• Antioxidants As Drugs Against Aging
• Pantothenate, a Vitamin That May Work   
• And Pyrodixonej (Vitamin B6) Is Another
• Procaine, the Famous One
• Deanol, a Test Case for Anti Aging Drugs
• Levodopa, the Hard Stuff
• Phenformin and Phenytoin, Two Drugs to Watch

Chapter 4: Pantothenate, a Vitamin that May Work

Pantothenic acid has very widespread occurrence in many biochemical reactions of living tissue. The major biochemical role of pantothenic acid seems to be as a constituent of Coenzyme A. This important biochemical is involved in many chemical reactions essential to life: it is an essential chemical for the oxidation of sugars or starches, and therefore essential to processes by which our cells get energy. It is important for the oxidation of fatty acids. Coenzyme A takes part in those processes by which our cells make fatty acids. Some fatty acids, such as the phospholipids, are essential constituents of cell walls; fats are also involved in the synthesis of other substances, such as parts of the hemoglobin molecule and various amino acids.

For longevist purposes, possibly the two most interesting roles of Coenzyme A are in the detoxification of toxic substances and the synthesis of cholesterol and steroid hormones made from cholesterol. Coenzyme A is involved in a very important type of reaction which occurs in the liver, called acetylation, by which our bodies dispose of many different kinds of toxic substances. The highest content of Coenzyme A is in the liver, the next highest concentration is in the adrenal glands. The adrenals make corticosterone, a steroid hormone very important in helping our bodies respond to stress of many kinds.

Since Coenzyme A appears in almost all living tissue, deficiencies of pantothenic acid are very hard to produce. However, with special diets scientists have produced pantothenic acid deficiencies in animals; among the symptoms of such deficiencies are hemorrhage in the adrenals, anemia, ulcers, and a spastic gait. Similar symptoms appear in dogs and monkeys deprived of pantothenic acid. The only clear case of natural deficiency in man seems to have occurred among prisoners of the Japanese during World War II; patients on diets without pantothenic acid showed similar symptoms to those of the animals, including tenderness of the feet.

The evidence that pantothenic acid will have a direct positive effect on longevity comes from a single experiment done in 1958. Roger J Williams, who had done extensive work on other properties of this vitamin, and Richard B, Pelton, then at the Clayton Foundation Biochemical Institute, fed large amounts of pantothenic acid to a group of 34 male and 40 female C-57 black mice to see if it might increase their lifespans. Two lines of evidence had led them to suggest that the vitamin might have such an effect: first, queen bees live much longer than workers, and pantothenic acid is the main compound in Royal Jelly, fed to larvae which are to become queens; second, much more suggestive, in 1948 one scientist had shown that pantothenic acid would actually increase the lifespan of fruit flies (Garder, TH, JOURNAL OF GERONTOLOGY 3(1948) 1). In their own experiment on mice, Williams and Pelton put 13 males and 20 females in the treated group, 21 males and 20 females in the control group; treated mice received 300 micrograms of the pantothenic acid salt, calcium pantothenate, per day through the experimental period. Since mice weigh about 30 grams each, this is a dose of 10 mg/kg. Results of the Williams and Pelton experiment were positive; treated mice lived about 19 percent longer than untreated control mice.

In their report, Pelton and Williams suggest that pantothenic acid merits much more investigation as a drug for aging. Unfortunately, no one seems to have followed up their suggestion. C-57 mice tend to be longlived, so that it would be hard to explain the lifespan increase as a curative effect on some kind of inherited pathology in C-57 mice. The major defect of their experiment lies in the small number of animals used and the fact that they worked with only one species, mice. It would be important to duplicate their experiment with more mice, to get better statistics, and with rats also so as to gain some idea of the action of the vitamin on different species.

The statistical significance of their experiments merits some comments. Several tests of significance are commonly used; Pelton and Williams used two, Student's t-test and the Mann-Whitney U-test. According to the t-test, there is a 95 percent chance that the difference in lifespans between treated and control mice was not accidental. This is just on the edge of what is normally counted as significant. According to the U-test, there is better than a 99 percent chance. The U-test is considered by many statisticians as possibly the best test to measure whether or not treated populations have different means, and it gives higher significance to the results.

Additional experiments with both rats and humans support the idea that pantothenic acid may increase lifespans. Moreover they suggest why it may have that effect. In both rats and humans large doses of pantothenic acid increase ability to withstand stress. Ralli and Dummm fed normal rats large amounts of pantothenic acid and tested their ability to swim in cold water (18 degrees C). Normal rats were only able to swim for about 30 minutes; treated rats could survive in cold water for 60 minutes, double the time for the untreated animals. Ralli has reported tests of response of human subjects to the same kind of stress, swimming in cold water; even though the test could not be taken to exhaustion for the humans, pantothenic acid signficantly increased the ability to withstand the stress.

The adrenal glands secrete corticosterone and other hormones assisting the body to withstand stress. Dumm and Ralli showed, in fact, that pantothenic acid could substitute in some way for the adrenals : rats whose adrenals had been removed, if fed large amounts of pantothenic acid, could swim in cold water as long as rats with intact adrenals but without pantothenic acid. In their paper, Ralli and Dumm point out that Coenzyme A is important to a large part of the energy production in the tissues, that adrenal hormones may normally cause energy production to go up, and that if the animal has a large store of Coenzyme A already present, it can increase its energy production, and so withstand stress, even if it lacks the adrenal hormones.

Some theories of aging suggest that its main effect is to cause aged animals to react to stress less well than younger animals. Disturbances in the ability of the adrenals to respond to stress with aging have been clearly found in rats (Riegle, GD, NEUROENDOCRINOLOGY 11(1973) 1-10; Riegle, GD and Hess, GD, NEUROENDOCRINOLOGY 9(1972) 175-187). A long series of measurements by N Shock over many years has shown decreases with aging in the ability of people to adapt to various physiological stresses such as cold, exercise, or consumption of sugar. Some but not all of these depend on the adrenals, so that pantothenic acid may increase lifespans by providing a substitute for the action of the adrenals, just as in Ralli's experiments rats fed pantothenic acid could respond as well as intact rats even though their adrenals had been removed. However it does not seem likely that pantothenic acid affects any basic mechanism of aging.

Toxicity and Dose

Toxicity results on pantothenic acid appear very good. At least 100 mg of pantothenic acid (as calcium pantothenate!) has been injected intravenously in humans without causing any toxic effects. Daily doses of 200 mg have been fed to young female rats for 190 days without causing any signs of toxicity; adult monkeys have eaten 1 gram of the salt, calcium pantothenate per kilogram of body weight for six months without showing any symptoms of harmful effects, even loss of body weight. Human beings have also eaten 10 to 20 grams of calcium pantothenate daily with no signs of toxicity other than an occasional diarrhea.

For use on aging we would also want to know the best dose. Pelton and Williams fed their mice 300 micrograms of calcium pantothenate daily; a dose of 10 mg per kilogram. A 70 kilogram man would therefore take about 700 mgs/day. This is far below the 10 grams fed to human subjects already with no ill effects.

Finally, we would like to know about availability of this drug; pantothenic acid is widely available without prescription. Calcium pantothenate bought in pharmacies does, however, turn out to be expensive. I have listed some less expensive sources from which readers may buy it by mail in Appendix 3 of this book.

TO LEARN MORE:

Dumm ME, Ralli EP "Factors influencing the response of adrenalectomized rats to stress" METABOLISM CLIN EXPTL 2 (1953) 153-164.

Goodhart, RS, Shils, ME MODERN NUTRITION IN HEALTH AND DISEASE, 5th Ed,