Vitamin A Is Not Only Related to the Eye, But Immunity and Organ Toxicity As Well

Shin

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Immunology meets vitamin A

“Among the micronutrients, vitamin A plays a central role in normal immune function,” writes Richard D. Semba, M.D., M.A., M.P.H. from Johns Hopkins University in chapter 12 of “Military Strategies for Sustainment of Nutrition and Immune Function in the Field.” Semba further quoted Scrimshaw et al. (1968) that “no nutritional deficiency is more consistently synergistic with the infectious disease than that of vitamin A.’’ Vitamin A deficiency is conventionally linked to night-blindness or problems with eye health. But an underappreciated role of vitamin A lies in the immune system.

First demonstrated in 1928 by Green and Mellandy that rats on a vitamin A-deficient diet were more susceptible to microbial infections. Analysis of their dead bodies revealed the presence of pathogenic bacteria — streptococci, staphylococci, and bacilli — in many of the deteriorated organs and tissues. This did not happen to any of the mice on a vitamin-A-rich diet. “Vitamin A as an Anti-Infective Agent” was the title of their paper.

There are two forms of vitamin A. Preformed vitamin A includes retinol, retinal, and retinoic acid that is stored in the liver and sourced from animal products such as eggs, liver, and dairy. Whereas provitamin A is called catenoids that are stored in the adipose tissues. Carotenoids are derived from plant sources like spinach, squash, and carrots.

Vitamin A performs a panoply of duties such as vision, cellular differentiation, growth, maintenance of skin and mucous membranes, and the maturation and deployment of immune cells. Remarkably, vitamin A can mount both arms — innate and adaptive — of the immune system, which is usually difficult with vaccines. Scientists, therefore, quickly started investigating vitamin A, in the hope that it could revolutionize how we fight microbial infections.

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Vitamin A deficiency

A 3-year longitudinal study found that low baseline levels of vitamin A (both retinol and carotenoids) in the blood were associated with a 10-fold greater risk of tuberculosis among household contacts of tuberculosis patients. This means that people near tuberculosis patients are 10 times more likely to contract tuberculosis themselves if they lack adequate vitamin A. This relationship is also dose-dependent — the lower the vitamin A levels, the greater the risk. Even in the broader context, tuberculosis patients often have lower plasma levels of vitamin A than the healthy population.

Most of the studies on the immunological roles of vitamin A involve children as their developing immune system makes them particularly vulnerable to the consequences of vitamin A deficiency. Children with this deficiency became highly susceptible to acute infections of the respiratory and intestinal tracts. In rural areas, 16% of deaths in children from microbial infections can be attributed to a mild vitamin A deficiency. Autopsies of vitamin A-deficient children's bodies discovered that their immune organs — thymus, spleen, and lymph nodes — shrink. Their immune system was crippled.

The World Health Organization (WHO), therefore, underscored the importance of vitamin A supplementation in infants and children for a healthy developmental trajectory. Routine vitamin A administration in low- and middle-income countries, therefore, became standard practice in many countries. It has helped them fight pneumonia, diarrhea, measles, and hand-foot-and-mouth disease, according to meta-analytic data. Randomized control trials also supported the therapeutic effects of vitamin A on malaria in children, and persistent cough and chronic diarrhea in HIV-infected children.

As a result of vitamin A supplementation, approximately 1.25 million lives have been saved since 1998. However, WHO reports that vitamin A deficiency still affects approximately 19 million pregnant women and 190 million children worldwide, mainly in Africa and South-East Asia and nearly non-existent in the US.

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Vitamin A surplus

Large amounts of carotenoids do not cause any complications, except transforming the skin color into yellow-orange. But it is the opposite for excessive preformed vitamin A that is fat-soluble, thus, being able to accumulate in the body. While vitamin A deficiency is rare in the US, its surplus and toxicity are relatively common with over 60,000 cases every year. The majority, if not all, of such cases, is due to supplements or therapeutic retinoids, and not from real foods.

The Eskimos and arctic travelers know that consuming the liver of polar bears is poisonous that can cause drowsiness, sluggishness, irritability, uncontrollable sleepiness, severe headache, vomiting, and sometimes the “skin peeled from head to foot.” These symptoms of hypervitaminosis A can also manifest over a long period, as a result of the gradual accumulation of preformed vitamin A (>10,000 IUs/day) to unhealthy levels. Such toxicity destroys many organs like the liver, bone, heart, and central nervous system. Unborn babies can also be affected by hypervitaminosis A of the pregnant mother, causing congenital disorders such as Down syndrome, cystic fibrosis, and cerebral palsy.

“A vitamin is a substance that makes you ill if you don’t eat it,” says Albert Szent-Gyorgyi, Nobel Prize in Physiology or Medicine, in 1937.

But Hippocrates Asclepiades, father of medicine (c. 460-c. 370 BC) says “everything in excess is opposed to nature.”

This article was originally published in Microbial Instincts.

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