Elsevier

Progress in Lipid Research

Volume 47, Issue 5, September 2008, Pages 307-318
Progress in Lipid Research

Review
Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome

https://doi.org/10.1016/j.plipres.2008.02.003Get rights and content

Abstract

Abnormal fatty acid metabolism and dyslipidemia play an intimate role in the pathogenesis of metabolic syndrome and cardiovascular diseases. The availability of glucose and insulin predominate as upstream regulatory elements that operate through a collection of transcription factors to partition lipids toward anabolic pathways. The unraveling of the details of these cellular events has proceeded rapidly, but their physiologic relevance to lifestyle modification has been largely ignored. Here we highlight the role of dietary input, specifically carbohydrate intake, in the mechanism of metabolic regulation germane to metabolic syndrome. The key principle is that carbohydrate, directly or indirectly through the effect of insulin, controls the disposition of excess dietary nutrients. Dietary carbohydrate modulates lipolysis, lipoprotein assembly and processing and affects the relation between dietary intake of saturated fat intake and circulating levels. Several of these processes are the subject of intense investigation at the cellular level. We see the need to integrate these cellular mechanisms with results from low-carbohydrate diet trials that have shown reduced cardiovascular risk through improvement in hepatic, intravascular, and peripheral processing of lipoproteins, alterations in fatty acid composition, and reductions in other cardiovascular risk factors, notably inflammation. From the current state of the literature, however, low-carbohydrate diets are grounded in basic metabolic principles and the data suggest that some form of carbohydrate restriction is a candidate to be the preferred dietary strategy for cardiovascular health beyond weight regulation.

Introduction

Recent studies support a shift in our understanding of dietary carbohydrate restriction and its interaction with lipid metabolism. Long considered a stratagem for weight loss, there has been a persistent concern of increased cardiovascular risk if the carbohydrate that was removed were replaced with fat. In fact, numerous experiments over the past four or five years have consistently shown that reduction in dietary carbohydrate leads to improvements in atherogenic dyslipidemia (reduced TG and increased HDL-C), metabolic syndrome and diabetes, even in the absence of weight loss [1], [2], [3] or even in the presence of saturated fat.

In addition to experimental demonstrations of its efficacy, the importance of carbohydrate restriction rests on two fundamental ideas. First, in distinction to strategies based on reduction on dietary fat, the rationale for reduction in dietary carbohydrate derives from basic mechanism. Carbohydrate is the major secretagogue of insulin and, beyond its role in providing a source of energy, serves as a control element, either directly via glucose or fructose or indirectly through the effects of insulin and other hormones. Significant advances have been made in unraveling the details of the downstream effects of such stimulation although the links between dietary effects of carbohydrate and the responses in lipid metabolism remain insufficiently explored.

Second, while there is some debate about the clinical applicability of metabolic syndrome (MetS), its intellectual impact has been that it defines a metabolic state encompassing seemingly unrelated processes so that conclusions from the study of diabetes, for example, can cross over to support approaches to dyslipidemia.

A final reason to re-examine low-carbohydrate diets is the historical perspective that aboriginal hunting and fishing cultures survived for millennia with little if any identifiable dietary carbohydrate intake. Examples include the Inuit of the Arctic and First Nations groups in Canada. When these ethnic groups underwent a transition from their high-fat, low-carbohydrate traditional diets, the prevalence of obesity and type-2 diabetes in these populations increased dramatically [4].

Here we present the results of recent dietary intervention studies and try to provide a continuum from clinical markers of health to the underlying physiology and downstream carbohydrate-related regulation of cell signaling. We argue that progress in the field will depend on our ability to integrate these two lines of research.

In light of recent results from dietary studies and the underlying biochemistry, we suggest that current recommendations of health agencies, which downplay or counsel against carbohydrate restriction, need to be re-evaluated.

Section snippets

Dietary carbohydrate is a robust regulatory mechanism signaling lipid metabolism

One of the current views integrating physiology and obesity is the idea that metabolic dysfunction arises from exposure of cells to an excess of nutrients [5] independent of their composition. We would argue that the emerging principle is that individual macronutrients, in particular carbohydrate, have different effects on the control of homeostasis. Carbohydrate, beyond its role as a source of energy, has an important regulatory function. Dietary carbohydrate stimulates insulin secretion,

Metabolic syndrome

Metabolic syndrome (MetS) represents a group of markers that predispose to obesity, diabetes, cardiovascular disease and hypertension. The underlying defect in MetS is generally considered to be a resistance to the actions of insulin in peripheral tissues that manifests as hyperglycemia, hyperinsulinemia, and atherogenic dyslipidemia (high TG, low HDL-C, and small LDL-C). Definitions are continually being modified and an expanding number of different physiologic effects are correlated with

Carbohydrate restriction and triglyceride levels

One of the most dramatic results reported by Volek et al. [27] is the differential effect of VLCKD vs. LFD on TG levels. The low-carbohydrate regimen reduced TG from an average at baseline of 211 ± 58 mg/dL to 104 ± 44. The corresponding change in the LFD group was 187 ± 58 to 151 ± 38. This kind of decrease in plasma TG is a hallmark of the response to a reduction in dietary carbohydrate and has been reported numerous times [61]. Well-controlled feeding studies indicate that low-fat/high-carbohydrate

Fatty acid composition in metabolic syndrome and diabetes

Consistent with the underlying role of insulin resistance in dysregulated lipid metabolism, development of MetS has been shown to be associated with a unique fatty acid composition characterized by higher circulating saturated fats (14:0, 16:0) and lower levels of 18:2n−6, with higher proportions of palmitoleic acid (16:1n−7, the MUFA product derived from palmitic acid) and dihomo-γ-linolenic acid (20:3n−6, the precursor to arachidonic acid) [105]. We emphasize the role of saturated fats

Discussion and recommendations

Discussion or even acknowledgement of carbohydrate restriction as an effective lifestyle modification to treat atherogenic dyslipidemia is notably absent from much of the current literature [88], [89], [90], [128]. Among researchers examining cellular mechanisms of hypertriglyceridemia there is a general disregard for carbohydrate restriction as a potent modulator of TG levels [29], [129]. The generally negative response of the medical community to low-carbohydrate diets has meant that the

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