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Men’s Sexual Health – Testosterone and Nitric Oxide Modulation

Men’s Sexual Health: Testosterone & Nitric Oxide Modulation

As men age, there is often a decline in libido and sexual function, which frequently interferes with intimacy in romantic relationships and has emotional ramifications, while also eroding self-confidence and quality of life. This has set the groundwork for the popularity of nitric oxide (NO)-enhancing drugs such as Viagra and Cialis, and consumer awareness of prescription testosterone (T) availability courtesy of the low “T” commercials. Here we’ll discuss the etiology of male sexual decline and the potential benefits offered by non-prescription alternatives.

Sexual Decline

Healthy sexual function is a multi-factoral process requiring (at least) healthy circulation, healthy hormone production, adequate energy levels and proper mental/emotional well-being. Unfortunately, aging and unhealthy lifestyle practices can negatively influence one or more of these processes.

In the case of T, a reduction in its production is common and implicated in reduced libido and sexual function. Research1 indicates that T levels in men fall progressively with age and that a significant percentage of men over the age of 60 years have serum T levels that are below the lower limits of young adult men (age 20 to 30 years). Some studies2 show that men experience a gradual and progressive decline in total T levels that takes place at a rate of approximately one percent per year beginning in their 30s, while other studies3 show an average annual decline of one to two percent total T levels, with an even more rapid decline in free T.

With regard to circulation, consider how it is affected by poor diet and lack of exercise. Beyond ramifications on cardiovascular and cerebrovascular health, poor circulation may also translate into an inadequate blood supply to the genital region, making it difficult to achieve and maintain an erection. Furthermore, inadequate endogenous production of the biochemical NO can exacerbate this problem since adequate NO is necessary for vasodilatation of blood vessels and, consequently, erectile function.

Testosterone Modulation

While there are many nutraceuticals on the market with claims to increase T levels, I have found that much of the human clinical research to support those claims is inadequate or in some cases non-existent. Three exceptions are the herb Eurycoma longifolia Jack, vitamin D and zinc.

• E. longifolia Jack (aka, Tongkat Ali or Long Jack) is a medicinal herb of South-East Asian origin (especially Malaysia, Thailand and Indonesia), traditionally used for its aphrodisiac activity to enhance male sexual performance.4-8 Modern scientific research has also demonstrated this benefit, apparently as a result of increasing serum T levels. 9,10 However, it is significant to note that the human clinical research has been done on a specific proprietary extract known as LJ100. This is important since the LJ100 extract of E. longifolia has been standardized for eurypeptides, naturally-occurring compounds which may be the active phytochemicals in E. longifolia, or at least serve as a marker for extract quality.

Human clinical studies on LJ100 have been conducted at different dosage levels, but 200 mg/day showed the most benefits. Studies included both controlled trials and open-label trials. It will not be possible to provide a detailed review all of the studies; however, here is a synopsis of the research results:

• Depending on the study, T increased 16.4-71.5 percent 11-13

• Depending on the study, cortisol decreased 16-32 percent14,11

• DHEA increased 47 percent9

• Sexual health scores improved significantly10,15, as much as 91 percent9

It appears that at least one of the mechanisms of action for LJ100 is the reduction of sex hormone-binding globulin (SHBG) levels. SHBG is a glycoprotein that binds to sex hormones. While bound to SHBG, T cannot bind to cellular androgen receptors—which means that it won’t have any of the valuable effects of T in this form. Of course, SHBG-bound T can be unbound, but it can take a while for this to happen. Furthermore, SHBG levels increase as we age.2 In one of the studies, LJ100 was shown to reduce SHBG levels in 36 percent of the cases after one week, and 66 percent after three weeks.9

• Vitamin D deficiency is present outright in 41.6 percent of the U.S. population16, while vitamin D insufficiency (i.e., lacking sufficient vitamin D) is present in 77 percent of the population.17 This is alarming considering that new studies are constantly being conducted that demonstrate a broad range of important functions that vitamin D performs in human health, including its role in maintaining healthy T levels.

Three different cross-sectional studies including thousands of men have demonstrated that higher vitamin D levels are associated with higher levels of T (especially free T), and lower levels of estrogen and SHBG in men.18-20 In regard to supplementation research, 54 healthy overweight men undergoing a weight reduction program participated in a randomized controlled trial.21

Participants received either 3,332 IU vitamin D daily for one year or placebo. Initially, vitamin D concentrations were in the deficiency range and T values were at the lower end of the reference range. The results were that in the vitamin D group, there was a significant 25 percent increase total T levels. By contrast, there was no significant change in any T measure in the placebo group.

• Zinc deficiency is prevalent throughout the world, including the U.S.22,23 This is problematic since zinc has been reported to have roles in the synthesis, transport and peripheral action of hormones. In fact, low dietary zinc status has been associated with low circulating concentrations of several hormones including T.24 Conversely, research25 has shown that male subjects with normal T levels had a significantly higher zinc level compared to those with low T levels. Zinc supplementation in marginally zinc-deficient normal elderly men for six months resulted in close to a doubling of serum T levels.26 In addition, research27 has shown that zinc supplementation prevented a decrease in T levels after exercising, and men undergoing hemodialysis28-30 or who had sickle cell anemia31 were able to maintain higher T levels when supplementing with zinc.

NO Enhancement

The amino acid L-arginine is a precursor (building material) for the synthesis of NO.32 Supplemental sources of L-arginine appear to augment NO production33, with the result being a measurable increase in blood flow34 (i.e., vasodilatation). Since penile erection requires the relaxation of the cavernous smooth muscle, which is triggered by NO, it might be expected that supplementation with L-arginine would help promote erectile function. In fact, this is the case.

Studies have shown that when supplementing with L-arginine in doses of 5 g35 or 2.8 g36 daily, men with erectile dysfunction (ED) or impotence experienced significant improvements in erectile function. These studies found that subjects were either responders or nonresponders (presumably based upon their levels of NO (i.e., those with low NO would be responders). The responders experienced significant improvements in sexual function.

Conclusion

Although the use of prescription drugs may offer a viable treatment for ED, there are alternatives with a high safety profile that may also offer an effective solution. It may make sense to experiment with supplements first to see if results are forthcoming before turning to medications, which are not without adverse effects.

References:

1 Wang C, Nieschlag E, Swerdloff R, Behre HM. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol. 2008;159:507–514.

2 Matsumoto AM. Andropause: Clinical Implications of the Decline in Serum Testosterone Levels With Aging in Men. Journal of Gerontology. 2002. 57A(2):M76–M99.

3 Araujo AB, Wittert GA. Endocrinology of the Aging Male. Best Pract Res Clin Endocrinol Metab. 2011 April ; 25(2): 303–319.

4 Bhat R, Karim AA. Tongkat Ali (Eurycoma longifolia Jack): a review on its ethnobotany and pharmacological importance. Fitoterapia. 2010 Oct;81(7):669-79.

5 Ramawat KG (Ed.). Herbal Drugs: Ethnomedicine to Modern Medicine. Heidelberg: Springer-Verlag;2009:76.

6 Handa SS, Rakesh DD, Vasisht K. Compendium of Medicinal and Aromatic Plants – Volume II: Asia. Trieste, Italy: ICS-UNIDO; 2006:81.

7 Singh R, Singh S, Jeyabalan G, Ali A. An Overview on Traditional Medicinal Plants as Aphrodisiac Agent. Journal of Pharmacognosy and Phytochemistry. 2012;1(4):43-56.

8 Samuel AJ, Kalusalingam A, Chellappan DK, Gopinath R, Radhamani S, Husain HA, Muruganandham V, Promwichit P. Ethnomedical survey of plants used by the Orang Asli in Kampung Bawong, Perak, West Malaysia. J Ethnobiol Ethnomed. 2010 Feb 7;6:5.

9 Tambi MIM, Saad JM. Water-soluble extract of Eurycoma longifolia Jack soluble extract as a potential natural energizer for healthy aging men. Specialist Reproductive Research Center, National Population & Family Development Board, Ministry of Women & Family Development, Malaysia. 2000:9 pgs.

20 Tambi MI. Nutrients and Botanicals for optimizing Men’s Health. Examining the evidence for Eurycoma longifolia longjack, the Malaysian Ginseng in men’s health. Asian Journal of Andrology. 2009;11(5 suppl):37-38.

11 Talbott S, Talbott J, Negrete J, Jones M, Nichols M, and Roza J. Poster 32: Effect of Eurycoma longifolia Extract on Anabolic Balance During Endurance Exercise. JISSN. 2006;3(1)S32.

32 Talbott SM, Talbott JA, George A, Pugh M. Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects. JISSN.2013;10:28.

43 LJ100® Saliva Testosterone Test. Unpublished report. HP Ingredients. Bandenton, PL. Retrieved August 24, 2012 from www.hpingredients.com/lj100_human_clinical_research.htm.

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65 Tambi MIBM, Imran MK, Henkel RR. Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster for managing men with late-onset hypogonadism? Andrologia. 2012;44:226–230.

16 Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48-54.

17 Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009;169:626-32.

18 Nimptsch K, Platz EA, Willett WC, Giovannucci E. Association between plasma 25-OH vitamin D and testosterone levels in men. Clin Endocrinol (Oxf). 2012 Jan 2. Doi: 10.1111/j.1365-2265.2012.04332.x. [Epub ahead of print].

19 Lee DM, Tajar A, Pye SR, et al. Association of hypogonadism with vitamin D status: the European Male Ageing Study. Eur J Endocrinol. 2012 Jan;166(1):77-85.

20 Wehr E, Pilz S, Boehm BO, März W, Obermayer- Pietsch B. Association of vitamin D status with serum androgen levels in men. Clin Endocrinol (Oxf). 2010 Aug;73(2):243-8.

21 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.
Horm Metab Res. 2011 Mar;43(3):223-5.

22 Prasad AS, Fitzgerald JT, Hess JW, et al. Zinc deficiency in elderly patients. Nutrition. 1993;9:218.

23 Prasad AS. Clinical spectrum and diagnostic aspects of human zinc deficiency. In: Prasad AS, ed. Essential and toxic trace elements in human health and disease. New York: Alan R. Liss; 1988:3.

24 Food and Nutrition Board, Institute of Medicine. Zinc. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, D.C.: National Academy Press; 2001:442-501.

25 Chang CS, Choi JB, Kim HJ, Park SB. Correlation between serum testosterone level and concentrations of copper and zinc in hair tissue. Biol Trace Elem Res. 2011 Dec;144(1-3):264-71.

26 Prasad AS, Mantzoros CS, Beck FW, Hess JW, Brewer GJ. Zinc status and serum testosterone levels of healthy adults. Nutrition. 1996 May;12(5):344-8.

27 Kilic M. in sedentary males supplemented with oral zinc. Neuro Endocrinol Lett. 2007 Oct;28(5):681-5.

28 Jalali GR, Roozbeh J, Mohammadzadeh A, et al. Impact of oral zinc therapy on the level of sex hormones in male patients on hemodialysis. Ren Fail. 2010 May;32(4):417-9.

29 Mahajan SK, Abbasi AA, Prasad AS, Rabbani P, Briggs WA, McDonald FD. Effect of oral zinc therapy on gonadal function in hemodialysis patients. A double-blind study. Ann Intern Med. 1982 Sep;97(3):357-61.

30 Antoniou LD, Shalhoub RJ, Sudhakar T, Smith JC Jr. Reversal of uraemic impotence by zinc. Lancet. 1977 Oct 29;2(8044):895-8.

31 Prasad AS, Abbasi AA, Rabbani P, DuMouchelle E. Effect of zinc supplementation on serum testosterone level in adult male sickle cell anemia subjects. Am J Hematol. 1981;10(2):119-27.

32 Tapiero H, Mathe G, Couvreur P, et al. I. Arginine. Biomedecine & pharmacotherapie (France). 2002; 56(9):439-45.

33 Nonami Y. The role of nitric oxide in cardiac surgery.
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34 Cheng JW, Baldwin SN, Balwin SN. L-arginine in the management of cardiovascular diseases. Annals of Pharmacotherapy. 2001; 35(6):755-64.

35 Chen J, Wollman Y, Chernichovsky T, et al. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. BJU Int. 1999;83:269-73.

36 Zorgniotti AW, Lizza EF. Effect of Large Doses of the Nitric Oxide Precursor, L-Arginine, on Erectile Dysfunction. Int J Impot Res. 1994; 6:33-5.

Gene Bruno, MS, MHS, the dean of academics for Huntington College of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications.

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