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A Randomized Study Comparing the Effects of a Low-Carbohydrate Diet and a Conventional Diet on Lipoprotein Subfractions and C-reactive Protein Levels in Patients With Severe Obesity

Purpose: To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects. Methods: We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low-carbohydrate or conventional diet for 6 months. Results: Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference =–0.26 mg/dL, p = .03) but more frequently developed detectable chylomicrons (44% vs 22%, p = .04). Both diet groups experienced similar decreases in the number of low-density lipoprotein (LDL) particles (difference = –30 nmol/L, p = .74) and increases in large high-density lipoprotein (HDL) concentrations (difference = 0.70 mg/dL, p = .63). Overall, C-reactive protein levels decreased modestly in both diet groups. However, patients with a high-risk baseline level (>3 mg/dL, n = 48) experienced a greater decrease in C-reactive protein levels on a low-carbohydrate diet (adjusted difference = –2 mg/dL, p = .005), independent of weight loss. Conclusions: In this 6-month study involving severely obese subjects, we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions. (Am J Med. 2004;117:398–405.)

COMMENT: Obesity, defined as a body mass index (BMI) >30 kg/m², is currently a growing problem in the United States.¹ Not only is obesity a health risk and burden, it is often accompanied with insulin resistance and atherogenic dyslipidemia (ie, reduced serum HDL cholesterol levels, elevated serum LDL cholesterol and triglyceride levels). Obesity is also characterized as a chronic, systemic inflammatory state.² Biomarkers of inflammation, such as the leukocyte count, tumor necrosis factor- (TNF-), interleukin-6 (IL-6), and C-reactive protein, are increased in obesity, associated with insulin resistance, and predict the development of type 2 diabetes mellitus and cardiovascular disease.^2,3

Many different diets claim to have beneficial effects in obese patients. It is currently not known whether weight loss associated with a low-carbohydrate diet decreases inflammation, as one would expect an increased insulin sensitivity; however, increased fat consumption may elevate serum C-reactive protein concentrations. This study investigated the controversy of whether low-carbohydrate or conventional calorie- and fat-restricted diets have more beneficial effects on lipid profiles and inflammation. Seshadri and colleagues evaluated the effects and outcomes of these 2 diet types in 132 severely obese (BMI 35 kg/m²) subjects from the Philadelphia Veterans Affairs Medical Center. Patients were randomly assigned to either a low-carbohydrate (n = 64) or conventional calorie- and fat-restricted diet (n = 68). The low-carbohydrate diet patients were instructed to keep carbohydrate intake 30 g/day, and those receiving the conventional diet were to reduce caloric intake by 500 kcal/day while choosing 30% of these calories from fat. After 6 months, 21 subjects (33%) receiving the low-carbohydrate and 32 subjects (47%) receiving the conventional calorie- and fat-restricted diet had dropped out. Interestingly, women were more likely to drop out, especially if they were receiving the low-carbohydrate diet. Of the remaining 79 patients, only 78 (43 low-carbohydrate and 35 conventional calorie- and fat-restricted diet) had stored serum samples for analysis. The majority (82%) of the patients were middle-aged (approximately 55 years) men, whereas 42.3% were white, 53.8% black, and 3.8% Hispanic. The BMI was approximately 44 kg/m² in both groups, whereas 40% had diabetes, and among those without diabetes, 46% had metabolic syndrome. Thirty-five subjects (45%) were concurrently taking lipid-lowering and 49 (63%) taking antihypertensive medications. In the low-carbohydrate group, lipid-lowering medications were initiated in 2 patients and discontinued in another patient.

Both groups experienced an insignificant increase in serum LDL cholesterol levels from baseline and no change in serum HDL cholesterol levels. However, compared with the conventional diet group, subjects in the low-carbohydrate diet group had a greater decrease in mean weight loss (–8.5 ± 9.3 kg vs –3.5 ± 4.9 kg; mean difference = 5 kg; 95% confidence interval, –8.4 to –1.8 kg, p = .003), a greater decrease in serum levels of triglycerides (p < .001) and insulin (p = .008), and a greater increase in insulin sensitivity (p = .02). The subjects receiving the low-carbohydrate diet also experienced a greater reduction in large VLDL particle concentration than the conventional group, which numerous other studies have shown is an independent risk factor for the progression of coronary artery lesions. The low-carbohydrate group also experienced a greater reduction in C-reactive protein levels if baseline levels were considered high risk (>3 mg/dL) compared with those receiving a conventional diet. Interestingly, if patients had a baseline low- to intermediate-risk C-reactive protein level (3 mg/dL), the low-carbohydrate diet patients experienced an increase in C-reactive protein level after 6 months of dietary intervention. The low-carbohydrate diet supplied approximately 10% more fat than the conventional diet when dietary composition was analyzed from baseline to 6 months.

Although these findings of this study seem impressive, the low-carbohydrate group also developed increased detectable chylomicrons, which is a potential concern. This study included a small group of severely obese subjects, those of which may not accurately represent the general obese population in the United States. This study also included a large number of obese subjects who were taking lipid-lowering and antihypertensive medications and did not address the use of other prescriptions, supplements, or over-the-counter medications. Exercise plays a vital role in weight loss and an overall improvement of health. In this study, it is unclear if the subjects participated in any form of exercise. A larger trial with more reported details is essential to truly decipher which diet is more beneficial to obese patients and if the more important component is weight loss or atherogenic reduction.

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Contributing Editor—Todd Canada, PharmD, BCNSP

University of Texas MD Anderson Cancer Center, Houston, Texas

Seshadri P, Iqbal N, Stern L, et al

Department of Internal Medicine, Division of Endocrinology and Cardiology, University of Pennsylvania Health System; Philadelphia Veterans Affairs Medical Center and Department of Family, Community and Preventative Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania

1. Bonow RO, Eckel RH. Diet, obesity and cardiovascular risk. N Engl J Med.2003; 348:2057 –2058.[Free Full Text]
2. Festa A, D'Agostino R, Howard G, Mykkanen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: the insulin resistance atherosclerosis study (IRAS). Circulation.2000; 102:42 –47.[Abstract/Free Full Text]
3. Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia.1997; 40:1286 –1292.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Nutrition in Clinical Practice, Vol. 21, No. 2, 187-188 (2006)
DOI: 10.1177/0115426506021002187


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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Moretti, L. Articles by Canada, T. Search for Related Content PubMed Articles by Moretti, L. Articles by Canada, T. Social Bookmarking                   What's this?