Extracts from the Yohimbe (Pausinystalia johimbe) tree are used in products for sexual and physical performance; two categories that receive extra attention from the FDA. Products often list the ingredient as yohimbe extract, yohimbe bark extract, or yohimbine – the key alkaloid in the bark of the tree.
While the American Herbal Products Association’s Botanical Safety Handbook (Second Edition, 2013) notes that doses up to 10 mg of yohimbine three times per day are generally well tolerated, detrimental side effects associated with high doses of yohimbe include elevated blood pressure, increased heart rate, and anxiety.
“Any company selling yohimbe products should have their labels adequately articulated with appropriate warnings,” said Mark Blumenthal, founder and executive director of the American Botanical Council.
Findings published in Drug Testing and Analysis by Cohen et al. indicated that only 2 of the 49 yohimbine supplement brands tested provided consumers with both accurate information about the quantity of yohimbine as well as information about the potential adverse effects.
Dr Cohen worked with scientists at the National Center for Natural Products Research at the University of Mississippi and Cornell University, and found that yohimbine levels varied greatly, from zero in some cases to 12.1 mg per recommended serving.
Only 11 of the 49 supplement brands listed a specific quantity of yohimbine on the label, added Cohen et al, while most of these were “inaccurately” labelled with actual contents ranging from 23% to 147% of the label claim.
The authors also reported that 39% of the supplements tested – or 19 out of 49 – did not contain corynanthine and rauwolscine, which are two alkaloids also found in the bark of P. johimbe. This suggested that the yohimbine in those supplements was either a “highly processed plant extract or synthetic in origin”.
“While dietary supplements often contained pharmaceutically relevant quantities of yohimbine, the supplement labels very infrequently provide consumers with accurate information regarding quantity of yohimbine or known adverse effects,” they wrote. “This is a particularly concerning finding given that many countries have already banned yohimbine from all over-the-counter products due to its potential serious health effects.”
Dr Cohen declined requests to comment directly to NutraIngredients-USA on this issue.
Yohimbe – an evergreen tree species native to Africa – is the number seven top-selling herbal in the mainstream multi-outlet channel, according to HerbalGram’s 2014 Herb Market Report. However, in the natural channel it is not even in the top 20.
The yohimbe market is growing at around 3%, according to data from SPINS provided to NutraIngredients-USA. Combined sales in the natural and conventional multi-outlet channels for the 52 weeks ending September 6th 2015 hit $27.10 million, up from $26.25 million for the previous 52 weeks. It is reportedly found in more than 550 dietary supplements in the US.
The products were allegedly purchased at GNC, Vitamin Shoppe, Walgreens, Walmart, CVS, RiteAid, and Whole Foods. All seven retailers were contacted prior to publication. Some did not respond, while others declined to comment because the paper does not disclose which specific brands were involved.
Vitamin Shoppe was the only retailer to respond to our request for comment, with Meghan Biango, its manager of corporate communications, saying: “The Vitamin Shoppe is committed to being our customers’ first choice for all of their health and wellness needs. Our third-party vendors represent to us that their labels are accurate and in compliance with all applicable laws. Additionally, none of the Vitamin Shoppe brand products contain yohimbine.”
Inconsistence with label claims
Two other studies published this year reported similar findings to the Cohen paper. One published in the Journal of AOAC International described an analytical method to rapidly determine if synthetic yohimbine was being used in products or if the products actually contained yohimbe bark or extract.
James Neal-Kababick, director of Flora Research Laboratories and co-author of the paper, explained, “This is an extremely sensitive method. We can determine if this material is synthetic yohimbine hydrochloride or if it is really yohimbe bark extract. A lot of these other alkaloids that might be in the bark extract have similar mass and similar structures and we were able to separate these and detect them”.
“We found levels and claims all over the place,” said Neal-Kababick. The authors purchased 10 products from dietary supplement stores in Oregon in the form of powders, gel caps, and tablets. The products and retailers were not identified.
“It is quite amazing how serious of an issue this is,” added Neal-Kababick, “and there is considerable risk to taking high doses of this alkaloid, especially when combined with caffeine and certain pharmaceutical drugs.”
The third paper, again published in the Journal of AOAC International, detailed the analysis of 17 yohimbe dietary supplements in tablet, capsule and liquid form purchased from local stores and over the internet using a UHPLC/MS system with a diode array detector, and then compared this with the suggested yohimbine intake amount listed on the product label. The researchers did not identify the brands nor did they report the retailers where the products were purchased.
“Our policy prohibits us to pass or fail the samples we tested,” said Pei Chen, PhD, research chemist at the Food Composition and Method Development Laboratory of the USDA, ARS, BHNRC, and lead author on the paper. “All I can say is the yohimbine content among the dietary supplements is inconsistent and, for some of them, inconsistent with the label claim as well.”
The papers have raised concerns, but Dr Rick Kingston, President, Regulatory and Scientific Affairs, SafetyCall International and Clinical Professor of Pharmacy, University of Minnesota, notes that he has not seen much in the way of serious adverse events being reported.
“We do have some companies [as clients at SafetyCall] with products with yohimbe as an ingredient but we don’t see much in the way of serious consequences,” he noted. “But the yohimbine content in those products is typically lower and that is only the SafetyCall universe.”
Dr Kingston told us that there is a relatively wide margin of safety for yohimbine and there is data to show that some individuals have tolerated large single doses without serious toxicity. But, sensitive individuals or those with medical conditions may not be able to tolerate even small doses.
“When you have people experiencing minor side effects such as restlessness or anxiety, a dose reduction may help but if not, they should stop using the product and the effects typically resolve spontaneously.” said Dr Kingston.
Commenting on the paper from Dr Chen at the USDA, Dr Kingston noted that their data showed that there is a 10-fold variation in yohimbine content. “If someone is taking a lower dose product without any problems and they switch to another product with a substantial increase, that could be a big deal,” he said.
Are yohimbe supplements are on the FDA’s radar? Several warning letters have been issued to companies marketing yohimbe bark products over the years, with the majority of those letters being for the claims being made (see list at the end of this article).
Marianna Naum, PhD, strategic communications and public engagement staff in the FDA’s Office of Foods and Veterinary Medicine, told NutraIngredients-USA that the agency is aware that yohimbe-containing products are targets for spiking with synthetic yohimbine.
“We continue to expand our understanding of this adulteration by reviewing the scientific literature, and product testing. Adulterated dietary supplements, including those with enhanced concentrations of the active ingredients beyond natural levels, remain a concern for the agency, and we will take appropriate action when necessary.”
“This is heating up,” noted Neal-Kababick. “It doesn’t surprise me that there is an increase in the attention around yohimbe.”
Drug Testing and Analysis (Open access article)
Published online ahead of print, doi: 10.1002/dta.1849
“Pharmaceutical quantities of yohimbine found in dietary supplements in the USA”
Authors: P.A. Cohen, Y-H. Wang, G. Maller, R. DeSouza, I.A. Khan
Journal of AOAC International (Subscription required for full access)
2015, Volume 98, No. 4, Pages 896-901
“Determination of Yohimbine in Yohimbe Bark and Related Dietary Supplements Using UHPLC-UV/MS: Single-Laboratory Validation”
Authors: P. Chen, N. Bryden
Journal of AOAC International (Subscription required for full access)
2015, Volume 98, No. 2, Pages 330-335
“Characterization and Quantitation of Yohimbine and Its Analogs in Botanicals and Dietary Supplements Using LC/QTOF-MS and LC/QQQ-MS for Determination of the Presence of Bark Extract and Yohimbine Adulteration”
Authors: D. Lucas, J. Neal-Kababick, J. Zweigenbaum
*Select FDA warning letters about yohimbe:
Maxam Nutraceutics/Maxam Laboratories for alleged drug claims (2010)
RT Naturals, LLC for alleged drug claims (2010)
Athletes.com, Inc./Higher Power, Inc./dba bodybuilding.com received a letter for alleged unsubstantiated structure/function claims (2006)
Bethel Nutritional Consulting, Inc. received a warning letter in 2014 for alleged drug claims.