Prototype Nutrition Ketoforce

Jun

18

A new stimulant or a new scam?

By Patrick Arnold

See the man in the picture above?  His name is Klein.  Klein recently has been singing the praises of a compound called N-methyltryamine.  You see, he is replacing his products which contain methylhexanamine (geranamine, 1,3-DMAA) with this N-methyltyramine (NMT).  Here are some of the things he says

 (the full link is http://www.ergogenix.com/products/nmt.html)

NMT is known to possess strong stimulant activity, resulting in long lasting smooth energy”

Oh really?  That is simply not true.  In fact it produces essentially no stimulant activity. I will explain why below from a chemical standpoint, but from a personal standpoint you should know I have tried the stuff in 50 and 100mg doses and felt nothing except perhaps some pressure in my head and chest.  Others have tried it with similar failed results.

Klein also said

NMT is a new version of the well-known stimulant L-Tyramine, but does not possess side effects that Tyramine has

I am not sure what he means here by side effects from tyramine but perhaps he means hypertension, which is greatly exaggerated in those taking MAO inhibitors.  N-methyl tyramine is well documented in the literature to possess similar pressor (blood pressure increasing) activity as tyramine so this statement is completely unfounded.  Klein appears to be making this one up in order to sell product.

.Now this one is a real head scratcher

“…the receptors in the body that NMT acts on prevent side effects like rapid breathing and tightness of breath, normally observed from using stimulants during exercise.”

First of all I am not familiar with the term “tightness of breath” (maybe he means shortness of breath, or tightness of chest”?)  Secondly I am at a loss as to what these unique NMT receptors might be.  Do you have any idea?  I think they might be called the bullshit receptors but I am not sure

And this one

The structure of 1,3,DMAA does not contain the key components that are required by any decent stimulant, making it not only relatively inferior in terms of energy to NMT, but also producing more side effects”

LOL. I would be happy to debate the chemistry of stimulants with Klein, and in fact I will do so now.  Mind you, this is some complicated chemistry for many of you.  Unfortunately facts don’t come in clever marketing quips but in actual science, so bear with me.

I refer to the following paper. 

Phenylisoproplyamine Derivatives, Structure and Action van der SCHOOT J, ARIENS EJ, van ROSSUM J, HURKMANS JAArzneimittelforschung. 1962 Sep;12:902-7.

This is an excellent paper on the relationships between chemical structure and pharmacological activity of symphathomimetic compounds.  The word sympathomimetic means stimulation of the sympathetic nervous system which is achieved by compounds such as adrenaline and ephedrine.  Such stimulation results in increased activity and energy expenditure.

In this study they determined sympathomimetic activity by examining the locomotor activity of mice in response to a wide variety of compounds.  They found some key characteristics that affected activity:

1)      For significant activity the carbon chain must be two carbons from the bulky substituent (phenyl ring or alkane ring / branched chain).  Methylhexanamine (1,3-DMAA) and N-methyltyramine both have this.

2)     The amino group must be bound to a secondary carbon atom.  If it is not then the compound will be quickly destroyed by monoamine oxidases.  Methylhexanamine has this, N-methyltyramine does not.

3)     The presence of an OH in the phenyl ring leads to definite loss of activity.  This is because it drastically reduces the ability of the compound to cross the blood brain barrier.  N-methyltyramine contains such  a group, for methylhexanamine it is not an issue.

Now beyond just discussing rules the paper specifically stated that methylhexanamine does have sympathomimetic activity, but you knew that (if you ever tried the stuff).  Although they did not test N-methyltyramine they did test tyramine, and tyramine showed no activity.  But this comes as no surprise since tyramine fails two of the key requirements for symphatomimetic activity.  N-methyltyramine fails these same two requirements, so it surely is inactive as well (but I already knew that from first hand experience). 

Anyway there is just one more thing Klein says that irks me yet amuses me at the same time

1,3,DMAA use may also result in an unsafe synergistic increase of sympathomimetic activity when combined with other compounds, common in the supplement industry. Users of 1,3,DMAA have reported side effects such as shallowness in breathing, fluctuating mood, paranoia, erectile dysfunction, and a severe crash following administration”

I have to completely disagree with Klein here.  The prevalence of most of these side effects is very small, and compared to any other stimulant ingredient that actually does anything (yohimbine, ephedra) is much, much less.

 In my opinion Klein discontinued 1,3-DMAA / methylhexanamine because he fears the FDA is going to rule against it soon and he does not want to be stuck with inventory he has to destroy.  And now he is saying all of this negative BS to hurt the sales of others who are not discontinuing the product.

Now what amuses me about this statement is that Klein made his living the past few years extolling the virtues of this ingredient.  That makes his about face seem so self-serving and hypocritical.  But what is so especially amusing to me is the public fashion in which he is doing this trashing.  He basically is admitting that he believes he sold a dangerous product for years, and so he is making himself defenseless against any civil lawsuits that might be filed against him for damages due to his products. 

Yes, I know there are many class action attorneys out there that would drool reading such a self incriminating statement by a company.  It doesn’t matter if the statement is not based in fact – it only matters that Klein said it and it is recorded.  But before any of these attorneys start shouting “ka-ching” I think there is something they need to know……….

There are three things Klein is known for:  Spitting in your face while he talks to you, a disturbing obsession with fitness model Jamie Eason, and never having any money when it comes time to pay.

8 Responses so far

Is 1,3-DMAA on its way out courtesy of the FDA?

There is no indication that the fda is ready to act on the ingredient. None that I know. of at least.

in the graphic, it says the nitrogen must be bound to a secondary carbon (“essential for activity”). can you clarify what type of activity you are referencing? i agree that it prolongs its half-life, but it doesn’t really have anything to do with its activity, correct? similarly, you note that the hydroxyl group off the benzene ring “leads to definite loss of activity.” Don’t you mean to say that a para-substituted hydroxyl group decreases adrenergic receptor activity (i.e. meta-substituted derivatives have decent activity [especially alpha adrenergic activity]? I agree that it decreases BBB penetration. great article, nonetheless.

That last paragraph was howl-arious!

High Tower, the article I referred to looked at the physical activity of rats after administration of various sympathomimetic like compounds. Increase in “locomotive behavior” as they refer to it is a reflection of the stimulant activity. This, to me, is the number one property one looks for in a diet and energy ingredient.

So the structural associations (lack of OH, presence of secondary carbon atom alpha to the nitrogen) have to do with pure stimulant activity. What happens peripherally in regards to catecholamine release in the heart or vascular system does not necessarily have anything to do with psychostimulatory activity

I appreciate you taking the time to show us the chemistry diagrams (what are these called?) and analyze the predicted effects based on structure.

I can’t say I have tried NMT myself. I noticed that the new Matt Cahill preworkout supplement depends on using a combination of NMT and PEA as its stimulant source.

Back in the old days, Cahill regarded you more or less as a reluctant mentor I believe. Today, Cahill and his colleague Andy are regarded as well-respected formulators, and few would believe they would use an ineffective compound in Driven supplements…but who knows?

Do you still hold firm to your position that NMT is ineffective?

Dendrobium extract is very hot at present.
dear Patrick, Do you have any comment on higenamine as well? Some guys said it is toxic, is that right?

Leave a comment

You must be logged in to post a comment.