Life Extension Magazine

Life Extension Magazine October 2007

Report

The Intimate Link Between Erectile Dysfunction and Heart Disease

By William Davis, MD

By William Davis, MD

Natural Remedies to Enhance Erectile Function

In addition to testosterone, a number of nutritional supplements may either accentuate the effects of testosterone or enhance the artery-dilating effects of nitric oxide.

The path to a healthy erection involves multiple steps, so the “recipe” for success varies among individuals and may involve some trial and error. It’s always worth discussing your erectile function with your doctor, who may need to consider pathological causes of erectile dysfunction. A doctor’s assistance is also necessary if you are considering one of the erection-promoting drugs.

Coming back to the powerful benefits of nitric oxide, one may wonder if it can be taken as a supplement. Unfortunately, the fleeting nature of this molecule makes that impossible. But the body manufactures nitric oxide directly from L-arginine, an amino acid in the diet. The average American generally ingests up to 5.4 grams (5,400 mg) of L-arginine per day through foods, as it is naturally contained in many proteins, especially meat, nuts, and dairy products.29 This amount is generally more than adequate to serve as a substrate for nitric oxide synthesis.

L-arginine also has modest erection-promoting effects in those patients not consuming adequate amounts of L-arginine in the diet. My clinic recommends 3,000–6,000 mg, twice a day, preferably on an empty stomach. Full erection-enhancing benefit may develop slowly and may require up to three months, although some individuals do experience more immediate effects. My clinic has used L-arginine in combination with prescription drugs for erectile dysfunction without complications (e.g. abnormally sustained erections, called “priapism”), but this should be discussed with your doctor. It may be prudent to take a reduced dose of L-arginine when initiating prescription therapy for erectile dysfunction, reserving the full dose of L-arginine only as needed.

Adverse effects of L-arginine are few, such as loose stools at higher doses. Simply cut back on the dose and build up gradually if you experience this. If you have any active gastrointestinal conditions associated with diarrhea or frequent loose stools, such as ulcerative colitis, Crohn’s disease, or malabsorption, first discuss the use of L-arginine with your doctor.30

Another way of increasing nitric oxide in the body is to prevent its rapid degradation by oxygen radicals. Pomegranate and a superoxide dismutase (SOD)-enhancing nutrient called GliSODin® have been shown to favorably affect nitric oxide activity31-34 and to reverse clinical measurements associated with endothelial dysfunction in humans.35,36 In the animal model, pomegranate has been shown to increase penile blood flow and improve erectile response to stimulation.37 In a preliminary study, men with mild-to-moderate erectile dysfunction experienced modest improvements after only four weeks of consuming pomegranate juice each day.38 Pomegranate juice has been reported to mildly inhibit an enzyme pathway that degrades certain medications, though this effect is dramatically less pronounced than that produced by the common beverage grapefruit juice.39

Achieving optimal nitric oxide levels may help:40-44

  • Relieve endothelial dysfunction
  • Lower blood pressure by promoting vasodilation throughout the body
  • Reduce inflammation
  • Increase insulin sensitivity.

Carnitine supplements may enhance erections as effectively as testosterone, according to an Italian study. Taking two forms of carnitine, propionyl-L-carnitine, 2,000 mg/day, and acetyl-L-carnitine, 2,000 mg/day, improved erectile function, modestly exceeding the benefit seen with oral testosterone. Interestingly, both testosterone and carnitine also yielded equal improvements in mood and energy.45 Another study revealed that propionyl-L-carnitine, 2,000 mg/day, when added to drug treatment with Viagra® increased the likelihood of successful erections in men who were initially unresponsive to the drug alone. Measurably improved erections increased from 23% with Viagra® alone to 68% when the supplement was added.46 Carnitine is generally considered safe and well tolerated, mild gastrointestinal symptoms being the only notable side effect.47

Life Extension’s Recommended Testosterone Levels

For optimal health—including sexual and cardiovascular function—Life Extension recommends that aging men maintain healthy levels of free testosterone. Life Extension considers optimal levels of free testosterone to be those that are within the upper one-third of the normal reference range for men between the ages of 20 and 29. (Note that the normal reference range varies depending on the laboratory performing the test.)

A deficiency of the adrenal hormone, dehydroepiandrosterone (DHEA) is also believed to play a role in erectile dysfunction. Over a decade ago, the Massachusetts Male Aging Study revealed blood levels of DHEA-sulfate (the major form of DHEA in the blood) to be closely correlated with erectile ability.2 Since then, several small trials, including one comparing DHEA, 50 mg/day, with placebo, have uncovered a significantly better erectile response in those taking DHEA.48 Individuals with hormone-dependent cancers should consult a physician before taking DHEA.

For centuries, the herb Korean ginseng has been reported to enhance sexual function and desire. Recent studies have confirmed these effects, suggesting that compounds called ginsenosides may produce a nitric oxide-dependent, artery-relaxing effect. A study using Korean ginseng showed an increase in erectile firmness and sexual satisfaction of 60% in men taking ginseng, compared with 30% in those taking placebo.49 Another study also showed a 60% response rate in men taking Korean ginseng, 900 mg three times per day, with improvements in penetration and maintenance of erection.50 Similar findings were confirmed by a recent Brazilian study, which also revealed that testosterone levels remained unchanged during supplementation, suggesting that erection-enhancing effects may not be mediated by a change in testosterone.51 Korean ginseng should not be combined with anticoagulant drugs, such as warfarin, or with nonsteroidal anti-inflammatory drugs that can increase bleeding, such as naproxen or indomethacin. Korean ginseng may decrease blood sugar levels, so you should consult a physician before combining the herb with insulin or other antidiabetic medications.52

Ginkgo biloba has displayed variable effects in enhancing erections. In one study of antidepressant-induced sexual dysfunction, 76% of men experienced improved erections and orgasmic function when given 60–240 mg of ginkgo supplement per day. Interestingly, women participants experienced an even greater improvement in sexual function than men.53 Responses can be highly variable, however, with some men experiencing dramatic improvement, while others derive no benefit. Combining ginkgo with aspirin, anticoagulant drugs such as warfarin (Coumadin®), or thrombolytic (clot-dissolving) medications may increase the risk of bleeding. Individuals with a history of hemorrhagic stroke should not use ginkgo prior to discussion with their doctor.54

Some interesting possibilities for enhancing erectile function may lie in the world of flavonoids. Flavonoids from red wine (resveratrol and others) and green tea (epigallocatechin and other green tea catechins) are emerging as facilitators of the artery-relaxing effects of nitric oxide.55

Using Testosterone: Practical Considerations

A prescription is required to obtain testosterone. It can either be formulated by special pharmacies (“compounding pharmacies”), or obtained as a prescription patch, gel, or injection. The prescribed dose depends on the form used and individual response. Some practitioners advise against using oral testosterone, as orally administered hormones must first undergo metabolism by the liver (termed the “first-pass” effect) before becoming available for functions throughout the body.25

Some doctors shy away from prescribing testosterone to enhance mood or energy, preferring to prescribe it only for “hypogonadism,” which is usually defined as a total testosterone level below 200 ng/dL.

My clinic has found testosterone to be useful in men over 40 years old who suffer from erectile dysfunction, have other symptoms such as low energy or mood, and whose total testosterone level is below 400 ng/dL or who have low “free” testosterone (in the lower half of normal laboratory range).

Unfortunately, insurance reimbursement is spotty for testosterone replacement. A doctor may diagnose “hypogonadism” for a starting testosterone level that is below normal, which somewhat increases the likelihood of insurance coverage. Most men, however, do not fall into this flagrantly deficient range; insurers therefore tend to regard testosterone replacement as “cosmetic” and will not provide coverage. Prescription patches generally cost $3-4 per day. This is one reason our clinic has gravitated towards formulated testosterone creams, as they are far cheaper, usually costing only $0.50-1.00 per day.

Is Testosterone Safe?

Some medical scientists have raised the concern that administration of testosterone may accelerate the growth of hidden prostate cancer; however, the bulk of existing clinical data has not shown an increased risk in prostate cancer with testosterone restoration if levels are low at baseline.26 Data also suggest that testosterone administered to men regarded as having high risk for prostate cancer at baseline does not necessarily increase prostate cancer diagnosis.27

Nonetheless, it is both wise and prudent to have both a prostate exam and a prostate-specific antigen (PSA, a marker for prostate cancer) blood test before starting testosterone and annually thereafter. It is also a good idea to have a periodic complete blood count (CBC) and liver function testing because of the occasional increase in hematocrit (the proportion of blood occupied by red blood cells) and liver function changes that could potentially develop in some men taking testosterone.28

Optimizing Erectile Function: A Rational Approach

Along with a nutritional program to support and optimize erectile health, it is important for your doctor to consider whether any of your current medications are contributing to erectile dysfunction. Common culprits include antidepressant and antihypertensive medications (especially beta blockers like atenolol and metoprolol; angiotensin-converting enzyme inhibitors like lisinopril and ramipril; and calcium channel blockers like diltiazem and amlodipine). Of course, speak to your doctor before stopping any medication.

As heart disease is so closely tied to erectile function, it is also wise to discuss the possibility of hidden heart disease with your doctor if you have erectile dysfunction. Struggles with erectile function usually precede the symptoms of heart disease by several years, so the time to act is now, when your preventive actions are more likely to result in success.8 My preferred method to screen for hidden heart disease is a computed tomography (CT) basic heart scan, which yields a heart scan “score.” A CT heart scan should not be confused with a CT coronary angiogram, commonly referred to as a 64-slice CT coronary angiogram. This is performed on the same CT-scanning device, but involves the use of an X-ray dye and far more radiation exposure than the modest amount required for a basic heart scan. A heart scan score greater than zero signifies the presence of coronary plaque—the disease process underlying a heart attack. The higher the score, the greater the plaque formation. In my opinion, a distant second choice is a stress test, though bear in mind this detects only advanced heart disease.

The formula for successful relief of erectile dysfunction will vary from one man to another, but a combination of useful agents, both non-prescription and prescription, can successfully enhance erectile health in the majority. Many of the same agents that support erectile health, including carnitine, pomegranate, and DHEA, may also yield benefits in the cardiac arena.

Dr. William Davis is a practicing cardiologist in Milwaukee, Wisconsin. He is the founder of the Track your Plaque program, a heart disease prevention program that shows how to use CT heart scans to control coronary plaque. He can be contacted through www.TrackYourPlaque.com.

If you have questions about the scientific content of this article, please call one of our Health Advisors at 1-800-226-2370.

References

1. Bacon CG, Mittleman MA, Kawachi I, et al. Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med. 2003 Aug 5;139(3):161-8.

2. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994 Jan;151(1):54-61.

3. Montorsi P, Ravagnani PM, Galli S, et al. Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: the COBRA trial. Eur Heart J. 2006 Nov;27(22):2632-9.

4. Beckman TJ, bu-Lebdeh HS, Mynderse LA. Evaluation and medical management of erectile dysfunction. Mayo Clin Proc. 2006 Mar;81(3):385-90.

5. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373-6.

6. Murad F. The 1996 Albert Lasker Medical Research Awards. Signal transduction using nitric oxide and cyclic guanosine monophosphate. JAMA. 1996 Oct 9;276(14):1189-92.

7. Desjardins F, Balligand JL. Nitric oxide-dependent endothelial function and cardiovascular disease. Acta Clin Belg. 2006 Nov-Dec;61(6):326-34.

8. Watts GF, Chew KK, Stuckey BG. The erectile-endothelial dysfunction nexus: new opportunities for cardiovascular risk prevention. Nat Clin Pract Cardiovasc Med. 2007 May;4(5):263-73.

9. Ignarro LJ, Cirino G, Casini A, Napoli C. Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardiovasc Pharmacol. 1999 Dec;34(6):879-86.

10. Heidler S, Temml C, Broessner C, et al. Is the metabolic syndrome an independent risk factor for erectile dysfunction? J Urol. 2007 Feb;177(2):651-4.

11. Makhsida N, Shah J, Yan G, Fisch H, Shabsigh R. Hypogonadism and metabolic syndrome: implications for testosterone therapy. J Urol. 2005 Sep;174(3):827-34.

12. Zumoff B, Strain GW, Miller LK, et al. Plasma free and non-sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity. J Clin Endocrinol Metab. 1990 Oct;71(4):929-31.

13. Miner MM, Seftel AD. Testosterone and ageing: what have we learned since the Institute of Medicine report and what lies ahead? Int J Clin Pract. 2007 Apr;61(4):622-32.

14. Khalil RA. Sex hormones as potential modulators of vascular function in hypertension. Hypertension. 2005 Aug;46(2):249-54.

15. Marin P, Holmang S, Jonsson L, et al. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes Relat Metab Disord. 1992 Dec;16(12):991-7.

16. Simon D, Charles MA, Lahlou N, et al. Androgen therapy improves insulin sensitivity and decreases leptin level in healthy adult men with low plasma total testosterone: a 3-month randomized placebo-controlled trial. Diabetes Care. 2001 Dec;24(12):2149-51.

17. Malkin CJ, Pugh PJ, Jones RD, et al. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004 Jul;89(7):3313-8.

18. Rosano GM, Sheiban I, Massaro R, et al. Low testosterone levels are associated with coronary artery disease in male patients with angina. Int J Impot Res. 2007 Mar-Apr;19(2):176-82.

19. Mikhail N. Does testosterone have a role in erectile function? Am J Med. 2006 May;119(5):373-82.

20. Shabsigh R. Testosterone therapy in erectile dysfunction and hypogonadism. J Sex Med. 2005 Nov;2(6):785-92.

21. Jain P, Rademaker AW, McVary KT. Testosterone supplementation for erectile dysfunction: results of a meta-analysis. J Urol. 2000 Aug;164(2):371-5.

22. Boloña ER, Uraga MV, Haddad RM, et al. Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007 Jan;82(1):20-8.

23. Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A. Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clin Endocrinol (Oxf). 2003 May;58(5):632-8.

24. Jeong HJ, Shin YG, Kim IH, Pezzuto JM. Inhibition of aromatase activity by flavonoids. Arch Pharm Res. 1999 Jun;22(3):309-12.

25. Jockenhövel F. Testosterone therapy—what, when and to whom? Aging Male. 2004 Dec;7(4):319-24.

26. Tan RS, Salazar JA. Risks of testosterone replacement therapy in ageing men. Expert Opin Drug Saf. 2004 Nov;3(6):599-606.

27. Rhoden EL, Morgentaler A. Testosterone replacement therapy in hypogonadal men at high risk for prostate cancer: results of 1 year of treatment in men with prostatic intraepithelial neoplasia. J Urol. 2003 Dec;170(6 Pt 1):2348-51.

28. Bhasin S, Calof OM, Storer TW, et al. Drug insight: Testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging. Nat Clin Pract Endocrinol Metab. 2006 Mar;2(3):146-59.

29. Wu G, Morris SM, Jr. Arginine metabolism: nitric oxide and beyond. Biochem J. 1998 Nov 15;336 ( Pt 1)1-17.

30. Available at: http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/lar_0024.shtml. Accessed July 27, 2007.

31. Ignarro LJ, Byrns RE, Sumi D, et al. Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide. Nitric Oxide. 2006 Sep;15(2):93-102.

32. de Nigris F, Williams-Ignarro S, Botti C, Sica V, Ignarro LJ, Napoli C. Pomegranate juice reduces oxidized low-density lipoprotein downregulation of endothelial nitric oxide synthase in human coronary endothelial cells. Nitric Oxide. 2006 Nov;15(3):259-63.

33. de Nigris F, Williams-Ignarro S, Lerman LO, et al. Beneficial effects of pomegranate juice on oxidation-sensitive genes and endothelial nitric oxide synthase activity at sites of perturbed shear stress. Proc Natl Acad Sci USA. 2005 Mar 29;102(13):4896-901.

34. Vouldoukis I, Conti M, Krauss P, et al. Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress. Phytother Res. 2004 Dec;18(12):957-62.

35. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr. 2004 Jun;23(3):423-33.

36. Cloarec M, Caillard P, Provost JC, Dever JM, Elbeze Y, Zamaria N. GliSODin, a vegetal sod with gliadin, as preventative agent vs. atherosclerosis, as confirmed with carotid ultrasound-B imaging. Allerg Immunol (Paris). 2007 Feb;39(2):45-50.

37. Azadzoi KM, Schulman RN, Aviram M, Siroky MB. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. J Urol. 2005 Jul;174(1):386-93.

38. Forest CP, Padma-Nathan H, Liker HR. Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study. Int J Impot Res. 2007 Jun 14; [Epub ahead of print].

39. Kim H, Yoon YJ, Shon JH, Cha IJ, Shin JG, Liu KH. Inhibitory effects of fruit juices on CYP3A activity. Drug Metab Dispos. 2006 Apr;34(4):521-3.

40. Candipan RC, Wang BY, Buitrago R, Tsao PS, Cooke JP. Regression or progression. Dependency on vascular nitric oxide. Arterioscler Thromb Vasc Biol. 1996 Jan;16(1):44-50.

41. Hamon M, Vallet B, Bauters C, et al. Long-term oral administration of L-arginine reduces intimal thickening and enhances neoendothelium-dependent acetylcholine-induced relaxation after arterial injury. Circulation. 1994 Sep;90(3):1357-62.

42. Piatti P, Fragasso G, Monti LD, et al. Acute intravenous L-arginine infusion decreases endothelin-1 levels and improves endothelial function in patients with angina pectoris and normal coronary arteriograms: correlation with asymmetric dimethylarginine levels. Circulation. 2003 Jan 28;107(3):429-36.

43. Cooke JP. ADMA: its role in vascular disease. Vasc Med. 2005 Jul;10 Suppl 1S11-7.

44. Wascher TC, Graier WF, Dittrich P, et al. Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin sensitivity. Eur J Clin Invest. 1997 Aug;27(8):690-5.

45. Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology. 2004 Apr;63(4):641-6.

46. Gentile V, Vicini P, Prigiotti G, Koverech A, Di SF. Preliminary observations on the use of propionyl-L-carnitine in combination with sildenafil in patients with erectile dysfunction and diabetes. Curr Med Res Opin. 2004 Sep;20(9):1377-84.

47. Available at: http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/lca_0060.shtml. Accessed July 27, 2007.

48. Reiter WJ, Pycha A, Schatzl G, et al. Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study. Urology. 1999 Mar;53(3):590-4.

49. Choi HK, Seong DH, Rha KH. Clinical efficacy of Korean red ginseng for erectile dysfunction. Int J Impot Res. 1995 Sep;7(3):181-6.

50. Hong B, Ji YH, Hong JH, Nam KY, Ahn TY. A double-blind crossover study evaluating the efficacy of korean red ginseng in patients with erectile dysfunction: a preliminary report. J Urol. 2002 Nov;168(5):2070-3.

51. de AE, de Mesquita AA, Claro JA, et al. Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction. Asian J Androl. 2007 Mar;9(2):241-4.

52. Available at: http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101250.shtml. Accessed July 27, 2007.

53. Cohen AJ, Bartlik B. Ginkgo biloba for antidepressant-induced sexual dysfunction. J Sex Marital Ther. 1998 Apr;24(2):139-43.

54. Available at: http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101240.shtml. Accessed July 27, 2007.

55. Achike FI, Kwan CY. Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway. Clin Exp Pharmacol Physiol. 2003 Sep;30(9):605-15.