltbush, Goosefoot, Buckwheat, Rhubarb, Mangold, Green cabbages, Tea, Chocolate, Almonds, White beans, Soyabean, Sweet potato, Ipomoea, Okra, Cocoa, Drumstick

Oxalic acid easily combines with cations to form oxalate crystals which are then excreted in urine as minute crystals. So calcium supplements given along with foods containing oxalic acid can cause calcium oxalate to precipitate out in the gut and reduce the levels of oxalate absorbed by the body by 97%. Calcium supplement like milk also has characteristics of digestive and metabolic utilization of minerals such as phosphorus, magnesium, and iron. It's calcium enrichment does not interfere in the bioavailability of the minerals but interferes with iron. So iron may not be utilized when milk is used which is an important aspect in the

soluble oxalate and also were used traditionally in treating kidney stones.

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

separates in attaining oxalate and acetate.

leaves, Coriander leaves, Radish leaves, etc.

**3.2 Vitamins and minerals**

management of kidney stones.

**3.1 Calcium oxalate in plants**

in harvested fruits.

#### **3. Role of vitamins and minerals in the management of calciphytoliths**

#### **3.1 Calcium oxalate in plants**

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

a semi-arid crop, but most are grown and consumed in India.

that slow down the absorption of blood glucose.

*2.1.4.2 Pharmacological effects and uses*

rats, helping to prevent kidney stones.

other dishes.

automatically.

and glucose.

*2.1.4.1 Chemical composition*

properties, fenugreek is used as a herb. It is native to the Middle and Near East and is widely used in the Indian subcontinent. There is even evidence that ancient Egyptians understood the benefits of Fenugreek because its seeds were found in tombs, especially Tutankhamen. The plant is grown in countries across the globe as

Fenugreek is used as a medicinal plant (leaves) as well as a spice (seeds). Parts that are used as a medicine of Fenugreek include stems, leaves, and seeds. Fenugreek seeds are yellow or amber and generally used for dipping food, dried and pasty curry powders, commonly found in Indian cuisine. Young leaves and buds of fenugreek are also used as a vegetable, while fresh or dried leaves are used to flavor

According to the study documents, fenugreek seeds contain 26.2% of protein, 5.8% of lipids, 3% of minerals including iron, calcium, phosphorus, magnesium, potassium, sodium, zinc, copper, manganese, vitamin C, folic acid, vitamins E, B1, B2, B3, 3% of fiber and 44.2% of powdered sugar. Besides, fenugreek seeds contain saponins, oil substances, flavonoids and mucus, 4-hydroxy isoleucine (amino acids that stimulate insulin secretion), and galactomannan

According to a study in 2014 published in the Journal of Nutrition, fenugreek contains soluble fiber, which can reduce the glucose absorption of cells, helping to low down blood sugar. Besides, it also contains trigonelline a compound that increases insulin sensitivity, and 4-hydroxy isoleucine -an amino acid that helps stimulate insulin release in pancreatic cells, helping to control blood sugar levels

Fenugreek contains polyphenols and flavonoids that have antioxidant effects, which reduce the amount of cholesterol and triglycerides in the body. The galactomannan forms a layer of mucus in the intestines limiting the absorption of lipids

Fenugreek seeds are commonly used in Northern Africa to prevent and treat kidney stones. In a study on an animal, it was found that fenugreek seeds significantly reduce kidney calcification and the total calcium content of kidney tissue in

According to a study of King Saud University, Riyadh, Saudi Arabia on the effects of fenugreek seeds and *Ammi majus* [39] on calcium oxalate urinary stones in rats, when treated daily by oral route with fenugreek extract, it significantly reduced the amount of calcium oxalate deposited in the kidneys while the inhibi-

In 2014, the Science University of Salahaddin, Kurdistan - Iraq region conducted a study on the effects of fenugreek in preventing the formation of kidney stones. The study result has proven its potential effects of antioxidants and Urolithiasis prevention, thus making a beneficial effect to prevent the formation of kidney

According to a study result on the effects of some medicinal plants used in the treatment of urinary stones of Abulcocation-Rabat University, Morocco, the extract of fenugreek seed has a good effect on dissolving cystine and carbapatite stones, probably due to the complex formation between stones and polyphenols or flavo-

tory effects obtained from *Ammi majus* grass were negligible.

stones and related free-radical complications in kidney tissues.

**132**

noids in the extract [40].

Calcium oxalate deposits in numerous plants and animal cells. Neither it excretes in urine nor retained in the form of urinary calculi. Calcium oxalate in plant sources was first described by "Leeuwenhoek" using a Simple microscope. Oxalate ranges in plants from 3 to 80%. Non-accumulating oxalate plants have less oxalic acid in them. In plants, oxalic acid is obtained from glycolate conversion. Oxidation takes place where glycolic acid is oxidase and glyoxylic acid is intermediate. Glyoxylic acid as intermediate is obtained by cleavage of isocitric acid and oxaloacetate separates in attaining oxalate and acetate.

It is present in numerous parts of plants and is considered the strongest acid present in plants. Oxalic acid as a chelating agent reacts with cations and results in the end product being oxalates. Oxalic acid is considered as the end product but in some cases, it converts to oxalate by several conditions as the alternate change in oxalate concentration. Oxalic acid acts as an "ionic balance" in plants and the formation of soluble or insoluble compounds. Oxalate in plants promotes antioxidant property. Content of oxalate more in plants results in attaining uncomfort taste but promotes plant protection from insects and animals and oxalic acid content fruits have high superoxide dismutase activity. This plays a major role in systematic resistance, programmed cell death, redox homeostasis, and anti-senescence effect in harvested fruits.

Calcium oxalate crystals form by oxalic acid interiorly present in plants and calcium obtained from the environment. Calcium oxalate occurs in many plant regions except pollen. The highest oxalic acid concentration commonly occurs in leaves and it is lowest in all other parts. It exerts its effects by binding calcium, magnesium, and other trace minerals like iron making them unavailable for assimilation. The calcium ions bind with free oxalic acid or oxalate and precipitates as insoluble crystals of calcium oxalate which may lead to hypocalcemia and urolithiasis. In the human being, <0.5% soluble oxalate in a diet may be acceptable. Plants accumulate oxalate in high proportion only during the young stage of growth and the content decreases with maturity and drying of the plant. Matured plant organs of the selected plants were discussed here which contain considerable calcium and very low amounts of soluble oxalate and also were used traditionally in treating kidney stones.

Generally oxalic acid is present in many plant families but commonly occurs in Amaranthaceae, Polygonaceae, Chenopodiaceae, Oxiladaceae, Convolvulaceae, etc. General natural products that contain oxalic acids are Sugarbeet, Spinach, Saltbush, Goosefoot, Buckwheat, Rhubarb, Mangold, Green cabbages, Tea, Chocolate, Almonds, White beans, Soyabean, Sweet potato, Ipomoea, Okra, Cocoa, Drumstick leaves, Coriander leaves, Radish leaves, etc.

#### **3.2 Vitamins and minerals**

Oxalic acid easily combines with cations to form oxalate crystals which are then excreted in urine as minute crystals. So calcium supplements given along with foods containing oxalic acid can cause calcium oxalate to precipitate out in the gut and reduce the levels of oxalate absorbed by the body by 97%. Calcium supplement like milk also has characteristics of digestive and metabolic utilization of minerals such as phosphorus, magnesium, and iron. It's calcium enrichment does not interfere in the bioavailability of the minerals but interferes with iron. So iron may not be utilized when milk is used which is an important aspect in the management of kidney stones.

A low oxalate diet is recommended for the prevention of CaOx stones, however, a recent study proved dietary oxalate had little effect on urinary oxalate excretion although vitamin C was highly correlated with urinary oxalate excretion. But high vitamin C intake can be a risk for stone formation by increasing endogenous oxalate.

A high vitamin D and protein content regimen increase hypercalciuria which lowers the pH of urine and increases uric acid level, which increases kidney stone. So consumption of deproteinized drugs is much better. All the plants discussed here contain considerable amounts of vitamin E but do not contain much vitamin D and anti-nutrient like phytates. The absorption of mineral nutrients is adversely affected by the presence of inhibitors like phytates. It is a higher calcium diet (1200 mg/day) associated with lower kidney stone formation because the higher calcium intake will bind oxalate in the gut. So calcium can bind with dietary oxalate and thus it is not absorbed. Potassium will improve hyperoxaluria and also it is a good source in the control of diuretic and hypertensive implications. Magnesium also forms a complex with oxalate and decreases oxalate in the urine, which can reduce the risk of stone formation. Hypomagnesium is not a risk factor for stone formation. Magnesium also binds with oxalate in gastrointestinal tract to reduce oxalate absorption. Citrate supplementation is one of the effective pharmacological options for preventing the recurrence of kidney stones. Calcium oxalate or calcium phosphate crystallization is antagonized by the citrate in the urine due to which recurrence of kidney stone is prevented by increased urinary citrate excretion. Potassium citrate along with thiazides are prescribed for kidney stone treatment at the same time it impaired by poor long term compliance, gastrointestinal upset and unpalatable taste. The remedy for this issue is taking potassium citrate with magnesium citrate combination. Magnesium can bind with oxalate due to which both diminishing and absorption of oxalate takes place thereby acting as a stone preventive. The binding of oxalate in urine is reduced by the binding of magnesium which results in the decrease in the recurrence of kidney stones. Patients who have diabetes, hypertension, and high blood cholesterol are often instructed to consume high oxalate foods such as fruits and vegetables. In this case, it is better to consume less and only selected fruits and vegetables to prevent kidney stones. The vitamins and mineral composition of the selected plants were given in **Figures 4** and **5** [41–56]. The plants discussed here contain all the nutrients in considerable quantities required for preventing and managing calculi forming oxalates.

#### **3.3 Impact of vitamin E in the management of disease and calciphytoliths**

#### *3.3.1 Renal insufficiency due to vitamin E deficiciency*

In rats, a combination of fat-soluble vitamin deficiency and Se or glutathione deficiency causes extreme and progressive aerophilic damage to the urinary organ's structure and function [57–59]. Furthermore, urinary organ dysfunction caused by ischemia–reperfusion damage causes 50% mortality in dietary E- and seleniumdeficient rats compared to controls [60], and a-tocopherol administration increases the fatality rate by 46% after 120 minutes of heat anemia [61]. During a marked increase in the creatinine/molar creatol magnitude relationship, aerophilic urinary organ injury in nutrients E-deficient rats is depicted.

Conversion is directly mediated by chemical group radicals [62]. The living nephrons enhanced the absorption of the element and the square oxide levels multiplied within the residual cortex of rats. Dietary fat-soluble vitamin administration 11 to 16 weeks after urinary tubule reduction has been shown to attenuate glomerulosclerosis by more than 500 weeks [63]. The fat-soluble vitamin deficiencies are never seen in humans and have been delineated by sensory neurological disorders.

**135**

**Figure 4.**

**Figure 5.**

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

It is due to diseases that hinder the streamlined absorption of fat (such as chronic disorders or abetalipoproteinemia) or, in rare highly contagious conditions, Deficit in the family of confined fat-soluble vitamins (FIVE) due to mutations in the a-tocopherol enzyme that export fat-soluble vitamins from the liver to blood [64]. If patients with permanent and high fat-soluble vitamin deficiency have urinary

Immune globulin nephrosis (formerly known as Berger's disease) is now confirmed to be the end-stage urinary organ dysfunction in twenty-five percent of affected patients over a 25-year follow-up period [65], despite being initially

organ dysfunction, this is not recognized.

*Mineral content in the selected plants (mg/100 g).*

*3.3.2 Inflammatory kidney disease*

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

*Vitamins and calcium content in the selected plants (mg/100 g).*

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths… DOI: http://dx.doi.org/10.5772/intechopen.97777*

**Figure 5.** *Mineral content in the selected plants (mg/100 g).*

It is due to diseases that hinder the streamlined absorption of fat (such as chronic disorders or abetalipoproteinemia) or, in rare highly contagious conditions, Deficit in the family of confined fat-soluble vitamins (FIVE) due to mutations in the a-tocopherol enzyme that export fat-soluble vitamins from the liver to blood [64]. If patients with permanent and high fat-soluble vitamin deficiency have urinary organ dysfunction, this is not recognized.

#### *3.3.2 Inflammatory kidney disease*

Immune globulin nephrosis (formerly known as Berger's disease) is now confirmed to be the end-stage urinary organ dysfunction in twenty-five percent of affected patients over a 25-year follow-up period [65], despite being initially

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

A low oxalate diet is recommended for the prevention of CaOx stones, however, a recent study proved dietary oxalate had little effect on urinary oxalate excretion although vitamin C was highly correlated with urinary oxalate excretion. But high vitamin C intake can be a risk for stone formation by increasing endogenous oxalate. A high vitamin D and protein content regimen increase hypercalciuria which lowers the pH of urine and increases uric acid level, which increases kidney stone. So consumption of deproteinized drugs is much better. All the plants discussed here contain considerable amounts of vitamin E but do not contain much vitamin D and anti-nutrient like phytates. The absorption of mineral nutrients is adversely affected by the presence of inhibitors like phytates. It is a higher calcium diet (1200 mg/day) associated with lower kidney stone formation because the higher calcium intake will bind oxalate in the gut. So calcium can bind with dietary oxalate and thus it is not absorbed. Potassium will improve hyperoxaluria and also it is a good source in the control of diuretic and hypertensive implications. Magnesium also forms a complex with oxalate and decreases oxalate in the urine, which can reduce the risk of stone formation. Hypomagnesium is not a risk factor for stone formation. Magnesium also binds with oxalate in gastrointestinal tract to reduce oxalate absorption. Citrate supplementation is one of the effective pharmacological options for preventing the recurrence of kidney stones. Calcium oxalate or calcium phosphate crystallization is antagonized by the citrate in the urine due to which recurrence of kidney stone is prevented by increased urinary citrate excretion. Potassium citrate along with thiazides are prescribed for kidney stone treatment at the same time it impaired by poor long term compliance, gastrointestinal upset and unpalatable taste. The remedy for this issue is taking potassium citrate with magnesium citrate combination. Magnesium can bind with oxalate due to which both diminishing and absorption of oxalate takes place thereby acting as a stone preventive. The binding of oxalate in urine is reduced by the binding of magnesium which results in the decrease in the recurrence of kidney stones. Patients who have diabetes, hypertension, and high blood cholesterol are often instructed to consume high oxalate foods such as fruits and vegetables. In this case, it is better to consume less and only selected fruits and vegetables to prevent kidney stones. The vitamins and mineral composition of the selected plants were given in **Figures 4** and **5** [41–56]. The plants discussed here contain all the nutrients in considerable quantities required for preventing and

**134**

managing calculi forming oxalates.

*3.3.1 Renal insufficiency due to vitamin E deficiciency*

organ injury in nutrients E-deficient rats is depicted.

**3.3 Impact of vitamin E in the management of disease and calciphytoliths**

In rats, a combination of fat-soluble vitamin deficiency and Se or glutathione deficiency causes extreme and progressive aerophilic damage to the urinary organ's structure and function [57–59]. Furthermore, urinary organ dysfunction caused by ischemia–reperfusion damage causes 50% mortality in dietary E- and seleniumdeficient rats compared to controls [60], and a-tocopherol administration increases the fatality rate by 46% after 120 minutes of heat anemia [61]. During a marked increase in the creatinine/molar creatol magnitude relationship, aerophilic urinary

Conversion is directly mediated by chemical group radicals [62]. The living nephrons enhanced the absorption of the element and the square oxide levels multiplied within the residual cortex of rats. Dietary fat-soluble vitamin administration 11 to 16 weeks after urinary tubule reduction has been shown to attenuate glomerulosclerosis by more than 500 weeks [63]. The fat-soluble vitamin deficiencies are never seen in humans and have been delineated by sensory neurological disorders.

thought to be mild. It is the most common form of nephrosis on the planet. The mechanism of harm is unknown, but related medical specialty insults to the kidneys seem to be introduced as a result of immune globulin accumulation, which induces chronic oxidative stress. There are currently no lucky drugs available that may bleed down the path of the disorder, with the exception of dominant cardiovascular disease and decreased dietary macromolecule use.

The associated experimental model of early immune globulin nephrosis in rats, mild oxidant-mediated inflammation and associated structure–functional changes in glomeruli have been shown to attenuate dietary fat-soluble vitamin levels from thirty to one hundred IU/kg of a biological attack, leading to a five-fold increase in humor-soluble vitamins. Nutrition E-supplemented rats had a four-fold reduced rate of symptom, the five-hundredth decline in albuminuria, eluted urinary organ tissue lipoid peroxidation, Stabilized urinary organ plasma flow, decreased expression of fibrinogenic protein transmission protein b1 (TGFb1), and had less extreme capillary hypertrophy than control animals [66]. During the additional analysis, supported by these initial observations, Chan et al. [67] indisputably argued that a two-and-a-half to five-fold increase in fat-soluble vitamin chow supplements (i.e. 250–500 IU/kg) may further reduce plasma and urinary organ lipoid peroxidation and albuminuria, but no further change in TGFb1 RNA has been identified. The use of fat-soluble vitamin 800 IU/day is expected to be useful in patients with immune globulin nephrosis and albuminuria but one g/day and a long-term regulated, double-blind trial are currently underway to explore this risk. Twenty-nine urinary organ response injuries may also be the product of advanced immune deposition directed to the capillary basement membrane. Anti-glomerular basement membrane (anti-GBM) nephrosis is concretely caused by anti-GBM antibodies in rats. 2 stages of capillary injury square measure are obvious. The first acute (heterologous) strategy involves the attachment of antibodies to the basement membrane amid neutrophils invasion and chronic capillary inflammation. Capillary vascular square measures blocked by microthrombus that reduces the rate of filtration and plasma flow [68].

The second delayed reaction is due to the target host (autologous phase) which ends up with symptomatic, multiplied urinary macromolecule excretion, capillary cardiovascular disease, capillary wall integrity defects, protein chemical action, and macrophages aggression. Convergence of urinary organ activity and improved maintenance of the capillary structure is detected in nephrosis-controlled rats with 5 mg/100 g fat-soluble vitamin weight 3 days before management of anti-GBM protein rather than in untreated controls [69]. The amendments were marked within the capillary filtration quantity, While chronic inflammation of immune globulin {nephropathy|renal disease|nephrosis|uropathy} and anti-GBM nephrosis is not the first event of the diseased part, it is crucial for aerophilic urinary organ injury seen in these situations. Fat-soluble vitamin decreases this injury by combining its medicinal and anti-coagulant effects and its ability to strengthen membranes. Potential for therapeutic action with fat-soluble vitamins may also arise during a host of alternative urinary organ abnormalities create through medical specialty insults and chronic inflammation.

Insufficiency and extreme albuminuria are two common examples. Fx1A [70, 71] PHN coupled with lipoid peroxidation was discovered in Passive Heymann nephrosis (PHN), a gnawing animal model for human membranous nephrosis resulting from sub-animal tissue immune absorption in capillary walls following injection of heterologous protein guided against a crude, autologous annular material. Wegener's granulomatosis, for example, is caused by the expansion of antineutrophil living antibodies (ANCAs) against proteins expressed on the surface of activated polymorph nuclear neutrophils. Subsequent degranulation releases toxic cell-degrading enzymes, oxygen-free radicals, and pro-inflammatory substances, a method that coincides with necrotizing crescentic capillary nephrosis.

**137**

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

The age-related improvements in the excretory organ function and the anatomy area are correlated with lipid peroxidation and oxidative stress. Excretory organ aging is characterized by gradual glomerulosclerosis, capillary filtration, and constriction. Old (13-month old) rats on an impact diet containing fifty IU/kg E have a three-fold increase in F2 isoprostane agent, a 60-percent decrease in capillary vessel filtration, and an increase in advanced glycosylation end product (AGE) compared to young animals (3–4 months of age) on a basic diet. Supplementing the old with a high E (5000 IU/kg) diet for an additional nine months, the liquid body substance level of the inhibitor increased by thirty percent and specifically improved the capillary vascular filtration rate by fifty percent, suppressed the initiation of F2 isoprostanes and amplified each glomerulosclerosis and AGE receptor expression, as well as decreasing the activation of excreting. It has been envisaged that a 40% decline in albuminuria seen in aged nutrients E-treated animals at twenty-two months compared to old controls may well be related to higher retention of capillary

There is a significant amount of evidence to support the involvement of oxidative stress in progressive urinary organ impairment. Mononucleate leukocytes in patients with chronic renal disease (CRF) area are additionally prone to lipid peroxidation of the membrane compared to those confined to healthy controls [73] and therefore red cells in patients with E-depleted quality area unit nutrient analysis [74–77]. Bochev et al. [78] stated that the development of nephropathy from chronic insufficiency to discontinued azotemia in the qualitative analysis was related to a lower blood inhibitor capacity; An increase in polymorphic nuclear blood cells due to aerophilic activity was correlated with an abnormally high level of lipid peroxidation. Penchant et al. [79] reported that in patients with advanced CRF, a very low macromolecule diet (0.3 g/kg per day) accompanied by essential amino acids and keto acids and vitamins, as well as E (a-tocopheryl acetate, 5 mg/day), A (7.5 mg/ day) and A (7.5 mg/day) was found. Sixty-one of the E levels in this patient cluster ranged from thirty-eighth to fifty-six of the management values [79] suggesting that although the sweetening was achieved, and a key red blood cell E deficiency persisted. Accumulated lipid peroxidation of red cell membranes and associated E deficiency contribute to their shortened half-life in circulation and the next anemia associated with pre-dialysis pathology seen in CRF. Thanks to dietary restrictions, CRF patients are also deficient in inhibitor vitamins and micronutrients. This is often markedly true for immediate post-hemodialysis in that the full inhibitor capacity falls from a pre-dialysis level of 1.54 to 1.38 mmol/L post-dialysis [80]. These rapid, degraded, standing inhibitor episodes could lead to windows that are usually vulnerable to general lipid peroxidation and subsequent aerophilic changes in transmitted lipoproteins, atherogenicity, and therefore distinctive upset and high blood pressure associated with CRF. In healthy plasma, salt and albumen account for seventy-five percent of full inhibitor activity in vitro, while ascorbate (vitamin C) and E account for 100 percent of full inhibitory action (a-tocopherol) [81]. Total post-dialysis inhibitors fall significantly, leading to a loss of soluble ascorbate and salt. Ha et al. [80] advised that water-soluble vitamin supplements up to one g/day should be routinely administered in qualitative analysis to reduce this temporary lack of soluble inhibitor capability. Although E is the major lipidsoluble inhibitor in plasma, the amount of nutritional inhibitor carotenoids (lutein, lycopene, a-and b-carotene) is also crucial for the effectiveness of lipoproteins from

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

vessel permeability, a parameter that reduces with age [72].

*3.3.4 Oxidative stress in kidney failure*

*3.3.3 Aging kidneys*

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths… DOI: http://dx.doi.org/10.5772/intechopen.97777*

#### *3.3.3 Aging kidneys*

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

disease and decreased dietary macromolecule use.

thought to be mild. It is the most common form of nephrosis on the planet. The mechanism of harm is unknown, but related medical specialty insults to the kidneys seem to be introduced as a result of immune globulin accumulation, which induces chronic oxidative stress. There are currently no lucky drugs available that may bleed down the path of the disorder, with the exception of dominant cardiovascular

The associated experimental model of early immune globulin nephrosis in rats, mild oxidant-mediated inflammation and associated structure–functional changes in glomeruli have been shown to attenuate dietary fat-soluble vitamin levels from thirty to one hundred IU/kg of a biological attack, leading to a five-fold increase in humor-soluble vitamins. Nutrition E-supplemented rats had a four-fold reduced rate of symptom, the five-hundredth decline in albuminuria, eluted urinary organ tissue lipoid peroxidation, Stabilized urinary organ plasma flow, decreased expression of fibrinogenic protein transmission protein b1 (TGFb1), and had less extreme capillary hypertrophy than control animals [66]. During the additional analysis, supported by these initial observations, Chan et al. [67] indisputably argued that a two-and-a-half to five-fold increase in fat-soluble vitamin chow supplements (i.e. 250–500 IU/kg) may further reduce plasma and urinary organ lipoid peroxidation and albuminuria, but no further change in TGFb1 RNA has been identified. The use of fat-soluble vitamin 800 IU/day is expected to be useful in patients with immune globulin nephrosis and albuminuria but one g/day and a long-term regulated, double-blind trial are currently underway to explore this risk. Twenty-nine urinary organ response injuries may also be the product of advanced immune deposition directed to the capillary basement membrane. Anti-glomerular basement membrane (anti-GBM) nephrosis is concretely caused by anti-GBM antibodies in rats. 2 stages of capillary injury square measure are obvious. The first acute (heterologous) strategy involves the attachment of antibodies to the basement membrane amid neutrophils invasion and chronic capillary inflammation. Capillary vascular square measures blocked by

microthrombus that reduces the rate of filtration and plasma flow [68].

method that coincides with necrotizing crescentic capillary nephrosis.

The second delayed reaction is due to the target host (autologous phase) which ends up with symptomatic, multiplied urinary macromolecule excretion, capillary cardiovascular disease, capillary wall integrity defects, protein chemical action, and macrophages aggression. Convergence of urinary organ activity and improved maintenance of the capillary structure is detected in nephrosis-controlled rats with 5 mg/100 g fat-soluble vitamin weight 3 days before management of anti-GBM protein rather than in untreated controls [69]. The amendments were marked within the capillary filtration quantity, While chronic inflammation of immune globulin {nephropathy|renal disease|nephrosis|uropathy} and anti-GBM nephrosis is not the first event of the diseased part, it is crucial for aerophilic urinary organ injury seen in these situations. Fat-soluble vitamin decreases this injury by combining its medicinal and anti-coagulant effects and its ability to strengthen membranes. Potential for therapeutic action with fat-soluble vitamins may also arise during a host of alternative urinary organ abnormalities create through medical specialty insults and chronic inflammation. Insufficiency and extreme albuminuria are two common examples. Fx1A [70, 71] PHN coupled with lipoid peroxidation was discovered in Passive Heymann nephrosis (PHN), a gnawing animal model for human membranous nephrosis resulting from sub-animal tissue immune absorption in capillary walls following injection of heterologous protein guided against a crude, autologous annular material. Wegener's granulomatosis, for example, is caused by the expansion of antineutrophil living antibodies (ANCAs) against proteins expressed on the surface of activated polymorph nuclear neutrophils. Subsequent degranulation releases toxic cell-degrading enzymes, oxygen-free radicals, and pro-inflammatory substances, a

**136**

The age-related improvements in the excretory organ function and the anatomy area are correlated with lipid peroxidation and oxidative stress. Excretory organ aging is characterized by gradual glomerulosclerosis, capillary filtration, and constriction. Old (13-month old) rats on an impact diet containing fifty IU/kg E have a three-fold increase in F2 isoprostane agent, a 60-percent decrease in capillary vessel filtration, and an increase in advanced glycosylation end product (AGE) compared to young animals (3–4 months of age) on a basic diet. Supplementing the old with a high E (5000 IU/kg) diet for an additional nine months, the liquid body substance level of the inhibitor increased by thirty percent and specifically improved the capillary vascular filtration rate by fifty percent, suppressed the initiation of F2 isoprostanes and amplified each glomerulosclerosis and AGE receptor expression, as well as decreasing the activation of excreting. It has been envisaged that a 40% decline in albuminuria seen in aged nutrients E-treated animals at twenty-two months compared to old controls may well be related to higher retention of capillary vessel permeability, a parameter that reduces with age [72].

#### *3.3.4 Oxidative stress in kidney failure*

There is a significant amount of evidence to support the involvement of oxidative stress in progressive urinary organ impairment. Mononucleate leukocytes in patients with chronic renal disease (CRF) area are additionally prone to lipid peroxidation of the membrane compared to those confined to healthy controls [73] and therefore red cells in patients with E-depleted quality area unit nutrient analysis [74–77]. Bochev et al. [78] stated that the development of nephropathy from chronic insufficiency to discontinued azotemia in the qualitative analysis was related to a lower blood inhibitor capacity; An increase in polymorphic nuclear blood cells due to aerophilic activity was correlated with an abnormally high level of lipid peroxidation. Penchant et al. [79] reported that in patients with advanced CRF, a very low macromolecule diet (0.3 g/kg per day) accompanied by essential amino acids and keto acids and vitamins, as well as E (a-tocopheryl acetate, 5 mg/day), A (7.5 mg/ day) and A (7.5 mg/day) was found. Sixty-one of the E levels in this patient cluster ranged from thirty-eighth to fifty-six of the management values [79] suggesting that although the sweetening was achieved, and a key red blood cell E deficiency persisted. Accumulated lipid peroxidation of red cell membranes and associated E deficiency contribute to their shortened half-life in circulation and the next anemia associated with pre-dialysis pathology seen in CRF. Thanks to dietary restrictions, CRF patients are also deficient in inhibitor vitamins and micronutrients. This is often markedly true for immediate post-hemodialysis in that the full inhibitor capacity falls from a pre-dialysis level of 1.54 to 1.38 mmol/L post-dialysis [80]. These rapid, degraded, standing inhibitor episodes could lead to windows that are usually vulnerable to general lipid peroxidation and subsequent aerophilic changes in transmitted lipoproteins, atherogenicity, and therefore distinctive upset and high blood pressure associated with CRF. In healthy plasma, salt and albumen account for seventy-five percent of full inhibitor activity in vitro, while ascorbate (vitamin C) and E account for 100 percent of full inhibitory action (a-tocopherol) [81].

Total post-dialysis inhibitors fall significantly, leading to a loss of soluble ascorbate and salt. Ha et al. [80] advised that water-soluble vitamin supplements up to one g/day should be routinely administered in qualitative analysis to reduce this temporary lack of soluble inhibitor capability. Although E is the major lipidsoluble inhibitor in plasma, the amount of nutritional inhibitor carotenoids (lutein, lycopene, a-and b-carotene) is also crucial for the effectiveness of lipoproteins from aerophilic changes, and there are also inequalities within the traditional level of this category of antioxidants throughout CRF. Of these compounds, carotenoid is the most impacted at physiological levels and its plasma concentration is significantly reduced in post-dialysis CRF patients (0.17 mmol/L) compared to healthy controls (0.44 mmol/L). The carotenoid deficiencies may additionally contribute to the associated obstructed plasma defense inhibitor system and make up one for dietary therapeutic intervention in addition to E.

#### *3.3.5 Effective dose of vitamin E in renal failure treatment*

Normalizing the standing inhibitor of CRF patients with dietary E victimization would be a cost-effective and straightforward therapeutic target. In healthy individuals, the common daily allowance of E is 8 mg (12 IU) for girls and 10 mg (15 IU) for men (1 mg = 1.5 IU) supported common levels needed to prevent symptoms of deficiency [82]. The Plasma pool-turnover is fast (1.4 ± 0.6 pools/day) [83] and therefore the traditional transmitted plasma varies among eleven. 5 and 35.0 m [84] and giant oral doses (1500–3200 IU/day) occur together to be safe, with minor and well-tolerated duct appearance effects [85] although current levels will only be increased by 2 to 4 times the standard quantity. (The higher limit is limited by the viscus E enzyme, which preserves the plasma levels within the slime, with excess tocopherols being excreted in the digestive juice.) [86]. Vitamin E has been tested in humans with some success in the treatment of system diseases involving oxygen-free radicals and aerophilic stress in their clinical expression, as well as Friedreich's neurological disease (400 IU/day) [87]. Alzheimer's disease (2000 IU/ day) [88]. Parkinson's disease (3200 IU/day) [89]. the first stages of Huntington's disease (3000 IU/day) [90] and dyskinesia (800–160 IU/day) [91–93].

The best dose of E for preventing human failure is also between 300 and 700 IU per day. (This is a healthy 'therapeutic variance,' meaning that the nutrient levels needed to prevent long-term muscular disease caused by aerophilic stress are below the edge for aspect effects.) Suha et al. [77] discovered that giving chronic dialysis patients 300 mg/day (450 IU/day) E for one month resulted in critical dialysis. Low doses of E, such as 100 mg/day (150 IU/day), have been shown to provide critical defense against the risk of upset, which is a major complication of CRF [94]. Dietary E supplements that boost plasma levels could be beneficial for sluggish people. E medical care may also be cost-effective in alleviating chronic kidney disease and standing pathophysiology.

Impaired plasma inhibitor arms are characterized by chronic kidney disease and standing pathology. Besides, E medical care is considered to be a method of correcting the position of plasma antioxidants and attenuating disorders related to kidney disease. In conclusion, the mixture of E and antioxidants protects against HLPinduced salt uropathy. Calculus disease has been known to be the leading disease of life in every human and animal. Calculus could destroy the excretory organ of hollow epithelial tissue, leading to impaired excretory organ function. Aerophilic stress in chronic inflammatory conditions, anti-glomerular basement membrane kidney disease, focal segmental glomerulosclerosis, rhabdomyolysis (myoglobin acute excretory organ failure), diabetic uropathy, and toxic poisoning compounds such as transition metals, weed killers, and medicines such as cyclosporine A and cisplatin all aggravate the progression to failure. E inhibitor membrane (5–007-tocopherol) is considered to be the possible therapeutic intervention that will make it easier to weigh reduce the level of decrease in excretory organ activity under these conditions. The impaired plasma inhibitor arm is indicative of chronic kidney disease and standing pathology. E medical care is also thought of as a method of correcting the status of plasma antioxidants.

**139**

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

Kidney stone disease has been identified together as a major disease in every human and animal. Calculus (stone) may harm the excretory hollow epithelial tissue of the organ, resulting in the impaired excretory activity of the organ. The most important of human excretory organ stones is the metallic element salt, which relates to the metallic element and the metabolism of salt in the tissue and urinary tract system [95–97]. CaOx stone also had a high incidence and recurrence rate in animals and iatrogenic aerobic stress [98]. Several previous studies have shown that increased aerobic stress has been associated with the formation of CaOx crystal and stone. As a result, intrusion with aerobic damage could also play a key role in stopping the continuous formation of stones and the resulting excretory organ pathology. Antioxidant supplement (Vit E) reduces metabolic stress, salt excretion, and crystal formation of CaOx in hyperoxaluric rats receiving antifreeze (EG) [99]. In hypertensive and hyperoxaluric patients, oral supplementation of Vit E at four hundred mg/day for 9 months may normalize the organic chemistry and kinetic properties of Tamm-Horsfall supermolecules that impede

Also, overproduction of antioxidants avoided metallic element salt accumulation by preventing peroxidant injury and preserving excretory organ tissue antioxidants and glutathione oxidation–reduction balance. Antioxidant medical aid may therefore protect against the accumulation of metallic element salt stones within the

It is reportedly stated that oxygen-free radicals square measure essential for the

In summary, although the use of herbal medicine in the treatment and prevention of urinary stones recurrence has been proven and promising, further studies are needed to understand disease physiology, the action mechanism of herbal medicine to develop an effective and safe lithophytic agent. At the same time, it is necessary to identify the mechanism of action for the discussed vitamins containing plants, thereby assessing the dosage, controlling herbal quality, and investigating their interactions and side effects. Vitamin E plants may completely prevent deposition of oxalate by preventing pre-oxidation injury and restoring renal tissue antioxidants. So vitamin E therapy also might protect against oxalate calculi deposition

pathology of multiple chronic disorders as well as renal failure. Enhanced element radical generation and/or compromised inhibitor weaponry leads to chronic oxidative stress that markedly worsens several things. Three excellent concerns were jointly endorsed by the likelihood of delaying the regression to kidney disease through inhibitor action. Restoration of capillary membrane integrity is important for urinary organ activity, and the biomembrane square measure is protected from aerophilic deterioration by the fat-soluble vitamin lipotropic inhibitor, primarily

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

**4. Discussion and conclusion**

CaOx crystal aggregation [100].

human circulatory organ [101].

within the species of a-tocopherol [102].

in the human kidneys.

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths… DOI: http://dx.doi.org/10.5772/intechopen.97777*

#### **4. Discussion and conclusion**

*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

therapeutic intervention in addition to E.

disease and standing pathophysiology.

status of plasma antioxidants.

*3.3.5 Effective dose of vitamin E in renal failure treatment*

aerophilic changes, and there are also inequalities within the traditional level of this category of antioxidants throughout CRF. Of these compounds, carotenoid is the most impacted at physiological levels and its plasma concentration is significantly reduced in post-dialysis CRF patients (0.17 mmol/L) compared to healthy controls (0.44 mmol/L). The carotenoid deficiencies may additionally contribute to the associated obstructed plasma defense inhibitor system and make up one for dietary

Normalizing the standing inhibitor of CRF patients with dietary E victimization would be a cost-effective and straightforward therapeutic target. In healthy individuals, the common daily allowance of E is 8 mg (12 IU) for girls and 10 mg (15 IU) for men (1 mg = 1.5 IU) supported common levels needed to prevent

symptoms of deficiency [82]. The Plasma pool-turnover is fast (1.4 ± 0.6 pools/day) [83] and therefore the traditional transmitted plasma varies among eleven. 5 and 35.0 m [84] and giant oral doses (1500–3200 IU/day) occur together to be safe, with minor and well-tolerated duct appearance effects [85] although current levels will only be increased by 2 to 4 times the standard quantity. (The higher limit is limited by the viscus E enzyme, which preserves the plasma levels within the slime, with excess tocopherols being excreted in the digestive juice.) [86]. Vitamin E has been tested in humans with some success in the treatment of system diseases involving oxygen-free radicals and aerophilic stress in their clinical expression, as well as Friedreich's neurological disease (400 IU/day) [87]. Alzheimer's disease (2000 IU/ day) [88]. Parkinson's disease (3200 IU/day) [89]. the first stages of Huntington's

The best dose of E for preventing human failure is also between 300 and 700 IU per day. (This is a healthy 'therapeutic variance,' meaning that the nutrient levels needed to prevent long-term muscular disease caused by aerophilic stress are below the edge for aspect effects.) Suha et al. [77] discovered that giving chronic dialysis patients 300 mg/day (450 IU/day) E for one month resulted in critical dialysis. Low doses of E, such as 100 mg/day (150 IU/day), have been shown to provide critical defense against the risk of upset, which is a major complication of CRF [94]. Dietary E supplements that boost plasma levels could be beneficial for sluggish people. E medical care may also be cost-effective in alleviating chronic kidney

Impaired plasma inhibitor arms are characterized by chronic kidney disease and standing pathology. Besides, E medical care is considered to be a method of correcting the position of plasma antioxidants and attenuating disorders related to kidney disease. In conclusion, the mixture of E and antioxidants protects against HLPinduced salt uropathy. Calculus disease has been known to be the leading disease of life in every human and animal. Calculus could destroy the excretory organ of hollow epithelial tissue, leading to impaired excretory organ function. Aerophilic stress in chronic inflammatory conditions, anti-glomerular basement membrane kidney disease, focal segmental glomerulosclerosis, rhabdomyolysis (myoglobin acute excretory organ failure), diabetic uropathy, and toxic poisoning compounds such as transition metals, weed killers, and medicines such as cyclosporine A and cisplatin all aggravate the progression to failure. E inhibitor membrane (5–007-tocopherol) is considered to be the possible therapeutic intervention that will make it easier to weigh reduce the level of decrease in excretory organ activity under these conditions. The impaired plasma inhibitor arm is indicative of chronic kidney disease and standing pathology. E medical care is also thought of as a method of correcting the

disease (3000 IU/day) [90] and dyskinesia (800–160 IU/day) [91–93].

**138**

Kidney stone disease has been identified together as a major disease in every human and animal. Calculus (stone) may harm the excretory hollow epithelial tissue of the organ, resulting in the impaired excretory activity of the organ. The most important of human excretory organ stones is the metallic element salt, which relates to the metallic element and the metabolism of salt in the tissue and urinary tract system [95–97]. CaOx stone also had a high incidence and recurrence rate in animals and iatrogenic aerobic stress [98]. Several previous studies have shown that increased aerobic stress has been associated with the formation of CaOx crystal and stone. As a result, intrusion with aerobic damage could also play a key role in stopping the continuous formation of stones and the resulting excretory organ pathology. Antioxidant supplement (Vit E) reduces metabolic stress, salt excretion, and crystal formation of CaOx in hyperoxaluric rats receiving antifreeze (EG) [99]. In hypertensive and hyperoxaluric patients, oral supplementation of Vit E at four hundred mg/day for 9 months may normalize the organic chemistry and kinetic properties of Tamm-Horsfall supermolecules that impede CaOx crystal aggregation [100].

Also, overproduction of antioxidants avoided metallic element salt accumulation by preventing peroxidant injury and preserving excretory organ tissue antioxidants and glutathione oxidation–reduction balance. Antioxidant medical aid may therefore protect against the accumulation of metallic element salt stones within the human circulatory organ [101].

It is reportedly stated that oxygen-free radicals square measure essential for the pathology of multiple chronic disorders as well as renal failure. Enhanced element radical generation and/or compromised inhibitor weaponry leads to chronic oxidative stress that markedly worsens several things. Three excellent concerns were jointly endorsed by the likelihood of delaying the regression to kidney disease through inhibitor action. Restoration of capillary membrane integrity is important for urinary organ activity, and the biomembrane square measure is protected from aerophilic deterioration by the fat-soluble vitamin lipotropic inhibitor, primarily within the species of a-tocopherol [102].

In summary, although the use of herbal medicine in the treatment and prevention of urinary stones recurrence has been proven and promising, further studies are needed to understand disease physiology, the action mechanism of herbal medicine to develop an effective and safe lithophytic agent. At the same time, it is necessary to identify the mechanism of action for the discussed vitamins containing plants, thereby assessing the dosage, controlling herbal quality, and investigating their interactions and side effects. Vitamin E plants may completely prevent deposition of oxalate by preventing pre-oxidation injury and restoring renal tissue antioxidants. So vitamin E therapy also might protect against oxalate calculi deposition in the human kidneys.

#### **Author details**

Ramu Govindan1 \*, Tilak Meenakshisundaram<sup>2</sup> , Navanita Sivaramakumar1 , Podila Naresh3 , Duraiswamy Basavan1 and Dhanabal Palanisamy1

1 Department of Pharmacognosy, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Nilgiris, Tamilnadu, India

2 Horticultural Research Station, Tamil Nadu Agricultural University, Nilgiris, Tamilnadu, India

3 Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Nilgiris, Tamilnadu, India

\*Address all correspondence to: ramupharmu@jssuni.edu.in

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**141**

*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths…*

stones in Shiraz, Med J Islam Repub

Nutritional Treatment of Kidney Stones, Journal of the American Herbalists,

[10] David Winston, Herbal and

[11] Phillip M.Hall, Nephrolithiasis: Treatment, causes, and prevention, Cleveland Clinic Journal of Medicine

[12] Chen H.J et al. Mast cell-dependent allergic responses are inhibited by ethanolic extract of Adlay testa, Journal of Agricultural and Food Chemistry,

[13] Tolkachev ON, Zhuchenko AA. Biologically active substances of flax: medicinal and nutritional properties (a review) Pharm Chem J. 2000, 34,

[14] Oomah BD. Flaxseed as a functional food source. J Sci Food Agric. 2001, 81,

commercial processing of flaxseed. Ind

[16] Singh K. K., Mridula D., Rehal J., and Barnwal P. Flaxseed: A Potential Source of Food, Feed, and Fiber Critical Reviews in Food Science and Nutrition

[17] Morris DH.: Flax Primer, A Health and Nutrition Primer. Flax Council of

[18] RubilarM, Gutiérrez C, Verdugo M, Shene C, Sineiro J.: Flaxseed as a source of functional ingredients. J Soil Sci Plant

Iran, 2019, 33(8), 1-7.

2012, 10(2), 61-71.

2009, 76(10), 583-592.

2010, 58(4), 2596-2601.

[15] Oomah BD, Mazza G. Compositional changes during

Crop Prod. 1998, 9, 29-37.

2011, 51, (3), 210-222.

Canada., 2007, p. 9-19.

Nutr., 2010, 10(3), 373-377.

[19] K.A. Faseehuddin Shakir and Basavaraj Madhusudhan, Effects of

360-367.

889-894.

*DOI: http://dx.doi.org/10.5772/intechopen.97777*

[1] Croppi E, Ferraro M. P and Taddei L. et al, Prevalence of renal stones in an Italian urban population: a general practice-based study, Urol Res, 2012,

[2] Andrew J., Portis and Chandru P, Diagnosis and Initial Management of Kidney Stones, Am Fam Physician,

[3] Kirkley Z., Rasooly R and Star A. R. et al, Urinary Stone Disease: Progress, Status, and Needs", Urology, 2015,

Abraham A, Saraswathi R, Mohanta GP

evaluation of herbal gel of Basella alba for wound healing activity, Journal of Pharmaceutical Sciences and Research,

[5] Tilahun Align and Beyene Petros, Kidney Stone Disease: An Update on Current Concepts, Researchgate 2018,

[6] Victoriano Romero, Haluk Akpinar, and Dean G Assimos, Kidney Stones: A Global Picture of Prevalence, Incidence, and Associated Risk Factors, Reviews in Urology, Spring-Summer; 2010, 12(2-3),

[7] Jalpa Ram, Pooja Moteriya and Sumitra Chanda, An overview of some promising medicinal plants with *in vitro* anti-urolithic activity, IOSR Journal of

[8] Alkhunaizi M. A. Urinary stones in Eastern Saudi Arabia, Urology Annals,

[9] Bazyar H. Ahmadi A. Zare Javid A., Irani D., Mohammadi Sartang M and Haghighizadeh MH. The association between dietary intakes and stone formation in patients with urinary

Pharmacy, 2015, 5(5), 23-28.

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*Impact of Vitamins and Minerals Enriched Flora in the Management of Calciphytoliths… DOI: http://dx.doi.org/10.5772/intechopen.97777*

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*Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects*

\*, Tilak Meenakshisundaram<sup>2</sup>

2 Horticultural Research Station, Tamil Nadu Agricultural University,

of Higher Education and Research, Nilgiris, Tamilnadu, India

\*Address all correspondence to: ramupharmu@jssuni.edu.in

provided the original work is properly cited.

, Duraiswamy Basavan1

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and Dhanabal Palanisamy1

1 Department of Pharmacognosy, JSS College of Pharmacy, JSS Academy of Higher

3 Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy

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Ramu Govindan1

Nilgiris, Tamilnadu, India

Podila Naresh3

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[82] Meydani M, Meisler JG. A closer look at vitamin E. Postgrad. Med. 1997; 102: 199-207. 65. Traber MG, Ramakrishnan R, Kayden HJ. Human plasma vitamin E kinetics demonstrate rapid recycling of Ra-tocopherol. Proc.

Natl Acad. Sci. USA 1994; 91: 10005-10008.

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**147**

Section 2

General Information on

Vitamin E

## Section 2
