DMAE: Cognitive-Enhancing Life-Extending Nutrient

Anti-Aging Nutrient Review and Update Part 4
Ward Dean, M.D.  

Dimethylaminoethanol (DMAE) is a naturally-occurring, mild cerebral stimulant nutrient found in such "brain" foods as anchovies and sardines.

A closely related substance—Diethylaminoethanol (DEAE, or its trademarked form DEANER™) (Fig. 1) was considered a drug by the Food and Drug Administration (FDA), and at one time was approved as being possibly effective for the following conditions:

1. Learning problems associated with underachieving and shortened attention span.
2. Behavior problems associated with hyperactivity.
3. Combined hyperkinetic behavior and learning disorders with underachieving, reading and speech difficulties, impaired motor coordination, and impulsive/compulsive behavior, often described as asocial, antisocial or delinquent.

In the late 1970s, DEANER was discontinued from the U.S. Pharmacopoeia by the FDA because its manufacturer, understandably, did not choose to undergo the rigorous and expensive retesting that the FDA was then requiring of many natural, no-longer-patentable preparations.
 

Fortunately, DMAE possesses all of the properties that were claimed for its close cousin, DEAE.

Safe, Effective Solution to Adult and Childhood Learning Disorders
The learning problems just mentioned, although usually childhood disorders, are also seen in adults, and not infrequently. The disorders are usually treated with much more potent and addictive amphetamines (like Ritalin®, or Adderal®).

DMAE provides a safe and non-addictive form of therapy. It has been used for years to improve behavioral disorders in children, and results in positive effects on intelligence and grades as well. DMAE produces a mild stimulant effect, which develops slowly over a period of several weeks. There is no drug-like letdown or depression if it is discontinued.1

In 1958, Dr. Leon Oettinger, Jr., found that DMAE:2
• Accelerated mental processes
• Improved concentration
• Stopped early morning "fogginess"
• Relieved lassitude and mild depression
• Was useful in schizophrenia of long duration (with prolonged treatment)
• Decreased irritability and reduced overactivity, leading to a much better overall social adaptation and improved scholastic functioning
• Increased attention
• Did not cause drowsiness
• Improved IQ!
Furthermore, Dr. Oettinger found that DMAE had numerous advantages over the amphetamines (like Ritalin) in that there were no effects on heart rate or blood pressure and no induced "jitteriness." Instead of causing anorexia (loss of appetite) like the amphetamines, he found that DMAE actually improved appetite in many patients and caused no interference with sleep. In fact, he found that DMAE actually reduced sleep requirements. Dr. Oettinger concluded that DMAE "was a most useful tool in the handling of the child with behavioral problems."

In 1960, Dr. Stanley Geller reported on a double-blind study of 75 children, that DMAE in doses of 50 mg twice daily resulted in improved functioning capacity, puzzle-solving ability and organization of activity.3

In another double-blind study of fifty children who had been diagnosed as suffering from "hyperkinetic syndrome," DMAE was administered in doses up to 500 mg/day (300 mg in the morning; another 200 mg at lunch). The authors concluded that DMAE, "when administered at doses of 300 to 500 mg per day for 12 weeks to moderately disturbed hyperkinetic children (six to 12 years of age) produces greater overall improvement in comparison to patients similarly treated with a placebo."4

Although most of the human studies involving DMAE and cognitive enhancement seem to have been conducted in the 1950s and 1960s, a recent animal study confirms the memory/intelligence-improving effects of DMAE.5
 


Reducing Chronic Fatigue and Depression, Enhancing Dreaming
DMAE has been demonstrated to be useful in the treatment of chronic fatigue and depression in children,6 and inducing lucid dreaming, and normalizing brain function and mood.7

A recent study in Germany evaluated the effects of DMAE in subjects suffering from borderline emotional disturbance and depression, using a combination of EEG (electroencephalogram) and psychometric testing. The scientists found that DMAE use results in decreased theta and alpha1 waves, characteristic of increased vigilance and attention. In addition, the subjects reported increased activity and better mood. The authors concluded that DMAE induces a psychophysiological state of enhanced well being as corroborated by mood analysis and brain electrical activity.8

DMAE Improves Movement Disorders and Prevents Adverse Effects of L-DOPA in Treatment of Parkinsonism
In 1974, Dr. Edith Miller added DMAE in doses ranging from 300 to 900 mg per day to the regimen of Parkinson's patients, who had begun to exhibit adverse effects from high dosages of L-DOPA (L-3, 4-dihydroxyphenylalanine, administered to treat Parkinson's Disease).9 DMAE administration resulted in a complete resolution of the L-DOPA-induced abnormal movements (diskenesias) in a majority of the patients.

Dr. Miller concluded that "DMAE seems to be the first effective measure to combat L-DOPA-induced dyskinesias safely and effectively without interfering with the beneficial effects of L-DOPA therapy." Studies in an animal model subsequently produced similar results.10

In a subsequent study, Dr. E. Daniel of the Portland VA Hospital used doses of DMAE ranging from 400 to 600 mg per day in a variety of patients with involuntary movement disorders, including benign essential tremor, tardive dyskinesia, and even blepharospasm (eyelid twitching). Use of DMAE resulted in improvement in all symptoms, with the exception of those suffering from Huntington's chorea.11

Improves Skin Tone
In a double blind study of the effects of DMAE on the skin of human volunteers, scientists in Belgium applied a gel containing a three percent concentration of DMAE to areas of "loose skin." They used a technique known as shear wave propagation, and found that the DMAE formulation resulted in an increased shear wave velocity. They concluded that the DMAE formulation increased skin tone and firmness.12 I think it is likely that the same benefits will result from long-term oral ingestion of DMAE.

DMAE Inhibits Formation of "Aging Pigment"
One of the most dramatic and well-documented effects of DMAE is its ability to inhibit the formation of aging pigment (lipofuscin)—the brownish pigment that causes "liver spots" (lentigo) on the backs of the hands of many people over 50 years of age.

Lipofuscin is believed to be formed by the inefficient metabolism of fatty acids, and its accumulation in the cells is one of the most obvious and regularly reported cytological (cellular) changes with age. Lipofuscin accumulates with age in all body tissues—especially, the heart, muscles, kidneys, nerves and brain.

Although no known adverse effects are known to result from lipofuscin accumulation, it certainly does no good, acting as "intracellular garbage." Even if it is not harmful, lipofuscin is often cosmetically unacceptable.

DMAE not only can prevent the formation of lipofuscin, but it also actually flushes it from the body.13 Many people gauge the rate of lipofuscin removal from their hearts and brains by watching their "liver spots" disappear with long-term supplementation of DMAE. It usually takes about six months for significant changes to take place—with many spots resolving completely.

Mechanisms of Action
DMAE has long been known to stimulate the production of choline, which in turn allows the brain to optimize production of acetylcholine (Fig. 2).14-16

Acetylcholine is the primary neurotransmitter involved in learning and memory However, Professor Imre Zs.-Nagy believes that enhanced acetylcholine is not the only explanation for DMAE's effect, since he believes that a choline-rich diet alone should have the same acetylcholine-increasing effect, which he believes is not the case. Zs.-Nagy proposes that other mechanisms of DMAE include its being a free radical scavenger (with particular ability to protect cellular membranes); cross-linkage inhibitor; and spin trapper (a type of free radical scavenger).17

In addition, Dr. Richard Hochschild proposed that DMAE's principal anti-aging mechanism is that of acting as a "cell membrane fluidizer."18

Life-Extending Effects of DMAE
In 1973, Dr. Hochschild evaluated the potential life-extending effect of DMAE on old mice. He administered DMAE in the drinking water to 21-month -old A/J mice. The DMAE-fed mice experienced a significant reduction in mortality and an increase in both mean and maximum survival time (Fig. 3).

Conclusion
DMAE deserves high ranking on the list of proven anti-aging supplements. Its multiple mechanisms of action (acetylcholine enhancer; antioxidant; cross-linkage inhibitor; spin trapper, and membrane fluidizer) amply support an extensive body of well-documented clinical benefits, including:
• Enhancing cognitive processes;
• Inhibiting lipofuscin formation;
• Elevating mood and combating depression;
• Improving skin tone and appearance, and;
• Extending life span of experimental animals.

DMAE has a long track record of safety and efficacy, and ongoing research continues to add to the already impressive list of potential benefits.

Recommended dose for children over 12 and adults is 250 to 500 mg per day. Overdosage may be manifest by slight headache, or jaw or neck tightness (due to overstimulation of the muscles), but these symptoms are transient, and can be relieved by simply reducing the dose.

Criteria for Selecting Anti-Aging Nutrients for This Series

For this series of articles reviewing top anti-aging nutrients, Ward Dean, MD, has selected substances based on several criteria:
1. The mechanism by which the substance is believed to act. Most substances discussed are involved in one or more theories of aging (i.e., antioxidants/free radical theory; cross linkage inhibitors/cross linkage theory; hormone receptor sensitizers/neuroendocrine theory, etc).

2. The health-enhancing effect of the substance.

3. Whether the substance has shown the capability to reverse or restore a biomarker to a more youthful state.

4. Has the substance demonstrated the ability to extend the maximum lifespan of one or more experimental organisms?

5. Practical considerations: An individual's "pill capacity"—how many capsules/ tablets is a person willing to take? Cost and availability—for example, some substances are beyond the reach of many people due to high cost or other impediments (i.e., legal issues, availability, requirement for a prescription, etc.).

Based on these criteria, the series of articles presents what Dr. Dean considers to be the most effective anti-aging/life extending substances readily available today. The substances featured are presented in no particular order. The first article in the series focused on DHEA, published in the June 2004 issue; part 2, on CoQ10, appeared in July; and part 3, on Melatonin, was featured in August.
 

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References
1. Pfeiffer G.C. Parasympathetic neurohormones. possible precursors and effect on behavior. Int Review of Neurobiology 1959;195-244.
2. Oettinger L. The use of Deanol in the treatment of disorders of behavior in children. J Pediat 1958, 53:761-675.
3. Geller, S. J. Comparison of a tranquilizer and a psychic energizer. JAMA 1960, 174:89-92.
4. Coleman, N., Dexheimer, P., Dimascio, A., Redman, W., and Finnerty, R. Deanol in the treatment of hyperkinetic children. Psychosomatics 1976, 17:68-72.
5. Levin E.D., Rose J.E., Abood L.Effects of nicotinic dimethylaminoethyl esters on working memory performance of rats in the radial-arm maze. Pharmacol Biochem Behav 1995 Jun-Jul;51(2-3):369-73.
6. Kugel R. B., Alexander T. The effect of a central nervous system stimulant (Deanol) on behavior. Pediatrics 1963, 31: 651-655.
7. Sergio W. Use of DMAE in the induction of lucid dreams. Med Hypotheses 1988, 26(4): 255-257.
8. Dimpfel W., Wedekind W., Keplinger I. Efficacy of dimethylaminoethanol (DMAE) containing vitamin-mineral drug combination on EEG patterns in the presence of different emotional states. Eur J Med Res 2003 May 30;8(5):183-91.
9. Miller E. Deanol (DMAE) in the treatment of levodopa-induced dyskinesias. Neurology February, 1974, 116-119.
10. Davis K.L., Hollister L.E., Vento A.L., Beilstein B.A., Rosekind G.R..Dimethylaminoethanol (deanol): effect on apomorphine-induced stereotype and an animal model of tardive dyskinesia. Psychopharmacology (Berl). 1979 May 25;63(2):143-6.
11. Daniel E. Mood alterations during deanol therapy. Psychopharmacology 197962 (2):187-191, 1979.
12. Uhoda I., Faska N., Robert C., Cauwenbergh G., Pierard G.E.Split face study on the cutaneous tensile effect of 2-dimethylaminoethanol (deanol) gel. Skin Res Technol 2002 Aug;8(3):164-7.
13. Zs.-Nagy I., Floyd R.A.Electron spin resonance spectroscopic demonstration of the hydroxyl free radical scavenger properties of dimethylaminoethanol in spin trapping experiments confirming the molecular basis for the biological effects of centrophenoxine. Arch Gerontol Geriatr 1984 Dec;3(4):297-310.
14. London E.D., Coyle J.T. Pharmacological augmentation of acetylcholine levels in kainate lesioned rat striatum. Biochem Pharmacol 1978, 27: 2962-2965.
15. Haubrich D.R., Wang P.F., D.E. Clody D.E.,Wedecking P.W. Increase in rat brain acetylcholine induced by choline or deanol. Life Sci 1975, 17: 975-980.
16. Jope R.S., Jenden D.J. Dimethylaminoethanol (deanol) metabolism in rat brain and its effect on acetylcholine synthesis. J Pharmacol Exp Ther 1979, 211:472-479.
17. Zs.-Nagy I. Pharmacological interventions against aging through the cell plasma membrane —a review of the experimental results obtained in animals and humans, Annals of the New York Academy of Sciences 2002, 959:308-320.
18. Hochschild R. Effect of dimethylaminoethanol on the life span of senile male A/J mice. Exp Gerontol 1973, 8(4): 185-191.

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