By Dwayne N. Jackson, PhD
Are you a male, over 30 years old, and feeling a little sluggish, soft, or chubby? Do you miss the drive and vigor you had when you were 25? If you answered yes to any of these questions, then you may have already considered testosterone replacement therapy (TRT). BUT WAIT, before you embark on a lifetime commitment of frequent and painful intramuscular testosterone injections, I encourage you to read this article!
Herein, I will educate you on the basics of testosterone production in the body and how we, the scientists at ATP Lab, formulated Alpha Jack in an effort to revitalize your endocrine system, support male health, and bring vigor back to your life.
What is testosterone and how do we produce this stuff?
Testosterone is an anabolic steroid synthesized primarily by the Leydig cells in the testes of males, the ovaries of females and adrenal glands in both sexes. It is synthesised from cholesterol, with androstenedione, androstenediol, dehydroepiandrosterone sulphate (DHEA), progesterone and pregnenolone acting as prohormones. The production and secretion of testosterone is regulated by hormones that act on the hypothalamus and pituitary gland in the brain through the hypothalamic–pituitary–testicular axis (HPTA).
Testosterone production and secretion ramp up in the morning, as the hypothalamus intermittently releases gonadotropin releasing hormone (GnRH) throughout the day. GnRH, acts on the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which respectively stimulate the Leydig (for testosterone secretion) and Sertoli cells (for sperm production) within the testes. LH and testosterone levels peak in the morning and decrease toward the evening. This is because elevated testosterone levels signal the hypothalamus to decrease LH release, thus decreasing testosterone secretion via negative feedback.
In addition to testosterone’s intimate relationship with the hypothalamus, it has been found that testosterone bioavailability is modified through negative feedback with the anterior pituitary gland. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein called sex hormone-binding globulin (SHBG). Most circulating testosterone is bound by SHBG and albumin; approximately 2% of total testosterone is free (not bound to protein). SHBG-bound testosterone is so tightly bound that it is not biologically active. Both free and albumin-bound testosterone are biologically active and together are referred to as the bioavailable testosterone. It is reported that the total, free and bioavailable testosterone varies widely among adult men.
Fig. 1: Major gonadal pathways for steroid hormone biosynthesis (From: Biol Sex Differ. 2015 Apr 29;6:9.).
Gonadotropin-releasing hormone (GnRH) secreted from the hypothalamus releases luteinizing hormone (LH) from the pituitary. LH binds to LH receptors on Leydig cells in the testes, stimulates Gs, and activates the cAMP/protein kinase A (PKA) pathway. PKA promotes the transport of cholesterol into mitochondria and increases transcription of genes involved in testosterone biosynthesis. Cholesterol is converted to pregnenolone, which diffuses into the endoplasmic reticulum for testosterone biosynthesis via ∆4 and ∆5 pathways. Testosterone is formed by 17β-hydroxysteroid dehydrogenase 3 (HSD17β3) in the ∆4 pathway and by 3β-hydroxysteroid dehydrogenase (HSD3β) in the ∆5 pathway. Testosterone is converted to dihydrotestosterone (DHT) by 5α-reductase, and some are aromatized to 17ß-estradiol.
Once testosterone is produced, its fate is determined primarily by the expression of enzymes like aromatase or 5α-reductase which transform testosterone to estradiol and dihydrotestosterone (DHT) respectively. Advanced age, stress, high levels of body fat, and poor dietary choices can all impact the expression and actions of these enzymes---leading to decreases in circulating testosterone levels.
Testosterone: total, bound, and free?
So, as you can see, optimizing serum testosterone levels goes beyond simply increasing total testosterone, as blood testosterone comes in 3 ‘flavors’--- total, bound, and free. Total testosterone refers to all testosterone (i.e., free + bound) found in the blood. Bound testosterone is all of the testosterone in the blood that is bound to sex hormone-binding globulin (SHBG), and to albumin. The largest fraction of blood testosterone is bound to SHBG and, since it cannot interact with testosterone receptors in the body, SHBG-bound testosterone is considered non-bioavailable. Free testosterone and albumin-bound testosterone are the most bioavailable fractions of testosterone in the blood, with albumin-bound testosterone being slightly less bioactive. However, since albumin binds testosterone weakly, it dissociates from albumin and becomes free testosterone in the capillaries (the smallest blood vessels and the site of molecular exchange in all of our organs and muscles).
Testosterone levels in North American men are declining; a result of inactivity, increased body fat, and high levels of psychological stress.
The significant decline in men’s testosterone levels is closely linked to the common medical conditions afflicting our population. Conditions such as obesity, metabolic syndrome, diabetes, and hypertension all correlate with male sexual dysfunction and hypogonadism.
A recent large scaled population study, published in The Journal of Clinical Endocrinology and Metabolism, tells us that testosterone levels have declined, even among relatively healthy American men, by ~17% overall in less than 20 years! This is alarming considering the study controlled for health and lifestyle characteristics, like smoking and obesity, known to decrease testosterone levels. This means that, although you may be a young and fit non-smoker, you are still susceptible to several factors that lower testosterone. Testosterone’s profound effects on strength, protein synthesis, recovery, appetite stimulation, focus, energy, and aggression highlight the importance to optimize blood testosterone in men of all ages and levels of fitness.
Many research studies question the efficacy of herbal testosterone “boosters”. The common discrepancy among the science seems to be in potencies of herbal preparations used across different studies. To address this, one study illustrated that the concentration of steroidal saponins in herbal extracts is greatly influenced by the geographical origin and standardization of plant material. At the end of the day, good quality products will always use standardized extracts and report what compound is standardized and at what concentration. Alpha Jack from ATP Lab clearly lists all ingredients and levels of standardization! After all, we are proud to use only the best, premium grade, standardized compounds in all of our nutraceuticals.
Beware of misleading TESTOSTERONE BOOSTING claims!
The issue with most testosterone “boosters” on the market is the unreasonable expectation that they will promote unnatural increases in testosterone levels that are comparable to testosterone injections. At ATP Lab we know this is misleading and, as such, we didn’t formulate Alpha Jack as a testosterone “booster”, but rather as science-based supplement to support and optimize testosterone’s actions in men.
Supplemental support for hormonal optimization
Alpha Jack from ATP Lab is formulated to positively support and optimize the actions of testosterone in males. In an effort to provide the greatest natural support for testosterone production, we formulated Alpha Jack by strategically targeting the primary biochemical pathways influencing testosterone’s actions in the body.
Each 6 capsule, serving of Alpha Jack provides:
D-aspartic Acid (D-Asp): 3 g
D-Asp is an endogenous amino acid found in neuroendocrine tissues throughout the body. Of interest to the discussion of testosterone optimization, several studies have shown that D-Asp is concentrated in the major sites of gonadal steroid hormone biosynthesis--- the pineal gland, the pituitary gland, and the testes.
In a recent systematic review published in the International Journal of Reproductive Biomedicine, it was concluded that D-Asp alters testosterone production and its actions by the following mechanisms:
1. D-Asp can directly increase the release of GnRH from the hypothalamus. Then GnRH induces the release of LH from the pituitary gland. As a result, there is increased signalling for testosterone production.
2. D-Asp can be converted to NMDA that stimulates the release of GnRH in the hypothalamus. GnRH release in the hypothalamus initiates the cascade of signalling events that promote testosterone production.
3. D-Asp stimulates the pituitary gland to release LH. LH signals the testes to produce more testosterone.
5. D-Asp increases the mRNA and protein levels of the steroidogenic acute regulatory protein (StAR). StAR protein levels must increase to support increased testosterone production.
6. In healthy young athletic men, high doses of D-Asp may enhance aromatase activity and may promote the conversion of testosterone to estradiol. (More on this below!)
7. D-Asp lowers the expression of 5α-reductase. 5α-reductase, converts testosterone into 5α-dihydrotestosterone (DHT), so with lower expression there is a decrease in the conversion of testosterone to DHT.
10. D-Asp induces up-regulation of androgen receptor and down-regulation of estrogen receptor expression.
Although supplemental D-Asp has shown great promise in men over 30 years old and younger men who are at risk for hypogonadism, there have been a few recent studies that question the efficacy of D-Asp in young (approximately 24 years old), healthy, lean, highly trained populations. The common findings among these studies is that 3g of D-Asp (like that found in Alpha Jack) does not increase blood levels of free or bound testosterone in these groups. This is not surprising, given the fact that the populations of young athletes used for these studies would carry few, if any, risks for hypogonadism. Further, one study showed that taking high doses of D-Asp (6 g) may increase the actions of aromatase and increase the production of estradiol and other estrogens from testosterone. Rest assured that Alpha Jack is perfectly formulated so that 6 capsules contains precisely 3 g of high potency D-Asp. For those looking to circumvent the possibility of increases in aromatase activity, we suggest taking ATP LAB’s Alpha Jack with Aromatek, our new aromatase inhibition formulation designed specifically for men.
Eurycoma Longifolia Jack (Tongkat ali, standardized extract 100 :1): 400 mgEurycoma Longifolia Jack (EL or Tongkat ali), has been used for centuries as a natural herbal remedy for male sexual disorders and infertility. EL, has been shown to improve libido, restore erectile function, stimulate production of testosterone, and enhance the level of bioavailable (free) testosterone (see Fig. 2). Preclinical work illustrates that the mechanisms involved in improving male sexual performance are mainly associated with increased conversion of pregnenolone to progesterone, DHEA, and testosterone.
Fig. 2, The published effects of Eurycoma Longifolia on male hormonal and sexual health. (From: Hnin Ei Thu, et al. / Chin J Nat Med, 2017, 15(1): 7180)
The EL used in Alpha Jack has been standardized to its highest potency (100:1), This means that each 6 capsule dose of Alpha Jack gives you the potency and benefits of taking 40,000 mg of EL root!
Cordyceps sinensis: 300 mg
Chinese Cordyceps is a fungus that includes up to 400 species. However, as a male hormone support supplement you want to be sure you are using Cordyceps sinensis (CS). Cordyceps sinensis is a fungal parasite that survives on caterpillars (or larvae) of moths and butterflies. In late fall, the fungus attacks the caterpillar and slowly consumes it. By the next summer, the fungus will have completely consumed the caterpillar resulting in its fruiting body protruding from the caterpillar’s head. Although this sounds creepy, I promise you won’t find me in a lab coat in a forest scavenging for zombie caterpillars, today we can mass-produce CS by growing it in cell culture laboratories.
Among its many benefits, it has been suggested to help maintain levels of hormones such as testosterone, increase the body's resistance to stress, improve cholesterol levels, regulate insulin release, and increase energy and mental focus. The active components in Cordyceps are reported to be cordycepin, nucleotides, polysaccharides, and amino acids. Preclinical research shows that CS and cordyceptin promote increased testosterone levels by stimulating Leydig cells in the testicles (see Fig. 3).
Fig. 3, Cordyceps sinensis and cordycepin can significantly stimulate in vitro and in vivo steroidogenesis in Leydig cells through the activation of the protein kinase A pathway. (From: J Food Drug Anal. 2017 Jan;25(1):197-205
Maca extract (12:1): 300 mg
Maca (Lepidium meyenii) is a plant that grows at over 4000 meters in the central Peruvian Andes. In the supplement world, maca is considered an adaptogen, which means it aids the body in resisting damage from stress, whether it be physical, chemical or biological. Maca constituents include fatty acids (palmitic, oleic, linoleic acids), sterols, aromatic glucosinolates and their derived isothiocyanates, and alkamides. Preclinical data illustrate that maca has nutritional, energizing, aphrodisiac, and fertility-enhancing properties. Clinical trials have shown that maca supplementation improves sexual function and increases sperm count and quality without affecting serum hormone levels. We have included maca in Alpha Jack in a 12:1 standardized extract, where just 300 mg of this high potency form of Maca provides the benefits of taking 3600 mg of maca root.
Shilajit: 250 mg
Shilajit is a brownish compound that is found oozing from sedimentary rocks during summer months throughout the Himalayas. Purified Shilajit is used in Ayurveda, the ancient system of medicine in India, as a remedy for several diseases. It is composed of rock humus, rock minerals and organic substances that have been compressed by layers of rock mixed with marine organisms and microbial metabolites. One of the main bioactive compounds in Shilajit is fluvic acid. A typical processed product may contain 50–60% fulvic acid, 0.3–0.4% dibenzo-a-pyrones (DBPs), 10–30% DBP chromoproteins (DCPs), and 10–15% minerals. Products are frequently standardized using DBPs, DCPs, and fulvic acids, with fulvic acid and equivalents being the most common standard. The physiological and pharmacological effects of shilajit are attributed to the DBPs, DBP chromoproteins (DBPs conjugated to proteins), fulvic acid, and various polymeric forms of fulvic acid. Some early studies showed that that the primary effects of shilajit were due to the ability of fulvic acid to naturally chelate the minerals associated within Shilajit, leading to their increased bioavailability.
In a randomised, double‐blind, placebo‐controlled clinical study published in Andrologica, treatment with Shilajit for 90 days (250 mg twice a day) in healthy men aged 45-55 years old increased total testosterone by 20%, free testosterone by 19% and dehydroepiandrosterone (DHEA) by 31%, compared with placebo. In another study, 35 infertile male subjects were given 100 mg of processed Shilajit twice a day for 90 days. Those who received Shilijit had significant increases in normal (18.9%) and total (61.4%) sperm count and sperm motility (12.4–17.4%). Furthermore, shilajit treatment resulted in increases in serum testosterone (23.5%) and FSH (9.4%) levels.
How to optimize hormones with Alpha Jack
So, hopefully you have learned a little about testosterone production and optimization. Now, it’s time to make a change for the better. If you are concerned with your current hormonal state or are looking to boost sexual vigor, give ATP LAB’s Alpha Jack a try! For best results take 6 capsules per day, split into 3 doses, take morning, noon, and night around meal time.
Farzad Roshanzamir and Seyyed Morteza Safavi. The putative effects of D-Aspartic acid on blood testosterone levels: A systematic review. Int J Reprod Biomed (Yazd). 2017 Jan; 15(1): 1–10.
Santillo A, Falvo S, Chieffi P, Burrone L, Baccari GC, Longobardi S, et al. d-aspartate affects NMDA receptor-extracellular signal-regulated kinase pathway and upregulates androgen receptor expression in the rat testis. Theriogenology 2014; 81: 744-751.
Furuchi T, Homma H. Free D-aspartate in mammals. Biol Pharma Bullet 2005; 28: 1566-1570.
Falvo S, Di Fiore MM, Burrone L, Baccari GC, Longobardi S, Santillo A. Androgen and oestrogen modulation by D-aspartate in rat epididymis. Reprod Fertil Dev. 2016 Oct;28(12):1865-1872.
Steels E, et al. Physiological aspects of male libido enhanced by standardized Trigonella foenum-graecum extract and mineral formulation. Phytother Res. 2011 Sep;25(9):1294-300.
Wilborn C, et al. 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.
Dinchev D, Janda B, Evstatieva L, Oleszek W, Aslani MR, Kostova I. Distribution of steroidal saponins in Tribulus terrestris from different geographical regions.
Phytochemistry. 2008 Jan;69(1):176-86.
Rogerson S, Weatherby RP, Deakin GB, Meir RA, Coutts RA, Zhou S, Marshall-Gradisnik SM. The effect of short-term use of testosterone enanthate on muscular strength and power in healthy young men. J Strength Cond Res. 2007 May;21(2):354-61.
Thu HE, Mohamed IN, Hussain Z, Jayusman PA, Shuid AN. Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies. Chin J Nat Med. 2017 Jan;15(1):71-80.
Chen YC, Chen YH, Pan BS, Chang MM, Huang BM. Functional study of Cordyceps sinensis and cordycepin in male reproduction: A review. J Food Drug Anal. 2017 Jan;25(1):197-205.
Onaolapo AY, Oladipo BP, Onaolapo OJ. Cyclophosphamide-induced male subfertility in mice: An assessment of the potential benefits of Maca supplement. Andrologia. 2018 Apr;50(3).
Ohta Y, Yoshida K, Kamiya S, Kawate N, Takahashi M, Inaba T, Hatoya S, Morii H, Takahashi K, Ito M, Ogawa H, Tamada H. Feeding hydroalcoholic extract powder of Lepidium meyenii (maca) increases serum testosterone concentration and enhances steroidogenic ability of Leydig cells in male rats. Andrologia. 2016 Apr;48(3):347-54.
Gonzales GF. Ethnobiology and Ethnopharmacology of Lepidium meyenii (Maca), a Plant from the Peruvian Highlands. Evid Based Complement Alternat Med. 2012;2012:193496.
Gonzales GF, Cordova A, Gonzales C, Chung A, Vega K, Villena A. Lepidium meyenii (Maca) improved semen parameters in adult men. Asian J Androl. 2001 Dec;3(4):301-3.
Dording CM, Fisher L, Papakostas G, et al. A doubleblind, randomized, pilot dose-finding study of maca root (L. meyenii) for the management of SSRI induced sexual dysfunction. CNS Neurosci Ther. 2008;14:182–191.
Gonzales GF, Gonzales C, Gonzales-Castañeda C. Lepidium meyenii (Maca): a plant from the highlands of Peru--from tradition to science. Forsch Komplementmed. 2009 Dec;16(6):373-80.
Gonzales GF, Córdova A, Vega K, Chung A, Villena A, Góñez C. Effect of Lepidium meyenii (Maca), a root with aphrodisiac and fertility-enhancing properties, on serum reproductive hormone levels in adult healthy men. J Endocrinol. 2003 Jan;176(1):163-8.
George A, Henkel R. Phytoandrogenic properties of Eurycoma longifolia as natural alternative to testosterone replacement therapy. Andrologia. 2014 Sep;46(7):708-21.
Pandit S, Biswas S, Jana U1, De RK, Mukhopadhyay SC, Biswas TK. Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers. Andrologia. 2016 Jun;48(5):570-5.
Biswas TK, Pandit S, Mondal S, Biswas SK, Jana U, Ghosh T, Tripathi PC, Debnath PK, Auddy RG, Auddy B. Clinical evaluation of spermatogenic activity of processed Shilajit in oligospermia. Andrologia. 2010 Feb;42(1):48-56.
Mishra RK, Jain A, Singh SK. Profertility effects of Shilajit on cadmium-induced infertility in male mice. Andrologia. 2018 Oct;50(8):e13064.