**3.8 Effects of replacement of SFA with other nutrients on plasma lipids, blood pressure, and other risk markers**

Replacing 1% of energy from SFA with 1% of energy from PUFA, MUFA, or complex carbohydrates decreased plasma LDL cholesterol by 2.1, 1.6, and 1.3 mg/dl, respectively [102]. HDL cholesterol decreased by 0.2, 0.2, and 0.4 mg/dl after substitution of SFA by PUFA, MUFA, or complex carbohydrate. The change in TG

## *Effects and Issues of Diet Fat on Cardiovascular Metabolism DOI: http://dx.doi.org/10.5772/intechopen.93261*

was 0.9, 0.4, and +1 mg/dl by substituting with PUFA, MUFA, or complex carbohydrates. These data indicate that in order to decrease LDL cholesterol or TG, the best strategy is to reduce the intake of SFA. SFA exert different LDL increasing ability depending on chain length. However, this difference is not clinically so important, because every oil contains several SFAs with various chain lengths. In general, there are progressive increases in LDL-C with diminishing chain length. The potency of the LDL-raising effects of individual SFAs is lauric acid (C12:0) > myristic acid (C14:0) > palmitic acid (C16:0) [103].

SFA may affect the risk of CV disease independently of LDL cholesterol, through the effects on inflammation, endothelial function, thrombosis, and ventricular arrhythmias [104]. One ex vivo randomized cross-over study showed that a breakfast with butter (35% SFA) induced a higher increase in TNF-alfa mRNA than breakfasts with olive oil (36% MUFA) or walnuts (16% PUFA), and also a higher response in IL-6 mRNA than the walnut breakfast in peripheral blood mononuclear cells (PBMCs) in healthy subjects (**Figure 10**) [105]. In another study, LDL-induced adhesion of monocyte to endothelial cells was also lower after MUFA consumption than after SFA in healthy individuals [106]. Some other ex vivo studies in humans have shown that consumption of butter was associated with more activated genes involved in the regulation of cell proliferation and inflammation compared with consumption of olive oil or vegetable oil [107, 108]. In these studies, activation of inflammatory markers has occurred without significant changes in the blood lipid profile [106, 108]. In summary, the previous findings strongly suggest that saturated and unsaturated fats have unique biological effects on vascular walls which are independent on the reduction in LDL cholesterol, which is like the effects of statins.

#### **3.9 Guideline recommendations for dietary intake of SFA**

Guidelines of authoritative opinions in Japan, the US, and Europe including cardiology, diabetes, and atherosclerosis societies except ADA [36] recommend less than 7% of calorie from SFA in subjects with background diseases (**Table 1**). In healthy subjects, the recommended upper limit of SFA is 7% in Japan [33] and 10% in the US [109]. Restriction of SFA to <10% rather than 7% in diabetic subjects as recommended by the ADA [36] may sound a little strange, because diabetes is associated with high CV risk, and on-target LDL cholesterol criteria is generally more stringent. This recommendation is based on the data from one small 3-week study that compared a low SFA diet (8% of total calories) vs. a high SFA diet (17% of total calories), and showed no significant difference in glycemic control and most CVD risk measures [110]. Therefore, there is limited research regarding effects of

#### **Figure 10.**

*Response of mRNA TNFα (left) and IL-6 (right) in breakfast with butter, olive oil, and walnuts measured in peripheral blood mononuclear cells (PBMCs) [105].*

**3.8 Effects of replacement of SFA with other nutrients on plasma lipids, blood**

*Sales of sugar-sweetened beverages (SSBs) in kcal/person/day by beverage type in 2009–2014 in some selected*

*Changes in the format of the nutrition label of the original and the new version on Jan 2020.*

Replacing 1% of energy from SFA with 1% of energy from PUFA, MUFA, or complex carbohydrates decreased plasma LDL cholesterol by 2.1, 1.6, and 1.3 mg/dl, respectively [102]. HDL cholesterol decreased by 0.2, 0.2, and 0.4 mg/dl after substitution of SFA by PUFA, MUFA, or complex carbohydrate. The change in TG

**pressure, and other risk markers**

**Figure 8.**

*New Insights into Metabolic Syndrome*

**Figure 9.**

**82**

*countries [95].*

SFA on diabetic control, and the ADA nutrition position paper recommends people with diabetes follow the guidelines for the general population, which is 10% according to USDA [109]. Despite insufficient data about effects of SFA on glycemic control, the evidence in many review manuscripts or meta-analyses so far accumulated has indicated that a Mediterranean diet helps prevent type 2 diabetes and causes HbA1c reduction in persons with established diabetes [111–115]. Therefore, food habits to restrict intake of SFA as in the Mediterranean diet is a very reasonable strategy in diabetic subjects.

**4. Cholesterol**

significant.

should be paid to reducing SFA in food.

**5. Polyunsaturated fat**

**5.1 n-3 and n-6 PUFA**

**85**

**4.1 Relation of plasma LDL cholesterol and dietary intake of cholesterol**

*Effects and Issues of Diet Fat on Cardiovascular Metabolism*

*DOI: http://dx.doi.org/10.5772/intechopen.93261*

estingly, repeated cholesterol loading has changed some nonresponders to

rather than a true difference between responders and nonresponders. In responders, both LDL and HDL cholesterol increased with no change in ratio of LDL to HDL. A gene of ABCG5/8 regulates absorption of dietary cholesterol and sterol from gut [128]. People carrying polymorphisms of ABCG5/8 have a higher absorption rate of cholesterol. In these subjects, the effects of manipulation of intake of cholesterol in food on plasma LDL cholesterol levels have been very

responders [126, 127]. The presence of two types of cholesterol response may reflect just day-to-day variation of cholesterol absorption from the gut in a single person

The possible link between dietary cholesterol and CHD risk is potentially distorted by confounding factors from other features in the diet, especially SFA [129]. A previous recommendation of less than 300 mg of dietary cholesterol has been removed from the 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk [38], stating that there is insufficient evidence to determine whether lowering dietary cholesterol reduces LDL-C. The same action was taken in the 2015 Dietary Guidelines of USDA [40] and the 2015 Japanese dietary intake standards by Ministry of Health, Labor and Welfare [33]. By contrast, other guidelines still restrict the dietary cholesterol intake, for instance, 200 mg/day in JAS [35] and AACE [130] guidelines, or 300 mg/day in ESC/EAS [39], ADA [36], and JDS [34] guidelines. These guidelines engender the risk of potentially increasing intake of SFA by abandoning the recommendation for dietary cholesterol intake. However, all of these, in common, stress risk evaluation of atherothrombotic diseases and execution of comprehensive management to reduce the risk. Even the guideline from JAS, which limits dietary cholesterol intake at 200 mg/day, states very clearly that only restricting dietary cholesterol intake is hardly efficacious in reducing plasma LDL cholesterol, and rather more attention

Every cooking oils or foods generally include several kinds of fatty acids. **Table 3** shows the amounts of different fatty acids in several commercially available oils and foods. In the US, people use soybean oil very frequently for cooking, and its dominant fatty acid is n-6 PUFA (50%), along with MUFA (25%). Olive oil, a very popular oil in the Mediterranean Sea area, is a well-known representative with

Plasma LDL cholesterol value changes depending on oral intake of cholesterol. One meta-analysis of 17 studies reported that a 100 mg increment in dietary cholesterol from eggs elevated plasma total cholesterol by 2.2 mg/dl [124]. On the contrary, many studies have brought into question the apparent association between dietary cholesterol consumption and blood cholesterol [38]. Plasma cholesterol undergoes a highly degree of regulation to balance absorption in the intestine and synthesis in the liver [125]. Low dietary cholesterol intake is compensated for by an increase in absorption. These mechanisms explain the inter-individual variability in absorption (20–80%) in humans. Thus, there are responders and nonresponders to intake of cholesterol in terms of plasma cholesterol levels. Inter-

Three Japanese cohort studies have shown that the incidence of brain hemorrhage is inversely related to intake of SFA [116–118], and this moved the JAS to define the lower limit (4.5%) of intake of SFA [35]. This relation has not been demonstrated in meta-analysis of subjects in the US and Europe. There have been no data showing high incidence of stroke in vegetarians who consume very little SFA. Therefore, none of the guidelines in the rest of the world have incorporated the lower limit of intake of SFA. One has to be cautious that limiting SFA in the diet tends to decrease intake of good fat, as PUFA, fish oil, or olive oil.

Intake of 7% of calories as SFA is equivalent to about 15 g of SFA in a person who needs 2000 cal/day. Average intake of SFA is 15.2 and 13.8 g/day for Japanese men and women at the age of 30–49 years old [119], and 31.4 and 20.3 g/day for American men and women at the age of 31–50 years old [120]. It is reasonable that refraining from red meat, processed meat, butter, or SFA-loaded snacks is a simple way to cut SFA in daily food habits. In the US, only approximately 5% of the population consumes less than 7% of their calories from saturated fat [120].

### **3.10 Guideline recommendations for dietary intake of PUFA and MUFA**

Beneficial effects of PUFA and MUFA seem to be fully recognized in guidelines in the US and Europe (**Table 1**). Guidelines from ADA, ACC/AHA, NLA, and USDA strongly recommend the Mediterranean and DASH diets. Regarding efficacy of decreasing blood glucose, the ADA provides the same recommendation for both PUFA and MUFA [36]. The 2013 AHA/ACC Guideline on Lifestyle Management [38] states that PUFA or MUFA should be used for reducing LDL cholesterol instead of SFA at the same recommendation level.

Literature has emerged that the biological effects of olive oil differ from those of plant-based MUFA or PUFA. Incorporating data from the PREDIMED study [6], the 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia [121] concretely recommend olive oil (>60 ml/day) and nuts (>30 g/ day) rather than using general terms for MUFA. An authoritative review of dietaries and policies for cardiovascular diseases in 2016 [122] has also listed its daily recommended doses of MUFA and PUFA, such as 10–30 ml/day of soybean oil (MUFA: 22%, PUFA: 56%, and SFA: 15%), extra virgin olive oil (MUFA: 74%, PUFA: 7%, and SFA: 13%), and canola oil (MUFA: 64%, PUFA: 28%, and SFA: 7%). These guidelines provide data of effects on plasma LDL cholesterol and CV events by substitution of SFA with PUFA and MUFA.

The differences in guideline recommendations of the fat intake appear to reflect the differences in food habits and in recognition of the benefits of healthy fats between countries. In 2010, nonoptimal intake of n-6 PUFA, SFA, and trans fat resulted in 710,000, 251,000, and 537,000 deaths from CHD per year worldwide [123]. In 80% of nations, including Japan, China, and other many Asian nations, CHD burdens attributable to n-6 PUFA were 2-fold higher than the SFAattributable burdens. These data indicate that it is more important to focus on increasing healthful n-6 rich vegetable oils in the diet than to focus on replacement of SFA and carbohydrates for public health benefits.
