Vitamin A

Vitamin A is actually a group of compounds that include retinol and beta-carotene among others. The science behind it dates back to 1816 when scientists noticed nutrition deprived dogs developed corneal ulcers. It was later found to be a fat soluble vitamin (as opposed to water-soluble) meaning it is stored in the fat (along with vitamins D, E, and K).

Vitamin A is indeed important in maintaining good vision. It is also important for cell growth and differentiation, skin health, and the immune system. For women the recommended daily allowance (RDA) is 700 mcg and 900 for men. The widely considered upper safe limit is considered to be 3000 mcg.

Animal sources of vitamin A include cheddar cheese, eggs, butter, and liver. Plant source include carrots, broccoli, kale and spinach. Dandelion greens have a particularly high amount of vitamin A and are used in natural medicine.

Worldwide Vitamin A deficiency is a huge problem. Approximately one-third of children are estimated to be vitamin A deficient. Nearly a half a million children a year go blind each year due to vitamin A deficiency. It often presents first with night blindness. Also early on a condition called xerophthalmia occurs where the eye is unable to produce tears. This leads to eye dryness, then plaques and eventually ulcerations. Other symptoms include increased infections due to an impaired immune system and poor forming of tooth enamel.

Vitamin A overdose is a significant risk as it is fat soluble, which means the body stores it in fat cells so excess amounts cannot be cleared easily. Excess vitamin A in pregnant women has been shown to cause birth defects in their offspring (however vitamin A deficiency also causes issues for the fetus as well). Toxic levels can cause nausea, vomiting, hair loss, weakness, and headaches and can lead to osteoporosis. Liver damage has also been seen at high doses. However, it is interesting to note that these toxicities and teratogenicity (damage to unborn fetuses) are only seen with preformed vitamin A (retinoid) as found in animal sources of Vitamin A such as in liver or supplements with retinol or retinoic acid. It is not seen with carotenoid forms (such as beta-carotene) which are found in plant sources such as carrots and are molecules that have to be converted into vitamin A by the body. Carotenoids are water-soluble and not stored by the body hence they are rarely if ever toxic. Beta-carotene is the most common carotenoid in supplements but there are many more (approximately 500 known so far) but only about 10% of those are made into vitamin A. Therefore if one is going to supplement vitamin A levels they should avoid retinol or retinoid acid and instead try to get a supplement with a mixture of carotenoids.

Vitamin A research is severely limited due to its overblown risks for toxicity. Most people I know during medical school were told of a group of arctic explorers that died due to Vitamin A toxicity from eating polar bear livers. Of course liver is the richest possible source of vitamin A in the diet. It is also all in the preformed retinoid form which is the most toxic. I personally have never, not once, seen a case of vitamin A toxicity. And that is in spite of the fact that I live within a short drive of Herbalife headquarters and in southern California where people take supplements galore.

Vitamin A is most commonly used to treat Acne most commonly in the form of isotretinoin (Accutane). It is effective but does come with significant side effects and very high risk for birth defects if a woman becomes pregnant on it. Therefore women have to pledge to use contraception while using it.

Vitamin A is also used rarely for cancer in the retinoid form which is the active metabolite of vitamin A. Mostly it is used in rare pediatric tumors such as acute promyelocytic leukemia and neuroblastoma. The role of Vitamin A and cancer is still being evaluated as described in this study. Vitamin A may also play a role in cancer prevention.

Research has also shown that Vitamin A can dramatically decrease the complications and death rate from measles. It has also been shown since the 1990s that vitamin A helps to decrease morbidity and mortality from HIV, however this has not been adequately looked at and few if any doctors given Vitamin A to their HIV patients despite these results.

Vitamin A is still plagued with incomplete research due to a variety of reasons. Lack of profit of course is one, but also Vitamin A’s multiple forms and knowing which one to use for trials is not clear. Also complicating the matter is its risk for toxicity and teratogenicity. However, the risk is quite low for toxicity if given in reasonable doses and I feel naturopathic doctors could give us a lot of guidance as to what forms to use for supplementation as they have been using them for centuries.

There are many possible exciting avenues for research for vitamin A. The pharmaceutical industry is already trying to form more patentable versions for cancer treatment. It would be interesting to see if traditional vitamin A supplements (particularly mixed carotinoids) would help with cancer treatment.

However, I feel given the dramatic results from HIV and measles research that has already been done, the most promising avenues of research would be those for viral illnesses. Hepatitis C and HIV are two of the most devastating and costly viral illnesses we struggle with. Hepatitis C has a very high treatment failure rate and it would be fascinating to see if treatment with Vitamin A supplements in addition to normal treatment for Hepatitis C increased the treatment success rate. It would also be great to see if Vitamin A supplements decrease viral load levels in HIV patients on medication. Preliminary research already points to the fact that it likely does.

One main issue with the studies done so far is that they are often done with the active forms (retinoids) which carry the high risk for toxicity. It is possible carotenoids may not have the same effects as the body may regulate the conversion by the body to levels not high enough to see the effects achieved with direct supplementation with active retinol vitamin A. However, studies would be much easier, safer, and more generalizable to medical practice if carotenoids were used. Many studies have been done with beta-carotene but this is likely flawed. This is only one of over 50 carotenoids the body makes into Vitamin A and when you eat Vitamin A naturally you get many of these all at once. They do not come in isolation. Studies are showing that likely this mixture of carotenoids is what leads to the beneficial effects of Vitamin A, so supplementing one carotenoid in isolation may have little or no effect or may even been detrimental. If one is to supplement vitamin A the best way of course is with Vitamin A rich foods such as carrots or spinach. But for studies to allow for a placebo they would have to be given as pills to allow for a placebo. So mixed carotenoids would be best to allow for a good chance of beneficial effect while avoiding the toxicity seen with retinol or retinoic acid.

It is time we stop fearing this Vitamin and start using it to our advantage. It could end up being one of our most powerful weapons against viruses and maybe even cancer.

References

Vitamin A in cancer study – http://www.ncbi.nlm.nih.gov/pubmed/21073338

Vitamin A and breast cancer – http://www.ncbi.nlm.nih.gov/pubmed/12452454

Vitamin A and cancer prevention – http://www.ncbi.nlm.nih.gov/pubmed/15134535

Vitamin A and measles – http://www.ncbi.nlm.nih.gov/pubmed/12521271

Vitamin A and multivitamin in HIV – http://www.ncbi.nlm.nih.gov/pubmed/17368322

Beta Carotene and HIV – http://www.ncbi.nlm.nih.gov/pubmed/8450402

Vitamin A and Hepatitis C – http://www.ncbi.nlm.nih.gov/pubmed/23213086

Vitamin D and Hepatitis C

Hepatitis virions, of an unknown strain of the organism (Photo credit: Microbe World)

You will see a recurring theme of using vitamin D more. I will write why it is logical vitamin D would be so such a useful and yet frequently deficient vitamin in another post.

But yet another use that does not get the attention it should is Vitamin D in Hepatitis C infection. Hepatitis C is a virus that can cause a chronic infection the person is unable to clear. This can lead to cirrhosis and liver cancer. There are treatments but they have very serious side effects, make the patient feel horrible, and have a fairly high failure rate. However, vitamin D might be able to change that.

A 2011 study in Hepatology showed that Vitamin D caused liver cancer cells to produce interferon (a chemical produced by the body that stimulates the immune system). It just so happens that interferon is one of the main drugs we use to treat Hepatitis C. In 2011  a study by Bitetto et al. showed that severe deficiency in vitamin D led to only 10% of patients responding to interferon therapy and being effectively treated for their hepatitis C. In only mildly deficient patients this rate improved to 30% and improved further to 50% in those with normal Vitamin D levels. A 2012 article in Hepatology actually directly showed that Hepatitic C levels decreased in a dose dependent fashion when exposed to Vitamin D. However it is interesting that a recent article in the Annals of Hepatology specifically looking at Spanish patients found no change in Hepatitis C viral levels in the blood after vitamin D supplementation. Some other studies have shown no difference in response to treatment in baseline low vs normal vitamin D level patients.

The preponderance of the evidence points towards a benefit but there is some that shows no benefit. Given that we have a plausible explanation as to why vitamin D would help suppress Hepatitis C and given the increasing evidence that it works I see no reason why a large randomized trial has not yet been done. Most studies so far have been small. There is really no excuse for this as Hepatitis C is a VERY common disease and a large study could be put together quickly.

Some evidence is showing the same possible benefit from Vitamin B12 as well. These are harmless substances that could potentially change people’s lives and save the healthcare system immense amounts of money if it makes treatment successful and prevents cirrhosis or liver cancer. We need to move forward with this soon.