For several years, hundreds of thousands of people have flocked to Romania annually to get their shots of GH3, the controversial “youth drug” developed Dr. Ana Aslan of Bucharest. Until recently, the drug was not permitted in the United States. Now the state of Nevada is allowing GH3 therapy. But people are still asking, “Does it really work? And what exactly is it supposed to do?”It has often been said that if our bodies could maintain homeostasis indefinitely, we might be immortal. Homeostasis is the chemical equilibrium of the body. The hypothalamus is very much involved in this aspect of biochemistry. Homeostasis regulates internal body temperature, blood pressure, perspiration rate, heart-pulse rate, blood sugar, hunger, thirst, sleeping and waking cycles, and almost every activity within the physical system. It also preserves the delicate balance between various enzymes, amines, and hormones in the body. As we age, many facets of our homeostatic harmony become imbalanced; unless they are compensated for, these imbalances may lead to far-reaching complications.
One aspect of homeostasis that alters with age and has a definite effect on some conditions of aging is the increase in monoamine oxidase (MAO) in the tissues. MAO is an enzyme that breaks down various amines that are formed in the body. Some of these amines, tyramine, for instance, are -products of certain foods. Others are biogenic substances that occur naturally in the body and serve specific functions, such as aiding brain and nerve-impulse transmission. When, for example, the body produces extra epinephrine (adrenaline) or norepinephrine for added stimulation or emergency, MAO rapidly deaminates the excessive amounts of these neurohormones in the tissues and returns the body to its normal homeostatic balance.
Because MAO levels tend to rise with age, usually starting at around 45, greater than normal amounts of these stimulant amines are destroyed. When norepinephrine levels fall too low, activity of the brain and central nervous system is depressed. The anxiety, depression, and loss of interest in life that often accompany old age are now understood to be caused excessive MAO, which causes a lack of norepinephrine and other catecholamines, especially in the hindbrain. To correct this problem, physicians have usually prescribed MAO inhibitors, or tricyclic compounds, which inactivate MAO. These drugs prevent the deamination of catecholamines in the brain and neuron vesicles, so that they can accumulate at the required levels. Depression is usually lifted, and energy increases enough that the person can function normally again.
Unfortunately, these MAO inhibitors have several disadvantages. The patient must avoid alcohol, amphetamines, and foods that are rich in tyramine or tyrosine (beer, chianti-type wines, and ripe cheeses), since these can interact with MAO inhibitors to cause a hypotensive crisis, which involves a sharp blood-pressure drop, chills, shivers, rapid heart palpitations, and breathing difficulties. Some combinations, though, can have an opposite effect, causing a steep blood-pressure rise (hypertensive crisis). Another disadvantage of most MAO inhibitors is that their effects are not easily reversed. When the body needs more MAO to cope with toxins or infection, the inhibitor occupying the normal MAO sites decreases the activity of the enzyme.
How much excesses of MAO have to do with the aging process is still under investigation. The condition may be more a symptom than a cause of senescence. There is no question, however, that it is involved in most of the depression and anxiety that occur in later years. Depression and anxiety are forms of stress, and must inevitably have a deleterious effect on the body and accelerate aging. Mental attitude has been shown to reverberate on the endocrine systems, which in turn determine much of the body’s total condition.
For many years, scientists and physicians have been looking for safer ways to control MAO levels in depressed or aging patients. Yet it appears that they may already have the agent they seek. It has been on every physician’s shelf for the past sixty years. That substance is procaine, better known as novocaine.
PROCAINE AND ANA ASLAN
Procaine was first synthesized Alfred Einhorn in 1905. It was developed primarily as a local anesthetic to substitute for cocaine, which had turned out to have unmanageable side effects. In 1940, F.J. Philpot reported in the Journal of Physiology his discovery that procaine was, at least in vitro, an MAO inhibitor. Nothing came of his finding at the time. A few enlightened physicians had noted that procaine injections relieved some forms of arthritis, but it was never established as a standard medication for this disorder.
Ana Aslan was born in Bucharest in 1899. She earned her medical degree in 1924 and became Romania’s first female physician as well as its first cardiologist. During the late 1940s as director of the government clinic at Timisoara in Romania, Dr. Aslan began using procaine injections to treat arthritis, angina pectoris, and other painful disorders. She had remarkable success in achieving the expected results, but what intrigued Aslan and her co-workers were the unexpected results, which could not be attributed to its local-anesthetic properties. Among the other things, older patients felt younger and more alive, less depressed and more energetic.
In 1951, Dr. Aslan became director of the Bucharest Geriatric Institute, and developed an improved procaine compound, which she called Gerovital H3 or GH3. Her GH3 formula consists of 200 mg of procaine hydrochloride in 10 ml of saline solution, with 16 mg of benzoic acid and 14 mg of potassium metabisulfite, buffered to a slightly acid pH of 3.3. It is usually administered intramuscularly three times a week for four weeks. This is followed a rest period of two to four weeks, after which another series of injections or tablets is given. With this drug she observed many other anti aging effects: high cholesterol levels dropped; skin elasticity improved; skin texture became smoother and less wrinkled; muscular strength increased; hair often regrew on balding areas; pigmentation was sometimes restored to graying hair; high and low blood pressure were normalized; and even failing memory was greatly improved.
In 1956, Ana Aslan reported her findings at a symposium in Karlsruhe, West Germany. Her claims were met largely with disbelief. The following year, supported further evidence, she addressed another symposium, and this time was well-received. Soon other researchers were corroborating her findings. Studies in France and Germany showed a 20 to 30 per cent increase in the life span of rats given regular injections of GH3.
In the early 1960s, however, some British and American workers challenged Aslan’s discoveries. They had attempted to duplicate her experiments, using ordinary procaine hydrochloride instead of her GH3 preparation, and quite understandably did not get the same results. The AMA, brandishing all negative findings and ignoring all positive ones, officially declared GH3 (procaine) useless as anything other than a local anesthetic. Despite the fact that the AMA is notorious for its blatantly unscientific habit of arriving at conclusions that suit its own prejudices and purposes, the statement was enough to dampen American interest in GH3 for ten years.
The destiny of this drug took a new turn in 1965, when a research group at the Chicago Medical School headed Arnold Abrams published the results of a series of carefully controlled double-blind tests with both GH3 and ordinary procaine. The intent of the experiments had been to disprove the claims made for the Romanian drug, but the honest conclusion these workers had to report was that, although procaine yielded only slight results, GH3 had beneficial physical and psychological effects that warranted further study.
In 1971, Alfred Sapse of UCLA revived interest in GH3 in the United States. He ran a computer check on all available procaine data, and received readouts that completely supported the idea that the drug is efficacious. He then had M. David MacFarlane of the University of Southern California test GH3 as an MAO inhibitor. MacFarlane reported that it is a mild, short acting, selective, fully competitive, and reversible MAO inhibitor. That is, GH3 inhibits certain forms of MAO that are effective in neutralizing particular catecholamines, such as nor epinephrine and serotonin, but has very little effect on others. It competes for MAO sites, but does not cling to them permanently. If extra MAO is needed, the inhibitor is easily displaced. Another advantage of GH3 as an MAO inhibitor is that the patient does not have to shun alcohol and certain foods and drugs in order to avoid hypotensive and hypertensive crises.
After Sapse was thoroughly convinced of GH3’s value as an MAO inhibitor and anti aging drug, he joined forces with Manfred Mosk and Nathan Kline and founded Rom-American Pharmaceuticals, Ltd. They negotiated with the Romanian government, and won a ten-year contract for exclusive rights to import the drug into the United States and to distribute it. Seven years later, Rom-Amer was still trying to gain FDA approval merely to conduct clinical tests with GH3 in this country. Finally, the company had to move from California to Nevada, the only state that no longer bans the drug. Since ordinary anesthetic procaine has been in common use for more than half a century, there is no serious question about its safety. Further information about its worth can only be derived clinical testing. The main obstacle seems to be the FDA’s general reluctance to approve foreign-produced drugs.
The public’s interest in the reports of GH3’s beneficial effects, coupled with the unavailability of the substance in this country, has created a market for inferior products that bear names similar to Gerovitol or GH3, but that contain no procaine. In Europe, however, several worthy variations on Dr. Aslan’s formula are produced and sold. Doctors Wolfgang Schwartzhaupt and Fritz Wiedermann have developed an oral version of the drug, potentiated with hematoporphyrin, and known as KH3. Hematoporphyrin has a regulating effect on the nervous system, is used for treating nervous depression, and also improves the functioning of the sexual glands.
Since excessive serotonin is known to be harmful and is now regarded as a probable trigger for the “death hormone” responses, it may seem contradictory that one of procaine’s virtues is that it prevents the deamination of this and other catecholamines, thus allowing them to accumulate. There is no actual contradiction, however. Brain amines, such as serotonin, dopamine, and norepinephrine, exist in a balanced relationship with each other, varying somewhat in different sections of the brain. The limbic structures, for instance, contain the highest concentrations of serotonin and norepinephrine, whereas the neocortical portions have almost none. In most brain tissues, the distributions of these two neurohormones are more or less similar. The hypothalamus has less serotonin, but the proportion increases with age. The “death hormone” response appears to be triggered an abnormal rise of serotonin and a simultaneous depletion of dopamine, the precursor of norepinephrine, in this organ. The object of using L-dopa and negative ions to control serotonin, then, is not to rid the brain tissues of this neurohormone, but rather to normaiize its distribution in proportion to the other amines.
Although procaine is a synthetic chemical, it is composed of two natural substances: para-aminobenzoic acid (the B vitamin, PABA) and diethylaminoethanol (DEAE, which apparently participates in the synthesis of choline and acetylcholine; it is similar to DMAE). When procaine enters the bloodstream, it is rapidly hydrolyzed into these two substances. For a while, some gerontologists believed that the benefits of procaine and GH3 might be entirely due to the vitamin effects of these two metabolites: But equivalent dosages of PABA and DEAE did not produce the same results as the drug. It has been suggested that procaine may reach important sites in the brain or in the individual cells not ordinarily permeated -PABA or DEAE, and is then converted to these vitamins.
Although the benzoic acid and potassium metabisulfite are added to GH3 as antioxidants and preservatives, they seem to have additional functions. The presence of the potassium ion aids in the absorption of the drug, and the benzoic acid may partially form a benzoate salt of procaine. This may slow down the otherwise rapid metabolism of the procaine and give it more time to accomplish its work.
It is not well understood why GH3 is so much more effective than procaine. Its gentle MAO-inhibiting properties explain its value in treating anxiety, depression, and abnormal blood pressure, but it also has a stimulating influence on cells and tissues. The late J. Earl Officer at the USC School of Medicine administered GH3 to embryonic wild-mouse tissue cultures during maturation and again during the normal decline period. He found that the aging of the cells was slowed down and possibly reversed. Ana Aslan had previously had similar results using chick-and monkey-cell cultures.
B. M. Zuckerman at the University of Massachusetts Laboratory of Experimental Biology slowed the aging process in a species of nematode adding GH3 to its medium. Many aging traits of this nematode are similar to those of human red blood cells. Both accumulate the aging pigment lipofuscin. Also, the cell membranes of both become fragile with age, while the cell becomes heavier and loses its negative surface charge. GH3 retards the formation of lipofuscin in nematodes, and inhibits the development of liver spots (lipofuscin deposits) in humans. GH3 seems to strengthen cell membranes, according to studies now in progress.
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.