**Abstract**

The Mediterranean diet is characterized by an increased consumption of fruits, vegetables, grains, and fish. Olive oil and herbs and spices are also essential components of this food regimen. Such a diet is associated with a reduced risk of cardiovascular disease, overall mortality, reduced incidence of Parkinson's and Alzheimer's diseases, and reduced cognitive impairment. Some of the bioactive components that exert beneficial effects are ω-3 fatty acids, polyphenols, and alkaloids that have neuroprotective, anti-inflammatory, antioxidant, antimicrobial, and gluco-regulating properties. These beneficial effects contribute to improved health including organ health and cognitive function. While the number of such bioactive plant constituents is numerous, this review will examine the role of specific bioactives and vitamins and assess the molecular mechanisms including the antioxidant and anti-inflammatory beneficial effects of the bioactive components in the Mediterranean diet.

**Keywords:** polyphenols, inflammation, fatty acids, kidney health, cognition

## **1. Introduction**

The Mediterranean diet (MedDiet) is characterized by an increased consumption of olive oil, fruits, vegetables, grains, and fish. It is defined as including olive oil as the main added lipid, two or more servings of vegetables at every meal, 1–2 servings of fruit at every meal, and two or more servings of fish on a weekly basis [1]. These ingredients impart specific nutrients which are the means for the MedDiet to have its beneficial effect. There are clearly advantageous consumptions of specific fatty acids such as oleic acid, a monounsaturated fat (MUFA) in olive oil, and the ω-3 fatty acids (polyunsaturated fat, PUFA) associated with fish consumption. Also, the plant-based ingredients: vegetables, breads and cereals, fruits, nuts, herbs, and spices which are components of the MedDiet impart specific nutrients that have a direct biological activity to enhance antioxidant support and reduce inflammation. This direct effect of the specific nutrients is likely the means to the reduced risk of cardiovascular disease, overall mortality, reduced incidence of Parkinson's and Alzheimer's diseases, and reduced cognitive impairment with aging.

A challenge in discovering the actual nutrients and their mode of action is that the MedDiet is often defined by a group of people consuming that food and then comparing that group to a cohort that is not consuming the MedDiet [2, 3]. This can generate likely benefits and an understanding of the ingredients which result in the observed beneficial effects of the MedDiet. It is apparent that these benefits come from specific ingredients. This leads to specific avenues of understanding of the biology behind the benefit of consuming the MedDiet. For example, some of the specific nutrients, which have been stated to be important components, are resveratrol from grapes, anthocyanins from vegetables and fruits, and polyunsaturated fatty acids especially those from olive oil and fish [4]. These nutrients were discussed in a recent review as well as the antioxidant nutrients such as selenium, the vitamins A, C, E, and the bioactive antioxidants of lycopene and the carotenoids [5]. These authors also stated that the increased consumption of specific phytochemicals played a role in the effectiveness of the MedDiet including resveratrol and epigallocatechin gallate, retinoids, phenolic acids, terpenes, isoflavones, and polyphenols.

These possibilities can then be further elucidated by specific individual factor experiments with focused outcomes in both human and nonhuman animals. This review will assess the molecular mechanisms of some of the most likely compounds which through their influence on the oxidant and inflammatory pathways result in the beneficial effects of the MedDiet.

#### **2. Discussion**

The antioxidant defense system protects the body from free radical damage and is an essential component of the control of prooxidant damage and pro-inflammatory cytokines [6–8]. The active antioxidant nutrients in the MedDiet include a number of phytopolyphenols including quercetin, resveratrol, curcumin, apigenin, and epigallocatechin gallate [9, 10]. Quercetin, a flavonoid polyphenol, is a free radical scavenger and binds transition metal ions; both activities provide support for the antioxidant defenses [11]. The defense against low-density lipoprotein (LDL) oxidation provided by quercetin may be of significant benefit in reducing the risk of coronary heart disease [12]. Resveratrol, a stilbene polyphenol found in grapes and berries, is a potent antioxidant with multiple biological effects [13] which support its positive influence in the MedDiet [14]. For example, acting as an antioxidant resveratrol was shown to be effective in reducing the neuroinflammation and memory loss in aged mice [15]. The role of curcumin, a polyphenol found in turmeric, as an antioxidant has been frequently reviewed [16, 17]. In a recent review [18], it was concluded that curcumin was effective in reducing protein and lipid oxidation. They noted a reduction in nitrotyrosines, thiols, protein carbonyls, and malondialdehyde. This was accompanied with an increased activity of glutathione peroxidase and superoxide dismutase both effective antioxidant enzymes. This enhanced antioxidant status is consistent with curcumin being a positive component of the benefits for those consuming the MedDiet. Apigenin, a flavonoid found in parlsey and celery, has been shown to be both an antioxidant and an anti-inflammatory compound [19, 20]. These antioxidant and anti-inflammatory effects suggest that the MedDiet benefits in protecting against cancer, cardiovascular disease, and all-cause death are partially the result of its consumption. Epigallocatechin gallate (EGCG), a major polyphenol found in green tea, is an effective antioxidant [21] that has been shown to be a benefit in modulating the molecular and cellular mechanisms associated with obesity and hypertension [22, 23]. *Influence of Bioactive Components of the Mediterranean Diet on Inflammation and Healthy Aging DOI: http://dx.doi.org/10.5772/intechopen.108448*

Because of these benefits, it is quite likely that epigallocatechin gallate has a positive role in the benefits of consuming the MedDiet. Taken as a group, the phytophenols associated with the MedDiet are a significant support for health outcomes through reduced oxidation and control of inflammation.

The vitamins including C, D, E, B12, B6, and folic acid [8] which are found in abundance in the MedDiet also support the oxidant defense system and overall health. Vitamins E, C, and β-carotene are well-known antioxidants present in the MedDiet which have been shown to be significant antioxidants with health benefits [24–27]. Circulating vitamin D is increased in the MedDiet [28]. In addition to the antioxidant effect of vitamin D [29], this may be a direct benefit and a factor in the reduced risk of bone fracture associated with the MedDiet [30]. It is possible that the enhanced B12, B6, and folic acid nutrition associated with the MedDiet have their beneficial effects through a reduction in homocysteine. These vitamins along with betaine (which is enhanced in the MedDiet because of the increased consumption of grains) are all influential in reducing homocysteine. This is a likely benefit associated with the consumption of the MedDiet because increased homocysteine is associated with more than 100 diseases [31].

The composition of olive oil is significant for understanding the role of fats in the MedDiet. Olive oil has as a majority fatty acid oleic acid (18:1) with between 2.8%–21.1% of linoleic and 0.49–1.9% linolenic [32]. Regarding the fatty acid composition of the MedDiet, the frequent servings of fish complement the ω-3 linolenic acid by adding EPA and DHA. In general, it is well known that the consumption of the ω-3 fatty acids (linolenic, EPA, and DHA) results in reduced inflammation as compared to the ω-6 fatty acids [33]. However, there are reports that oleic acid is also antiinflammatory [34, 35] although it is not elongated or desaturated to the eicosanoids through which the ω-3 and ω-6 fatty acids have their effects [36]. The pro-inflammatory and regulatory effects of the eicosanoids have been reviewed showing the relative anti-inflammatory role of the ω-3 fatty acids [37].

A decline in certain domains of cognitive function including attention, memory, and executive function, with normal aging has been reported [38, 39]. Structural and functional changes in the brain associated with aging also contribute to a decline in cognitive performance. There is evidence to indicate that increased intake of antioxidant and polyphenol-rich MedDiet combined with physical activity may be associated with less brain atrophy in humans without dementia [39, 40]. While dietary interventions, in particular MedDiet, have shown promising results in improving cognitive function [41, 42], further studies are needed as results have been inconsistent. Nevertheless, a diet rich in polyphenols, vitamins, and essential fatty acids, which together form a core component of MedDiet, is an important interventional strategy to minimize the modifiable risk of aging-associated cognitive decline. **Table 1** highlights the role of the MedDiet ingredients dietary legumes and nuts on cognitive function.

#### **3. Conclusions**

This review highlights that the ingredients associated with the MedDiet impart specific nutrients. The nutrients discussed here do not explain all of the benefits of consuming the MedDiet. However, they have been shown to reduce systemic chronic inflammation and optimize the normal oxidative balance. These changes contribute to the enhanced length of life and well-being, including a beneficial effect on cognitive function, observed with this dietary regimen.


**Study model Methodology and results Results for cognition or learning and memory References** Study investigated the relation between food patterns and mild cognitive impairment (MCI) among elderly Chinese population (n=2311, 60–88 yr participants from 760 communities of six districts in China) A 49-item food frequency questionnaire survey was administered and 4 dietary patterns were identified. Chinese version of the Mattis Dementia Rating Scale (CDRS) was used to assess the general cognitive status as well as the Chinese version of MMSE. Food pattern that included a higher intake of legumes, vegetables, fruits, milk and dairy products, nuts but a low intake of noodles and cereals was significantly correlated with better cognitive function including memory and language function. [47] Study investigated the cross- sectional association between adherence to MedDiet and cognitive performance (n= 1607 men and women, 20–70 yr) in Holland. Study conducted using the cross- sectional data of the Nutrition Questionnaires plus (NQplus) study Dietary intake was assessed using a 183-item Food Frequency Questionnaire. MedDiet intakes were measured on a scale based on consumption of vegetables, legumes, fruits/nuts, cereals, fish/seafood, meat/poultry, dairy, ethanol and the MUFA:SFA ratio. Cognitive function was assessed using three standardized neuropsychological tests including the Letter Fluency test (LFT), Symbol Digit Modalities Test (SDMT), and the Rivermead Behavioral Memory Tests (RBMT) Increased adherence to MedDiet was associated with poorer everyday memory. While higher vegetable intake was associated with better processing speed in cognitive tests, higher legume intake was with related to poorer processing speed. [48] Study analyzed the consumption of foods among elderly Italian individuals (n = 214 subjects, aged ≥65 years) and cognitive function over a period of 12 months. Food choice was measured by a combination of the dietary intake data, assessed by a 24-h recall and a seven-day diet record. MMSE and the cognitive sub-test of ADA Scale were used to detect cognitive decline progression over 12 months. While there was a positive association between a food pattern that included high legume consumption and improved MMSE after an interval of 1 year, there was an inverse association with basal and 1 year ADAS-cog test. Dietary pattern that included plant proteins and PUFAs was independently associated with an improvement on ADAS-cog after 1 year. [49] Study assessed the efficacy of a MedDiet approach to reduce the onset of cognitive decline, and promote optimal cognitive performance among healthy older adults (n = 137 men and women, >65 yr) in Australia The MedLey Study A randomized 2-cohort parallel group intervention trial, examining the effect of a Mediterranean dietary pattern (MedDiet) for six months that extended for a duration of 18 months Experimental group consumed traditional Cretan MedDiet (i.e. vegetables, fruits, olive oil, legumes, fish, whole grain cereals, nuts and seeds and low consumption of processed foods, dairy products, red meat and vegetable oils). Control group were asked to maintain their customary lifestyle and diet. A neuropsychological test battery that included 11 individual tests. MedDiet group did not perform significantly better than control group in tests to assess executive functioning, speed of processing, memory, visual-spatial ability. Thus, there was little evidence of a beneficial effect of a MedDiet intervention on cognitive function among healthy older adults. [50]

*Influence of Bioactive Components of the Mediterranean Diet on Inflammation and Healthy Aging DOI: http://dx.doi.org/10.5772/intechopen.108448*


**Table 1.** *The role of Mediterranean diet ingredients on cognitive function.* *Influence of Bioactive Components of the Mediterranean Diet on Inflammation and Healthy Aging DOI: http://dx.doi.org/10.5772/intechopen.108448*
