Oral ketone supplements have surged in popularity in recent years, fueled by claims of enhanced athletic performance, cognitive function, and metabolic benefits. This article delves into the science behind these claims, scrutinizes the existing evidence, and exposes the potential pitfalls and scams associated with "team keto fuel" and similar products.
The Rationale Behind Ketone Supplementation
The human body naturally produces ketone bodies (acetoacetate, acetone, and β-hydroxybutyrate - βHB) during periods of energy deficiency, such as prolonged fasting, ketogenic diets (low-carbohydrate), and extended exercise. These ketone bodies serve as an alternative fuel source for the brain, heart, and skeletal muscles, replacing glucose.
The purported ergogenic effect of ketone supplementation rests on the idea that increasing ketone body concentrations in the blood before or during exercise could provide an extra energy supply for muscle work, potentially sparing muscle glycogen stores. Myofiber glycogen is the primary energy substrate during intense endurance exercise, and its depletion leads to fatigue. Therefore, ketone supplementation has been proposed as a complementary strategy to carbohydrate loading, potentially boosting endurance sports performance through different metabolic pathways. Ketone bodies seem to inhibit glycolytic flux.
Conflicting Evidence on Sports Performance
Despite the biological rationale, the evidence supporting improved sports performance with ketone supplements remains controversial. A recent systematic review deemed the results across studies as mixed and equivocal. While a seminal study by Cox et al. reported a slight (∼2%) increase in total distance covered during a fixed time on a cycloergometer with acute administration of ketone esters alongside carbohydrates, subsequent studies have largely failed to replicate these findings. Some studies have even reported performance decrements.
Factors influencing the effects of ketone supplements on performance include the type and dose of the supplement (ketone esters vs. salts) and the exercise modality used for assessment. Studies using different dosages and various endurance exercise modalities, such as cycloergometer-simulated time trials, incremental tests to exhaustion, and anaerobic tests, have yielded inconsistent results.
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Notably, studies employing more ecologically valid time trials have often found no beneficial effects after acute oral intake of ketone supplements. For example, Leckey et al. found a detrimental performance effect (−2%) after acute ingestion of ketone esters in professional cyclists during a 31-km time trial.
It's important to consider that most studies have assessed performance using tests with a duration of less than 60 minutes. While the glucose-sparing effect of ketone supplementation could be potentially beneficial for performance, ketones could also impair carbohydrate metabolism and consequently reduce performance during intense endurance exercise, which relies mostly on muscle glycolytic flux for rapid provision of energy.
Strategies aimed at reducing reliance on muscle glycogen during exercise, such as low-carbohydrate, high-fat diets, have also failed to provide clear benefits on competitive performance and might reduce the capacity to sustain high-intensity exercise. Burke et al. reported that a ketogenic diet increased muscle fat oxidation rate in elite race walkers but impaired exercise economy and performance at race intensities. Similar results have been replicated in a different cohort of elite race walkers.
However, a positive association was recently found between the increase in plasma ketone concentrations during a multistage ultramarathon (240 km) and average running speed in the race, suggesting that acute ketone supplementation might be beneficial during long-duration low/moderate-intensity endurance exercise.
Metabolic Effects and Controversies
Controversy exists regarding whether oral ketone supplements can produce a meaningful metabolic effect during exertion. While the study by Cox et al. reported increased plasma concentrations of D-βHB (∼2-3.5 mmol/L) and a shift in metabolic fuel preference during exercise, with reduced muscle carbohydrate oxidation, other studies have shown mixed results.
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Mixed evidence exists for the effects of ketone supplements on plasma concentrations of ketone bodies, with mean plasma D-βHB concentrations reported to range between ∼0.3 and 0.7 mmol/L after ketone salt ingestion and between ∼0.3 and 3.5 mmol/L for ketone esters. Whether the fact that circulating ketone bodies do not consistently show a high increase after supplementation reflects that they are utilized by gut cells and/or rapidly oxidized by other tissues remains to be determined.
In addition, the reported effects of ketone supplements on blood lactate concentration during exercise are not consistent, with some authors finding lower concentrations, but others finding no effects. Similarly, some studies have found lower plasma glucose concentrations with ketone supplementation, but others have reported no differences compared with a control intervention.
Cognitive Performance: Limited and Mixed Evidence
Cognitive performance is crucial in many sports, particularly those requiring fast decision-making. Ketone bodies can cross the blood-brain barrier, stimulate acetylation of histones at the brain-derived neurotrophic factor (Bdnf) gene promoters, and induce the production of hippocampal BDNF, a neurotrophin crucial for brain plasticity and regulation of cognitive function.
Evidence on the effects of ketone supplements on cognitive function is scarce and mixed. Preclinical data suggest that nutritional ketosis increases cognitive function in rats, and moderate nutritional ketosis has been recommended for people with cognitive impairment. Some data suggest that ketone supplements might attenuate the transient impairment in cognitive performance that is frequently observed upon termination of strenuous exercise.
However, other studies have reported no benefits of acute ketone monoester supplementation on reaction time and multitasking.
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Ketogenic Diets and Mental Health
A pilot study led by Stanford Medicine researchers found that a ketogenic diet not only restores metabolic health in patients with schizophrenia or bipolar disorder taking antipsychotic medications but also further improves their psychiatric conditions.
The four-month pilot trial followed 21 adult participants with schizophrenia or bipolar disorder, taking antipsychotic medications, and had a metabolic abnormality. Participants were instructed to follow a ketogenic diet, with approximately 10% of the calories from carbohydrates, 30% from protein, and 60% from fat.
The results showed significant improvements in metabolic health, including reversal of obesity, metabolic syndrome, and insulin resistance. The psychiatric benefits were also striking, with participants reporting improvements in their energy, sleep, mood, and quality of life.
Keto Diet Pill Scams: A Growing Concern
As ketone supplements and ketogenic diets gain popularity, so do the scams associated with them. The Federal Trade Commission (FTC) and Food & Drug Administration (FDA) warn that dietary supplements do not require approval before they are marketed. AARP's Fraud Watch Network Helpline has logged increasing reports of keto pill scams where fraudsters promise pills that supposedly will help dieters shed pounds faster than just adhering to a keto diet's high-fat, low-carbohydrate regimen.
These scams often involve pop-up ads promising quick weight loss, followed by unauthorized charges and difficulties in obtaining refunds. Consumers are advised to be cautious of such claims and to use credit cards instead of debit cards for online purchases, as credit cards offer more protection in fraud cases.