FDA has advised supplement manufacturers about safety issues associated with using the botanical kratom as a dietary ingredient, but the industry so far has no guidance on whether the agency will move either to ban the botanical or require proof of its safety.

Kratom (mitragyna speciosa korth) is a tropical deciduous and evergreen tree native in Southeast Asia, where its leaves long have been chewed for medicinal purposes but also can be used for narcotic effect. Kratom is in the same biological family as coffee, rubiacea.

While FDA acknowledges the ingredient’s botanical origin and long-established dietary use, kratom is shipped and packaged with labels stating “not for human consumption,” according to the agency and to firms marketing products with the ingredient.

It is “certainly on our radar and it probably should be on your radar as well,” Corey Hilmas of FDA’s Division of Dietary Supplement Programs said Sept. 26 during a U.S. Pharmacopeia workshop on economically motivated adulteration of supplements and food ingredients Also see "Labels Offer FDA Clues To Spiked Supplements, Health Fraud" - Pink Sheet, 1 October, 2013..

Hilmas noted that the white-vein variety of kratom is “kind of euphoric, energetic and stimulating,” while the second variety, red-vein, is more sedating.

The Drug Enforcement Administration has put kratom on its list of drugs and chemicals of concern, though it has not listed the ingredient as a controlled substance.

A DEA fact sheet notes pharmacology studies show mitragynine, the primary active alkaloid in kratom, has opioid-like activity in animals. Kratom can lead to addiction, and psychotic symptoms manifested in several cases, DEA says, noting “there is no legitimate medical use for kratom in the U.S.”

DEA reports analyses conducted by federal, state and local forensic laboratories indicate mitragynine is increasingly present in seized drugs. It was identified in one report in 2010, 44 reports in 2011 and 81 in the first six months of 2012.

According to Sage Wisdom Botanicals, a marketing group affiliated with an herbal research center, low doses of kratom can be a stimulant, while high doses can be used as a sedative, painkiller and diarrhea treatment, as well as a recreational drug or opiate addiction treatment.

Sage Wisdom says powdered kratom can be mixed with fruit juice or applesauce, which partially masks the taste and allows quick swallowing, and dried kratom leaves often are made into a tea, the most common use in western countries.

Online distributor TheKratom King, of Austin, Tex., says on its frequently asked questions page that it does not provide recipes or instructions for use. “Our product is not intended for human consumption. … However, there are a number of great forums out there … [to] answer your questions.”

Kratom King also advises customers that it will not identify its suppliers, but says it has multiple suppliers that “all provide quality product and meet our standards.”

Firms Need Regulatory Specifics

FDA in early 2013 delivered a message of concern about kratom, but should be more specific about whether the botanical is not a legitimate supplement ingredient, said Duffy MacKay, VP of scientific and regulatory affairs for the Council for Responsible Nutrition.

“We really need FDA to clarify in a public forum, like a letter to the industry or some other way, where they affirmatively say this is not a legal dietary ingredient. …Then we can move forward with education,” MacKay said in an interview

MacKay said CRN’s members are not using kratom as an ingredient. “This is not something that we’re familiar with as a typical dietary ingredient.” For one thing, he noted, “my understanding is that people use it to get high and that’s not an appropriate structure/function claim. … There’s no real nutritional reason to use it.”

CRN, the Consumer Healthcare Products Association and the United Natural Products Alliance asked DDSP Director Daniel Fabricant in a July letter to make the clarification, saying it would “assist industry members to understand the FDA’s concerns and deter further marketing of kratom under the mistaken belief that it is a legitimate product.”

The trade groups want to get ahead of the issue and prevent another problem for the industry similar to dimethylamylane, or DMAA, about which FDA warned manufacturers in 2012 but which continues to turn up in supplements marketed in the U.S.

“We don’t want an ingredient that can cause another black eye, the potential that someone gets their hands on this and there’s an adverse effect or something,” MacKay said.

FDA sent warning letters to 10 marketers of products that contain DMAA and has announced multiple consumer alerts about the ingredient touted as an aid to bodybuilding. The agency says no research has shown that DMAA is a dietary ingredient and warns it can elevate blood pressure and lead to cardiovascular problems Also see "FDA Using “All Available Tools” To Remove DMAA From Market" - Pink Sheet, 15 April, 2013..

Some firms and other stakeholders suggested that DMAA could be used in supplements with the filing of a new dietary ingredient notification, which is required to show the safety of an ingredient not commonly used as food or drink and not marketed as a dietary ingredient before the Oct. 15, 1994, grandfathering date under DSHEA Also see "DMAA Warnings Shed Light On FDA NDI Enforcement" - Pink Sheet, 7 May, 2012..

FDA may not have the option of requiring an NDI for kratom. Kratom could qualify as a dietary ingredient because its source is known – it is a botanical – and apparently was in use pre-DSHEA.

Attorney Marc Ullman suggests, however, FDA could argue that kratom’s use has not been dietary. Although people for centuries in Southeast Asia and for a shorter period in the U.S. have ingested the substance, FDA could assert that its use has been as a drug, not as nutrition.

“It’s a health hazard and I think FDA is very concerned about it,” said Ullman, a partner in Ullman, Shapiro & Ullman in New York.

FDA Could Dust Off Risk-Benefit Standard

With sufficient evidence, FDA could take action against kratom using the regulatory path the agency followed in 2004 to ban the use of ephedra in supplements.

FDA based the ephedra ban on its finding that the Dietary Supplement Health and Education Act allowed the agency to rule that a product that presents an “unreasonable risk of illness or injury” is adulterated and is ineligible for use in supplements Also see "FDA Regulatory Framework For Ephedra Ban Expected To Get Court Review" - Pink Sheet, 5 January, 2004..

Products containing ephedrine alkaloids were promoted for weight loss, sports performance and energy, but FDA found little scientific evidence of their effectiveness, except for short-term weight loss without a clear health benefit. FDA also cited research showing the alkaloids raised blood pressure, stressed the circulatory system and were linked with significant adverse health outcomes.

The Supreme Court in 2007 declined to hear Nutraceutical Corp.'s appeal of lower court decisions upholding FDA’s risk-benefit standard to determine product adulteration. The firm questioned FDA's application of a risk-benefit standard in banning the use of ephedra, arguing that DSHEA does not include such a standard Also see "Supreme Court Refuses Ephedra Case, Battle Against Risk-Benefit Continues" - Pink Sheet, 21 May, 2007..

Although few other industry stakeholders supported the continued use of ephedra in supplements, many questioned FDA’s use of a risk-benefit standard to evaluate a supplement ingredient and predicted another ingredient would emerge that could spur another risk-benefit decision in the agency’s regulation of the supplement space Also see "NPA To Supreme Court: Risk-Benefit Standard Would “Unravel” DSHEA" - Pink Sheet, 9 April, 2007..

But attorney Jonathan Emord, who represented Nutraceutical in the challenge to FDA’s ephedra action, said the use of kratom in supplements does not appear to represent an unreasonable risk.

Emord, of Emord & Associates in Clifton, Va., acknowledged that as FDA points out, a dietary ingredient cannot be lawfully sold if it presents an unreasonable risk of illness or injury to the public. But “little evidence supports that conclusion,” he said.

Despite concerns about consumers’ use of kratom for other than nutritional purposes, he said FDA so far appears to have little on which to base an order to ban use of the ingredient in supplements.

“The substance appears to be psychoactive with some comparing it to a mild form of morphine. It has quite a stigma attached to it, but a stigma without evidence is a slender reed for regulatory action,” Emord added.

Imports Marked With Supplement Codes

FDA’s efforts on kratom have focused on seizing imports that come to the U.S. under a dietary supplement line code, which makes them FDA-regulated imports, Hilmas said.

Often kratom is labeled “not for human consumption and might be listed as ethno-botanical for individual research purposes only, just to get it through our ports,” he said. “In order to get it, usually we do a lot of work as to who it’s going to, and a lot of work as to where it’s coming from, to verify what it’s being used for.”

Hilmas added that kratom has various names and looks like other crushed botanicals. “Now we see firms that are trying to get this material in labeling it as green tea. We’re constantly sampling and analyzing the alkaloids so we can verify it does contain kratom.”

Kratom’s sedating qualities could make it an ingredient for relaxation products, a “big, emerging topic,” Hilmas pointed out. “Relaxation drinks are really, really coming around with ingredients like kava and melatonin in there,” he said, noting that those products “may be adulterated with kratom in the future, something that we wouldn’t be expected to be looking for.”

FDA issued a warning in 2002 that kava “may be associated with severe liver injury.” Supplement trade associations subsequently adopted requirements that members label their kava-containing products to urge consumers to consult a health care professional prior to use if they have liver problems, take any medication or frequently drink alcohol Also see "Kava Labeling Revisions Adopted By Trade Groups; FDA Issues Advisory" - Pink Sheet, 1 April, 2002..

Kratom Action Presents Regulatory Puzzle For FDA

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