J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website http://www.jofem.org

Review

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

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

**Table 1.** Meta-Analyses Which Evaluated Effects of Various Fatty Acid Consumption on HDL-C
Authors	Assessed studies	Subjects studied	Effects on HDL-C	Effects on other lipids and metabolic parameters
CI: confidence interval; CLA: conjugated linoleic acid; ESRD: end-stage renal disease; GGT: gamma-glutamyl transferase; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density-cholesterol; MD: mean difference; MUFA: mono-unsaturated fatty acid; NA: not available; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PUFA: poly-unsaturated fatty acid; RCT: randomized controlled trial; SFA: saturated fatty acid; TC: total cholesterol; TFA: trans fatty acid; TG: triglyceride; UFA: unsaturated fatty acid.
Sun et al [5]	RCTs of at least 2-week duration that compared the effects of palm oil consumption with any of the predefined comparison oils: vegetable oils low in SFA, TFA-containing partially hydrogenated vegetable oils, and animal fats	NA	Palm oil increased HDL-C by 0.02 mmol/L (95% CI: 0.01, 0.04 mmol/L) compared with vegetable oils low in SFA and by 0.09 mmol/L (95% CI: 0.06, 0.11 mmol/L) compared with TFA-containing oils	Palm oil significantly increased LDL-C by 0.24 mmol/L (95% CI: 0.13, 0.35 mmol/L) compared with vegetable oils low in SFA
Gayet-Boyer et al [6]	RCTs to assess the impact of ruminant-TFA (R-TFA) intake on changes in TC/HDL-C ratio	13 RCTs were included, yielding a total of 23 independent experimental groups of subjects	R-TFA did not influence the changes in the ratios of TC/HDL-C and LDL-C/HDL-C	R-TFA did not influence the changes in the ratios of TC/HDL-C and LDL-C/HDL-C
Fattore et al [7]	Studies included original data comparing palm oil-rich diets with other fat-rich diets and analyzed at least one of the following biomarkers: TC, LDL-C, HDL-C, TC/HDL-C, LDL-C/ HDL-C, TG, apolipoprotein A-I and B, very-low-density lipoprotein cholesterol and lipoprotein(a)	51 studies were included. Intervention times ranged from 2 to 16 week, and different fat substitutions ranged from 4% to 43%	Comparison of palm oil diets with diets rich in stearic acid, MUFA and PUFA showed significantly higher HDL-C and apolipoprotein A-I. Comparison of palm oil-rich diets with diets rich in TFA showed significantly higher HDL-C and apolipoprotein A-I	Comparison of palm oil diets with diets rich in stearic acid, MUFA and PUFA showed significantly higher TC, LDL-C and apolipoprotein B, whereas most of the same biomarkers were significantly lower when compared with diets rich in myristic/lauric acid. Comparison of palm oil-rich diets with diets rich in TFA showed significantly lower apolipoprotein B, TG and TC/HDL-C
Aronis et al [8]	RCTs that examined the role of TFA intake on glucose homeostasis	7 RCTs were included	Increased TFA intake led to a significant decrease in HDL-C (-0.25 mmol/L (95% CI: -0.48 to -0.01))	Increased TFA intake did not result in significant changes in glucose or insulin concentrations. Increased TFA intake led to a significant increase in TC (0.28 mmol/L (0.04 - 0.51)) and LDL-C (0.36 mmol/L (0.13 - 0.60))
Hannon et al [9]	The evidence of the effect of SFA replacement with UFA in metabolically healthy adults with overweight and obesity on dyslipidemia and body composition	8 RCTs enrolling 663 participants were included, with intervention durations between 4 and 28 weeks	NA	Although non-significant (P = 0.06), meta-analysis found UFA replacement to reduce TC by 10.68 mg/dL (95% CI: -21.90 - 0.53). Reductions in LDL-C and TG were statistically non-significant
Zhang et al [10]	Evidence for the efficacy of n-3 PUFA in managing overweight and obesity	A total of 11 RCTs involving 617 participants were included	There was no significant effect on HDL-C	A statistically non-significant difference was revealed in weight loss between n-3 PUFA and placebo, whereas n-3 PUFA was superior to placebo in reducing serum TG (P = 0.0007; WMD: -0.59; 95% CI: -0.93 to -0.25). A significant reduction in waist circumference (P = 0.005; WMD: -0.53; 95% CI: -0.90 to -0.16) was observed. There were no significant effects on BMI, LDL-C and fasting glucose levels
Xu et al [11]	RCTs focused on serum lipids and inflammatory markers in patients with ESRD. MDs were used to measure the effect of n-3 PUFA supplementation on parameters	20 RCTs involving 1,461 patients with ESRD	n-3 PUFA had no significant effect on HDL-C	n-3 PUFA supplementation reduced TG by 0.61 mmol/L, LDL by 0.35 mmol/L and CRP by 0.56 mmol/L. However, n-3 PUFA had no significant effect on TC, glucose and lipoprotein(a)
Perna et al. [12]	RCTs to estimate the pooled effect of hazelnuts on blood lipids and body weight	9 studies representing 425 participants were included. The intervention diet lasted 28 - 84 days with a dosage of hazelnuts ranging from 29 to 69 g/day	HDL-C remained substantially stable (MD = 0.002 mmol/L)	A significant reduction in LDL-C (MD = -0.150 mmol/L) in favor of a hazelnut-enriched diet was observed. TC showed a marked trend toward a decrease (MD = -0.127 mmol/L). No effects on TG and BMI were found
He et al [13]	RCTs of n-3 PUFA treatment for NAFLD	7 RCTs involving 442 patients (227 for the experimental group and 215 for the control group)	Beneficial changes in HDL-C (6.97 mg/dL (2.05 - 11.90), P = 0.006) favored n-3 PUFA treatment	Beneficial changes in TC (-13.41 mg/dL (-21.44 to -5.38), P = 0.001), TG mg/dl (-43.96 (-51.21 to -36.71), P < 0.00001) favored n-3 PUFA treatment. n-3 PUFA tended towards a beneficial effect on LDL-C ( -7.13 mg/dL (-14.26 to 0.0), P = 0.05)
Lu et al [14]	RCTs on the effects of n-3 PUFA in patients with NAFLD	577 cases of NAFLD/NASH in 10 RCTs were included	n-3 PUFA improved HDL in patients with NAFLD/NASH	No significant effects on ALT, AST, TC and LDL. n-3 PUFA improved liver fat, GGT and TG in patients with NAFLD/NASH
Qian et al [15]	Comparing diets high in cis-MUFA to diets high carbohydrates or in PUFA on metabolic risk factors in patients with type 2 diabetes	24 studies totaling 1,460 participants comparing high-MUFA to high-carbohydrate diets and 4 studies totaling 44 participants comparing high-MUFA to high-PUFA diets	When comparing high-MUFA to high-carbohydrate diets, there were significant increases in HDL-C (0.06 mmol/L (0.02 - 0.10))	When comparing high-MUFA to high-carbohydrate diets, there were significant reductions in fasting plasma glucose (-0.57 mmol/L (95% CI: -0.76 to -0.39)), TG (-0.31 mmol/L (-0.44 to -0.18)), body weight (-1.56 kg (-2.89, -0.23)) and systolic blood pressure (-2.31 mm Hg (-4.13, -0.49)). When high-MUFA diets were compared with high-PUFA diets, there was a significant reduction in fasting plasma glucose (-0.87 mmol/L (-1.67 to -0.07))
Khalesi et al [16]	The evidence which identifies the effects of sesame consumption on blood lipid profiles	10 RCTs were identified based on the eligibility criteria	Consumption of sesame did not significantly change HDL-C (0.01 mmol/L; 95% CI: -0.00 - 0.02; P = 0.16)	Consumption of sesame did not significantly change TC and LDL-C. A significant reduction was observed in serum TG (-0.24 mmol/L; 95% CI: -0.32 to -0.15; P < 0.001) after consumption of sesame
Derakhshande-Rishehri, et al [17]	The association of foods enriched in CLA with serum lipid profile in human studies	Healthy adult population	Foods enriched with CLA were associated with non-significantly increased HDL-C (+0.075 mmol/L; 95% CI: 0.121 - 0.270; P = 0.455)	Foods enriched with CLA were associated with significantly decreased LDL-C (-0.231 mmol/L; 95% CI: -0.438 to -0.024; P = 0.028), non-significantly decreased TC (-0.158 mmol/L; 95% CI: -0.349 - 0.042; P = 0.124) and non-significantly decreased TG (-0.078 mmol/L; 95% CI: -0.274 - 0.117; P = 0.433)
Schwingshackl et al [18]	RCTs assessing the long-term effects of low-fat diets compared with diets with high amounts of fat on blood lipid levels	32 studies were included	Rise in HDL-C (+2.35 mg/dL, 95% CI: 1.29 - 3.42; P < 0.0001) was more distinct in the high-fat diet groups. Meta-regression revealed that increases in HDL-C were related to higher amounts of total fat largely derived from MUFA in high-fat diets	Decreases in TC (-4.55 mg/dL, 95% CI: -8.03 to -1.07; P = 0.01) and LDL-C (-3.11 mg/dL, 95% CI: -4.51 to -1.71; P < 0.0001) were significantly more pronounced following low-fat diets, whereas reduction in TG (-8.38 mg/dL, 95% CI: -13.50 to -3.25; P = 0.001) was more distinct in the high-fat diet groups. Meta-regression revealed that lower TC was associated with lower intakes of SFA and higher intakes of PUFA, whereas increases in TG were associated with higher intakes of carbohydrates
Sanders [19]	NA	NA	Compared with carbohydrates, C12-C16 SFAs raise HDL-C without affecting the TC/HDL-C ratio. Replacing 3% dietary SFA with MUFA or PUFA lowers TC/HDL-C ratio by 0.03	Compared with carbohydrates, C12-C16 SFA raises TC, LDL-C without affecting the TC/HDL-C ratio; other SFAs have neutral effects on serum lipids. Replacing 3% dietary SFA with MUFA or PUFA lowers LDL-C by 2% and TC/HDL-C ratio by 0.03
Schwingshackl et al [20]	RCTs and cohort studies investigating the effects of MUFA on cardiovascular and diabetic risk factors	17 relevant papers were identified	Several studies indicated an increase of HDL-C following a MUFA-rich diet	Several studies indicated a decrease in TG following a MUFA-rich diet. The effects on TC and LDL-C appeared not consistent, but no detrimental effects on blood lipids were observed. In type 2 diabetic subjects, MUFA exerted a hypoglycemic effect and reduced glycosylated hemoglobin in the long term
Pei et al [21]	The lipid-modulating effects of n-3 PUFA by combining evidences from RCTs including patients with ESRD	10 RCTs including 557 patients with ESRD	Consumption of n-3 PUFA elevated HDL-C by 0.25 mmol/L, but this change was not statistically significant	Pooled analysis revealed that n-3 PUFA intake significantly reduced serum TG by -0.78 mmol/L (95% CI: -1.12 to -0.44, P < 0.0001). Consumption of n-3 PUFA reduced LDL-C by -0.09 mmol/L, but this change was not statistically significant
Huth et al [22]	The published research on the relationship between milk fat containing dairy foods and cardiovascular health	NA	A diet higher in SFA from whole milk and butter may increase HDL-C and therefore might not affect or even lower theTC/HDL-C	A diet higher in SFA from whole milk and butter increases LDL-C when substituted for carbohydrates or UFA. Cheese intake lowers LDL-C compared with butter of equal milk fat content

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

Authors

Assessed studies

Subjects studied

Effects on HDL-C

Effects on other lipids and metabolic parameters

CI: confidence interval; CLA: conjugated linoleic acid; ESRD: end-stage renal disease; GGT: gamma-glutamyl transferase; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density-cholesterol; MD: mean difference; MUFA: mono-unsaturated fatty acid; NA: not available; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PUFA: poly-unsaturated fatty acid; RCT: randomized controlled trial; SFA: saturated fatty acid; TC: total cholesterol; TFA: trans fatty acid; TG: triglyceride; UFA: unsaturated fatty acid.

Sun et al [5]

RCTs of at least 2-week duration that compared the effects of palm oil consumption with any of the predefined comparison oils: vegetable oils low in SFA, TFA-containing partially hydrogenated vegetable oils, and animal fats

Palm oil increased HDL-C by 0.02 mmol/L (95% CI: 0.01, 0.04 mmol/L) compared with vegetable oils low in SFA and by 0.09 mmol/L (95% CI: 0.06, 0.11 mmol/L) compared with TFA-containing oils

Palm oil significantly increased LDL-C by 0.24 mmol/L (95% CI: 0.13, 0.35 mmol/L) compared with vegetable oils low in SFA

Gayet-Boyer et al [6]

RCTs to assess the impact of ruminant-TFA (R-TFA) intake on changes in TC/HDL-C ratio

13 RCTs were included, yielding a total of 23 independent experimental groups of subjects

R-TFA did not influence the changes in the ratios of TC/HDL-C and LDL-C/HDL-C

Fattore et al [7]

Studies included original data comparing palm oil-rich diets with other fat-rich diets and analyzed at least one of the following biomarkers: TC, LDL-C, HDL-C, TC/HDL-C, LDL-C/ HDL-C, TG, apolipoprotein A-I and B, very-low-density lipoprotein cholesterol and lipoprotein(a)

51 studies were included. Intervention times ranged from 2 to 16 week, and different fat substitutions ranged from 4% to 43%

Comparison of palm oil diets with diets rich in stearic acid, MUFA and PUFA showed significantly higher HDL-C and apolipoprotein A-I. Comparison of palm oil-rich diets with diets rich in TFA showed significantly higher HDL-C and apolipoprotein A-I

Comparison of palm oil diets with diets rich in stearic acid, MUFA and PUFA showed significantly higher TC, LDL-C and apolipoprotein B, whereas most of the same biomarkers were significantly lower when compared with diets rich in myristic/lauric acid. Comparison of palm oil-rich diets with diets rich in TFA showed significantly lower apolipoprotein B, TG and TC/HDL-C

Aronis et al [8]

RCTs that examined the role of TFA intake on glucose homeostasis

7 RCTs were included

Increased TFA intake led to a significant decrease in HDL-C (-0.25 mmol/L (95% CI: -0.48 to -0.01))

Increased TFA intake did not result in significant changes in glucose or insulin concentrations. Increased TFA intake led to a significant increase in TC (0.28 mmol/L (0.04 - 0.51)) and LDL-C (0.36 mmol/L (0.13 - 0.60))

Hannon et al [9]

The evidence of the effect of SFA replacement with UFA in metabolically healthy adults with overweight and obesity on dyslipidemia and body composition

8 RCTs enrolling 663 participants were included, with intervention durations between 4 and 28 weeks

Although non-significant (P = 0.06), meta-analysis found UFA replacement to reduce TC by 10.68 mg/dL (95% CI: -21.90 - 0.53). Reductions in LDL-C and TG were statistically non-significant

Zhang et al [10]

Evidence for the efficacy of n-3 PUFA in managing overweight and obesity

A total of 11 RCTs involving 617 participants were included

There was no significant effect on HDL-C

A statistically non-significant difference was revealed in weight loss between n-3 PUFA and placebo, whereas n-3 PUFA was superior to placebo in reducing serum TG (P = 0.0007; WMD: -0.59; 95% CI: -0.93 to -0.25). A significant reduction in waist circumference (P = 0.005; WMD: -0.53; 95% CI: -0.90 to -0.16) was observed. There were no significant effects on BMI, LDL-C and fasting glucose levels

Xu et al [11]

RCTs focused on serum lipids and inflammatory markers in patients with ESRD. MDs were used to measure the effect of n-3 PUFA supplementation on parameters

20 RCTs involving 1,461 patients with ESRD

n-3 PUFA had no significant effect on HDL-C

n-3 PUFA supplementation reduced TG by 0.61 mmol/L, LDL by 0.35 mmol/L and CRP by 0.56 mmol/L. However, n-3 PUFA had no significant effect on TC, glucose and lipoprotein(a)

Perna et al. [12]

RCTs to estimate the pooled effect of hazelnuts on blood lipids and body weight

9 studies representing 425 participants were included. The intervention diet lasted 28 - 84 days with a dosage of hazelnuts ranging from 29 to 69 g/day

HDL-C remained substantially stable (MD = 0.002 mmol/L)

A significant reduction in LDL-C (MD = -0.150 mmol/L) in favor of a hazelnut-enriched diet was observed. TC showed a marked trend toward a decrease (MD = -0.127 mmol/L). No effects on TG and BMI were found

He et al [13]

RCTs of n-3 PUFA treatment for NAFLD

7 RCTs involving 442 patients (227 for the experimental group and 215 for the control group)

Beneficial changes in HDL-C (6.97 mg/dL (2.05 - 11.90), P = 0.006) favored n-3 PUFA treatment

Beneficial changes in TC (-13.41 mg/dL (-21.44 to -5.38), P = 0.001), TG mg/dl (-43.96 (-51.21 to -36.71), P < 0.00001) favored n-3 PUFA treatment. n-3 PUFA tended towards a beneficial effect on LDL-C ( -7.13 mg/dL (-14.26 to 0.0), P = 0.05)

Lu et al [14]

RCTs on the effects of n-3 PUFA in patients with NAFLD

577 cases of NAFLD/NASH in 10 RCTs were included

n-3 PUFA improved HDL in patients with NAFLD/NASH

No significant effects on ALT, AST, TC and LDL. n-3 PUFA improved liver fat, GGT and TG in patients with NAFLD/NASH

Qian et al [15]

Comparing diets high in cis-MUFA to diets high carbohydrates or in PUFA on metabolic risk factors in patients with type 2 diabetes

24 studies totaling 1,460 participants comparing high-MUFA to high-carbohydrate diets and 4 studies totaling 44 participants comparing high-MUFA to high-PUFA diets

When comparing high-MUFA to high-carbohydrate diets, there were significant increases in HDL-C (0.06 mmol/L (0.02 - 0.10))

When comparing high-MUFA to high-carbohydrate diets, there were significant reductions in fasting plasma glucose (-0.57 mmol/L (95% CI: -0.76 to -0.39)), TG (-0.31 mmol/L (-0.44 to -0.18)), body weight (-1.56 kg (-2.89, -0.23)) and systolic blood pressure (-2.31 mm Hg (-4.13, -0.49)). When high-MUFA diets were compared with high-PUFA diets, there was a significant reduction in fasting plasma glucose (-0.87 mmol/L (-1.67 to -0.07))

Khalesi et al [16]

The evidence which identifies the effects of sesame consumption on blood lipid profiles

10 RCTs were identified based on the eligibility criteria

Consumption of sesame did not significantly change HDL-C (0.01 mmol/L; 95% CI: -0.00 - 0.02; P = 0.16)

Consumption of sesame did not significantly change TC and LDL-C. A significant reduction was observed in serum TG (-0.24 mmol/L; 95% CI: -0.32 to -0.15; P < 0.001) after consumption of sesame

Derakhshande-Rishehri, et al [17]

The association of foods enriched in CLA with serum lipid profile in human studies

Healthy adult population

Foods enriched with CLA were associated with non-significantly increased HDL-C (+0.075 mmol/L; 95% CI: 0.121 - 0.270; P = 0.455)

Foods enriched with CLA were associated with significantly decreased LDL-C (-0.231 mmol/L; 95% CI: -0.438 to -0.024; P = 0.028), non-significantly decreased TC (-0.158 mmol/L; 95% CI: -0.349 - 0.042; P = 0.124) and non-significantly decreased TG (-0.078 mmol/L; 95% CI: -0.274 - 0.117; P = 0.433)

Schwingshackl et al [18]

RCTs assessing the long-term effects of low-fat diets compared with diets with high amounts of fat on blood lipid levels

32 studies were included

Rise in HDL-C (+2.35 mg/dL, 95% CI: 1.29 - 3.42; P < 0.0001) was more distinct in the high-fat diet groups. Meta-regression revealed that increases in HDL-C were related to higher amounts of total fat largely derived from MUFA in high-fat diets

Decreases in TC (-4.55 mg/dL, 95% CI: -8.03 to -1.07; P = 0.01) and LDL-C (-3.11 mg/dL, 95% CI: -4.51 to -1.71; P < 0.0001) were significantly more pronounced following low-fat diets, whereas reduction in TG (-8.38 mg/dL, 95% CI: -13.50 to -3.25; P = 0.001) was more distinct in the high-fat diet groups. Meta-regression revealed that lower TC was associated with lower intakes of SFA and higher intakes of PUFA, whereas increases in TG were associated with higher intakes of carbohydrates

Sanders [19]

Compared with carbohydrates, C12-C16 SFAs raise HDL-C without affecting the TC/HDL-C ratio. Replacing 3% dietary SFA with MUFA or PUFA lowers TC/HDL-C ratio by 0.03

Compared with carbohydrates, C12-C16 SFA raises TC, LDL-C without affecting the TC/HDL-C ratio; other SFAs have neutral effects on serum lipids. Replacing 3% dietary SFA with MUFA or PUFA lowers LDL-C by 2% and TC/HDL-C ratio by 0.03

Schwingshackl et al [20]

RCTs and cohort studies investigating the effects of MUFA on cardiovascular and diabetic risk factors

17 relevant papers were identified

Several studies indicated an increase of HDL-C following a MUFA-rich diet

Several studies indicated a decrease in TG following a MUFA-rich diet. The effects on TC and LDL-C appeared not consistent, but no detrimental effects on blood lipids were observed. In type 2 diabetic subjects, MUFA exerted a hypoglycemic effect and reduced glycosylated hemoglobin in the long term

Pei et al [21]

The lipid-modulating effects of n-3 PUFA by combining evidences from RCTs including patients with ESRD

10 RCTs including 557 patients with ESRD

Consumption of n-3 PUFA elevated HDL-C by 0.25 mmol/L, but this change was not statistically significant

Pooled analysis revealed that n-3 PUFA intake significantly reduced serum TG by -0.78 mmol/L (95% CI: -1.12 to -0.44, P < 0.0001). Consumption of n-3 PUFA reduced LDL-C by -0.09 mmol/L, but this change was not statistically significant

Huth et al [22]

The published research on the relationship between milk fat containing dairy foods and cardiovascular health

A diet higher in SFA from whole milk and butter may increase HDL-C and therefore might not affect or even lower theTC/HDL-C

A diet higher in SFA from whole milk and butter increases LDL-C when substituted for carbohydrates or UFA. Cheese intake lowers LDL-C compared with butter of equal milk fat content

**Table 2.** Summary of Effects of Various Fatty Acids Consumption on Serum Lipids
	HDL-C	LDL-C	TG
CLA: conjugated linoleic acid; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density-cholesterol; MUFA: mono-unsaturated fatty acid; PUFA: poly-unsaturated fatty acid; SFA: saturated fatty acid; TFA: trans fatty acid; TG: triglyceride.
SFA	↑	↑
TFA
Industrially produced-TFA	↓	↑
Ruminant-TFA	→	→
CLA (ruminant-TFA)	→	↓	→
n-3 PUFA	→ or ↑	→ or ↓	↓
MUFA	→ or ↑	↓ or →	→ or ↓

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

HDL-C

LDL-C

CLA: conjugated linoleic acid; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density-cholesterol; MUFA: mono-unsaturated fatty acid; PUFA: poly-unsaturated fatty acid; SFA: saturated fatty acid; TFA: trans fatty acid; TG: triglyceride.

SFA

↑

TFA

Industrially produced-TFA

↓

↑

Ruminant-TFA

→

CLA (ruminant-TFA)

→

↓

→

n-3 PUFA

→ or ↑

→ or ↓

↓

MUFA

→ or ↑

↓ or →

→ or ↓