Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss

Abstract

BACKGROUNDMetabolic syndrome (MetS) is highly correlated with obesity and cardiovascular risk, but the importance of dietary carbohydrate independent of weight loss in MetS treatment remains controversial. Here, we test the theory that dietary carbohydrate intolerance (i.e., the inability to process carbohydrate in a healthy manner) rather than obesity per se is a fundamental feature of MetS.METHODSIndividuals who were obese with a diagnosis of MetS were fed three 4-week weight-maintenance diets that were low, moderate, and high in carbohydrate. Protein was constant and fat was exchanged isocalorically for carbohydrate across all diets.RESULTSDespite maintaining body mass, low-carbohydrate (LC) intake enhanced fat oxidation and was more effective in reversing MetS, especially high triglycerides, low HDL-C, and the small LDL subclass phenotype. Carbohydrate restriction also improved abnormal fatty acid composition, an emerging MetS feature. Despite containing 2.5 times more saturated fat than the high-carbohydrate diet, an LC diet decreased plasma total saturated fat and palmitoleate and increased arachidonate.CONCLUSIONConsistent with the perspective that MetS is a pathologic state that manifests as dietary carbohydrate intolerance, these results show that compared with eucaloric high-carbohydrate intake, LC/high-fat diets benefit MetS independent of whole-body or fat mass.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02918422.FUNDINGDairy Management Inc. and the Dutch Dairy Association.

Keywords: Lipoproteins; Metabolism; Obesity.

Conflict of interest statement

Conflict of interest: JSV receives royalties for low-carbohydrate nutrition books. He is founder, consultant, and stockholder of Virta Health Corp.; a member of the advisory boards for Atkins Nutritionals Inc., UCAN Co., Ketone Sciences, and Axcess Global; and has received honoraria from Metagenics and Pruvit. SDP receives royalties for low-carbohydrate nutrition books. He is founder and stockholder of Virta Health Corp. and a member of the advisory board for Atkins Nutritionals Inc. RMK has had investigator-initiated research funding from Dairy Management, Inc. and the Almond Board of California. He receives royalties from a patent for ion mobility analysis of lipoproteins and from a textbook on nutrition and cardiometabolic health. He is on the scientific advisory boards of, and has stock options from, Virta Health, and DayTwo, and is a part-time employee of JumpstartMD.

Figures

Figure 1. Participant flow through the study.

Figure 2. Overview of study design and experimental diets.

(A) Experimental approach. (B) Macronutrient distribution and daily saturated fat intake of controlled diets.

Figure 3. A eucaloric weight-stable LC diet rapidly reverses MetS in individuals who are obese, independent of weight loss.

(A) Individual diagnosis of MetS after LC, MC, and HC diets. Women are represented as pink figures and men are in blue. (B) Change in criteria for MetS relative to baseline after LC, MC, and HC diets. Circles represent individual participants, the thick line is the mean, and thin lines are 95% CIs. P value from 3-way (LC, MC, HC) repeated-measures ANOVA. Values not sharing a common letter are different (P < 0.05). All data n = 16.

Figure 4. An LC diet improves LDL phenotype independent of weight loss and LDL-C concentration.

(A) Individual characterization of LDL phenotype (A, I, and B). Women are represented as pink figures and men are in blue. (B) Peak LDL diameter responses to LC, MC, and HC diets. (C) Change in lipoprotein particle concentrations from largest (LDL-I) to smaller (LDL-IIIa and IIIb) relative to baseline after LC, MC, and HC diets. Circles represent individual participants, the thick line is the mean and thin lines are 95% CIs. P value from 3-way (LC, MC, HC) repeated-measures ANOVA. Values not sharing a common letter are different (P < 0.05). All data n = 16.

Figure 5. Despite being higher in saturated fat, carbohydrate-restricted diets decrease plasma total saturated fatty acids.

(A and B) Saturated fatty acid responses (normalized to baseline values) in PLs and TGs. (C and D) Palmitoleic responses (normalized to baseline values) in plasma PLs and TGs. Circles represent individual participants, the thick line is the mean and thin lines are 95% CIs. P value from 3-way (LC, MC, HC) repeated-measures ANOVA. Values not sharing a common letter are different (P < 0.05). All data n = 16.

Figure 6. Carbohydrate restriction uniformly increases PL 20:4n6 while decreasing its immediate biosynthetic precursor.

(A) Biosynthesis of 20:4n6 from 18:2n6. (B) 20:4n6 responses (normalized to baseline values) in PLs. (C) DGLA responses (normalized to baseline values) in plasma PLs. Circles represent individual participants, the thick line is the mean and thin lines are 95% CIs. P value from 3-way (LC, MC, HC) repeated-measures ANOVA. Values not sharing a common letter are different (P < 0.05). All data n = 16.