The Benefits of Pregnenolone for Athletes: The Evidence Base
Pregnenolone is sold to athletes as a "hormonal foundation," a means for recovery, concentration, and stress resistance. It sounds convincing, since all steroid hormones are indeed synthesized from it. But what do studies say if you look specifically for athletic results? The editorial team has analyzed the available evidence base by levels of quality and separated experimental data from marketing promises.
Where expectations about pregnenolone came from
The first studies of pregnenolone with humans were conducted as early as the 1940s. At that time it was studied as a remedy against fatigue in workers and pilots, and also in patients with rheumatoid arthritis. The results were contradictory, and the methodology of those years does not meet modern standards: small samples, lack of proper blinding, subjective criteria.
With the appearance of cortisone and other corticosteroids, which had a significantly stronger anti-inflammatory action, interest in pregnenolone almost disappeared. However, these early works are still cited in advertising as evidence of an "anti-fatigue" action, without mentioning their limitations.
The second source of expectations is biochemical logic: if pregnenolone is a precursor of testosterone, DHEA, and cortisol, then taking it supposedly should "feed" the entire hormonal system. However, hormone synthesis is regulated at the level of cholesterol transport into the mitochondria and pituitary signals, not by the amount of the starting substrate.
The third source is neurobiology. Pregnenolone sulfate affects receptors associated with memory and neuronal excitability, so it began to be positioned as a means for concentration. These data are mostly obtained in animals.
Data in animals and in the laboratory
In rodents, pregnenolone sulfate injected into the brain improved memory indicators in learning tests in a number of experiments. The mechanism was linked to positive modulation of NMDA receptors and negative modulation of GABA-A receptors. However, the doses and methods of administration in these studies have no direct equivalent in a person taking capsules.
The most famous modern work is the study by Vallée and colleagues in Science (2014). In mice and rats, high doses of THC increased the synthesis of pregnenolone in the brain, and pregnenolone, in turn, weakened the effects of CB1 receptor activation. This is an interesting feedback mechanism, but it has no direct relation to athletic performance.
In the available literature there are practically no animal studies that would assess the effect of pregnenolone on muscle mass, strength, endurance, or recovery after exercise. That is, even at the preclinical level the athletic hypothesis has not been tested.
Laboratory data are useful for understanding mechanisms, but the history of sports supplements knows many substances that "worked" in a test tube or in mice and showed no effect in humans. Pregnenolone is no exception here, until the opposite is proven.
Clinical studies in humans
The most modern randomized studies of pregnenolone have been conducted in psychiatry. In a pilot study by Marx and colleagues in patients with schizophrenia, pregnenolone as a supplement to antipsychotics was associated with an improvement in negative symptoms, although the sample was small.
Ritsner and colleagues compared pregnenolone and DHEA as a supplement to the treatment of schizophrenia and schizoaffective disorder and reported certain improvements, in particular regarding attention and some side effects of antipsychotics. Brown and colleagues studied pregnenolone in patients with bipolar depression and observed a reduction in depressive symptoms compared with placebo.
These studies are important in that they show: pregnenolone has biological activity in humans and changes the levels of neurosteroids, in particular allopregnanolone. But they were conducted in patients with specific diagnoses, under the supervision of doctors, and with amounts that have nothing in common with the "sports" recommendations on labels.
Transferring these results to healthy athletes is incorrect. An improvement in the negative symptoms of schizophrenia or depression does not mean an improvement in concentration, motivation, or stress resistance in a healthy person.
| Type of data | Example | What is shown | Significance for the athlete |
|---|---|---|---|
| Early clinical observations | 1940s, fatigue in workers | Contradictory results | Low, outdated methodology |
| Animal models | Vallée et al., 2014 | Modulation of CB1 signaling | Indirect |
| RCT in psychiatry | Marx et al., 2009; Ritsner et al., 2010; Brown et al., 2014 | Certain symptom improvements | Indirect, different population |
| RCT in athletes | — | No data | Benefit not proven |
Strength, muscle, recovery: what is lacking
In order to speak of benefit for athletes, randomized placebo-controlled studies are needed with trained people that assess specific results: strength, power, endurance, muscle mass, recovery markers. There are practically no such studies with pregnenolone in the peer-reviewed literature.
Indirect arguments are also not in favor of the "anabolic" hypothesis. For DHEA, which is located closer to testosterone in the synthesis chain, controlled studies with young men did not show a rise in testosterone or strength. There are no grounds to expect that an even more distant precursor will give a greater effect.
Nor has the idea been confirmed that pregnenolone can "protect" testosterone from stress cortisol. The concept of "pregnenolone steal" does not correspond to the modern understanding of the tissue-specific regulation of steroidogenesis.
As for cognitive effects: athletes often buy pregnenolone for "focus." However, there are not enough quality studies in healthy young people to speak of a real improvement in attention or reaction speed.
- there are no RCTs on strength and muscle mass;
- there are no RCTs on endurance and recovery;
- there are no data on the effect on testosterone in healthy male athletes;
- there are no reliable data on cognitive benefit in healthy people.
How to evaluate manufacturers' promises
When the label states that pregnenolone "supports hormonal balance," "improves concentration," or "promotes recovery," it is worth asking: on which studies is this based? For the most part, the answer is biochemical logic, animal data, or studies in patients, not in athletes.
It should also be remembered that pregnenolone can be converted into progesterone, DHEA, and further into sex hormones. Thus, even without a proven benefit, it potentially carries hormonal risks, especially for people with hormone-dependent conditions.
For athletes undergoing doping control, an additional argument for caution is the risk of supplement contamination and a possible effect on the steroid profile. Pregnenolone is not directly named on the WADA Prohibited List, but this does not guarantee the safety of a particular product from the standpoint of anti-doping rules.
A sensible position is to invest resources in agents with proven effectiveness: creatine, caffeine, sufficient protein, rational planning of training and sleep. Pregnenolone so far remains an object of scientific interest, not a sports tool.
Editorial conclusions
The evidence base on pregnenolone consists of biochemistry, animal models, and small randomized studies in psychiatry. There are practically no studies in athletes.
Benefit for strength, muscle mass, endurance, or recovery has not been proven, and the biochemical "centrality" of the molecule does not guarantee the effect of a supplement.
Pregnenolone is biologically active and can affect hormones, so the absence of proven benefit is combined with potential risks.
We recommend also reading "Pregnenolone: What It Is and How It Works," "Side Effects of Pregnenolone," and "Myths About DHEA."
References
- Marx CE, Keefe RS, Buchanan RW, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology. 2009;34(8):1885–1903.
- Ritsner MS, Gibel A, Shleifer T, et al. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry. 2010;71(10):1351–1362.
- Brown ES, Park J, Marx CE, et al. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology. 2014;39(12):2867–2873.
- Vallée M, Vitiello S, Bellocchio L, et al. Pregnenolone can protect the brain from cannabis intoxication. Science. 2014;343(6166):94–98.
- Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32(1):81–151.
- Brown GA, Vukovich MD, Sharp RL, et al. Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men. J Appl Physiol. 1999;87(6):2274–2283.
- World Anti-Doping Agency. Prohibited List. Montreal: WADA; чинна редакція.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
