Part of Our Deep Dive Genetics Series
Vitamin A and its role in the body
Vitamin A is a fat-soluble vitamin that is made up of a group of retinoids which include retinol, retinal, and retinyl ester. Vitamin A acts as an antioxidant in the body but it is also necessary for numerous other biological processes including vision, cell growth, cell differentiation, immune function, reproduction, healthy skin, and proper functioning of many organs including the lungs, heart, and kidneys. Additionally, observational studies have shown that maintaining high serum levels of vitamin A and their precursors, carotenoids, helps to protect against age-related decline of muscle strength, physical and cognitive disability, and chronic morbidity (1, 2, 3).
Ideally, most healthy adults should strive to maintain circulating serum levels above 1.05 micromoles per liter of vitamin A as data shows that values below 0.70 micromoles/L indicate a vitamin A deficiency and even values between 0.70 to 1.05 micromoles/L may be suboptimal for certain populations (4). In order to maintain optimal serum levels of vitamin A the recommended daily allowance (RDA) for adult females is 700 micrograms per day, although this value increases with pregnancy or if a woman is breastfeeding, and 900 micrograms per day for males (5).
Sources of Vitamin A
Humans are able to acquire vitamin A as two basic forms in the diet, active vitamin A (preformed vitamin A) and provitamin A. The active forms of vitamin A, retinols, cannot be made by our bodies and must be obtained from foods in the diet such as eggs, liver, and dairy. Vitamin A from these sources is highly bioavailable. Likewise, provitamin A compounds, which include carotenoids and carotenes, must also come from the diet however, they must be further converted into the active form of vitamin A, retinol, for them to function properly in the body. The most prevalent and important provitamin A is beta-carotene which is found in foods such as carrots, sweet potatoes, kale, and butternut squash.
Conversion of beta-carotene to vitamin A
In most individuals, the conversion of beta-carotenes to active vitamin A is a relatively inefficient process. Moreover, the body has a reduced ability to absorb beta-carotene and other carotenoids as compared to the active forms of vitamin A (6, 7). Factors such as diet, chronic diseases, digestive problems, lipid metabolism disorders, alcohol use, certain medications, as well as genes can further impact the body’s ability to absorb and convert beta-carotene into vitamin A (8).
In order to convert beta-carotene into vitamin A retinol, the body relies on BCMO1 enzymes which are encoded by the gene BCMO1. The proteins encoded by the BCMO1 gene, called beta-carotene 15,15′-monooxygenase and beta-carotene 15,15’-dioxygenase. These enzymes act to separate beta-carotene into retinal molecules. This process is carried out primarily in the lining of the gastrointestinal tract, the intestinal mucosa (the gut barrier), as well as the liver. The retinal form of vitamin A can then be further converted into retinol which can be stored or readily transported throughout the body. Having reduced BCMO1 enzyme activity coupled with the already low rate of conversion of beta-carotene to vitamin A can severely affect the ability of some individuals, especially those who rely on plant-only diets, to maintain adequate serum levels of vitamin A.
Variations in the BCMO1 gene and Vitamin A levels
It has been estimated that up to 45% of the population has one or more variations in the BCMO1 gene that results in decreased enzyme activity (9). This decreased activity can significantly impact individuals who have variants in the BCMO1 gene such as single nucleotide polymorphisms (SNPs) rs7501331 and rs12934922. In fact, research demonstrates that individuals who have at least one risk T allele in one or both of these variants of the BCMO1 gene have a significantly reduced ability to convert beta-carotene into retinal by 32% up to 69% (10).
Although limited, further research indicates that additional variants of the BCMO1 gene, including A carriers of rs11645428 and G carriers of rs6564851, has been shown to reduce catalytic activity of the BCMO1 enzymes by up to 59%. The reduced catalytic activity can contribute to suboptimal circulating vitamin A levels which may increase risk of certain conditions including problems with vision and cardiovascular disease (11).
How to deal with poor Vitamin A conversion
For individuals who may have low vitamin A levels as a result of genetically reduced BCMO1 activity, or a “non-converters” there are several proactive measures that can be taken to support vitamin A concentrations and potentially improve health outcomes including increasing dietary intake of active vitamin A from foods such as liver, eggs, fish liver oils, seafood, or full-fat dairy. If you do choose mainly a plant-based diet or are following a dietary protocol that does not allow for animal products, you can likewise improve your absorption of beta-carotene from the foods that you do eat by being mindful of including sources of healthy fats with foods rich in beta-carotene. Even small amounts of fat can increase the absorption of beta-carotene. Indeed, research has shown that adding as little as 2.4 grams of fat to a meal was just as effective as adding 10 grams of fat when evaluating the ability of the body to enhance beta-carotene absorption (12). Another step in helping the body absorb and utilize both vitamin A from animal sources as well as pro-vitamin A from plant-based sources is by making sure that the diet also contains plenty of synergistic nutrients such as iron, which is necessary for BCMO1 to function properly (13, 14), as well as zinc, niacin, and riboflavin, which act as cofactors for the enzymes involved in vitamin A conversion (15, 16).
Final Word: Vitamin A from the diet versus supplements
Vitamin A is a fat-soluble micronutrient that is easily stored in fat tissue and when consumed in excessive amounts can lead to adverse outcomes such as skin irritation, dizziness, headaches, nausea, increased likelihood of hip fractures, and increased intracranial pressure (17). Therefore, focusing on getting vitamin A from the diet, both as preformed vitamin A and beta-carotene, versus relying on supplements, may be more beneficial and have less risk of complications (18, 19).
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