Dr. Brett Wisniewski
It is a beautiful day in the world of Natural Medicine because we are finally seeing mass acceptance from the general public, mostly under the guise of Functional Medicine. Unfortunately, with this “new-found” medicine, everyone is in a mad dash to stake their fame with the next fad diet or rare botanical combination. It seems like popularity and book sales take precedence over solid research and effective medicine. We are at a crossroads in medicine – if the focus does not shift back to providing science-driven, quality care, I’m afraid we will lose our credibility.
I’m over it.
You’re over it.
We’ve begun to lose sight of what Natural Medicine is all about: simple, effective and inexpensive solutions for acute and chronic conditions. It’s an important alternative in this polluted world where Western Medicine continues its affair with politics and the pharmaceutical industry.
Stick to the Basics
Vitamins A, D, C and E have always provided a solid base when it comes to nearly any patient and any condition. It couldn’t get much easier, but it’s also not novel or sexy, which is why it’s often forgotten or ignored. Thankfully, we have seen a resurgence in information surrounding vitamins C and D. But what about the others?
Today, we concentrate on Vitamin A. Information about vitamin A has been around since the early 1800s. Around 1940, vitamin A slowly became a household name within the scientific community. Vitamin A exists in nature as a provitamin called a “carotenoid” and is found in fruits and vegetables. Provitamins do not function in the body until they are converted into active forms. Hundreds of carotenoids are synthesized by plants, but only about 10% of them are capable of being converted into active forms that the human body can use. This is an important point because the large portion of the population who cannot convert carotenoids into active vitamin A, are deficient without supplementation. Preformed vitamin A (usable by the body without conversion) can be found in foods from animal sources. Organ meats will have the highest levels of preformed vitamin A but are rarely consumed in the standard American diet.
Active forms circulate our blood stream as:
- Retinol
- Retinal
- Retinoic acid
Clinically, vitamin A has been misunderstood for decades and dosing has even instilled fear in clinicians. Much of this fear is due to the misunderstanding of the forms of vitamin A that exist, as well as its “fat-soluble” label. Fat-soluble simply means that these compounds dissolve in fats or oils. They are said to accumulate in the body’s fatty tissues, which could potentially create a toxic state with ensuing symptoms. Other fat-soluble vitamins include vitamins K, E and CoQ10 – all said to pose similar risks if accumulated at high levels.
The Bad
Vitamin A is a morphogen-stimulating factor and toxicity can lead to some severe symptoms such as hemorrhaging and birth defects like teratogenicity. Ironically, teratogenicity can also occur in a vitamin A deficient mother.
Note: Topical vitamin A, although it can affect the skin, does not appear to have the same teratogenic risk as the internal form. It is important to note that many of the studies on this topic have been performed with the pharmaceutical vitamin A analogue, trans retinoic acid and isotretinion. Most full synthetic forms of vitamins have a higher potential for toxicity due to their altered interaction with host’s receptors. They will also be broken down into different metabolites that could be harmful. Our best example of this is the administration of natural estrogen and synthetic estrogen. Full synthetic estrogens hold a much higher risk of negative consequences compared to their semi-synthetic and natural counterparts.
Reading through the literature, it quickly becomes apparent that this vitamin has had difficulties finding its place. Numerous accounts of patients suffering from consequences of vitamin A toxicity commonly have comorbid conditions such as general liver dysfunction, similar to viral or alcohol induced hepatitis. Diabetes may cause a condition known as non-alcoholic fatty liver disease, which can make someone more vulnerable to vitamin A toxicity.
Keep in mind, that a deficiency in vitamin A can be just as detrimental to the body as a toxic accumulation of it. In some cases, it can even lead to death, especially in pediatrics. About 700,000 pediatric deaths, world-wide, are attributed to vitamin A deficiency. It may also lead to, or contribute to, infertility, acne, psoriasis and night blindness.
The Good
I like to describe vitamin A as “simply complex.” It is inexpensive, readily available and wildly effective for many conditions. However, the far-reaching biochemical effects of vitamin A are a bit more complicated. Many of the world’s “outbreaks” can be lessened by proper dosing of vitamin A. The World Health Organization (WHO) recognizes vitamin A deficiency as a risk factor for some viruses such as measles.
A small study published in The New England Journal of Medicine, introduced 400,000IU of vitamin A (retinyl palmitate) to 96 pediatrics with an active measles infection (average age of 10 months). These children were compared to a control group who received a placebo. They concluded: “The children who received vitamin A had markedly diminished mortality and morbidity, with no clinically apparent adverse effects.”
(https://www.nejm.org/doi/full/10.1056/NEJM199007193230304)
Proper vitamin A levels are critical in the functioning of several body systems and organs. It is necessary for epithelial integrity (barrier system) in multiple regions of the body, especially in the lungs. This is one of the reasons why we see a strong benefit using vitamin A for respiratory infections and why we have seen good outcomes with its use in treating SARS-CoV-2. Another organ system that can benefit from proper barrier function is the GI tract. Vitamin A helps maintain healthy antibody level in the lower GI tract, as well as appropriate mucous production.
Vitamin A also aids in proper vision. A deficiency in vitamin A is the leading cause of night blindness.
It is a function-limiting nutrient in white blood cells and is imperative for proper immune maturation and responsiveness. Vitamin A also affects the way various proteins are regulated, which may be why high dose vitamin A has shown promise in some cancer research. This same mechanism is responsible for body-wide hormonal regulation.
High Dose Vitamin A
High dose vitamin A can, in fact, have undesired health consequences. So, first we must define ‘high dose’. The RDA’s current recommendations are about 2,000 IU or 700-900mcg for adults. Most clinicians consider high dose vitamin A therapy to be greater than 100,000IU (30,000 mcg) per day, for weeks at a time, without breaks. It is important to note that the forms of vitamin A preferred for this therapy are those that are emulsified or micellized preform vitamin A, retinyl palmitate or vitamin A palmitate. The Merck Manual indicates that greater than 100,000 IU/day (30,000 mcg) for MONTHS may cause toxicity in adults.
You can monitor vitamin A levels in the serum as retinol (sometimes just labeled Vitamin A, Serum); yet acute ingestion is almost certainly going to temporarily increase blood retinol levels. Acute toxicity may be hard to distinguish from acute exposure, thus paying close attention to the patient’s symptoms is important. In addition, serum retinol levels do not always coincide with the liver’s levels (retinyl ester) and the impact on the liver may need to be determined by more traditional liver blood markers such as ALT, GGT and triglycerides. End organ damage is customarily from high dose therapy for years at a time.
Vitamin A Burst therapy – this should never be performed without your doctor’s supervision
The goal of vitamin A therapy is to increase levels of vitamin A rapidly, without causing negative symptoms. To do this, we formulate an amount appropriate for the patient and their condition. Normally, this amount ranges from 100,000-500,000IU (30,000 – 150,000 mcg) per day. This amount is then scheduled in a cycle-on, cycle-off format. Here is an example:
300,000IU/day for 3 days followed by one day off. This is considered 1 cycle. The patient will run through a number of cycles and then the vitamin A will be reduced down to a lower dose that requires less monitoring and is less likely to cause concerns with long-term use.
10,000-15,000 IU/day appears to be well-tolerated in most cases as a maintenance dose. Note that the patient’s dietary and overall status is important to determine an appropriate long-term dose.
The most common initial symptoms of acute vitamin A toxicity will be that of the skin – erythema, dryness. Another symptom that is reported is a headache that is out of the ordinary and is often described as a headache behind the eyes. Chronic toxicity can cause more severe side-effects, such as: vomiting, osteoporosis, central nervous system complaints and liver disease. Keep in mind that chronically ill patients, especially those that are suffering from sustained viral load, will almost always be deficient in vitamin A.
At this time, our research on vitamin A therapy is continuing but certainly incomplete. However, the unanimous fear among clinicians when vitamin A is mentioned, needs to be addressed. I feel we now have enough anecdotal evidence to reopen the text books and re-evaluate our recommendations. Most of the reported issues with vitamin A toxicity stem from the form of vitamin A, coupled with either improper dosing and/or a comorbid condition. Vitamin A is involved in many processes and especially the immune system. With today’s concerns that surround novel pathogens, we need to see wider therapeutic acceptance of vitamin A as a safe, inexpensive and effective treatment.
Resources
Barclay, A. J. G., A. Foster, and A. Sommer. 1987. Vitamin A supplements and mortality related to measles: a randomised clinical trial. Br. Med. J. 294:294–296.
Olson JM, Shah NA. Vitamin A Toxicity. [Updated 2019 Oct 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532916/
Degos, L., Wang, Z. All trans retinoic acid in acute promyelocytic leukemia. Oncogene 20, 7140–7145 (2001) doi:10.1038/sj.onc.1204763
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Georg Lietz et al. wo common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15%u2019-monoxygenase alter beta-carotene metabolism in female volunteers. The FASEB Journal, DOI: 10.1096/fj.08-121962
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Pozniakov SP. Mekhanizmy deĭstviia vitamina A na differentsirovku i funktsii kletok [Mechanism of action of vitamin A on cell differentiation and function]. Ontogenez. 1986;17(6):578‐586.