Cutting fat resulted in more body fat loss as measured by metabolic balance

Cutting carbohydrates increased net fat oxidation, but cutting fat by equal calories had no effect

19 adults with obesity were confined to a metabolic ward for two 2-week periods

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.

We performed an in-patient metabolic balance study examining the effect of selective isocaloric reduction of dietary carbohydrate versus fat on body weight, energy expenditure, and fat balance in obese volunteers. A mechanistic mathematical model of human macronutrient metabolism () was used to design the study and predict the metabolic response to each diet before the study was conducted (). Here, we report the results of this experiment and use the mathematical model to quantitatively integrate the data and make in silico predictions about the results of long-term diet studies that are not practical to perform in the real world. In agreement with our model simulations, we found that only the reduced carbohydrate diet led to significant changes in metabolic fuel selection, with sustained reductions of carbohydrate oxidation and increased fat oxidation. Remarkably, fat oxidation on the reduced-fat diet remained unchanged and resulted in a greater rate of body fat loss compared to the reduced carbohydrate diet, despite being equivalent in calories.

Several randomized controlled trials have demonstrated greater short-term weight loss when advising obese patients to restrict dietary carbohydrates (), but such outpatient studies are difficult to interpret mechanistically because it is not currently possible to accurately measure adherence to the recommended diets since the instruments for assessing food intake rely on self-report and have been demonstrated to be biased (). Therefore, outpatient studies cannot determine to what extent any observed differences in weight loss are due to a metabolic advantage of reduced carbohydrate diets versus a greater reduction in overall energy intake.

Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial.

While the first law of thermodynamics requires that all calories are accounted, could it be true that reducing dietary fat without also reducing carbohydrates would have no effect on body fat? Could the metabolic and endocrine adaptations to carbohydrate restriction result in augmented body fat loss compared to an equal calorie reduction of dietary fat?

Weight loss diets often recommend targeted restriction of either carbohydrates or fat. While low-fat diets were popular in the latter part of the 20century, carbohydrate restriction has regained popularity in recent years, with proponents claiming that the resulting decreased insulin secretion causes elevated release of free fatty acids from adipose tissue, increased fat oxidation and energy expenditure, and greater body fat loss than restriction of dietary fat (). One influential author concluded that “any diet that succeeds does so because the dieter restricts fattening carbohydrates …Those who lose fat on a diet do so because of what they are not eating—the fattening carbohydrates” (). In other words, body fat loss requires reduction of insulinogenic carbohydrates. This extraordinary claim was based on the observation that even diets targeting fat reduction typically also reduce refined carbohydrates. Since the primary regulator of adipose tissue fat storage is insulin, and a reduction in refined carbohydrates reduces insulin, carbohydrate reduction alone may have been responsible for the loss of body fat—even with a low-fat diet.

Why we get fat and what to do about it.

Why we get fat and what to do about it.

Since it might be possible that different ratios of carbohydrate and fat would lead to different results, we simulated body weight and fat mass changes after 6 months of eating a variety of 30% reduced-energy isocaloric diets varying in carbohydrate and fat, with protein fixed at baseline levels as illustrated in Figure 3 H. The model predicted that weight loss increased with decreasing carbohydrate. However, body fat loss was relatively insensitive to isocaloric substitutions of dietary fat and carbohydrate, suggesting that the body acts to minimize differences in fat loss when the diet calories and protein are held constant. In fact, the experimental RC and RF diets resulted in close to the maximum predicted differences in body fat loss. In other words, the modest differences in body fat loss achieved by the diets used in our experiment are probably greater than would be observed with other ratios of carbohydrate and fat.

Overnight-fasted plasma hormone and metabolite levels during the last 3 days of the baseline diet and their changes over the last 3 days of the isocaloric reduced-carbohydrate (RC) and reduced-fat (RF) diets. The data were analyzed using a repeated-measures mixed model controlling for sex and order effects and are presented as least-squares mean ± SEM. The p values refer to the diet effects and were not corrected for multiple comparisons.

Several days of the RF diet led to a steady fat imbalance of 840 ± 60 kcal/day, or equivalently 89 ± 6 g/day of body fat loss ( Figure 3 A), which was significantly greater than the steady rate of body fat loss of 500 ± 60 kcal/day, or 53 ± 6 g/day, achieved during the RC diet (p = 0.0002) ( Figure 3 A). In contrast, the RC diet led to significantly greater transient carbohydrate imbalance ( Figure 3 B) with little difference in protein balance ( Figure 3 C) compared with the RF diet.

Mean ± 95% CI. ∗∗ indicates p < 0.001 between RC and RF. ∗ indicates p = 0.004 between RC and RF.

(I) Model simulated changes in average fat balance and total energy expenditure (TEE) were reciprocally related and non-monotonic with respect to carbohydrate content. The experimental RC and RF diets are indicated by the vertical dashed lines.

(H) Simulating 6 months of adherence to a 30% reduced-energy diet varying in carbohydrate and fat percentage, but with protein fixed at baseline, indicated that weight loss was linearly related to carbohydrate content, but fat mass was non-monotonic and relatively unaffected by carbohydrate content.

(G) Mathematical model simulations of 6 months of perfect adherence to the RC and RF diets predicted slightly greater fat mass loss with the RF diet compared with the RC diet.

(F) The RC and RF diets both led to weight loss, but significantly more weight was lost following the RC diet.

(E) Fat mass change as measured by DXA revealed significant changes from baseline, but did not detect a significant difference between RF and RC diets.

(D) Cumulative fat balance indicated that both the RF and RC diets led to body fat loss, but the RF diet led to significantly more fat loss than the RC diet.

(C) Protein balance tended to be lower for the RC diet compared to the RF diet.

(B) Net carbohydrate balance was more negative for the RC diet compared to the RF diet and returned toward balance at the end of the study with both diets.

(A) Daily fat balance was negative for both the RF and RC diets, indicating loss of body fat. The RF diet led to consistently greater fat imbalance compared with the RC diet.

The mean changes in overall energy expenditure, energy balance, 24-hr RQ, fat oxidation, and carbohydrate oxidation during the RC and RF diets are quantified in Table 3 and mirror the day-by-day results above that are presented in Figure 2

Only the RC diet led to significant sustained adaptations of carbohydrate and fat metabolism. At the end of the RC diet period, net fat oxidation increased by 463 ± 63 kcal/day (p < 0.0001) ( Figure 2 G) and net carbohydrate oxidation decreased by 595 ± 57 kcal/day (p < 0.0001) ( Figure 2 H). In contrast, only the first day of the RF diet led to a significant reduction in net fat oxidation by 96 ± 64 kcal/day (p = 0.01) ( Figure 2 G) and an increase in net carbohydrate oxidation of 147 ± 49 kcal/day (p = 0.01) ( Figure 2 H) compared to baseline. The mathematical model simulations agreed well with the observed changes in fat oxidation ( Figure 2 G), but slightly overestimated the decrease in carbohydrate oxidation during the RC diet ( Figure 2 H). The model also indicated that the RC diet would lead to increased net protein oxidation compared to the RF diet ( Figure 2 I), a trend that was apparent in the 24-hr urinary nitrogen data ( Table 3 ).

The 24-hr respiratory quotient (RQ) provides a measure of the overall metabolic fuel mixture being used by the body to produce energy, with RQ values approaching 1 indicating primarily carbohydrate oxidation and values near 0.7 indicating primarily fat oxidation. The 24-hr RQ was the primary endpoint of this study, and the mathematical model of human macronutrient metabolism predicted in advance that the RF diet would lead to no significant change in RQ whereas the RC diet would lead to a decrease in RQ (). Figure 2 C illustrates the 24-hr RQ data and mathematical model simulations in response to the RC and RF diets. In agreement with the model simulations, only the RC diet resulted in RQ changes, indicating a shift toward increased fat oxidation. In contrast, only the first day of the RF diet led to a significant increase in RQ from baseline (p < 0.0001), but there was no significant change in RQ overall, implying that changes in dietary fat have little effect on carbohydrate or fat oxidation ( Table 3 ).

RC, reduced carbohydrate; RF, reduced fat. The data were analyzed using a repeated-measures mixed model controlling for sex and order effects and are presented as least-squares mean ± SEM. The p values refer to the diet effects and were not corrected for multiple comparisons.

One female subject had changes in DXA % body fat data that were not physiological and were clear outliers, so these data were excluded from the analyses.

a One female subject had changes in DXA % body fat data that were not physiological and were clear outliers, so these data were excluded from the analyses.

One female subject had changes in DXA % body fat data that were not physiological and were clear outliers, so these data were excluded from the analyses.

a One female subject had changes in DXA % body fat data that were not physiological and were clear outliers, so these data were excluded from the analyses.

Body Composition and Energy Metabolism Changes following the Isocaloric Reduced-Carbohydrate and Reduced-Fat Diets

Table 3 Body Composition and Energy Metabolism Changes following the Isocaloric Reduced-Carbohydrate and Reduced-Fat Diets

The experimental diets were designed such that they were 30% lower in calories than the baseline diet ( Table 2 ), and the reduced carbohydrate (RC) and reduced fat (RF) diets led to selective reductions in carbohydrate intake and fat intake, respectively, whereas protein intake was practically unchanged from baseline ( Figure 2 A). Note also that the RF diet did not have a decrease in sugar content compared to baseline ( Table 2 ). This was important since a decrease in sugar content with the RF diet would be expected to decrease insulin secretion despite no change in total carbohydrate content compared to baseline. As a result, only the RC diet resulted in a 22.3% ± 7.0% decrease in daily insulin secretion (p = 0.001) as measured by 24-hr urinary excretion of C-peptide and depicted in Figure 2 B. Therefore, the experimental reduced-energy diets resulted in substantial differences in insulin secretion despite being isocaloric.

Mean ± 95% CI. ∗ indicates a significant difference from baseline at p = 0.001; ∗∗ indicates a significant difference between RC and RF at p < 0.0001.

(I) Net protein oxidation was not significantly altered by the RF or RC diets.

(H) Net carbohydrate oxidation decreased during the RC diet and was relatively unchanged during the RF diet apart from a slight initial increase on the first day.

(G) Net fat oxidation increased substantially during the RC diet and reached a plateau after several days, whereas the RF diet appeared to have little effect.

(E) Energy expenditure as measured in the metabolic chamber (24-hr EE) decreased with the RC diet but not the RF diet.

(D) Energy intake was reduced equivalently during the RC and RF diets.

(C) The 24-hr respiratory quotient was practically unchanged during the RF diet but fell during the RC diet, indicating an increased reliance on fat oxidation.

(B) Insulin secretion throughout the day was assessed by 24-hr urinary C-peptide excretion and was significantly reduced only following the RC diet.

(A) The reduced carbohydrate (RC) diet achieved 30% energy restriction via selective reduction in carbohydrate intake (CI) whereas the isocaloric reduced-fat (RF) diet resulted from selective reduction of fat intake (FI). Protein intake (PI) was unchanged from baseline on both diets.

Nutrient Content of the Baseline and Reduced-Carbohydrate and Reduced-Fat Diets

Table 2 Nutrient Content of the Baseline and Reduced-Carbohydrate and Reduced-Fat Diets

We investigated ten male and nine female subjects who all had obesity with a BMI of (mean ± SEM) 35.9 ± 1.1 kg/m Table 1 ). While the men and women had similar body weight and BMI, the women had significantly higher body fat and lower rates of energy expenditure and food intake, as expected. All subjects were admitted to the metabolic unit at the NIH Clinical Center where they resided for a pair of 2-week inpatient periods separated by a 2- to 4-week washout period ( Figure 1 ). The subjects exercised on a treadmill for 1 hr each day at a clamped pace and incline to maintain a relatively constant physical activity. For the first 5 days of each visit, they consumed a eucaloric baseline diet composed of 50% carbohydrate, 35% fat, and 15% protein with a total energy content of 2,740 ± 100 kcal/day, which was not significantly different from their average total energy expenditure (TEE) of 2,880 ± 160 kcal/day (p = 0.19) as measured by the doubly labeled water method. During the days spent residing in a metabolic chamber, 24-hr energy expenditure (EE) was 2,560 ± 110 kcal/day, which was slightly less than the baseline energy intake (p = 0.001) as well as TEE (p = 0.008). This was likely due to decreased spontaneous physical activity when confined to the metabolic chamber, as confirmed by an overall 23.4% ± 4% reduction in accelerometer counts during chamber days (not shown, p < 0.0001).

Adults with obesity were admitted to the metabolic unit at the NIH Clinical Center where they received a eucaloric baseline diet for 5 days followed by a 30% energy-restricted diet achieved either through selective reduction of fat (RF) or carbohydrate (RC) for a period of 6 days. Subjects spent 5 days residing in metabolic chambers and had a dose of doubly labeled water (DLW) administered on the first inpatient day. Body composition was assessed by dual-energy X-ray absorptiometry (DXA) during baseline and at the end of the reduced-energy diets. Subjects returned after a 2- to 4-week washout period to undergo the opposite RC or RF diet following the same 5-day baseline phase. The order of the RC and RF diet periods was randomized.

Discussion

This study demonstrated that, calorie for calorie, restriction of dietary fat led to greater body fat loss than restriction of dietary carbohydrate in adults with obesity. This occurred despite the fact that only the carbohydrate-restricted diet led to decreased insulin secretion and a substantial sustained increase in net fat oxidation compared to the baseline energy-balanced diet.

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Phinney S.D. Low-carbohydrate nutrition and metabolism. Taubes, 2011 Taubes G. Why we get fat and what to do about it. In contrast to previous claims about a metabolic advantage of carbohydrate restriction for enhancing body fat loss (), our data and model simulations support the opposite conclusion when comparing the RF and RC diets. Furthermore, we can definitively reject the claim that carbohydrate restriction is required for body fat loss ().

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Phinney S.D. Low-carbohydrate nutrition and metabolism. Dietary fat contributed only about 8% to the total energy content of the RF diet, making it a very low-fat diet. The RF diet did not reduce refined carbohydrates from baseline and resulted in no significant changes in 24-hr insulin secretion. In contrast, carbohydrates were about 29% of the energy content of the RC diet with a mean absolute carbohydrate intake of about 140 g/day, which induced a substantial drop in 24-hr insulin secretion. Thus, while the RC diet qualifies as a low-carbohydrate diet, it was clearly not a very low-carbohydrate diet, which typically requires carbohydrates to be less than 50 g/day (). Given the composition of the baseline diet, it was not possible to design an isocaloric very low-carbohydrate diet without also adding fat or protein. We decided against such an approach due to the difficulty in attributing any observed effects of the diet to the reduction in carbohydrate as opposed to the addition of fat or protein.

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et al. Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: a 1-y randomized controlled trial. Randomized controlled trials often involve hundreds or thousands of subjects prescribed to follow different diet regimens, with investigators providing instructions and support to participants on how to eat the prescribed diets. However, there is little evidence that people actually adhere to the diet prescriptions. Such studies actually test the effects of different diet prescriptions rather than the effects of different diets and cannot shed much light on the underlying physiology. As an alternative, controlled feeding studies can provide more useful physiological information, but diet adherence is often poor in outpatient studies even when participants are provided with all of their food (). Therefore, inpatient feeding studies are required to properly control the diets and measure physiological effects, but such studies are very expensive and labor intensive, making them typically small in size.

The most sensitive method for detecting the rate of body fat change requires calculating daily fat balance as the difference between fat intake and net fat oxidation (i.e., fat oxidation minus de novo lipogenesis) measured by indirect calorimetry while residing in a metabolic chamber. At the end of the diet periods, our study had a minimum detectable difference in daily fat balance of 220 kcal/day (or 23 g/day) and the cumulative fat loss had a minimum detectable difference of 110 g. The observed differences in fat balance and cumulative body fat loss between RC and RF diets were substantially larger than these values and were statistically significant. While the fat balance method does not determine the anatomical location of lost fat, decreased adipose tissue triglyceride likely makes up the majority. Any additional loss of ectopic fat from liver or skeletal muscle would likely be even more beneficial.

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Madani N. Protein metabolism during weight reduction with very-low-energy diets: evaluation of the independent effects of protein and carbohydrate on protein sparing. Model simulations suggest that the differences in fat loss were due to transient differences in carbohydrate balance along with persistent differences in energy and fat balance. The model also implicated small persistent changes in protein balance resulting from the fact that dietary carbohydrates preserve nitrogen balance to a greater degree than fat (). The timing and magnitude of the observed change in net fat oxidation and fat balance with the RC diet were accurately simulated by the model and indicated that the adaptation to the experimental carbohydrate restriction achieved a plateau after several days. In contrast, the RF diet led to little adaptation with a relatively constant net fat oxidation rate, thereby leading to a greater fat imbalance compared to the RC diet.

Our relatively short-term experimental study has obvious limitations in its ability to translate to fat mass changes over prolonged durations. It could be argued that perhaps the fat balance and body fat changes would converge with continuation of the diets over the subsequent weeks. However, this would require that the net fat oxidation rate somehow increase above the observed plateau with the RC diet, and/or the RF diet would have to result in a swifter decrease in fat oxidation. Neither of these possibilities was apparent in the data and did not occur in the mathematical model simulations of prolonged diet periods. If such a convergence in body fat loss were to occur with prolonged RC and RF diets, the physiological mechanism is unclear.

The mathematical model simulations suggest that the diet with selective reduction in fat would continue to outpace the reduced carbohydrate diet over 6 months. However, further reducing dietary carbohydrate from the RC diet (with a corresponding addition of fat to maintain calories) was predicted to decrease body fat to a greater extent than the experimental RC diet. Very low carbohydrate diets were predicted to result in fat losses comparable to low fat diets. Indeed, the model simulations suggest that isocaloric reduced-energy diets over a wide range of carbohydrate and fat content would lead to only small differences in body fat and energy expenditure over extended durations. In other words, while the present study demonstrated the theoretical possibility that isocaloric diets differing in carbohydrate and fat can result in differing body fat losses, the body acts to minimize such differences. The endocrine and metabolic adaptations that allow for the relative insensitivity of body fat to dietary macronutrient composition may themselves have effects on health over the long term, but this was not investigated in the present study.

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et al. Dietary Intervention Randomized Controlled Trial (DIRECT) Group

Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. Translation of our results to real-world weight-loss diets for treatment of obesity is limited since the experimental design and model simulations relied on strict control of food intake, which is unrealistic in free-living individuals. While our results suggest that the experimental reduced-fat diet was more effective at inducing body fat loss than the reduced-carbohydrate diet, diet adherence was strictly enforced. We did not address whether it would be easier to adhere to a reduced-fat or a reduced-carbohydrate diet under free-living conditions. Since diet adherence is likely the most important determinant of body fat loss, we suspect that previously observed differences in weight loss and body fat change during outpatient diet interventions () were primarily due to differences in overall calorie intake rather than any metabolic advantage of a low-carbohydrate diet.

In summary, we found that selective reduction of dietary carbohydrate resulted in decreased insulin secretion, increased fat oxidation, and increased body fat loss compared to a eucaloric baseline diet. In contrast, selective isocaloric reduction of dietary fat led to no significant changes in insulin secretion or fat oxidation compared to the eucaloric baseline diet, but significantly more body fat was lost than during the carbohydrate-restricted diet.