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Chapter 5: And Pyridoxine
(Vitamin B6) is Another
Immortalists who follow the many experiments on drugs against aging will have noted that still again another drug has joined the list of all those drugs for which AT LEAST ONE experiment has shown a lifespan increase in a MAMMAL. This drug is the vitamin pyridoxine, or Vitamin B6. Only one experiment has shown an effect thus far; J Miquel, K Lindseth and M Dictor at the NASA Ames Research Center report their results of an experiment in which they fed a
dose of 100 mg/kg a day to a group of aged (18 months old) mice of the C57BL6J strain. This chapter shall provide a brief discussion of the prospects for Vitamin B6 as a drug for use against aging.
One of the most favorable facts about this experiment is the strain of mouse used by Miquel and his colleagues. The C57BL6J strain is a long-lived strain and among those for which antioxidant treatment was NOT effective. Robert Kohn, in a famous experiment, tried to produce a lifespan increase by giving BHT to this strain and found no significant increase in the lifespan of their experimental mice (RR Kohn J GERONT 26 (1971) 378). It is really quite notable if a drug can produce an increase in a strain which before has resisted such increases. The increase itself, on the other hand, was comparatively small, only 11%, although we should temper our disappointment about the small size of the increase because Miquel et al only started drug treatment at 18 months, which corresponds to late middle age for these mice. Miquel, Lindseth, et al report also that the doses of pyridoxine decreased levels of blood cholesterol and increased the levels of HDL cholesterol.
What sort of dosage of drug would a human being require if he/she were to adopt pyridoxine as an antiaging drug? Miquel et al do not give the average weight of their mice, but mice on average weigh about 35 grams to 50 grams. An adult human being weighs (about) 70 kilograms; we therefore weigh about 2000 times as much as a mouse. At a dose of 100 mg/kg per day the mice were receiving about 3.5 to 5 mg of pyridoxine per day. Immortalists who follow this issue closely will all know of the problems we have in establishing the right DOSAGE of drug for a human being from animal studies. I myself believe (on no grounds which I am willing to defend against all attack!) that the best way to extrapolate dosage, in the absence of other information, is to scale it by the 2/3rds power of body weight. On this scaling we then get a
drug dosage of pyridoxine required by a human being who wants to duplicate these experiments of about 550 to 650 mg per day. Another suggestion is that we should scale dosage proportionally to body weight; if we did so this would mean a dosage of about 10 grams a day. For antioxidants this is not even an unreasonable amount; however for pyridoxine this begins to enter the toxic range, as readers will see below. For what it's worth, my suggestion would be to use the 2/3rds rule. >
Scientists and biochemists have known the vitamin pyridoxine since before the Second World War and by now know a great deal about its possible toxicity and the dangers of taking it. Since all known antiaging drugs need quite high dosages for their effect we'll need to know a lot about their toxicity before we think of taking them; a drug for which we have a long experience therefore has much more interest than one newly discovered.
Toxicity of pyridoxine is very widely thought to be quite low, although information on the effects of really high doses in human beings seems quite scanty. The dose of pyridoxine which will kill 50% of animals receiving it by mouth is (for rats) 5500 mg/kg. High enough doses of pyridoxine will certainly cause toxic effects; one study reports that doses of 1 gram per kg in rats or dogs will cause damage to peripheral nerves, degeneration of the spinal cord, and paralysis of the hind legs.
What we really want, of course, is reports of the effects of high dosage in human beings. There is one condition in children for which doctors have given pyridoxine in doses as high as 500 mg/day; this is the form of genetic mental and metabolic deficiency known as homocystinuria (called this because children who have it excrete large amounts of the amino acid homocystine in their urine). One doctor reports treating two children with pyridoxine for homocystinuria at a dose as high as 1200 mg/day (GE Gaull et al LANCET 14 Dec 1968, 1302). The total number of patients treated with these large doses seems small, at least from published reports. The only toxic effect reported from these studies was lowered levels of the vitamin folic acid in the tissues of the affected children (B Wilcken, B Turner ARCH DIS CHILD 48 (1973) 58-62). This observation suggests that we should take extra folic acid with our pyridoxine. However there have also been other reports of toxic effects at doses much less than 500 mg/day. One encephalitis patient taking 200 mg/day of pyridoxine had aggravated seizures, and another had changes in the electrical activity of his brain as measured by the EEG. Two patients who were also taking oral contraceptives responded to supplemental pyridoxine by showing lethargy (in one case) and insomnia in the other. There is also a
significant chance that prolonged existence on high doses of pyridoxine might produce a dependency upon the drug: you might find it hard to stop taking it without prolonged discomfort; one author reports a case of dependency arising after taking 200 mg/day for 33 days, which is not a long time (JE Canham et al PROC VI INT CONG NUTRIT 1964, p. 537) . Although not strictly a toxic effect, this would mean that you would risk complications if you suddenly stopped taking your accustomed dose of pyridoxine. Finally the possible neurological changes as suggested by the experiments on dogs and cats described above would certainly merit caution.
There have also been other toxic effects, much less serious but also better established. The most prominent toxic effect may be ACNE. Women seem particularly subject to this reaction; in each case the patient took quite small doses of pyridoxine, often by injection, for other reasons, and the report of acne from pyridoxine contains no controlled studies but only case reports. Doses were about 30 mg/day orally and injections of 2 mg per week. In all the case reports the doctors had combined injections of pyridoxine with injections of Vitamin B12. (O Braun-Falco, MUNCH MED WOCHENSCHRIFT 118 (1976) 155-160).
Pyridoxine also has quite a number of other favorable effects. In all sanity, we would want to temper our appreciation of these effects with an equal appreciation of the possible toxicity of the drug. Nevertheless these uses of pyridoxine need mention.
By far the most outstanding is pyridoxine in pregnancy. One very well established ill effect of pregnancy is due to pyridoxine deficiency. Urine of pregnant women contains metabolic products characteristic of pyridoxine deficiency, and treatment of pregnant women with extra pyridoxine is highly recommended. The first effect of pyridoxine deficiency is depression, though depression is subjective and hard to measure. However, subjective or not, depression can cause suicides and disrupt lives, a very serious effect. One quite measurable effect of pyridoxine lack is its promotion of diabetes, obviously both objectively measurable and serious. Supplemental pyridoxine very significantly helps this problem, with fewer women showing diabetes during gestation on the extra pyridoxine than otherwise (HJT Coelingh Bennick et al BRITISH MED J 3(1975) 13-15; 11 out of 13 patients recovered from their diabetes after treatment). Women on oral contraceptives also have increased need for pyridoxine, since present contraceptives work by creating a pseudopregnancy.
Some further uses of extra doses of pyridoxine are for radiation sickness (150 to 300 mg/day), used particularly for treatment of radiation sickness due to radiation treatment for cancer. Secondly, pyridoxine has been helpful in cases of schizophrenia; one doctor reports treating 15 chronic schizophrenics with extra pyridoxine at doses of 150 mg/day. The pyridoxine treatment needed 2 to 3 months to show any objective effects. Thirdly, extra doses of pyridoxine have helped deal with drunkenness, at doses of 100 mg/day combined with fruit sugar in the form of honey or otherwise combined with antihistamines. The authors reporting this effect point out that it cannot abolish the effects of alcohol but will help calm very drunken patients and speed their recovery. Finally, some interesting papers suggest that extra pyridoxine may help prevent tooth decay (LP Strean et al NY STATE DENTAL J 24 (1958) 133; A Cohen et al BULL PHIL CTY DENTAL SOC 22(1958) 84).
Taking Pyridoxine
If we propose to take pyridoxine for our own aging we'd also like some information on how this drug may work. It is simply untrue that we can maximize our chances of longevity by taking large doses of all known drugs, since many of these may interfere with one another. Some knowledge of how the drug acts therefore becomes pertinent. Of course we don't know how pyridoxine increases longevity and won't find out in a reasonable time; however the metabolism of pyridoxine gives us some suggestive hints. Pyridoxine plays an important role in our biochemical handling of the amino acid tryptophan. Tryptophan itself plays a very suggestive role in aging; prolonged tryptophan deficiency inhibits development and also slows aging, as P. Segall and others have found. Furthermore, high levels of supplemental pyridoxine will increase levels of brain dopamine. Previous to the use of L-Dopa, some doctors even used pyridoxine as a treatment for Parkinsonism, and work on pyridoxine seems to have played an important historical role in the discovery of L-Dopa as a treatment (P Holtz, D Palm PHARMACOL REV 16 (1964) 113). This fact may be very important for immortalists, since it suggests strongly that
PYRIDOXINE WORKS LIKE L-DOPA AGAINST AGING;
I am speculating but the speculation seems well based. Pyridoxine also antagonizes the effect of L-Dopa itself, an excellent example of how two different antiaging substances may interfere with one another. Since it is a common vitamin, pyridoxine is far more available than L-Dopa or any of the other possible antiaging drugs, such as procaine or Deaner, which may act through the same pathway.
We would like more information on the effects of pyridoxine on aging, particularly other studies confirming the original experiment. We would also like much harder information on dosage, but this is a problem with all antiaging drugs. Nevertheless the recent experiment on pyridoxine suggests that pyridoxine will indeed act significantly against aging.
To Learn More:
Bucci, L,"Pyridoxine and schizophrenia", BRIT J PSYCHIAT 122 (1973) 240
Carson, NAJ; Carre, IJ, "Treatment of homocystinuria with pyridoxine. A preliminary trial", ARCHIV DIS CHILDHD 44(1969) 387
Coelingh Bennick HJT et al "Improvement of oral glucose tolerance in gestational diabetes" BRITISH MED J 3(1975) 13-15
Gaull, GE, "Pyridoxine dependency in homocystinuria", letter in LANCET 2(1968) 1302
Hooft, C et al, "Pyridoxine treatment in homocystinuria", letter in LANCET 1(1967) 1384
Lindseth, K; Dictor, M; Miquel, J, "Favorable effects of pyridoxine HCl on the aging process of C57BL6J mice", AGE 5(4)(1982) 143
Sebrell, WH, Jr; Harris, RS, THE VITAMINS Vol II, Academic Press 1968
Martindale, THE EXTRA PHARMACOPEIA. Entry on pyridoxine hydrochloride, p.1694.
| This article contains chapters from the book, A GUIDE TO ANTIAGING DRUGS, published by PERIASTRON.
Dr. Donaldson aimed to provide, in the GUIDE, a discussion of both the good points and the bad points, of every drug shown by experiment to prolong the healthy lifespan of some mammal. The mammals involved must normally reach at least the average lifespan of their species.
This Web Site provides only samples of only part of the GUIDE, which discusses other drugs also. | |