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Low Carbohydrate and High Protein Diets for Treatment of Obesity
Edward Saltzman, M.D.

Dr. Saltzman is Assistant Professor of Medicine, Director, Obesity Consultation Center, and Chief, Division of Clinical Nutrition, Tufts-New England Medical Center, and Scientist II, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University School of Medicine, Boston.

Within the past three years, Dr. Saltzman has been a consultant for Ortho-McNeil and has been on the Speakers' Bureau for Roche and Abbott Pharmaceuticals.

Release Date: 02/18/2004
Termination Date: 02/18/2007

Estimated time to complete: 1 hour(s).

Albert Einstein College of Medicine designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Albert Einstein College of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
Learning Objectives
Upon completion of this Cyberounds®, you should be able to:
  • Describe the mechanisms by which macronutrient composition could influence weight loss
  • Discuss the potential risks associated with low carbohydrate diets
  • Identify classes of patients in whom low carbohydrate/high fat or high carbohydrate diets could worsen cardiovascular risk factors.


Approximately two-thirds of Americans are now classified as overweight or obese.(1) Consistent with the increasing prevalence of obesity, attempts at dieting are common -- in 1999 44% of women and 29% of men reported trying to lose weight at any given time.(2) While losing weight is difficult, maintaining lost weight is even more difficult. Approximately 85% of those who lose weight will regain to their original weight within five years.

So it comes as little surprise that a wide variety of weight loss diets have appeared in the media. Many of these approaches entail a significant change in the proportion of dietary macronutrients (carbohydrate, protein, and fat) in comparison to the "average" U.S. diet. Among the most popular current recommendations are programs that limit dietary carbohydrate, the so-called "low carb" diets.

Goal: Energy Intake = Energy Output

To change body weight, an imbalance between energy intake from food and energy expenditure must occur. Energy expenditure can be divided into three components: resting energy expenditure (REE), which accounts for approximately two-thirds of daily expenditure and is largely determined by the amount of lean body mass; the thermic effect of feeding (TEF), approximately 10-15% of daily expenditure resulting from the energy stimulated by the intake, digestion and absorption of nutrients; and energy spent on physical activity (Figure 1).

Figure 1. Components of Energy Expenditure.

Figure 1

Energy intake is influenced by numerous factors, including dietary factors, hunger, and emotions, as well as environmental factors such as food availability and social norms. Many dietary factors also influence food intake (Table 1).

Table 1. Dietary Factors Proposed to Influence Energy Intake.

  • Macronutrient composition
  • Fiber content
  • Palatability
  • Energy density (calories per unit weight of food)
  • Glycemic index
  • Food form (liquid vs. solid)
  • Location (home, restaurant, etc.)
  • Variety

Dietary macronutrient composition is expressed either as an absolute amount of each macronutrient, or as a percent of the contribution of each macronutrient to the total energy content of the diet. When expressed as a percent of dietary energy, it is important to remember that any reduction in carbohydrate will necessarily increase the percentage of fat and/or protein in the diet. To assess the effects of a low carbohydrate diet, therefore, the role of the other increased macronutrients must also be considered.

Do Low Carbohydrate Diets Influence Energy Expenditure and Nutrient Partitioning?

Food energy must ultimately be: stored as body energy, used in the conversion to chemical energy (e.g., ATP), released as heat, or excreted (as in glycosuria with uncontrolled diabetes). It would be advantageous if a particular diet composition could influence its own oxidation, which we could then measure as an increase in energy expenditure. In the most ideal weight loss program, we would want the composition of the diet itself to selectively cause loss of body fat but not other tissues.

The process by which food energy is stored in the body as protein, glycogen, or fat is termed nutrient partitioning. In studies where subjects were fed weight-maintaining diets, little effect of macronutrient composition on the total energy needed to maintain weight was observed.(3) In studies where subjects were deliberately overfed beyond their maintenance needs, the major factor in determining deposition of body fat was the amount of excess energy beyond maintenance needs, and the macronutrient composition had a relatively minor impact on the storage of excess energy as fat.(4)

When individual macronutrients are compared, there are indeed some differences in the efficiency of storing excess dietary energy as body fat. Efficiency may sound like a good thing, but being efficient indicates a favorable ability to store ingested food as body weight. Protein is stored less efficiently than carbohydrate, which in turn is stored less efficiently than fat. But the range is rather narrow -- approximately 90-95% of ingested fat is stored compared to 80-85% of carbohydrate.(4) Since we don't exclusively consume only one macronutrient or another, these differences in efficiency, with moderate changes in macronutrient pattern, are unlikely to result in important changes in expended energy.

One explanation for this difference in energy storage between nutrients is that the macronutrients have different TEFs. While only a few precent of fat energy is "burned off" after fat is ingested, the TEF of protein can be more than 25% of ingested calories. Carbohydrate "burn off" is intermediate between fat and protein. These differences in TEF could result in marked variability in body weight over the long-term, but only if an extremely high or low amount of a macronutrient was consumed.

The mixed meals, however, that are typically consumed by non-dieting persons do not reflect a wide enough range of macronutrients to have a meaningful effect on body weight. For example, on a 2000 calorie/day diet, shifting protein from 15% of dietary energy to 30%, with a commensurate decrease in carbohydrate from 55% to 40%, would increase energy expenditure by only 23 calories/day.(5)

In a review of trials prior to 2002, Eisenstein et al.(5) evaluated the influence of hypocaloric diets with increased dietary protein (mostly associated with decreased carbohydrate) on loss of body weight and loss of lean mass. In trials where identical calories were provided, no consistent benefit of increased protein on lost weight was found and these higher protein diets did not spare lean mass during weight loss. Further, diets that induced ketosis had no consistent effect on preservation of lean mass.

Bravata et al.(6) conducted an exhaustive review of low carbohydrate diets to assess efficacy and safety. They found no overall advantage of lower carbohydrate diets with respect to weight loss or preferential fat loss, although not all studies compared isocaloric diets. According to the researchers, the most important factors contributing to weight loss were the degree of energy restriction and the duration of the study. In addition, those with greater body mass index lost more weight, a logical finding given the greater energy expenditure that accompanies increased body mass.

Some advocates of low carbohydrate diets have claimed that fat loss occurs with these diets while sparing lean mass. Layman and colleagues,(7) in a recent study, provided two isocaloric reducing diets that differed in protein (mean 125 vs. 68 g/day) and carbohydrate (mean 171 vs. 246 g/day) to overweight women for 10 weeks. They found no difference in the total mean weight lost, 7.53 vs. 6.95 kg (higher vs. lower protein). Body composition assessed by dual x-ray absorptiometry revealed that there were no statistically significant differences in the amount of fat or lean mass lost between the diets, although there was a trend toward a lower loss of lean mass for those on the higher protein diet (loss of lean mass 0.88 vs. 1.21 kg for the higher vs. lower protein diets). Only when lost weight was expressed as a ratio of fat/lean did the difference become statistically significant.

The amount of weight lost by subjects in Layman is very typical of that experienced among free-living persons attempting to lose weight, though it is possible that subjects may have needed to lose considerably more weight to allow the differences in nutrient partitioning to become statistically significant. The relatively small differences in loss of fat and lean mass observed between the two diets suggest that we need to remain cautious before extrapolating from statistical significance to meaningful clinical significance.

Macronutrient Effects on Energy Intake

Thus far it appears that no clear superior advantage is conferred by a particular macronutrient composition on energy expenditure or nutrient partitioning. Within the studies cited above, diets are often isocaloric so that differences in macronutrient content can be isolated without confounding effects from differences in total energy intake. However, it is possible that a particular macronutrient composition might result in lower spontaneous energy intake, reduced hunger, or greater satiety. Since hunger is a frequent complaint of those trying to decrease intake, it is possible that macronutrient manipulation might result in increased ability to tolerate a calorie deficit.

We do know that satiating power does differ among the macronutrients. After a single meal, for example, the satiating power of protein is superior to carbohydrate, which is in turn superior to fat.(5) If this effect persists over weeks to months, it is possible that increased protein content might allow a greater overall decrease in intake.

The effects of increasing dietary protein content were evaluated by Skov et al.(8) who utilized an ingenious method to control macronutrient content of the diet while allowing free living subjects to select food. Over a six-month period, subjects were able to choose food from a small shop created by the investigators. The food that was removed from the shop, as well as the amount of food that was consumed, was monitored by the investigators. After six months, subjects eating a diet with 25% protein/45% carbohydrate/30% fat consumed fewer calories and lost more weight (8.9 kg) compared to those consuming a diet with 12% protein and a commensurate increase in carbohydrate (loss of 5.1 kg). In this study, the increased protein content and decreased carbohydrate content, while still in the range consumed by many Americans, resulted in decreased food intake and superior weight loss.

More recently, a very dramatic reduction in carbohydrate intake has been the subject of several trials. Foster et al.(9) educated moderately overweight subjects to follow either an ad libitum low carbohydrate diet (subjects tried to reduce carbohydrate to an initial goal of 20 g/day of carbohydrate and were given a copy of Dr. Atkins New Diet Revolution or a low fat diet with a calorie goal of 1200-1500 calories/day). The low carbohydrate diet initially resulted in significantly greater weight loss and at six months the weight loss in the groups was 7.0 vs. 3.2 kg. However, at the 12-month end of the study, the difference in weight between lower and higher carbohydrate diet groups was no longer significant (4.4 vs.2.5 kg).

In another study, reported in tandem with the Foster study, Samaha et al.(10) provided instruction to extremely obese subjects (mean BMI 43 kg/m2) to either reduce carbohydrate to 30 g/day, or to consume a diet based on an energy restriction of 500 calories/day below expected maintenance needs and to consume <30% of calories from fat. At the six-month end of the trial, the low carbohydrate diet resulted in a significantly greater loss of 5.8 kg in comparison to 1.9 kg lost on the more conventional diet.

The mechanisms by which low carbohydrate diets favorably reduce energy intake and body weight remain speculative. One potential mechanism relies on the concept of glycemic index, or the blood glucose response to food in comparison to a standard such as dextrose or white bread. In short-term studies, lower glycemic index meals suppressed appetite and reduced intake later in the same day in comparison to higher glycemic index meals.(11) Proponents of this strategy suggest that the insulin response following glucose absorption mediates subsequent food intake, and the blunted insulin response to a lower glycemic index meal translates to decreased food intake. While short trials of this mechanism appear promising, longer-term data have not yet confirmed this effect on weight loss. In the Samaha and Foster studies, as well as in others, improvements in fasting glucose, insulin, or insulin sensitivity, are not consistently observed in response to low carbohydrate diets.(6),(9),(10),(12)

Ketosis has been reported to suppress appetite, and this remains a potential mechanism that might decrease intake. Because the range of foods that can be consumed while following a low carbohydrate diet is limited, it is possible that the reduced number of food choices results in better diet compliance. This phenomenon, termed stimulus narrowing, is essentially the elimination of the option to choose foods that might typically be over-consumed. This principle is best illustrated by very low calorie formula diets where no other food is consumed.

It appears that reducing carbohydrate to very low levels, as with the Foster and Samaha studies, may confer an advantage over several months. If hunger is suppressed, and intake is reduced, this macronutrient mix might be an effective strategy for some. Critics of this strategy, however, cite potential effects on bone health and cardiovascular risk factors from a high fat, high protein diet. High protein intake, especially of sulfur-containing amino acids, results in increased bone resorption and promotes calciuria.(13) A potential mechanism is the role of bone in buffering acid loads induced by amino acids.(13) However, a buffering effect of other dietary constituents such as fruit and vegetables has also been observed,(14) and adequate calcium intake may also minimize deleterious effects on bone.(15) At present, the effects of high protein diets on bone health remain unresolved.

In general, the low carbohydrate weight loss diets described above, as well as others, have not resulted in increased total and LDL cholesterol predicted by some (Figure 2).

Figure 2. Effects of Low Carbohydrate and Low Fat Diets on Blood Lipids.

Figure 2

From Foster GD, Wyatt HR, Hill JO, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 2003;348:2082-90. Copyright 2003 Massachusetts Medical Society. All rights reserved.

With regard to HDL cholesterol, greater increases (vs. smaller increases or decreases) have been observed, although HDL subfractions remain unclear in some studies.(16) The increase in triglycerides, at times observed with diets high in carbohydrates, is also not seen with reduced carbohydrate diets. Does this mean that low carbohydrate diets will not adversely influence blood lipids? As noted in an editorial accompanying the Foster and Samaha studies, consumption of high levels of saturated fat without adverse effects on cardiovascular disease is inconsistent with a large body of epidemiologic and intervention data.(16)

Is Reconciliation Possible?

How can these two camps be reconciled? First, the low carbohydrate diet studies have been conducted in relatively small numbers of subjects for relatively short periods of time. It is possible that the effects of low carbohydrate diets on lipids may change over a period of time exceeding the study durations.

Second, it is likely that several factors determine the susceptibility of individuals to adverse lipid responses. It is possible that genetic susceptibility plays a significant role in determining the individual response, but at present there are no methods to identify such individuals. Without such methods at present, it seems prudent to avoid diets at the extremes of high fat or high triglyceride intake in those individuals who demonstrate very high levels of total LDL cholesterol or triglycerides (respectively).

Third, the effect of diet composition may be minimized by negative energy balance. This principle is best illustrated by the effects of very low calorie diets on blood glucose control in diabetics. If the change in blood sugar is examined relative to the duration of the very low calorie diet, it becomes clear that reducing intake, even without significant weight loss, has a powerful effect on blood sugar. Within a week of consuming a very low calorie diet, blood sugar decreases almost 50% of the total decrease observed following 16 weeks of dieting.(17)


The macronutrient content of the diet affects both sides of the energy equation, intake and expenditure. It appears that the most meaningful effects are observed on food intake, while the effects on energy expenditure and nutrient partitioning may have a less significant role on body weight regulation. Diets comprised of very low carbohydrate content may be effective for some, but the long-term efficacy remains questionable. In addition, while no overall ill effects on blood lipids or other cardiovascular risk factors have thus far been observed, further research is needed to identify those individuals who may be more susceptible to the ill effects of diets traditionally associated with increased cardiovascular risk.


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