Exploring the Impact of Alternative Sources of Dietary Nitrate Supplementation on Exercise Performance.

An increase in the level of nitric oxide (NO) plays a key role in regulating the human cardiovascular system (lowering blood pressure, improving blood flow), glycemic control in type 2 diabetes, and may help enhance exercise capacity in healthy individuals (including athletes). This molecule is formed by endogenous enzymatic synthesis and the intake of inorganic nitrate (NO3-) from dietary sources. Although one of the most well-known natural sources of NO3- in the daily diet is beetroot (Beta vulgaris), this review also explores other plant sources of NO3- with comparable concentrations that could serve as ergogenic aids, supporting exercise performance or recovery in healthy individuals. The results of the analysis demonstrate that red spinach (Amaranthus spp.) and green spinach (Spinacia oleracea) are alternative natural sources rich in dietary NO3-. The outcomes of the collected studies showed that consumption of selected alternative sources of inorganic NO3- could support physical condition. Red spinach and green spinach have been shown to improve exercise performance or accelerate recovery after physical exertion in healthy subjects (including athletes).

Mexidol, Cytoflavin, and succinic acid derivatives as antihypoxic, anti-ischemic metabolic modulators, and ergogenic aids in athletes and consideration of their potential as performance enhancing drugs.

Emoxypine (ethylmethylhydroxypyridine) is a synthetic derivative of vitamin B6 . Emoxypine succinate is a registered drug in Russia and Ukraine under various trade names including Mexidol, Mexicor, and Armadin Long. Mexidol demonstrates antihypoxic and anti-ischemic effects and also modulates metabolism. The use of Mexidol by Russian athletes has been confirmed in the past. Current use by athletes is unknown as this drug is not monitored or included in drug testing protocol. Metabotropic and antihypoxic effects of Mexidol were compared to the effects of meldonium or trimetazidine, both of which are included on the World Anti-Doping Agency (WADA) Prohibited List in category S4.4. Metabolic Modulators. The conjugation of emoxypine with succinate elevates the therapeutic effectiveness of the Mexidol formulation as succinic acid itself has important impacts to consider despite being a common food additive and drug excipient. Other succinic acid salts like ammonium succinate, found as dietary supplement, have been patented as performance enhancers. Available research on healthy subjects suggests that combinations of selected 3-substituted pyridine derivatives with succinate including Mexidol and a related drug Cytoflavin can enhance the performance of athletes. Cytoflavin is a multi-component formula containing meglumine sodium succinate, nicotinamide (vitamin B3 ), inosine (riboxin), and riboflavin. Other related succinate-based drugs include Remaxol, Reamberin, and Cogitum. Mexidol and Cytoflavin and related substances exhibit similar biological effects as drugs on the WADA Prohibited List, and if they are used for performance enhancement by athletes, they could be worthy of consideration as prohibited substances in sport.

Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: Analysis of suspected cases.

PURPOSE: Selective androgen receptor modulators (SARMs) have demonstrated agonist activity on the androgen receptor in various tissues, stimulating muscle mass growth and improving bone reconstruction. Despite being in clinical trials, none has been approved by the Food and Drug Administration (FDA) or European Medicines Agency for pharmacotherapy. Still, SARMs are very popular as performance-enhancing drugs. The FDA has issued warnings about the health risks associated with SARMs, but the long-term exposure and possible adverse events still need to be fully understood. This review aims to evaluate the adverse events associated with using SARMs by humans. METHODS: PubMed database was searched from September 16, 2022, to October 2, 2023. In total, 20 records were included in the final review. Data from preclinical and clinical studies supported the review. RESULTS: Since 2020, 20 reports of adverse events, most described as drug-induced liver injury associated with the use of SARM agonists, have been published. The main symptoms mentioned were cholestatic or hepatocellular liver injury and jaundice. Limited data are related to the dosages and purity of SARM supplements. CONCLUSION: Promoting SARMs as an anabolic agent in combination with other performance-enhancing drugs poses a risk to users not only due to doping controls but also to health safety. The lack of quality control of consumed supplements makes it very difficult to assess the direct impact of SARMs on the liver and their potential hepatotoxic effects. Therefore, more detailed analyses are needed to determine the safety of using SARMs.

Unauthorized ingredients in "nootropic" dietary supplements: A review of the history, pharmacology, prevalence, international regulations, and potential as doping agents.

The first nootropic prohibited in sport was fonturacetam (4-phenylpiracetam, carphedon) in 1998. Presented here 25 years later is a broad-scale consideration of the history, pharmacology, prevalence, regulations, and doping potential of nootropics viewed through a lens of 50 selected dietary supplements (DS) marketed as "cognitive enhancement," "brain health," "brain boosters," or "nootropics," with a focus on unauthorized ingredients. Nootropic DS have risen to prominence over the last decade often as multicomponent formulations of bioactive ingredients presenting compelling pharmacological questions and potential public health concerns. Many popular nootropics are unauthorized food or DS ingredients according to the European Commission including huperzine A, yohimbine, and dimethylaminoethanol; unapproved pharmaceuticals like phenibut or emoxypine (mexidol); previously registered drugs like meclofenoxate or reserpine; EU authorized pharmaceuticals like piracetam or vinpocetine; infamous doping agents like methylhexaneamine or dimethylbutylamine; and other investigational substances and peptides. Several are authorized DS ingredients in the United States resulting in significant global variability as to what qualifies as a legal nootropic. Prohibited stimulants or ß2-agonists commonly used in "pre-workout," "weight loss," or "thermogenic" DS such as octodrine, hordenine, or higenamine are often stacked with nootropic substances. While stimulants and ß2-agonists are defined as doping agents by the World Anti-Doping Agency (WADA), many nootropics are not, although some may qualify as non-approved substances or related substances under catch-all language in the WADA Prohibited List. Synergistic combinations, excessive dosing, or recently researched pharmacology may justify listing certain nootropics as doping agents or warrant additional attention in future regulations.

Effect of Cordyceps spp. and Cordycepin on Functions of Bones and Teeth and Related Processes: A Review.

Cordyceps spp. (belonging to the Ascomycota group) are entomopathogenic mushrooms that have traditionally been used in ethnomedicine in Asian countries such as China, Japan, Korea, and India. They are unique parasites of larvae of selected species of moths. Cordyceps militaris is one of the best sources of cordycepin. Worldwide, osteoporosis is one of the most common bone diseases, whose pharmacotherapy includes various medical interventions; however, the research and development of new molecules and new drugs is required. The impact of adenosine receptors (ARs) on the purinergic signaling pathway may regulate proliferation, differentiate dental pulp stem cells and bone marrow, and modulate osteogenesis and bone repair. The aim of the review was to collect and analyze the available data on the effects of Cordyceps spp. or cordycepin on bone function and related processes. To the best of our knowledge, this is the first systematic review in this perspective, not necessarily using mushroom raw material or even the isolated parent compound cordycepin, but new molecules that are analogs of nucleosides, such as those from C. militaris. This review found that Cordyceps spp. or isolated cordycepin interacts via the AR, 5' adenosine monophosphate-activated protein kinase (AMPK), and adenosine-5'-triphosphate (ATP) signaling pathway and evaluated their impact on bones, teeth, and dental pulp. Cordyceps spp. was found to have the potential to develop regenerative medicines, thus providing an opportunity to expand the treatment or intervention methods in the recovery after traumatic injuries, convalescence, and terminal-stage or devastating diseases.

Cordyceps militaris-Fruiting Bodies, Mycelium, and Supplements: Valuable Component of Daily Diet.

Cordyceps militaris has long been used in Eastern medicine for alleviating fatigue and as an immunostimulant. The present study aimed to determine the content of biologically active substances (bioelements and organic compounds), the total phenolic content, and the antioxidant activity of fruiting bodies (commercially available and self-cultivated), mycelia, and two food supplements. The results show that substrate composition and cultivation method had an influence on the properties of mushroom materials. An important aspect of the study is the estimation of the content of bioactive substances present after extraction into digestive juices in the artificial gastrointestinal tract model, which can allow for determining the amount of these substances that is potentially bioavailable for the human body. The best results for cordycepin (81.4 mg/100 g d.w.) and lovastatin (53.6 mg/100 g d.w.) were achieved for commercially available food supplements. Furthermore, after digestion in artificial intestinal juice, the highest amount of cordycepin was determined in the fruiting bodies from commercially obtained (25.9 mg/100 g d.w.) and self-cultivated mushroom (25.8 mg/100 g d.w.). In conclusion, the mycelium and fruiting bodies of C. militaris are ideal food supplements and pharmaceutical agents and can serve as a good source of prohealth substances potentially bioavailable for humans.

Edible Mushrooms as a Potential Component of Dietary Interventions for Major Depressive Disorder.

Dietary interventions for people suffering from major depressive disorder (MDD) are an ongoing field of research. In this article, we present a comprehensive background for understanding the possibility of using edible medicinal mushrooms as an adjunctive treatment for MDD. We start with a brief history of MDD, its diagnosis, epidemiology and treatment, and the effects of diet on depression symptoms, followed by a review of neurobiological, behavioral, and clinical studies of medicinal mushrooms. We specifically highlight the results of preclinical and clinical studies on dietary supplementation with three selected mushroom species: Lion's mane (Hericium erinaceus), Caterpillar mushroom (Cordyceps militaris), and Lingzhi/Reishi (Ganoderma lucidum). Preliminary small-sample clinical studies suggest that Lion's mane can influence well-being of humans. In the case of Reishi, the results of clinical studies are equivocal, while in the case of Caterpillar Mushroom, such studies are underway. Edible mushrooms contain 5-hydroxy-L-tryptophan (5-HTP), which is a direct precursor of serotonin-a neurotransmitter targeted in pharmacotherapy of MDD. Therefore, in light of the well-recognized role of stress as a pathogenic factor of MDD, we also describe the neurobiological mechanisms of the interaction between stress and serotonergic neurotransmission; and summarize the current state of knowledge on dietary supplementation with 5-HTP in MDD.

Cordyceps militaris: An Overview of Its Chemical Constituents in Relation to Biological Activity.

Cordyceps spp. mushrooms have a long tradition of use as a natural raw material in Asian ethnomedicine because of their adaptogenic, tonic effects and their ability to reduce fatigue and stimulate the immune system in humans. This review aims to present the chemical composition and medicinal properties of Cordyceps militaris fruiting bodies and mycelium, as well as mycelium from in vitro cultures. The analytical results of the composition of C. militaris grown in culture media show the bioactive components such as cordycepin, polysaccharides, γ-aminobutyric acid (GABA), ergothioneine and others described in the review. To summarize, based on the presence of several bioactive compounds that contribute to biological activity, C. militaris mushrooms definitely deserve to be considered as functional foods and also have great potential for medicinal use. Recent scientific reports indicate the potential of cordycepin in antiviral activity, particularly against COVID-19.

Risk Associated with the Use of Selected Ingredients in Food Supplements.

This review focuses on four new product categories of food supplements: pre-workout, fat burner/thermogenic, brain/cognitive booster, and hormone/testosterone booster. Many food supplements have been shown to be contaminated with unauthorized substances. In some cases, the ingredients in the new categories of dietary supplements were medicinal products or new synthetic compounds added without performing clinical trials. Some of the new ingredients in dietary supplements are plant materials that are registered in the pharmacopoeia as herbal medicines. In other cases, dietary supplements may contain plant materials that have no history of human use and are often used as materials to 'camouflage' stimulants. In the European Union, new ingredients of dietary supplements, according to European Food Safety Authority or unauthorized novel food. Furthermore, selected ingredients in dietary supplements may be prohibited in sports and are recognized as doping agents by World Anti-Doping Agency.