June 26, 2012 (Boston, Massachusetts) — A small mechanistic study comparing three different eating patterns--a low-fat diet, a low-glycemic-index diet, and a low-carbohydrate diet--has found that participants used up the most energy with the last, but there were metabolic disadvantages to this approach [1].

The findings reinforce the message that a low-glycemic-index diet is best for weight loss and cardiovascular disease prevention and illustrate a novel concept--that not all calories are alike from a metabolic perspective, say Dr Cara B Ebbeling (New Balance Foundation, Obesity Prevention Center, Children's Hospital, Boston, MA) and colleagues in their paper published in the June 27, 2012 issue of the Journal of the Medical Association.

Extreme restriction of fat or carbs can have bad effects.

Senior author Dr David S Ludwig (New Balance Foundation, Obesity Prevention Center) told heartwire : "Extreme restriction of fat or carbs can have bad effects. The best long-term approach will be to avoid restriction of any major nutrient--either fat or carbohydrate--and instead focus on the quality of nutrients. This is not to say that the number of calories isn't important, but it's now saying we should also pay attention to the quality of those calories. So the argument that the food industry likes to make--that all foods can be part of a healthful diet as long as you watch calories--is really misleading at best.

"Relatively unprocessed, low-glycemic-index foods are best, things that our grandmother would recognize. Choose relatively unprocessed foods whenever you can and cut back on white bread, white rice, potato products, prepared breakfast cereals, and, of course, concentrated sugars."

The argument that the food industry likes to make--that all foods can be part of a healthful diet as long as you watch calories--is really misleading at best.

Dr Arne Astrup (Department of Human Nutrition, University of Copenhagen), who was not involved with the study, said it adds to previous research and demonstrates that "a slight reduction in carbs (and increase in protein) with a focus on low [glycemic-index]/whole-grain carbs and 20% to 30% of calories from protein from shellfish, fish, poultry, dairy, nuts, lentils, and beans is the optimal diet today for weight control and reduction of cardiovascular risks."

To this end, Ludwig believes it's time to change recommendations. "Most of the professional nutritional associations continue to feature, expressively or implicitly, targets on fat reduction. Our work--and really many other studies--now suggest that there is absolutely no benefit by selectively targeting fat for reduction."

Low-Fat and Low-Carb Diets Both Have Important Downsides

The researchers conducted a three-way crossover design feeding study between June 2006 and June 2010 involving 21 overweight and obese young adults in Boston who were recruited by newspaper advertisements and postings.

After losing 10% to 15% of body weight during a run-in phase, participants were allocated to a low-fat diet (20% fat, 60% carbohydrate, 20% protein), a low-glycemic-index diet, and a very low-carbohydrate diet (10% carbohydrate, 60% fat, 30% protein) in random order, each for four weeks. The primary outcome was resting energy expenditure with secondary outcomes of total energy expenditure, hormone levels, and metabolic syndrome components.

Ludwig notes these type of studies are "difficult to perform," because for each participant there were seven months of feeding, "and that's about the limit you can put a human subject through, so we could only examine each diet for a month at a time."

The reduction in resting energy expenditure was greatest with the low-fat diet, intermediate with the low-glycemic-index one, and least with the low-carb diet. The decrease in TEE showed a similar pattern.

Those on the low-carb diet burned 350 calories per day more than those on the low-fat one, even though they consumed the same amount of calories on all these diets.

"Those on the low-carb diet burned 350 calories per day more than those on the low-fat one, even though they consumed the same amount of calories on all these diets. That's equivalent to one hour of moderate-intensity physical exercise," Ludwig said. And those on the low-glycemic-index diet lost about 150 calories per day more than those on the low-fat one, "equal to about an hour of light physical activity," he added. (Neither total physical activity nor time spent in moderate- to vigorous-intensity physical activity differed among the diets.)

But he explained that, as well as energy expenditure, "we also looked at heart disease risk factors, and the two restrictive diets both had important downsides."

Strongest Support for Concept That Not All Calories Are the Same

With the low-carb diet, the researchers observed increases in CRP, a measure of chronic inflammation, and 24-hour cortisol, the key stress hormone, "suggesting that any initial advantages were eroded over time by these biological stressors," Ludwig notes.

And the low-fat diet--as well as resulting in the least energy expenditure--"exacerbated many of the components of the metabolic syndrome, so insulin resistance, triglycerides, and HDL cholesterol were all worse on this diet," he explained.

Hence the study, despite its limitations, "provides the strongest support for a novel concept, that all calories are not alike from a metabolic perspective. This has been postulated before, but never shown in this context," Ludwig says.

"We are emphasizing mechanisms that underlie how diets affect body weight and saying that this knowledge should be used to design more effective and least-restrictive approaches to weight loss and heart disease prevention. We want to line up biology and behavior. Losing weight is hard enough for anybody. We need every advantage we can get. We've wasted a lot of energy pursuing ineffective approaches like a low-fat diet."

The authors report no conflicts of interest.