4.1. Overview of Metabolism During Exercise
Actively-contracting muscles receive the contributions of three major energy pathways, which are influenced by the time and intensity of the exercise [54
]. The phosphocreatine (PCr) to ATP reaction, regulated by creatine kinase (e.g., the phosphagen system), is essential in resynthesizing ATP during immediate, high intensity work, and is a dominant system during the initial seconds of exercise. In moderate to high-intensity exercise sessions, lasting up to ~90 s, the short-term lactic acid system is a major contributor. During this interval, ATP resynthesis is primarily met by glycogen-dependent glycolysis [55
]. In moderately intense, long-duration exercise, the long-term aerobic system supplies metabolic substrates to support oxidative metabolism. Oxygen demands and oxygen uptake determine the contribution of the above energy systems during the metabolic response to exercise. During the initial moments of exercise, a large increase in oxygen uptake is required to match the energetic demands of the contracting muscle cells. However, a mismatch between the metabolic demands and oxygen uptake exists for several seconds to several minutes, called the “oxygen deficit” [56
]. During the oxygen deficit, the phosphagen system and lactic acid system are the major supporters of ATP resynthesis. Once oxygen uptake and oxygen demand are in balance, oxidative phosphorylation via the aerobic system becomes the dominant pathway to maintain ATP regeneration.
Once steady-state aerobic metabolism is reached, a steady supply of exogenous substrates are needed to maintain exercise. As shown in Figure 2
, these exogenous substrates are supplied by the liver and adipose tissue. During aerobic exercise, the liver has the primary role of maintaining blood glucose levels via glycogenolysis, and to a smaller degree, gluconeogenesis. In addition, the liver can produce ketone bodies from elevated serum concentrations of fatty acids. A sustained rise in serum fatty acids occurs due to the lipolysis of adipose tissue, activated by beta-adrenergic stimulation [57
]. Through these coordinated efforts of the liver and adipose tissue, a sufficient supply of substrates, namely, glucose, ketone bodies, and fatty acids, fuels the contraction of cardiac and skeletal muscle. Cardiac muscle has an added benefit, as it demonstrates an increased capacity to utilize lactate produced by the skeletal muscle during higher workloads [58
4.2. The Effects on Aerobic Endurance Exercise
The contribution of fatty acids to oxidative metabolism varies with exercise intensity and duration [59
]. During low-to-moderate intensity exercise, the oxidation of exogenous fatty acids is a significant source of energy. During exercise of a moderate intensity, the contribution of fatty acids to oxidative metabolism increases, as the duration of the exercise bout is prolonged. In that regard, strategies that promote the availability of fatty acids may be critical to optimizing endurance exercise performance. The KD may be advantageous, especially for aerobic endurance exercise, by promoting fat usage, rather than carbohydrates, for fuel. Fat from adipose tissue is considered a steady supply of energy, while endogenous carbohydrate stores from glycogen in the skeletal muscle and the liver are finite. Elevated ketone bodies, resulting from the KD, may provide an alternative or supplemental fuel source to sustain endurance exercise.
There are numerous studies over the past decade that examined the effect of low carbohydrate (LC) or KD (LC/KD) diets on endurance exercise performance in humans [20
]. A vast majority of the studies focused on endurance-trained individuals, and included primarily male athletes. The diets utilized in the studies varied with the average caloric intake percentage from fat at 73% (range 63–80%); carbohydrates 7% (3.5–15%); and protein 20% (15–29%). Treatment times varied from as little as 3 weeks [60
] up to 20 months [20
]. Serum ketone body concentrations (mostly βOHB) reportedly increased anywhere from 0.5mM to 1.2mM, and did not appear to relate to the fat composition or treatment time of the diets. Most of these studies reported significant decreases in body weight or fat mass [60
]. Therefore, LC/KD diets appear to be an effective dietary strategy to induce weight loss and improve body composition in trained athletes.
However, despite the positive changes in body and fat mass, LC/KD diets are not effective in producing significant improvements in exercise performance, despite significant decreases in respiratory exchange ratio (RER), representing an increase in fatty acid oxidation (FAO). LC/KD did not significantly alter total time to exhaustion (TTE) [62
], maximal oxygen uptake (VO2
], or endurance cycling performance [65
]. In contrast, the consumption of a LC/KD for 3 weeks, combined with exercise training, impaired the training adaptations of elite race walkers by elevating oxygen consumption rates during activity [60
]. In 30-year-old endurance trained males fed a LC/KD for 1 month, TTE was reduced at 70% intensity, despite no change at 60% intensity [67
]. Two studies that included a population of females presented interesting results [63
]. In a small study of endurance athletes, 90% comprised of females, TTE was significantly decreased after 10 weeks of LC/KD [69
]. Similarly, LC/KD fed females from a recreational-trained Cross-Fit cohort experienced a non-significant 5% decrease in VO2
max, while males were unaffected by the diet [63
]. These studies clearly show that LC/KD in trained individuals offers no enhancement in exercise performance, and may lead to decreased performance, particularly in females.
Studies on the effects of LC/KD on exercise performance in overweight/obese individuals are limited and revealed varying results [70
]. An early study suggested that moderately obese individuals (primarily female) following a reduced carbohydrate (CHO) diet (45% calories) lost significant body weight and fat mass, and had improved endurance times during moderate exercise intensity [72
]. Although obese females consuming a diet of 33% CHO combined with exercise training experienced 20% greater weight loss, the improvement in TTE was similar to high CHO diet [72
]. A LC/KD for middle-aged, obese adults for 52 weeks led to a greater decrease in body weight and fat mass, compared to a low calorie or mixed diet, but did not result in improved exercise performance [74
]. In overweight/obese adults, a LC/KD diet led to significant weight loss only in males, with no significant change in TTE or VO2
max in males or females compared to a low fat diet [70
]. However, a 2-week LC/KD diet in overweight adults did not lead to weight loss, but increased fatigue and perceived effort [73
]. It should be noted that the keto-adaptation period is suggested to be 2–4 weeks [75
], so results of very short dietary interventions should be interpreted with caution. Although LC/KDs appear effective in the management of body weight and fat mass in overweight and obese individuals, the effects on exercise performance remain unclear and may depend on the degree of carbohydrate restriction and length of the dietary intervention.
Studies in rodents fed a LC/KD diet may provide some additional mechanistic insight into the effects of the LC/KD on exercise performance, particularly since the diet can be well controlled and the capability of performing bio-molecular measures is not limited. The composition of the LC/KD fed to rodents typically ranges from 70–78% fat with 1–5% CHO and 9–20% protein [76
]. In C57BL6/J male mice, 8 weeks of KD improved exercise treadmill times and molecular markers of recovery [77
]. However, 4 weeks of KD fed to female C57BL6 mice decreased aerobic capacity [80
]. In Sprague Dawley rats, voluntary running distance was not different during 6 weeks of KD [76
]; however, run time to exhaustion on a treadmill was improved after 1 or 5 weeks of KD [79
], compared to chow-fed controls. In addition to variable reports in exercise performance, some potential negative side effects, including increased adipose tissue mass [78
], decreased muscle glycogen content [79
], increased serum triglycerides [80
], and decreased cardiac function [80
], were noted. However, KDs may decrease mortality [81
], improve memory [81
], and increase muscle citrate synthase [82
] in aged mice. Perhaps additional studies in animal models are necessary to help derive definitive conclusions.
4.3. Its Effects on Anaerobic Exercise
Anaerobic exercise is a high intensity, low duration exercise that lasts less than 2 min. Energy demands are met by the phosphagen system and lactic acid system, which are highly dependent upon skeletal muscle glycogen. During anaerobic exercise, high contractile forces occur within the muscle, and muscle fibers become damaged. In addition to the replenishment of carbohydrates during the recovery period, adequate consumption of essential amino acids is important to support the protein synthesis necessary to repair and rebuild the muscle. In this regard, LC/KDs typically provide sufficient protein intake (~15% of daily calories) to avoid amino acid deficiency. However, due to the low carbohydrate intake, the increased reliance of amino acids toward gluconeogenesis and the impairment of glycogen-store restoration may adversely affect anaerobic performance.
Several studies evaluated the effects of LC/KDs on anaerobic performance, primarily assessing power or strength parameters, in various populations, including endurances athletes [65
], Cross-Fit participants [83
], gymnasts [85
], and powerlifters [86
]. Dietary interventions ranged from 6 weeks up to 12 weeks, and included normal training regimens typical of the populations studied. In general, consumption of the LC/KD did not result in strength [64
] or power [83
] measures that were significantly different from the control groups. One study reported a significant increase in relative power, but not absolute power, which was due to the decreased body weight experienced by the subjects [65
]. In some studies, significant decreases in skeletal muscle thickness [64
] or lean body mass [83
] were noted. Moreover, muscle hypertrophy from resistance training may be blunted with the LC/KD [87
]. These studies demonstrate that the LC/KD diet is not an effective strategy to increase anaerobic performance in trained individuals or athletes, and it has the potential to negate the expected increases in lean body mass from anaerobic training.