DMAE and PABADMAE and PABA An Alternative to Gerovital (GH3), the Romanian Youth Drug
Ward Dean, MD
In Romania, Gerovital, or GH3, has been used for over 50 years to help people look and feel younger. It has attracted thousands of people each year to the spas of Romania and Western Europe where this therapy has been widely used. GH3 is a modification of the local anesthetic, procaine. It was developed for anti-aging uses by Professor Ana Aslan in Romania in the 1940s (Fig. 1). The discovery of procaines potential anti-aging properties was a serendipitous finding. Prof. Aslan was experimenting with the pain-relieving effects of procaine on patients with severe arthritis by injecting it into the arteries (!) which supplied blood to the area of the affected joints. She logically theorized that procaine, being an anesthetic, would relieve the joint pain. She was surprised to find that in addition to dramatic relief of joint pains, many patients also noted (1) improved memory, (2) less depression, (3) more energy, (4) restoration of normal hair color, (5) improved skin tone, and (6) a generalized feeling of well-being. (1) These provocative results encouraged Prof. Aslan to carry out additional studies to test the effects of procaine on thousands of people. She did this at the Romanian National Institute of Gerontology and Geriatrics which she founded in 1950 — the first government-sponsored aging research institute in the world. Aslan found that by adding benzoic acid as a preservative, and potassium metabisulfite as an antioxidant, the procaine molecule was stabilized, and the effects were even more dramatic than with procaine alone. She called her improved form of procaine Gerovital, or GH3. She later added pyridoxine (vitamin B6), mesoinositol, and glutamic acid to this formula, to form yet another version called Aslavital. Aslavital was reported to have even more powerful and beneficial effects on memory, atherosclerosis, and other degenerative conditions than the original Gerovital H3. (2)
H3 is approved by the Romanian equivalent of the FDA for use in the treatment of numerous diseases, including: (1) prevention and treatment of the aging process; (2) depression; (3) arthritis; (4) asthma; (5) gastric and duodenal ulcers, (6) osteoporosis, and many other conditions.
In 1987, I traveled to Romania to attend and present a paper at the Romanian National Congress of Gerontology and Geriatrics (Dean). (3) I was interested in learning more
about Gerovital and Aslavital — to see first-hand how it was administered, meet patients undergoing the therapy, and review the scientific studies that had been performed. I was impressed by the body of scientific research that supported the use of procaine, Gerovital H3, and Aslavital as prophylactic and therapeutic agents against the aging process.
How Does Gerovital Work?
Procaine, as Gerovital H3 and Aslavital, has numerous documented mechanisms of action. These include (1) inhibition of monoamine oxidase (an enzyme in the brain which increases with age); (4,5,6) (2) nootropic properties; (7) and (3) antioxidant action. (8)
When procaine enters the body, it is broken down into para-aminobenzoic acid (PABA, a para B-vitamin), and diethylaminoethanol (DEAE), both of which are naturally present in the body (Fig. 2). Both of these substances are biologically active and have numerous beneficial effects of their own. Although the majority of the research involving Gerovital and Aslavital attribute the benefits to the procaine molecule, there is still controversy as to whether the effects are due to the procaine molecule itself, or to its breakdown products, PABA and DEAE. (9)
Anti-Aging Effects of PABA
PABA has been used as a component of many commercially available sunscreens due to its ability to block damaging ultraviolet rays. Skin damage due to sunlight causes or accelerates many of the characteristic skin changes that we attribute to aging. (10) PABA, both topically and orally, is truly an antiaging substance in terms of protecting
the skin from the sun.
PABA is a naturally occurring, water-soluble compound which is found in many foods as a cofactor of the vitamin B complex (associated with folate). It first became popular due to the writings of pioneer nutritionists like Gaylord Hauser, Lelord Kordell, and Adelle Davis. (11,12,13) Several decades later, life extension scientists Durk Pearson and Sandy Shaw extolled the potential virtues of PABA in their best-seller, Life Extension — A Practical Scientific Approach.
Is PABA a Vitamin?
By definition, a vitamin is a biologically active organic compound that is essential for an organisms normal health and growth, a deficiency of which results in a deficiency disease or disorder. Though PABA has many vitamin-like qualities, it fails to meet the strict definition of a vitamin. Early animal studies did, however, demonstrate that PABA increased lactation in rodents and increased the weight of chicks that were fed a diet with low levels of folate. These early studies suggested that PABA was essential, and it has erroneously been described as a B vitamin by many nutritionists and health educators in dozens of books. PABA is actually a structural part of folic acid. Although PABA is not technically a vitamin, it does appear to have a number of interesting and potentially valuable uses.
The Anti-Gray Hair Vitamin
One very interesting application for this versatile substance is its potential to restore hair to its natural color. In 1941, Dr. B. F. Sieve reported that administration of 200 mg of PABA per day for two months resulted in marked darkening of the hair in 30 patients with gray hair. (15) Brandaleone and colleagues (1944) reported that 2 of 33 individuals with grey hair had significant hair color change when administered 200 mg of PABA with 100 mg of calcium pantothenate (vitamin B5) and 50 grams (approx. 2 ounces) of brewers yeast for eight months. (16)
Dr. Chris Zarafonetis (1964) of Temple University followed these investigations with a report that described 5 cases of dramatic hair color change and hair regrowth in 20 patients with markedly gray hair, who were taking 6-24 grams of PABA per day for other conditions. (17) The hair color changes were serendipitous results of this therapy.Zarafonetis concluded that consumption of 6-24 grams of PABA per day for at least 6 weeks restored the natural hair color of 25% of people with markedly gray hair. He did not speculate on the mechanism for hair color restoration and pointed out that the effects were highly variable and might require extended periods of administration.
Zvak (1986) confirmed that forty years ago, large doses of PABA were clearly shown to darken grey hair; the regained color was lost within 3-4 weeks of stopping the treatment.(18) While it is clear that the hair color restoration effects of PABA were less than universal, any therapy which results in 10-25% reversal of an irreversible condition (like hair grayness) must certainly be considered significant.
PABA as an Antioxidant
It has been well established that PABA is a potent neutralizer of singlet molecular oxygen, a potent free radical which is a common by-product of normal metabolism. (19)
In theory, use of antioxidants protects cellular membranes and mitochondrial DNA from free radical attack. The mitochondria are the energy-producers of the cells. Mitochondrial degradation results in reduced cellular energy production which causes numerous undesirable physiological conditions, which may include fatigue and the aging process itself. As an antioxidant, PABA also provides protection against ozone, smoking, and other air pollutants that damage other cell structures and membranes through oxidative stress. PABA promotes cell membrane fluidity by preventing such oxidant damage.
PABA as an Anti-Crosslinking Agent
The crosslinkage theory of aging was proposed by Professor Johan Bjorksten in 1974. Bjorksten believed that the aging process was due to crosslinks (undesirable bonds induced by excess free radicals) which formed between molecules). Bjorksten theorized that these crosslinks progressively impaired the function of the body, the end
result of which was aging. (20) PABA appears to slow and in some cases even reverse crosslinking in the protein structures of connective tissues such as collagen.
In addition to resulting in the loss of flexibility with age, and perhaps the aging process itself — also is the primary process in a number of fibrotic diseases, including: Peyronies disease (formation of fibrotic plaques of the penis, usually in men over 50, resulting in painful, crooked erections, rendering intercourse difficult or impossible); Dupuytrens contracture (wherein the flexor tendons of the fingers of the hands become fibrotic and contract, rendering the fingers useless); and scleroderma (a rare condition
characterized by heavily crosslinked skin and tissues, with disabling systemic results). Zarafonetis (1964) found PABA to have a marked therapeutic effect in these conditions, in doses of 12 grams per day. (21) Zarafonetis also used PABA to treat dermatitis herpetiformis (200 mg, 4-5 times daily), and vitiligo (a depigmenting disease). By slowing crosslinking, PABA may promote greater body flexibility in normally aging individuals.
Potential Side Effects and Cautions
High-dose PABA is generally well-tolerated, its most significant adverse side effects being diarrhea and nausea, which resolved with cessation of use, or lowering of the dose. As PABA is water soluble, it is rapidly excreted in the urine, and must therefore be administered in divided doses throughout the day. High-dose PABA should be discontinued when taking sulfa antibiotics (like Bactrim or Septra).
Pearson and Shaw described PABA as an antioxidant which could: (1) slow crosslinking; (2) enhance flexibility; (3) promote membrane fluidity; (4) provide protection against ozone, secondhand smoke and other air pollutants; (5) alleviate the inflammation of arthritis; and (6) restore the original color of hair in perhaps 10-25% of cases. Pearson and Shaw reported they consumed as much as three grams of PABA per day. (14)
Dimethylaminoethanol (DMAE) is a substance that is closely related to DEAE (Figure 3) — the other metabolic by-product of GH3. DMAE is a naturally occurring nutrient found in such brain foods as anchovies and sardines. It stimulates the production of choline, which in turn allows the brain to optimize production of acetylcholine (Fig. 4). Acetylcholine is the primary neurotransmitter involved in learning and memory.
DMAE is a mild cerebral stimulant, which was at one time approved by the FDA as being possibly effective for the following conditions:
DMAE for Adult and Childhood Learning Disorders
For those children and adults who suffer from ADD, ADHD, and other learning disorders (and even for those who dont) I recommend DMAE (dimethylaminoethanol). DMAE has been used for years to improve behavioral disorders in children, and may have positive effects on intelligence and grades as well.
In 1958, Dr. Leon Oettinger, Jr., found that DMAE:
Furthermore, he 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.(23)
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. (24)
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 author concluded that DMAE, when administered at doses of 300-500 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. 25)
DMAE for Chronic Fatigue, Depression, and to Enhance Dreaming
Kugel and Alexander reported that DMAE had also been demonstrated to be useful in the treatment of chronic fatigue and depression in children, (26) and Sergin reported the phenomena of DMAE-induced lucid dreaming, and speculated on its effects in normalizing brain function and mood. (27)
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 300-900 mg per day to the regimen of Parkinsons patients who had begun to exhibit adverse effects from high dosages of L-DOPA. DMAE administration resulted in a complete resolution of the L-DOPA-induced abnormal movements 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. (28)
In a subsequent study, Dr. E. Daniel of the Portland VA Hospital used doses of DMAE ranging in dosages from 400 to 600 mg/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 Huntingtons chorea. (29)
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). 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. 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, as it is the brownish pigment that causes liver spots on the backs of the hands of many people over 50 years of age.
DMAE not only can prevent the formation of lipofuscin, but it also actually flushes it from the body. 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 — many spots resolving completely.
Life-Extending Effects of DMAE
Richard Hochschild, designer of the H-SCAN (probably the most well tested system designed to measure human biological age), evaluated the potential life-extending effect of DMAE on old mice. DMAE administration in the drinking water resulted in a reduction in mortality and an increase in both mean and maximum survival times (Fig. 5). (30)
In his book, Secrets of Life Extension, John Mann wrote that GH3 may not be the key to extraordinary life extension, but it appears to help, treat and delay the onset of many of the symptoms and side effects of aging. It can be a useful adjuvant to other longevity agents, and will, most likely, potentiate their effectiveness.(31) I agree with Johns assessment.
Gerovital and Aslavital are unapproved by the FDA, and are therefore largely unavailable in the US. Nevertheless, it is still possible for people who wish to avail themselves
of this therapy by asking their physicians to prescribe it for them through a compounding pharmacy. Although not approved for anti-aging use, physicians can legally prescribe drugs that are not approved in this country, but which are not specifically illegal.
An alternative is to use a PABA-DMAE complex containing the ingredients that Prof. Aslan found to work synergistically with her formula. DMAE and PABA in the proper concentrations may have effects as dramatic as those of GH3 itself, and may provide a variety of independent positive effects as well. Consequently, since DMAE and PABA are both readily available, inexpensive dietary supplements, this may be a satisfactory (and perhaps, a superior) alternative.
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