Monday, April 13, 2015

"God Damn the Pusher Man" - Especially when Enabled by the FDA Revolving Door

Who is watching the watchers?  A story this week involving "speed" like drugs added to "dietary supplements" suggests how far the once respected US Food and Drug Administration has fallen.

An Amphetamine-Like Drug Spiking "Nutritional Supplements"

The story began with a paper by Cohen and colleagues published a relatively obscure medical journal, and then picked up by the news media.(1)  The main points of the article were:

BMPEA (beta-methylphenylethylamine) is a compound first synthesized in the 1930s as a "potential replacement" for amphetamines.  Animal tests revealed amphetamine-like properties.  The compound was never tested on humans, and never marketed.


BMPEA remained known only as a research chemical until early 2013 when the FDA identified BMPEA in multiple supplements labelled as containing ‘Acacia rigidula’, even though the stimulant has never been identified or extracted from Acacia rigidula, a shrub native to Texas.


More than two years after the FDA's discovery, the FDA has yet to warn consumers about the presence of the amphetamine isomer in supplements.

So Cohen et al undertook to identify "nutritional supplements" said to contain acacia rigidula and test them for BMPEA.  They found 21 such supplements, all of which tested positive. The authors then recommended,

that supplement manufacturers immediately recall all supplements containing BMPEA, and that the FDA use all its enforcement powers to eliminate BMPEA as an ingredient in dietary supplements. Consumers should be advised to avoid all supplements labelled as containing Acacia rigidula. Physicians should remain alert to the possibility that patients may be inadvertently exposed to synthetic stimulants when consuming weight loss and sports supplements.
Note that while the power of the FDA to regulate "nutritional supplements" is limited by a 1994 law, Cohen and colleagues wrote that it

is tasked with identifying and removing mislabelled, adulterated, and dangerous dietary supplements from the marketplace.

Since BMPEA is apparently not found in nature, and was not sold prior to 1994, putting BMPEA in a "dietary supplement" appears to be adulteration. 

The Risks of BMPEA in Nutritional Supplements

The study was then picked up by the media.  In the Los Angeles Times, Pieter Cohen, the lead author of the journal article,

said that while the effects of BMPEA are unknown, the compound is potentially dangerous. He said the FDA's failure to act is 'completely inexcusable.'

Furthermore, in a CBS report,

BMPEA has not been tested in humans, but led to increased blood pressure in cats and dogs.

'These are things that are signals that in humans will later turn into heart attacks, strokes and maybe even sudden death,' Cohen said.

The point is that while it has never been tested fully on humans, there is every reason to suspect that BMPEA acts very similarly to amphetamine, colloquially called "speed."  Amphetamines, as we discussed here, have dangerous side effects, including severe blood pressure elevations, and increased risks of stroke, myocardial infarction (heart attack), and other cardiac events.  The drugs also have a high potential for abuse. 

Why Did the FDA Do Nothing? 

Despite the likely riskiness of BMPEA, the FDA did nothing when it found it in numerous dietary supplements in 2013, and has not indicated that it will do anything now.  According to the LA Times,

FDA spokeswoman Juli Putnam acknowledged that the agency published research on the occurrence of BMPEA in Acacia rigidula supplements in 2013.

'While our review of the available information on products containing BMPEA does not identify a specific safety concern at this time, the FDA will consider taking regulatory action, as appropriate, to protect consumers,' she said.

In a Consumers Report item, Dr Cohen responded to that,

'It’s mind boggling,' said Pieter Cohen, M.D., the Harvard physician who is the lead author of the new study, published online in the journal Drug Testing and Analysis. 'The companies think they have complete impunity. They assume the FDA will do nothing about it. And they’re right.'

A post in the NY Times Well blog reiterated, 

Under federal law, dietary supplements — with some exceptions — can contain only ingredients that are part of the food supply or that were already on the market before 1994. Dr. Cohen said that BMPEA has never been sold as a food or supplement, and as a result any product that contains it is considered adulterated, which would give the F.D.A. the authority to send warning letters to companies that add it to their supplements.

Yet while the FDA had authority to do something, it did nothing.

Was the Revolving Door the Reason?

Back in 2014, we posted about two transitions through the revolving door by the FDA official in charge of the regulation of nutritional supplements.  We reproduce the relevant section of the post below:

This round trip through the door was noted rather obliquely in a New York Times article in late April, 2014, focused on how slowly the FDA has reacted to apparently dangerous "dietary supplements,"

Before joining the F.D.A. in 2011, Dr. [Daniel] Fabricant was a top executive at an industry trade group, the Natural Products Association.

The article had previously identified Dr Fabricant as

the director of the division of dietary supplement programs in the agency’s Center for Food Safety and Applied Nutrition.


The F.D.A. recently announced that Dr. Fabricant is leaving the agency this month to return to the trade group as its chief executive.

While the NY Times article thus mentioned as an aside that a government official with major responsibility for regulating dietary supplements had these relationships with the dietary supplement industry, it did not then question whether that relationship had anything to do with slow responses by the FDA to reports of toxic dietary supplements. 

In 2014, the Times drew no conclusions about Mr Fabricant's career trajectory.  However, this time

But public health experts contend that the F.D.A.’s reluctance to act in this case is symptomatic of a broader problem. The agency is not effectively policing the $33 billion-a-year supplements industry in part because top agency regulators themselves come from the industry and have conflicts of interest, they say. In recent years, two of the agency’s top officials overseeing supplements — including one currently on the job — were former leaders of the largest supplement industry trade and lobbying group.

Daniel Fabricant, who ran the agency’s division of dietary supplement programs from 2011 to 2014, had been a senior executive at that trade group, the Natural Products Association, which has spent millions of dollars lobbying to block new laws that would hold supplement makers to stricter standards. He left the F.D.A. last year and returned to the association as its chief executive. His current replacement at the F.D.A.’s supplement division also comes from the trade group.

'To have former officials in the supplement industry become the chief regulators of that industry at the F.D.A. is like the fox guarding the hen house,' said Michael F. Jacobson, the executive director of the Center for Science in the Public Interest, a consumer advocacy group.

Also, the new Well blog post noted 

Shortly before Dr. Fabricant left the F.D.A. in 2014 to return to the association, the F.D.A. hired another official from the group, Cara Welch. She is now the acting director of the agency’s supplement division. Dr. Cohen, who is also an internist at the Cambridge Health Alliance, said he repeatedly wrote to Dr. Welch asking what the agency was going to do about BMPEA, and that she did not respond.

Dr. Welch declined repeated requests for interviews. In a statement, Juli Putnam, an F.D.A. spokeswoman, said that the agency 'has found that hiring experienced leaders with diverse backgrounds in public health, industry, academia, and science enriches the professional environment and leads to the best health policy outcomes for the American public.'

Before joining the F.D.A., Dr. Welch was the vice president of scientific and regulatory affairs at the Natural Products Association, where she was a staunch defender of the supplement industry. When JAMA, a leading medical journal, raised concerns in a 2011 editorial that the federal law allowed the supplements industry to police itself, Dr. Welch responded that the industry had 'an excellent safety record.'

'The industry itself supports and has implemented strong self-regulatory mechanisms,' she said in an industry news release at the time.


To summarize, from 2011 to now, the leadership of the part of the FDA that is supposed to regulate dietary supplements was dominated by former top executives of the Natural Products Association, the trade organization for dietary supplement manufacturers.  In 2013, FDA scientists found that multiple dietary supplements contained BMPEA, a compound closely related to amphetamines, and hence potentially dangerous and addictive, although it had never been tested on or previously used by humans.  Although the FDA had authority to do something about this apparent adulteration of these products, it so far had done nothing.  Thus it appears that the currently legal revolving door that allows government regulation to be run by people who come directly from the industries that government is supposed to regulate could be responsible for exposing people to dangerous, addictive drugs.

Remember, BMPEA is a first cousin of amphetamine, amphetamine is "speed," and as the drug epidemics of the 1960s and 1970s showed us, "speed kills."  So a plausible argument is that the revolving door, as relevant to FDA, has enabled manufacturers of nutritional supplements to become the "pusher man," a la the Steppenwolf sound track of Easy Rider,

As we noted here, some experts consider the revolving door per se to be corruption, not merely conflict of interest.  The current case plausibly suggests not only that the revolving door is corrupt, but that when applied to health care can pose dangers to patients, not merely danger to government finances, government ethics, and the integrity of representative democracy.  Nonetheless, up to now, a few people have decried the revolving door (and very occasionally in health care), but nothing has been done about it.   

So it is surprising that today (13 April, 2015), the New York Times published an editorial inspired by the BMPEA case, which concluded

consumer advocates are surely right that putting the industry in charge of supplement regulation is like appointing the fox to guard the henhouse. Clearly, the F.D.A. should not allow industry insiders to fill key positions. A permanent solution is for Congress to enact conflict-of-interest laws forcing employees above a certain grade level at any agency to recuse themselves from official actions that affect a former employer or client, including trade associations and their members.

As a minimum, that would be a good start.  Unfortunately, even a NY Times editorial hardly guarantees action.  At least, however, the problem of the revolving door as a danger to patients has gotten a little less anechoic.

As we last wrote, the continuing egregiousness of the revolving door in health care shows how health care leadership can play mutually beneficial games, regardless of the their effects on patients' and the public's health.  Once again, true health care reform would cut the ties between government and corporate leaders that have lead to government of, for and by corporate executives rather than the people at large.

ADDENDUM (20 April, 2015) - This post was republished on Naked Capitalism


1.  Cohen PA, Bloszies C, Yee C, Gerona R. An amphetamins isomer whose efficacy and safety in humans has never been studied, beta-methylphenylethylamine (BMPEA), is found in multiple dietary supplements.  Drug Testing Analysis 2015; DOI: 10.1002/dta.1793  Link here.


David J. Littleboy said...

This is an excellent and important article. Good work, and thank you! The lack of oversight of the supplement industry is, I strongly agree, a major problem.

But, if you will forgive an extremely minor quibble from an aging hippie*, I think you got the wrong song. I could be wrong, of course, but I'm pretty sure Steppenwolf was singing about _heroin_; the line "smoked a lot of grass, popped a lot of pills" is in contrast to the soul-killing aspects of heroin. The song you want is Canned Heat's "Amphetamine Annie".

*: I wasn't much of a hippie, but I did go catch the Velvet Underground's banana album tour back in the day (in Boston), when they also were more concerned with heroin than amphetamines.

Anonymous said...

As usual, excellent post. My biggest take away. It is no longer conflict of interest ~ it is outright corruption. White collar crime is alive and thriving! Kinda like the Asian carp.

Roy M. Poses MD said...

David J Littleboy,

Thanks for the comments. One argument is my recollection is that there were issues with narcotics and stimulants in the late 1960s - 1970s, and so "The Pusher Man" could be reasonably interpreted as applying to both.

But you may be right.

On the other hand, we used "Amphetamine Annie" in our previous post on amphetamines, here:

Steve Lucas said...

This will get your motor running and get you out on the highway.

Steve Lucas

Anonymous said...

FDA is more focused on Health bars .....calling out the KIND bars. Gheez!

Anonymous said...

Considering that the FDA approved Vyvanse (which is actual amphetamine) for binge eating disorder it seems rather moot that they are ignoring an amphetamine-like compound, BMPEA.

Hal Dall, MD said...

Imagine if the FDA in an analogous situation hired an exec from PhARMA.(likely has already happened?).

Unfortunately, for modern regulatory agencies, the revolving door is the rule, and there is less regulating than capturing.