DMAE

DMAE occurs naturally in fish. There is evidence to back up its claims of tightening and firming sagging skin, though the mechanism by which it achieves these effects is not yet well understood.

Effects


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments

A

Increased skin elasticity

Strong

Firms the skin as assessed by both subjective clinical evaluations and instrumental measurements.

A

Wrinkle treatment

Mild

A 3% DMAE gel improved forehead lines in one study, and DMAE in formulations containing other active ingredients improved both facial fine lines and wrinkles.

B

Tighter skin

Strong

3% DMAE with mineral salts had a skin lifting effect after only 1 week in a double-blind, placebo-controlled clinical trial.

B

Increased skin hydration

Mild

A 3% DMAE gel increased skin moisturization more than a placebo gel in a double-blinded clinical trial.

C

Rosacea treatment

Mild

Reduced skin redness in rosacea patients when included in a facial cleanser.

D

Antioxidant

Moderate

Capable of scavenging hydroxyl, ascorbyl and lipid radicals.

D

Increased skin thickness

Mild

Increased the thickness of the dermis in an experiment on mice. Also increased the thickness of the epidermis of rabbit ear.

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Scientific Research


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Table of contents:

1. Sources

DMAE is short for 2-dimethylaminoethanol, an amine-based alcohol that occurs abundantly in fish such as sardines and anchovies.[1] It is also known as deanol.

An analog of choline, DMAE was once thought to be a possible precursor of the neurotransmitter acetylcholine due to reports of its elevating brain choline and acetylcholine levels,[2] but its influence on brain choline and acetylcholine levels is now known to be due at least in part to its competitive inhibition of choline uptake from the bloodstream into the brain[3] as well as its inhibition of choline metabolism in tissues,[4] leading to an accumulation of free choline which later enters the brain.

DMAE has been used as a treatment for neurological disorders including ADHD,[5] senile dementia[6] and tardive dyskinesia,[7] apart from its uses in cosmetic formulations.

2. Bioavailability

Both DMAE and its bitartrate salt are stable in aqueous solutions kept under room temperature, 40°C or 60°C for 30 days, and can hence be used in the preformulation stage to prepare liquid formulas.[8]

There have not been any studies on the skin absorption of DMAE to our knowledge.

3. Effects on the skin

Several manufacturer-sponsored studies support the positive influence of DMAE on the skin. The first was a study conducted by Johnson & Johnson, which found that DMAE in combination with the mineral salts of magnesium, zinc and copper led to a marked rise in fibroblast proliferation, in addition to stimulating collagen and glycosaminoglycan synthesis. On the basis of these results, a double-blind and placebo-controlled clinical study was performed on 41 volunteers, who applied a test product containing DMAE + the mineral salts and a placebo to each half of their faces twice daily. After 1 week, statistically significant effects on wrinkle reduction, skin lifting and skin firmness were evidenced by clinical assessment, compared to the placebo, and the results on skin firmness were confirmed using measurements of acoustic sound wave propagation.[9]

Johnson & Johnson published the findings of 3 other randomized clinical trials a year later.[10] The first trial was multicenter, double-blind and placebo-controlled. It included 156 patients with moderate to moderately severe photodamage, who were randomized to receive either a 3% DMAE gel or a placebo gel for 16 weeks, followed by a 2-week period of regression evaluation. Compared to patients who had received the placebo gel, skin moisturization was better in those who received the DMAE gel, lip thickness was significantly increased after 16 weeks and forehead lines were significantly more improved at the end of the 2 week regression phase.[11] 35 patients from one center who completed this 16-week study enrolled in an open-label 8-month extension, which further confirmed the skin-firming ability of the 3% DMAE gel.[12] Because the first 2 trials relied on subjective clinical evaluations, the third trial sought to objectively quantify the skin-firming ability or skin tensile effect of DMAE via sensorial assessment, measurements of skin distension under suction, and measurements of shear-wave propagation. 30 women were recruited and evaluated 45 minutes after applying a pea-sized amount of 3% DMAE or placebo gel. Relative to the placebo gel, the DMAE formulation produced both a significant increase in skin firmness as well as a decrease in mechanical anisotropy of the skin, but did not cause a statistically significant improvement in the measure of the skin's average tensile strength. Importantly, the skin firming effect was limited to the looser areas of the skin, indicating that DMAE firms facial skin in areas where it is most needed.[13]

These results are similar to that obtained in a Swedish study, where a commercial product (Dermyn) containing a patented complex called Tricutan[14] (which in turn contained 3% DMAE in addition to rosemary extract, ursolic acid, Centella asiatica extract and tetrahydrocurcumin) was tested on 25 women. The women were given the Dermyn gel and a placebo gel for use on the left or right halves of their faces for 28 days, and skin firmness was assessed by measuring the speed of propagation of ultrasound shear waves in the skin. By the end of the treatment period, the active product had resulted in a significantly increased skin firmness compared to the placebo, as evidenced by mean readings that were more than 20% lower that those obtained from placebo treatment. Patient self-evaluations, too, agreed that the active product was significantly more effective than the placebo.[15]

Moreover, a collaboration between the clinical research company Hill Top Research and NV Perricone, also revealed that a concentrated restorative cream containing a vitamin C ester, DMAE, allatoin, rosemary and green tea polyphenols effectively improved fine lines, wrinkles and skin elasticity over 8 weeks. The study was conducted on 42 women who applied the cream once daily, and efficacy endpoints included clinical evaluations plus instrumental measurements such as a ballistometer for quantifying skin elasticity. However, statistical significance was not reported.[16]

Another small split-face study performed by Hill Top Research on 25 women found that a facial moisturizer containing alpha lipoic acid and DMAE led to significant differences in various parameters between the side of the face treated with the test product and the side of the face treated with the subjects' usual moisturizer product after 2 weeks. The exact parameters that saw statistically significant improvements were not mentioned, but efficacy assessments included wrinkles and lines, pores, skin tone, skin redness and skin firmness.[17]

However, one study showed that neither a single application of DMAE nor application for 8 weeks altered the mechanical properties of human skin in vivo, though it did increase the thickness of the dermis and the thickness of collagen fibers in hairless mice. [18]

Because DMAE is an analog of choline and keratinocytes and fibroblasts are known to possess cholinergic receptors,[19][20][21][22] it has been suggested that DMAE may increase the firmness of the skin by modulating dermal smooth muscle contraction or by increasing the contractility and adhesion of other epidermal and dermal cells.[13]

Another explanation for DMAE's effect on skin fullness was put forward in a 2007 paper. In this study, cultured human fibroblasts were observed to respond to DMAE by massive vacuolization. 3% DMAE also induced significant thickening of the epidermis of the rabbit ear, in addition to clear perinuclear swelling, which was taken to be an indication of vacuolization. It was proposed, therefore, that the cellular basis of DMAE's antiwrinkle effect may be due to vacuolar cytopathology.[23]

3.2 Antioxidant effect

DMAE has been demonstrated to directly react with hydroxyl radicals, ascorbyl radicals and lipid radicals. Because it scavenges hydroxyl radicals (87% inhibition) and ascorbyl radicals (79% inhibition) more efficiently than lipid radicals (44% inhibition), it is thought to work better in a hydrophilic environment.[24]

3.3 Rosacea treatment

A study sponsored by Neutrogena claimed that a DMAE facial cleanser was overwhelmingly preferred by rosacea sufferers over a benchmark cleanser for its mildness, aesthetics and redness reduction, presumably due to its anti-inflammatory function, but further details were not provided.[25]

4. Side Effects

4.1 Potential cytotoxicity

DMAE may be mildly cytotoxic; it decreased fibroblast proliferation and changed the cell cycle in one study, causing an increase in apoptosis.[26] It has been suggested that this may be due to an extreme vacuolization reaction, perhaps leading to vacuole rupture.[23] An earlier study however found that DMAE combined with magnesium, zinc and calcium salts actually increased fibroblast proliferation, and did not report cytotoxicity.[9]

Scientific References


  1. Honegger CG, Honegger R. Occurrence and Quantitative Determination of 2-Dimethylaminoethanol in Animal Tissue Extracts. Nature. (1959)
  2. Zahniser NR, Chou D, Hanin I. Is 2-dimethylaminoethanol (deanol) indeed a precursor of brain acetylcholine? A gas chromatographic evaluation. J Pharmacol Exp Ther. (1977)
  3. Millington WR, McCall AL, Wurtman RJ. Deanol acetamidobenzoate inhibits the blood-brain barrier transport of choline. Ann Neurol. (1978)
  4. Haubrich DR, Gerber NH, Pflueger AB. Deanol affects choline metabolism in peripheral tissues of mice. J Neurochem. (1981)
  5. Lewis JA, Lewis BS. Deanol in minimal brain dysfunction. Dis Nerv Syst. (1977)
  6. Ferris SH, et. al. Senile dementia: treatment with deanol. J Am Geriatr Soc. (1977)
  7. Simpson GM, et. al. Deanol in the treatment of tardive dyskinesia. Psychopharmacology (Berl). (1977)
  8. Clares B, et. al. Structural characterization and stability of dimethylaminoethanol and dimethylaminoethanol bitartrate for possible use in cosmetic firming. J Cosmet Sci. (2010)
  9. Oddos T, et. al. Anti-aging efficacy of the combination of dimethylaminoethanol (DMAE) and mineral salts. J Am Acad Dermatol. (2004)
  10. Grossman R. The role of dimethylaminoethanol in cosmetic dermatology. Am J Clin Dermatol. (2005)
  11. Grossman R, Gisoldi E, Cole C. Safety and efficacy evaluation of a new skin firming technology: dimethylethanol and tyrosine. J Am Acad Dermatol. (2002)
  12. Grossman RM, Gisoldi EM, Cole CA. Long-term safety and efficacy evaluation of a new skin firming technology: dimethylethanol. J Am Acad Dermatol. (2002)
  13. Uhoda I, et. al. Split face study on the cutaneous tensile effect of 2-dimethylaminoethanol (deanol) gel. Skin Res Technol. (2002)
  14. Fredriksson L, Starlander U. New skin improving composition. US Patent 1915126 (2008)
  15. Sommerfeld B. Randomised, placebo-controlled, double-blind, split-face study on the clinical efficacy of Tricutan on skin firmness. Phytomedicine. (2007)
  16. Kaul N, et. al. Clinical evaluation of a new concentrated restorative cream acting on wrinkles, fine lines and loss of firmness. J Am Acad Dermatol. (2007)
  17. Kaul N, et. al. Efficacy of alpha-lipoic acid and dimethylaminoethanol in reducing signs of aging. J Am Acad Dermatol. (2006)
  18. Tadini KA, Campos PM. In vivo skin effects of a dimethylaminoethanol (DMAE) based formulation. Pharmazie. (2009)
  19. Grando SA, et. al. Activation of keratinocyte nicotinic cholinergic receptors stimulates calcium influx and enhances cell differentiation. J Invest Dermatol. (1996)
  20. Grando SA. Biological functions of keratinocyte cholinergic receptors. J Investig Dermatol Symp Proc. (1997)
  21. Ndoye A, et. al. Identification and mapping of keratinocyte muscarinic acetylcholine receptor subtypes in human epidermis. J Invest Dermatol. (1998)
  22. Buchli R, et. al. Human skin fibroblasts express m2, m4, and m5 subtypes of muscarinic acetylcholine receptors. J Cell Biochem. (1999)
  23. Morissette G, Germain L, Marceau F. The antiwrinkle effect of topical concentrated 2-dimethylaminoethanol involves a vacuolar cytopathology. Br J Dermatol. (2007)
  24. Malanga G, et. al. New insights on dimethylaminoethanol (DMAE) features as a free radical scavenger. Drug Metab Lett. (2012)
  25. Leyden JJ, et. al. DMAE contributes to mildness of a facial cleanser designed for sensitive skin. J Am Acad Dermatol. (2004)
  26. Gragnani A, et. al. Dimethylaminoethanol affects the viability of human cultured fibroblasts. Aesthetic Plast Surg. (2007)