Ian Spohn, ND, is a staff naturopathic doctor for Energique who enjoys challenging the dogmas of both conventional and alternative medicine. He is a passionate supporter of the paleo diet and classical homeopathy.
With the immune system on everyone’s mind, there has recently been a proliferation of strategies and supplements recommended to help with immune support. While some sources have suggested old favorites like vitamin C, vitamin D, zinc, and elderberry, others have gone so far afield as to dare recommend oleander, a poisonous herb containing dangerous levels of cardiac glycosides that has no real basis in traditional herbalism for immune support. It’s hard to know what’s best to take, and it’s overwhelming to consider the sheer multitude of things one possibly should be taking. One nutrient that is never mentioned as often as it should be is vitamin A, which despite being largely ignored, and in some cases feared, is possibly the single most critical element in maintaining a healthy immune system.
As an essential nutrient in the absence of which the body cannot function, vitamin A (also known as retinol) is best known for its role in the eye, and indeed retinol is named for the retina, in which it is highly concentrated. But to suggest that the main role of vitamin A is to maintain healthy eyesight would be to almost criminally oversimplify its overall importance. Possibly the reason why explanations of retinol’s necessity are often relegated to the eye is because it is actually important for so many functions that it becomes difficult to precisely define what it actually does. Unlike most vitamins which act as catalysts to chemical reactions, retinol acts as a nuclear binding hormone, meaning that it enters the nuclei of cells and alters gene expression. Given the complexity of gene expression and its regulation in the body, what vitamin A actually does can only really be surmised by studying the diverse effects of its being deficient. The genes that seem to be most controlled and affected by vitamin A are those which regulate cell differentiation. It is well known that vitamin A is crucial during embryonic development, when cells are differentiating most rapidly, and vitamin A deficiency tends to affect tissues which need to constantly regenerate (and therefore differentiate) from pluripotent stem cells. The best way to think of vitamin A is as a hormone necessary to direct the growth and regeneration of tissue throughout the body, something which occurs constantly in utero, rapidly throughout childhood, and in a few select tissues persistently throughout the lifespan.
The primary effect of vitamin A deficiency in adults is keratinizing metaplasia, a term which describes specialized cells of the body’s numerous epithelial linings failing to adequately differentiate. The epithelial tissues which line the body’s surfaces, both inner and outer, constantly rub off as dead skin cells and therefore must constantly regenerate from naïve stem cells. When vitamin A is absent, the new skin cells are unable to specialize into mucus-secreting goblet cells, ciliated epithelium, etc., and instead become basic keratinized cells such as predominate on the surface of the skin. On the epidermis, this presents as the rough scaly bumps known as hyperkeratosis pilaris, which is at most a cosmetic concern. On the inner skin however, which includes the linings of the digestive tract, respiratory tract, and urinary tract, the failure of cells to differentiate properly has far more dire consequences, as these inner skin tissues need to be far more specialized to perform their vital functions.
Another tissue whose cells must constantly regenerate is the blood. Both red blood cells and white blood cells have limited lifespans and are constantly replenished from dividing stem cells in the bone marrow. It is remarkable to consider that each red and white blood cell started off as a pluripotent stem cell with the capacity to become anything, and the body somehow knows and regulates making enough of each. A complex reorganization of the genome determines whether the stem cell becomes a red or white blood cell, and if it becomes a white blood cell, which specialized type of white blood cell. It is now known that the body’s immune system is not simply made up of “white” blood cells, but rather such diverse defenders as basophils, eosinophils, neutrophils, macrophages, dendritic cells, mast cells, B cells, killer T cells, helper T cells, regulatory T cells, not to mention platelets, which all develop from the same stem cell. As is the case with regenerating epithelial cells, this process of differentiation cannot occur without adequate vitamin A.
While vitamin A’s function as a necessary coordinator of cell differentiation seems vague at first, it soon becomes easy to conceptualize why it is critical to both the innate and adaptive immune systems. Consider mucus, a protective substance which lines the epithelial surfaces of the respiratory, digestive, and genitourinary tracts. Mucus plays an important role in blocking the entry of bacteria and viruses into cells, essentially forming a moat of sticky quagmire that the microbes cannot penetrate. One of the effects of vitamin A deficiency is a reduction in mucus-secreting goblet cells throughout the epithelium[i] because the specialized goblet cells that gradually die off are replaced instead with basic keratinized epithelium. So a single vitamin deficiency would increase one’s risk of colds, the flu, pneumonia, gastroenteritis, parasite infestation, urinary tract infections, and even sexually transmitted infections, simply by stripping vulnerable cell surfaces of their protective mucus layer. This has an added consequence in the lungs, which are normally lined with highly differentiated ciliated epithelium. Vitamin A deficiency leads to a loss of highly specialized ciliated cells in the lungs as well,[ii] which normally help to sweep inhaled debris and old respiratory secretions up and out of the lungs, leaving them doubly vulnerable to infection.
And none of this even mentions white blood cells, which comprise the entirety of the adaptive immune system. When one speaks of maintaining a healthy immune system, this literally refers to replacing old, dead immune cells with fresh, newly differentiated cells. Immune cells die of old age, some in as little as two weeks, and they, of course, die much faster during an immune response, like soldiers in battle. When it comes to nutrients for immune support, most people think only of vitamin C, vitamin D, and zinc, forgetting entirely about vitamin A despite the fact that it has easily the most impressive scientific backing. Vitamin A deficiency on the population level is widely recognized to be at the root of the high burden of infectious disease throughout developing nations. While vitamin C is often thought of to help with the common cold, vitamin A has proven to be of benefit in a long list of serious diseases including measles, mumps, pneumonia, infectious diarrhea, tuberculosis, malaria, and hand, foot, and mouth disease.[iii] At some point, one reaches the inescapable generalization that vitamin A deficiency is probably the underlying cause of most infectious disease, and vitamin A supplementation is probably one’s best defense against “catching” anything.
In case you need another reason to take vitamin A seriously as an immune support nutrient, consider that vitamin D is entirely ineffectual without vitamin A. Vitamin D has been recently popularized as a crucial element in maintaining a healthy immune system, yet boosting vitamin D levels cannot be expected to have much benefit without the support of vitamin A. Both vitamins are similar in that they act as nuclear hormones and modify gene expression, leading to a diversity of complex effects. Vitamin D mediates its effects by binding to a vitamin D receptor, but this receptor still does not become activated until it forms a complex known as a heterodimer with another receptor, the retinoid X receptor, which itself must be activated by 9-cis-retinoic acid, a derivative of vitamin A.[iv] In other words, vitamin D has no effect on anything in the absence of vitamin A. The importance of supplementing these synergistic nutrients together has long been recognized. Cod liver oil is a natural source of both nutrients, and vitamin D has long been supplemented on the population level through fortified milk, which is already a good source of vitamin A. It is possible that some of the dangers of taking high doses of vitamin D involve creating a relative state of vitamin A deficiency, and vice versa. High dose vitamin D supplements can in theory deplete the body’s vitamin A levels by increasing demand for the vitamin A derivative 9-cis-retinoic acid.
Preformed vitamin A, the active form in the body, is found in only one type of food: animal fat. It is the relative lack of animal fat in the diets of impoverished nations which accounts for the global scourge of vitamin A deficiency, and even in developed nations vitamin A intake may be suboptimal due to decades of misinformation regarding the supposed dangers of animal fats and the replacement of animal fat with processed vegetable oils in most processed foods. While beta-carotene in colorful vegetables can be converted to vitamin A in the body, this conversion is inherently inefficient and subject to significant genetic variation. Vitamin A supplements should therefore be in the form of retinol or retinyl palmitate. Another excellent way to get vitamin A is to eat liver, the richest food source, or alternatively to take it as a supplement in the form of cod liver oil or freeze-dried liver capsules.
[1] McCullough FS, Northrop-Clewes CA, Thurnham DI. The effect of vitamin A on epithelial integrity. Proc Nutr Soc. 1999;58(2):289-293. doi:10.1017/s0029665199000403
[1] Biesalski HK, Stofft E, Wellner U, Niederauer U, Bässler KH. Vitamin A and ciliated cells. I. Respiratory epithelia. Z Ernahrungswiss. 1986;25(2):114-122. doi:10.1007/BF02020741
[1] Huang Z, Liu Y, Qi G, Brand D, Zheng SG. Role of Vitamin A in the Immune System. J Clin Med. 2018;7(9):258. Published 2018 Sep 6. doi:10.3390/jcm7090258
[1] Sanchez-Martinez R, Castillo AI, Steinmeyer A, Aranda A. The retinoid X receptor ligand restores defective signalling by the vitamin D receptor. EMBO Rep. 2006;7(10):1030-4. doi:10.1038/sj.embor.7400776
Any homeopathic claims are based on traditional homeopathic practice, not accepted medical evidence. Not FDA evaluated.
These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.