The A-mazing Vitamin A

In the developing world, vitamin A supplementation was one of the most successful interventions of the 1980s, helping children grow, avoid illness, and preserve and improve eyesight.^[1] However, despite this relative success, deficiency rates for many vitamins, including vitamin A, continue to climb. In 1987, the World Health Organization estimated that 39 countries struggled with vitamin A deficiency, but by 2005, that number had more than tripled to 122 countries- including developed ones!^[2] For example, according to the USDA approximately 5 out of 10 Americans are deficient in vitamin A. The sad truth is, vitamin A deficiency in the developing world is responsible for over a million instances of unnecessary death and blindness each year, and among children in developing nations is the leading preventable cause of blindness.^[3]

As researchers and authors in the area of micronutrient therapy, who are particularly interested in bone health, (remember Mira had advanced osteoporosis when she was just 30) we have noticed that all the hype about the importance of vitamin D for strong bones often overshadows the role of its partners in bone-growing-excellence,^[4] namely the fat soluble vitamins A and K2. But bone health and eyesight are not the only reasons to ensure you get enough vitamin A! Read on to learn more about this a-mazing vitamin, how you can improve your intake from food and proper supplementation, and what is not only safe, but effective.

What is Vitamin A?

Discovered in 1912, Vitamin A comes in two forms – preformed vitamin A (the active form) and provitamin A (the inactive form). Preformed vitamin A comes in three varieties: retinol, retinal, and retinoic acid (RA), which all belong to a class of coumpounds called retinoids. It is important to note that preformed vitamin A is naturally only found in foods of animal origin, and is typically in an esterified storage form called retinyl ester. This is the type you eat. This storage form is then converted in your body to the active retinol form. Because vitamin A can damage your tissues if it runs wild, your body keeps extra vitamin A stored in your liver or bound to a special protein in your bloodstream. Vitamin A levels are tightly controlled.

In 1932 a precursor (inactive form) to vitamin A, known as Beta-carotene was identified as an antioxidant found in many plant foods, where it helps the plant harvest electrons from light energy.^[5] Beta-carotene belongs to a family of compounds called carotenoids, and is called a provitamin because your body must have enough of the right enzyme to cleave it into retinal, a preformed active form of vitamin A. The problem with using beta-carotene as your primary or exclusive form of vitamin A is that it can lead to a vitamin A deficency in that research is finding that converting beta-carotene to retinal is more difficult than previously thought depending on your genetics and enzyme levels. Early estimates of 6:1 (takes 6 parts beta-carotene to make 1 part retinal) were revised to 12:1 and in a recent study conducted by Johns Hopkins Bloomberg School of Public Health and published in the Journal of Nutriton (JN) researches found that a rate of 21:1 is more likely. Regardless of your conversion abilities, beta-carotene has other important roles to play in your skin as a natural form of sunscreen and supports liver detoxifcation.

A-mazing Benefits

From your time in the womb to retirement, vitamin A is constantly on the job. You have likely heard to “eat carrots for your eyes,” but that’s not all vitamin A does for you! Vitamin A also supports:

Gene Transcription. Like vitamin D, vitamin A acts more like a bossy hormone than other vitamins you may have met. It marches right into a cell, talks to the nuclear machinery, and tells it to make important proteins. Vitamin A binds to several types of nuclear receptors- it is very dynamic!^[6],^[7]
Embryonic Development. Retinol and retinoic acid play important roles regulating cell division (making more cells) and differentiation (transforming cells into specific types). This is how the role of retinoic acid was discovered- putting pellets of it into the mesoderm of chicken embryos and noting with fascination that wherever a pellet was placed, a wing bud would develop and a new wing would form!^[8] Vitamin A is required for you to grow specialized tissues, from muscles to bones to organs.
Immunity (and Autoimmunity). A 2015 review article found that of the estimated 250 million preschool children who are deficient in vitamin A, 10% will die because they are more susceptible to infection – that’s 25,000,000 children that will die needlessly due to this single micronutrient deficiency. Even mild deficiency in children risks a higher incidence of respiratory complications, diarrhea, and a higher mortality rate from measles.^[9] In its immune-boosting glory, retinoic acid helps recruit white blood cells to your gut (and other mucus membranes) and boosts your production and specialization of micro-managing “regulatory” T cells. This T cell support improves the integrity of your mucosal barrier and your resistance to infection,^[10] especially by helping to recognize what is “self” and avoid mounting an immune response against it. Without vitamin A, a compound called TGF-B stimulates T cells to become regulatory T cells that could mount an autoimmune response- highly undesirable.^[11]
Skin Cell Growth and Differentiation. Many of us have seen or used vitamin A and D ointment, which helps skin heal and regrow after an insult- like a diaper rash or tattoo. Vitamin A is also found in many treatments for acne vulgaris, psoriasis, ichthyosis, and other skin conditions (but very high doses are no longer supported due to their controversial psychological effects).^[12]
Bone Building, Breaking, and Re-making. Sufficient vitamin A is required to build bones successfully as we grow up, but it also has a role to play in maintaining bone density as an adult! In our successful efforts to reverse Mira’s osteoporosis, we looked in depth at every micronutrient that she needed beneficial amounts of. The goal is to get the right amount of vitamin A- not too much and not too little- as a deficiency in vitamin A limits calcium absorption and both low and excessively high serum vitamin A concentrations are associated with an increased risk of hip fracture.^[13]
(Night) Vision. Note the similarity of retinal to the word retina, the membrane on the back of your eye containing the cell layers that convert the images and light entering your eye into signals your brain can process. When retinal combines with the right opsin protein to form rhodopsin, a molecule found in your retina that helps you see light, there is a red shift in vitamin A’s absorbance to the human visible range. In evolutionary history, unicellular organisms used vitamin A only to harvest light energy (instead of chlorophyll- and some archaebacteria still do today). Today, vitamin A is the most widely used light sensor throughout evolution for one and many-celled organisms.^[14] The first sign of vitamin A deficiency is usually reduced night vision, but extreme deficiency risks blindness.

Vitamin A Deficiency Increases Disease Risk

Because of the many roles it plays, vitamin A deficiency is known to be correlated with challenges from conception to old age:

Growth Challenges during Pregnancy, Infancy, and Childhood. Third-trimester mothers are particularly susceptible to vitamin A deficiency as the growing fetus takes what it needs to grow. Especially in the developing world, where deficiency is common and life-threatening infections are more likely, reduced growth and compromised immunity can be a deadly combination for a child. Moreover, because a growing infant needs vitamin A so badly, pregnant women in the third trimester in developing countries are very susceptible to night blindness.
Night Blindness and Xerophthalmia (a drying of the eye leading to blindness). This is the most well known result of vitamin A deficiency, especially in the developing world. Reduced lubrication of the cornea alongside reduced rhodopsin production is a toxic combination for vision.
Difficulty with Taste and Smell. Though we do not yet understand the mechanism, we see that vitamin A supplementation can improve the taste and smell challenges of patients with liver cirrhosis, and vitamin A deficiency in rats leads to a loss of preference for salt and aversion to bitter foods.^[15]
Thyroid dysfunction. Vitamin A deficiency can interfere with communication between the pituitary gland and thyroid, leading to a bigger thyroid gland, reduced iodine uptake, and increased levels of thyroid stimulating hormone and lower circulating concentrations of thyroid hormones. In the developing world, iodine deficiency and vitamin A deficiency together significantly increase risk of goiter beyond iodine deficiency alone.^[16]
Obesity. Obesity is associated with lower vitamin A levels because fat sequesters this vitamin. While vitamin A affects the metabolism of carbohydrate, fat, and protein in ways that we are still learning about,^[17] its role in insulin resistance is one assured way that low vitamin A status contributes to obesity.^[18] Interestingly, vitamin A has been shown to enhance thermogenic activity (relasing calores through heat) stimulate Brown Adipose Tissue (BAT), and reduce the Body Mass Index (BMI) in rats.
Type 2 Diabetes. Studies involving Type 2 diabetics and others with insulin resistance have revealed that RBP4, a retinol transporter, is often elevated. This happens at the same time as a levels of GLUT4, the insulin-sensitive glucose transporter, decrease.^[19] Vitamin A may also upregulate antioxidant activity, reducing damage from free radicals and helping to support insulin sensitivity.^[20]
Aberrant Lipid Levels. In vitamin A deficient rats, we have observed that liver glycogen and glucose made locally from acetate, lactate, and glycerol is significantly reduced, which can starve the liver of energy (alongside insulin resistance) leading to high triglycerides.^[21] Once again, over-supplementation of vitamin A is not desirable either, as it is correlated with high cholesterol, high LDL-cholesterol, and high triglycerides as well.^[22]
High Blood Pressure. As noted above, vitamin A deficiency has been shown to increase LDL-c and drive insulin resistance. High blood sugar can damage the inside of arteries, encouraging plaque buildup and inflammation that can raise blood pressure.
Cancer. Insulin resistance, which vitamin A can push back on, is a risk factor for cancer. In addition, both vitamin A deficiency and over-supplementation have been shown to be risk factors for cancer. We continue to study the role of cytosolic retinol (and retinoic acid) binding protein as it is downregulated in particularly aggressive breast, ovarian, and nose-and-throat cancers, while increasing the expression of the binding protein has been shown to reduce the lifespan of ovarian cancer cells in a laboratory setting.^[23] Because of the need to get vitamin A levels “just right,” more research is needed.

Who is likely to be vitamin A deficient?^[24]

Premature Infants
Infants and Young Children in Developing Countries
Pregnant and Lactating Women in Developing Countries
People with Cystic Fibrosis / Pancreatic Insufficiency / Low Lipase Production
Vegans, and to a lesser extent Vegetarians
Obese Individuals
Low Fat Dieters
People with Poor Gallbladder Function / Gallbladder Removal
People with Liver Disease
People with Recent Gastric Bypass Surgery

Having too much vitamin A is possible when supplementing because it is stored in your liver; the only known cases of getting too much vitamin A from food involve those eating liver as a primary food source, including arctic explorers and people who practice cannibalism. Let’s break down how to optimize your vitamin A status from food, lifestyle, and supplements so you get all the benefits from adequacy and none of the drawbacks from overdoing it!

Vitamin A – The Right Way

STEP ONE – FOOD: Some foods can actually reduce your vitamin A absorption while others can promote it.
- Allow some animal protein as part of your diet. Liver, meats, chicken, and eggs are some of the best sources of preformed vitamin A because you do not easily convert beta-carotene to vitamin A. For most, eating some animal foods will ensure that you have your bases covered regardless of your ability to convert beta-carotene- and for those on a primarily plant-based diet, we recommend supplementing with a safe daily dose of preformed vitamin A in the form of retinyl.
- Go Organic. Organic foods are not permitted to be irradiated. Irradiation destroys vitamins, nutrients, and essential fatty acids- including up to 95 percent of the vitamin A in chicken. Organically grown fruits and vegetables may boast better beta-carotene levels as well, such as a team of Spanish scientists reported in their 2008 study published in the Journal of the Science of Food and Agriculture. They found that organically grown mandarin oranges have 40 percent more vitamin A than their conventionally-grown counterparts.^[25]
- Choose high quality proteins that deliver high quality fats. According to the USDA National Nutrient Database, pasture-raised eggs contain two-thirds more vitamin A than their conventionally-raised counterparts. A joint research study by the USDA and Clemson University found that grass-fed beef has over 400 percent more vitamin A than grain-fed beef.^[26] We could go on, but you’d be here all day. Build your high-quality body from other high-quality bodies.
- Avoid Antinutrients. Foods containing trypsin inhibitors, a plant’s natural insect repellent, can wreak havoc on your digestion because trypsin is an important digestive enzyme. Trypsin inhibitors can prevent you from absorbing not only fat soluble vitamins (A, D, E, and K), but also vitamin B12 and amino acids. Excessive trypsin inhibitors can even damage your gut lining and pancreas. Be wary of consuming excessive quantities in beans, grains, nuts, seeds, and nightshade vegetables (such as potatoes, peppers, tomatoes, goji berries, and eggplant). Sprouting and soaking your grains, nuts, and seeds can reduce this effect.^[27]
STEP TWO – LIFESTYLE: Consider your digestive health, medications, and overall health to support your vitamin A status.
- Living a vegan or vegetarian lifestyle can easily increase your risk of deficiency. Even if you consume a lot of beta-carotene, the average conversion rate of 21:1 leaves much to be desired. This is why we recommend that vegans and most vegetarians supplement vitamin A in a safe way (see below).
- Mind your Medications. Avoid supplementing vitamin A if you are taking a retinoid medication, such as isotretinoin (Accutane) or acitretin (Soriatane). If you do take these medications, be aware of the symptoms of vitamin A toxicity: nausea, vomiting, dizziness, blurred vision, and poor muscle coordination. The upper limit of vitamin A for adults is 10,000 IU.
- Munch Mindfully. Giving your body time to eat makes a huge difference in the production of digestive juices (acid, enzymes, and bile) that can do the hard work of digesting food and helping you to absorb this fat-soluble vitamin. Take your time, appreciate that an organism died so that you may live, and savor.
STEP THREE – SUPPLEMENTATION: Goldilocks (“just right”) is the key with all fat-soluble vitamins – including vitamin A.
- Recent research found that excessive supplementation of vitamin A can reduce absorption of and negate the beneficial effects of vitamin D. It is important to get adequate vitamin D as well as vitamin A so they can both do their best work. An optimal multivitamin, for instance, will not contain both vitamins A and D in the same dose- that’s why we separate them into AM and a PM doses in our multivitamin – nutreince. A lesser vitamin may increase the amounts of both to reduce counter-absorption, but this only makes the competition worse, and is an unwise strategy for taking a vitamin you do not want in excess.^[28]
- Roll with the RDA for Vitamin A. Our nutreince multivitamin contains the goldilocks amount of vitamin A, which (for this nutrient) is the RDA (3000 IU). We recommend taking 2500 IU of preformed vitamin A per day to hit the sweet spot. Nutrience provides 3000 IU per day of mixed vitamin A from retinyl palmitate or acetate (2500 IU) as well as beta-carotene (500 IU) (which, even if unconverted, has antioxidant benefits you won’t want to miss out on!)^[29]
- Be Wary of Cod Liver Oil. While this not-so-delicious-substance that haunts our elders’ dreams is a great source of preformed vitamin A and D, don’t forget these fat soluble vitamins are natural competitors! Instead, try a triple threat shake (or cheesecake- yum!), a combination of our multivitamin nutreince, our amino acid packed protein powder POWER and our SKINNYFat fat-burning MCT oil with just enough long chain fats to promote bile flow. Bile will help you optimally absorb your fat-soluble vitamins, including vitamin A!

Vitamin A is both a huge player in our evolutionary history and our present growth, reproduction, and maintenance. Find that “just right” spot in your diet and/or supplementation to ensure you are getting the goldilocks amount of vitamin A. Your bones- and the rest of your body- will thank you!

^[1] https://www.ncbi.nlm.nih.gov/pubmed/25808452

^[2] https://caltonnutritionstore.com/collections/books/products/calton-nutrition-books?variant=26672936393

^[3] https://www.ncbi.nlm.nih.gov/pubmed/23053551

^[4] https://www.bones.nih.gov/health-info/bone/bone-health/nutrition/vitamin-and-bone-health

^[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1693050/

^[6] https://www.ncbi.nlm.nih.gov/pubmed/23440512

^[7] https://www.ncbi.nlm.nih.gov/pubmed/26459513

^[8] https://www.ncbi.nlm.nih.gov/pubmed/1683800

^[9] https://www.ncbi.nlm.nih.gov/pubmed/11781377

^[10] https://www.ncbi.nlm.nih.gov/pubmed/25808452

^[11] http://science.sciencemag.org/content/317/5835/256

^[12] https://www.ncbi.nlm.nih.gov/pubmed/22361284