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Why weight loss supplements with N-methyltyramine may not work

Slimming supplements with N-methyltyramine [structural formula below] probably work less well than products without this addition. Supplements containing only N-methyltyramine probably even make you fatter. Sidney Stohs and Michael Hartman, both researchers for the American supplements manufacturer Advocare [] come to this conclusion in Phytotherapy Research.

N-Methyltyramine is found in barley, and therefore also in beer. It's also found in relatively small quantities in Citrus aurantium, or Bitter Orange. When DMAA was banned worldwide, a couple of supplements manufacturers promoted N-methyltyramine as a successor.

Already in the summer of 2011 the chemist, genius and supplements manufacturer Pat Arnold wrote on his blog that he had little confidence in N-methyltyramine as a slimming supplement. [] [] Nearly all the studies that Arnold referred to are also mentioned in the article by Stohs and Hartman, which was published in 2014.

Adrenergic receptors
At first glance N-methyltyramine does seem to resemble the natural pep-hormone adrenalin [structural formula on right]. Going by its chemical structure you'd expect that N-methyltyramine could react with the receptors that are intended for adrenalin. And N-methyltyramine does indeed do this, as does the simpler compound tyramine.

Substances that imitate the effect of adrenalin are called stimulants. They induce a state of alertness in the body, suppress feelings of fatigue and hunger and force fat cells to release their contents into the bloodstream. That's why supplements manufacturers often put stimulants into their slimming products. Extracts of Citrus aurantium are popular candidates, as they appear to contain a cocktail of stimulants.

Why weight loss supplements with N-methyltyramine may not work

According to a 2011 French study, if you add some of the components of Citrus aurantium, such as synephrine and octopamine, to fat cells in test tubes, the latter release their contents [lipolysis]. [J Physiol Biochem. 2011 Sep;67(3):443-52.]

The same study also suggests that tyramine and N-methyltyramine, even though they can attach themselves to adrenergic receptors, do not stimulate fat cells to release their contents either.

Why weight loss supplements with N-methyltyramine may not work

The figure below, which comes from the same study, shows that tyramine and N-methyltyramine actually inhibit the release of fat by fat cells.

Why weight loss supplements with N-methyltyramine may not work

N-Methyltyramine appetite enhancer?
Stohs and Hartman continue by saying that N-methyltyramine has more biological effects. The substance not only reacts with the adrenergic receptors, but according to Japanese studies it also stimulates the release of the hormone gastrin in the stomach. [Alcohol Alcohol. 1999 Mar-Apr;34(2):161-8.] [Alcohol Clin Exp Res. 2010 Feb;34 Suppl 1:S14-7.] Gastrin in turn induces the production of hydrochloric acid in the stomach, which improves digestion. This is not exactly what you require of a slimming supplement.

N-Methyltyramine also stimulates the pancreas to release more substances that are needed for the absorption of nutrients. These also include substances that boost appetite. To make matters worse this mechanism could mean that N-methyltyramine also boosts feelings of hunger.

"If given orally and present in appropriate amounts, N-methyltyramine will have an effect opposite to that which is widely and erroneously believed to occur with respect to metabolic rate and appetite", the researchers wrote. "In other words, N-methyltyramine will stimulate appetite and the absorption of fats and carbohydrates but inhibit the breakdown of fats to energy."

Phytother Res. 2015 Jan;29(1):14-6.

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