AML™ TEST; A SCIENTIFIC REVIEW
By Robert Schinetsky
The COVID-19 pandemic has rocked the world in ways no one could have foreseen.
And, with each passing week, researchers glean greater insight into what makes this virus “tick” as well as what factors may contribute to its severity or outcomes.
Previously, researchers have noted associations between obesity and severity/mortality of infection from COVID-19 as well as vitamin D deficiencies and increased risk of poorer outcomes from infection.[1,2,3]
More recently, the scientific community has observed that men appear to be more susceptible to severe outcomes from COVID-19 than women. This has led some in the research community to postulate that sex hormones may play a role in the severity and outcome of the disease.
Namely, estrogen may be protective against COVID-19 in women, and/or androgens may worsen COVID-19 outcomes in men.
Research from Italy found that individuals with prostate cancer who were treated with androgen deprivation therapy (ADT) were less likely to become infected with COVID-19 and die from the disease than other individuals, including those with cancer.[4]
More specifically, the team of Italian researchers noted that individuals with prostate cancer receiving androgen deprivation therapy had a four-fold decreased risk of COVID-19 infection compared to individuals who did not receive ADT.[4]
This begs the question -- how do androgens impact COVID-19 infection, if at all?
Well, COVID gains entry into human cells by binding to ACE2 (angiotensin-converting enzyme 2) receptors. Additionally, the spike protein of SARS-CoV-2 is primed by TMPRSS2.[5]
TMPRSS2 (Transmembrane protease, serine 2) is an enzyme that is encoded by the TMPRSS2 gene and is involved in a number of processes including viral infections and cancer.
Regarding its role in viral infections, TMPRSS2 primes the Spike protein of COVID, which results in diminished viral recognition by neutralizing antibodies and activation of SARS‐CoV‐2 for virus‐cell fusion.[7]
Moreover, TMPRSS2 is an androgen-regulated gene that is upregulated in prostate cancer.
Since androgen deprivation therapy can decrease TMPRSS2 levels, it is thought that androgen receptor antagonists may help block or decrease the severity of COVID-19 infection in male patients.[6]
However, this presents a problem. Androgen deprivation therapy causes a decline in androgens, namely testosterone. Now, testosterone levels can be recovered following cessation of ADT, but that depends on a number of factors, including age, duration of ADT, and baseline testosterone levels prior to ADT.[8]
As if things weren’t complicated enough, it’s about to get worse.
Testosterone, in addition to being the primary sex hormone in men, also plays a role in the body’s immune response as does testosterone’s “little brother” dihydrotestosterone (DHT).
Research out of Germany found that critically ill COVID-19 patients suffer from severe testosterone and dihydrotestosterone (DHT) deficiencies.[9]
Researchers note that deficiencies of these hormones can impair the immune system’s ability to combat pathogens, creating a “cytokine storm”, which is a hyper-inflammatory condition caused by an overactive immune system.
This “storm” has been observed in many individuals fighting COVID-19.
It should be mentioned that all patients in the German study had comorbidity (hypertension, cancer, obesity, Type 2 diabetes, or heart disease), and these comorbidities could factor into the low T levels of the male subjects (as well as their age).
As you’re likely aware, testosterone levels (as with most other things in the human body) decline with age.
Interestingly, the same study noted that the majority of female COVID-19 patients had elevated testosterone levels without changes to their DHT levels.[9]
This presents researchers with an interesting predicament -- explore androgen deprivation therapies to improve COVID outcomes, but risk torpedoing testosterone levels, which could itself worsen COVID outcomes?
Or, sidestep ADT and focus on boosting testosterone through other means?
There may be a more natural route that has yet to be fully vetted by researchers -- the “parent” hormone of testosterone (and all other sex hormones for that matter) -- DHEA.
What is DHEA?
DHEA is a naturally occurring steroid prohormone synthesized in the adrenal glands, brain, and gonads. It serves as a precursor to the major sex hormones testosterone and estrogen.
DHEA levels peak in early adulthood (around age 30) and slowly, steadily decline with age, reducing recovery, muscle growth, and testosterone levels while increasing aging and muscle breakdown.
In fact, research notes that DHEA levels decline ~80% between the ages of 25 and 75.[10]
Additionally, research also notes an association between low DHEA and increased abdominal fat storage as well as a greater risk of cardiovascular disease.
To help stave off this decline, many adults (both men AND women) supplement with DHEA.
What Does DHEA Do?
Research notes that supplementation with DHEA may help[10,11,12,13,14]:
- Enhance the anabolic effects of weight training
- Decrease body fat
- Increase metabolism
- Bolster immune function
- Reduce cortisol levels (which helps indirectly increase testosterone)
- Strengthen bones
- Increase IGF-1 (insulin-like growth factor-1)
- Reduce protein breakdown and muscle loss
More pertinent to our discussion at the outset of this article, DHEA supplementation also has been noted to increase free testosterone levels, especially when used in combination with intense physical activity such as resistance training or high-intensity interval training (HIIT).[10,11]
DHEA supplementation (when used in combination with resistance training) also led to greater increases in muscle mass and strength in adults than resistance training alone.[10]
Even more importantly, as opposed to other testosterone elevating compounds, DHEA has low androgenicity. It also does NOT negatively affect sex hormone-binding globulin (SHBG) or estrogen, in men or women.[15]
This is important when you consider that testosterone is found in the body in both free and bound forms. The bound form of testosterone is inert thanks to the actions of SHBG.
Free testosterone is the biologically active form of testosterone that supports energy, strength, recovery, immune function and sexual health.
More Benefits of DHEA!
DHEA has also been noted to support nitric oxide production, erectile function, and prostate health.[16,17,18]
Taken together, DHEA promotes higher testosterone levels while keeping androgens low, giving all the benefits of other testosterone-boosting options with none of the drawbacks.
AML Test contains the research-backed dose of 50mg DHEA.
As mentioned above, research conducted in healthy adults shows that consuming 50mg DHEA before training significantly increases free testosterone levels.
This is why it is recommended to consume your serving of AML Test 30 minutes prior to exercise.
What Else is in AML Test?
As you’re well aware, AML takes a multi-tiered approach to supplement formulation. As such, AML Test offers much more in addition to DHEA.
Vitamin D
Previously, we’ve discussed the importance vitamin D plays in immune function.
But, you might also be interested to know that vitamin D also plays a role in testosterone production.
However, a significant portion of the population is deficient in vitamin D due to a mixture of factors, not the least of which is not spending enough time outdoors in sunshine.
Low vitamin D levels are not only associated with low testosterone, but an increased risk of cardiovascular disease and cancer.
The good news is that research has noted that Vitamin D3 (cholecalciferol) supplementation may be effective for increasing testosterone levels (as much as 20%).[20,21]
Research indicates that vitamin D supports testosterone levels by reducing in sex-hormone binding globulin (SHBG) activity and aromatase expression, which helps limit the conversion of testosterone into estrogen.
Additionally, Vitamin D3 supplementation has been shown to raise levels of the IGF-1.[22,23]
To top it off, vitamin D3 supplementation may also help reduce body fat while increasing athletic performance as evidenced by a study which found that individuals taking 4,000 IU of vitamin D per day improved peak power output and waist-to-hip ratio.
Zinc
Similar to vitamin D3 supplements, zinc supplements have experienced a renaissance recently in large part for their role in immunity. Specifically, zinc possesses anti-viral properties in humans and has been noted to help lower inflammation.
Zinc also plays an important role in testosterone production, and deficiencies in the essential mineral have been associated with low testosterone levels.[24]
Addressing these deficiencies through supplementation can help increase testosterone levels.
AML Test supplies 30mg elemental zinc from zinc gluconate.
Fenugreek
Fenugreek (Trigonella Foenum-Graecum) is a staple botanical with a long history of use in Ayurveda as an anti-diabetic and cholesterol-lowering agent.
Fenugreek is rich in two classes of compounds (glycosides and steroidal saponins) that have been noted in human research trials to inhibit aromatase and increase free testosterone levels.[25,26]
Specifically, research demonstrates that college-aged men who consumed 500mg of a standardized fenugreek extract for 4 weeks experienced significant increases in free testosterone.[25] They also experienced a decrease in body fat!
Additional studies from 2015 give evidence that consuming 600mg daily of a standardized fenugreek extract for eight weeks can increase free testosterone levels compared to placebo.[26]
You might be interested to know the group receiving the fenugreek supplement also experienced an increase in athletic performance and a reduction in body fat without losing strength.
It’s also important to note that fenugreek is non-hormonal (as are all the other ingredients in AML Test) and comes without any significant clinical side effects.
Eurycoma Longifolia
Eurycoma longifolia is another staple of Ayurveda, and it can be found under various names, including Tongkat Ali and Longjack.
The plant has long been used as an aphrodisiac, and modern studies have shown it to be effective in both men and women for improving libido and free testosterone concentrations as well as lean muscle mass and strength!
Specifically, a 2011 study demonstrated that supplementation with 100mg longjack extract enhanced muscle size and strength.
Additional studies find that subjects consume higher doses of the plant extract (200mg and 400mg), they experienced increases in both free and total testosterone levels.[27,28,29]
Better still, longjack has shown to benefit both older and younger men and women (most natural testosterone support ingredients really only show benefit in men over the age of 40).
Grape (Red Wine) Polyphenols
Grapes (and by proxy red wine) are an abundant source of polyphenols and antioxidants.
Grape extracts and their polyphenols have been extensively studied and noted to boost nitric oxide production, enhance blood flow, improve exercise performance, and potentially help protect against various health problems, such as Type 2 diabetes, cardiovascular disease, and neurodegenerative disorders.[30,31]
Red wine polyphenols have also been investigated for their potential to raise free testosterone via reduction of sex-hormone-binding globulin (SHBG).[32]
Interestingly, researchers believe these polyphenols might reduce the amount of testosterone excreted by the body, which could further boost testosterone levels in the body.
Boron
The final pro-testosterone agent in AML Test is another essential trace mineral -- boron.
Much like zinc and vitamin D, boron is involved in many biological processes, including[33]:
- Bone growth and maintenance
- Magnesium absorption
- Wound healing
- Utilization of hormones, including vitamin D, testosterone, and estrogen
- Reduction of inflammatory biomarkers, including C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α)
It comes as little surprise then that boron supports healthy testosterone levels, and deficiencies in the mineral can adversely impact testosterone production.
Fortunately, supplementation with boron has been shown to correct these deficiencies and boost testosterone levels.
Specifically, research shows that supplementation with 10 mg of boron per day for seven days increased free testosterone by 28% and decreased estrogen levels by 39%![33]
Boron can also help reduce levels of SHBG, thereby leading to more free testosterone.
Additional benefits noted with boron supplementation include decreased levels of inflammatory biomarkers (such as CRP) and improved cognitive function.[34,35]
AML Test -- The Premier Natural Testosterone Support Supplement
AML TEST was formulated to enhance free testosterone levels using natural ingredients that DO NOT cause suppression or any other unwanted effects commonly experienced with more “aggressive” supplement protocols.
But, simply supplementing with AML Test isn’t enough to maximize natural testosterone production, you also need to be doing the right things in daily life, such as stress management, adequate sleep, regular physical activity, and (of course) a healthy diet.
By doing all of these things, you’ll foster the ideal environment to optimize testosterone production, leading to greater vitality, immunity, mood, cognitive function, and performance (both in the gym and in the bedroom!).
Click here to learn more about AML Test and why it’s the premier testosterone support supplement on the market!
References
- Sattar, N., Mcinnes, I. B., Mcmurray, J. J. V, & Sciences, M. (n.d.). Obesity a Risk Factor for Severe COVID-19 Infection : Multiple Potential Mechanisms, 44(0), 1–8.
- Strong circumstantial evidence suggests vitamin D could improve COVID-19 outcomes. (2020, May 20). Diabetes. https://www.diabetes.co.uk/news/2020/05/strong-circumstantial-evidence-suggests-vitamin-d-could-improve-covid-19-outcomes/
- Mitchell, F. (2020). Vitamin-D and COVID-19: do deficient risk a poorer outcome? The Lancet Diabetes & Endocrinology. https://doi.org/10.1016/S2213-8587(20)30183-2
- Montopoli, M., Zumerle, S., Vettor, R., Rugge, M., Zorzi, M., Catapano, C. V, Pagano, F. (2020). Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2 : a population-based study ( N [ 4532 ). Annals of Oncology, xxx(xxx), 1–6. https://doi.org/10.1016/j.annonc.2020.04.479
- Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Pöhlmann, S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(2), 271-280.e8. https://doi.org/https://doi.org/10.1016/j.cell.2020.02.052
- Montopoli, M., Zumerle, S., Vettor, R., Rugge, M., Zorzi, M., Catapano, C. V, Alimonti, A. (2020). Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (<em>N</em> = 4532). Annals of Oncology. https://doi.org/10.1016/j.annonc.2020.04.479
- Wambier CG, Goren A, Vaño-Galván S, et al. Androgen sensitivity gateway to COVID-19 disease severity [published online ahead of print, 2020 May 15]. Drug Dev Res. 2020;10.1002/ddr.21688. doi:10.1002/ddr.21688
- Nascimento B, Miranda EP, Jenkins LC, Benfante N, Schofield EA, Mulhall JP. Testosterone Recovery Profiles After Cessation of Androgen Deprivation Therapy for Prostate Cancer. J Sex Med. 2019;16(6):872‐ doi:10.1016/j.jsxm.2019.03.273
- Schroeder, M., Jarczak, D., & Nierhaus, A. (2020). The majority of male patients with COVID-19 present low testosterone levels on admission to Intensive Care in Hamburg , Germany : a retrospective cohort study .
- Villareal, D., & Holloszy, J. (2006). DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. American Journal of Physiology. Endocrinology and Metabolism, 291, E1003-8. https://doi.org/10.1152/ajpendo.00100.2006
- Liu, TC., Lin, CH., Huang, CY. et al. Effect of acute DHEA administration on free testosterone in middle-aged and young men following high-intensity interval training. Eur J Appl Physiol (2013) 113(7): 1783-92. https://doi.org/10.1007/s00421-013-2607-x
- Villareal DT, Holloszy JO. Effect of DHEA on Abdominal Fat and Insulin Action in Elderly Women and Men A Randomized Controlled Trial. JAMA. 2004;292(18):2243–2248. doi:10.1001/jama.292.18.2243
- Tarig Elraiyah, Mohamad Bassam Sonbol, Zhen Wang, Tagwa Khairalseed, Noor Asi, Chaitanya Undavalli, Mohammad Nabhan, Osama Altayar, Larry Prokop, Victor M. Montori, Mohammad Hassan Murad; The Benefits and Harms of Systemic Dehydroepiandrosterone (DHEA) in Postmenopausal Women With Normal Adrenal Function: A Systematic Review and Meta-analysis, The Journal of Clinical Endocrinology & Metabolism, Volume 99, Issue 10, 1 October 2014, Pages 3536–3542, https://doi.org/10.1210/jc.2014-2261
- Collomp, C. Buisson, F. Lasne, R. Collomp, DHEA, physical exercise and doping, The Journal of Steroid Biochemistry and Molecular Biology, Volume 145, 2015, Pages 206-212
- Ponholzer A , et al. "Association of DHEA-S and Estradiol Serum Levels to Symptoms of Aging Men. - PubMed - NCBI." National Center for Biotechnology Information.
- El-Sakka AI. Dehydroepiandrosterone and Erectile Function: A Review. World J Mens Health. 2018;36(3):183‐ doi:10.5534/wjmh.180005
- Julia T. Arnold, Marc R. Blackman, Does DHEA Exert Direct Effects on Androgen and Estrogen Receptors, and Does It Promote or Prevent Prostate Cancer?, Endocrinology, Volume 146, Issue 11, 1 November 2005, Pages 4565–4567, https://doi.org/10.1210/en.2005-0901
- Julia T. Arnold, Marc R. Blackman, Does DHEA Exert Direct Effects on Androgen and Estrogen Receptors, and Does It Promote or Prevent Prostate Cancer?, Endocrinology, Volume 146, Issue 11, 1 November 2005, Pages 4565–4567, https://doi.org/10.1210/en.2005-0901
- Williams MR, Dawood T, Ling S, Dai A, Lew R, Myles K, et al. Dehydroepiandrosterone increases endothelial cell proliferation in vitro and improves endothelial function in vivo by mechanisms independent of androgen and estrogen receptors. J Clin Endocrinol Metab. 2004;89:4708–4715.
- Pilz, S.; Frisch, S.; Koertke, H.; Kuhn, J.; Dreier, J.; Obermayer-Pietsch, B.; Wehr, E.; Zittermann, A. Effect of Vitamin D Supplementation on Testosterone Levels in Men. Hormone and Metabolic Research 2011; 43(03): 223 – 225 DOI: 10.1055/s-0030-1269854
- Effects of vitamin D supplementation on upper and lower body muscle strength levels in healthy individuals. A systematic review with meta-analysis Tomlinson, Peter B. et al. Journal of Science and Medicine in Sport, Volume 18 , Issue 5 , 575-580
- Salehpour A, Hosseinpanah F, et al. A 12-week double-blind randomized clinical trial of vitamin D3 supplementation on body fat mass in healthy overweight and obese women. Nutr. J 2014; 11, 78
- Carrillo AE, Flynn MG, Pinkston C, et al. Impact of vitamin D supplementation during a resistance training intervention on body composition, muscle function, and glucose tolerance in overweight and obese adults. Clinical nutrition (Edinburgh, Scotland). 2013;32(3):375-381. doi:10.1016/j.clnu.2012.08.014.
- Prasad AS, Mantzoros CS, Beck FW, Hess JW, Brewer GJ. Zinc status and serum testosterone levels of healthy adults. Nutrition. 1996;12(5):344‐ doi:10.1016/s0899-9007(96)80058-x
- Wilborn C, Taylor L, Poole C, Foster C, Willoughby D, Kreider R. Effects of a purported aromatase and 5α-reductase inhibitor on hormone profiles in college-age men. Int J Sport Nutr Exerc Metab. 2010 Dec;20(6):457-65.
- Sachin Wankhede, Vishwaraman Mohan, Prasad Thakurdesai, Beneficial effects of fenugreek glycoside supplementation in male subjects during resistance training: A randomized controlled pilot study, Journal of Sport and Health Science, Volume 5, Issue 2, 2016, Pages 176-182.
- Thu HE , et al. "Eurycoma Longifolia As a Potential Adoptogen of Male Sexual Health: a Systematic Review on Clinical Studies. - PubMed - NCBI." National Center for Biotechnology Information, ncbi.nlm.nih.gov/pubmed/28259255.
- Tambi MI: Water soluble extract of Eurycoma longifolia in enhancing testosterone in males. In Proceedings of the SupplySide West International Trade Show and Conference. Virgo Publishing; 2003. Oct 1–3.
- Hamzah S, Yusof A: The ergogenic effects of Tongkat ali (Eurycoma longifolia): A pilot study. British J Sports Med 2003, 37:464–470.
- Rasines-Perea Z, Teissedre PL. Grape Polyphenols' Effects in Human Cardiovascular Diseases and Diabetes. Molecules. 2017;22(1):68. Published 2017 Jan 1. doi:10.3390/molecules22010068
- Caruana M, Cauchi R, Vassallo N. Putative Role of Red Wine Polyphenols against Brain Pathology in Alzheimer's and Parkinson's Disease. Front Nutr. 2016;3:31. Published 2016 Aug 12. doi:10.3389/fnut.2016.00031
- Shufelt C, Merz CN, Yang Y, et al. Red versus white wine as a nutritional aromatase inhibitor in premenopausal women: a pilot study. J Womens Health (Larchmt). 2012;21(3):281‐ doi:10.1089/jwh.2011.3001
- Pizzorno L. Nothing Boring About Boron. Integr Med (Encinitas). 2015;14(4):35-48.
- Naghii M R, Mofid M, Asgari A R, Hedayati M, Daneshpour M S. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. Physiol Pharmacol. 2011; 15 (3) :403-414
- Naghii MR1, Samman S. The effect of boron supplementation on its urinary excretion and selected cardiovascular risk factors in healthy male subjects. Biol Trace Elem Res. (1997)