The Science

There are several proposed mechanisms for the impact Ashwagandha has on male androgens such as DHEA and testosterone [1]:

1. The first relates to the reduction in the stress hormone cortisol released from the adrenal gland. High blood levels of cortisol disrupt the androgen synthesis pathways in the Leydig cells in the testes thus reducing testosterone levels. The net result is that by reducing glucocorticoids homones in the body, testosterone production and serum concentration increases [2].

2. Ashwagandha is an aromatase inhibitor. Aromatase is the enzyme that converts testosterone to oestradiol (an oestrogen hormone) and therefore by inhibiting aromatose activity there is less breakdown of testosterone resulting in higher levels in the bloodstream [3].

3. Ashwagandha is also shown to upregulate the activity of gonadotropin-releasing hormone (GnRH) released from the hypothalamus in the brain which stimulates release of pituitary hormones stimulating the Leydig cells in the testes to produce testosterone [4].

There are a large number of scientific studies highlighting this medicinal plant’s apparent ability to protect against neurodegenerative diseases such as Alzheimer's, Huntington’s and Parkinson's disease.

The proposed mechanism is related to anti-inflammatory activity and supporting endothelial and mitochondrial function in maintaining cell health and viability [5].

The definitive mechanisms that uphold the nootropic (cognitive enhancing) or ‘smart drug’ properties of Ashwagandha are unclear. There are some suggested hypotheses in the literature:

1. Improved quality and depth of sleep secondary to the reduction in stress hormone release (cortisol) as stress, anxiety and disorders of sleep affect normal cognitive function [6].

2. Ashwagandha has an effect on important neurotransmitters in the brain such as serotonin,GABA & dopamine. Dopamine especially is recognised to be a transmitter in the nerves incorporated into a large number of pathways in the brain, which can positively enhance memory and cognition and hence act in a nootropic fashion [7], [8].

Ashwagandha is an adaptogen – meaning that it is a based plant derivative that helps the body to respond to stress, anxiety, fatigue and overall wellbeing.

In a randomised double blind controlled study vs placebo KSM-66 ashwagandha was able to significantly improve the focal aspects of stress (anxiety & insomnia), and also positively impacted self-assessed feelings of depression [9].

1. The positive effects that adaptogens on the feelings of stress are believed to be related to cellular homeostasis (stability of cell matrix) involving a number of pathways and mechanisms. The suggested areas of actions include the ‘master endocrine pathway’ i.e the Hypothalamic–pituitary–adrenal (HPA) axis and some of the key molecules and hormones involved in the ‘stress response’. Importantly there is a putative effect at cellular level of specific proteins that stabilise other proteins in cells during times of stress e.g the Hsp70 molecular chaperone – (cf Heat-shock Proteins) [10].

2. Hsp70 protein acts to protect cells from oxidative & thermal stress. This protein interacts directly with glucocorticoid receptors and therefore interferes with cortisol (the stress hormone) processing lessening the molecular effects of cortisol on cellular function [11].

There is less in the clinical literature about the interaction between administering Shilajit and Testosterone however the consensus is that there is a positive correlation.

In a study where healthy men (aged 45-55) took 500mg of purified Shilajit per day, the two gonadotropic hormones, the levels of Luteinizing hormone (LH) and Follicle Stimulating Hormone (FSH) fell. LH & FSH inhibit testosterone synthesis and release and falling levels lead to significantly higher levels of testosterone & free testosterone (20% higher after 90-days) to be present in the body after its secretion [20].

These results were duplicated in another human clinical study targeting oligospermic males (see below). The results were very impressive with a 23.5% increase in testosterone levels after 90 days [21].

Although more clinical research is needed there are promising results about Shilajit’s ability to aid in male fertility [21].

1. Processed Shilajit (in the form found in ATS™) contains the biologically active compound di-benzo-alpha-pyrone (DPB). DPB improves spermatogenesis in patients with oligospermia (low sperm counts) [20].

2. Shilajit has been shown in animal and human studies to have an impact on molecules which are considered as reactive oxidative species (ROS) which in semen can decrease spermatozoa quality and hence the effects of ROS are mitigated with shilajit supplementation [22].

In Ayurveda, Shilajit is most well known for being a natural re-vitaliser; a way of reducing fatigue and improving energy levels.

1. As discussed, above processed Shilajit (in the form found in ATS™) contains the biologically active compound di-benzo-alpha-pyrone (DPB) which is known to stimulate mitochondria, the energy producing structures in the cells to promote generation of adenosine triphosphate (ATP), which the cells use for energy and bioenergetic reactions. Cells will die without adequate concentrations of ATP [23].

As inferred above, Zinc is one of the most researched elements when it comes to naturally stimulating, maintaining and supporting testosterone levels and therefore male sexual health. There are several proposed mechanisms:

1. Low Zinc levels have been shown to cause the cells that synthesise Testosterone (a.k.a. Leydig cells) to fail. Therefore Zinc levels have to be optimal to stimulate Testosterone production [25], [26].

2. Zinc is also known to be necessary for cell membrane receptor function (which allows signalling and messaging between cells. It also has a role in the ability for cells to be responsive to hormones such as chorionic-gonadotropin-hormone (HCG). HCG promotes testosterone production [27].

3. Zinc has also been highlighted in studies not only enhancing the conversion of Androstenedione to Testosterone [28], but also decreasing the breakdown of testosterone in the liver maintaining blood Testosterone levels.

Zinc, aside from its effects on hormones, also has a role in promoting cardiovascular health and has a positive impact on heart disease and evidence is emerging that Zinc supplements can reduce blood pressure which is, of course, beneficial for cardiovascular health [30].

A meta-analysis of more than 20 clinical studies which considered the effects of Zinc supplementation on serum lipids (fats) found that Zinc significantly reduced LDL (bad) cholesterol and & triglycerides – which are two leading risk factors in coronary heart disease [29].

Sex hormone binding globin (SHGB) binds with Testosterone to transport around the blood circulation as Testosterone is not soluble in blood. However, bound T to SHGB is not biologically active meaning that it does not have an effect. Only free testosterone is biologically active and Magnesium is required to allow dissociation of the bond between T and SHBG, allowing T to be unbound, released and therefore more bioavailability to act on those cells responsive to T in the body. [13].

As with many of the other ingredients in our Atlas Testosterone Support, Magnesium maintains the capacity of antioxidants and controls oxidative stress. This reduces the inhibiting effect on testosterone production that inflammatory cytokines (cell signalling molecules) have at the pituitary gland and testes [14].

What is becoming clearer is that Magnesium is important for sleep and sleep quality. It not only aids with the process of falling asleep, but also the quality of deep rest that is achieved throughout the night [15]. Magnesium deficiency is an important reason for sleep disturbance.

1. Cortisol release and levels are regulated by Magnesium. Specifically, Magnesium supplementation has been shown to significantly reduce cortisol in the first half of sleep cycle [16] potentially by modulating HPA activity [17] and the resulting reduction of stress hormone levels should make it easier to have a better night’s sleep.

2. Studies in animals have implicated Magnesium in melatonin production, which is a hormone that is closely associated with circadian rhythms and sleep.[18].

3. There is interesting data accumulating that Magnesium binds to gamma-aminobutyric (GABA) receptors in the brain which are associated with sedation and anaesthesia which may explain why Magnesium plays a role in sleep [19].

1. Vitamin D is essential for spermatogenesis and function of the Leydig cells in the testes, where there are specific receptors for vitamin D (Vitamin D receptors -VDR’s). The Leydig cells are the main sites of testosterone production and so low levels of Vitamin D will negatively impact testosterone levels [37].

2. Because of the close interrelationship between Calcium and Vitamin D and the role vitamin D has in Calcium metabolism, it is obvious that as Calcium is essential in spermatogenesis and sperm motility that Vitamin D is vital for male reproductive health [38].

This has been previously discussed on the previous page. If there is any doubt of the importance of Vitamin D and its role in the absorption of calcium [39] and bone health it is worth recalling the skeletal disease Rickets caused by a lack of Vitamin D. The effects of Vitamin D deficiency on bone formation is devastating with lifelong deformities such as bow legs, skull deformities, pigeon chest and pain.

A underrecognized component of western diets, when it comes to cardiovascular and human health, vitamin K2’s heart disease preventing effects again come from its interaction with calcium.

1. The mechanism by which the protective effects are initiated by the impact of vitamin K and its involvement in intermediary metabolism eg on the of matrix GLA (mGLA) proteins, which are strong biomarkers for vascular diseases such as arterosclerosis (arterial stiffness) resulting from blood vessel wall calcification [41]. This is particularly relevant as Vitamin K2 supplementation has been strongly associated to reduction in arterial calcification through activation of mGLA proteins.

1. Vitamin K2 is able to activate osteocalcin via a carboxylation reaction - higher serum osteocalcin levels are found after vitamin K2 supplementation [42].

2. Osteocalcin is a hormone made in the bones and plates that plays a primary role in bone strength, specifically to allow calcium to bind to bones [43].

Although there is a rarity of clinical studies and of those undertaken the only few small studies have been done, but observed results following Boron supplementation on free Testosterone and Estradiol levels are staggering.

For instance one study documented a 28% increase in free testosterone levels of subjects after a week of boron supplementation, coupled with a significant reduction in serum estradiol (E2) [31]. Alongside this, inflammatory biomarkers (IL-6, hs-CRP & TNF-alpha) were significantly reduced at the end of the study.

The proposed mechanism for this increase is due to the fact that the majority of free testosterone ins bound to sex hormine binding globulin (SHBG) (as well as almbium and cortisol-bindong globulin). Boron was shown to significantly increase free (bioavailable testosterone) and so likely increase the conversion of total testosterone to free testosterone in the metabolic pathway.

This is particularly pertinent for ageing men who not only does their testosterone decrease with age but also their SHGB rises thus binding for bioavailable testosterone up [32].

A less researched issue, but a growing area of study, is the effect of Boron supplementation and its positive impact on cardiovascular health. It is well understood that chronic oxidative stress and the resulting inflammation can amplify the effects of cardiovascular health risks such as obesity, hypertension, diabetes, & poor diet. Boron appears to have an anti-inflammatory effect and reduces the cardiac risks [34].

Boron seems to have a low public profile in relation to bone health.

A metanalysis of 11 studies with around 600 subject, indicated that Boron supplementation has a positive impact on maintenance of bone density. Several mechanisms for this have been proposed:

1. Boron has a synergistic relationship with Cholecalciferol (vitamin D3) and calcium – where it seems to promote mineral absorption and bone matrix synthesis which is important in bone health bone [35].

2. Boron’s impact on bone may also be mediated by its role in intermediary metabolism DNA synthesis and energy production. Suspicions are that borates (such as sodium tetraborate found in ATS™), have an affinity for hydroxyl groups in the structure of the building blocks of cell function, such as biological sugars (e.g. ribose). Many of these ribose containing chemical compounds such as Adenosine phosphates (ATP/ADP) and Nicotinamide Adenine Dinucleotide NAD, are vital for cellular survival and not unsurprisingly the formation and maintenance of healthy bones. [36].