Supplement Actions & Interactions

The potential for vitamin toxicity is real. Most Americans believe that vitamins and other supplements are safe. That’s true if they are used correctly. Too many people still think that if one is good, ten is better. Especially alarming is the scenario in which a well-meaning mother tells her youngster to chew his daily animal-shaped gummy vitamin because it’s good for him and will make him grow to be big and strong, like Daddy.  Junior doesn’t know that ten is not better, climbs up to the counter, struggles to open the bottle, and eats a handful of vitamins. If the vitamins are made from food the worry is minor, but still there. If synthetic, like most, the danger for an adverse reaction is much greater and becomes a medical emergency.  Fat-soluble vitamins have a higher potential for poisoning because they can accumulate in the body, but there is comfort knowing that, even with more than 71,000 vitamin overdose reports to poison control centers in 2010, no one ever died from a vitamin excess (Bronstein, 2011). The actual number is 71,545 out of 2,784,907, representing about 2.5% of all exposures. The medical community that reviewed total toxic exposures ruled vitamins to be safe.

Antioxidants: Vitamin A Vitamin A is a group of fat-soluble substances called retinoids, including retinol, retinal, retinoic acid and retinyl esters that are involved in immunity, vision, reproduction, and cellular communication. As an essential component of rhodopsin, vitamin A is critical for vision. Since it supports healthy cell growth and division, it is likewise important to the heart, lungs, kidneys, and other organs. This nutrient exists in two forms. Pre-formed vitamin A is called retinol, found mostly in animal foods and converted to the metabolically active forms known as retinal and retinoic acid. The other form of vitamin A is the provitamin carotenoid, beta-carotene, although other carotenes exist as alpha-carotene and beta-cryptoxanthin, all of which are converted to vitamin A and metabolized to retinal and retinoic acid. All forms of the vitamin are made into micelles and are absorbed by the duodenum. In a cascade of metabolic events, retinol is converted to retinal and then to retinoic acid. Much of the vitamin A from food comes as retinol. About one third of the dietary source comes from plants, especially grains, oils, and green and yellow fruits and vegetables, such as carrots and pumpkin.

Because the liver maintains vitamin A levels within a narrow window, overdose is possible by overzealous supplementation, and can be serious in children. But that does not exempt adults from the hazard. Intake of much more than 1.5 milligrams of supplemental A each day (5000 IU), particularly of preformed vitamin A, can backfire and reduce bone mineral density by as much as 10% in the femur and 6% for the total body, thereby increasing risk for hip fractures (Melhus, 1998). But vitamin A precursors are not totally exculpated (Feskanich, 2002). Observational studies on retinol conclude that total vitamin A intake is more important than the source, whether from supplements or from foods, and that twice the current RDA (3000 IU or 900 mcg for adults) is enough to compromise bone integrity (Crandall, 2004). The Brazilians noted an increase in risk of skeletal fractures when intake of dietary vitamin A from retinol was excessive, as bone resorption was stimulated and bone formation inhibited (Genaro, 2004).

Nutrition Labels Have a Purpose Good intentions are insufficient to ward off the throes of taking too much of a supplement, whether alone or as part of a multi-vitamin or other complex. This is why you need to read labels of all the supplement bottles you open. If each bottle contains a little bit of the same nutrient, you need to add the numbers to arrive at the value you swallow, lest you take too much and possibly suffer harm. Water-soluble nutrients are not usually the problem; fat-soluble ones are. High doses of vitamin A over long periods of time, regardless of source, can antagonize vitamin K and reduce its effectiveness as a clotting agent and cause internal hemorrhage (Grubbs, 1985). Most people don’t monitor vitamin K intake from supplements. Neither do they watch how many green leafy vegetables they eat to account for vitamin K supply. Except for that prescribed by a medical doctor, high doses of vitamin A means taking more than twice the daily recommendation.

Deficiencies of nutrients often parallel one another. Low zinc levels limit the bioavailability of vitamin A, regardless of how much is ingested (Rahman, 2992).  Iron deficiency is a known cause of anemia. In the absence of ample vitamin A stores, even supplemental iron is inhibited despite its enhanced hematological response by vitamin C (Fishman, 2000). Certain foods can inhibit or facilitate supplemental nutrient uptake and absorption, too. In the presence of fiber, vitamin A absorption is enhanced (Kasper, 1979).

Vitamin A and Your Liver Because vitamin A is handled by the liver, anything that burdens that organ might contribute to problems down the line. Acetaminophen is notorious for causing liver damage, even fatalities, and  amiodarone, carbamazepine, methotrexate, and a slew of other drugs can cause liver concerns in the presence of excess vitamin A. Taking 25,000 IU of vitamin A daily for several months will turn your eyes and skin yellow and, for a pregnant, woman, can cause birth defects (Hathcock, 1990). Mixing vitamin A, often prescribed for acne, with tetracycline antibiotic prescribed for the same condition can cause intracranial hypertension with resultant headaches, nausea and vomiting, as well as pulsate tinnitus and vision symptoms (Walters, 1981). Heaven forbid you take an Rx blood thinner and overdo the vitamin A at levels greater than 10,000 IU a day.  Vitamin K will be antagonized and hemorrhage becomes a possibility (Hardman, 1996).

When it comes to fat-soluble vitamins, be careful not to overdo it. Although toxicity is relatively rare, is it especially possible in the elderly, chronic alcohol users and those with a genetic predisposition to high cholesterol (Russell, 2000). Avoid taking more than the RDA of pre-formed vitamin A (retinol) during pregnancy, being alert to fortification of food and counting it as part of daily intake. Synthetic derivatives, such as those used to treat skin conditions (Accutane, Retin-A) either orally or topically are no less dangerous merely because they come from a pharmacist. The terms “acetate” and “palmitate” describe preformed vitamin A. Although beta-carotene is safer, use common sense.

Alvin C. Bronstein, MD ; Daniel A. Spyker, MD, PhD ; Louis R. Cantilena, Jr, MD, PhD, et al 2010 Annual Report of the American Association of Poison Control Centers ’ National Poison Data System (NPDS): 28th Annual Report Clinical Toxicology (2011), 49, 910–941

Crandall C. Vitamin A intake and osteoporosis: a clinical review. J Womens Health (Larchmt). 2004 Oct;13(8):939-53.

Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA. 2002 Jan 2;287(1):47-54.

Fishman SM, Christian P, West KP. The role of vitamins in the prevention and control of anaemia. Public Health Nutr. 2000 Jun;3(2):125-50.

Genaro Pde S, Martini LA. Vitamin A supplementation and risk of skeletal fracture. Nutr Rev. 2004 Feb;62(2):65-7.

Grubbs CJ, Hill DL, Farnell DR, Kalin JR, McDonough KC. Effect of long-term administration of retinoids on rats exposed transplacentally to ethylnitrosourea. Anticancer Res. 1985 Mar-Apr;5(2):205-9. Hardman JG, Limbird LL, Molinoff PB, eds. Goodman and Gillman's The Pharmacological Basis of Therapeutics, 9th ed. New York, NY: McGraw-Hill, 1996.

Hathcock JN. Metabolic mechanisms of drug-nutrient interactions. Fed Proc. 1985 Jan;44(1 Pt 1):124-9.

Hathcock JN, Hattan DG, Jenkins MY, McDonald JT, Sundaresan PR, Wilkening VL. Evaluation of vitamin A toxicity. Am J Clin Nutr. 1990 Aug;52(2):183-202.

Kasper H, Rabast U, Fassl H, Fehle F. The effect of dietary fiber on the postprandial serum vitamin A concentration in man. Am J Clin Nutr. 1979 Sep;32(9):1847-9.

Melhus H, Michaëlsson K, Kindmark A, Bergström R, Holmberg L, Mallmin H, Wolk A, Ljunghall S. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med. 1998 Nov 15;129(10):770-8.

Michaëlsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med. 2003 Jan 23;348(4):287-94.

Allen LH, Peerson JM; Maternal Micronutrient Supplementation Study Group Collaborators (37) Impact of multiple micronutrient versus iron-folic acid supplements on maternal anemia and micronutrient status in pregnancy. Food Nutr Bull. 2009 Dec;30(4 Suppl):S527-32

Rahman MM, Wahed MA, Fuchs GJ, Baqui AH, Alvarez JO. Synergistic effect of zinc and vitamin A on the biochemical indexes of vitamin A nutrition in children. Am J Clin Nutr. 2002 Jan;75(1):92-8.

Russell RM. The vitamin A spectrum: from deficiency to toxicity Am J Clin Nutr. 2000 Apr;71(4):878-84.

Vetrugno M, Maino A, Cardia G, Quaranta GM, Cardia L. A randomised, double masked, clinical trial of high dose vitamin A and vitamin E supplementation after photorefractive keratectomy. Br J Ophthalmol. 2001 May;85(5):537-9.

Walters BN, Gubbay SS. Tetracycline and benign intracranial hypertension: report of five cases. Br Med J (Clin Res Ed). 1981 Jan 3;282(6257):19-20.

*These statements have not been evaluated by the FDA. These products are not intended to treat, diagnose, cure, or prevent any disease.