Dendrobium, PEA Supplements Carry Risks For Manufacturers

FDA warns against using dendrobium and phenethylamines in dietary supplements, but firms that move forward anyways should do so “with eyes wide open” and conduct extra identity, safety and quality assurance tests, CRN’s MacKay advises.

Dietary supplement firms that continue to market products with phenethylamines (PEAs) and dendrobium despite concerns voiced by FDA and the U.S. Anti-Doping Agency should add extra safety and quality assurance layers, advises the Council for Responsible Nutrition’s Duffy MacKay.

“You need to add a layer of due diligence on this because these are on the radar” of multiple regulators, MacKay, CRN’s VP of Scientific & Regulatory Affairs, said in an interview.

FDA Division of Dietary Supplement Programs Director Daniel Fabricant at CRN’s annual meeting Sept. 19 in Park City, Utah, warned industry not to use dendrobium or PEAs (Also see "Ingredient Safety Concerns Rise Among FDA Enforcement Priorities" - Pink Sheet, 23 Sep, 2013.). He noted FDA “is concerned and looking at these sorts of products very, very closely, so if you’re involved … with these sorts of products you want to have a discussion with us or perhaps reformulate.”

Dendrobium entered the spotlight as dimethylamylamine, or DMAA, “was cycling through its tornado” of destruction in early 2012, and now is popular as a replacement for the controversial bodybuilding ingredient, MacKay said. FDA has warned consumers and industry that DMAA is not a valid dietary ingredient and ordered it off the market.

Dendrobium is a stimulant that when taken in high enough doses can cause significant adverse events, “particularly when used in combination with exercise,” according to an alert published in July 2012 by the Human Performance Resource Center, a Defense Department initiative under the Force Health Protection and Readiness Program. HPRC warns the ingredient can slow breathing and heart rate, drop blood pressure, cause seizures and convulsions (Also see "DMAA Warnings Shed Light On FDA NDI Enforcement" - Pink Sheet, 7 May, 2012.).

Dendrobium also removes muscle inhibition, and appears related to the prohibited stimulant strychnine, which weight-lifters in the past injected to remove muscle inhibition so they could lift more, said Amy Eichner, special advisor on drugs and supplements at USADA.

At CRN’s meeting Sept. 18, Eichner said USADA is watching the ingredient, which would be prohibited in competition based on its activity and chemical structure.

She questioned whether the ingredient labeled as dendrobium and used in significant amounts in supplements really is a natural constituent of the nobile orchid as claimed by some or if it is a synthetic chemical masquerading as a dietary ingredient.

The question recalls the doubts about DMAA’s purported derivation from geranium. Some argued that it would be impossible to extract the massive amount of DMAA used in products from the flower, which included only miniscule amounts of the ingredient if any at all (Also see "DMAA Is Synthetic And Needs NDI Notification – Study" - Pink Sheet, 2 Jul, 2012.). FDA determined the ingredient was synthetic and needed a new dietary ingredient notification.

Eichner noted the dendrobium nobile orchid is on the endangered list, which should make the ingredient rare and expensive. Those factors do not seem to align with the “extremely high volume products” claiming to contain dendrobium on the market. “I don’t know how those two go together,” she said.

“I just really don’t want to see this happen again [where] someone puts an herbal on the label to gain acceptance in the industry and in the eyes of the FDA, but instead of putting the actual plant material in, they put however many synthetic or other derived compounds into the product,” Eichner said, referencing DMAA.

MacKay agreed dendrobium “could be the next explosion” in the supplement industry, and added that while “not a lot of very responsible firms have scooped up this ingredient,” those that do “must do so with eyes wide open and do extra identity testing” to assure the ingredient they use actually comes from the orchid.

Identity tests should also check dendrobium for PEAs, which some claim occur naturally in dendrobium. HPRC says there is little scientific evidence to support the natural occurrence of PEAs in dendrobium though, and therefore the supplements may be spiked.

Finally, identity tests should be fine-tuned because dendrobium “is a little bit of a synthetic chemist’s darling” in that its chemical structure can be easily modified to create multiple analogs, which can affect the body differently, Eichner said.

FDA Discourages Giving PEAs A Chance

Firms that opt to use PEAs should follow the same strategy as those that use dendrobium by heavily researching the ingredient’s safety alone and in combination with other ingredients, Eichner said.

She noted PEA is a broad class of ingredients, some of which can act like amphetamines, commonly used in workout, diet and mood supplements.

“This category stresses me out – the fact that the list is un-ending,” and includes everything from dopamine and phenylephrine, which are not prohibited in competition, to amphetamine and pseudoephedrine, which are prohibited, she said.

Eichner asked firms that include PEAs in products to check if the ingredient is banned for use during competition by the World Anti-Doping Agency and if it is, then warn consumers on the label of its presence.

“We just don’t want athletes to accidently take something that is otherwise legitimate and then get in trouble,” she said.

Such a scenario can harm a product manufacturer, too, because an athlete who tests positive due to an ingredient in a legitimate supplement likely will complain about the product, which will hurt a firm’s reputation and sales, Eichner said.

Some PEAs are found in trace amounts in plants and are technically usable in supplements, but MacKay said these type of ingredients that are pharmacologically active and sometimes promoted for use in abusive ways raise safety concerns and “start to get on the edge of what is appropriate” for supplements.

He encourages firms to perform “extra due diligence and safety assessments,” when considering including PEAs in a product.

FDA’s Fabricant went one step further and advised firms not to use PEAs at all because of safety concerns. He also noted that PEAs are the “chemical du jour,” with multiple analogs popping up.

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