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DMAA: Efficacious but is it Safe?

by Igor I. Bussel & Andrey A. Pavlov Jr.

Jann Bellamy has recently authored an excellent piece on the limitations of the FDA and how the DSHEA actually protects the profits of supplement manufacturers rather than the health and well-being of consumers. Bellamy used the very poignant and currently “controversial” example of DMAA (methylhexanamine or 1,3-dimethylamylamine) to illustrate her point regarding the loopholes and lack of enforcement power of the FDA. The authors of this piece had been considering writing about DMAA and felt this would be an excellent time to further expound on Bellamy’s work. The goal of this article will be twofold: 1) to discuss the known history and pharmacology of DMAA, especially in regards to the basic methodology for evaluating novel substances or novel uses of substances in the context of lacking RCT level evidence (i.e. the concept of science vs. evidence based medicine) and 2) how the DMAA story clearly and unequivocally demonstrates how the DSHEA allows for unscrupulous profiteers to game the system with little, if any, consequence and nothing but profit until the cost in lives forces the issue.

History

DMAA was originally developed by Eli-Lilly in 1948 and then later trademarked as Forthane to be used as a nasal decongestant (there are varying accounts but it seems that Eli Lilly patented the molecule in the early 1940’s and then trademarked and marketed it as Forthane in 1971 for allergic rhinitis and then voluntarily withdrew it in 1983). The mechanism of action was vasoconstriction – the blood vessels in the nose would constrict so that less blood flow would lead to less nasal discharge. This is a mechanism used by common OTC nasal sprays like oxymetazoline (Afrin) and is indeed quite effective. However, Forthane was later withdrawn from the market because of significant side effects including headaches, tremors, and increased blood pressure. These effects likely occur because DMAA is structurally similar to amphetamine and as a result, the compound is not only a vasoconstricting agent but is also a central nervous system (CNS) stimulant. 

Pharmacology

A 2011 study looked at the physiological effects of DMAA and claimed that “[t]o our knowledge, no data are available concerning the effects of oral geranamine intake on heart rate (HR) and blood pressure in individuals.”  Literature searches for any of a number of variations of DMAA including various equivalent chemical names, trade names, and geranium derivatives also revealed no studies on the physiological effects of DMAA (except for one article in JAMA from 1950 which has no text available entitled “NEW and nonofficial remedies: methylhexamine; forthane.”) prior to the 2011 study. Since then, there have only been a few studies, many of them done this year. The only data available on the compound is from chemical safety manuals like the Merck Index; an Encyclopedia of Chemicals, Drugs, and Biologicals from 1989 listing toxicological data of the compound in animals. The toxicology report is rather telling:

  • TYPE OF TEST: LDLo — Lowest published lethal dose
  • ROUTE OF EXPOSURE: Unreported
  • SPECIES OBSERVED: Rodent — mouse
  • DOSE/DURATION: 20 mg/kg
  • TOXIC EFFECTS:
    • Behavioral — convulsions or effect on seizure threshold
    • Behavioral — ataxia
    • Lungs, Thorax, or Respiration — other changes

Based on this limited report, it is difficult to determine clinical safety and efficacy effects of the compound. As with all vague things in the biomedical world, unsubstantiated declarations can be fabricated as long as they don’t make specific disease claims. 

But do were really have no idea what this compound could or would do? Is there truly an absence of evidence? From the strictest interpretation of the hierarchy of evidence in EBM there is so little evidence as to be akin to no evidence. This is where science-based medicine steps in. Here at SBM we often talk about prior probability in the context of most CAM modalities having none, thus a p-value can indeed be spurious and safely disregarded in the proper context, regardless of “how significant” it is. But prior probability also works the other way and is indeed the basis physicians use for off-label prescription of medications, amongst other things. So in the case of DMAA we can look at the chemical structure, the side effects that led to the withdrawal of Forthane decades ago, the known vasoconstrictive effects that Eli Lilly exploited as the mechanism for their drug, the Merck toxicology data, and especially the fact that DMAA interferes with immunoassays for amphetamines to draw a conclusion that in the absence of better evidence it is quite reasonable to conclude that the primary and side effects, as well as dangers of DMAA would be very close to those of amphetamine – a compound we have studied extensively. A little bit of intellectual honesty would then lead someone to realize quite rapidly that unless we felt comfortable putting amphetamines out on the open market for anyone of any age to buy and consume, we shouldn’t do the same for DMAA. This is regardless of the source since coming from a plant won’t magically make the compound any safer or have different effects. Unless of course you believe in magic.
 
In a recent Google search, many websites devoted to bodybuilding and health supplementation have made the claim that DMAA is safe or at least is safe in “appropriate” doses while recognizing that taking too much can have adverse effects. Yet what can this possibly be based on? We have no idea what the elimination route actually is, what the half life is, if it builds up in tissues over time, if it causes damage to particular organs (like the liver or kidneys), or what the long term effects would be at any dosage. Many of these sites use anecdotal data – individuals using it didn’t die or have horrible effects and felt great whilst taking it. Yet this cannot possibly take into account the previously mentioned considerations. Some sites even list recommended dosages and frequencies of administration. Once again, based on what? Nobody has any idea if the compound accumulates in the body or what the half-life is to make such a claim. But, such claims are perfectly legal and reasonable in the world of the DSHEA.

How to game the system using the DSHEA

So now that we have established that DMAA is a synthetically derived amphetamine-like molecule, how did we go from a drug that was discarded from medical use decades ago to a “natural” and “safe” dietary “supplement?”

It seems to have started in 1996 with an article out of China called “A study on the chemical constituents of geranium oil” (Ping et al. Journal of Guizhou Institute of Technology, 1996.) Despite our best search efforts, we could not find that actual article, merely hundreds of references to it. We attempted to go directly to the journal website, but none exists. Despite this, it is the most commonly cited reference for the “natural” origins of DMAA as it claimed that this study found evidence of DMAA in geranium extracts.
 
That’s it. Really. That is all that was needed, despite all of the long synthetic history of the compound, to make it legal to market under the DSHEA. The Human Performance Resource Center has a pretty comprehensive list of all the companies and products that sell DMAA-containing compounds (PDF) under the protection of the DSHEA. There are 79 different products with almost as many companies. And that is just the list of products still currently marketed. There is a much longer list of products that are no more or no longer use DMAA. Sure makes that FDA warning to 10 companies seem even more pitiful, doesn’t it?
 
Since the unfindable Ping et al. study there have been a few more that have used extremely sensitive techniques and not been able to find any DMAA in geranium extracts. USPLabs rebuts by claiming that these studies didn’t look at the correct (and incredibly specific) geranium plant and states that “critics are uninformed”. Interestingly enough, in that same article “[a USPLabs spokesperson] did not clarify whether the DMAA contained in Jack3d and OxyElite Pro was actually sourced from geranium…” Thankfully, we have science to help us answer that question.
 
A recent study did actually find some DMAA in geranium extracts. However this was in the 0.6 to 1.4 ng/g range. That’s nanograms – as in one billionth of a gram, or 1/10^-9 grams of active substance per gram of geranium. The amount of DMAA in Jack3d by USPLabs appears to be a secret. Reading that thread from the USPLabs official blog is quite telling in and of itself, with comments from USPLabs claiming it has been studied and determined safe, citing their own in-house studies and press releases as evidence of this (as well as one actual peer reviewed study). However, in perusing the various sources and recommendations on the web anything ranging from 20 mg-75 mg is the recommended dosage with 50 mg being most commonly mentioned. That means USPLabs would have to be processing 50,000 kg of geranium to produce one dose of their product. What was that about prior plausibility again? If that weren’t enough yet another study demonstrated that:

the enantiomeric and diastereomeric ratios of two different known synthetic DMAA compounds, as well as the total concentrations of DMAA and its stereoisomeric ratios in 13 different supplements, were determined by gas chromatography. The stereoisomeric ratios of DMAA in the synthetic standards and in all the commercial supplements were indistinguishable.

In organic chemistry, molecules that have the exact same number and type of atoms can have different configurations in three dimensions. Even if they have the same exact number and type of bonds this can occur. This is biologically very important since most of our enzymes have evolved to process one particular configuration of compounds that have multiple configurations. In synthetic chemistry, making a compound that has exactly the three dimensional shape that you want is often rather tricky and is called “controlling” the stereogenic or chiral centers. So when you do a synthetic reaction, you often get a mixture of these various configurations and the ratios are determined by the initial conditions and the reaction conditions. What this paper is telling us is that an actual sample of products that contain DMAA has ratios that are identical to what you would get from the standard laboratory synthesis of the compound. Of course, it is possible that this could be entirely coincidental and the geranium plant just happens to have the exact same ratios as well. However, for reasons that would go well beyond the scope of this article, that is almost as likely as homeopathy working. For a more in-depth discussion of how incredibly implausible the claims are, there is an excellent article dissecting every claim and every molecule as well.
 
Since there is a potential profit, USPLabs has created an entire website devoted to trying to prove many of these studies to be false accusations. They only address a handful of the criticisms above and none of them actually demonstrate the safety of DMAA. So why even bother? Because if DMAA is not a “natural” compound used for “hundreds” of years and generally recognized as safe (GRAS) then DMAA would be considered a novel drug and USPLabs would actually have to demonstrate safety and efficacy data in order to stay on the market. By asserting it is a “natural geranium extract” it can be shielded by the DSHEA and make all the burden of proof lay with the FDA while selling their product. Some consumers clearly know it is an amphetamine and use it as such for performance enhancement. At least they are (marginally) informed consumers. But many do not realize this and believe the marketing hype that this is a safe and an all-natural product, and have paid with their health and their lives.

Conclusion

Despite USPLabs protestations, there is no reasonable way that DMAA can be considered a natural or safe product for sale as a supplement under the DSHEA. And even if it did meet DSHEA requirements, this is an excellent example of the dangers of the law in the first place that allows so-called natural compounds to be marketed without prior safety and efficacy testing. The authors recognize that in the vast majority of cases such compounds have no effect at all, whether positive or negative, and the primary harm is in wasting people’s money with claims that are tantamount to fraud. However, there are clearly cases where that is not the case and harm is established about as clearly as one could expect without people dropping like flies. And that doesn’t take into account the less severe or acute harms experienced by vast numbers of people taking untested supplements.

But even more alarming to us is the fact that this DMAA saga exposes quite clearly how unscrupulous companies driven by nothing more than profit can game the system using the DSHEA as a shield with such incredibly paltry evidence as a single article that can’t even be found as anything but a reference to support their claim for exemption under the DSHEA. While it is not established to any legal certainty, it seems quite clear to these authors that there is a preponderance of evidence demonstrating USPLabs and potentially other DMAA product manufacturers are knowingly selling a synthetically-derived drug and using the popular notion of the Naturalistic Fallacy to market it for significant profits.

Authors

bussel-igorIgor I. Bussel graduated from the University of California, Irvine in 2006 with a BS in Biological Sciences and distinction for excellence in research, and matriculated at the Chicago Medical School at RFUMS as a dual-degree student and has earned an MS in Healthcare Administration and Management. Igor recently completed the Doris Duke Clinical Research Fellowship at the University of Pittsburgh ophthalmic imaging research laboratory and will be pursuing residency training in ophthalmology and aspires to become a clinician-scientist.


andrey-pavlovAndrey Pavlov Jr. graduated from the University of California, Irvine in 2005 with BS in Biological Sciences and a BA in Anthropology. After graduation he worked in the ER at a Level 1 Trauma facility for 3 years and then entered the University of Queensland-Ochsner medical program. During this time he lead development of the US Medical Licensing Examination adjunct curriculum for the School of Medicine and was an executive founding member of the Ochsner Medical Student Association of which he is currently President. Andrey will be pursuing Internal Medicine residency training followed by a Critical Care and Pulmonology fellowship, with specific interest in sepsis, space medicine, and comparative effectiveness research.

Posted in: Herbs & Supplements, Legal, Science and Medicine

Leave a Comment (29) ↓

29 thoughts on “DMAA: Efficacious but is it Safe?

  1. windriven says:

    It is my understanding that traditionally FDA has taken a relaxed approach to synthetic equivalents to biological compounds for DSHEA purposes. But draft guidance* currently in circulation contests that and seems to suggest that FDA will crack down on synthetics in the future.

    “Is a synthetic copy of a constituent or extract of an herb or other botanical a dietary ingredient?

    No. A synthetic copy of a constituent of a botanical was never part of the botanical and thus cannot be a “constituent” of the botanical that qualifies as a dietary ingredient under section 201(ff)(1)(F) of the FD&C Act (21 U.S.C. 321(ff)(1)(F)).[13] Similarly, a synthetic version of a botanical extract is not an “extract” of a botanical under section 201(ff)(1)(F) because it was not actually extracted from the botanical.”

    While that would seem to put an end to the issue of DMAA sooner rather than later, I would expect BigQuackery to be lobbying both FDA and our wise and scientifically astute members of Congress to see that this gets watered down. It isn’t just DMAA. One assumes that a myriad of DSHEA products currently contain synthetic compounds.

    I would also guess that the Society for Admiring Pelargoniums (SAP) will fight for synthetic DMAA to protect the lives of millions of precious geraniums.

    *http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/DietarySupplements/ucm257563.htm

  2. Andrey Pavlov says:

    @windriven:

    It is my understanding that anything synthetic cannot be considered legal to market under the DSHEA. However if a synthetic compound is found to have a “natural” analogue then that analogue can be used if it meets one of two criteria – either it was grandfathered in when the DSHEA passed in 1994 and was already on the list of approved/used natural supplements or you can establish a “history of use” such that it can be deemed GRAS.

    That is why the Ping study of 1996 is the cornerstone of the claim for DSHEA exemption – it supposedly demonstrates that geranium extract both contains DMAA and that it has been used in TCM for “hundreds of years.” It was our intent to demonstrate that not only is this insufficient criteria to protect consumers, but that even if it were there is good reason to believe that USPLabs has never actually used “natural geranium extract” in its product. Also, it is a bit ludicrous that a single study, the text of which cannot even be found, is sufficient to meet the requirements of the DSHEA but, we believe that technically it does which is a pitfall secondary only to the fact that this places the burden on the FDA to prove USPLabs wrong, not the other way around.

    I’ll try and post and respond throughout the day but I am on ICU service today and will have limited opportunity so apologies for any delays and/or brevity in responses today.

    1. JOE says:

      Thank you for your article and your time. Having used Jack3D with the original formula in the past, I can say that it did produce the desired acute effects. I am not promoting nor condemning this product. However, I am curious about the L-Arginine’s vasodilator effects and does it offset the potential damage of a vasoconstrictor when used simultaneously. As so many variables exist, or could exist, it seems that only a controlled study performed in an unbiased scientific lab/environment would yield the facts that I seek. Do bl thinners and/or anti hypertensives provide protection? Does acute use vs chronic use result in similar findings. I understand the safety issues, but so few deaths compared with the number of users of these products could be said of a vast number of medications and supplements.

      1. WilliamLawrenceUtridge says:

        So, you’re looking for a way to offset the poorly-understood risk of death caused by an unregulated, unproven ergogenic supplement, which doesn’t even have medical benefits, by proposing the use of blood thinners and pressure droppers? Oy vay, just give up on that extra rep or shaving a minute off of your 5-k run.

      2. WilliamLawrenceUtridge says:

        On reflection, the even funnier thing about this comment is that it would solicit advice from this website on how to offset the risk of sudden cardiac death by loading up on unnecessary medicines.

  3. rwk says:

    Welcome back, Nybgrus! Excellent article. You could probably post many more like that.
    How about one on Rhodiola, as I think you mentioned you’d done research on that herb.

  4. Andrey Pavlov says:

    @rwk:

    haha – so much for my not-so-secret identity, eh? Thanks for the welcome back, and the compliment. I have now finished all of my undergraduate board exams and made strong headway on my research projects so I was ready to come back and this article was a timely way to do it. Though, I will likely not be commenting quite as much as I used to.

    As for Rhodiola – funny you should mention that. My co-author and I met (and became good friends) in that lab where we did work on Rhodiola. He is far more expert in it than I am having spent much more time doing research on it than I did. However, it actually is on our “list of potential topics.”

  5. Xplodyncow says:

    Clearly, Big Pharma has the wrong business model. Why bother with pesky, costly phase 3 trials? Just claim your synthetic compound is found in nature, cite some obscure (possibly nonexistent?) paper, and throw your product on the market — thereby making millions rather than spending billions. Ha, ha, understaffed, overworked FDA! Your move!

  6. Andrey Pavlov says:

    Yes, that is the model that CAM has been taking. And – as we all know around these parts – one of the biggest problems with the DSHEA and these “health freedoms” initiatives. It is just that this time it is reasonably obvious that this is exactly what has been going on and people have actually died directly as a result (well, as directly as we could really hope to link it). In most cases it would be reasonable to assume that there is minimal harm or that the harm is in exacerbating co-morbities which then would mask the true cause of death by the more proximal cause.

    The thing I am personally more surprised about is that there haven’t been more unscrupulous people taking advantage of this sort of thing. As Phil Plait once said, if the likes of us didn’t have “morals” and “scruples” and “ethics” we could make a fortune exploiting the cognitive loopholes we know about. On such example would be Burzynski.

  7. Fracescodel says:

    Seems like a total scam, where the FDA tries, once again, to kill a formidable product to protect the interests of the pharmaceutical and doctor prescriptions lobbies. The end result is to take away cost effective supplements, that are not regulated…leaving the consumer at the mercy of expensive visits, prescriptions, and RX grade pharmaceuticals, which are often more dangerous and pushed on the public without too much concern. Had a friend that was given amphetamine to loose weight; strong, much stronger than DMAA will ever be, and my friend was just a little overweight. I take this chance to tell the FDA: take your hands of DMAA, and any other cost effective non regulated product available to the consumer; your allegiance is with the public, not with corporate Pharma!

    1. WilliamLawrenceUtridge says:

      DMAA is not a medicine, it’s a supplement designed to help the already fit get fitter (assuming it even works). It’s not a right to have such ergogenic aids available, they do not preserve or protect life – they are purely for entertainment, a form of exercise masturbation. Drugs have recognized risk:benefit ratios that are assessed and measured, but above all – proven. DMAA has no proven benefits, and even if it did, since it’s not a medicine there’s no real defence for it being a purchasable product if it has adverse health effects.

      All you are proving with your anecdote is that your friend saw a bad or corruptible doctor; rather than legalizing DMAA because “this guy got something more dangerous”, don’t you think a more acceptable response would be taking steps to ensure that dangerous drugs are better controlled?

  8. Andrey Pavlov says:

    Our noon conference was canceled so I have some time in between patients.

    Fracescodel’s complaint goes a bit deeper, though I doubt (s)he realizes it. At the core of his argument (I’ll assume a male gender for simplicity) is the question of whether we should regulate anything at all. Considering that we do, in fact, regulate many substances I think that ship has sailed. So the question becomes how and what do we regulate?

    The point of my article with Igor was to demonstrate why using a second standard of regulation via the DSHEA fails to protect consumers and their health. The reality is that DMAA is efficacious. I have absolutely no doubt that it works and that (almost) all the claims of Jack3d are reasonably correct. But the reason it works is that this is an amphetamine no different than adderal, ritalin, or the stuff Walter White makes and you can buy on the street.

    So a better question, Fracescodel, is do you think that we should allow manufacturers to including amphetamine in soft drinks that kids can buy? Or at all? Coca-Cola used to actually contain cocaine and it was wildly popular and efficacious. We’ve since seen fit to remove the cocaine from the beverage (well, the active compounds anyways – they still actually use “depleted” coca leaves in the manufacture of Coke).

    The further point is that the DSHEA allows for obviously synthetic chemicals – which by any other definition would be called a drug and regulated as such – to be marketed and sold on an unsuspecting public simply by claiming it is a “natural” plant derivative and making a highly tenuous connection to “traditional use” because that meets the incredibly flimsy criteria of GRAS.

    And the problem is that the onus to prove that isn’t the case falls on the FDA which of course doesn’t happen unless people actually die and press the issue. Which is exactly what has happened with DMAA.

    So, Fracescodel, the question is are you comfortable arguing that we should openly allow the marketing of amphetamines in soft drinks or not? If so, why not cocaine in coke?

    And I’ll say that I am generally for the legalization of drugs. Criminalizing them has ample evidence to demonstrate it is a complete failure and engenders more criminal activity than it curbs. There is also evidence that the legalization of certain drugs – the highly addicting ones – do have significantly detrimental effects on societies and people. However, education campaigns, support systems, and age restrictions do ameliorate those societal ills and mitigate the concern to a certain degree. The money saved in criminalizing drugs can instead be used for those purposes. There will be new and different negatives, but I believe the preponderance of evidence demonstrates that overall it would be a net benefit.

    So that said, I am generally OK with the notion that people can buy amphetamine over the counter – so long as it is advertised properly with informed consent, education as to the dangers of using it, and support for those who become addicted. But doing so under the guise of “all natural” and lying to consumers about what they are actually consuming by abusing the DSHEA is certainly not the way to go about it.

    (and yes, there are nuanced arguments about legalization of drugs and I would like to see them well regulated and primarily prescription which creates issues vis-a-vis opioids and stimulates, but that is a whole separate conversation not directly pertinent here)

  9. Stacey says:

    Thank you for this article. I am honestly shocked at the notion that the manufacturer used a natural extract to cover a synthetically created compound being used in their supplements. Why I am shocked I don’t know, but I am nontheless. I have been scouring the internet for the last 24 hours after coming across articles about the FDA actions against supplements containing DMAA. I was taking Oxyelite Pro for a couple months earlier this year at a third of the dose “suggestion” (1 pill a day on the days I worked out). In March, I had what I am now guessing was an adverse reaction to the supplements and was diagnosed as having a TIA due to a spike in blood pressure. All my life I have had unusually low blood pressure so I and my doctor could not wrap our heads around what all of a sudden caused this dangerous spike that lead to a cognitive disturbance, mystery rash (the weirdest symptom by far), and ultimately the TIA. After reading all I have over the last 24 hours I feel a little duped by their marketing. I thought I had put enough research into choosing this supplement and it is very apparent I did not. It certainly did not help that they were not honestly marketing. The fact that I was not even taking the maximum dosage frightens me thinking about those out there who did/do.

    Thank you again for shedding a little more light on this topic.

    1. Andrey Pavlov says:

      Hello Stacey,

      Thank you for the kind words. It is indeed frightening just how much leeway the DSHEA gives manufacturers, scrupulous or not.

      I am also sorry to hear about your medical ailments, but glad that you didn’t have a worse outcome. As we have seen from DMAA young healthy people have died as a result of taking this “natural” supplement.

      Marketing is incredibly powerful. A really big part of why I do this, and why the rest of SBM contributors do as well, is we know and understand how easy it is to get duped. We are experts in this field and can rapidly and (relatively) easily parse through this stuff. But I know how hard it is for me to not get duped on goods I purchase in fields I have much less expertise in. Shopping on Amazon can be difficult when I am trying to get items for hobbies that I am not expert in. And I don’t have the pressure of it being something that could harm my health – just my wallet. Finding a good, science and evidence based source for reviews and answers is difficult indeed.

      I am glad that our article has helped you in some way and hope others have found it useful as well.

    2. WilliamLawrenceUtridge says:

      Congratulations on acknowledging your mistake. Many, many people don’t. Not admitting you are wrong is an unfortunate and powerful human trait, and you should be proud of the fact that you are willing to do so. Others may criticize you for changing your mind. They are idiots. Be proud.

  10. mike says:

    I was a dmaa user for approximately 1 year. It does in fact give you a buzz. I recall using it for the first time, and after completing my weight lifting routine, sat on my couch and felt its very distinct euphoric effect. I built up a tollerance in a very short period of time, and never felt that feeling again. It seems to me that dmaa blocks or calms the negative thoughts associated with exercise. While on dmaa I would regularly do 4 or 5 heavy lifting excersises before my mind would say ok that’s enough. Now that I stopped using it, after 2 or 3 I get the same feeling. Dmaa didn’t give me energy, it simply masks the mental stress which comes with exercise. I miss it and my workouts are considerably less intense.

    1. Andrey Pavlov says:

      That sounds about right. It is amphetamine, after all. I remember taking a supplement called “Redline” once when I was in my hardcore training phase and I absolutely went bonkers. I cycled 80 miles with 3,000 feet of vertical ascent in >100 degree F heat, then ran 5 miles, and still couldn’t sit still so I started doing push ups, jumping jacks, and lifting weights at home until I finally settled down. I have no idea what was in that stuff, but boy was it potent.

      The problem with Jack3d/DMAA is not that it doesn’t work (which is the most common issue with “alternative” and “natural” therapies and supplements) but that it is amphetamine disguised as a “natural” supplement. If you wish to take stimulants like amphetamine to aid in your workouts, then that becomes your choice. But there are indeed significant health consequences to that and as a (soon-to-be-) physician I would strongly advise you against doing so.

      Whether it should be legal or not to obtain OTC is a different conversation, but the point of the matter here is that it is certainly much more dangerous to have an OTC amphetamine that people don’t know about; hidden in the marketing guise of “all natural” and slipping through the fingers of the FDA thanks to the DSHEA and making people think it is not just effective (which it is) but safe as well (which it most certainly is not).

  11. Chemmomo says:

    Completely off topic question for Andrey Pavlov: Is that your photo over at Panda’s Thumb? It’s beautiful, and had they put it into the contest my co-conspirator in selecting which gets our vote and I would have had much more difficult decision.

    1. Andrey Pavlov says:

      I guess we must read the same things… yes, that is my photo at PT. I was slightly disappointed that it didn’t make the finals, but do realize it is more of a bio sci site and it was really nice of them to publish it anyways. I had no idea they were going to do that, nor use as much of my verbiage in describing it as they did.

      In any event, thank you for the kind words! I took that photo (along with a series of others) as a study break when I was preparing for Step 1 of the medical board exams. I have many more (and a few other science photos I’ve attempted) over at my fiance’s Flickr account. Happy to send you the link if you are interested.

  12. Paul Memoli says:

    “DMAA is not a medicine, it’s a supplement designed to help the already fit get fitter (assuming it even works). It’s not a right to have such ergogenic aids available, ” Who the hell are you to impose such a moral judgement on everyone else? What is wrong with wanting to be stronger, faster and healthier – any which way you can? Why don’t you go after canned tuna fish, something that many bodybuilders eat daily for a high protein intake, yet contains the toxic substance mercury?

  13. Paul Memoli says:

    OK, I am taking the liberty of posting this Consumer Reports article about the dangers of canned tuna and how the FDA has never gone after any sellers of canned tuna fish, as a counterpoint to this war of words on the DSHEA.

    This article appeared in
    January 2011 Consumer Reports Magazine.

    Canned tuna, Americans’ favorite fish, is the most common source of mercury in our diet. New tests of 42 samples from cans and pouches of tuna bought primarily in the New York metropolitan area and online confirm that white (albacore) tuna usually contains far more mercury than light tuna.

    Children and women of childbearing age can easily consume more mercury than the Environmental Protection Agency considers advisable simply by eating one serving of canned white tuna or two servings of light tuna per week. A serving is about 2.5 ounces. Expect a 5-ounce can to contain about 4 ounces of tuna plus liquid.

    The heavy metal accumulates in tuna and other fish in an especially toxic form, methylmercury, which comes from mercury released by coal-fired power plants and other industrial or natural sources, such as volcanoes.

    Fortunately, it’s easy to choose lower mercury fish that are also rich in healthful omega-3 fatty acids. That’s especially important for women who are pregnant or might become pregnant, nursing mothers, and young children, because fetuses and youngsters seem to face the most risk from methylmercury’s neurotoxic effects.

    Results from our tuna tests, conducted at an outside lab, underscore the longheld concern for those people. We found:
    Every sample contained measurable levels of mercury, ranging from 0.018 to 0.774 parts per million. The Food and Drug Administration can take legal action to pull products containing 1 ppm or more from the market. (It never has, according to an FDA spokesman.) The EPA compiles fish advisories when state and local governments have found high contaminant levels in certain locally caught fish.
    Samples of white tuna had 0.217 to 0.774 ppm of mercury and averaged 0.427 ppm. By eating 2.5 ounces of any of the tested samples, a woman of childbearing age would exceed the daily mercury intake that the EPA considers safe.
    Samples of light tuna had 0.018 to 0.176 ppm and averaged 0.071 ppm. At that average, a woman of childbearing age eating 2.5 ounces would get less than the EPA’s limit, but for about half the tested samples, eating 5 ounces would exceed the limit.

    In 2006 we scrutinized the results of the FDA’s tests in 2002 to 2004 of mercury levels in hundreds of samples of canned tuna. The agency’s white-tuna samples averaged 0.353 ppm; light tuna, 0.118 ppm. But we found that as much as 6 percent of the FDA’s light-tuna samples had at least as much mercury as the average in white tuna—in some cases more than twice as much.

    Given the uncertainties about the impact of occasional fetal exposure to such high levels, we urged the FDA to warn consumers about occasional spikes in mercury levels in canned light tuna. More than four years later, the FDA still hasn’t issued such a warning. When we asked why, an FDA spokesman indicated that the agency had already taken the spikes into account when formulating its mercury advice.

    Bottom line

    Canned tuna, especially white, tends to be high in mercury, and younger women and children should limit how much they eat. As a precaution, pregnant women should avoid tuna entirely. Our answers to the questions in Fish Q & A can help you get the nutritional benefits of fish and minimize exposure to mercury.

  14. WilliamLawrenceUtridge says:

    Who the hell are you to impose such a moral judgement on everyone else? What is wrong with wanting to be stronger, faster and healthier – any which way you can?

    DMAA shows serious indications of being acutely fatal to some. Despite this, it is not presented as having such risks. Not to mention, there is no good evidence it is even effective at making people stronger or faster, and if it kills you, you’re certainly not healthier.

    Unlike tuna, DMAA does not have a serious discussion and ubiquitous set of warnings about the dangers, proven or potential, of consuming it. DMAA is not tuna. Tuna is not accompanied by acute risk of death, unless you bring up choking. The world is aware of the long-term effects of consuming large amounts of tuna, the same can not be said for DMAA.

  15. Andrey Pavlov says:

    I’m not entirely sure the point you are trying to make with the discussion about tuna. The whole of it smacks of a tu quoque fallacy. Regardless of the whether the FDA has been an utter failure regarding tuna or not, does not in any way change the thesis of my article. In fact, it only further reinforces the lack of resources and means that the FDA has at its disposal to adequately enforce health dangers.

    In any event, as WLU pointed out, the dangers of mercury in tuna fish are well known, well publicized, with advisories on consumption in particular with regards to pregnant women. So the entirety of that post of yours can be written off as a completely separate topic.

    As for your second post….

    Please read my response to fracasdocel which is where WLU’s response was aimed. That said, the availability of such drugs is a tenuous and difficult discussion. One thing that is certain, however, and indeed the point of my article is that in any case there should be well informed consent on the part of the user. That means we need to know exactly what is in a product and what the effects, side effects, and risks are.

    I would argue that from a public health perspective WLU is more or less correct. Allowing people free access to a compound that can give them heart attacks and lead to sudden death in otherwise healthy young people seems like a bad idea. Particularly if the marketing does not include that as a risk. Having someone be prescribed an amphetamine for weight loss by a physician at least carries with it the onus of follow up by someone trained to do so. Buying it OTC does not. However, in the case of weight loss it becomes a risk benefit analysis. I would argue that in most cases the benefit does not outweigh the risk and perhaps it was a not-so-good doctor that offered the prescription. In the case of simple performance enhancement in an otherwise healthy person, the risk benefit certainly does not pan out. In that case we but against the issues of personal freedom, autonomy, and informed consent. In which case we are right back at my previous comment.

    1. WilliamLawrenceUtridge says:

      It’s weird to see you agreeing with someone :P

      1. Har har: :-P I’ll agree with anyone who has a good point. But I’ll still point out a tu quoque fallacy when I see it.

  16. Andrey Pavlov says:

    Thanks for your comment. However, I think we have enough knowledge on basic principles to say that your idea is rather dangerous. It is never a good idea to counterbalance one effect with an antagonist effect. In a complex system that invariably leads to differential effects that we can’t predict. We only do so when we are forced to in extreme circumstances and the only other options are severe morbidity or death.

    Firstly, when it comes to arginine, it seems that the data for the pharmacokinetics is a bit sparse. I don’t have the time to do a full lit review at the moment, but let’s assume it does have some reasonable vasodilator effects (since there is indeed evidence that it does). The effect is mediated through conversion to nitric oxide and thus smooth muscle relaxation.

    The effects of amphetamines (such as DMAA) is mediated through adrenergic responses releasing cathecholamines and stimulating both direct cathecholamine and sympathetic nervous vasoconstriction.

    How would these two competing effects actually pan out in vivo? Nobody can say for sure. However, one thing that is pretty certain is that it would be highly variable from individual to individual.

    Firstly, the pharmacokinetics of arginine would be highly variable. It is depending on both availability, serum levels, tissue penetration, and, of course, the conversion to NO.

    Contrast this with amphetamine which acts more centrally and thus the effects would be more uniform and it becomes easy to see how you can have areas in which vasoconstriction predominates. If that area is in your coronary arteries, the fact that your peripheral arterioles are not significantly vasoconstricted means very little.

    They also act through two completely different mechanisms with completely different half lives of effect. NO is extremely short acting and only over small distances. Catecholamines have a rather longer half life and are distantly acting. Catecholamines also stimulate Gs coupled pathways which would inactivate some of the downstream components that would be used in conversion of arginine to NO so it is reasonable to assume that any beneficial neutralization of effect from arginine would be outlived by the amphetamine action.

    And, of course, that doesn’t address the other harms of having a hypermetabolic state and the other harms of amphetamine use that aren’t directly related to vasoconstriction.

    So all in all, it is a rather poor strategy that is likely to have more unwanted side effects rather than less (and be less predictable along the way). It does seem to me rather silly to take performance enhancing drugs since there are very often long term sequelae (just look at Arnie) and most people regret it later in life when they have to deal with those effects.

    Ultimately it boils down to personal choice and public health burden for those choices (which can be competing interests). Either way, informed consent is necessary and the point of my article is to demonstrate that we absolutely do NOT have informed consent with any of these DMAA containing products and in fact have clear evidence of intentional misinformation to sell a product.

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