Vitamin A: Part 2

By James P. Meschino, DC, MS

Editor's note: This is part two of a two-part article on vitamin A. Part one (www.chiroweb.com/archives/24/13/11.html) discussed general features, functions and health benefits of vitamin A. Part two includes a complete list of references spanning both parts of the article.

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The North American Vitamin A Status Update

The National Health and Nutrition Examine Surveys (I and II), along with the Continuing Survey of Food Intakes by Individuals and 1994-96 Diet and Health Knowledge Survey (ARS Food Surveys Research Group. Internet - 1997), indicate that approximately 56 percent of Americans do not meet the daily requirement for vitamin A intake. In fact, in many cases, individuals only consume 50 percent of the RDA level on a daily basis. Thus, marginal deficiency of vitamin A is not uncommon in developed countries. As such, the use of a daily multiple vitamin supplement providing 2,500-3,000 IU of preformed vitamin A and 10,000-15,000 IU of beta-carotene may be highly beneficial to health optimization and the prevention of epithelial cancers, according to epidemiological studies and experimental data. However, consuming a multiple vitamin containing 5,000 IU or more of preformed vitamin A may increase risk of toxicity over the long-term, increase risk of osteoporosis in postmenopausal women, and may increase risk of birth defects. On the other hand, there are special cases in which higher doses of vitamin A can be used on a therapeutic basis, but higher doses require proper monitoring for toxicity and should not be used during pregnancy or lactation (see note about supplementation for pregnant and lactating women at the end of this article), or by individuals with liver or kidney disease.

Vitamin A Toxicity

Toxicity has been associated with abuse of vitamin A supplements and with diets extremely high in preformed vitamin A. Consumption of 25,000-50,000 IU/day for periods of several months or more can produce multiple adverse effects. Individuals at highest risk have liver function previously comprised by drugs, viral hepatitis, alcohol, or protein-energy malnutrition.

• Children: Adverse effects have been shown to occur with intakes as low as 1,500 IU/kg/day.
• Pregnant women: Increased risk of birth defects has occurred with maternal intakes as low as 25,000 IU/day.

From a clinical standpoint, toxicity typically occurs in patients taking high-dose vitamin A ( 50,000 IU) for various skin conditions (e.g. acne, psoriasis, eczema). Even synthetic water-soluble vitamin A has been shown to cause toxicity at doses of 18,500 IU to 60,000 IU per day over a period of months.

Signs and Symptoms of Vitamin A Toxicity

Children: Anorexia, bulging anelles, drowsiness, increased intracranial pressure, irritability, and vomiting.

Adults: Abdominal pain, anorexia, blurred vision, drowsiness, headache, hypercalcenia, irritability, muscle weakness, nausea and vomiting, peripheral neuritis, skin desquamation, brittle nails, cheilosis, gingivitis, alopecia.

Birth defects associated with high maternal intake of vitamin A (18,000-100,000 IU before and throughout pregnancy): abnormal-ities of the head, face, ears, eyes, mouth, lips, jaw, heart and urinary system; other defects.²

Dosages greater than 10,000 IU during pregnancy, specifically during the first seven weeks after conception, may lead to birth defects. Women who are at risk for becoming pregnant should keep their supplemented vitamin A levels below 5,000 IU per day.³ A study showed that among 59 women who became pregnant while taking prescription vitamin A 13-cis retinoic acid (Accutane) for acne, 12 spontaneous abortions and 21 malformed infants occurred.

Vitamin A Supplementation

Acute viral infection: 50,000 IU for one or two days.

Cancer treatment and prevention: Wolback and Howe noted that retinoid-deficient epithelial tissues had a premalignant phenotype (appearance), characterized by enhanced mitotic activity (rapid cell turnover) and loss of differentiation.⁴ Retinoids are known to possess antiproliferative, differentiative, immunomodulatory and apoptosis-inducing properties. A growing body of evidence supports the hypotheses that the retinoic acid receptor B2 gene is a tumor suppressor gene, and that the chemopreventive effects of retinoids are due to induction of this receptor.⁵ A unique vitamin A compound presently is being used in cancer prevention and treatment. This form of vitamin A, known as 9-cis-retinoic acid, has been used to suppress premalignant oral lesions and prevent the development of secondary primary cancers among patients with head, neck and lung cancers. This form of vitamin A is now being considered in the treatment of breast cancer, which often displays under expression of the retinoic acid receptor B2.^6-9

Note that a number of alternative and holistic health practitioners recommend high doses of water-soluble vitamin A (50,000-300,000 IU per day) as part of the adjunctive nutritional support for patients with certain cancers. Many of these practitioners suggest it is a useful intervention to help prevent recurrence of certain cancers and control the spread of existing lesions (www.diagnoseme.com). In these cases, monitoring for vitamin A toxicity is mandatory.

Acne: There is some evidence that vitamin A supplementation at 25,000 IU per day may improve acne. However, this dose may lead to signs of toxicity. (Headache, cracking and chapped lips, fatigue, dry skin, and joint pain are early warning signs and symptoms.) Doses above 5,000 IU per day also increase the risk of birth defects in children born to mothers ingesting these higher levels of vitamin A at the time of conception.¹⁰

In my experience, a safer and more appropriate natural treatment for acne is the ingestion of P73 wild oregano capsules in conjunction with topical application overnight of the P73 wild oregano cream. This form of wild oregano has been shown to kill many bacteria, viruses and fungi, including the bacteria involved in acne.

Drug-Nutrient Interactions

• Bile acid sequestrants such as cholestyramine and colestipol are known to reduce vitamin A absorption.^11,12
• Neomycin is known to reduce the absorption of vitamin A and increase its excretion, which increases the need for supplemention.¹³
• Mineral oil decreases the absorption of vitamin A.¹⁴
• Vitamin A-derivative drugs (isotretinoin) may increase risk of toxicity by potentiating the effects of vitamin A. Caution should be exercised with respect to supplementation in these types of cases.¹⁵
• Orlistat decreases vitamin A levels in the body, which increases the demand for vitamin A supplementation.^16,17
• Corticosteroid drugs may decrease vitamin A levels in the body, which increases demand for supplementation.¹⁸
• High doses of vitamin A may impair the absorption of vitamin E if taken concurrently.¹⁹

*Pregnancy and Lactation

During pregnancy and lactation, the only supplements considered safe include standard prenatal vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the developing fetus, and there is generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other than a prenatal supplement. Any supplementation practices beyond a prenatal supplement (e.g., magnesium for the treatment of pre-eclampsia) should involve the cooperation of the attending physician.

References

1. Standard textbooks of nutritional science: Shils M, Shike M, Olson J, Ross C. Modern Nutrition in Health and Disease, 9^th edition. Baltimore, MD: Lippincott Williams & Wilkins; 1993; Escott-Stump S, Mahan LK, editors. Food, Nutrition and Diet Therapy, 10^th edition. Philadelphia, PA: W.B. Saunders Company; 2000; Bowman B, Russell RM, editors. Present Knowledge in Nutrition, 8^th edition. Washington, DC: ILSI Press; 2001; and Kreutler PA, Czajka-Narins DM, editors. Nutrition in Perspective, 2^nd ed. Upper Saddle River, NJ: Prentice Hall Inc.; 1987.
2. Hathcock JN, Hattan DG, Jenkins MY, et al. Evaluation of vitamin A toxicity. Am J Clin Nutr 1990;52:183-202.
3. Rothman KJ, et al. Teratogenecity of high vitamin A intake. N Engl J Med 1995;333:1396-1373.
4. Wolbach SB, Howe PR. Tissue changes following deprivation of fat-soluble A vitamin. J Exp Med 1925;42:753-77.
5. Spoon M. Retinoids and demethylation agents - looking for partners. J Natl Cancer Inst 2000;92(10):780-1.
6. Widschwendter M, et al. Methylation and silencing of the retinoic acid receptor-B2 gene in breast cancer. J Natl Cancer Inst 2000;92(10):826-38.
7. Sporn MB, Newton DL. Chemoprevention of cancer with retinoids. Fed Proc 1979;38:2528-34.
8. Hong WK, Lippman SM, Hittelman WN, Lotan R. Retinoid chemoprevention of aerodigestive cancer: from basic research to the clinic. Clin Cancer Res 1995;1:677-86.
9. Pastorino U, Infante M, Maioli M, et al. Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol 1993;11:1216-22.
10. Kugman O, Mills J, Leyden, et al. Oral vitamin A in acne vulgaris. Int J Dermatol 1981;20:278-85.
11. Longenecker JB, Basu SG. Effect of cholestyramine on absorption of amino acids and vitamin A in man. Fed Proc 1965;24:375.
12. Schwarz KB, Goldstein PD, Witztum JL, Schonfeld G. Fat-soluble vitamin concentrations in hypercholesterolemic children treated with colestipol. Pediatrics 1980;65(2):243-50.
13. Jacobson ED, Faloon WE. Malabsorptive effects of neomycin in commonly used doses. J Am Med Assoc 1961;175:187-90.
14. Diarrhea and constipation. In: Berkow R, Fletcher AJ, Beers MH, et al., editors. The Merck Manual of Diagnosis and Therapy, 16^th edition. Rahway, NJ: Merck Research Laboratories; 1992.
15. Accutane (isotretinoin), product prescribing information. Nutley NJ: Roche Laboratories Inc.; 2000.
16. Xenical (Orlistat), product prescribing information. Nutley NJ: Roche Laboratories Inc., 2000.
17. Melia AT, Koss-Twardy SG, Zhi J. The effect of Orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers. J Clin Pharmacol 1996;36(7):647-53.
18. Atukorala TM, Basu TK, Dickerson JW. Effect of corticosterone on the plasma and tissue concentrations of Vitamin A in rats. Ann Nutr Metab 1981;25(4):234-8.
19. Eicher SD, Morrill JL, Velazco J. Bioavailability of alpha-tocopherol fed with retinal and relative bioavailability of D-alpha-tocopherol or DL-alpha-tocopherol acetate. J Dairy Sci 1997;80(2):393-9.

Resources for Pregnancy and Lactation Information:

1. Murray M. Encyclopedia of Nutritional Supplements. Prima Publishing, 1998.
2. Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and Company, Inc., 1998.
3. Murray M. The Healing Power of Herbs, 2^nd edition. Prima Publishing, 1995.
4. Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine. Institute of Applied Complementary Medicine, Inc., 1997.

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