Gerovital

From Wikipedia, the free encyclopedia

Gerovital H3 (or procaine hydrochloride and products known as GH3 and other variants which may or may not be identical to Gerovital H3) is a controversial preparation developed during the 1950s and promoted by its advocates as an effective anti-aging treatment. During Gerovital's "jet-set" heyday, Gerovital treatments were reportedly administered to John F. Kennedy, Marlene Dietrich, Kirk Douglas and Salvador Dalí.^{[citation needed]} In the United States, the FDA bans Gerovital H3 from interstate commerce as an unapproved drug and, since 1982, has prohibited its importation.
As with many scientific discoveries, the claimed regenerative potential of the anesthetic procaine, a primary ingredient, came to light by accident. Over the years, physicians using it reported unusual and unexpected effects in patients.^[1] Arthritis sometimes would improve, hair would re-grow or recolor, and skin quality often would improve. These reports came for the most part from surgeons, who were not particularly interested in gerontology.^{[citation needed]}
Ana Aslan, MD was a Doctor of the National Institute of Gerontology and Geriatrics in Romania. She was the first to seriously investigate the possibilities of procaine as a tool in the fight against aging. Dr Aslan recognised that procaine in a sense "attacks" the body's cells by numbing them. The body counterattacks with the enzyme cholinesterase. Cholinesterase hydrolyses the procaine in about one hour (66`±14`). Dr Aslan speculated that the compound could be stabilised so that it would not numb the cells. The body would not then reject it and the regenerative effects would be extended.^{[citation needed]}
This notion launched her on a research mission lasting two years. In 1951 she had perfected a procaine product called Gerovital H3 (often called G.H.3 for short). It contained antioxidants and stabilising agents.
Claims coming out of the Institute's clinics for the next few years were viewed as outlandish. Patients treated with GH3 supposedly showed improvements in circulatory function, skin elasticity, ulcers, Parkinsonism, arthritis, hair loss, senility, memory, muscular power, lung capacity and depression. According to the reports, practically all ageing phenomena diminished in severity with GH3.^{[citation needed]}

Development and marketing

It was developed in Romania by Ana Aslan (January 1, 1897 – May 20, 1988). The main active ingredient is the well-known local anesthetic procaine hydrochloride, (often referred to by the old brand name, Novocaine). It also contains small amounts of benzoic acid, potassium metabisulfite and disodium phosphate which are said to be important in the formulation, rendering it more effective by "stabilizing" it. Some advocates acknowledge that despite the stabilizers, the procaine in Gerovital H3 breaks down rapidly into DMAE and PABA, but ascribe the beneficial effects to these breakdown products.
From the 1950s until her death in 1988, Aslan promoted Gerovital H3 with great success. In the 1960s and 1970s her Romanian clinic, the Parhon Institute, became a mecca for celebrities seeking treatment, and an upscale tourist attraction. The New York Times referred to Gerovital's "jet-set aura," noting that Aslan had been covered in "society columns where such public figures as Nikita S. Khrushchev, Konrad Adenauer, and Ibn Saud have been listed among the multitudes said to have taken the drug." As late as 1988 an advertisement by the Romanian National Tourist Office lauded "the picturesque and exciting cities, scenic delights, famous resorts (including Gerovital H3 treatment centers), cultural and historic treasures that await the traveler to Romania."^[2]

Denouncement

A 1973 New York Times article said "cold water was thrown on [Gerovital]'s reputation years ago" by "three reports published simultaneously in British Medical Journal [that] found no merit for procaine hydrochloride for any of the problems of aging."^[3]
A flurry of clinical trials in the mid-to-late 1970s suggests that Gerovital H3 acts as a weak, competitive, reversible MAO inhibitor, and so may have some antidepressant value, but otherwise has negligible effect on disease (see Clinical Trials, below).
In 1994, the U.S. FDA Consumer magazine said: "No health claims for Gerovital have been substantiated, and FDA considers it an unapproved new drug. It has caused low blood pressure, respiratory difficulties, and convulsions in some users."^[4] Suppliers assert that the product is safe, and one cites a brief quotation from a newspaper article that says "while as early as 1973 Elmer Gardner of the FDA's Bureau of Drugs stated 'There is no safety problem with Gerovital H-3.'"^[5]

Clinical Trials

Anti-aging Efficacy

• Zdichynec B. [Successes in novocain therapy in the control of premature ageing (author's transl)] ZFA. 1977;32(3):267-9. German. PMID 337694.

"[...]The treatment with Gerovital H3 according to A. Aslan's method gave very good results in the treatment of diseases like: heart ischemia, systemic arteriosclerosis, predominant cerebral arteriosclerosis, arteriosclerotic Parkinsons disease; obvious results were also obtained in the treatment of psychical disturbances related to arteriosclerosis. The comparison with the control group (patients with placebo) emphasized the good results of the treatment of Aslan: Gerovital H3."

• National Institute of Gerontology and Geriatricts Bucharest Romania (Al. Vrăbiescu, MD, D.Sc) Third English printing summarizing 30 years of Clinical studies.

• E. Bucci and J Saunders (1960 USA): "We observed a new liveliness and mental vigour in 16 of the 25 patients treated"

• U.Khöler & E Mampel (1958 Germany 1958) "Our experiment has shown that an evident improvement in the general condition of old people is possible through the administration of a systematic procain treatment"

• Bogdanova A.I. and Gaiducova I. V. (Russia 1969) "After the medication was administered the vital capacity considerably in 26 out of the 44 patients with reduced vital capacity, the pulmonary ventilation considerably increased in 20 cases".

• Mircea Dimutru M.D./Ph.D. (Mexico 1998) "Gerovital-H3 is indicated for people older than 40 years in order to retard the aging process and as a preventative and curative treatment for chronic degenerative diseases. Gerovital-H3 has been shown to be efficacious in all the following;

•moderate and light depressive states. •in troubles concerning attention, concentrating, cognitive processes and in balancing the neurovegative distinies. •chronic fatique syndrome. •sleep disorders. •distrophias, trophic ulcers, atonic wounds. •osteoarthritis, degenerating rheumatism, osteoporosis and during fracture consolidation periods. •sexual management and improving sex drive •Gerovital-H3 is an active anti-aterogenous factor and recommended in cerebral and peripheral artherosclerosis and in the treatment of post-infarct and hemiplegia consequences. •Parkinson and Parkinson syndromes. •Gerovital-H3 ameliorates the hair resistance and quality, repigmentation, reduces the allpecia (hair loss), head skin seborrgoea and helps eliminate the pruritus. •due to the inhibition on the generation of the superoxide radical, Gerovital-H3 is a powerful antioxidant, a free radical quencher.

Lack of efficacy

• Zwerling I, Plutchik R, Hotz M, Kling R, Rubin L, Grossman J, Siegel B. Effects of a procaine preparation (Gerovital H3) in hospitalized geriatric patients: a double-blind study. J Am Geriatr Soc. 1975 Aug;23(8):355-9. PMID 1097490.

"The overall results of this double-blind study strongly indicated that, among these hospitalized geriatric patients with organic symptoms, Gerovital H3 had no ameliorative effect on either psychologic or physiologic functioning."

• Olsen EJ, Bank L, Jarvik LF. Gerovital-H3: a clinical trial as an antidepressant. J Gerontol. 1978 Jul;33(4):514-20. PMID 376578.

"Twenty-five volunteers, all in their fifth decade or beyond, all with mild to moderate, nonpsychotic depression of at least several months' duration participated in a double-blind study of Gerovital vs placebo. There was no significant difference between the Gerovital and placebo groups; both groups showed significant improvement on self-rating as well as observer rating scales."

• Ostfeld A, Smith CM, Stotsky BA. The systemic use of procaine in the treatment of the elderly: a review. J Am Geriatr Soc. 1977 Jan;25(1):1-19. PMID 12204.

"This article is a review and evaluation of the world literature on the systemic use of procaine in the treatment of the aging process and the common chronic diseases of later life. Included are data from 285 articles and books, describing treatment in more than 100,000 patients in the past 25 years. Except for a possible antidepressant effect, there is no convincing evidence that [Gerovital] has any value in the treatment of disease in older patients. If procaine has an antidepressant effect, there is some likelihood that this accounts for the reports of decreased complaints referable to the musculoskeletal, cardiovascular, endocrine sexual, gastrointestinal and respiratory systems."

• Rissanen V, Rissanen P, Tuomisto J. Procaine (Gerovital): no effect on the rehabilitation result in patients with back or hip disease. Ann Med. 1990 Jun;22(3):151-6. PMID 2203382.

"Gerovital was compared with placebo and another procaine preparation in a double blind study of 88 rehabilitation patients suffering from back or hip disease. [...] In patients treated with Gerovital or another procaine no clinical, physiological or psychological benefits were found in addition to the improvements following rehabilitation compared with placebo treatment. Clinical examination showed that the benefits of rehabilitation were similar in patients receiving Gerovital, another procaine and placebo."

Cognitive Effects

• Cruceanu A, Bucsa L. Age differences in the glucose-6-phosphate dehydrogenase activity of homogenates from the liver of rats. The effect of Gerovital H3 on the glucose-6-phosphate dehydrogenase activity. Physiologie. 1979 Jan-Mar;16(1):71-5. PMID 106418.

"Studies on liver homogenates obtained from Wistar rats revealed that the ageing process produces the loss of glucose-6-phosphate dehydrogenase activity and higher values in the thermolabile fraction of this enzyme. The biotrophic treatment with Gerovital H3 has a strong influence upon glucose-6-phosphate dehydrogenase with tendency to diminish the thermolabile fractions."

• MacFarlane MD. Procaine HCl (Gerovital H3): a weak, reversible, fully competitive inhibitor of monoamine oxidase. Fed Proc. 1975 Jan;34(1):108-10. PMID 1109354.

"A specially stabilized form of procaine hydrochloride (Gerovital H3) has been shown to be a more potent inhibitor of monoamine oxidase than procaine HCl itself and a weaker inhibitor of this enzyme than iproniazid. [...] Analysis of studies using Lineweaver-Burk and Dixon plots revealed that Gerovital H3 was a fully competitive inhibitor of monoamine oxidase. That Gerovital H3 is a weak, reversible, competitive inhibitor of monoamine oxidase [(MAO inhibitor)] may explain the absence of adverse reactions associated with the clinical use of Gerovital H3 as compared to the severe adverse reactions that have been associated with the use of irreversible monoamine oxidase inhibitors."

• Bhaskaran D, Radha E. Murine regional brain monoamine oxidase activity: time- and age-dependent response to inhibitors. Gerontology. 1984;30(2):87-93. PMID 6706127.

"The inhibitory effect of procaine hydrochloride and Gerovital-H3 on monoamine oxidase (MAO) activity in the rat brain was studied at six time points during the 24-hour cycle. It was found that the percent inhibition is time dependent. Both drugs showed maximum inhibition when the MAO activity was at the lowest values during the 24-hour period. In addition to time dependence, these drugs are also age dependent because the MAO activity varies with age."

• Pop M, Tarba C. Changes induced in the bioelectric activity of rat subcortical nervous structures by Gerovital H3 and Aslavital as compared to procaine. Physiologie. 1988 Jul-Sep;25(3):137-49. PMID 3144011.

"Intravenous injection of Gerovital H3 and procaine (20 mg/kg b.w.) into white Wistar rats anaesthetized with nembutal (40 mg/kg b.w.) produces a constant decrease of the wave frequency, more visible at the level of the lateral hypothalamus, but also present in the midbrain reticular formation (the two subcortical nervous structures studied). The wave amplitude is also decreased, especially in the lateral hypothalamus, but the differences gradually recover, a fact more visible in the case of Gerovital H3. Aslavital has similar effects on the wave amplitude, whereas the changes produced in the wave frequency are generally more superficial and transitory. Moreover, the frequency variations in the reticular formation are opposite to those observed in the lateral hypothalamus (i.e., an increase instead of a decrease). Direct intrahypothalamic administration of the drugs (16 micrograms procaine/animal) induces a pattern of responses which is generally opposite to that observed for intravenous injection. Also, the changes produced in the lateral hypothalamus are more superficial this time. An opposition between the effects of Aslavital and of the other two drugs can be observed in this case for the wave amplitude, which is usually increased by procaine and Gerovital H3 and decreased by Aslavital. In many cases, Aslavital induces a burst of positive sharp waves reminiscent of the epileptiform abnormality. The differences observed are tentatively explained by us in terms of dose, drug composition and selective action upon different nervous structures."

Risks

• Forstrom L, Hannuksela M, Idanpaan-Heikkila J, Salo OP. Hypersensitivity reactions to Gerovital. Dermatologica. 1977;154(6):367-9. PMID 142033.

"Procaine chloride, which was a common cause of allergic reactions in earlier years, has lost importance as a contact allergen because its use for local anesthesia has ceased. Recently, we have seen hypersensitivity reactions in three patients after the use of Gerovital, which is known to contain procaine chloride. A word of warning is warranted against indiscriminate use of Gerovital, particularly of its topical preparations."

• Somsen GA, Schut NH. Acute renal failure due to self-medication. Neth J Med. 1998 Jul;53(1):45-6. PMID 9718943.

"A patient with rhabdomyolysis and transient renal failure due to auto injection of [...] "Gerovital" is described. This case illustrates the hazards of self-regulated alternative treatment."

Drug or nutrient?

Procaine itself is universally considered to be a drug. Earlier references by advocates of Gerovital H3 always refer to it as a drug. Hoffer and Walker (1980) call it a "youth drug." Mircea Dumitru, Dr. Aslan's colleague and personal physician, describes it as "a complex drug acting like the procaine molecule ... The addition of benzoic acid, potassium and disodium phosphate increase the effects of Gerovital-H3 biotrophic treatment."^[6] Web-based suppliers outside and inside the United States, that offer to ship the preparation to the U.S. generally characterize it as a "nutrient" "vitamin" or "Dietary Supplement", perhaps because of less strict legal treatment of nutritional supplements in the U. S. under the Dietary Supplement Health and Education Act of 1994. A federal court in decision June 17, 1994, US vs Rodger Sless/TMI classified GeroVital H3 as a dietary supplement.^{[citation needed]}

Quality control

It is notable that virtually every company claiming to supply Gerovital H3 to the U. S. warns of widespread distribution of fake formulations. Many companies suggest that products supplied by its competitors are phony (while asserting that they and only they are the only supplier of the real Romanian formula).

• One company says it sells "real" Gerovital H3 and warns that "the American market is flooded with fake GH3."
• Another says it has "the ONLY ORIGINAL FORMULA BEING IMPORTED TO USA."
• A third says "Beware of the many phony GH3's... we are the only company willing and able to supply documented proof of our GH3's authenticity."

One Gerovital advocate states that the only way for a U. S. consumer to get authentic Gerovital H3 is to have a compounding pharmacy in the U. S. prepare it from a doctor's prescription. He adds, "don't bother with a conventional doctor [who] will have the usual American medical establishment brain wash attitude."^[7]

FDA Ban

As of 2004^[update], the FDA's 1982 automatic detention alert is still in effect and bans the import of Gerovital H3 into the U.S. as "a new drug within the meaning of 201(p), without an approved new drug application [Unapproved New Drug, Section 505(a)]."^[8]
The ban covers:

• Gerovital, GH3, KH3, Zell H3, GH3 etc. This order was rescinded for GEROVITAL Cosmetics Lines, not containing procaine.
• finished injectable or oral Procaine Hydrochloride

2003 UK Trademark revocation

In the UK the term "Gerovital H3" was formerly considered to be a trademark of Prof Dr. A. Aslan, registered to Gerovital Cosmetics SA, but the trademark was challenged in 2003 by Societatea Comercială “Farmec” SA and subsequently revoked.^[9]

References

1. ^ Peter DeMarco, MD
2. ^ "Our colorful TOUROMANIA booklet has it all". New York Times. 1988-03-06. 
3. ^ Harold M. Schmeck Jr (1973-03-18). "Disputed Drug Is Restudied for Use in Geriatrics". New York Times. 
4. ^ Jed Disbennett (March 1994). "Unproven Medical Treatments Lure Elderly". FDA Consumer Magazine. http://www.fda.gov/bbs/topics/CONSUMER/CON00275.html. 
5. ^ "FDA Quotes". Tierra Mega-Nutrients. Archived from the original on 2006-06-20. http://web.archive.org/web/20060620065731/http://realgh3.com/quotes.html. Retrieved 2006-11-28. 
6. ^ Dumitru M.D. Ph. D., Mircea. "Professor Ana Aslan and Gerovital-H3, the Original and First Anti-Aging Medicine". International Antiaging Systems. http://www.antiaging-systems.com/extract/geroh3.htm. Retrieved 2006-12-02. 
7. ^ "Gerovital". The Doctors' Medical Library. http://www.medical-library.net/sites/framer.html?/sites/_gerovital_(gh3).html. Retrieved 2006-12-02. 
8. ^ "Automatic Detention [for Gerovital (IA#61-01)"]. U.S. Food and Drug Administration. Archived from the original on 2006-09-30. http://web.archive.org/web/20060930123927/http://www.fda.gov/ora/fiars/ora_import_ia6101.html. Retrieved 2006-11-28. 
9. ^ "Trade Mark Revocation Decision (o/206/03)" (PDF). UK Patent Office. http://www.patent.gov.uk/tm/t-decisionmaking/t-challenge/t-challenge-decision-results/o20603.pdf. Retrieved 2006-11-28.