By Luke Fortney, MD

UnityPoint-Meriter McKee Clinic, Madison, WI

Dr. Fortney reports no financial relationships relevant to this field of study.

SYNOPSIS: Be wary of and avoid over-the-counter products that claim to boost libido and sexual function, particularly for erectile dysfunction, which are often of spurious quality and contaminated with PDE-5 analogues.
SOURCE: ElAmrawy F, ElAgouri G, Einoweam O, et al. Adulterated and counterfeit male enhancement nutraceuticals and dietary supplements pose a real threat to the management of erectile dysfunction: A global perspective. J Diet Suppl 2016;13:660-693.

Editor’s Note

Dr. Fortney’s review highlights the problems with mislabeled and/or adulterated dietary supplements. In the case of “herbal Viagras,” it can be a common and dangerous problem. A further shame of this illegal marketing and distribution is to overshadow some of the legitimate work being done (and published) on some dietary supplements that may have efficacy for erectile dysfunction, including Panax ginseng, L-arginine, Coryananthe yohimbe, pycnogenol, and Ginkgo biloba.

SUMMARY POINTS

  • In general, erectile dysfunction (ED) supplements are less effective and often less safe than cardiovascular lifestyle modifications and appropriate use of quality-controlled pharmaceutical options. However, there is some evidence that supports the judicious use of specific high-quality supplements in appropriate situations.
  • The FDA continues to update and re-issue statements warning consumers to avoid ED supplements.
  • Given the common practice of adulteration of over-the-counter ED proprietary products and for safety concerns, healthcare providers should counsel patients to avoid email promotions, internet advertisements, and convenience store products that claim to enhance male libido and sexual function. Quality products, proven by third-party certification and accompanied by expert medical supervision, should be the focus of prescribing and use.
  • Recent developments in quality testing have revealed rampant adulteration of “natural” herbal supplements with synthetic PDE-5 analogues.

Erectile dysfunction (ED) prevalence globally is high, and it is the most common sexual problem among men.1 ED is defined with relative subjectivity as the inability to achieve or maintain a sufficient erection for satisfactory sex. Normally, an erection is stimulated by a combination of neurovascular, hormonal, and environmental factors beginning with sexual interest and desire (which is mediated predominantly by testosterone). Through parasympathetic activation, nitric oxide (NO) synthase in endothelial cells is activated to produce NO from the amino acid precursor L-arginine. With NO present, the corpus cavernosum is engorged with arterial blood as a result of smooth muscle endothelial relaxation while venous return is simultaneously restricted. Most ED treatments ultimately make use of this biological pathway and mechanism.

Although psychosocial factors, hormonal disorders, recreational drug abuse, and adverse effects from prescribed medications contribute to ED, the overall prevalence increases with age and, in many cases, is associated with poor cardiovascular health. With an aging population worldwide, a recent review by ElAmrawy et al highlighted the growing concern about counterfeit and adulterated nutraceuticals that claim to be effective, safe, and of natural origin.2 Given the flood of products that have invaded global markets with little or no safety and quality control, great effort has been undertaken in recent years to develop cost-effective but efficient and effective laboratory techniques that test quality and determine adulteration of these nutraceuticals products.

COMMENTARY

The review article by ElAmrawy et al highlights a concerning trend among “natural” ED products that are now widely available via the internet.2 In particular, trans-national pharmacies have aided the widespread sale and availability of various spurious products. What is alarming is that most (> 60%) of these products are adulterated with active pharmaceutical ingredients but are mislabeled as “natural,” which is a significant health hazard for consumers.3 For example, Eurycoma longifolia, an herbal product from a flowering plant native to Indonesia and Malaysia, has been marketed as an “herbal Viagra,” but this and many other “natural” products have been found to contain sildenafil (Viagra) or similar synthetic analogues.4 That said, one recent meta-analysis of 139 participants concluded that daily use of Eurycoma over the 12-week study may improve mild ED symptoms but failed to show improvement in more severe cases.5

Another recent product analysis study found that three different nutraceutical products contained unregistered synthetic phosphodiesterase type 5 inhibitor (PDE-5) analogues.6 These contaminants are variants of sildenafil, in particular dimethylsildenafil, thiodimethylsildenafil, and thiomethisosildenafil. Another recent analysis study of one “all-natural” product found similar results.7 Not only was the product adulterated with PDE-5 synthetic analogues, but different capsules also contained unreliable and varying concentrations. Another analysis study from 2013 found that among 20 different dietary supplements for ED, eight contained actual sildenafil while another was found with nor-acetildenafil (another synthetic sildenafil analogue).8

Similarly, in 2013, a study coordinated by Pfizer Global Security obtained and analyzed 91 different “herbal” or “natural” ED supplements from various convenience stores and gas stations in the United States.9 Sixty-two products claimed to be manufactured in the United States, while 15 were from unspecified “Asian” origin. The remaining 14 products did not clearly identify the country of manufacturing origin. Although no product made claim to inclusion of synthetic PDE-5 substances, 74 (81%) were found to contain pharmaceutical PDE-5 ingredients or synthetic analogues. What was particularly frightening is that 18 of these products contained more than 110% of the highest FDA-approved medication strength of sildenafil or tadalafil (Cialis). There was also pronounced variability of contents between samples of the same product, indicating poor quality control. Perhaps most concerning, only 14 products warned against concomitant nitrate medication use.9

Nutraceutical options

In the context of a healthy lifestyle the following supplements can be considered adjunctive treatment options for some men.10 Look for GMP (good manufacturing practice) and USP (United States Pharmacopeia) quality assurance labels on reputable products):

  • Yohimbine: 5 to 10 mg daily as needed
  • Panax ginseng: 500 to 1000 mg daily as needed
  • L-arginine: 1000 to 2000 mg daily as needed
  • Propionyl-L-carnitine: 1000 mg daily as needed

ED Prevention Prescription10

  • Exercise at least three hours a week to maintain a body mass index < 30 kg/m2.
  • Follow a healthy, calorie-controlled, Mediterranean-style diet that is rich in fruits and vegetables, omega-3 fatty acids, whole-grains, nuts, seeds, and legumes.
  • Reduce stress through exercise, rest, meditation, breathing exercises, yoga, journaling, etc.
  • Maintain healthy sexual relationships with good communication.
  • Avoid tobacco, heavy alcohol use, marijuana, and recreational drug use.
  • Avoid highly processed foods that contain high amounts of “anti-nutrients” (e.g., high-fructose corn syrup, trans-fats, artificial sweeteners/colors/preservatives, etc).
  • Avoid over-exposure to pesticides and herbicides, and overuse of chemical or cleaning products.
  • Avoid heating or storing food in plastics (e.g., endocrine and hormone disruptors such as bisphenol-A).

RESOURCES

http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048386.htm

REFERENCES

  1. Bacon CG, et al. Sexual function in men older than 50 years of age: Results from the health professionals follow-up study. Ann Intern Med 2003;139:161-168.
  2. ElAmrawy F, et al. Adulterated and counterfeit male enhancement nutraceuticals and dietary supplements pose a real threat to the management of erectile dysfunction: A global perspective. J Diet Suppl 2016;13:660-693.
  3. Cohen PA, Venhuis BJ. Adulterated sexual enhancement supplements: More than mojo. JAMA Intern Med 2013;173:1169-1170.
  4. Said MM, et al. Rapid detection of sildenafil analogue in Eurycoma longifolia products using a new two-tier procedure of the near infrared (NIR) spectra database. Food Chem 2014;158:296-301.
  5. Kotirum S, et al. Efficacy of Tongkat Ali (Eurycoma longifolia) on erectile function improvement: Systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 2015;23:693-698.
  6. Bortolini C, et al. “One-shot” analysis of PDE-5 inhibitors and analogues in counterfeit herbal natural products using an LC-DAD-QTOF system. Anal Bioanal Chem 2015;407:6207-6216.
  7. Schramek N, et al. Pyrazolopyrimidines in “all-natural” products for erectile dysfunction treatment: The unreliable quality of dietary supplements. Food Addit Contam 2015;32:127-140.
  8. Shi F, et al. Application of a high resolution benchtop quadrupole-Orbitrap mass spectrometry for the rapid screening, confirmation and quantification of illegal adulterated phosphodiesterase-5 inhibitors in herbal medicines and dietary supplements. J Chromatogr A 2014;1344:91-98.
  9. Campbell N, et al. Adulteration of purported herbal and natural sexual performance enhancement dietary supplements with synthetic phosphodiesterase type 5 inhibitors. J Sex Med 2013;10:1842-1849.
  10. Fortney L. Erectile Dysfunction. In: Integrative Medicine, 3rd ed. Rakel D, ed. Philadelphia: Saunders/Elsevier; 2012.