The proposed fat loss advantage of carbohydrate reduction beyond a mere reduction in total energy is based largely on insulin-mediated inhibition of lipolysis and presumably enhanced fat oxidation. However, a single-arm study by Hall et al. [51] examined the effect of 4 weeks on a low fat diet (300 g CHO) followed by 4 weeks on a KD (31 g CHO). Blood ketone levels plateaued at ~1.5 mmol/l within two weeks into the KD. A transient increase in energy expenditure (~100 kcal/day) lasting a little over a week occurred upon switching to the KD. This was accompanied by a transient increase in nitrogen loss, potentially suggesting a stress response including the ramping up of gluconeogenesis. Although insulin levels dropped rapidly and substantially during the KD (consisting of 80% fat, 5% CHO), an actual slowing of body fat loss was seen during the first half of the KD phase.
It has been postulated that the production and utilization of ketone bodies impart a unique metabolic state that, in theory, should outperform non-ketogenic conditions for the goal of fat loss [45]. However, this claim is largely based on research involving higher protein intakes in the LCD/KD groups. Even small differences in protein can result in significant advantages to the higher intake. A meta-analysis by Clifton et al. [52] found that a 5% or greater protein intake difference between diets at 12 months was associated with a threefold greater effect size for fat loss. Soenen et al. [53] systematically demonstrated that the higher protein content of low-carbohydrate diets, rather than their lower CHO content, was the crucial factor in promoting greater weight loss during controlled hypocaloric conditions. This is not too surprising, considering that protein is known to be the most satiating macronutrient [54]. A prime example of protein’s satiating effect is a study by Weigle et al. [55] showing that in ad libitum conditions, increasing protein intake from 15 to 30% of total energy resulted in a spontaneous drop in energy intake by 441 kcal/day. This led to a body weight decrease of 4.9 kg in 12 weeks.
With scant exception [56], all controlled interventions to date that matched protein and energy intake between KD and non-KD conditions have failed to show a fat loss advantage of the KD [51, 53, 57, 58, 59, 60]. A recent review by Hall [61] states, “There has never been an inpatient controlled feeding study testing the effects of isocaloric diets with equal protein that has reported significantly increased energy expenditure or greater loss of body fat with lower carbohydrate diets.” In light of this and the previously discussed research, the ‘special effects’ of LCD and KD are not due to their alleged metabolic advantage, but their higher protein content. Perhaps the strongest evidence against the alleged metabolic advantage of carbohydrate restriction is a recent pair of meta-analyses by Hall and Guo [60], which included only isocaloric, protein-matched controlled feeding studies where all food intake was provided to the subjects (as opposed to self-selected and self-reported intake). A total of 32 studies were included in the analysis. Carbohydrate ranged from 1 to 83% and dietary fat ranged from 4 to 84% of total energy. No thermic or fat loss advantage was seen in the lower-CHO conditions. In fact, the opposite was revealed. Both energy expenditure (EE) and fat loss were slightly greater in the higher-CHO/lower-fat conditions (EE by 26 kcal/day, fat loss by 16 g/d); however, the authors conceded that these differences were too small to be considered practically meaningful.
A common criticism of the existing literature is that trials need to run longer (several months instead of several weeks) to allow sufficient “ketoadaptation,” which is a physiological shift toward increased fat oxidation and decreased glycogen utilization [62]. The problem with this claim is that the rise in fat oxidation – objectively measured via decreased respiratory quotient – reaches a plateau within the first week of a KD [51]. Increased oxidation of free fatty acids, plasma triacylglycerol, and intramuscular triacylglycerol during exercise is a well-established response to fat-rich diets [63]. However, this rise in fat oxidation is often misconstrued as a greater rate of net FM reduction. This assumption ignores the concomitant increase in fat intake and storage. As a result of fat-adaptation, increased intramuscular triacylglycerol levels indicate increased fat synthesis over degradation during the rest periods between exercise bouts [64]. To reiterate a previous point, rigorously controlled isocaloric, protein-matched studies have consistently demonstrated that ketoadaptation does not necessarily amount to a net decrease in fat balance, which is ultimately what matters.
If there is any advantage to KD over non-KD for fat loss, it is potentially in the realm of appetite regulation. Under non-calorically restricted conditions, KD has consistently resulted in body fat and/or body weight reduction [65, 66, 67, 68, 69]. This occurs via spontaneous energy intake reduction, which could be due to increased satiety through a suppression of ghrelin production [70]. Moreover, KD has demonstrated hunger-suppressive effects independent of protein content. In a 4-week crossover design, Johnstone et al. [66] found that a KD consumed ad libitum (without purposeful caloric restriction) resulted in an energy intake reduction of 294 kcal/day. The latter results were seen despite a relatively high protein intake (30% of energy) matched between KD (4% CHO) and non-KD (35% CHO) conditions. In further support of this idea, a meta-analysis by Gibson et al. [71] found that KD suppresses appetite more than VLED. However, it remains unclear whether the appetite suppression is due to ketosis or other factors such as an increased protein or fat intake, or restriction of carbohydrate.
An area of growing interest is the effect of KD on athletic performance. Since training capacity has the potential to affect body composition, the effect of KD on exercise performance warrants discussion. Carbohydrate restriction combined with high fat intake to become fat-adapted (or ketoadapted) is a tactic that attempts to improve performance by increasing the body’s reliance on fat as fuel, thereby sparing/decreasing glycogen use, which ostensibly could improve athletic performance. However, in contrast to the proposed benefits of fat-adaptation on performance, Havemann et al. [72] found that 7 days of a high-fat diet (68%) followed by 1 day of high-CHO diet (90%) expectedly increased fat oxidation, but decreased 1-km sprint power output in well-trained cyclists. Stellingwerff et al. [73] compared substrate utilization, glycogenolysis, and enzymatic activity from either 5 days of a high-fat diet (67%) or high-CHO (70%) followed by one day of high-CHO with no training, followed by experimental trials on the seventh day. The high-fat diet increased fat oxidation, but also lowered pyruvate dehydrogenase activity and decreased glycogenolysis. These results provide a mechanistic explanation for the impairment in high-intensity work output as a result of high-fat, CHO-restricted diets [62, 65, 67]. Recently, an ergolytic effect from ketoadaptation has been observed at lower intensities as well. Burke et al. [74] reported that after 3 weeks on a KD at a slight energy deficit, elite race walkers showed increased fat oxidation and aerobic capacity. However, this was accompanied by a reduction in exercise economy (increased oxygen demand for a given speed). The linear and non-linear high-CHO diets in the comparison both caused significant performance improvements, while no significant improvement was seen in the KD (there was a nonsignificant performance decrease). It is notable that Paoli et al. [75] found no decrease in bodyweight-based strength performance in elite artistic gymnasts during 30 days of KD. Furthermore, the KD resulted in significant loss of FM (1.9 kg) and non-significant gain of LM (0.3 kg). However, unlike Burke et al.’s study, which equated protein between groups (~2.2 g/kg), Paoli et al.’s protein intakes were skewed in favor of the KD (2.9 vs. 1.2 g/kg). Wilson et al. [56] recently reported similar increases in strength and power in a protein and calorie-matched comparison of a KD and a Western diet model, suggesting that KD might have less ergolytic potential for strength training than it does for endurance training.
