A misunderstood Vitamin

Vitamin A is vital for good immune function (viruses deplete vitamin A), fertility, skin health, and healthy hormones. If you get frequent colds in the winter, have dry skin or acne, fertility problems or have night vision issues, you may want to increase vitamin A-rich foods.

When you search for sources of vitamin A, you will find many books and articles declaring carrots and kale good sources of vitamin A. However, true vitamin A is found only in animal foods such as meat, fish, milk and eggs. Natural vitamin A consists of a mixture of different alcohols, esters and aldehydes (retinol,  retinal and retinoic acid).  All of these compounds are collectively referred to as vitamin A. Vitamin A is carried in the blood by retinol-binding protein (RBP), which is synthesized in the liver₁. The storage form of vitamin A is retinol, which is stored by the stellate cells in the liver. Retinol is converted in the body to the active forms: Retinal, important for retinal function, and retinoic acid, which regulates gene expression and cell development. Synthetic vitamin A consists of retinol or retinyl palmitate, which needs to be converted to the active forms, whereas natural vitamin A provides all the different forms of Vitamin A. Interestingly, symptoms of vitamin A toxicity from synthetic vitamin A mimic those of vitamin A deficiency, possibly because an excess of the storage form interferes with the activity of the active forms.

Beta-carotene vs. Vitamin A

Plant foods contain carotenoids that can be converted to vitamin A by the liver and intestinal cells. Beta-carotene is the most common carotene and can be split into two molecules of vitamin A. Alpha and gamma-carotenes are less efficiently converted than beta-carotene. According to nih.gov, 1/2 cup of raw carrot provides ~9000 IUs of vitamin A from beta-carotenes. This assumes a 100% conversion rate of beta-carotene to vitamin A. However, actual conversion rates in humans seem to be much lower than 100%. A 2002 study found a mean conversion ratio of beta-carotene to retinol of only 3%₂ in men given a beta-carotene supplement. The authors also found a conversion ratio of 14% for raw carrots consumed with 20g of fat, and 4%-8% for cooked carrots.

Conversion Rate of Beta-carotene

Furthermore, there are genetic variations in human ability to convert beta-carotene. Some individuals show little or no increase in blood beta-carotene after an oral dose of beta-carotene (they are called non-responders) ₂. The conversion ratio in responders was found to be between 5 and 7%₂. Conversion is also gender-dependent: men show a smaller rise in plasma beta-carotene than do women after a similar oral dose₃, as well as dose-dependent: Vitamin A activity of beta-carotene was 50% with a small dose and only 3% with a large dose of beta-carotene₄. In conclusion, vitamin A activity of carotenoids is variable, surprisingly low, gender and dose-dependent, genetically variable and dependent on dietary fats₂. Therefore sufficient vitamin A can only be obtained from animal foods. The fact that vitamin A supplements, but not beta-carotene supplements, are teratogenic₁ is likely due to the low conversion rate.

Vitamin A and Protein Metabolism

Vitamin A is also important for protein metabolism. A 2010 study on weanling rats found lower weight gain, higher protein catabolism and higher nitrogen excretion with vitamin A deficiency. The authors concluded that vitamin A deficiency may induce a catabolic state associated with growth hormone resistance and decreased expression of IGF-1₅.

Hence, elderly people with sarcopenia and malabsorption may benefit from vitamin A supplementation in addition to protein or amino acids.

Does Vitamin A cause birth defects?

Since vitamin A is essential for embryogenesis, growth and epithelial differentiation₇ it as been implicated in teratogenicity. A widely publicized 1995 study found increased risk of birth defects with consumption of more than 10000 IUs of vitamin A/day from food and supplements during pregnancy₆. However, the study did not differentiate between natural and synthetic sources, and all seven babies with cranial-neural-crest defects were born to mothers with high supplemental (synthetic) retinol intake. Natural vitamin A in food is a mixture of different isomers of retinol, retinal and retinoic acid, whereas synthetic vitamin A is retinyl palmitate or retinyl acetate. Since retinoic acid is needed for cell differentiation, supplementation with high doses of retinol may cause a functional retinoic acid deficiency if conversion to retinoic acid is low (just as supplementation with alpha-tocopherol causes a functional gamma-tocopherol deficiency), leading to birth defects (my hypothesis). In any case, this study does not provide evidence that high intake of natural vitamin A from food sources alone causes birth defects.

Sources of Natural Vitamin A

True Vitamin A is only found in animal foods. This means vegan diets do not supply vitamin A. Since vitamin A is a fat-soluble vitamin stored in the liver, stores will gradually decrease over time on a vegan diet so the effects of vitamin A deficiency will not be apparent for a while. Grass-fed meat has 5 times more vitamin A than grain-fed, and wild fish has higher levels than farmed (grain-fed) fish. Good sources are grass-fed liver, meats, grass-fed raw dairy, pastured eggs, wild fish and seafood. If you are looking to supplement, look for a natural, undistilled cod liver oil.

References

1. Michael Zimmermann, Burgerstein’s Handbook of Nutrition
2. Hickenbottom et al., Variability in conversion of beta-carotene to vitamin A in men as measured by using a double-tracer study design, Am J Clin Nutr, 2002 May;75(5):900-7.
3. Sauberlich HE et al., Vitamin A metabolism and requirements in the human studied with the use of labeled retinol., Vitam Horm, 1974;32:251-75.
4. Tang et al., Vitamin A equivalence of beta-carotene in a women as determined by a stable isotope reference method. Eur JNutr 2000;39:7-11
5. Esteban-Pretel G et al., Vitamin A deficiency increases protein catabolism and induces urea cycle enzymes in rats, J Nutr 2010 Apr;140(4):792-8.
6. Rothman et al., Teratogenicity of high vitamin A intake, N Engl J Med, 1995 Nov 23;333(21):1369-73.