FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, April 26, 2022

Erectile Dysfunction and Niacin

by W. Todd Penberthy, PhD and Andrew W. Saul

OMNS (Apr. 26, 2022) There is solid evidence that niacin (the standard form of vitamin B3) on its own can help effectively treat erectile dysfunction. [1] Niacin's long-term circulatory benefits may include facilitating a male's erection, which is dependent on blood supply to the penis, because niacin normalizes blood lipids. Niacinamide will not achieve this. [2,3]

It's important to appreciate that an ED diagnosis likely denotes greater significance than just the loss of ability to have satisfactory sex. In fact, ED is considered to be one the earliest presentations prognostic of atherosclerotic cardiovascular disease - the most common age-related cause of death. [4] Hyperlipidemia, hypercholesterolemia, tobacco abuse, diabetes, or coronary artery disease are common risk factors present in ED. [5]

Fortunately, pennies a day of over-the-counter high-dose niacin is established as an effective treatment for directly addressing atherosclerosis, hyperlipidemia, hypercholesterolemia, and coronary disease and niacin has been used safely and effectively for over 60 years in clinical medicine. [6-8] Generally, the higher the dose of niacin, the more effective it is. [9] It is always best to take it with food and not in a fasted state.

Similar to popular ED drugs, niacin is also a vasodilator, but the vasodilation induced by ED drugs may be longer-lasting. For example, the niacin flush itself, commonly ends within half an hour or so. Still, it is not entirely known whether the flush pathway is the primary mechanism of action for how niacin works to provide benefits for ED patients as there are many therapeutic mechanisms for high-dose niacin treatment.

In short, the engorgement of the penis relies on a healthy circulation and niacin directly addresses these concerns in a safe fashion.

The biochemistry of a male erection initiates from a cascade nerve signals starting in the brain and running the length of the spinal cord down to the penis. In response to these signals, nerves within a spongy vasculature (corpus cavernosom) release nitric oxide gas molecules that drive production of cyclic guanosine monophosphate (CGMP) that ultimately exerts the relaxing expansive effect characteristic of an erection.

However, a permanent erection is of course unacceptable, so nature provided the phosphodiesterase type 5 (PDE5) enzyme to break down the CGMP and accordingly pharmaceutical companies developed drugs like Viagra to inhibit PDE5 to keep the cGMP levels elevated with stimulation of erection as desired. While Viagra is the most used approach, penile injections of prostaglandin (PGE1) mimetics were used prior to the introduction of Viagra and have been considered the gold standard for directly addressing ED, albeit with more side effects. [10] Niacin treatment increases nitric oxide synthase production and niacin causes a massive release of prostaglandins including PGE2 in the flush, but it is unknown whether niacin boosts PGE1 as well.

eNOS: Endothelial nitric oxide synthase, an enzyme that helps to make nitric oxide (NO),
PDE5: Phosphodiesterase type 5 (PDE5) breaks down cGMP (below)
cGMP: Cyclic guanosine monophosphate is involved in producing more NO
IIEF: International Index of Erectile Function, an accepted standard for measuring ED outcomes.

There is evidence that niacin alone does work for ED. The first niacin-only for treating ED study was "Effect of Niacin on Erectile Function in Men Suffering Erectile Dysfunction and Dyslipidemia." [1] The authors wrote:

"[W]hen patients were stratified according to the baseline severity of ED, the patients with moderate and severe ED who received niacin showed a significant improvement in IIEF-Q3 scores and IIEF-Q4 scores compared with baseline values, but not for the placebo group. The improvement in IIEF-EF domain score for severe ED patients in the niacin group were 5.28 (p≤0.001) as compared to 2.65 (p < 0.04) for placebo respectively."

The results had high statistical significance (meaning they were almost certainly not due to chance). The authors concluded that "Niacin alone can improve the erectile function in patients suffering from moderate to severe ED and dyslipidemia."

Sildenafil (a common generic version of the better-known Viagra) is prescribed for pulmonary hypertension. It is a vasodilator. While niacin has not been commonly recognized as a treatment for hypertension, it can assist in lowering blood pressure. However, the effect of niacin is much more continuous than sildenafil, with a far greater number of clinically proven benefits than the PDE5 inhibitors.

This makes perfect sense, given that increased circulation is the very basis of the male erection and any dyslipidemia-associated blockage can be expected to interfere with this process.

While PDE5 inhibitors work ultimately by increasing nitric oxide (NO), niacin is also known to increase NO.

Severe ED most commonly involves poor circulation that can be effectively treated with high-dose niacin therapy. This comes with the side benefit of possibly saving your life from a cardiovascular event. Reduction in mortality by the most common cause of death has been proven for niacin in RCTs even 9 years after cessation of treatment (2.4g/d), but not for Viagra/sildenafil except in neonates, but not adults with pulmonary hypertension. [11-13]

One study has examined the PDE5 inhibitor vardenafil, with or without niacin, with propionyl-l-carnitine and l-arginine (NCA). Treatment with NCA alone increased IEFF5 by 2 points, vardenafil increased it by 4 points, NCA plus vardenafil increased it by 5 points, and placebo exerted no change at all. [14]

In addition to ED, sildenafil (Viagra) is used for pulmonary hypertension, high altitude edema, and Raynaud's phenomena. We personally know people whose Raynaud's disappeared after 2 weeks of treatment with high dose niacin. The vasodilation effect has been reported to be sufficient to noticeably help, and the warming sensation of the flush is welcomed by people with cold extremities. It is about dose: enough niacin must be taken to get the flush. This varies greatly from person to person. Remember that vasodilation occurs with standard niacin but not with other niacin forms. Niacinamide will not work, and inositol niacinate probably will not work. For comfort, niacin should be taken with food and not in a fasted state.

To the amazement of physicians and patients, high doses of niacin routinely correct dyslipidemia. Higher doses generally confer the greatest effect. This includes high-dose niacin-mediated routine correction of elevated total cholesterol, triglycerides, VLDL, and LDL, while simultaneously boosting HDL ("good cholesterol") more than any known pharmaceutical.

It should also be noted that there are many different marketed laboratory tests for assessing the lipid contributions to the risk of atherosclerotic cardiovascular disease. Among the most significant contributors prognostic of future cardiovascular events is high Lp(a) and fibrinogen. [15,16] Niacin lowers Lp(a) and fibrinogen. [1,6,16] By contrast, statins in fact raise Lp(a), which is completely undesirable, and they well known to have many side effects, including some that can be serious. Still statins are commonly used and continue to be explored in new clinical trials given the great profit incentive.

Sildenafil (Viagra) is used for ED, pulmonary hypertension, high altitude edema, and Raynaud's phenomena. We personally know people whose Raynaud's disappeared after 2 weeks of treatment with high dose niacin.

PDE5 inhibitors (sildenafil/Viagra, vardenafil, tadalafil, and avanafil) do not directly cause penile erections but instead affect the response to sexual stimulation. Sildenafil was the first to be approved and is most effective in men with mild-to-moderate ED. Sexual stimulation is necessary to activate the response. The side effects of sildenafil include headache, flushing, indigestion, nasal congestion, and impaired vision, including photophobia and blurred vision. By comparison, niacin has been around much longer than sildenafil/Viagra. Since the 1930s, niacin has been examined in many more trials than sildenafil/Viagra, which was first marketed for ED in 1998.

Niacin's dyslipidemia-correcting benefits are highly dose-dependent, with plain old original immediate release niacin exerting the greater benefits than timed release. [9] These studies have clearly shown that correction of dyslipidemic measures of HDL cholesterol, triglycerides, total cholesterol, and LDL-C are greater when administering the high dose of 3g/d as compared to 2g, 1g, or 500mg.

Niacin requirements and dosing is highly individual. Some individuals are more sensitive than others to the niacin flush response. First, one should always take high-dose niacin with food and not in a fasted state; Secondly, the more one takes a high dose of niacin, the more one can tolerate it. So, one may start their "high-dose" at 50mg three times a day and go for 1-2 weeks before increasing this to higher doses. Ideally an individual can eventually comfortably take 500mg or up to 2g per administration taken once or twice a day. Some are very sensitive to even 50mg, while others can take 2g and notice nothing. Generally, the latter is not a good sign.

To prevent ED, it will likely be most effective to correct deficiencies in ED-associated biochemical pathways, including the levels of niacin and arginine, because these pathways depend on niacin and arginine for nitric oxide production. Further, the simple fact that niacin costs less than three percent of the cost of ED drugs is in itself reason to investigate further.

(Research biochemist Dr. W. Todd Penberthy is a continuing medical education writer and consultant [ www.cmescribe.com ]. In addition to numerous journal publications, he has contributed chapters describing the latest vitamin research to textbooks including Present Knowledge in Nutrition and Biochemical, Physiological, and Molecular Aspects of Human Nutrition. Andrew Saul, along with Drs. Abram Hoffer and Harold Foster, is author of Niacin: The Real Story, which has been translated into German, Polish, and Chinese. In addition to authoring or coauthoring a dozen other books, Saul is editor of the textbook The Orthomolecular Treatment of Chronic Disease.)

References

1. Ng C-F, Lee C-P, Ho AL, et al. (2011) Effect of niacin on erectile function in men suffering erectile dysfunction and dyslipidemia. J Sex Med. 8:2883-2893. https://pubmed.ncbi.nlm.nih.gov/21810191

2. Hoffer A, Saul AW, Foster HD (2015) Niacin: The Real Story. Basic Health Pubs. ISBN-13: ‎ 978-1591202752. Summary and detailed contents at http://www.doctoryourself.com/niacinreviews.html .

3 Parsons W (2000) Cholesterol Control Without Diet. Lilac Press. ISBN-13: ‎ 978-0966256871

4. Nehra A, Jackson G, Miner M, et al. (2012) The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease. Mayo Clin Proc 87:766-778. https://pubmed.ncbi.nlm.nih.gov/22862865

5. Miner M, Seftel AD, Nehra A, et al. (2012) Prognostic utility of erectile dysfunction for cardiovascular disease in younger men and those with diabetes. Am Heart J. 164:21-28. https://pubmed.ncbi.nlm.nih.gov/22795278

6. Carlson LA (2005) Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Intern Med. 258:94-114. https://pubmed.ncbi.nlm.nih.gov/16018787

7. Creider JC, Hegele RA, Joy TR (2012) Niacin: another look at an underutilized lipid-lowering medication. Nat Rev Endocrinol. 8:517-528. https://pubmed.ncbi.nlm.nih.gov/22349076

8. Guyton JR, Bays HE (2007) Safety considerations with niacin therapy. Am J Cardiol. 99:22C-31C. https://pubmed.ncbi.nlm.nih.gov/17368274

9. Pieper JA (2002) Understanding niacin formulations. Am J Manag Care 8:S308-S314. https://pubmed.ncbi.nlm.nih.gov/12240702

10. Preckshot J (1999) Male impotency and the compounding pharmacist. Int J Pharm Compd. 3:80-83. https://pubmed.ncbi.nlm.nih.gov/23985547

11. Canner PL, Berge KG, Wenger NK, et al. (1986) Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 8:1245-1255. https://pubmed.ncbi.nlm.nih.gov/3782631

12. Kelly LE, Ohlsson A, Shah PS. (2017) Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev. 8:CD005494. https://pubmed.ncbi.nlm.nih.gov/28777888

13. Wang R, Jiang F, Zheng Q, et al. (2014) Efficacy and safety of sildenafil treatment in pulmonary arterial hypertension: a systematic review. Respir Med. 108:531-537. https://pubmed.ncbi.nlm.nih.gov/24462476

14. Gentile V, Antonini G, Antonella Bertozzi M, et al. (2009) Effect of propionyl-L-carnitine, L-arginine and nicotinic acid on the efficacy of vardenafil in the treatment of erectile dysfunction in diabetes. Curr Med Res Opin. 25:2223-2228. https://pubmed.ncbi.nlm.nih.gov/19624286

15. Tunstall-Pedoe H, Woodward M, Tavendale R, et al. (1997) Comparison of the prediction by 27 different factors of coronary heart disease and death in men and women of the Scottish Heart Health Study: cohort study. BMJ 315:722-729. https://pubmed.ncbi.nlm.nih.gov/9314758

16. Jacobson TA (2013) Lipoprotein(a), cardiovascular disease, and contemporary management. Mayo Clin Proc. 88:1294-1311. https://pubmed.ncbi.nlm.nih.gov/24182706

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