dimetiletanolamina (DMEA)

Dimethylethanolamine (DMEA / DMAE): A Comprehensive Reference

1. Identity and Chemical Character

Dimethylethanolamine (DMAE or DMEA) is an organic compound with the formula (CH₃)₂NCH₂CH₂OH. It is commonly referred to as 2-(dimethylamino)ethanol, dimethylaminoethanol (DMAE), or dimethylethanolamine (DMEA), and carries the CAS registry number 108-01-0. The compound also goes by the names N,N-dimethyl-2-aminoethanol, beta-dimethylaminoethyl alcohol, beta-hydroxyethyldimethylamine, and Deanol.

It is bifunctional, containing both a tertiary amine and a primary alcohol functional group, and presents as a colorless viscous liquid. It has a distinct, fishy odor, engages in typical amine reactions such as forming salts with acids, and is soluble in water and various organic solvents.

Natural Sources

Dimethylaminoethanol is related to choline and is a biochemical precursor to the neurotransmitter acetylcholine; it is found naturally in fish like sardines and anchovies. DMAE is also an amine produced in small amounts in the human brain, and is present in high levels in seafood such as anchovies and sardines.

Common Forms and Preparations

DMAE is marketed as a free base or as a salt, and in theory the two forms should be equally effective and able to substitute for each other in pharmaceutical formulations. The most frequently encountered salt in dietary supplements is DMAE bitartrate. In one or more formulations, the DMAE used is specifically DMAE bitartrate. DMAE is sold in pharmacies, health food stores, and online as a nutritional supplement. It is also widely incorporated into topical cosmeceutical products such as creams and gels, particularly those marketed for anti-aging skin care. DMAE is a novel ingredient initially used in the treatment of hyperkinetic disorders and to improve memory, and is now being used in cosmeceutical products, gaining popularity from its activity as a precursor to acetylcholine.

2. Traditional and Historical Use

DMAE does not have a traditional botanical or ethnopharmacological history in the same sense as herbal medicines. Rather, its documented history of use is rooted in mid-twentieth-century pharmaceutical development in Western medicine.

Dimethylaminoethanol salts have been used to manage learning and behavioral problems, Huntington's chorea, chronic fatigue, and neurasthenia. The prescription drug Deaner® (deanol p-acetamidobenzoate) was used in the United States for more than 20 years to treat learning and behavioral problems in children, but was withdrawn from the market in 1983 due to better alternatives becoming available.

Deanol was previously sold by Riker Laboratories as the prescription drug Deaner. It was prescribed for the management of children with behavior problems and learning difficulties. It has also been used in the treatment of attention deficit-hyperactivity disorder (ADHD), Alzheimer's disease, autism, and tardive dyskinesia. It has additionally been used as an ingredient in skin care, and in cognitive function- and mood-enhancing products, and was classified as an antidepressive agent and anti-dyskinesia agent.

Dimethylaminoethanol was once marketed in the US as Deaner but was withdrawn in 1980 because the FDA required proof for its claims of efficacy in treating symptoms of minimal brain dysfunction. Nevertheless, several placebo-controlled trials performed in the 1960s and 1970s had shown that it was effective in improving symptoms of ADHD in children at doses of 500 mg/day or higher.

The compound also has a long parallel history as an industrial chemical. Dimethylaminoethanol is used as a curing agent for polyurethanes and epoxy resins, in the synthesis of dyestuffs, textile auxiliaries, pharmaceuticals, emulsifiers, and corrosion inhibitors, and as an additive to paint removers, boiler water, and amino resins. This industrial context is relevant to occupational safety but distinct from its use as a dietary supplement.

3. Key Constituents, Chemistry, and Mechanisms of Action

Structural Relationship to Choline

DMAE is a close structural analog of choline (N,N,N-trimethylaminoethanol), an essential nutrient. The key structural difference is that DMAE has two methyl groups on its nitrogen atom, whereas choline has three. DMAE is an analog of the B vitamin choline and a precursor of acetylcholine. Although the role of acetylcholine as a neurotransmitter is well known, growing evidence points to acetylcholine as a ubiquitous cytokine-like molecule that regulates basic cellular processes such as proliferation, differentiation, locomotion, and secretion in a paracrine and autocrine fashion.

Proposed Mechanism: Cholinergic Modulation

The most discussed proposed mechanism of action for DMAE is its relationship to the cholinergic system — specifically, its putative ability to raise acetylcholine (ACh) levels in the brain. However, this mechanism is substantially contested in the scientific literature. The mechanism of action is not well understood.

Researchers have speculated that DMAE may increase acetylcholine levels in the brain by inhibiting choline metabolism in peripheral tissues. By preventing the use of choline by other tissues, DMAE increases choline levels in the bloodstream. Once DMAE crosses the blood-brain barrier, it increases choline levels in the brain. With higher choline levels present, elevated levels of acetylcholine would be expected. But research has shown this is not always what happens when DMAE reaches the brain.

A 1977 study by Zahniser, Chou, and Hanin, published in the Journal of Pharmacology and Experimental Therapeutics, directly questioned whether DMAE is a bona fide precursor to brain acetylcholine. These findings suggest that deanol increases the choline concentration in blood by inhibition of its metabolism in tissues. Deanol may ultimately produce its central cholinergic effects by inhibiting choline metabolism in peripheral tissues, causing free choline to accumulate in blood, enter the brain, and stimulate cholinergic receptors.

Antioxidant and Free Radical Scavenging Properties

A distinct line of investigation has examined DMAE as a direct antioxidant. DMAE is a precursor of choline, which allows the brain to optimize the production of acetylcholine. Research has shown its ability to scavenge specific free radicals, assessed by Electron Spectroscopic Resonance (EPR), further analyzing the role of DMAE as an antioxidant. DMAE's ability to directly react with hydroxyl, ascorbyl, and lipid radicals was tested employing in vitro assays. This work, published by Malanga et al. in Drug Metabolism Letters (2012), represents the most rigorous direct examination of DMAE's antioxidant properties; however, it remains in vitro only and has not been replicated in human clinical trials.

Anti-inflammatory Properties (In Vitro)

Initially utilized as a firming and anti-aging product, new functions including anti-inflammatory and antioxidant activities have been elucidated. In vitro, DMAE inhibits IL-2 and IL-6 secretion in addition to its actions as a free radical scavenger. In vitro studies in peripheral blood lymphocytes indicate that DMAE is a moderately active anti-inflammatory agent. Although its mechanisms of action in the skin remain to be elucidated, evidence suggests that the skin is an active site of acetylcholine synthesis, storage, secretion, metabolism, and receptivity.

Cutaneous Mechanism

Although the exact mechanism of action of DMAE in the skin is unclear, its acetylcholine-like functions increase contractility and cell adhesion in the epidermis and dermis, resulting in the appearance of firmer skin. Growing evidence points to acetylcholine as a ubiquitous cytokine-like molecule that regulates basic cellular processes such as proliferation, differentiation, locomotion, and secretion; this modulatory role may contribute to the cutaneous activity of DMAE.

4. Scientific Evidence by Area of Use

4.1 Attention Deficit / Hyperactivity Disorder (ADHD) and Behavioral Disorders in Children

This is the area with the longest documented clinical history for DMAE, stemming primarily from studies conducted during the 1960s and 1970s. Some evidence suggests that DMAE may be helpful for attention deficit disorder (ADD) and attention-deficit/hyperactivity disorder (ADHD).

Dimethylaminoethanol was once marketed in the US as Deaner but was withdrawn in 1980 because the FDA required proof for its claims of efficacy in treating symptoms of minimal brain dysfunction. Nevertheless, several placebo-controlled trials performed in the 1960s and 1970s showed that it was effective in improving symptoms of ADHD in children at doses of 500 mg/day or higher.

Some users claim that DMAE helps with ADHD and other attention disorders, but the evidence for this is scarce. A three-month treatment with deanol (DMAE, 500 mg) improved school performance in 74 children with behavior and learning disorders. However, this study was noted to have significant methodological drawbacks.

In one study, 108 children with a learning disabilities behavior profile were given supplemental DMAE. Improvement was observed in the vast majority (71%) of the learning disabled/hyperactive children in the areas of increased attention span, decreased irritability, scholastic improvement, and, in some children, a rise in IQ.

Evidence strength: The available evidence for ADHD is based on older, small-scale studies with methodological limitations. The compound's withdrawal from the U.S. market reflects regulatory concern about the adequacy of this evidence base. These findings have not been replicated in modern, large-scale, randomized controlled trials, and the evidence cannot be considered conclusive by contemporary standards.

4.2 Cognitive Function, Mood, and Neurological Measures in Healthy Adults

A psychophysiological model of provoking different emotional states by watching film excerpts with various emotional contents was used to characterize drug action in 80 subjects (male/female = 50%) with threshold emotional disturbance within a randomized, group-parallel, double-blind, placebo-controlled study. Analyzing the brain's electrical reaction during presentation of five video clips of 7 minutes' duration revealed a content-specific representation of topographical frequency changes. This study by Dimpfel, Wedekind, and Keplinger (2003), published in the European Journal of Medical Research, found EEG changes consistent with improved alertness and mood in the DMAE-containing supplement group. Analysis of emotional change in mood profile revealed a better mood for the active drug group, corroborating the EEG results.

A significant caveat applies: This study tested a combination supplement (DMAE plus vitamins and minerals) rather than DMAE in isolation. Its results cannot be attributed exclusively to DMAE.

Studies have shown an increase in vigilance and alertness, with a positive influence on mood, based on the use of dimethylethanolamine. Overall, human evidence for cognitive benefits from oral DMAE supplementation in healthy subjects remains limited, and no large, well-controlled trials have demonstrated clear, DMAE-specific cognitive improvement.

4.3 Alzheimer's Disease and Senile Dementia

Multiple clinical trials have specifically tested DMAE as a treatment for Alzheimer's disease and other dementias, and the results have been largely negative. Taking deanol by mouth does not seem to improve memory in people with Alzheimer's disease.

DMAE provided no significant improvement in two studies involving over 260 Alzheimer's disease patients. Some patients even had to quit due to major side effects. Notable published studies include a double-blind trial by Fisman, Mersky, and Helmes (American Journal of Psychiatry, 1981) and a study by Ferris et al. (Journal of the American Geriatric Society, 1977) examining deanol in senile dementia — neither found significant benefit. People use deanol for Alzheimer disease, a movement disorder called tardive dyskinesia, ADHD, autism, and many other conditions, but there is no good scientific evidence to support these uses.

Evidence strength: Human clinical evidence is negative for Alzheimer's disease. This use is not supported by available data.

4.4 Tardive Dyskinesia and Movement Disorders

Considerable clinical investigation was conducted on DMAE for tardive dyskinesia (TD) — an involuntary movement disorder often caused by antipsychotic medications — given the theoretical rationale that enhancing cholinergic tone might counteract dopamine-driven dyskinetic movements.

Deanol acetamidobenzoate, 2.0 g/day for four weeks, was administered in a double-blind, placebo-controlled crossover trial to 14 patients with tardive dyskinesia. The patient population included both inpatients and outpatients. The response was evaluated by subjective clinical impression and scoring of filmed sequences. Patients' conditions improved significantly from baseline scores while receiving both deanol and placebo, but there was no distinction between the two treatments.

There is no evidence to back up the anecdotal benefits of DMAE for movement disorders. Clinical trials have found no significant improvement of tardive dyskinesia, chorea, and other movement disorders.

Multiple double-blind, placebo-controlled trials published in the late 1970s and early 1980s — including studies by de Montigny et al. (Psychopharmacology, 1979) and George et al. (Australian and New Zealand Journal of Psychiatry, 1981) — found deanol ineffective for TD. A Cochrane systematic review of cholinergic drugs for neuroleptic-induced tardive dyskinesia reached similar conclusions. Taking deanol by mouth does not seem to improve symptoms of tardive dyskinesia.

Notably, a case report by Haug and Holzgraefe (European Neurology, 1991) suggested that DMAE might itself cause orofacial and respiratory tardive dyskinesia as a potential side effect — a paradoxical finding that warrants attention.

Evidence strength: Human clinical evidence is consistently negative for tardive dyskinesia. This use is not supported by current data.

4.5 Cosmetic Dermatology: Skin Firmness and Anti-Aging Effects

The strongest body of human clinical evidence for DMAE pertains to its topical use in cosmetic dermatology. In a randomized clinical study, 3% DMAE facial gel applied daily for 16 weeks was shown to be safe and efficacious (p < 0.05) in the mitigation of forehead lines and periorbital fine wrinkles, and in improving lip shape and fullness and the overall appearance of aging skin. These effects did not regress during a 2-week cessation of application.

Beneficial trends (p > 0.05 but ≤ 0.1) were noted in the appearance of coarse wrinkles, under-eye dark circles, nasolabial folds, sagging neck skin, and neck firmness. Application was found to be well tolerated, with no differences in the incidence of erythema, peeling, dryness, itching, burning, or stinging between the DMAE and placebo groups. An open-label extension of the trial showed that the long-term application of DMAE gel for up to 1 year was associated with a good safety profile.

The acute skin-firming effects of DMAE have been confirmed by quantitative measures of cutaneous tensile strength. A separate split-face study by Uhoda et al. (Skin Research and Technology, 2002) also confirmed the cutaneous tensile effect of DMAE gel.

In pre-clinical work, in order to evaluate potential antiaging effects of low-dose DMAE administered intradermally by localized microinjection (Mesotherapy), tissue structure and collagen metabolism of D-galactose-induced aging skin were measured in a rat model. Mesotherapy by delivering DMAE and amino acids directly to target tissue showed marked antiaging effects by promoting collagen synthesis and remodeling skin texture and improving the thickness of aging skin. These are animal data and direct clinical translation is not established.

Evidence strength: Moderate. The 16-week randomized clinical trial of 3% topical DMAE gel is the best-quality human study for any DMAE application. The evidence supports modest improvements in skin firmness and fine lines with topical application, though this must be interpreted alongside the in vitro safety concerns discussed below (see Section 7).

4.6 Physical Performance

A study by Pieralisi, Ripari, and Vecchiet examined the effects of a standardized ginseng extract combined with DMAE bitartrate, vitamins, minerals, and trace elements on physical performance during exercise. This combination supplement showed positive outcomes, but — as with the Dimpfel EEG study — the DMAE-specific contribution cannot be isolated from the combination formulation. No stand-alone human trial of DMAE for athletic performance has been identified.

4.7 Lipofuscin Accumulation (Aging Pigment)

Lipofuscin, a fluorescent aggregation of oxidized proteins and lipids, accumulates in post-mitotic cells with age and has been associated with cellular aging and cognitive decline. Animal data suggest that centrophenoxine — a drug that is metabolized to DMAE in the body — can reduce lipofuscin levels. Centrophenoxine breaks down into DMAE once in the body, and it is the DMAE in this compound that provides the lipofuscin scavenger effects. However, these findings are from animal studies using centrophenoxine injections, and no human clinical trial has directly demonstrated that oral DMAE supplementation reduces lipofuscin in humans.

5. Body Systems and Health Areas Associated with DMAE

• Central Nervous System: DMAE is a natural chemical that has been used to treat a number of conditions affecting the brain and central nervous system. It is primarily marketed for its proposed benefits in enhancing cognitive function and addressing disorders such as ADD and ADHD.
• Cholinergic / Neurotransmitter System: DMAE is believed to increase levels of acetylcholine, a neurotransmitter linked to memory and mood regulation, although scientific support for this claim is limited.
• Mood and Affect: DMAE has been classified as an antidepressive agent. The 2003 Dimpfel EEG study suggested mood improvement with a DMAE-containing combination product.
• Integumentary System (Skin): DMAE's acetylcholine-like functions increase contractility and cell adhesion in the epidermis and dermis, resulting in the appearance of firmer skin.
• Antioxidant / Cellular Protection: DMAE has demonstrated the ability to scavenge specific free radicals assessed by Electron Spectroscopic Resonance (EPR), with its ability to directly react with hydroxyl, ascorbyl, and lipid radicals tested in vitro.
• Movement Disorder / Extrapyramidal System: Historically investigated but without evidence of efficacy in clinical trials.
• Developmental Biology: Implicated in choline metabolism during embryonic development, with safety concerns during pregnancy (see Section 7).

6. Dosage Forms and Dosages Reported in Studies

DMAE is sold in pharmacies, health food stores, and online as a nutritional supplement. Manufacturers' recommended dosages and those used in clinical studies vary between 400 and 1,800 milligrams (mg) daily.

Several placebo-controlled trials performed in the 1960s and 1970s used doses of 500 mg/day or higher for ADHD in children.

The FDA has approved a human study of DMAE recommending a daily dose of 200 mg; doses used in clinical studies have ranged from 300 to 2,000 mg/day.

In the tardive dyskinesia double-blind crossover trial, deanol acetamidobenzoate was administered at 2.0 g/day for four weeks.

In humans, 10 to 20 mg of DMAE tartrate administered orally produced mild mental stimulation. At 20 mg/day there was a gradual increase in muscle tone and perhaps an increased frequency of convulsions in susceptible individuals. Larger doses produced insomnia, muscle tenseness, and spontaneous muscle twitches. Doses of DMAE as high as 1,200 mg/day produced no serious side effects.

For topical dermatological use: in a randomized clinical study, 3% DMAE facial gel applied daily for 16 weeks was found to be safe and efficacious.

Oral supplement tablets and capsules are available commercially; DMAE dosage in tablets or capsules are typically in the range of 100 to 350 mg.

7. Safety Considerations and Interactions

General Adverse Effects (Oral)

Many clinical investigations using DMAE reported that participants experienced no side effects, though researchers found adverse reactions, which suggests some caution is appropriate. One study reported increased confusion, drowsiness, and elevated blood pressure; another reported headache and muscle tension as possible adverse effects; and another suggested that weight loss and insomnia may accompany the use of DMAE.

Treatment with DMAE for tardive dyskinesia was associated with serious cholinergic side effects including nasal and oral secretions, shortness of breath, and respiratory failure.

Topical Safety: In Vitro Cytopathology

A significant concern for topical DMAE emerged from a 2007 study by Morissette, Germain, and Marceau, published in the British Journal of Dermatology. DMAE is a tertiary amine found in high concentrations in numerous topical antiwrinkle preparations. The researchers hypothesized that a 3% DMAE reservoir applied to the skin could reproduce cytopathology induced by other amines by maintaining a millimolar drug concentration within the skin layers, and that vacuolar cell expansion could account for the rapid effect on apparent skin fullness.

Fibroblasts responded to DMAE (2.5–10 mmol/L) by massive vacuolization (0.5–4 h). Triethanolamine, another chemical frequently used topically, was also active. The vacuolar ATPase inhibitor bafilomycin A1 prevented DMAE-induced vacuolization; adding bafilomycin A1 or cell washout slowly reversed the established vacuolization. Further effects of DMAE in cultured fibroblasts included a moderate cytotoxicity, a concentration-dependent mitotic arrest, and transient and mild effects on cell ploidy.

In the hours following the application of DMAE, the researchers observed an important slowing of cell division, sometimes coming to a complete stop, the inhibition of certain metabolic reactions, and the death of a significant percentage of fibroblasts. The mortality rate of fibroblasts, which varied according to DMAE concentration, was above 25% after 24 hours at a concentration similar to that resulting from normal use of an antiwrinkle cream. The thickening of the skin induced by pathological swelling of the fibroblasts would explain the antiwrinkle effect of DMAE according to the researchers.

Critically, the adverse effects reversed after DMAE had been washed out of the culture following short-term exposure. Long-term exposure has not been studied. This means the clinical relevance of these in vitro findings to long-term topical use in humans remains unresolved.

Teratogenicity and Reproductive Concerns

This is the most evidence-supported safety concern for DMAE. A role for choline during early stages of mammalian embryogenesis has been established, and inhibitors of choline uptake and metabolism, including 2-dimethylaminoethanol (DMAE), produce neural tube defects in mouse embryos grown in vitro.

DMAE reduced embryonic choline uptake and inhibited phosphocholine, phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin synthesis. Results suggest that endogenous phosphatidylcholine synthesis is important during neurulation and that perturbed choline metabolism contributes to neural tube defects produced by DMAE.

DMAE is a close structural analog of choline, and hence there is potential for DMAE to disrupt choline uptake and metabolism and interfere with biological processes such as development.

These findings are from in vitro and animal studies; no controlled human studies on DMAE teratogenicity have been conducted. Nevertheless, the mechanistic plausibility is considered strong enough to support avoidance of DMAE during pregnancy. DMAE supplementation is contraindicated during pregnancy and lactation.

Neurological Contraindications

DMAE is also contraindicated for treatment of people with symptoms of schizophrenia and clonic-tonic seizure disorders. This is consistent with the stimulant-like cholinergic properties of the compound, which can theoretically lower seizure threshold in susceptible individuals.

Cholinergic Drug Interactions

DMAE bitartrate may interact with certain medications or supplements, particularly those affecting cholinergic neurotransmission. Because DMAE operates via the cholinergic pathway, combining it with other cholinergic agents — such as anticholinesterase medications (e.g., donepezil, rivastigmine, galantamine) or choline precursors — raises the theoretical risk of cholinergic excess, though direct human interaction studies have not been published.

Occupational Exposure

In one occupational study involving the manufacture of polyurethane foam insulation, adverse effects were observed including disorders of the upper respiratory tract and nervous system, along with significant changes in immune status. This finding relates to industrial inhalation exposure at far higher concentrations than supplement use, but illustrates the compound's biological activity at mucosal surfaces.

Regulatory Status

In the United States, DMAE is sold as a dietary supplement and in cosmetics; supplements are not pre-approved by the FDA for safety or efficacy before marketing. In contrast, some European authorities consider DMAE an unauthorized ingredient in food supplements.

References

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