Consumption and biochemical impact of commercially available plant-derived nutritional supplements. An observational pilot-study on recreational athletes

It is commonly accepted that nutritional habits play an important role in the individual capacity of reaching optimal physical performance and this idea has been strongly underlined by the American Dietetic Association [1]. Unfortunately, a parallel nutritional information pathway is growing day by day promoting innovative diets able, in theory, to enhance physical performances. Usually, the information provided to the public is to combine, to a defined nutritional regimen, specific supplements with the aim of reducing the length of time needed for reaching the desired results. Nowadays, the culture of dietary supplementation is widely diffused not only among professional athletes, but also among “recreational” athletes as well as active subjects. Indeed, the global supplement use in athletes is estimated ranging between 40% and 88% [2], showing an increasing diffusion among adolescents [3]. Common supplements used with ergogenic intents include: creatine, proteins, carbohydrates, aminoacids, vitamin complex and caffeine [4]. However, beside these “traditional” supplements, a growing consumption of natural (plant-derived) products has been registered over the last years. It is estimated that more than 1400 herbs are commonly commercialized for medicinal uses worldwide and these supplements represent a multi-billion-dollar business. In the sport environment, these products are usually marketed as performance enhancing aids and they are presented as legal and free of side effects, according to the misconception that “natural” corresponds to “not harmful”. However, the publicized effects of these products and the recommended dosages are often based on little or no scientific evidence, leading the scientific community to a great concerns when considering their safety [5].

Unfortunately, the sport environment has shown an increasing interest in those “alternative natural approaches”. In fact, it is appealing for the athletes the use of a natural therapeutic variant which promises similar activity to the pharmacological approach, in term of increasing physical performances, which is not considered doping and which is considered side-effect free. In this setting, herb derived products are usually suggested because the high title of active principles promises results similar to those obtained with pharmaceutical drugs but in absence of side effects and without the risk of testing positive for doping. Among the “natural” supplements, the most “attractive” are those containing plant-derived hormones such as ecdysteroids, phytoestrogen s and vegetal sterols and other substances with referred hormone modulating properties such as tribulus terrestris.

Ecdysteroids are the steroid hormones of arthropods. They also occur in certain plant species, where they are known as phytoecdysteroids and are believed to contribute to the deterrence of invertebrate predators. In insects, they regulate moulting and metamorphosis and have been implicated in the regulation of reproduction and diapause. Most actions of ecdysteroids are mediated by intracellular receptor complexes, which regulate gene expression in a tissue and development specific manner. Ecdysteroids are apparently non-toxic to mammals and a wide range of beneficial pharmacological (adaptogenic, anabolic, anti-diabetic, hepatoprotective, immunoprotective, wound-healing, and perhaps even anti-tumour) activities are claimed for them [6]. Moreover, the reported anabolic properties have led to a large (and unregulated) market for ecdysteroid-containing preparations, the most of which are advertised on specialized websites as legally allowed and non-toxic substances useful to gain muscular mass [7].

Phytoestrogens have acquired popularity for a multitude of health benefits, including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms, that have been attributed to them. Consequently, a global movement towards increased consumption of phytoestrogen-rich foods and tabletized concentrated isoflavone extracts have been heavily promoted in western countries over the last two decades. However, more recently, phytoestrogens have been considered endocrine disruptors having the potential to cause adverse health effects [8], as well the effects of phytoestrogens in preventing osteoporosis and menopausal symptoms have not been confirmed in more recent studies [9–11].

Phytosterols (including campesterol, stigmasterol and sitosterol) are plant steroids with a similar chemical structure and cellular function to human cholesterol. They are recommended as dietary modifiers of serum lipids [12]. In addition, plant sterols exert beneficial effects on other lipid variables, such as apolipoprotein (apo) B/apoAI ratio and, in some studies, high-density lipoprotein cholesterol (HDL-C) and triglycerides [13] and may also affect inflammatory markers, coagulation parameters, as well as platelet and endothelial function.

Finally, the main claimed effect of Tribulus Terrestris (TT) is an increase of testosterone, anabolic and androgenic action, through the activation of endogenous testosterone production [4]. Even if this biological pathway is not entirely proven, TT is regularly used by many athletes as “legal” anabolic aid. However, different studies concluded that TT do not produce the large gains in strength or lean muscle mass that many manufacturers claim can be experienced within 5–28 days and the possible health risks deriving from TT assumption have not been investigated [14].

Most of the previously mentioned commercially available supplements have not been studied for long-term safety and it’s likely that many habitually users are not aware of the real efficacy of these products, or the adverse effects related to their consumption. Questions regarding their possible side effects on endocrine and reproductive systems should be raised even in light of their advertised high-dose use.

With those premises, the present study was carried out in order to evaluate the real knowledge of plant-derived nutritional supplements among physically active people, in order to quantify the real use of these supplements and to evaluate the effects of these supplements on the health profile of the users.

As far as our knowledge goes, this is the first study investigating the real consumption of plant-derived nutritional supplements with ergogenic intent on recreational athletes and the possible side effects deriving from this practice. The study highlighted that, among Italian athletes, these products are poorly known when compared to the “traditional” supplements and that their use is still limited. Noteworthy, even with the limitations due to the smallness of the sample, the study seems to demonstrate that the regular use of this types of nutritional supplements, even in the form of poly consumption, do not cause organ suffering or damage, in particular to liver and kidneys. On the contrary, the significant alterations of the sexual hormone profile, emerged in habitual users, represents the major finding of this investigation.

The use of nutritional supplements with ergogenic aims is as ancient as the sport itself [17] and it’s almost utopian thinking that sportive practice would be completely free from these substances. Indeed, athletes are mainly vulnerable to substance use, and abuse, in situations where much depends on sporting success; however, the use of ergogenic supplements is currently an accepted practice also among the “recreational” athletes and such practice is favored by an aggressive market, mainly expressed trough dedicated websites. Actually, it has been estimated that over 30 thousand different products referred to as “nutritional supplements” are commercially available [18]. Over the last years, this business have been considerably enlarging for the introduction of the so called “natural” or herbal products including those with hormonal effects (ecdysteroids, phytoestrogens, phytosterols and tribulus terrestris). These products have been quickly spreading all over the western world mainly through the network, even though they still remain less known in respect to the traditional supplements, as our investigation highlighted.

Undoubtedly, “natural” products are more appealing than the chemical ones because of the common misconception that what is natural is also harmless. Actually, many athletes trust in these products that promise effects comparable to those of steroids hormones or growth hormone, without the side effects of those prohibited substances. However, most of the users do not know that the ergogenic gains advertised for most of the nutritional supplements, including the natural ones, are often not based on scientific evidence and the possible risks for health deriving from their mid-term and long-term consumption are still not known.

The notable finding of this study is the evidence of highly significant alteration of sexual hormone levels in habitual users of plant-derived nutritional supplements. Although these biochemical alterations were not associated with signs or symptoms of disease at the moment of the study, it cannot be excluded that, in the mid/long-term, these subjects would suffer of health problems secondary to chronic exposure to heavily altered hormonal levels.

Mechanisms at the basis of these alterations are not known and the exact consequences are not predictable. However, it is known that hyperestrogenism may cause significant medical problems in both males and females. In particular, hyperestrogenism has been related to gynecomastia, hypogonadism, reduced fertility in men, macromastia, enlarged uterus and menstrual irregularities in women [19]. In addition, hyperestrogenism represents a major risk factor for the rare male breast cancer [20, 21].

In our study, hyperestrogenism was observed in athletes who consumed high dosage of soy protein, the main food source of phytoestrogens. Actually, besides the known beneficial effects, these herbal hormones may have possible unfavorable effects in humans by interfering with the function of normal cellular activities, such as receptor-mediated signal transduction and DNA replication, as well as genotoxic, mutagenic and proliferation of some cancer cells [22]. This observation must be carefully considered when reflecting upon the increasing number of vegan and vegetarian athletes for whom soy represents the main source of protein, consumed in the form of protein powders and bars [23–25].

With the exception of soy protein, the knowledge and the use of plant-derived nutritional supplements, with ergogenic aims in recreational athletes, appears to be limited even though the flourishing market of these products on internet sites portray the contrary. Nonetheless, the results of the present study confirmed that “natural” does not necessarily mean harmless and safe, and strongly advises against the use of nutritional supplements for superficial purpose. Undoubtedly, further larger scale studies are needed to confirm the results of this pilot study as well as to investigate the biological mechanisms at the base of the observed hormonal alterations.