Applied Trophology, Vol. 5, No. 5
(May 1961)

“Some Side Effects of Drugs,” plus High Points of For-Til B12

The following is a transcription of the May 1961 issue of Dr. Royal Lee’s Applied Trophology newsletter, originally published by Standard Process Laboratories.

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Some Side Effects of Drugs

Reprinted from Side Effects of Drugs, L. Meyler, MD, pp. 151–154, Excerpta Medica Foundation, Amsterdam, New York, pp. 151–154, 1958 (194 pages, $5.00).

Chapter XXV: Vitamins

Vitamin A

By way of experiment, a doctor took 1,000,000 U of vitamin A daily, first for fourteen days and a few months later again for twenty-five days. He noted headache, itching, desquamation of the skin, and aggravation of an existing seborrhoea and alopecia. The fingernails became brittle. Further phenomena were cheilosis, epistaxis, anorexia, nausea, constipation alternating with diarrhea, tenesmus, impaired visual acuity with muscae volitantes, dizziness, myasthenia, fatigue, arthralgia, and pain in the long bones, especially the tibiae.¹

A twenty-one-year-old woman treated her acne with 160,000–180,000 U of vitamin A daily for seven months. She then had pain in the bones and joints and suffered from fatigue and insomnia. The ankles were swollen, and cutaneous hemorrhages and blisters in the mouth were present. There was diuresis. The liver was enlarged. The vitamin A content of the blood was 832 mg per 100 ml. Recovery followed when she stopped taking vitamin A. Four other patients further presented the following symptoms: loss of hair, anorexia, emaciation, lassitude, polyuria, pruritus, exophthalmos, and headache.²

Hypervitaminosis A was observed in two children as follows:³

a) A six-year-old boy who had been treated for six weeks with 460,000 U of vitamin A per day had diuresis, nocturnal enuresis, vomiting, anorexia, emaciation, and pain in the forehead, arms, and legs. The subcutaneous tissue over the bones was painful and swollen. The liver and spleen were enlarged. There were conjunctivitis, fissures at the angles of the mouth, and edema of the face. The child ran a temperature and appeared ill. Protein was detected in the urine, and the blood urea content was increased.

b) A four-year-old girl treated for the past two years with 340,000 U of vitamin A per day had fever, painful bones, and hepatomegaly, and, more especially, loss of hair, desquamative exanthema, palpebral edema, epistaxis, and bleeding lips. The sensitivity of the bones, anorexia, and irritability disappeared within a week after withdrawal of vitamin A.

Vitamin B1 (aneurine; thiamine): Intravenous administration was followed by anaphylactic shock and generalized edema. The skin test and nephelometric reaction were positive.⁴ Anaphylactic shock occurred 5 minutes after an intramuscular injection of 100 mg of vitamin B1. In addition to the disturbances due to the fall in blood pressure, there were evident signs of bronchospasm. Recovery followed intravenous administration of diphenhydramine.⁵

Nicotinic acid: Provoked pruritus and urticaria in a patient after oral as well as parenteral administration.²³

Folic acid: Exanthema, painful, swollen joints, and fever developed after ingestion of folic acid.⁶

One patient took 3 mg of folic acid without side effects. A few weeks later, he took 20 mg orally and forty minutes afterwards he felt ill, had pain in the chest, and breathed with difficulty. Again, twenty minutes later, the palmar and plantar regions began to itch and erythema developed. A positive intracutaneous reaction was found.⁷

Vitamin B12 (cyanocobalamin): A severe and painful glossitis and cheilosis may be produced by administration of vitamin B12. Two cases are reported. In one the mouth was so painful that no solid food could be taken, and even drinking was impossible for some time. These symptoms developed while the blood responded favorably. The oral symptoms rapidly regressed under treatment with folic acid, and it is therefore assumed that vitamin B12 had caused a relative folic acid deficiency.⁸ The development of polycythemia after treatment of pernicious anemia with vitamin B12 has been described.²⁴

Vitamin D2 (calciferol): Several cases of vitamin D2 poisoning have been described, mainly in children. It is especially the consequences of the hypercalcemia that may lead to a dangerous condition. Perhaps the hypercalcemia is not primary but is the result of the toxic action of vitamin D2 on tubular function. The hypercalciuria and polyuria might be primary and might point to a disturbed reabsorption.¹³

In two children the condition was fatal. One had received thirteen intramuscular injections of 500,000 IU in two years, the other four injections in fourteen months. Both had calcium deposits found in the arteries, especially in the tunica media. Calcium was also demonstrated in the renal tubuli and further in the gastric mucosa and in the heart and lungs. In one case, calcium was found in the heart valves. During life a systolic murmur had been heard.⁹

In several patients a blood calcium content of 17–18 mg per 100 ml was found. There were signs of impaired concentrating power of the kidneys, polyuria, uremia, and dehydration.¹⁰ One patient had attacks of renal colic.¹¹ The first signs are often pallor, emaciation, and apathy. In a case of anemia of unknown etiology and resistant to the usual treatment, it is advisable to consider the possibility of vitamin D poisoning.¹² Sulkowitch’s test on the urine may lead to the diagnosis.

Some publications suggest that cortisone and other corticosteroids have a beneficial effect in vitamin D2 poisoning.¹⁴ The rapid recovery and especially the rapid fall in the blood calcium, as well as the strongly negative calcium balance as compared with that of patients not treated with cortisone, are arguments in favor of this new mode of treatment.

A six-year-old boy who had received 3.7 million U of vitamin D2 in six weeks developed a particularly threatening picture. He was effectively treated with fluids, a low-calcium diet, and cortisone. For four weeks he was first given 30 mg and subsequently 60 mg of cortisone daily. The author is of the opinion that the cure was aided by cortisone.²²

Some publications point to a special sensitivity to vitamin D2, as a result of which hypercalcaemia is produced by doses that are not excessively high.¹⁵

Vitamin D3 (vigantol): An infant had tonic spasms after administration of at least 6.8 million U of vitamin D3, associated with calcium and ultraviolet treatment. In addition to hypercalcemia and a renal affection with uremia, calcium deposits were found in the brain.¹⁶

A nine-month-old child was given 80 mg of vitamin D3 in eight weeks on an (incorrect) diagnosis of rickets. He developed signs of hypervitaminosis with fever, anorexia, polyuria and polydipsia, vomiting, constipation, and muscular hypotony. The serum calcium was 18 mg per 100 ml. X-rays of the hands and knees revealed calcium deposits in the metaphyses. In this case, too, cortisone was administered in addition to the usual treatment.¹⁷

Vitamin K Group

Menadiol (2-methyl-1,4-naphthalenediol); diphosphate, tetra-Na salt (kappadione, synkavite, synkayvite, thylokay, vikasol)

Menadione (2-methyl-1,4-naphthoquinone; menaquinone; menaphthone; vitamin K3; hemodal, kappaxan, kappaxin, kayklot, klottone, koaxin, kolklot, menaphthene, prokayvit, synkay, vitavel-K); bisulfite compound (hykinone, vitavel-K soluble)

Vitamin K1 (2-methyl-3-phytyl-1,4-naphthoquinone; 3-phytylmenadione; phytomenadionum; phytonadione; phylloquinone; koniakon, mephyton)

Vitamin K4 (2-methyl-1,4-naphthalenediol diacetate; menadiol diacetate; acetomenaphthone; kapilon, kappaxan oral, prokayvit oral, vitavel-K oral) (See also Menadiol)

Vitamin K5 (4-amino-2-methyl-1-naphthol-HCl; kavitrate, kayvisin, solvika, synkamin): In the past few years, it has transpired that the amount of vitamin K usually given to prematures in the first days of life is far too high. These excessive doses are capable of producing increased hemolysis and occasionally even kernicterus.

It is considered that 1 mg of vitamin K1 or menadione bisulfite as prophylaxis—and double this amount in cases of manifest hemorrhages—is sufficient.¹⁸ One publication reports fourteen cases of hemolytic anemia in premature infants following administration of 40–170 mg of menadiol diphosphate. One premature, weighing 770 g, was given 5 mg immediately after birth and another 20 mg in the next ten days. Hemolytic anemia developed and had a fatal course.¹⁹

It is also reported that an intravenous injection of 1 mg of vitamin K5 provoked anaphylactic shock.²⁰

Injection of vitamin K1 was followed by reactions occurring in two patients. These were probably due to allergy and consisted of cyanosis, swelling of the neck and face, and edema.²¹

References

1. Jol. Clin. Nutr., 4:603, 1956.
2. Amer. Med. Ass., 161:1157, 1956.
3. Dis. Childh., 31:229, 1956.
4. Med. Acta., 24:27, 1957.
5. Intern. Med., 45:134, 1956.
6. Acta Med. Scand., 157:233, 1957.
7. Med. Jol., 1162, 1957, I.
8. Jol. Med., 21:461, 1956.
9. Amer. Med. Ass., 163:65, 1957.
10. Med. Liege, 11:200, 1956.
11. Lancet, 668, 1957, I.
12. New Engl. Jol. Med., 255:1207, 1956.
13. Vitamine D2-Intoxicatie, Thesis, Groningen, 1956.
14. Presse Med., 65:1562, 1957; Actapaediat., 45:96, 1956.
15. Med. Wschr., 81:1365, 1956; Helv. Paediat. Acta., 11:118, 1956.
16. Kinderlteilk., 105:350, 1957.
17. Wscltr., 35:555, 1957.
18. T. Geneesk., 101:705, 1957.
19. Paediat. Acta., 11:325, 1956.
20. A.M.A., 163:410, 1957.
21. Med. Wschr., 86:996, 1956.
22. T. Geneesk., 101:2004, 1957.
23. Med., 4/13:191, 1956.
24. Intern. Med., 47:544, 1957.

It is probable that all these effects were created by synthetic forms of the products involved, since most of the commercial sources are of this type. Even if purified natural vitamins are used, they are not to be compared with the action of a natural, unrefined complex. Mice die in a few days on a diet of hamburger plus refined sugar yet live indefinitely on hamburger plus unrefined sugar. (Editor, Applied Trophology)

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High Points of Standard Process Nutritional Adjuncts

For-Til B12: For-Til B12 contains an extract of tillandsia fortified with natural vitamin B12 (with intrinsic factor). The vitamin B12 supplies known geriatric factors, and the tillandsia extract supplies vitamin E/chlorophyll complex factors. Clinically, the contents of For-Til have been observed to offset some of the problems of aging, such as symptoms of senility or other degenerative conditions. In younger patients these factors have in some instances increased libido and have also been observed to reestablish delayed sexual development.