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 2-3, May 2018, pages 27-31

Effects of Energy and Carbohydrate Intake on Serum High-Density Lipoprotein-Cholesterol Levels

**Table 1.** Meta-Analyses Evaluated Effects of Carbohydrate Intake on HDL-C
Authors	Assessed studies	Subjects studied	Effects on HDL-C	Effects on other lipids	Effects on body weight, body composition
BMI: body mass index; CI: confidence interval; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; MD: mean difference; NA: not available; RCT: randomized controlled trial; TC: total cholesterol; TG: triglyceride; WMD: weighted mean difference.
Mansoor et al [7]	RCTs assessing the effects of low-carbohydrate (LC) diets vs. low-fat (LF) diets on weight loss and risk factors. The dietary intervention had a duration of 6 months or longer	11 RCTs with 1,369 participants	Compared with LF diets, LC diets showed a greater increase in HDL-C (WMD: 0.14 mmol/L; 95% CI: 0.09, 0.19)	Compared with LF diets, LC diets showed a greater reduction in TG (WMD: -0.26 mmol/L; 95% CI: -0.37, -0.15), but a greater increase in LDL-C (WMD: 0.16 mmol/L; 95% CI: 0.003, 0.33)	Compared with LF diets, LC diets showed a greater reduction in body weight (WMD: -2.17 kg; 95% CI: -3.36, -0.99)
Naude et al [8]	Effect of changes in carbohydrate and fatty acid intake on serum lipid and lipoprotein levels	19 trials were included (n = 3,209)	Little or no difference was detected at 3 - 6 months and 1 - 2 years for HDL-C	Little or no difference was detected at 3 - 6 months and 1 - 2 years for LDL-C, TC and TG	Little or no difference in mean weight loss in the two groups at 3 - 6 months and 1 - 2 years
Bueno et al [9]	Individuals assigned to a very-low-carbohydrate ketogenic diets (VLCKD) (a diet with no more than 50 g carbohydrates/day) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet	13 studies	Individuals assigned to a VLCKD showed increased HDL-C (WMD: 0.09; 95% CI: 0.06, 0.12 mmol/L; 1,257 patients)	Individuals assigned to a VLCKD showed decreased TG (WMD: 20.18; 95% CI: 20.27, 20.08 mmol/L; 1,258 patients) and LDL-C (WMD: 0.12; 95% CI: 0.04,0.2 mmol/L; 1,255 patients)	Individuals assigned to a VLCKD showed decreased body weight (WMD: 20.91; 95% CI: 21.65, 20.17 kg; 1,415 patients)
Ajala et al [10]	RCTs with interventions that lasted ≥ 6 months that compared low-carbohydrate, vegetarian, vegan, low-glycemic index (GI), high-fiber, Mediterranean, and high-protein diets with control diets including low-fat, high-GI, American Diabetes Association, European Association for the Study of Diabetes, and low-protein diets, in patients with type 2 diabetes	20 RCTs were included (n = 3,073 included in final analyses across 3460 randomly assigned individuals)	An increase in HDL-C was seen in the low-carbohydrate, low-GI, Mediterranean diets	NA	Low-carbohydrate and Mediterranean diets led to greater weight loss (-0.69 kg (P = 0.21) and -1.84 kg (P < 0.00001), respectively)
Huntriss et al [11]	RCTs were searched for which included adults with type 2 diabetes aged 18 years or more. The intervention was a low-carbohydrate diet as defined by the author compared to a control group of usual care	18 studies (n = 2,204)	The meta-analyses showed statistical significance in favor of the low-carbohydrate intervention arm (LCIA) for HDL-C (estimated effect : 0.06 mmol/L; 95% CI: 0.04, 0.09; P < 0.00001)	The meta-analyses showed statistical significance in favor of the LCIA for TG (estimated effect : -0.24 mmol/L, 95% CI: -0.35, -0.13; P < 0.0001). Meta-analyses for TC and LDL-C did not demonstrate a statistically significant difference between interventions	Meta-analyses for weight did not demonstrate a statistically significant difference between interventions
Meng et al [12]	RCTs assessed the efficacy of low carbohydrate diet (LCD) compared with a normal or high carbohydrate diet in patients with type 2 diabetes.	9 studies with 734 patients with diabetes	The LCD intervention significantly increased HDL -C (WMD: 0.07 mmol/L; 95% CI: 0.03, 0.11 mmol/L; P = 0.00)	The LCD intervention significantly reduced TG (WMD: -0.33 mmol/L; 95% CI: -0.45, -0.21 mmol/L; P = 0.00), but, the LCD was not associated with decreased level of TC and LDL-C	Subgroup analyses indicated that short term intervention of LCD was effective for weight loss (WMD: -1.18 kg; 95% CI: -2.32, -0.04 kg; P = 0.04).
Santos et al [13]	Effects of low-carbohydrate diet (LCD) on weight loss and cardiovascular risk factors (search performed on PubMed, Cochrane Central Register of Controlled Trials and Scopus databases)	A total of 23 reports, corresponding to 17 clinical investigations, were identified as meeting the pre-specified criteria. Meta-analysis carried out on data obtained in 1,141 obese patients	LCD was associated with a significant increase in HDL-C (1.73 mg/dL; 95% CI: 1.44, 2.01)	LCD was associated with significant decreases in TG (-29.71 mg/dL; 95% CI: -31.99, -27.44). LDL-C did not change significantly.	LCD was associated with significant decreases in body weight (-7.04 kg; 95% CI: -7.20, -6.88), body mass index (-2.09 kg/m²; 95% CI: -2.15, -2.04), abdominal circumference (-5.74 cm; 95% CI: -6.07, -5.41)

Table 1. Meta-Analyses Evaluated Effects of Carbohydrate Intake on HDL-C

Authors

Assessed studies

Subjects studied

Effects on HDL-C

Effects on other lipids

Effects on body weight, body composition

BMI: body mass index; CI: confidence interval; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; MD: mean difference; NA: not available; RCT: randomized controlled trial; TC: total cholesterol; TG: triglyceride; WMD: weighted mean difference.

Mansoor et al [7]

RCTs assessing the effects of low-carbohydrate (LC) diets vs. low-fat (LF) diets on weight loss and risk factors. The dietary intervention had a duration of 6 months or longer

11 RCTs with 1,369 participants

Compared with LF diets, LC diets showed a greater increase in HDL-C (WMD: 0.14 mmol/L; 95% CI: 0.09, 0.19)

Compared with LF diets, LC diets showed a greater reduction in TG (WMD: -0.26 mmol/L; 95% CI: -0.37, -0.15), but a greater increase in LDL-C (WMD: 0.16 mmol/L; 95% CI: 0.003, 0.33)

Compared with LF diets, LC diets showed a greater reduction in body weight (WMD: -2.17 kg; 95% CI: -3.36, -0.99)

Naude et al [8]

Effect of changes in carbohydrate and fatty acid intake on serum lipid and lipoprotein levels

19 trials were included (n = 3,209)

Little or no difference was detected at 3 - 6 months and 1 - 2 years for HDL-C

Little or no difference was detected at 3 - 6 months and 1 - 2 years for LDL-C, TC and TG

Little or no difference in mean weight loss in the two groups at 3 - 6 months and 1 - 2 years

Bueno et al [9]

Individuals assigned to a very-low-carbohydrate ketogenic diets (VLCKD) (a diet with no more than 50 g carbohydrates/day) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet

13 studies

Individuals assigned to a VLCKD showed increased HDL-C (WMD: 0.09; 95% CI: 0.06, 0.12 mmol/L; 1,257 patients)

Individuals assigned to a VLCKD showed decreased TG (WMD: 20.18; 95% CI: 20.27, 20.08 mmol/L; 1,258 patients) and LDL-C (WMD: 0.12; 95% CI: 0.04,0.2 mmol/L; 1,255 patients)

Individuals assigned to a VLCKD showed decreased body weight (WMD: 20.91; 95% CI: 21.65, 20.17 kg; 1,415 patients)

Ajala et al [10]

RCTs with interventions that lasted ≥ 6 months that compared low-carbohydrate, vegetarian, vegan, low-glycemic index (GI), high-fiber, Mediterranean, and high-protein diets with control diets including low-fat, high-GI, American Diabetes Association, European Association for the Study of Diabetes, and low-protein diets, in patients with type 2 diabetes

20 RCTs were included (n = 3,073 included in final analyses across 3460 randomly assigned individuals)

An increase in HDL-C was seen in the low-carbohydrate, low-GI, Mediterranean diets

Low-carbohydrate and Mediterranean diets led to greater weight loss (-0.69 kg (P = 0.21) and -1.84 kg (P < 0.00001), respectively)

Huntriss et al [11]

RCTs were searched for which included adults with type 2 diabetes aged 18 years or more. The intervention was a low-carbohydrate diet as defined by the author compared to a control group of usual care

18 studies (n = 2,204)

The meta-analyses showed statistical significance in favor of the low-carbohydrate intervention arm (LCIA) for HDL-C (estimated effect : 0.06 mmol/L; 95% CI: 0.04, 0.09; P < 0.00001)

The meta-analyses showed statistical significance in favor of the LCIA for TG (estimated effect : -0.24 mmol/L, 95% CI: -0.35, -0.13; P < 0.0001). Meta-analyses for TC and LDL-C did not demonstrate a statistically significant difference between interventions

Meta-analyses for weight did not demonstrate a statistically significant difference between interventions

Meng et al [12]

RCTs assessed the efficacy of low carbohydrate diet (LCD) compared with a normal or high carbohydrate diet in patients with type 2 diabetes.

9 studies with 734 patients with diabetes

The LCD intervention significantly increased HDL -C (WMD: 0.07 mmol/L; 95% CI: 0.03, 0.11 mmol/L; P = 0.00)

The LCD intervention significantly reduced TG (WMD: -0.33 mmol/L; 95% CI: -0.45, -0.21 mmol/L; P = 0.00), but, the LCD was not associated with decreased level of TC and LDL-C

Subgroup analyses indicated that short term intervention of LCD was effective for weight loss (WMD: -1.18 kg; 95% CI: -2.32, -0.04 kg; P = 0.04).

Santos et al [13]

Effects of low-carbohydrate diet (LCD) on weight loss and cardiovascular risk factors (search performed on PubMed, Cochrane Central Register of Controlled Trials and Scopus databases)

A total of 23 reports, corresponding to 17 clinical investigations, were identified as meeting the pre-specified criteria. Meta-analysis carried out on data obtained in 1,141 obese patients

LCD was associated with a significant increase in HDL-C (1.73 mg/dL; 95% CI: 1.44, 2.01)

LCD was associated with significant decreases in TG (-29.71 mg/dL; 95% CI: -31.99, -27.44). LDL-C did not change significantly.

LCD was associated with significant decreases in body weight (-7.04 kg; 95% CI: -7.20, -6.88), body mass index (-2.09 kg/m²; 95% CI: -2.15, -2.04), abdominal circumference (-5.74 cm; 95% CI: -6.07, -5.41)

**Table 2.** Meta-Analyses Evaluated Effects of Sugar Intake on HDL-C
Authors	Assessed studies	Subjects studied	Effects on HDL-C	Effects on other lipids	Effects on body weight, body composition
CI: confidence interval; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; MD: mean difference; NA: not available; RCT: randomized controlled trial; TC: total cholesterol; TG: triglyceride.
Fattore et al [14]	RCTs to compare diets that provide a given amount of energy from free sugars with a control diet that provides the same amount of energy from complex carbohydrate	28 studies involving 510 volunteers	A significant increase in HDL-C	Significant increases in LDL-C and TG, although for LDL-C and TG there was significant heterogeneity between studies and evidence of publication bias	The substitution of free sugars for complex carbohydrates had no effect on body weight
Te Morenga et al [15]	Studies that reported intakes of free sugars and at least one lipid or blood pressure outcome. The minimum trial duration was 2 weeks.	39 trials reported lipid outcomes	Higher compared with lower sugar intakes significantly raised HDL-C (MD: 0.02 mmol/L; 95% CI: 0.00, 0.03 mmol/L; P = 0.03).	Higher compared with lower sugar intakes significantly raised TG (MD: 0.11 mmol/L; 95% CI: 0.07, 0.15 mmol/L; P < 0.0001), TC (MD: 0.16 mmol/L; 95% CI: 0.10, 0.24 mmol/L; P < 0.0001), LDL-C (0.12 mmol/L; 95% CI: 0.05, 0.19 mmol/L; P = 0.0001)	Dietary sugars influence serum lipids. The relation is independent of effects of sugars on body weight.
Chiavaroli et al [16]	Controlled feeding trials with follow-up ≥ 7 days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids	51 isocaloric trials (n = 943) and 8 hypercaloric trials (n = 125)	No effect on HDL-C in isocaloric trials	No effect on LDL-C, non-HDL-C, apolipoprotein B, TG in isocaloric trials. In hypercaloric trials, fructose increased apolipoprotein B (n = 2; MD: 0.18 mmol/L; 95% CI: 0.05, 0.30; P = 0.005) and TG (n = 8; MD: 0.26 mmol/L; 95% CI: 0.11, 0.41; P < 0.001).	NA
Zhang et al [17]	Controlled, feeding trials involving isocaloric fructose exchange for other carbohydrates to quantify the effects of fructose on serum TC, LDL-C, and HDL-C in adult humans	24 trials with a total of 474 participants	Fructose exerted no effect on HDL-C	Isocaloric fructose exchange for carbohydrates increased TC by 13.0 mg/dL (95% CI: 4.7, 21.3; P = 0.002) and LDL-C by 11.6 mg/dL (95% CI: 4.4, 18.9; P = 0.002) at >100 g fructose/day. However, no effect was shown on TC or LDL-C when the fructose intake was ≤ 100 g/day	NA

Table 2. Meta-Analyses Evaluated Effects of Sugar Intake on HDL-C

Authors

Assessed studies

Subjects studied

Effects on HDL-C

Effects on other lipids

Effects on body weight, body composition

CI: confidence interval; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; MD: mean difference; NA: not available; RCT: randomized controlled trial; TC: total cholesterol; TG: triglyceride.

Fattore et al [14]

RCTs to compare diets that provide a given amount of energy from free sugars with a control diet that provides the same amount of energy from complex carbohydrate

28 studies involving 510 volunteers

A significant increase in HDL-C

Significant increases in LDL-C and TG, although for LDL-C and TG there was significant heterogeneity between studies and evidence of publication bias

The substitution of free sugars for complex carbohydrates had no effect on body weight

Te Morenga et al [15]

Studies that reported intakes of free sugars and at least one lipid or blood pressure outcome. The minimum trial duration was 2 weeks.

39 trials reported lipid outcomes

Higher compared with lower sugar intakes significantly raised HDL-C (MD: 0.02 mmol/L; 95% CI: 0.00, 0.03 mmol/L; P = 0.03).

Higher compared with lower sugar intakes significantly raised TG (MD: 0.11 mmol/L; 95% CI: 0.07, 0.15 mmol/L; P < 0.0001), TC (MD: 0.16 mmol/L; 95% CI: 0.10, 0.24 mmol/L; P < 0.0001), LDL-C (0.12 mmol/L; 95% CI: 0.05, 0.19 mmol/L; P = 0.0001)

Dietary sugars influence serum lipids. The relation is independent of effects of sugars on body weight.

Chiavaroli et al [16]

Controlled feeding trials with follow-up ≥ 7 days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids

51 isocaloric trials (n = 943) and 8 hypercaloric trials (n = 125)

No effect on HDL-C in isocaloric trials

No effect on LDL-C, non-HDL-C, apolipoprotein B, TG in isocaloric trials. In hypercaloric trials, fructose increased apolipoprotein B (n = 2; MD: 0.18 mmol/L; 95% CI: 0.05, 0.30; P = 0.005) and TG (n = 8; MD: 0.26 mmol/L; 95% CI: 0.11, 0.41; P < 0.001).

Zhang et al [17]

Controlled, feeding trials involving isocaloric fructose exchange for other carbohydrates to quantify the effects of fructose on serum TC, LDL-C, and HDL-C in adult humans

24 trials with a total of 474 participants

Fructose exerted no effect on HDL-C

Isocaloric fructose exchange for carbohydrates increased TC by 13.0 mg/dL (95% CI: 4.7, 21.3; P = 0.002) and LDL-C by 11.6 mg/dL (95% CI: 4.4, 18.9; P = 0.002) at >100 g fructose/day. However, no effect was shown on TC or LDL-C when the fructose intake was ≤ 100 g/day