50 VITAMIN RETAILER Celebrating 20 Years of Excellence 1994-2014 WWW.VITAMINRETAILER.COM ■ MARCH 2014

As men age, there is oftena decline in libido andsexual function, whichfrequently interferes withintimacy in romantic rela-

tionships and has emotional ramifica-tions, while also eroding self-confidenceand quality of life. This has set thegroundwork for the popularity of nitricoxide (NO)-enhancing drugs such asViagra and Cialis, and consumer aware-ness of prescription testosterone (T)availability courtesy of the low “T” com-mercials. Here we’ll discuss the etiologyof male sexual decline and the potentialbenefits offered by non-prescriptionalternatives.

Sexual DeclineHealthy sexual function is a multi-fac-toral process requiring (at least) healthycirculation, healthy hormone produc-tion, adequate energy levels and propermental/emotional well-being.Unfortunately, aging and unhealthylifestyle practices can negatively influ-ence one or more of these processes.

In the case of T, a reduction in its pro-duction is common and implicated inreduced libido and sexual function.Research1 indicates that T levels in menfall progressively with age and that asignificant percentage of men over theage of 60 years have serum T levels thatare below the lower limits of youngadult men (age 20 to 30 years). Some

studies2 show that men experience agradual and progressive decline in totalT levels that takes place at a rate ofapproximately one percent per yearbeginning in their 30s, while other stud-ies3 show an average annual decline ofone to two percent total T levels, withan even more rapid decline in free T.

With regard to circulation, considerhow it is affected by poor diet and lackof exercise. Beyond ramifications oncardiovascular and cerebrovascularhealth, poor circulation may also trans-late into an inadequate blood supply tothe genital region, making it difficult toachieve and maintain an erection.Furthermore, inadequate endogenousproduction of the biochemical NO canexacerbate this problem since adequateNO is necessary for vasodilatation ofblood vessels and, consequently, erec-tile function.

Testosterone ModulationWhile there are many nutraceuticals onthe market with claims to increase T lev-els, I have found that much of thehuman clinical research to supportthose claims is inadequate or in somecases non-existent. Three exceptionsare the herb Eurycoma longifolia Jack,vitamin D and zinc.

• E. longifolia Jack (aka, Tongkat Alior Long Jack) is a medicinal herb ofSouth-East Asian origin (especiallyMalaysia, Thailand and Indonesia), tradi-

tionally used for its aphrodisiac activityto enhance male sexual performance.4-8

Modern scientific research has alsodemonstrated this benefit, apparentlyas a result of increasing serum T lev-els.9,10 However, it is significant to notethat the human clinical research hasbeen done on a specific proprietaryextract known as LJ100. This is impor-tant since the LJ100 extract of E. longi-folia has been standardized foreurypeptides, naturally-occurring com-pounds which may be the active phyto-chemicals in E. longifolia, or at leastserve as a marker for extract quality.

Human clinical studies on LJ100 havebeen conducted at different dosage lev-els, but 200 mg/day showed the mostbenefits. Studies included both con-trolled trials and open-label trials. It willnot be possible to provide a detailedreview all of the studies; however, hereis a synopsis of the research results:

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

• Depending on the study, cortisoldecreased 16-32 percent14,11

• DHEA increased 47 percent9

• Sexual health scores improved sig-nificantly10,15, as much as 91 percent9

It appears that at least one of themechanisms of action for LJ100 is thereduction of sex hormone-binding glob-ulin (SHBG) levels. SHBG is a glycopro-tein that binds to sex hormones. Whilebound to SHBG, T cannot bind to cellu-

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Men’s Sexual Health: Testosterone & Nitric Oxide ModulationBy Gene Bruno, MS, MHS

MARCH 2014 ■ WWW.VITAMINRETAILER.COM Celebrating 20 Years of Excellence 1994-2014 VITAMIN RETAILER 51

lar androgen receptors—which meansthat it won’t have any of the valuableeffects of T in this form. Of course,SHBG-bound T can be unbound, but itcan take a while for this to happen.Furthermore, SHBG levels increase aswe age.2 In one of the studies, LJ100was shown to reduce SHBG levels in 36percent of the cases after one week,and 66 percent after three weeks.9

• Vitamin D deficiency is present out-right in 41.6 percent of the U.S. popula-tion16, while vitamin D insufficiency (i.e.,lacking sufficient vitamin D) is present in77 percent of the population.17 This isalarming considering that new studiesare constantly being conducted thatdemonstrate a broad range of impor-tant functions that vitamin D performsin human health, including its role inmaintaining healthy T levels.

Three different cross-sectional studiesincluding thousands of men havedemonstrated that higher vitamin D lev-els are associated with higher levels ofT (especially free T), and lower levels ofestrogen and SHBG in men.18-20 Inregard to supplementation research, 54healthy overweight men undergoing aweight reduction program participatedin a randomized controlled trial.21

Participants received either 3,332 IUvitamin D daily for one year or placebo.Initially, vitamin D concentrations werein the deficiency range and T valueswere at the lower end of the referencerange. The results were that in the vita-min D group, there was a significant 25percent increase total T levels. By con-trast, there was no significant change inany T measure in the placebo group.

• Zinc deficiency is prevalent through-out the world, including the U.S.22,23

This is problematic since zinc has beenreported to have roles in the synthesis,transport and peripheral action of hor-mones. In fact, low dietary zinc statushas been associated with low circulatingconcentrations of several hormonesincluding T.24 Conversely, research25 hasshown that male subjects with normal Tlevels had a significantly higher zinclevel compared to those with low T lev-els. Zinc supplementation in marginallyzinc-deficient normal elderly men for sixmonths resulted in close to a doublingof serum T levels.26 In addition,research27 has shown that zinc supple-

mentation prevented a decrease in Tlevels after exercising, and men under-going hemodialysis28-30 or who had sick-le cell anemia31 were able to maintainhigher T levels when supplementingwith zinc.

NO EnhancementThe amino acid L-arginine is a precursor(building material) for the synthesis ofNO.32 Supplemental sources of L-argi-nine appear to augment NO produc-tion33, with the result being a measura-ble increase in blood flow34 (i.e., vasodi-latation). Since penile erection requiresthe relaxation of the cavernous smoothmuscle, which is triggered by NO, itmight be expected that supplementa-tion with L-arginine would help promoteerectile function. In fact, this is the case.

Studies have shown that when sup-plementing with L-arginine in doses of 5g35 or 2.8 g36 daily, men with erectiledysfunction (ED) or impotence experi-enced significant improvements in erec-tile function. These studies found thatsubjects were either responders or non-responders (presumably based upontheir levels of NO (i.e., those with lowNO would be responders). The respon-ders experienced significant improve-ments in sexual function.

ConclusionAlthough the use of prescription drugsmay offer a viable treatment for ED,there are alternatives with a high safetyprofile that may also offer an effectivesolution. It may make sense to experi-ment with supplements first to see ifresults are forthcoming before turningto medications, which are not withoutadverse effects. VR

References:1 Wang C, Nieschlag E, Swerdloff R, Behre HM.

Investigation, treatment and monitoring of late-onsethypogonadism in males: ISA, ISSAM, EAU, EAA and ASArecommendations. Eur J Endocrinol. 2008;159:507–514.

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

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

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

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

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

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

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

9 Tambi MIM, Saad JM. Water-soluble extract ofEurycoma longifolia Jack soluble extract as a potentialnatural energizer for healthy aging men. SpecialistReproductive Research Center, National Population &Family Development Board, Ministry of Women & FamilyDevelopment, Malaysia. 2000:9 pgs.

20 Tambi MI. Nutrients and Botanicals for optimizingMen’s Health. Examining the evidence for Eurycomalongifolia longjack, the Malaysian Ginseng in men’shealth. 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 Extracton Anabolic Balance During Endurance Exercise. JISSN.2006;3(1)S32.

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

43 LJ100® Saliva Testosterone Test. Unpublishedreport. HP Ingredients. Bandenton, PL. Retrieved August24, 2012 from www.hpingredients.com/lj100_human_clinical_research.htm.

54 Talbott SM, Talbott JA, George A, Pugh M. Effect ofTongkat Ali on stress hormones and psychological moodstate in moderately stressed subjects. JISSN.2013;10:28.

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

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

17 Ginde AA, Liu MC, Camargo CA Jr. Demographicdifferences and trends of vitamin D insufficiency in the USpopulation, 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 testos-terone levels in men. Clin Endocrinol (Oxf). 2012 Jan 2.doi: 10.1111/j.1365-2265.2012.04332.x. [Epub ahead ofprint].

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

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

21 Pilz S, Frisch S, Koertke H, Kuhn J, Dreier J,Obermayer-Pietsch B, Wehr E, Zittermann A. Effect of vita-min 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 defi-ciency in elderly patients. Nutrition. 1993;9:218.

23 Prasad AS. Clinical spectrum and diagnostic aspectsof human zinc deficiency. In: Prasad AS, ed. Essential andtoxic trace elements in human health and disease. NewYork: 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, man-ganese, molybdenum, nickel, silicon, vanadium, and zinc.Washington, D.C.: National Academy Press; 2001:442-501.

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

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

27 Kilic M. in sedentary males supplemented with oralzinc. 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 hormonesin male patients on hemodialysis. Ren Fail. 2010May;32(4):417-9.

29 Mahajan SK, Abbasi AA, Prasad AS, Rabbani P,Briggs WA, McDonald FD. Effect of oral zinc therapy ongonadal function in hemodialysis patients. A double-blindstudy. 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 Oct29;2(8044):895-8.

31 Prasad AS, Abbasi AA, Rabbani P, DuMouchelle E.Effect of zinc supplementation on serum testosteronelevel in adult male sickle cell anemia subjects. Am JHematol. 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 sur-gery. Surgery Today (JAPAN). 1997; 27(7):583-92.

34 Cheng JW, Baldwin SN, Balwin SN. L-arginine in

the management of cardiovascular diseases. Annals ofPharmacotherapy. 2001; 35(6):755-64.

35 Chen J, Wollman Y, Chernichovsky T, et al. Effect oforal administration of high-dose nitric oxide donor L-argi-nine in men with organic erectile dysfunction: results of adouble-blind, randomized, placebo-controlled study. BJUInt. 1999;83:269-73.

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

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Circle Reader Service #35

Gene Bruno, MS, MHS, the deanof academics for HuntingtonCollege of Health Sciences, is anutritionist, herbalist, writer andeducator. For more than 30 yearshe has educated and trained nat-ural product retailers and healthcare professionals, hasresearched and formulated natu-ral products for dozens of dietarysupplement companies, and haswritten articles on nutrition,herbal medicine, nutraceuticalsand integrative health issues fortrade, consumer magazines andpeer-reviewed publications.

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