As a hormone precursor, many articles have been written about vitamin D, espousing its benefits in fighting infections and bringing down the odds of getting multiple sclerosis, diabetes, heart disease, cancer (colon, breast, skin and prostate), osteoporosis, dental caries, lupus and rheumatoid arthritis.
But this isn’t another vitamin D article. It’s about an often ignored, but extremely important fat soluble co-factor that’s constantly talking to vitamin D. The co-factor is vitamin A.
The BIG deal about Vitamin A
First discovered between 1913 and 1915 by US scientists Elmer Verner McCollum and Marguerite Davis, vitamin A is nearly 100 years old.1 So, it would be easy to become blasé about it; after all it’s so old, it sounds quite boring. For this reason, we often forget that vitamin A and D are co-factors in bone and immune system health.2,3 When referring to vitamin A, we generally talk about the three forms we find in the body; retinol, the storage form; retinal crucial for vision; and retinoic acid. Retinoic acid functions like a hormone and binds to two receptors (RAR and RXR), impacting over 500 genes.4
Vitamin A’s genius lies in the sophisticated role it plays in the digestive system and the control of immune tolerance across the entire gut lining. Immune tolerance is vital to our health. An intolerant system will eventually lead to chronic diseases. It’s this tolerance that allows us to eat a wide variety of food without reacting badly or developing allergies.
The gut is where our health begins and is home to billions of micro-organisms important in maintaining wellness. Vitamin A is key in ensuring the gut is making the correct decisions, and when there’s a deficiency, the immune system swings towards increased inflammation and the risk of developing autoimmune disease increases. Conversely, when vitamin A stores are sufficient, gut tolerance is maintained and inappropriate inflammation will be quenched.6
Over the last few decades, our diets have changed dramatically and many people no longer consume as much vitamin A-rich food as they did in the past. What we’ve lost in fresh, farm-grown produce and pasturised dairy and meat, we’ve replaced with fortified food. Those who can’t tolerate fortified milk, wheat and cereal, and don’t eat organ meats, or are poor converters of carotene, a deficiency in vitamin A can occur.7
Added to this, latest findings suggest that supplementing with carotenoids, which can be converted to vitamin A, isn’t as efficient as once believed. Recent research shows that as many as 50% of women studied were unable to efficiently convert carotenoids into vitamin A and thus may be deficient in retinoic acid.8 There’s also concern that high doses of carotenoids can lead to an increase in breakdown products called carotenoic acids, which can form toxins. This may partly explain why some studies have shown increased levels of lung cancer in smokers taking high levels of beta-carotene. This doesn’t in any way mean that carotenoids are bad or dangerous. Carotenoids have many health benefits other than their ability to convert to vitamin A, so the concern is only when used in high doses.
Vitamin A and D are ancient bed mates whose relationship has been honed by evolution over time, with their receptors being found in every cell in the body.9 They share a common receptor in the nucleus of the cell known as retinoid X receptor (RXR). RXR regulates blood lipid balance and talks to very important steroid receptors – such as thyroid, glucocorticoid, estrogen, progesterone and testosterone. Vitamin A binds to its own retinoic acid receptor (RAR), while vitamin D binds to its vitamin D receptor (VDR), and then together, they bind to RXR.10
Given the symbiotic relationship above, it makes sense that we would need adequate levels of both vitamins available for the RXR receptor to work effectively. A good example of an imbalance between the two is the high rate of osteoporosis found in northern Europe, where sunlight (vitamin D) is limited and vitamin A intake is high (through oily fish).11 Other research also supports the belief that a balance is key, with adequate amounts of each required for healthy bones.12 The immune system also requires both nutrients to work optimally, with vitamin D dampening autoimmune responses and decreasing pro-inflammatory immune reactions, while vitamin A increases regulatory T-cells that help dampen hypersensitivity reactions.13,14 Once again, this illustrates the need to take both nutrients correctly.
It’s clear that vitamin A and D form part of an ancient RXR complex that requires each to be balanced to achieve optimal health. In fact, the latest research indicates that all the lipid-based vitamins may be intricately linked through shared receptors.15 This means vitamins A, D, K and E enhance each other as a group to profoundly influence our genes. So, make sure you have an adequate intake of each nutrient to ensure you get the full health benefits.
1 Ross, C. Vitamin A and Retinoids. Japanese Society for Retinoids Research. 21 Nov 2008
2 Maruotti N, Cantatore FP. Vitamin D and the immune system. J Rheumatol. Mar 2010;37(3):491-5
3 Dong P, Tao Y, et al. Expression of retinoic acid receptors in intestinal mucosa and the effect of vitamin A on mucosal immunity. Nutrition. 19 Nov 2009
4 Acin-Perez R, Hoyos B, et al. Control of oxidative phosphorylation by vitamin A illuminates a fundamental role in mitochondrial energy homoeostasis. FASEB J. Feb 2010;24 (2):627-36
5 Iwata M, Hirakiyama A, et al. Retinoic Acid Imprints Gut-Homing Specificity on T Cells. Immunity. Oct 2004;21(4):527-38
6 Nolting J, Daniel C, et al. Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines. J Exp Med. 28 Sep 2009;206(10):2131-9
7 Leung WC, Hessel S, et al. Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15’-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB J. Apr 2009;23(4):1041-53
8 See reference 6
9 Racz A, Barsony J. Hormone-dependent translocation of vitamin D receptors is linked to transactivation. The Journal of Biological Chemistry. 2 Jul 1999;274(27):19352-60
10 See reference 4
11 Rosengren BE, Ahlborg HG, et al. Bone mineral density and incidence of hip fracture in Swedish urban and rural women 1987-2002. Acta Orthop. Aug 2010;81(4):453-9
12 See reference 11
13 Kriegel MA, Manson JE, Costenbader KH. Does Vitamin D Affect Risk of Developing Autoimmune Disease? A Systematic Review. Semin Arthritis Rheum. 1 Nov 2010
14 Zhou X, Kong N, et al. Cutting edge: all-trans retinoic acid sustains the stability and function of natural regulatory T cells in an inflammatory milieu. J Immunol. 1 Sep 2010;185(5):2675-9
15 Chawla A, Repa JJ, et al. Nuclear receptors and lipid physiology: opening the X-files. Science. 30 Nov 2001;294