Our study has 2 main findings. First, neither dietary fat nor carbohydrate intake influenced weight loss when combined with a comprehensive lifestyle intervention. Second, because both diet groups achieved nearly identical weight loss, we were able to determine that a low-carbohydrate diet has greater beneficial long-term effects on HDL cholesterol concentrations than a low-fat diet.
Our participants had similar and clinically significant weight losses with either a low-carbohydrate or low-fat diet at 1 year (11%) and 2 years (7%), demonstrating that either diet can be used to achieve successful long-term weight loss if coupled with behavioral treatment. The weight losses are similar to those obtained with the best available pharmacotherapy for obesity (19
). Data from the most previous studies found greater weight loss among low-carbohydrate than low-fat dieters (1
), presumably because short-term adherence to a low-carbohydrate diet was easier than complying with a low-fat diet. We found a strong trend for greater short-term (3 month) weight loss among the low-carbohydrate participants, but the difference was small (1.3%) and not clinically significant. Our data suggest that the difference in adherence may be overcome by behavioral treatment, although a 2 × 2 analysis (both diets with and without behavioral treatment) would be required to rigorously test this hypothesis. The similar weight losses observed with low-carbohydrate and low-fat diets demonstrate that the comprehensive lifestyle intervention produced the same energy deficit in both groups, despite marked differences in their behavioral targets (carbohydrates vs. calories and fat). This long-term finding in an outpatient setting is consistent with data from short-term metabolic ward studies showing that macronutrient composition did not influence weight loss when energy content was fixed (21
The nearly identical weight loss in the 2 diet groups during our study provided a unique opportunity to assess the relative effects of the macronutrient content of the 2 diets on cardiovascular disease risk factors. The results demonstrate that dietary macronutrient composition had differential effects on plasma lipid concentrations. At 3 and 6 months, LDL cholesterol concentrations increased in the low-carbohydrate group but decreased in the low-fat group, such that the differences between groups were statistically significant. These differences cannot be explained by differences in weight loss and are probably due to the increase in total fat intake in participants who consumed the carbohydrate-restricted diet. Over the long-term, however, plasma LDL cholesterol concentration in the low-carbohydrate diet group was similar to baseline values, and changes in LDL cholesterol concentrations did not statistically differ between groups. Therefore, the short-term increases in plasma LDL cholesterol concentration in the low-carbohydrate diet group are unlikely to be of clinical importance. Moreover, assessment of LDL cholesterol concentration without information on LDL particle size has limitations as an indicator of coronary heart disease risk because small, dense LDL particles are more atherogenic than large LDL particles (24
). Data from carefully controlled studies demonstrated that isocaloric replacement of dietary carbohydrate with fat increases plasma LDL cholesterol concentration but shifts LDL particle size from smaller to larger and less atherogenic LDL (25
). Nonetheless, weight loss with the low-carbohydrate diet was not associated with the decrease in LDL cholesterol observed in the low-fat diet group and usually observed with weight reduction (26
The low-carbohydrate diet caused a decrease in plasma triglyceride concentration that was more than double the reduction observed with a low-fat diet at 3, 6, and 12 months. However, at 2 years, plasma triglyceride concentration returned toward baseline in the low-carbohydrate group to values that did not differ from those in the low-fat group. Similarly, the decline in directly measured VLDL cholesterol concentration was also greater in the low-carbohydrate than in the low-fat group at 3, 6, and 12 months. However, as with triglyceride levels, at 2 years we found no significant differences between groups. The close relationship and tracking between fasting plasma triglyceride concentrations (which are primarily contained within VLDL) and VLDL cholesterol concentrations supports a model in which the low-carbohydrate diet decreased hepatic VLDL secretion, enhanced VLDL clearance, or both compared with the low-fat diet during the first year of the study.
The low-carbohydrate diet produced a much greater increase in plasma HDL cholesterol concentration than did the low-fat diet at all assessments during the 2-year study. Plasma HDL cholesterol concentration increased by approximately 20% at 6 months in the low-carbohydrate diet group, which persisted throughout the study and was more than twice the increase observed in the low-fat diet group. The magnitude of the changes observed in the low-carbohydrate group approximates that obtained with the maximal doses of nicotinic acid (niacin), the most effective HDL-raising pharmacologic intervention currently available (28
). The fact that the HDL cholesterol levels remained substantially elevated at 24 months, when the plasma triglyceride levels had returned to baseline in the low-carbohydrate group, argues against the conventional explanation that the increase in plasma HDL cholesterol concentration is solely secondary to a reduction in plasma triglyceride levels. The increased HDL cholesterol during a low-carbohydrate diet could result, at least in part, from the increased intake of dietary fat (29
). Although weight loss and increased physical activity undoubtedly contributed to the elevation of HDL cholesterol in both groups, the marked difference in HDL cholesterol between the 2 groups, despite similar weight loss, demonstrates that macronutrient composition has independent effects on HDL. The mechanism responsible for the robust and sustained increase in HDL cholesterol levels among low-carbohydrate participants is unknown and will require additional mechanistic studies. The clinical implications of this increase in HDL cholesterol, which is conventionally believed to be beneficial, are uncertain and will probably depend on the mechanism responsible for this effect.
Weight loss caused a decrease in bone mineral density, which was within the range reported in previous weight-loss studies (30
). The changes in bone mineral density did not differ between diet groups, suggesting the hypothetical concerns that weight loss induced by a low-carbohydrate diet causes greater bone loss than weight loss induced by a low-fat diet (31
) are unfounded. In addition, the decrease in body fat mass and fat-free mass were within the range reported in previous weight-loss studies, and no differences were found between diet groups.
Our study has several important strengths, including a long duration, a large sample that contained both men and women, and the first long-term assessment of bone and adverse symptoms. Our study also has several limitations. First, the comprehensive behavioral therapy program used in this study makes it difficult to extrapolate our results to general weight management in the community. However, the clinically significant weight losses achieved at 24 months underscore the need for providing patients with long-term behavioral support, whether by registered dietitians or other allied health professionals (32
). Our protocol was based on an Atkins version of a low-carbohydrate plan, which prescribes an increase in carbohydrate intake over time; thus, the effects of longer than 12 weeks of severe (20 g/d) carbohydrate restriction could not be assessed. Finally, our findings should not be generalized to obese persons who have obesity-related diseases that were excluded from our study population, such as diabetes and hypercholesterolemia.
In conclusion, this 2-year, multicenter study of more than 300 participants revealed that neither dietary fat nor carbohydrate intake influenced weight loss when combined with a comprehensive lifestyle intervention. Both diet groups achieved clinically significant and nearly identical weight loss (11% at 6 months and 7% at 24 months), and persons who received the low-carbohydrate diet had greater 24-month increases in HDL-cholesterol concentrations than persons who received the low-fat diet. We found no differences between the groups for changes in bone or body composition. These long-term data suggest that a low-carbohydrate approach is a viable option for obesity treatment for obese adults.