Metabolic Syndrome

Does a Low-Carbohydrate High-Fat diet reduce of risk factors for Metabolic Syndrome?

By Gabriel MacSharry 2006

Metabolic Syndrome has had numerous definitions (see part C) but currently the criteria that best defines this condition is one which includes the following components: adiposity, increased triglycerides/decreased HDL, increased blood pressure, and dysglycemia.(1)

Clinical Trials

In reviewing the literature, there was a lot of research available on LCHF diets that had some conflicting conclusions as to whether this dietary regime was healthy practice. Manco and Mingrone (2) authored a review of this area and compared the results of ten similar clinical trials in tablature form (table 1).

Table 1. Recent clinical trials on low-carbohydrate high-fat diets showing subjects enrolled, duration and parameters of glucose homeostasis.

Authors	Subjects	Duration	Calorie (kcal/day)	Weight loss (kg)	Fasting glycaemia (mg/dl)	Insulin- aemia (mUI/ml)	HBA1c	Insulin sensitivity
Brehm et al.	42 Obese BMI ~34 kg/m2 BW ~92 kg	6 Months	1302 (30% CHO; 46% fat; 23% P) vs 1247 (53% CHO; 29% fat; 18% P)	~8 vs ~4 P < 0.001	~90 vs ~87 P = NS	~14 vs ~18 P= NS	-	-
Brinkworth et al.	43 Obese BMI ~34 kg/m2 BW ~94 kg	17 Months	1816 (40%CHO; 30% fat; 30% P)vs 2150 (55% CHO;30% fat; 15%P)	~3 vs ~3 P =NS	~101 vs~99 P =NS	~13 vs ~12 P =NS	-	~3 vs ~3 P=NS (HOMA)
Brinkworth et al.	38 T2DM BMI ~33 kg/m2 BW ~94 kg	15 Months	1816 (40%CHO; 30% fat; 30% P) vs 2150 (55% CHO; 30% fat; 15% P)	~4 vs ~2 P =NS	~155 vs ~155 P =NS	~17 vs ~18 P =NS	~6.6 vs ~6.6 P =NS	vs 6.5 P =NS (HOMA)
Farnsworth et al.	57 Obese BMI ~34 kg/m2 BW ~99 kg	4 Months	1911 (44% CHO; 29% fat; 27% P) vs 1959 (57% CHO; 27% fat; 16% P)	~8 vs ~8 P =NS	~99 vs ~94 P =NS AUC ~19.7 vs ~22.8b P =NS	~12 vs ~11.5 P =NS AUC ~5.9 vs ~8.7c P < 0.05	-	2.8 vs 2.5 P=NS (HOMA)
Foster et al.	37 Obese BMI ~34 kg/m2 BW ~98 kg	12 Months	1200–1800 (data not reported) vs (60% CHO; 25% fat; 15% P)	~7.5 vs ~4.5a P =NS	Data not reported AUC ~3 vs ~2.4d P =NS	Data not reported AUC ~18 vs ~16.5a,e P =NS	-	~4.8 vs ~5.4a P=NS (ISCI)
Johnston et al.	16 OW BMI ~29 kg/m2 BW ~81 kg	6 Weeks	~1700 kcal/day (41% CHO; 29% fat; 30% P or 66% CHO; 19% fat; 15% P)	~5.7 vs ~5.9a P =NS	~4.2 vs ~3.9a P =NS	~24 vs ~24a P =NS	-	~4.8 vs ~4.8a P=NS (ISCI)
Meckling et al.	31 OW GNT/T2DM BMI ~32 kg/m2 BW ~88 kg	10 Weeks	~1200–2200 (18.4% CHO; 55.5% fat; 26.2% P or 62% CHO; 18% fat; 19% P)	~7.0 vs ~6.8 P =NS	~104 vs ~88 P =NS	~17 vs ~20 P < 0.05	-	~2.91 vs ~4.12 P < 0.05 (IGR)
Samaha et al.	79 Obese GNT/ MS/T2DM BMI ~43 kg/m2 BW ~131 kg	6 Months	1630 (37% CHO; 41% fat; 22% P) vs 1576 (51% CHO; 37% fat; 16% P)	~6 vs ~2 P =0.002	GNT~100 vs ~104 P =NS T2DM ~142 vs ~153 P =0.01	GNT~19 vs ~16 P =0.008 T2DM ~36 vs ~32 P =NS	~7.4 vs ~7.2 P =0.06	GNT ~0.31 vs ~0.33 P=0.01 (ISCI)
Stern et al.	87 Obese GNT/T2DM BMI ~43 kg/m2 BW ~130 kg	12 Months	1462 (33% CHO; 46% fat; 22% P) vs 1822 (50% CHO; 32% fat; 18% P)	~5.6 vs ~7.2 P =0.02	GNT~102vs ~103 P =NS T2DM ~138 vs ~134 P =NS	GNT ~17 vs ~29 P =NS T2DM ~43 vs ~33 P =NS	~5.6 vs ~7.7 P =0.02f	~0.31 vs ~0.32 P=NS (ISCI)
Yancy et al.	79 Obese BMI ~34 kg/m2 BW ~97 kg	24 Weeks	1461 (8% CHO; 68% fat; 26% P) vs 1502 (52% CHO; 29% fat; 19% P)	~12 vs ~6.5 P < 0.001	-	-	-	-

Table index
BMI, body mass index; BW, body weight; CHO, carbohydrate;GIR, glucose to insulin ratio; GNT, glucose normotolerant; HOMA, homeostasis model assessment; ISCI, insulin sensitivity check index; MS, metabolic syndrome; OW, overweight subjects; P, protein; T2DM, type 2 diabetes mellitus. We included in the table articles describing adult, outpatient recipients of low-carbohydrate high-fat (LCHF) diets compared with conventional low-fat diets. The percentages content of carbohydrate, fat and protein are reported when available. Biochemical parameters (fasting glucose and insulin, glycated haemoglobin (HbA1c) and indices of insulin sensitivity or resistance) and weight loss are expressed as approximate absolute values or percentages with respect to the baseline. Whenever available, the glucose and insulin area under the curve (AUC) is reported. Statistical significance is reported if P ~ 0.05. a Percentage reduction with respect to the baseline. b g~180 min/l. c UI~180 min/l. d Percentage reduction of the glucose AUC during 120 min oral glucose tolerance test with respect to the baseline. e Percentage reduction of the insulin AUC during 120 min oral glucose tolerance test with respect to the baseline. f Significance of response in HBA1c was not confirmed by an analysis that included only individuals who completed the study.

Summary of the research

Stern et al. found the significant reduction of HBA1c after one year of LCHF diet in T2DM, whereas Samaha et al. and Brinkworth et al. failed to find it, despite a decrease in fasting glucose levels after 6 months of diet by the former authors. Farnsworth and colleagues showed a diet-related effect on the insulin response to the glucose oral load after 4 months of diet treatment. Meckling et al. found an effect on fasting insulin after 4 months; Samaha et al. found an improvement in insulin sensitivity, but only in normotolerant obese individuals. I feel in general that the results of these ten trials show a LCHF diet to be of benefit to risk factors of metabolic syndrome. For some trials, small sample size and/or trial duration as well as the amount of carbohydrates in the LCHF groups being too high, may explain areas where no statistically significant benefit was found.

In a study by Volek et al(3) thirteen normolipidemic, moderately overweight (body fat >30%) women were prescribed two hypocaloric (-500 kcal/day) diets for 4 week periods, a very low-carbohydrate (<10% carbohydrate) and a low-fat (<30% fat) diet, to compare fasting blood lipids, LDL subclasses, postprandial lipemia, and insulin resistance. It was found that after the very low-carbohydrate diet, fasting total cholesterol, LDL-C, and HDL-C were significantly (p < 0.05) lower, whereas fasting glucose, insulin, and insulin resistance (calculated using the homeostatic model assessment) were significantly higher after the low-fat diet. Both diets significantly decreased postprandial lipemia and resulted in similar nonsignificant changes in the total cholesterol/HDL-C ratio and fasting triacylglycerols. The limitations of this study were a short duration and small sample size.

In an offspring study of the Framingham study(1991-1995) cross-sectional associations were examined between carbohydrate-related dietary factors, insulin resistance, and the prevalence of the metabolic syndrome in 2,834 subjects(4). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated using the following formula (fasting plasma insulin / plasma glucose)/22.5. The metabolic syndrome was defined using the National Cholesterol Education Program criteria. After adjustment for potential confounding variables, intakes of total dietary fiber, cereal fiber, fruit fiber, and whole grains were inversely associated, whereas glycemic index and glycemic load were positively associated with HOMA-IR. The prevalence of the metabolic syndrome was significantly lower among those in the highest quintile of cereal fiber (odds ratio [OR] 0.62; 95% CI 0.45– 0.86) and whole-grain (0.67; 0.48–0.91) intakes relative to those in the lowest quintile category after adjustment for confounding lifestyle and dietary factors. Conversely, the prevalence of the metabolic syndrome was significantly higher among individuals in the highest relative to the lowest quintile category of glycemic index (1.41; 1.04 –1.91). Total carbohydrate, dietary fiber, fruit fiber, vegetable fiber, legume fiber, glycemic load, and refined grain intakes were not associated with prevalence of the metabolic syndrome. However while associations between dietary variables and HOMA-IR were independent of obesity, it remains unclear whether the associations with the metabolic syndrome were largely mediated by effects on obesity or by effects on insulin resistance and blood lipids as well because whole grain intake was not significantly related to blood pressure, HDL cholesterol, triglycerides, or fasting glucose after controlling for BMI in an earlier report from this study population.

Dietary guidelines for the treatment of Metabolic Syndrome

National Health and Nutrition Examination Survey (NHANES III), indicate that approximately one fourth of the US adults 20 years or older meet the diagnostic criteria for metabolic syndrome(5) Metabolic syndrome was recognized first in an article in 1923 by the Swedish physician Eskil Kylin,(6) who described the association of hypertension, hyperglycemia, and hyperuricemia. Jean Vague,(7) from the University of Marseilles, France, introduced the concept of central adiposity in the 1940s. In 1967, Avogaro and coworkers(8) noted the metabolic consequences of central adiposity. In 1988, Gerald Reaven, MD,(9) introduced "syndrome X," which is composed of resistance to insulin-stimulated glucose uptake, glucose intolerance, hyperinsulinemia, increased very low-density lipoprotein (VLDL) triglycerides, reduced high-density lipoprotein (HDL) cholesterol, and hypertension. A series of subsequent papers used the terms "metabolic syndrome," "metabolic syndrome X," "dysmetabolic syndrome," and "insulin resistance syndrome”.

In 1999, the World Health Organization (WHO) attempted to create interest and debate by developing a definition of the syndrome that required the presence of type 2 diabetes, impaired glucose tolerance, or insulin resistance (based on no specific criteria) as well as at least 2 of the following: hypertension, obesity, raised triglycerides or low HDL cholesterol, and microalbuminuria. The European Group for the Study of Insulin Resistance (EGIR) definition released in the same year required insulin resistance plus 2 or more of the following: central obesity, with a waist circumference of 94 cm in men and 80 cm in women; dyslipidemia, again which is based on raised triglycerides or low HDL cholesterol; hyperglycemia excluding diabetes; and blood pressure > 140/90 mm Hg or treatment for hypertension. The National Cholesterol Education Program Adult Treatment Panel (ATP) III simplified the definition to require 3 of the following 5 components: waist circumference > 102 cm in men, 88 cm in women; HDL cholesterol < 40 mg/dL in men, < 50 mg/dL in women; triglycerides > 150 mg/dL, counted as a criterion in addition to HDL; blood pressure > 130/85 mm Hg; and fasting serum glucose > 110 (later 100) mg/dL. (1)

Because of the confusion the International Diabetes Federation held a conference which included agreement that components of the syndrome must include adiposity, increased triglycerides/decreased HDL, increased blood pressure, and dysglycemia.(1)

Conclusion

(Adult Treatment Panel)ATP III recommendations for diet composition for patients with metabolic syndrome are consistent with general dietary recommendations in the USA (10,11,12).These guidelines call for low intake of saturated fats, trans fats, and cholesterol; reduced consumption of simple sugars; and increased intakes of fruits, vegetables, and whole grains. Yet from the literature it is not very convincing that a high carb low fat diet is the best diet to reduce the overall risk factors for metabolic syndrome.

Scott et al(13) believes an important question is whether patients with metabolic syndrome will benefit from a shift to relatively more unsaturated fats? They state that very high-carbohydrate diets may accentuate atherogenic dyslipidemia, and this risk factor is reduced by isocalorically substituting a higher intake of unsaturated fats. The clinical significance of diet-induced atherogenic dyslipidemia, however, is undetermined(13).

Yet it has been shown that a limited intake of dietary carbohydrate with a complementary increase in dietary fat is able to promote a certain degree of unintentional calorie reduction through a blunting of appetite(14), as a result of several factors including ketosis (14), reduced gastrointestinal motility(14), satiating sensation of protein (15), increased energy expenditure (15), and a sparing effect on lean body mass during the weight loss (15).

In the literature LCHF diets have shown positive effects on risk factors of the epidemics of today, mainly, diabetes, obesity, coronary heart disease and hence metabolic syndrome. There is however a need for further research in this area as the current literature in inconsistent. There is a need for a clinical trial on a large sample group for a long duration (12 months +) that has an intervention diet that is low in carbohydrate (approx. 20%) and a high fat intake (approx. 50%). I feel the true benefits can be fully established at this level of intervention.

References

1 Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome -- a new worldwide definition. Lancet. 2005;366:1059-1062

2 Manco M and Mingrone G. ‘Effects of weight loss and calorie restriction on carbohydrate metabolism’ Current Opinion in Clinical Nutrition and Metabolic Care 2005, 8:431–439

3 Volek J, Sharman M, Go´mez A, DiPasquale C, Roti M, Pumerantz A, Kraemer W. ‘Comparison of a Very Low-Carbohydrate and Low-Fat Diet on Fasting Lipids, LDL Subclasses, Insulin Resistance, and Postprandial Lipemic Responses in Overweight Women’ J American Col. of Nut., Vol. 23, No. 2, 177–184 (2004)

4 McKeown N, Meigs J, Liu S, Saltzman E, Wilson P, Jacques P. ‘Carbohydrate Nutrition, Insulin Resistance, and the Prevalence of the Metabolic Syndrome in the Framingham Offspring Cohort’ Diabetes Care 27:538–546, 2004

5 Ford GS, Giles WH, Dietz WH. Prevalence of the Metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey. JAMA 2002;287:356-9

6 Kylin E. Studien uber das hypertonie-hyperglykamie-hyperurikamiesyndrom. Zentrabl f innere Med Leipz. 1923;81:105-127.

7 Vague J. Sexual differentiation. A factor affecting the forms of obesity. Presse Med. 1947;30:339-340.

8 Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37:1595-1607

9 Zachary T. Bloomgarden, MD ‘Debating the Metabolic Syndrome’ American Diabetes Association 66th Scientific Sessions 2006

10 US Department of Agriculture and US Department of Health and Human Services. Nutrition and Your Health: Dietary Guidelines for Americans. 5th ed. Home and Garden Bulletin No. 232. Washington, DC: US Department of Agriculture; 2000.

11 Krauss RM, Eckel RH, Howard B, et al. AHA Dietary Guidelines: revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation. 2000;102: 2284–2299

12 American Diabetes Association position statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. American Diabetes Association Task Force for Writing Nutrition Principles and Recommendations for the Management of Diabetes and Related Complications. J AmDiet Assoc. 2002;102:109–118

13 Scott M. Grundy, Barbara Hansen, Sidney C. Smith, Jr, James I. Cleeman, Richard A. ‘Clinical Management of Metabolic Syndrome: Report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association Conference on Scientific Issues Related to Management’ Arterioscler. Thromb. Vasc. Biol. 2004;24;19-24

14 Lara-Castro C, Garvey WT. Diet, insulin resistance, and obesity: zoning in on data for Atkins dieters living in South Beach. J Clin Endocrinol Metab 2004; 89:4197–4205

15 Brehm BJ, Seeley RJ, Daniels SR, D’Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003; 88:1617–1623

In Health

Gabriel

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