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Journal of Endocrinology & Metabolism

Review

Volume 8, Number 5, October 2018, pages 94-99

Effects of Consumption of Various Fatty Acids on Serum HDL-Cholesterol Levels

Atherogenic dyslipidemia is characterized as elevated serum levels of triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C), and low serum levels of high-density lipoprotein-cholesterol (HDL-C). Since HDL is an anti-atherogenic lipoprotein which plays a role in reversing cholesterol transport from the peripheral tissues to the liver, low HDL-C levels are associated with the development of coronary heart diseases (CHDs) [1, 2], and all-cause mortality [3].

We previously studied effects of intake of various dietary fat on serum HDL-C levels to make “Dietary Reference Intakes for Japanese 2015”, by using meta-analyses of clinical trials which evaluated effects of various dietary fat consumption on HDL-C [4]. We found that the substitution of fatty acids (FAs) for carbohydrates is beneficially associated with HDL metabolism, monounsaturated FA (MUFA) intake may not affect HDL-C and trans FA (TFA) is significantly associated with reduction of HDL-C. Consumption of n-3 poly-unsaturated fatty acids (PUFA), especially docosahexaenoic acid (DHA) consumption, was favorably associated with HDL metabolism.

Here we review meta-analyses on the effects of various FA consumption on serum HDL-C levels, to make “Dietary Reference Intakes for Japanese 2020”.

To make “Dietary Reference Intakes for Japanese 2020”, we searched meta-analyses of randomized controlled trial (RCT). A search was conducted by using PubMed, Embase and Google Scholar, with the following keywords: trans FA (TFA) and HDL and meta-analysis or saturated FA (SFA) and HDL and meta-analysis or MUFA and HDL and meta-analysis. The search period was comprised from 2012 up to July 2018.

Meta-analyses which evaluated effects of various FA consumption on HDL-C were shown in Table 1.

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Table 1. Meta-Analyses Which Evaluated Effects of Various Fatty Acid Consumption on HDL-C

Compared with most other vegetable oils such as olive and sunflower oils, palm oil contains a high amount of SFA (40-50% of total fat) with the majority being in the form of palmitic acid (16:0). Palm oil consumption significantly increased LDL-C compared with vegetable oils low in SFA [5]. Further, palm oil increased HDL-C by 0.02 mmol/L compared with vegetable oils low in SFA and by 0.09 mmol/L compared with TFA-containing oils.

In another meta-analysis of palm oil on serum lipids, comparison of palm oil diets with diets rich in stearic acid which is a long chain (C18:0) dietary SFA, MUFA and PUFA showed significantly higher HDL-C and apolipoprotein A-I [7]. Comparison of palm oil-rich diets with diets rich in TFA showed significantly higher concentrations of HDL-C and apolipoprotein A-I.

Compared with carbohydrates, C12-C16 SFAs raise serum LDL-C and HDL-C without affecting the TC/HDL-C ratio; other SFAs have neutral effects on serum lipid profile [19]. Results from short-term intervention studies on serum lipids have indicated that a diet higher in SFA from whole milk and butter increases LDL-C when substituted for carbohydrates or unsaturated FA (UFA); however, they may also increase HDL-C and therefore might not affect or even lower the TC/HDL-C ratio [22].

Since the 1990s, TFAs have been reported to link to harmful effects, as they induce not only an increase in LDL-C but also a decrease in HDL-C [23]. The generic term of TFA represents two independent dietary sources, i.e. an industrial one (industrially produced TFA; IP-TFA) and a natural counterpart (ruminant TFA; R-TFA). R-TFAs are generally present in food at low levels (up to 8% of total FA in milk fat), whereas IP-TFA may reach up to 61% of total FA in pastries and shortenings [24]. R-TFA includes vaccenic acid and conjugated linoleic acid (CLA) that are synthesized by rumen bacteria via the metabolism of MUFA and PUFA [25-27].

The meta-analysis of R-TFA on serum lipids showed that doses of R-TFA did not influence the changes in the ratios of plasma TC/HDL-C and LDL-C/HDL-C [6]. Foods enriched with CLA were associated with a non-significant increase of HDL-C [17]. The meta-analysis showed that increased TFA (IP-TFA) intake led to a significant increase in LDL-C and a significant decrease in HDL-C [8].

In the meta-analysis to evaluate evidence for the efficacy of n-3 PUFA in managing overweight and obesity, a significant reduction in waist circumference was obtained; however, a significant effect of n-3 PUFA on HDL-C was not observed [10]. The meta-analysis of n-3 PUFA on serum lipids in patients with end-stage renal disease (ESRD) also failed to prove a statistically significant beneficial effect of n-3 PUFA on HDL [11, 21]. However, two meta-analyses to identify the effectiveness of n-3 PUFA in non-alcoholic fatty liver disease (NAFLD) showed that n-3 PUFA improved HDL metabolism [13, 14].

Hazelnuts are rich in MUFA and antioxidant bioactive substance. The meta-analysis of effect of hazelnuts on blood lipids did not show a significant effect of hazelnuts on HDL [12].

Sesame contains considerable amounts of vitamin E, MUFA, dietary fiber and lignans, which are thought to be associated with its plasma lipid-lowering properties. Consumption of sesame did not significantly change HDL-C [16].

When comparing high-MUFA to high-carbohydrate diets, there were significant increases in HDL-C [15]. Rise in HDL-C was more distinct in the high-fat diet groups, and meta-regression revealed that increases in HDL-C were related to higher amounts of total fat largely derived from MUFA in high-fat diets [18].

According to the synopsis of the evidence available from systematic reviews and meta-analyses using RCTs and cohort studies investigating the effects of MUFA on cardiovascular and diabetic risk factors, several studies indicated an increase of HDL-C following a MUFA-rich diet [20].

To make “Dietary Reference Intakes for Japanese 2015”, we studied effects of intake of various dietary fat on serum HDL-C levels, by using meta-analyses of RCTs which have been published up to 2012 [4]. In our previous report, the substitution of FA for carbohydrates is beneficially associated with HDL-C, and MUFA intake may not affect HDL-C [4]. However, the present study showed high-MUFA diet significantly increased HDL-C as compared with high-carbohydrates diets [15, 18], and found that several studies indicated an increase of HDL-C following a MUFA-rich diet [20].

We previously reported that TFA is significantly associated with reduction of HDL-C, and that TFA is also adversely related with TC/HDL-C [4]. In the present study, we studied the influences of IP-TFA and R-TFA including CLA on HDL. Interestingly, R-TFA did not influence the changes in the ratios of plasma TC/HDL-C and LDL-C/HDL-C [6], and foods enriched with CLA were associated with a non-significant increase of HDL-C [17]. IP-TFA intake led to a significant increase in LDL-C and a significant decrease in HDL-C [8]. When considering the influence of TFA on serum lipid, it was suggested that IP-TFA and R-TFA have to be considered separately.

Our previous study suggested that n-3 PUFA consumption, especially DHA consumption, may be favorably associated with HDL metabolism [4]. The present study showed that n-3 PUFA did not increase HDL-C in patients with obesity and ESRD [10, 11, 21]; however, n-3 PUFA significantly increased HDL in patients with NAFLD [13, 14]. This result indicates that the effect of n-3 PUFA on HDL-C varies by the difference of clinical backgrounds of studied patients. Our recent study reported that DHA induces a greater increase of HDL-C as compared with eicosapentaenoic acid (EPA) [28], supporting our previous study.

In this study, we also examined the influence of SFA intake on HDL. Palm oil consumption increased HDL-C compared with vegetable oils low in SFA; however, palm oil increased LDL-C [5]. Comparison of palm oil diets with diets rich in stearic acid, MUFA and PUFA showed significantly higher HDL-C and apolipoprotein A-I; however, showed significantly higher LDL-C and apolipoprotein B [7]. Compared with carbohydrates, C12-C16 SFAs raise LDL-C and HDL-C without affecting the TC/HDL-C ratio; other SFAs have neutral effects on serum lipid profile [19]. Replacing 3% dietary SFA with MUFA or PUFA lowers LDL-C by 2% and TC/HDL-C ratio [19]. Both elevation of LDL-C and reduction of HDL-C are very crucial determinants for atherogenesis. Meta-analyses of prospective cohort studies reported the relative risks (95% CI) of high versus low intakes of SFA to be 1.07 (95% CI: 0.96 - 1.19) for CHD, which was not statistically significant [29]. Meta-analysis of RCTs reports mean reductions of 14% (95% CI: 4 - 23) in CHD incidence and 6% (95% CI: -25 - 4; non-significance) in mortality, where SFA was lowered by decreasing and/or modifying dietary fat [30].

The systematic review and meta-analysis which analyzed the associations between intake of SFA and TFA and all-cause mortality, cardiovascular disease (CVD) and associated mortality, CHD and associated mortality, ischemic stroke and type 2 diabetes, was reported [31]. SFA intake was not associated with all-cause mortality (relative risk: 0.99, 95% CI: 0.91 - 1.09), CVD mortality (0.97, 0.84 - 1.12), total CHD (1.06, 0.95 - 1.17), ischemic stroke (1.02, 0.90 - 1.15) or type 2 diabetes (0.95, 0.88 - 1.03) [31]. TFA intake was associated with all-cause mortality (1.34, 1.16 - 1.56), CHD mortality (1.28, 1.09 - 1.50) and total CHD (1.21, 1.10 - 1.33), but not ischemic stroke (1.07, 0.88 - 1.28) or type 2 diabetes (1.10, 0.95 - 1.27) [31]. Industrial, but not ruminant, TFAs were associated with CHD mortality (1.18, 1.04 - 1.33) and CHD (1.42, 1.05 - 1.92) [31].

Summary of effects of various FA consumption on serum lipids was shown in Table 2. Consumption of ruminant-TFA including CLA may not affect HDL-C, and an intake of n-3 PUFA and MUFA was associated with an increase of HDL-C. These FAs may not induce atherosclerosis even by considering the effects of such FA on other serum lipids. The effect of SFA on atherosclerosis has to be carefully considered by accumulation of the effect of HDL-C/LDL-C ratio on CV events. Judging from effect on CV events and serum lipids, IP-TFA consumption may induce atherosclerosis.

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Table 2. Summary of Effects of Various Fatty Acids Consumption on Serum Lipids

Conflict of Interest

The authors declare that they have no competing interests.

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