Vitamin A: What You Probably Didn’t Know
Chester J. Zelasko, Ph.D. | November 27, 2007

Of all the questions I get about vitamins, vitamin A is the one I get asked about most frequently. Why? Because Vitamin A is the one nutrient that seems scary. Vitamin A can build up in the liver and cause serious liver problems. If you read anything about vitamin A, without question it will warn you that too much vitamin A has been associated with birth defects and hip fractures in the elderly. If you’re pregnant, it’s the one nutrient that your obstetrician will tell you to limit.

I finally decided that it was time to look again at what the research says--not the latest study highlighted on the evening news, but at the Dietary Reference Intake document from the U.S. Institutes of Medicine (1). How did the scientists and physicians determine how much vitamin A was too much for adults? What I found is the basis for this Newsletter.

Vitamin A
Vitamin A is necessary for vision, a healthy immune system, and growth and development from fertilized egg through adulthood. Vitamin A is also known as retinol. Vitamin A as retinol is found in meats, especially liver, as well as an additive to milk, cereals, and other products.

What confuses some people is the relationship between beta-carotene, now called provitamin A, and vitamin A. If the body needs vitamin A, it can make it from beta-carotene as well as some of the other carotenoids; there is no toxicity associated with carotenoid precursors to vitamin A, so those can be disregarded for the purposes of this Newsletter.

The Recommended Dietary Allowance (RDA) for men is set at 900 micrograms retinol activity equivalents per day and for women 700 micrograms retinol activity equivalents per day. Many supplements report the vitamin A level in International Units (IU). To convert the retinol units to IUs, simply multiply the micrograms by 3.3. That translates to 3,000 IU for men and 2,300 IU for women. Vitamin A intake at this level should be able to sustain normal functions of the body; in other words, it should prevent night blindness and allow for a healthy immune system. But what if you exceed these levels?

Tolerable Upper Intake Level
The Tolerable Upper Intake Level (UL) is the highest amount most adults should take in a day as estimated by the Institutes of Medicine. The Institute lists an exception, and that’s for people who are participating in clinical trials to see what high amounts of vitamin A can do to the body; that should give you some insight as to how conservative the UL really is. The UL for adults is set at 3,000 micrograms/day (10,000 IU) of preformed vitamin A whether pregnant or not. The question is: how did they determine the UL?

In order to set the UL, the panel for the Institutes of Medicine had to examine previous research to see what negative effects might occur from taking too much vitamin A. Two general areas came to light: the possibility of bone loss and liver toxicity.

Bone Mineral Content: The panel reviewed three studies on bone mineral content with high levels of vitamin A intake (2-4). Two of the studies did not demonstrate any detrimental effects of vitamin A on bone mineral content (2,3).

In the third study they referenced, there was a direct relationship with vitamin A intake and fractures (4). However, the vitamin A intake was estimated from food frequency questionnaires. The use of this type of questionnaire is fraught with error: can you remember what you ate regularly over the past 10 years? I’m guessing you can’t, so the data that they used to determine the hazards to bone mineral content were weak at best. Since the Dietary Reference Intakes for vitamin A were published in 2000, other studies have demonstrated equivocal results between vitamin A intake, bone mineral content, and fractures. If there’s any risk, it may occur in the elderly.

Toxicity: Read this section very carefully because this is the part that you probably didn’t know: there are no real studies to examine exactly what the toxicity of vitamin A could be. The best data available come from case studies. These are individuals who go to their physician or emergency room with a health challenge, and the doctors determine that vitamin A is the culprit. The recommendations cite 11 case studies and one study with 41 subjects. The relationship between excessive vitamin intake and liver damage seems clear. However, it’s the rest of the story that makes it interesting.

The average vitamin A intake among the 52 case studies and study subjects was 14,800 micrograms of retinol per day--doing the math, that’s close to 50,000 IU per day. The average time for this high amount of vitamin A intake was over nine years. In a couple of cases, some people took upwards of 100,000 IU of vitamin A per day. The reasons people took these amounts varied, but the real story is that it took years of supplementing at very, very high levels before enough damage occurred that the person took action.

The panel determined that a safety factor of five should be used in the calculation for the UL because that’s the level where liver damage seemed to occur in these 52 people. That works out to 3,000 micrograms or 10,000 IU.

Pregnancy: These studies are even more rare--imagine trying to convince a pregnant woman to participate in a study that might harm her baby--but the level at which birth defects seemed begin was 4,500 micrograms (15,000 IU). A safety factor of 1.5 was used so 3,000 micrograms (10,000 IU) was set as the UL for pregnancy. Remember, this is actual vitamin A or retinol. If a supplement contains beta-carotene instead, the UL does not apply because no negative effects have been found during pregnancy.

Bottom Line
The point of this Newsletter is not to encourage you to take more vitamin A, it was to show you that the data on which some of the RDAs and ULs are based are less than clear. For the vitamin A UL, the data are limited to 52 people who clearly abused vitamin A--but we have to use that because it’s the best available data. When you must encompass close to 100% of the population, it’s better to err on the conservative side and recommend just enough rather than too much, especially with a substance such as vitamin A that can be toxic.

I also wanted illustrate that vitamin A is not as scary as some have suggested. Respect vitamin A for the benefits it can give your body in terms of vision, growth, and immune function, but remember that it can be toxic at very high intakes. Your best bet is to get it from foods, and if you don’t eat enough foods that contain vitamin A or beta-carotene, then take a good multivitamin. Just don’t be afraid of vitamin A. There’s more to scare you from what people say than from what the data actually show.

References:
  1. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Food and Nutrition Board, Institute of Medicine. Pps 82-161. National Academy Press. Washington, D.C. 2000.

  2. Freudenheim JL, et al. Relationships between usual nutrient intake and bone mineral content of women 35–65 years of age: Longitudinal and cross-sectional analysis. Am J Clin Nutr 1986;44:863–876.

  3. Houtkooper LB, et al. Nutrients, body composition and exercise are related to change in bone mineral density in premenopausal women. J Nutr 1995;125:1229–1237.

  4. Melhus H, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 1998;129:770–778.
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