Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity

Kevin Hall, Thomas Bemis, Robert Brychta, Kong Chen, Amber Courvillle, Emma Crayner, Stephanie Goodwin, Juen Guo, Lillian Howard, Nicolas Knuth, Bernard Miller, Carla Prado, Maria Siervo, Monica Skarulis, Mary Walter, Peter Walter and Laura Yannai

Cell Metabolism 2015. 22: 427-436.

Abstract

Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5-day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 ± 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 ± 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat.

Our Thoughts on This Paper

Rationale

It has been suggested that low carbohydrate diets lead to a greater fat loss than diets of reduced fat content. The rationale behind this claim is that insulin promotes lipid synthesis and storage in adipose tissue, therefore a reduction in dietary carbohydrate would reduce circulating insulin concentrations and discourage fat storage. However, the first law of thermodynamics clearly states that energy cannot be created or destroyed, only transformed; therefore, all calories are equal, no matter their origin, and net energy balance is determined solely by the difference between energy intake and expenditure. Given that thermodynamic law does not consider metabolic and endocrine factors, Hall et al aimed to compare isocaloric reduction of dietary carbohydrate versus dietary fat on body composition and energy expenditure changes in obese volunteers. Prior to the study, a mechanistic mathematical model was used to predict the metabolic responses to each diet.

Methods

The study was a randomized crossover design with nine women and ten men enrolled. Participants were weight-stable with a BMI greater than 30 kg/m2 and were considered to be generally healthy. To control for the variability of free-living conditions, the study was conducted in an in-patient setting. Participants reported to the metabolic clinic where their total energy expenditure was calculated following consumption of doubly labelled water. Participants received a eucaloric baseline diet for 5 d (2740 kcal/d; 35.3% fat, 50.2% carbohydrate and 14.5% protein), followed by 6 d of either a reduced carbohydrate diet with a 30% reduction in total energy (1918 kcal/d; 50.1% fat, 29% carbohydrate and 20.9% protein) or a reduced fat diet with a 30% reduction in total energy (1918 kcal/d; 7.7% fat, 71.2% carbohydrate and 21.1% protein). Following a washout period, participants returned to the metabolic ward and repeated the same protocol, only this time they received the opposite isocaloric diet. Body composition was monitored (DEXA and indirect calorimetry) and respiratory gasses, blood and urine were collected throughout both in-patient periods. Rates of substrate oxidation were determined using indirect calorimetry. Plasma hormone concentrations were determined using a multiplex assay panel, whereas plasma metabolite concentrations were determined using colorimetric assay kits. 24 hr urinary C-peptide excretion was measured by ELISA.

Findings

At baseline, male and female participants differed in several metabolic parameters, including total body fat (absolute and percent), sleeping metabolic rate, 24 hr energy expenditure, 24 hr respiratory quotient, total energy expenditure and total energy intake. Despite these baseline sex differences, the authors present the combined data analysis in the paper (both males and females) and the sex-separated data as a supplementary file. All three data sets will be described below.

For the combined analysis, both experimental diets caused a reduction in body weight, BMI, absolute fat mass, energy intake, energy expenditure, the HOMA index and plasma values for cholesterol, HDL, leptin, insulin and adiponectin. The change in body weight and BMI was greater following the reduced carbohydrate diet, but changes in fat mass were similar (as measured by DEXA), and greater following the reduced fat diet (when measured by indirect calorimetry). Reductions in cholesterol and HDL were of a greater magnitude after the reduced fat diet. Both diets caused a cumulative fat imbalance, however this effect was almost double after the reduced fat diet. Only the reduced carbohydrate diet caused a reduction in 24 hr C-peptide (a measure of insulin release), however both diets reduced overnight fasting levels of C-peptide. Only the reduced carbohydrate diet lowered the respiratory quotient, reduced carbohydrate oxidation, increased fat oxidation, lowered carbohydrate balance and lowered sleeping metabolic rate. Only the reduced carbohydrate diet lowered plasma triglycerides and increased beta hydroxybutyrate, ghrelin and resistin levels. Blood glucose, plasma PAI-1 and 24 hr urinary nitrogen were only lowered after the reduced fat diet. The mathematical model closely predicted many of the variables measured, with slight over estimations for changes in carbohydrate oxidation in response to the reduced carbohydrate diet. For females, both diets reduced body weight, BMI and energy balance similarly. Although both diets caused a cumulative fat imbalance, this effect was greater in the reduced fat diet. Only the reduced carbohydrate diet lowered the sleeping metabolic rate, 24 hr carbohydrate oxidation and increased 24 hr fat oxidation. 24 hr energy expenditure was only reduced in the reduced fat diet. The HOMA index was reduced similarly between diets, whereas although HDL and leptin were reduced by both diets, the effect was greater for leptin after the reduced carbohydrate diet and for HDL after the reduced fat diet. Only the reduced carbohydrate diet reduced insulin concentrations, whereas only the reduced fat diet reduced fasting glucose, cholesterol and LDL levels. Although non-significant for either diet, there was a significant divergent response between the diets for both GIP and PAI-1 concentrations, which were each increased following the reduced carbohydrate diet and decreased after the reduced fat diet.

For males, both diets reduced body weight, BMI, fat mass and energy balance; however, unlike the females, the effects for body weight and BMI were greater after the reduced carbohydrate diet in the males, whereas the reduction in energy balance was greater after the reduced fat diet. Similarly, cumulative fat balance was reduced by both diets, however the effect was greatest after the reduced fat diet. Only the reduced carbohydrate diet lowered 24 hr energy expenditure, 24 hr respiratory quotient and 24 hr carbohydrate oxidation, and increased 24 hr fat oxidation. Conversely, the reduced fat diet increased the 24 hr respiratory quotient and 24 hr carbohydrate oxidation. Decreases in 24 hr urinary nitrogen were only seen after the reduced fat diet. Both diets reduced leptin, increased adiponectin, reduced ghrelin and reduced cholesterol levels similarly. Both diets reduced PAI-1, however this was only significant for the reduced carbohydrate diet. A reduced HOMA index, insulin concentration and HDL were seen only after the reduced fat diet, whereas there was an increase in C-peptide only after the reduced fat diet. Beta hydroxybutyrate was increased after both diets, but this was only significant for the reduced carbohydrate diet.

Gender Differences

Some divergent results were seen between males and females. Although neither result was significant, the % body fat increased for females but decreased for males after both diets. For females, 24 hr energy expenditure was reduced by both diets but this effect was only seen in the males after the reduced carbohydrate diet. The reduced fat diet had no effect on respiratory quotient or 24 hr carbohydrate oxidation in the females, however both variables increased in the males after the reduced fat diet. The reduction in 24 hr urinary nitrogen was only seen in males following the reduced fat diet. Ghrelin was slightly (non-significantly) increased in the females after both diets, yet reduced in the males.

Interpretation

Acute isocaloric diets that are low in either fat or carbohydrate will cause a similar reductions in body weight despite the reduced fat diet being able to cause a greater fat imbalance and a greater fat loss (as calculated through indirect calorimetry). This suggests that although the energy transformation pathways may differ when weight loss is initiated through a reduced carbohydrate versus reduced fat diet, the body acts to reorganize energy storage when the two diets are isocaloric (at least in the acute phase). A major limitation of this study includes the combing of both male and female data for the analysis when it was clear from the baseline data that there are many sex differences across the variables measured. Indeed, divergent responses were observed between males and females for many of the variables following the different diets. Furthermore, it is difficult to interpret the body composition data without information about lean mass or hydration status of the participants. This study would benefit greatly from a higher number of participants and analyses that assess at the male and female data independently. Such a study would provide valuable information about how diet composition can alter metabolism and weight loss in a sex-specific manner.

Written by Erin Stephenson on Sept. 16, 2015.

Comments

comments powered by Disqus

Share This Paper

Metrics