The Dendrobium Craze, Or What Happens if You Ignore the Obvious Difference Between "A" and "B" - Latest Study: At Best Trace Amounts of "Meth Analog" in DS Craze

DS Craze was not the only dendobrium containing supplement that disappeared from the market, when "the craze" about meth in dietary supplements broke lose.

You will certainly remember the craze about Craze and other dendrobium based pre-workout supplements. In an article published in Drug Testing and Analysis on October 14, 2013, scientists from Harvard Medical School and NSF International, a respected third-party testing organization, reported the presence of the "methamphetamine analog" N,α-diethyl-phenylethylamine (N,α-DEPEA) in three samples of Driven Sports' flagship pre-workout product "Craze" they purchased from various retailers.

Using what they considered established reference standards and sensitive analytical methods, Cohen et al. found what they thought was N,α-DEPEA at concentrations ranging from 21 to 35 mg per serving in the supplements (Cohen. 2013)

Citrulline is another pre-workout ingredient - a 100% safe one ;-)

Citrulline prevents muscle catablism more than leucine

Arginine & citrulline for blood lipid control

EAA, BCAA, or citrulline for anti-catabolism?

Glutamine not citrulline to heal the gut?

Citrulline to ignite fatty acid oxidataion?

High & low dose arginine ineffec- tive NO boosters

The results from this the study Cohen et al. conducted in 2013 were later officially confirmed by researchers from the Korean Forensic Service who found 0.40 and 0.44% N,α-DEPEA, respectively — the equivalent of roughly 23 mg per serving in their samples of Craze (Lee. 2014).

Now, N,α-DEPEA is only one out of several phenylethylamines aka "PEAs", of which even Cohen et al., whose paper started the whole craze say that the spectrum of PEAs "range[s] from benign compounds found in chocolate to synthetically produced illicit drugs" (Cohen. 2014). In that, minimal structural differences determine, whether we are dealing with a harmless ingredient of chocolate or a methamphetamine analog like N,α-DEPEA with the difference in the chemical structure of the agents being small, in some cases marginal (Lee. 2014).

Figure 1: Different phenylethylamines (PEAs) with different degrees of structural resemblance
and different physiological effects (Wahlstom. 2014)

In this context, it's important to know that N,α-DEPEA is not the only isomer of diethyl phenethylamine. Next to N,α-diethyl phenethylamine (the N,α isomer), there are also N,β-diethyl-phenethylamine (the N,β isomer), and N,N-diethyl-phenethylamine (the N,N isomer). Three agents of which Dallas Wait writes in a recent issue of the AHPA Report that specifically the...

"[...] N,α and N,β isomers have very similar chromatographic characteristics and are difficult to resolve unless the test method being used is optimized to properly separate both isomers" (Wait. 2014)

This similarity makes the two DEPEA isomers very difficult to distinguish. More importantly, the existence of the N,β isomer implies that anyone who analyzes dietary supplements for N,α-diethyl phenethylamine runs the risk of generating false positive  - yet unfortunately, this is exactly what Cohen et al. (2013) and Lee et al. (2013) and before them Mahmoud A. ElSohly & Waseem Gul (2013) obviously did.

My previous Craze article is now obviously obsolete | read more.

"As such, the alleged presence of the N,α isomer may actually be the N,β isomer, or a combination of the two.

Unequivocal identifiation of the N,β and N,α isomers is particularly critical since the N,β isomer does not share the same structural similarities that N,α shares with methamphetamine (also alkylated in the α position, not the β position)." (Wait. 2014)

Needless to say that the existence of said structural difference does also imply that the agent won't fit into the corresponding receptor site or interact with the same enzymes N,α-DEPEA and "real" methamphetamies do. Accordingly, the biological activity associated with that compound are certainly different from those of N,α-diethyl phenethylamine.

What is phenethylamine? Phenethylamine (PEA) is a natural monoamine alkaloid that belongs to a class of chemicals with many compounds of known psychoactive and stimulant effects (Glen. 2005). It functions as a neuromodulator or neurotransmitter (Sabelli. 1976) with similar actions as amphetamine: Norepinephrine + dopamine release (Parker. 1988; Paterson. 1993). PEA and its substituted forms NDP and ETH is rapidly metabolized when taken orally (Shulgin. 1995-2009).

Obviously I wouldn't be telling you all this if it wasn't related to the (un?)surprising results of a recent study. Results a group of researchers from Q&Q Labs AB in Gothenburg, Sweden, published in issue #6 of the peer-reviewed journal Analytical Methods that is published by the Royal Society of Chemstry (Wahlstom. 2014).

In said paper, the authors, Wahlstrum, Styles and Hägglund present the results of an analysis of two samples of Driven Sports' pre-workout product Craze ("Candy Grape", batch # 1305323 and "Berry Lemonade" batch # 1303298) that was conducted with a new analytical method that can "reliably" identify and quantify the individual amounts of N,α-diethyl phenethylamine (N,α isomer), N,β-diethyl-phenethylamine (N,β isomer), and N,N-diethyl-phenethylamine (N,N isomer) in a sample.

Table 1: Amounts and relative standard deviations (RSD) for the two samples of
DS Craze with lot no. 1303298 and 1305323 (Wahlstrom. 2014)

Usually I would plot the results, but in view of the fact that the amount of N,α-diethyl phenethylamine that was previously reported to be in the milligram range is de facto in the nanogramm range (1/1000 mg = 1 µg = 1000 ng), I decided to stick to the tabular overview (Table 1) from the original publication by Wahlstrom et al. (2014).

Figure 2: Mean amount of N,α-diethyl phenethylamine (in ng) in one serving of Craze according to Wahlberg (2014) and Lee (2014) - mind the logarithmic scaling of the graph!

So what does all that mean? You don't have to be a mathematics professor to see that even with the calculated standard deviations of 6.6% and 8.9% we are miles away (103303% to be precise) from the previously reported 23mg of N,α-diethyl phenethylamine per 5.8g serving of Craze (Lee. 2014).

This does not necessarily mean that all the craze was for nothing, though. As far as I know it is likely that N,β-diethyl-phenylethylamine is harmless. Studies which would investigate its biological effects on rodents, let alone animals, on the other hand, are as of yet not available; and if we are honest this and not the presence of "structural analogs" of whatever should be what we as supplement users are interested in, right?

Assuming that Driven Sports was willing to pay not just for the study at hand which was "made possible", as the authors of the study say, "by support from Driven Sports Inc" (Wahlstrom. 2014), but also for an analysis of what exactly the major DEPEA compound in the product does, this may finally solve the whole conundrum. A safety analysis for the complete supplement is - at lest for short-term use - available, anyway (Kedia. 2014) | Comment on Facebook!

References:

• Cohen, Pieter A., John C. Travis, and Bastiaan J. Venhuis. "A methamphetamine analog (N, α‐diethyl‐phenylethylamine) identified in a mainstream dietary supplement." Drug testing and analysis (2013). 
• ElSohly, Mahmoud A., and Waseem Gul. "LC–MS-MS Analysis of Dietary Supplements for N-ethyl-α-ethyl-phenethylamine (ETH), N, N-diethylphenethylamine and Phenethylamine." Journal of analytical toxicology (2013): bkt097. 
• Kedia, A. William, et al. "Effects of a Pre-workout Supplement on Lean Mass, Muscular Performance, Subjective Workout Experience and Biomarkers of Safety." International journal of medical sciences 11.2 (2014): 116.
• Lee, Jaesin, et al. "Identification and quantitation of N, α-diethylphenethylamine in preworkout supplements sold via the internet." Forensic Toxicology 32.1 (2014): 148-153.
• Wait, D. "The importance of reliable product chemistry data: A case study." In AHPA Report | The Official Publication of the American Herbal Products Association 29.10 (2014). 
• Wahlstrom, R., C. Styles, and G. Hägglund. "Reliable identification and quantification of three diethylphenethylamines in a Dendrobium-based dietary supplement." Analytical Methods 6.19 (2014): 7891-7897.

The European Horse Meat Scandal - Looking Beyond the Hysteria: Why "Horse-Powered" Lasagna Would Actually be Nutritionally Superior to Its "Beefed-Up" Counterpart

Lots of good meats on Fury from the slaughterhouse ;-)

I am not sure if all of the US and other international students of the SuppVersity have already gotten wind of the huge "scandal" *rofl* about horse meat in convenient foods. In case you ain't no clue what I am talking about, here is the gist: About a week ago the first reports surfaced that some of the junk... ah, I mean instant meals that are sold by the largest supermarket chains in Europe and produced by such "reputable" companies as Nestlé and Co. are "adulterated" with horse meat (if you want to, you can read up on the whole story in the online version of the NY Times; read more).

Actually things started out with frozen Lasagna and now horse meat appears to be in everything the average convenient food lover packs into his shopping basket. Now, frozen lasagna (unless self-prepared) is nothing I would expect the average SuppVersity reader to consume on a regular basis, anyway. And the mislabeling of the products alone would certainly not qualify as being "SuppVersity newsworthy", either. The fact that it may be a smart move of yours to actually buy horse-meat lasagna (obviously not the one that was made with the meat of potentially sick animals) instead of regular one is however exactly the kind of stuff you read about here at the SuppVersity - and I would venture the guess only at the SuppVersity.

"Horse meat? You're kiddin' right?"

If we disregard the argument that horses are "amiable animals" that are "not supposed to be eaten" that's brought forward by many of the costumers as their main rationale why they would not buy horse-meat lasagna or a "Mac Fury" (would certainly be a major advantage over the other "Mac's" you are served at everyone's favorite fastfood chain ;-), there are actually no convincing arguments against the consumption of horse meat.

There is another study, unfortunately in Russian that reports 54% reduction in excess body weight in overweight individuals, whose diets contained obviously significant (yet in the abstract undisclosed) amounts of horse meat, of which the scientists write that it is "a product that possesses lipotropic and choleretic properties" and was the main reason for the "markedly" reduction in body weight, the participants experienced. Moreover, the latter went hand in hand with "a considerable improvement of liver function" (Kadyrova. 1984). Without access to the full-text, I am yet unable to say anything but "interesting" about this study... although, I guess I may add that it is not just interesting, but intriguing that these two were the only horse meat based dietary interventions I could come up with.

That being said, it's certainly no coincidence that the editors of the International Journal of Food Sciences and Nutition decided to finally include the 2012 paper by Chritian Del Bo et al. that has hitherto only been available as an ePub in the March 2013 issue of this monthly Journal. In the said study, the researchers from the Dipartimento di Scienze per gli Alimenti, la Nutrizione e l'Ambiente (that's what I call a well-sounding name ;-) at the University of Milano investigated the "long-term" (=90 days) effects of regular horse meat (2x 175g per week) consumption on the health of 26 of the 52 healthy volunteers who participated in their study and compared them to the 26 participants who were told to abstain from horse-meat for the full three months study period. The results were absolutely unequivocal: Horse meat, as red and culturally depreciated as it may be let to..

• significant reductions in serum levels of total (-6.2%) and low-density lipoprotein cholesterol (LDL; -9.1%) and transferrin levels (- 4.6%), as well as
• increases in total omega-3 content /+7.8%), omega-3s (+8%) and docosahexeanoic acid (DHA; +11%) in the red blood cells of the subjects (p < 0.005 for all)

As exciting as these observations may sound, the study design makes it difficult to say whether they were a result of replacing horse-meat for other meats or simply eating meat at all (I know you that common wisdom tells us that red meat kills, but you've heard me talk about the fallacy of this assumption on one of the last installments of the Science Round Up).

Aside from the common (and flawed) wisdom about the ill health-effects of meat eating aside, there is another important and obviously way more convincing argument for the former explanation (replacement effects), which pertains to the omega-6 to omega-3 ratio in horse-meat.

Table 1: Omega-6 (N6) to omega-3 (N3) ratio of selected foods (extended version of Bourre. 2005)

With an omega-6 to omega-3 ratio of 0.6 and thus 1 gram of omega-6 fatty acids per 1.7 grams of omega-3s, horse meat is almost on par with farmed salmon (see "Making the Right Fish Choices") and far superior to grass-fed beef, which contains 2 grams of omega-6 fatty acids for every single gram of omega-3s (n-6/n-3 ratio of 2.29; see previous SuppVersity post).

"Hold on! Where is the downside? Where the "on the other hands?"

With 100g of horse meat offering 21g of quality protein, 5g fat (approx. 1g saturated fat, 2g monounsaturated fat and 1g PUFAs) and obviously zero grams of carbohydrates, the ideal protein source, but wait: All this does in fact sound a little "too good too be true" and there are in fact a couple of "on the other hands" attached:

• The Lance-Armstrong factor: As already mentioned before, there is currently a large concern about medicine residues in the horse meat that was added to the instant meals over here in Europe. Yet despite the fact that you can certainly argue that there is a certain chance you would be eating a former race-horse, which collapsed from an overdose of performance enhancing drugs, regular horse meat is as tightly controlled as all other meats and your chances to consume consume any sort of medication are thus not higher lower than with other meats, as long as you don't buy them on the gray market in Romania (where the horse meat in the scandal is supposed to come from) or China ;-)

• 

  I guess you may have heared about toxoplasma gondii being transfered from rodents to cat and accidentally to humans, but do you also know that infected men have higher testosterone levels? No? Well, in the end this is not a recommended way to up your testosterone production, anyway (lean more)

  The nasty bugs factor: Another commonly heard argument against eating horse-meat is based on some horror stories about people dying from bacterial infections after consuming old, imported and improperly stored (the scaremongerish reports obviously don't mention that) raw horse-meat (Gill 2005). This is obviously another non-horse-specific problem and can be easily avoided by buying your meats from the right sources and heating them to temperatures >67°C. The heat will also take care of any Toxoplasma gondii contaminations and the larvae of Trichinella. Both parasites are often named in the same breath as "horse meat", despite the fact that they are not horse-specific and have almost exclusively been found in meats imported from overseas (Pozio. 2001; Pomares. 2011).

• The polar-bear factor: Just as in the case of the polar bears this does not affect the meat of the horses, but their organs. Depending on the soil on which the horses were housed, their livers and kidneys may contained high amounts of heavy metals (cadmium, Gill. 2005; lead, Kosla. 1989) and are thus not recommended for human consumption unless prior testing was done. 

So, basically this leaves us with only one "on the other hand": The "I don't want to eat Black Beatuy or Fury" Factor. But let's face it: Who of the bacon lovers would say he'd like a piece of Babe?

---

You have been eating dozens of "Babes" and now you refuse to eat the much healthier Black Beauty?

Bottom line: Unless your horse meat is imported from questionable sources, the only valid argument why you shouldn't eat horse meat, and maybe even prefer it over beef, let alone pork, are your own scruples culturally rooted scrouples about eating such a "noble" animal as a horse.

And by the way, when it's cooked its pretty hard to distinguish from beef, anyway. Only when you eat it raw (which is something I don't recommend) you may be able to recognize the slight tinge of sweetness that's a result of the 7x higher glycogen content of horse vs. beef meat.

 
References:

• Bò CD, Simonetti P, Gardana C, Riso P, Lucchini G, Ciappellano S. Horse meat consumption affects iron status, lipid profile and fatty acid composition of red blood cells in healthy volunteers. Int J Food Sci Nutr. 2013 Mar;64(2):147-54.
• Bourre, JM. Where To Find Omega-3 Fatty Acids And How Feeding Animals With Diet Enriched In Omega-3 Fatty Acids To Increase Nutritional Value Of Derived Products For Human : What Is Actually Useful. The Journal of Nutrition, Health & Aging. 2005; 9(4): 232-242.
• Gill CO. Safety and storage stability of horse meat for human consumption. Meat Sci. 2005 Nov;71(3):506-13.
• Kadyrova RKh, Salkhanov BA, Shakieva RA. [Effect of diet therapy using horse meat on liver function of patients with metabolic-alimentary obesity]. Vopr Pitan. 1984 May-Jun;(3):22-7.
• Kośla T, Anke M, Grün M. The lead status of horses from central Europe depending on breed, sex, age and living area. Arch Tierernahr. 1989 Jul;39(7):667-74. 
• Pomares C, Ajzenberg D, Bornard L, Bernardin G, Hasseine L, Darde ML, Marty P. Toxoplasmosis and horse meat, France. Emerg Infect Dis. 2011 Jul;17(7):1327-8.
• Pozio E, Tamburrini A, La Rosa G. Horse trichinellosis, an unresolved puzzle. Parasite. 2001 Jun;8(2 Suppl):S263-5.
• Wise J. "Bute" in horse meat presents very low risk to health, says England's chief medical officer. BMJ. 2013 Feb 15;346:f1066.