Moringa protein drink increases testosterone and anabolic status of men with hyperlipidemia: A randomized controlled study

Year 2021, Volume: 7 Issue: 1, 1 - 15, 31.03.2021

Ciara Angeli Juan

https://doi.org/10.31459/turkjkin.851832

Cited By: 1

Abstract

Testosterone is important in health, sexual function, body composition, and athletic performance. However, hormonal levels decrease with metabolic syndrome. Moringa oleifera, traditionally used as an aphrodisiac, has been shown to improve testosterone levels in metabolic syndrome. However, there is a dearth of studies on humans, and the mechanisms involved remain to be elucidated. This randomized, repeated measures study aims to determine if four-week supplementation of Moringa leaf powder in the form of a protein drink can improve resting levels of testosterone and related hormones, and whether any improvement translates to improved anabolic status during hypertrophy weight training. Relationships between hormonal levels and lipid profile were also explored. Three young men (28.33 ± 2.08) with hypercholesterolemia but normal testosterone levels were blood tested for hormonal levels and lipid profile at three time points: baseline, after Moringa supplementation, and after placebo supplementation. Pre-exercise and post-exercise testosterone and cortisol levels were measured on each testing day. Significant differences were found between Moringa and placebo in resting testosterone, anabolic status, and acute exercise-induced anabolic response. No significant difference was observed in any of the markers of lipid profile. Four-week supplementation of Moringa leaf powder in the form of a protein drink significantly increased resting testosterone and anabolic status in men with hyperlipidemia but with normal testosterone levels. Men with hyperlipidemia showed blunted anabolic response to a hypertrophy weight training protocol, which was attenuated by Moringa supplementation. Mechanisms may be independent of improvements in lipid profile.

Keywords

anabolic status, cortisol, exercise, moringa, testosterone, weight training

Supporting Institution

University of the Philippines Diliman, University of the Philippines Manila Research Ethics Board

Project Number

2020-530-01

References

• Abdelhalim, M. & Abdelhalim, K. (2010). The potential influence of high cholesterol diet-induced oxidative stress on composition and properties of red blood cells in rabbits. Afr J Microbiol Res, 4, 836-843.
• Ahtiainen, J.P., Pakarinen, A., Alen, M., Kraemer, & W.J., Häkkinen, K. (2003). Muscle hypertrophy, hormonal adaptations and strength development during strength training in strength-trained and untrained men. Eur J Appl Physiol, 89(6), 555-63.
• Alegbeleye, O.O. (2018). How functional is moringa oleifera? A review of its nutritive, medicinal, and socioeconomic potential. Food Nutr Bull, 39(1), 149–170.
• Allen, N.E., Appleby, P.N., Davey, G.K., Key, T.J. (2000). Hormones and diet: Low insulin-like growth factor-I but normal bioavailable androgens in vegan men. Br J Cancer, 83(1), 95–97.
• Anthanont, P., Lumlerdkij, N., Akarasereenont, P., Vannasaeng, S., Sriwijitkamol, A. (2016). Moringa Oleifera Leaf Increases Insulin Secretion after Single Dose Administration: A Preliminary Study in Healthy Subjects. J Med Assoc Thai, 99(3), 308-313.
• Antinozzi, C., Marampon, F., Corinaldesi, C., Vicini, E., Sgrò, P., Vannelli, G.B., Lenzi, A., Crescioli, C., & Di Luigi, L. (2017). Testosterone insulin-like effects: an in vitro study on the short-term metabolic effects of testosterone in human skeletal muscle cells. J Endocrinol Invest, 40(10), 1133–1143.
• Armstrong, L.E., Casa, D.J., Millard-Stafford, M.L., Morán, D.S., Pyne, S.W., & Roberts,W.O. (2007). American College of Sports Medicine Position Stand: Exertional heat illness during training and competition. Med Sci Sports Exerc, 39 (3), 556-72.
• Aybek, H., Aybek, Z., Rota, S., Şen, N., & Akbulut, M. (2008). The effects of diabetes mellitus, age, and vitamin E on testicular oxidative stress. Fertility & Sterility, 90(3), 755–760.
• Barichella, M., Pezzoli, G., Faierman, S.A., Raspini, B., Rimoldi, M., Cassani, E., Bertoli, S., Battezzati, A., Leone, A., Iorio, L., Ferri, V., Pinelli, G., Pusani, C., Bolliri, C., Cilia, R., Caronni, S., De Marco, P., & Cereda E. (219). Nutritional characterisation of Zambian Moringa oleifera: acceptability and safety of short-term daily supplementation in a group of malnourished girls. Int J Food Sci Nutr, 70(1), 107-115.
• Bedwal, R.S., & Bahuguna, A. (1994). Zinc, copper and selenium in reproduction. Experientia, 50(7), 626-640.
• Belcher, J.D., Balla, J., Balla, G., Jacobs, D.R. Jr, Gross, M., Jacob, H.S., & Vercellotti, G.M. (1993). Vitamin E, LDL, and endothelium. Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro. Arterioscler Thromb, 13(12), 1779-1789.
• Bethin, K.E., Vogt, S.K., Muglia, L.J. (2000) Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation. Proc Natl Acad Sci USA 97(16), 9317-22.
• Bianchi, V.E. (2018). The anti-inflammatory effects of testosterone. Journal of the Endocrine Society, 3(1), 91–107.
• Biswajit, R. (2013). Zinc and male reproduction in domestic animals: A review. Indian Journal of Animal Nutrition, 30(4), 339-350.
• Bosco, C., Colli, R., Bonomi, R., von Duvillard, S.P., Viru, A. (2000). Monitoring strength training: neuromuscular and hormonal profile. Med Sci Sports Exerc, 32(1), 202-8.
• Brownlee, K. K., Moore, A. W., & Hackney, A. C. (2005). Relationship between circulating cortisol and testosterone: influence of physical exercise. J Sports Sci Med, 4(1),76–83.
• Chen, S., Jiang, H., Wu, X., & Fang, Jet. (2016). Therapeutic Effects of Quercetin on Inflammation, Obesity, and Type 2 Diabetes. Mediators Inflamm, 2016, 9340637.
• Coffey, V.G., Zhong, Z., Shield, A., Canny, B.J., Chibalin, A.V., Zierath, J.R., & Hawley, J.A. (2006) Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans. The FASEB Journal, 20, 190–192.
• Crewther, B., Cronin, J., Keogh, J., & Cook, C. (2008). The salivary testosterone and cortisol response to three loading schemes. J Strength Cond Res, 22(1), 250–255.
• Crewther, B., Keogh, J., Cronin, J., & Cook, C. (2006). Possible stimuli for strength and power adaptation: acute hormonal responses. Sports Med, 36(3), 215-238.
• Crewther, B.T., Carruthers, J., Kilduff, L.P., Sanctuary, C.E., & Cook, C.J. (2016). Temporal associations between individual changes in hormones, training motivation and physical performance in elite and non-elite trained men. Biology of Sport, 33(3), 215–221.
• Csonka, C., Sárközy, M., Pipicz, M., Dux, L., & Csont. T. (2016). Modulation of hypercholesterolemia-induced oxidative/nitrative stress in the heart. Oxidative Medicine and Cellular Longevity, 2016.
• Culty, M., Luo, L., Yao, Z.X., Chen, H., Papadopoulos, V., & Zirkin, B.R. (2002). Cholesterol transport, peripheral benzodiazepine receptor, and steroidogenesis in aging Leydig cells. J Androl, 23(3), 439-447.
• Dachana, K., Rajiv, J., Indrani, D. & Prakash, J. (2010). Effect of dried moringa (moringa oleifera lam) leaves on rheological, microstructural, nutritional, textural and organoleptic characteristics of cookies. J Food Qual, 33, 660-677.
• Das, N., Ganguli, D., & Dey, S. (2015). Moringa oleifera Lam. seed extract prevents fat diet induced oxidative stress in mice and protects liver cell-nuclei from hydroxyl radical mediated damage. Indian J Exp Biol, 53(12):794-802.
• Diemer, T., Allen, J.A., Hales, K.H., & Hales, D.B. (2003). Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis. Endocrinology,144(7), 2882-2891.
• Eacker, S.M., Agrawal, N., Qian K., Dichek, H.L., Gong, E.Y., Lee, K., Braun, R.E. (2008). Hormonal regulation of testicular steroid and cholesterol homeostasis. Molecular Endocrinology, 22(3), 623–635.
• Eid, H.M., Martineau, L.C., Saleem, A., Muhammad, A., Vallerand, D., Benhaddou-Andaloussi, A., Nistor, L., Afshar, A., Arnason, J.T., & Haddad, P.S. (2010). Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea. Mol Nutr Food Res, 54(7), 991-1003.
• Eid, H.M., Nachar, A., Thong, F., Sweeney, G., & Haddad, P.S. (2015). The molecular basis of the antidiabetic action of quercetin in cultured skeletal muscle cells and hepatocytes. Pharmacogn Mag, 11(41), 74-81.
• Emanuel, A. S., McCully, S. N., Gallagher, K. M., & Updegraff, J. A. (2012). Theory of planned behavior explains gender difference in fruit and vegetable consumption. Appetite, 59(3), 693–697.
• Fallah, A., Mohammad-Hasani, A., Colagar, A. H. (2018). Zinc is an essential element for male fertility: A review of ZN roles in men's health, germination, sperm quality, and fertilization. J Reprod Infertil, 19(2), 69–81.
• Farrelly, D., Owens, R., Elliott, H., Walden, H., & Wetherell, M. (2015). The effects of being in a "new relationship" on levels of testosterone in men. Evol Psychol, 13(1), 250-261.
• Febbraio, M.A., Hiscock, N., Sacchetti, M., Fischer, C.P., & Pedersen, B.K. (2004) Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction. Diabetes 53(7), 1643-1648.
• Feldman, H.A., Longcope, C., Derby, C.A., Johannes, C.B., Araujo, A.B., Coviello, A.D., Bremner, W.J., & McKinlay, J.B. (2002). Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab, 87(2), 589-598.
• Fuhrman, B. & Aviram, M. (2001). Flavonoids protect LDL from oxidation and attenuate atherosclerosis. Curr Opin Lipidol, 12(1), 41-48.
• Ganatra, T. H., Umang, H. J., Payal, N. B., Tusharbindu, R. D., & Pravin, R. T. (2012). A panoramic view on pharmacognostic, pharmacological, nutritional, therapeutic and prophylactic values of Moringa oleifera. International Research Journal of Pharmacy, 3(6), 1–7.
• Gar, C., Rottenkolber, M., Haenelt, M., Potzel, A.L., Kern-Matschilles, S., Then, C., Seissler, J., Bidlingmaier, M., & Lechner, A. (2020). Altered metabolic and hormonal responses to moderate exercise in overweight/obesity. Metabolism, 107.
• Gargaglioni, L. H., & Marques, D. A. (2020). Let's talk about sex in the context of COVID-19. J Appl Physiol, 128(6), 1533–1538.
• Geisler, S., Aussieker, T., Paldauf, S., Scholz, S., Kurz, M., Jungs, S., Rissmeyer, M., Achtzehn, S., & Zinner C. (2019). Salivary testosterone and cortisol concentrations after two different resistance training exercises. J Sports Med Phys Fitness, 59(6), 1030-1035.
• Giagulli, V.A., Guastamacchia, E., Magrone, T., Jirillo, E., Lisco, G., De Pergola, G., & Triggiani V. (2021). Worse progression of COVID-19 in men: Is testosterone a key factor? Andrology, 9(1), 53-64.
• Gleicher, S., Daugherty, M., Ferry, E., & Byler, T. (2020). Looking beyond hypogonadism: Association between low testosterone and metabolic syndrome in men 20–59 years. Int Urol Nephrol, 52(12), 2237–2244.
• Glover‐Amengor, M., Aryeetey, R., Afari, E. and Nyarko, A. (2017), Micronutrient composition and acceptability of Moringa oleifera leaf‐fortified dishes by children in Ada‐East district, Ghana. Food Sci Nutr, 5, 317-323.
• Gopalakrishnan, L. et al. (2016). Moringa oleifera: A review on nutritive importance and its medicinal application. Food Sci Hum Well, 5(2), 49-56.
• Goswami, S. K., Inamdar, M. N., Dethe, S. M., Gururaj, G. M., Jamwal, R., Bhaskar, A., Mundkinajeddu, D., and Agarwal, A. (2016) Erectogenic and Aphrodisiac Property of Moringa oleifera: Involvement of soluble epoxide hydrolase enzyme. Phytother Res, 30, 1119– 1127.
• Gupta, R., Mathur, M., Bajaj, V.K., Katariya, P., Yadav, S., Kamal, R., & Gupta, R.S. (2012). Evaluation of antidiabetic and antioxidant activity of Moringa oleifera in experimental diabetes. J Diabetes, 4(2), 164-171.
• Hackney, A. C., & Walz, E. A. (2013). Hormonal adaptation and the stress of exercise training: the role of glucocorticoids. Trends Sport Sci, 20(4), 165–171.
• Han, B., Yu, Y. Q., Yang, Q. L., Shen, C. Y., & Wang, X. J. (2017). Kaempferol induces autophagic cell death of hepatocellular carcinoma cells via activating AMPK signaling. Oncotarget, 8(49), 86227–86239.
• Harman, M., Metter, J., Tobin, J., Pearson, J., Blackman, M. (2001). Longitudinal effects of aging on serum total and free testosterone levels in healthy men. The J Clin Endocrinol Metab, 86(2), 724–731.
• Hoffmann, C. & Weigert, C. (2017). Skeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations. Cold Spring Harb Perspect Med, 7(11), a029793.
• Hollman, P.C., van Trijp, J.M., Mengelers, M.J., de Vries, J.H., & Katan, M.B. (1997). Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Lett, 114(1-2), 139-140.
• Idohou-Dossou, N., Diouf, A. Gueye, A.L., Guiro, A.T., & Wade, S. (2011). Impact of daily consumption of Moringa (Moringa oleifera) dry leaf powder on iron status of Senegalese lactating women. African Journal of Food, Agriculture, Nutrition and Development, 11(4), 4985-4999.
• Ieronymaki, E., Ieronymaki, E., Daskalaki, M.G., Lyroni, K., & Tsatsanis, C. (2019). Insulin signaling and insulin resistance facilitate trained immunity in macrophages through metabolic and epigenetic changes. Frontiers in Immunology, 10, 1330.
• Jalali, G.R., Roozbeh, J., Mohammadzadeh, A., Sharifian, M., Sagheb, M.M., Hamidian Jahromi, A., Shabani, S., Ghaffarpasand, F., & Afshariani, R. (2010). Impact of oral zinc therapy on the level of sex hormones in male patients on hemodialysis. Ren Fail, 32(4), 417-419.
• Juan, C.A. (2019). Acute weight training-induced testosterone responses of trained males across age groups and diets: A pilot study. J Eurasia Sports Sci Med, 1(2), 79-93.
• Karthikesan, K., Pari, L., & Menon, V.P. (2010). Antihyperlipidemic effect of chlorogenic acid and tetrahydrocurcumin in rats subjected to diabetogenic agents. Chem Biol Interact, 188(3), 643-50.
• Kelly, D. M., Akhtar, S., Sellers, D. J., Muraleedharan, V., Channer, K. S., & Jones, T. H. (2016). Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse. Endocrine, 54(2), 504–515.
• Kelly, D.M., & Jones, T.H. (2013). Testosterone: A metabolic hormone in health and disease. J Endocrinol, 217(3), R25-45.
• Kraemer, W.J., Häkkinen, K., Newton, R.U., McCormick, M., Nindl, B.C., Volek, J.S., Gotshalk, L.A., Fleck, S.J., Campbell, W.W., Gordon, S.E., Farrell, P.A., & Evans, W.J. (1998). Acute hormonal responses to heavy resistance exercise in younger and older men. Eur J Appl Phvsiol, 77, 206-211.
• Kraemer, W.J., Ratamess, N. A., Hymer, W.C., Nindl, B.C., & Fragala, M.S. (2020). Growth hormone(s), testosterone, insulin-like growth factors, and cortisol: Roles and integration for cellular development and growth with exercise. Frontiers in Endocrinology, 11, 33.
• Kumagai, H., Zempo-Miyaki, A., Yoshikawa, T., Tsujimoto, T., Tanaka, K., & Maeda, S. (2016). Increased physical activity has a greater effect than reduced energy intake on lifestyle modification-induced increases in testosterone. J Clin Biochem Nutr, 58(1), 84–89.
• Kumar, N., Verma, R.P., Singh, L.P., Varshney, V.P., & Dass R.S. (2006). Effect of different levels and sources of zinc supplementation on quantitative and qualitative semen attributes and serum testosterone level in crossbred cattle (Bos indicus × Bos taurus) bulls. Reprod Nutr Dev, 46, 663–675.
• Kumari, D.J. (2010). Hypoglycaemic effect of Moringa oleifera and Azadirachta indica in type 2 diabetes mellitus. Bioscan 5, 211–214.
• Lako, J., Trenerry, V.C., Wahlqvist, M., Wattanapenpaiboon, N., Sotheeswaran, S., & Premier, R.. (2007). Phytochemical flavonols, carotenoids and the antioxidant properties of a wide selection of Fijian fruit, vegetables and other readily available foods. Food Chem, 101(4), 1727–1741.
• Leone, A., Spada, A., Battezzati, A., Schiraldi, A., Aristil, J., & Bertoli, S. (2015). Cultivation, Genetic Ethnopharmacology, Phytochemistry, and Pharmacology of Moringa oleifera Leaves: An Overview. Int J Mol Sci, 16(6), 12791-835.
• Leproult, R., & Van Cauter, E. (2011). Effect of 1 week of sleep restriction on testosterone levels in young healthy men. JAMA, 305(21), 2173–2174.
• Loke, W.M. et al. (2008). Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem, 56(10), 3609-3615.
• Lopes, J., Araujo, S.S., Estevam, C.S., Lima, C.A., Carvalho, C.R.O., Lima, F.B., Marcal, A.C. (2017). Molecular Mechanisms of Muscle Glucose Uptake in Response to Resistance Exercise: A Review. JEPonline, 20(4), 200-211.
• Lunenfeld, B., Arver, S., Moncada, I., Rees, D. A., & Schulte, H. M. (2012). How to help the aging male? Current approaches to hypogonadism in primary care. Aging Male, 15(4), 187–197.
• Majumdar, P., & Srividhya Jr., S. (2010). Monitoring training load in Indian male swimmers. Int J Exerc Sci, 3(3), 102–107.
• Martínez-Martos, J.M., Arrazola, M., Mayas, M.D., Carrera-González, M.P., García, M.J., Ramírez-Expósito, M.J. (2011). Diet-induced hypercholesterolemia impaired testicular steroidogenesis in mice through the renin-angiotensin system. Gen Comp Endocrinol 173(1), 15-9.
• Maso, F., Lac, G., Filaire, E., Michaux, O., Robert, A. (2004). Salivary testosterone and cortisol in rugby players: correlation with psychological overtraining items. Br J Sports Med, 38(3), 260-3.
• Mbikay, M. (2012). Therapeutic potential of moringa oleifera leaves in chronic hyperglycemia and dyslipidemia: A review. Frontiers in Pharmacology, 3, 24.
• McMurray, R.G. & Hackney, A.C. (2005). Interactions of metabolic hormones, adipose tissue and exercise. Sports Med, 35, 393–412.
• Miller, W.L., & Bose, H.S. (2011). Early steps in steroidogenesis: intracellular cholesterol trafficking. J Lipid Res, 52(12), 2111–2135.
• Mohamed, M.A. (2019). Molecular effects of Moringa leaf extract on insulin resistance and reproductive function in hyperinsulinemic male rats. Journal of Diabetes and Metabolic Disorders, 18, 487-494.
• Mohamed, M.S., Moulin, T.C. & Schiöth, H.B. (2020). Sex differences in COVID-19: The role of androgens in disease severity and progression. Endocrine, 71(1), 3-8.
• Mulligan, T., Frick, M.F., Zuraw, Q.C., Stemhagen, A., & McWhirter, C. (2006). Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract, 60(7), 762-769.
• Munawar, M. et al. (2019). Depleted levels of testosterone instigated by statins in patients with hyperlipidemia can be avoided if substituted by moringa leaves. International Journal of Biology, Pharmacy, and Allied Sciences, 8(10), 1908-1915.
• Muraleedharan, V., & Jones, T.H. (2010). Testosterone and the metabolic syndrome. Ther Adv Endocrinol Metab, 1(5), 207–223.
• Nagata, C., Takatsuka, N., Shimizu, H., Hayashi, H., Akamatsu, T., & Murase, K. (2001). Effect of soymilk consumption on serum estrogen and androgen concentrations in Japanese men. Cancer Epidemiol Biomarkers Prev, 10(3), 179-184.
• Nambiar, V.S., Guin, P., Parnami, S. & Daniel, M. (2010). Impact of antioxidants from drumstick leaves on the lipid profile of hyperlipidemics. Journal of Herbal Medicine and Toxicology 4,165–172.
• Ndong, M., Uehara, M., Katsumata, S., & Suzuki, K. (2007). Effects of oral administration of Moringa oleifera on glucose tolerance in Goto-Kakizaki and Wistar rats. J Clin Biochem Nutr, 40, 229–233.
• Ogunsola, O.A., Owolabi, J.O., Fabiyi, O.S., Nwobi, N.L., Faluyi, B., & Akinbola, A.S. (2017). Moringa plant parts consumption had effects on reproductive functions in male and female rat models. Journal of Dental and Medical Sciences, 16, 82-86.
• Olayaki, L.A., Irekpita, J.E., Yakubu, M.T., Ojo, O.O. (2015). Methanolic extract of Moringa oleifera leaves improves glucose tolerance, glycogen synthesis and lipid metabolism in alloxan-induced diabetic rats. J Basic Clin Physiol Pharmacol, 26(6), 585-593.
• Omi, N., Shiba, H., Nishimura, E., Tsukamoto, S., Maruki-Uchida, H., Oda, M., & Morita, M. (2019) Effects of enzymatically modified isoquercitrin in supplementary protein powder on athlete body composition: a randomized, placebo-controlled, double-blind trial. J Int Soc Sports Nutr 16(1), 39.
• Ong, K.W., Hsu, A., Tan, B.K. (2013). Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by AMPK activation. Biochem Pharmacol, 85(9), 1341-1351.
• Paula, P.C., Oliveira, J.T., Sousa, D.O., Alves, B.G.T., Carvalho, A.F.U., Franco, O.L., & Vasconcelos, I.M. (2017). Insulin-like plant proteins as potential innovative drugs to treat diabetes. The Moringa oleifera case study. N Biotechnol, 39, 99–109.
• Pitteloud, N. (2005). Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care, 28(7), 1636-1642.
• Pivonello R., Menafra D, Riccio, E., Garifalos, F., Mazzella, M., de Angelis, C., & Colao, A. (2019). metabolic disorders and male hypogonadotropic hypogonadism. Front Endocrinol, 10, 345.
• Pozzilli, P. & Lenzi, A. (2020). Testosterone, a key hormone in the context of COVID-19 pandemic. Metabolism, 108, 154252.
• Prabsattroo, T., Wattanathorn, J., Iamsaard, S., Somsapt, P., Sritragool, O., Thukhummee, W., & Muchimapura, S. (2015). Moringa oleifera extract enhances sexual performance in stressed rats. Journal of Zhejiang University. Science. B, 16(3), 179–190.
• Proschinger, S. & Freese, J. (2019). Neuroimmunological and neuroenergetic aspects in exercise-induced fatigue. Exerc Immunol Rev 25, 8-19.
• Randle, P.J., Garland, P.B., Hales, C.N. & Newsholme, E.A. (1963). The glucose fatty-acid cycle: Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet, 1, 785–789.
• Rao, P.M., Kelly, D.M., Jones, T.H. (2013). Testosterone and insulin resistance in the metabolic syndrome and T2DM in men. Nat Rev Endocrinol, 9(8), 479-493.
• Rasmussen, J. J., Selmer, C., Østergren, P. B., Pedersen, K. B., Schou, M., Gustafsson, F., Faber, J., Juul, A., & Kistorp, C. (2016). Former abusers of anabolic androgenic steroids exhibit decreased testosterone levels and hypogonadal symptoms years after cessation: a case-control study. PloS One, 11(8), e0161208.
• Ratamess, N.A., Kraemer, W.J., Volek, J.S., Maresh, C.M., Vanheest, J.L., Sharman, M.J., Rubin, M.R., French, D.N., Vescovi, J.D., Silvestre, R., Hatfield, D.L., Fleck, S.J., Deschenes, M.R. (2005). Effects of heavy resistance exercise volume on post-exercise androgen receptor. J Steroid Biochem Molec, 93, 35-42.
• Riggio, O., Ariosto, F., Merli, M., Caschera, M., Zullo, A., Balducci, G., Ziparo, V., Pedretti, G., Fiaccadori, F., Bottari, E., et al. (1991). Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial. Dig Dis Sci, 36(9), 1204-1208.
• Roelfsema, F., Yang, R.J., Liu, P.Y., Takahashi, P.Y., & Veldhuis, J.D. (2018). Feedback on LH in Testosterone-Clamped Men Depends on the Mode of Testosterone Administration and Body Composition. Journal of the Endocrine Society, 3(1), 235–249.
• Sarkola, T., Eriksson, C.J. (2003). Testosterone increases in men after a low dose of alcohol. Alcohol Clin Exp Res, 27(4), 682-5.
• Sattler, F., He, J., Chukwuneke, J., Kim, H., Stewart, Y., Colletti, P., Yarasheski, K.E., & Buchanan, T.A. (2014). Testosterone supplementation improves carbohydrate and lipid metabolism in some older men with abdominal obesity. J Gerontol Geriatr Res, 3(3), 1000159.
• Saxe, G. A., Major, J. M., Westerberg, L., Khandrika, S., & Downs, T. M. (2008). Biological mediators of effect of diet and stress reduction on prostate cancer. Integrative Cancer Therapies, 7(3), 130–138.
• Sellami M, Dhahbi W, Hayes LD, Kuvacic G, Milic M, Padulo J. (2018). The effect of acute and chronic exercise on steroid hormone fluctuations in young and middle-aged men. Steroids, 132, 18-24.
• Steensberg, A., Fischer, C.P., Keller, C., Møller, K., Pedersen, B.K. (2003) IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 285(2), E433-7.
• Stohs, S. J., & Hartman, M. J. (2015). Review of the Safety and Efficacy of Moringa oleifera. Phytotherapy Research, 29(6), 796–804.
• Suarni, N.M., Oka, I.G.L., Mahardika, I.G., Suyadnya, I.P. (2019). Testosterone level and mating capability of male rabbit fed commercial feed substituted with moringa oleifera leaf meal. IOP Conference Series, 347(1).
• Syarifuddin, N.A., Toleng, A.L., Rahardja, D.P., Ismartoyo, I., & Yusuf, M. (2017). Improving libido and sperm quality of Bali bulls by supplementation of moringa oleifera leaves. Media Peternakan, 40(2), 88-93.
• Tanaka, M., Nakaya, S., Kumai, T., Watanabe, M., Matsumoto, N., Kobayashi, S. (2001). Impaired testicular function in rats with diet-induced hypercholesterolemia and/or streptozotocin-induced diabetes mellitus. Endocr Res 27(1-2), 109-17.
• Tang, Y., Choi, E.J., Han, W.C., Oh, M., Kim, J., Hwang, J.Y., Park, P.J., Moon, S.H., Kim, Y.S., & Kim, E.K. (2017). moringa oleifera from cambodia ameliorates oxidative stress, hyperglycemia, and kidney dysfunction in type 2 diabetic mice. J Med Food, 20(5), 502-510.
• Thirumalai, A., Rubinow, K.B., & Page, S.T. (2015). An update on testosterone, HDL and cardiovascular risk in men. Clinical Lipidology, 10(3), 251–258.
• Tshingani, K., Donnen, P., Mukumbi, H., Duez, P., & Dramaix-Wilmet, M. (2017). Impact of Moringa oleifera lam. Leaf powder supplementation versus nutritional counseling on the body mass index and immune response of HIV patients on antiretroviral therapy: a single-blind randomized control trial. BMC Complement Altern Med, 22, 17(1), 420.
• Vaamonde, D., Da Silva-Grigoletto, M.E., García-Manso, J.M., Barrera, N., & Vaamonde-Lemos, R. (2012). Physically active men show better semen parameters and hormone values than sedentary men. Eur J Appl Physiol, 112(9), 3267-73.
• Van Anders, S.M. & Watson, N.V. (2006). Relationship status and testosterone in North American heterosexual and non-heterosexual men and women: Cross-sectional and longitudinal data. Psychoneuroendocrinology, 31(6), 715-723.
• Vargas, N.T. & Marino, F. (2014) A neuroinflammatory model for acute fatigue during exercise. Sports Med, 44(11), 1479-1487.
• Vargas-Sánchez, K., Garay-Jaramillo, E., & González-Reyes, R. E. (2019). Effects of Moringa oleifera on Glycaemia and Insulin Levels: A Review of Animal and Human Studies. Nutrients, 11(12), 2907.
• Villaruel-López, A., López-de la Mora, D., Vasquez-Paulino, O., Puebla-Mora, A., Torres-vitela, M., Guerrero-Quiroz, L., Nuño, K. (2018). Effect of Moringa oleifera consumption on diabetic rats. BMC Complement Altern Med, 18, 127.
• Wambier, C.G. & Goren, A. (2020). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J Am Acad Dermatol, 83(1), 308–309.
• Wang, W., Yang, X., Liang, J., Liao, M., Zhang, H., Qin, X., Mo, L., Lv, W., & Mo, Z. (2013). Cigarette smoking has a positive and independent effect on testosterone levels. Hormones (Athens), 12(4), 567-77.
• Waterman, C., Rojas-Silva, P., Tumer, T.B., Kuhn, P., Richard, A.J., Wicks, S., Stephens, J.M., Wang, Z., Mynatt, R., Cefalu, W., & Raskin, I. (2015). Isothiocyanate-rich Moringa oleifera extract reduces weight gain, insulin resistance, and hepatic gluconeogenesis in mice. Mol Nutr Food Res, 59(6), 1013–1024.
• Wong, T., Harber, V. (2006). Lower excess postexercise oxygen consumption and altered growth hormone and cortisol responses to exercise in obese men. J Clin Endocrinol Metab, 91(2), 678-86.
• Xiao, J., Huang, W.H., Peng, J.B., Tan, Z.R., Ou-Yang, D.S., Hu, D.L., Zhang, W., & Chen, Y. (2014). Quercetin significantly inhibits the metabolism of caffeine, a substrate of cytochrome P450 1A2 unrelated to CYP1A2*1C  (-2964G>A) and *1F (734C>A) gene polymorphisms. Biomed Res Int, 2014, 405071.
• Xu, Y.B., Chen, G.L., Guo, M.Q. (2019). Antioxidant and anti-inflammatory activities of the crude extracts of moringa oleifera from Kenya and their correlations with flavonoids. Antioxidants (Basel), 8(8), 296.
• Yang, J., Zhang, X., Liu, Z., Yuan, Z., Song, Y., Shao, S., Zhou, X., Yan, H., Guan, Q., Gao, L., Zhang, H., Zhao, J. (2016). High-cholesterol diet disrupts the levels of hormones derived from anterior pituitary basophilic cells. J Neuroendocrinol, 28(3), 12369.
• Yassa, H.D. & Tohamy, A.F. (2014). Extract of Moringa oleifera leaves ameliorates streptozotocin-induced Diabetes mellitus in adult rats. Acta Histochem, 116(5), 844-854.
• Yu, C., Jiang, F., Zhang, M., Luo, D., Shao, S., Zhao, J., Gao, L., Zuo, C., & Guan, Q. (2019). HC diet inhibited testosterone synthesis by activating endoplasmic reticulum stress in testicular Leydig cells. J Cell Mol Med 23(5), 3140-3150.
• Zade, V., Dabhadkar, D., Thakare, V., Pare, S. (2013). Evaluation of potential aphrodisiac activity of Moringa oleifera seed in male Albino rats. International Journal of Pharmacy and Pharmaceutical Sciences, 5, 683-689.
• Zhao, J.L., Zhao, Y.Y., Zhu, W.J. (2017). A high-fat, high-protein diet attenuates the negative impact of casein-induced chronic inflammation on testicular steroidogenesis and sperm parameters in adult mice. Gen Comp Endocrinol 252, 48-59.