Fatigue is a prevalent issue affecting both young and older adults, with significant implications for their well-being. It is a common symptom reported by a substantial number of individuals receiving medical treatment and can greatly impact self-care and overall quality of life. Furthermore, fatigue is a predictor of future health complications and mortality. As individuals age, the prevalence of fatigue tends to increase, highlighting the importance of strategies to mitigate its effects.
Additionally, aging in men is often accompanied by a decline in steroid hormones, such as testosterone and DHEA-S. These hormones play crucial roles in various aspects of health, including sexual function, mental well-being, bone density, and cardiovascular health. Low levels of testosterone have been associated with increased morbidity and reduced quality of life. Therefore, finding ways to slow down the decline of these hormones in aging men is of great significance.
Ashwagandha, an adaptogenic herb widely used in Ayurvedic medicine, has gained attention for its potential to promote vitality, strength, and overall health. Previous studies have explored its positive effects on reducing stress, anxiety, and improving memory and cognition. In recent research, Ashwagandha has shown promising results in increasing sperm quality and testosterone levels in men. Animal studies have also suggested its influence on hormonal pathways, including the hypothalamic-pituitary-gonadal axis.
This study aimed to investigate the effects of Ashwagandha supplementation over an 8-week period on overweight men aged 40-70 years, specifically targeting mild-to-moderate fatigue. The study also explored the potential influence of Ashwagandha on testosterone, DHEA-S, cortisol, and estradiol levels, considering their significant impact on overall well-being and the aging process.
This 16-week study employed a randomized, double-blind, placebo-controlled, crossover design to evaluate the effects of an Ashwagandha extract (Shoden beads) on salivary hormones and fatigue symptoms in overweight men. The trial adhered to the guidelines outlined in the Declaration of Helsinki and received approval from the Human Research Ethics Committee at Murdoch University, Western Australia. It was also prospectively registered with the Australian New Zealand Clinical Trials Registry.
Participants were recruited between December 2017 and February 2018 through social media advertisements across Western Australia. Prior to their involvement in the study, written informed consent was obtained from all participants. The study utilized a convenience sample due to its pilot nature. Based on previous research demonstrating the effect size of Ashwagandha on stress and anxiety symptoms in stressed adults, a sample size calculation was performed to determine the number of participants required.
The randomization process allocated participants equally into two groups: one receiving the placebo followed by Ashwagandha, and the other receiving Ashwagandha followed by the placebo. Randomization was achieved using a randomization calculator and involved seven randomly permuted blocks with eight participants per block. The intervention codes, which indicated the treatment allocation, were held by the sponsor and an independent university investigator not directly involved in recruitment and data collection.
To ensure blinding, all tablets were identical in appearance and packaged in containers labeled with intervention code numbers. Neither the participants nor the study investigators were aware of the treatment group allocation until all questionnaire data had been collected. A no-washout period was included in the crossover design to examine the durability of changes after discontinuation of the active treatment.
The study aimed to enroll a total of 57 participants, considering an anticipated dropout rate of 10% and statistical power of 80%, with a type I error rate (alpha) of 5%. Eligibility for participation was assessed by the principal investigator based on predefined inclusion and exclusion criteria.
The study enrolled 57 participants, with 50 completing the first 8-week period and 43 completing the entire 16-week study. As the trial progressed, participants reported notable improvements in fatigue levels, vigor, and overall sexual and psychological well-being. Although no statistically significant differences were observed between the Ashwagandha group and the placebo group regarding these improvements, the study revealed fascinating findings related to hormone levels.
- Effect of Ashwagandha on Hormones and Symptoms:
o This 16-week study evaluated the impact of an Ashwagandha extract on salivary hormones and symptoms of fatigue and vitality in healthy, overweight men.
o Ashwagandha supplementation resulted in significant changes in salivary DHEA-S and testosterone levels.
o However, there were no significant changes in salivary cortisol or estradiol levels.
o Both Ashwagandha and placebo supplementation showed improvements in fatigue, vigor, and sexual and psychological well-being, with no significant differences between the groups.
o Ashwagandha supplementation was well-tolerated with no reported adverse events or participant withdrawals.
- Mood-Lifting and Anti-anxiety Effects of Ashwagandha:
o Previous studies have confirmed the positive anti-anxiety effects of Ashwagandha in stressed, healthy adults and those with diagnosed anxiety disorders.
o Animal studies have also shown anti-stress and antidepressant effects of Ashwagandha.
o Ashwagandha supplementation has demonstrated positive effects on energy and fatigue in adults undergoing resistance training and breast cancer patients undergoing chemotherapy.
- Lack of Significant Differences in Fatigue, Vigor, and Sexual Vitality:
o In the current study, improvements in vigor and emotional or sexual well-being were observed with Ashwagandha supplementation, but there were no significant differences compared to the placebo.
o Possible explanations for these findings include the mild intensity of fatigue and other symptoms at the beginning of the study, which may have limited the potential for significant improvements.
o The method of participant recruitment, which involved motivated individuals seeking general well-being improvements, could have led to positive changes in energy, vigor, and well-being through other lifestyle factors.
o The presence of shift workers and individuals employed in remote mining communities may have affected the therapeutic efficacy of Ashwagandha due to sleep-related disturbances and ongoing stress.
o The high observed placebo effect in this study, which was significantly higher than in previous studies, suggests greater treatment expectations in the Australian population recruited for this study.
- Hormonal Changes and Sustained Effects of Ashwagandha:
o Ashwagandha supplementation over 8 weeks was associated with higher levels of salivary testosterone and DHEA-S compared to the placebo.
o However, these hormone levels did not remain significantly different after 8 weeks of discontinued Ashwagandha supplementation.
o Ongoing intake or longer supplementation may be necessary to sustain the hormonal changes induced by Ashwagandha.
o Lower levels of DHEA-S and testosterone in aging males are associated with increased morbidity, reduced longevity, and lower quality of life.
- Lack of Significant Effects on Cortisol and Estradiol:
o Ashwagandha did not significantly affect morning salivary cortisol levels or estradiol concentrations in this study.
o Previous studies have shown cortisol-lowering effects of Ashwagandha in stressed adults, but the cortisol measurements in this study were done using salivary samples rather than serum.
o The presence of shift workers in the study population may have moderated the potential effects of Ashwagandha on cortisol and other steroid hormones.
o The recruitment of a population reporting fatigue rather than stress or anxiety may have influenced the cortisol levels, as low cortisol concentrations are associated with symptoms of burnout and chronic fatigue syndrome.
- Mechanisms of Ashwagandha’s Influence on Hormones:
o DHEA is primarily produced in the zona reticularis of the adrenal cortex and is influenced by the activity of the hypothalamus-pituitary-adrenal (HPA) axis, specifically the levels of adrenocorticotropic hormone (ACTH). Ashwagandha has been shown to lower cortisol levels in previous studies, indicating a dampening effect on HPA axis activity. It is possible that Ashwagandha’s influence on the HPA axis may lead to increased concentrations of DHEA and testosterone.
o Leydig cells in the testes are responsible for the production of DHEA and testosterone, and their activity is influenced by gonadotropin-releasing hormone (GnRH). In vitro and animal studies have demonstrated that Ashwagandha can up-regulate the activity of GnRH. Therefore, it is plausible that Ashwagandha, through its effect on GnRH activity, may contribute to increased levels of DHEA and testosterone.
o There is a bidirectional relationship between inflammation, oxidative stress, and androgen hormones like testosterone, which has been observed in both animal and human studies. Ashwagandha has shown antioxidant and anti-inflammatory properties, which may potentially contribute to its influence on DHEA and testosterone levels.
o While Ashwagandha supplementation did not result in statistically significant changes in estradiol concentrations, there was a trend indicating reduced levels. This is in contrast to the increased levels of estradiol pro-hormones, DHEA-S, and testosterone. Normally, elevated estradiol levels would be expected. The hypothesis is that Ashwagandha may act as an inhibitor of aromatase, an enzyme involved in the conversion of testosterone into estradiol. A study on a plant from the same family as Ashwagandha, Withania coagulans, demonstrated aromatase-inhibiting effects. This speculative observation requires further investigation in future studies. Overall, while there are plausible mechanisms that could explain how Ashwagandha influences DHEA and testosterone production, more research is needed to fully understand these mechanisms and their impact.