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Spotlight on: Dimethylaminoethanol (DMAE)

Ubiquitously used in one of the priciest skin care lines—Perricone MD, DMAE is without equivalence, the star ingredient of that brand. But does DMAE deserve such attention?

dmaeWhat is DMAE?

4aaa941b3de473ae4c7e255121b96b12Dimethylaminoethanol or DMAE is a structural relative of choline (CH), which is the direct precursor to acetylcholine (ACh). ACh is of course, the all-important neurotransmitter that regulates everything from memory to muscle control. It is this characteristic of ACh that generates the most hype around DMAE; because if the former can affect the muscles of the face and bring about a more tightened appearance, then DMAE must do the same, since it’s a precursor to ACh. But that’s just it.

Does DMAE Actually Convert to ACh in the Skin?

The immediate precursor to ACh is CH, which can be seen here:
Choline Choline
Here is DMAE:
Dimethylaminoethanol Dimethylaminoethanol
As you can see, DMAE lacks a 3rd methyl group (CH3) on the lone nitrogen atom.
Choline metabolism Choline metabolism
Now, because ACh can only be directly synthesized from CH via choline acetyltransferase (ChAT), this is known as the rate-limiting metabolic step. Furthermore, because CH can only be directly synthesized from phosphatidylcholine via phosphatidylethanolamine N-methyltransferase (PEMT), it would appear that DMAE cannot even be converted to either CH or ACh.

How Did this Idea Arise?

DMAE is taken up by synapsosomes, but nothing happens. DMAE is taken up by synaptosomes, but nothing happens.
The idea that DMAE would increase ACh levels first become plausible based on earlier studies such as this one, which was published in 1979. It was shown that DMAE supplementation increased levels of CH. Therefore, in the eyes of the researchers back then, it was theoretically possible that the CH would eventually be converted to ACh. However, the findings referenced in this much later study, indicate that the increase of CH was due to DMAE’s ability to inhibit CH metabolism. Basically, it created a sort of backlog of free CH by acting as a competitive substrate for ChAT. As the 1979 study observed, DMAE “was rapidly taken up by rat brain synaptosomes, but was neither methylated nor acetylated.” While this was likely written off as some anomaly, it supports the claim that after DMAE administration, the CH concentrations only increases due to a lack of ACh formation, NOT an increase of CH formation. This is likely why DMAE was abandoned as a treatment for hyperactivity (ADHD). However, even if I’m completely wrong and some DMAE does actually covert to ACh, it still doesn’t matter. This is because when DMAE was administered intravenously to mice, this “inhibition of CH metabolism” was only seen in the kidneys and liver, which indicate that this interaction only occur in these peripheral organs. There was no “direct serum effects of DMAE,” meaning that DMAE administration did not affect the concentrations of CH in the blood. Since only blood is in contact with the skin—no hepatic or renal tissues here, the likelihood of any ACh formation from topical DMAE application is nil. And that’s too bad, because who wouldn’t want tighter facial contours?! Even the Governator wouldn’t decline!

Then How Does DMAE Firm the Skin?

This needs to be addressed because DMAE has been shown to possess skin firming capabilities. In that same comprehensive study cited above, which was done by Johnson & Johnson, a well-designed (multicenter, double-blind, placebo-controlled) experiment was performed to test the efficacy of a 3% DMAE gel over 16 weeks. Based on a physician’s subjective analysis (with the naked eye), there were statistically significant improvements in the reduction of forehead and periorbital fine lines of those using the DMAE gel, compared to those using the placebo. Furthermore, instrumental (objective) evaluations recorded an increase in skin hydration. After 16 weeks, the subjects were eligible to participate in an open-label 8-month extension of the same study. The skin firming benefits were maintained in the remaining thirty-five patients. No adverse reactions were seen, which indicate that DMAE has a good safety profile. Now as we saw above, this increase in skin firmness cannot be attributed to ACh. Therefore, what mechanism of action is responsible? This study suggests that the skin firming effects of DMAE can be accredited to a type of vacuolization, a process by which vacuoles or large pools of water are formed in cells. Upon application of 3% DMAE, rabbit fibroblasts were shown to swell to massive sizes, with the epidermis of the (rabbit) ear exhibiting significant thickening and clear perinuclear swelling. Cultured human cutaneous epithelial cells responded similarly. A similar study confirmed this epidermal and dermal thickening.

But is This Type of Firming (Vacuolization) Beneficial?  

Vacuoles are important. But imagine thousands of these babies floating around. Vacuoles are important. But imagine thousands of these babies floating around.
If all you want is firmer skin, then yes DMAE will be beneficial. However, it is important to note that vacuolization is a process that will hasten cellular death or apoptosis; cells can literally drown if too much water is present inside. This vacuolization may be why this study demonstrated that DMAE affects the viability of cultured human fibroblasts. It was shown that “a decrease in fibroblast proliferation was associated with an increase in DMAE concentration…causing an increase in apoptosis.” And as all three of the previously cited studies indicated statistically significant increases in skin hydration from DMAE application, the claim that the increase of water in the skin is due to vacuolization, appears more and more valid. Granted, any compound at sufficiently high concentrations will kill cultured fibroblasts; whether it’s water, L-ascorbic acid, retinol, or green tea. So consider this data cautiously. ***Note that this vacuolization is slowly reversible, suggesting that after discontinued use of topical DMAE, the temporary firming benefits may disappear and the skin will somewhat revert to its previous state.

Ingredient Profile of DMAE: Conclusion

Ultimately, the choice of whether or not to use DMAE is up to you. It’s pretty obvious that it does induce firming of the skin via vacuolization (which may or may not be harmful), rather than ACh generation. But is it worth the risk? On one hand, clinical studies show that DMAE is able to penetrate and thicken the dermis, indicating that vacuolization does occur at that depth. On the other hand, volunteers used a 3% DMAE gel for an entire year without exhibiting adverse reactions. Furthermore, as vacuolization can be slowly reversed and is a partially reversible process, stopping applications of DMAE may result in varying degrees of loss in terms of skin firmness.
DMAE's high pH requirement makes it difficult to stably include in formulations. DMAE's high pH requirement makes it difficult to stably include in formulations.
Factoring in everything discussed above, I personally will not be looking for DMAE in my skin care products, as there are other more documented, effective, and risk-free ingredients that I can use to firm the skin, not to mention exercise and diet! Furthermore, because free DMAE requires a very alkaline pH (~10) in order to function, I don’t want to have to deal with the consequences of having a non-acidic epidermal environment. And while in theory, a neutral salt form can be just as effective as free DMAE, I’d still rather not have to deal with all the associated unknowns and risks. I hope that was an enlightening read and make sure to check out my extensive review on the popular Blue Plasma Peel by Perricone MD! Let me know what you think of both articles!
By: John Su
Date: February 7 2013 at 5:15 PM
Skin Care, acetylcholine, choline, contour, conversion, Dimethyl MEA, DMAE, DMEA, expensive, firming, muscle, perricone md, tightening, urea

Comments (6)

  1. Lucas
    February 8 2013 at 7:39 AM

    A very helpful post! I always wondered what was the deal with DMAE, but never made an effort to find out about it (since skin firming isn't what I'm looking for), but still, it's nice to read such an informative post. I really enjoyed it.

  2. John Su
    February 9 2013 at 4:08 PM

    @Lucas Glad that you liked this information. :)

  3. Raymond Skinner
    April 3 2013 at 5:38 AM

    I generally consume 130mg of dmae for its nootropic quality daily. My neurochemistry is sensitive to changes, and I notice the difference cognitively. Initial onset: colors brighten. Duration: three hours. Effect: words come without effort and memory recall occurs more readily. (Question: since you refute the claim of dmae-to-Ach metabolism, is my perception just placebo or detection of misplaced choline?)

  4. John Su
    April 3 2013 at 1:04 PM

    @Raymond Skinner Well, based on the studies referenced above and the fact that DMAE is no longer used to treat conditions that require additional ACh, it seems likely that the improvement you notice is due to the initial backlog of choline that appears after DMAE supplementation (due to it being a competitive substrate), which then floods back into the system and becomes ACh after the DMAE "competition" disappears. So what you perceive as a boost in attention is only so because you lose some of that initially (and gain it back quickly); hence the change in perception. But DMAE doesn't actually increase the total concentration of ACh. Finally, like with anything, the placebo effect could be playing a part as well.

  5. Jennifer
    April 16 2013 at 8:50 AM

    Hi John, Can you tell me what DMAE is derived from? Are there natural sources? Thanks

  6. John Su
    April 17 2013 at 5:35 AM

    @Jennifer Mhm. DMAE has a characteristic ammonia-like (fish) smell. So logically , it's present in many edible species of fish such as sardines.

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