Category: Vitamin A
Written By: Maria Vardapetyan, Eric Baghdasaryan, Osheen Abnous
Vitamins are chemicals that facilitate many processes in the human body such as blood clot formation, good vision, fight infections etc. There are two classes of vitamins. Water soluble vitamins and fat soluble vitamins. Water soluble vitamins dissolve in water. This makes it possible for them to be absorbed through all mucous membranes. Fat soluble vitamins on the other hand do not dissolve or pass through mucous membranes. Fat-soluble vitamins are absorbed in the intestine along with fats in the diet. These vitamins have the ability to be stored in the fat tissues of the human body. Water-soluble vitamins are not stored in the body and have to be taken in daily with the food and dietary supplements. Solubility of a vitamin is not a function of its physical state. There are fat soluble vitamins that have a liquid form and almost all of the water soluble vitamins come in form of pills or powders.
In this article, we are going to focus on fat soluble vitamins. They are all complex molecules made of carbon, hydrogen, and oxygen in different arrangements (see figures 1, 2, 3 and 4). These fat soluble vitamins are vitamin A, D, E and K.
Vitamin A has a major role in vision, immune function, cell growth, and maintenance of organs such as heart, kidneys, lungs, etc. It plays a pivotal role in the health of our eyes, specifically the retina1. Rhodopsin protein, a major protein that has the leading role in the process of vision, is found in the retina where it allows us to perceive light. This protein requires vitamin A to function properly. Without vitamin A, rhodopsin cannot sense light and thus cannot initiate the process by which vision occurs.
Figure 1: Chemical structure of Vitamin A molecule
Vitamin D regulates different chemical reactions that are associated with bones, muscles, and the immune system. The simplified way it does this regulation is it helps absorb calcium from dietary nutrients which in turn strengthens the bones, helps neurons exchange signals to move muscles and helps the immune system to fight against viruses and bacteria2.
Figure 2: Chemical structure of Vitamin D molecule
Vitamin E acts as an antioxidant. Antioxidants are naturally occurring chemicals that neutralize toxic byproducts of many chemical reactions in the human body. When food is consumed and digested, the human body converts it into energy. As a result of metabolism free radicals (toxic byproducts) are formed and are neutralized with the help of vitamin E. In addition, free radicals are also in the environment. Furthermore, vitamin E stimulates the immune system to fight against bacteria and viruses3.
Figure 3: Chemical structure of Vitamin E molecule
Vitamin K can be obtained from food and dietary supplements. There are two forms of vitamin K: phylloquinone (Vitamin K1), which is found in spinach, kale and other greens and menaquinone-4 (Vitamin K2), which is found in animal products. Vitamin K1 is involved in blood clotting, and Vitamin K2 is involved in bone tissue building. Vitamin K1 is the main Vitamin K in human diet (75-90% of all vitamin K consumed), however, it is poorly absorbed in the body4,5.
Figure 4: Chemical structures of Vitamin K1 and K2 molecules
Absorption of fat soluble vitamins
Polarity describes the inherent charge(positive or negative) or lack of charge for any given substance or molecule. Molecules that are charged are referred to as “polar”, while those that lack charge are “nonpolar”. When discussing solubility, it is important to remember the phrase “like dissolves like”. That means polar (charged) substances like to interact with a polar environment like water, since water contains a slight negative charge. Hence, charged substances are water-soluble. Nonpolar substances on the other hand readily interact with nonpolar environments such as fat, which contains no charge. Therefore, molecules that lack a charge such as vitamins A, D, E, and K are referred to as fat soluble.
Due to their water fearing nature, these fat soluble vitamins cannot simply be absorbed directly into the bloodstream (which is mostly water) like the sugars and amino acids in our diet. As their name suggests, these fat soluble vitamins like to be embedded in fatty droplets, which facilitate their absorption in the following way. Fat soluble vitamins group together with other fat molecules to form fatty droplets, effectively reducing the amount of interaction with the watery environment of the intestines. Therefore, without an adequate amount of fat in your diet, your body is unable to effectively absorb these fat-soluble vitamins. This may be true in an intact anatomy, however, post weight loss surgical patients can not increase their fat soluble vitamin levels by increasing their fat intake. This is due to the fact that a high fat diet causes excessive bowel movement which in turn washes away any vitamins taken by mouth. DS limits fat absorption (thus the great weight loss) which can cause vitamin A and D deficiency that can not be easily corrected with oral supplementation.
As mentioned before, fat soluble vitamins are hydrophobic and nonpolar, which means they are also fat loving or lipophilic. Excess fat soluble vitamins can be stored in the liver and fat tissue. Therefore, these vitamins do not need to be eaten every single day since stores of these vitamins can sustain a person for some time. It may take several weeks or months for our body to deplete these stores of fat soluble vitamins which is why it generally takes a longer amount of time for fat soluble vitamin deficiencies to manifest themselves. The ability to store these fat soluble vitamins in tissues can also lead to vitamin toxicity – marked by an excess of vitamin stores in our body.
Clinical manifestations of A, D, E, K deficiency
|Vitamin||Clinical Deficiency manifestations|
|Vitamin A||Vision Problems
Dryness of the eye
|Vitamin D||Softening and weakening of the bones
Bone shape distortion
Bowed legs (generally in children)
|Vitamin E||Damage to red blood cells
Tissue/organ damage due to inability to supply enough blood
Nervous tissue malfunction
|Vitamin K1||Excessive bruising
Increased bleeding time
Small blood clots under nails
Increased bleeding in mucous membrane
|Vitamin K2||Weak bones
Increased plaque deposits along gumline
- Office of Dietary Supplements – Vitamin A. NIH Office of Dietary Supplements. https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/#. Accessed April 26, 2020.
- Office of Dietary Supplements – Vitamin D. NIH Office of Dietary Supplements. https://ods.od.nih.gov/factsheets/VitaminD-Consumer/. Accessed April 26, 2020.
- Office of Dietary Supplements – Vitamin E. NIH Office of Dietary Supplements. https://ods.od.nih.gov/factsheets/VitaminE-Consumer/. Accessed April 26, 2020.
- Vitamin K. The Nutrition Source. https://www.hsph.harvard.edu/nutritionsource/vitamin-k/. Published July 2, 2019. Accessed April 26, 2020.
- Beulens JWJ, Booth SL, van den Heuvel EGHM, Stoecklin E, Baka A, Vermeer C. The role of menaquinones (vitamin K₂) in human health. The British journal of nutrition. https://www.ncbi.nlm.nih.gov/pubmed/23590754. Published October 2013. Accessed April 26, 2020.
Obesity is related to as many as 400,000 deaths each year in the US and it has increasingly been recognized as a risk factor for several nutrient deficiencies. This may seem surprising given the likelihood of over consumption of calories, however these additional calories are not from nutritious sources. One of the main reason for these nutritional deficits is the greater availability of inexpensive foods that are rich in calories and are nutrient deficient. This has led some medical professional to conclude that there is a certain group of people who are overfed but undernourished. Even with the epidemic of the obesity, there is significant nutritional deficiencies noted.
Obese subjects have increased blood volume, cardiac output, adiposity, lean mass and organ size all of which can influence volume of distribution, in addition, treatment for severe obesity involving surgical procedures can worsen these nutrient deficiencies and in some cases may cause new ones to develop.
This table shows the percentage of population below the estimated average requirement (EAR) by body weight status in adults more tan 19 years old, showing that almost 90 to 100 percent of people including normal weight (NW) are below the EAR of vitamin D and Vitamin E.
Nutritional deficiencies in obese patients may promote the development of chronic diseases including increased insulin resistance, pancreatic B-cell disfunction and diabetes, this is because specific micronutrients are involved in glucose metabolic pathways; There are other chronic diseases related to obesity that are being investigated such as decrease in focal grey matter volume and cognitive impairment or inadequate sleep due to low intake of antioxidant vitamins.
We would like to thank Miguel Rosado, MD for his significant contribution provided for this Blog.
Vitamin A is one of the 4 fat soluble vitamins along with vitamin D, Vitamin E and Vitamin K. It is multifunctional and essential which means that it is not produced by the body. In this article we will touch on aspects of Vitamin A absorption and it’s effect on wound healing as well as its metabolism.
We often think of Vitamin A as the critical vitamin for vision, however it has several other roles that related to immune function, protein synthesis, and cellular communication. Vitamin A deficiency is a concern world wide because of the natural of the side effects. Vitamin A deficiency is the leading cause of preventable childhood blindness in the world according to UNICEF and sometimes it may be undetected until there is irreversible damage.
There are 2 chemical forms of vitamin A in diet:
Retinoids (Preformed vitamin A) This group include retinol, retinyl esters, and retinal they are mostly found in animal sources like liver, egg yolk or fish oils.
Carotenoids (Provitamin A) This group includes beta-carotene, alpha-carotene and lycopene, mainly found in plant sources like leafy vegetables or yellow/orange vegetables and fruits.
1.- Ingested food is digested in the stomach where retinyl palmitates (esters) are released from proteins. Retinol and beta-carotene are absorbed directly into the small intestine where retinyl esters and betacarotene are transformed into retinol . Retinol is the most easily absorbed form of vitamin A.
2.-That retinol absorbed by the enterocytes in the ileum (small intestine) along with bile is then transported to the liver with the help of chylomicrons a protein that transports fat.
3.-Fifty to 80% of the vitamin A is stored in the liver and the remaining is deposited into adipose tissue, lungs and kidneys.
4.-When stored retinol is released from the liver into the circulation to target organs, it is bound to plasma retinol-binding protein (RBP4) a transporting protein produced by the liver that requires ZINC, which is synthesized by the liver; This complex is stabilized by transthyretin (TTR), which reduces renal excretion.
Retinol is a crucial component for reproduction, embryological development, cellular differentiation, growth, protein synthesis, and immunity in the form of retinoic acid and vision in the form of retinal.
One of Vitamin A additional roles is in epithelial health of skin and mucous membranes. It increases epithelial turnover which is crucial during would healing. It also has anti-oxidative effects which prevent cell damage and can prevent or reverse the effects of other damaging agents. In addition to these benefits it has also been associated with increasing collagen, fibronectin, keratinocytes and fibroblast, all important in wound tissue structure. There have been some studies that suggest giving higher doses of Vitamin A in patients with non or slow healing wounds.
It is important to remember that we have documents delayed diagnosis of adult vitamin A deficiency leading to significant night blindness in adults. It is critical that the patients and their primary care physicians are acutely aware of this possibility. In majority of the patients with low vitamin A, post weight loss surgery, aggressive supplementations, including injections need to be considered as a part of the treatment regimen.
We would like to thank Miguel Rosado, MD for his significant contribution provided for this Blog.
New FDA regulations for compounding pharmacies has spurred changes in our pricing and ability to provide injectable Vitamin A and Vitamin D. The compounding pharmacies are no longer compounding injectable Vitamin A and there is a nationwide shortage of the national brand of injectable Vitamin A. We have a tentative date of February 2018 when we may be able to obtain injectable Vitamin A. We won’t be able to quote pricing on Vitamin A injections until we are able to orders.
We are able to obtain and supply our patients with injectable Vitamin D but with a price increase.
The following is the letter we received from our compounding pharmacy.
“The healthcare industry has continuously undergone changes in regulations and legislation. The compounding industry is no exception and has faced rigorous regulatory requirements this past year such as new testing specifications and compliance standards.
We are set on facing these demanding challenges by meeting and exceeding these new regulatory requirements. We want to assure you we will continue to provide the best products on the market for you and your patients. Quality and safety remain a top priority. We understand that our pharmacy plays a vital role in providing care to your patients. The increase in pricing is a reflection of the additional cost in producing and testing the product based on regulatory specifications.”
Unfortunately, we have been informed that the company we order our Vitamin A injections from will no longer have Vitamin A available. We have contacted several other companies and they also do not have it available. The manufacturer of Vitamin A states that there is a nationwide shortage of injectable Vitamin A and it may be available next year.
Our office has a few vials left and we are hoping that we can get to as many people as possible before we are completely out. We will continue to look for a source of Vitamin A injections. We will let you know when it is no longer available and when we receive a new shipment. Thank you for your understanding and we apologize for this issue.
Information on Vitamin A deficiency here.
You can find our list of recommended supplements here.
Just as a reminder, we have no financial interest in any of the vendors that are recommended on our website. Also, please note that this is not in ANY form or fashion a substitute for the evaluation by your surgeon or primary care physician. This is informational only and is not to be taken as a recommendation for any patients’ condition.
We have received notice that the FDA and the compounding pharmacy have changed their regulations for several medications. Unfortunately, this affects our office and Duodenal Switch patients in regards to injectable Vitamin D and Vitamin A. In the past, we have been able to have injectable Vitamin A and injectable Vitamin D in bulk in our office. The new regulations require that a patient be assigned to the medication, so we will be unable to have it on hand in our office. This is out of our hands and control.
We are requesting that if you are anticipating the need for injectable vitamins that you have your laboratory results in our office at least 3 weeks prior to your office visit. This will give our staff adequate time to order your injectable vitamins to be available at your visit.
Injectable Vitamin D may be needed in some cases of Vitamin D deficiency or inability to increase Vitamin D level with oral supplements. Vitamin D is a fat soluble vitamin. It plays an important role in bone metabolism and structure. It has also been found to affect the immune regulation, control off- inflammatory reactions, and also be involved in a number of broad cellular functions throughout the body.
Research and information regarding Injectable Vitamin D.
Thank you for your understanding in this manner.
Weight loss surgical procedures may result in varying degrees of nutritional deficiencies. Some of these nutritional deficiencies may cause neuromuscular disease if left untreated, these include vitamins, minerals, and protein. The long-term effect of these deficiencies may presents as neuromuscular conditions including, weakness, numbness, confusion and all others if not-diagnosed and untreated. It is important to note that all weight loss surgical procedures require lifetime vitamin, mineral supplements and protein monitoring and possible supplements.
The table below outlines some of the specific neurological and neuromuscular disease complications following bariatric surgery. The most common deficiencies seen with the duodenal switch operation are fat soluble vitamin deficiencies. These include, Vitamin A, D, E and K. Duodenal Switch patients need oral supplements of Dry “Water Miscible” type of Vitamin A, D, E, and K based on their laboratory studies and needs.
The neurological deficiencies are manifested much more frequently with the Gastric Bypass than the duodenal switch operation. The most common nutritional deficients are that of B1, B12, Folate deficiencies that are common in Gastric Bypass. A list of possible neurologic deficiencies and there associated symptoms were summarized by Becker (2012). Another article with Nutritional Neuropathies.
Nutritional deficiencies are seen in a number of illnesses including weight loss surgery patients.
Nycalopia or Night Blindness is a side effect of Vitamin A deficeincy. Vitamin A is a fat soluble vitamin that occurs in animal tissue as retinol. There are a number of different provitamins in food of vegetable origin. Beta carotene and other carotenoids, yellow and red carotenoid pigments, can be changed to vitamin A in the liver.
A number of functions for vitamin A have been found, including immune mechanisms, maintenance of healthy epithelial tissues, facilitates the mobilization iron from stores to developing red blood cells, and most importantly, a function in the visual system. Vitamin A deficiency may manifest itself by: 1.) A scale-like appearance in the skin and occasional acne, 2.) A failure of growth in young animals, including C. station of skeletal growth, and 3.) A failure of reproduction associated with atrophy of the epithelial cells of the testes and interruption of the female sexual cycle. Zinc works with Vitamin A by converting retinol to retinal and also protects from toxicity of Vitamin A. Vitamin A deficiency can worsen Iron Deficiency Anemia. It has been shown that treatment for Iron Deficiency Anemia responds better when Vitamin A and Iron are supplemented together.
Vitamin A deficiency may also represent a decreased visual acuity, more specifically, night blindness. Night Blindness was found in a patient who reported that they were unable to read a particular sign at night while driving, but was able to read it during the day. The body uses Vitamin A to make retinal, part of a molecule called rhodopsin. Rhodopsin is found in the rods of the eye. The rods are the cells of the retina that allow you to see in low light conditions. Here is a video of a patient exhibiting the effect of night blindness.
If Vitamin A deficiency is left untreated at the stage of night blindness it can progress to Xerophthalmia. Xerophthalmia is also caused by Vitamin A deficiency. The symptoms of Xerophthalmia is lack of tear production which are the lubrication of the eye. This leads to corneal and conjunctiva inflammation and thickening. The cornea can become cloudy and foamy spots (Bitot’s spots) leading to scarring and damage that effect the sight.
When a patient is diagnosed with vitamin A deficiency, the treatment will require aggressive oral supplementation. Duodenal Switch patients will only respond to “Dry” water miscible form of Vitamin A, which is pictured below/right. This “Dry” water miscible form is a powder which is designed to dissolve in water without the addition of bile for absorption. When taking oral vitamin A, it is important for patients who have had the Duodenal Switch operation to specifically look for a “Dry” water miscible form of vitamin A. This is to maximize the amount of vitamin A that can be absorbed even in the presence of reduced fat absorption.
For cases in which vitamin A levels do not respond to “Dry” water miscible Vitamin A oral supplementation, intramuscular injections may be required. The usual injected dosage of vitamin A is between 25,000-50,000 international units. Repeated injections in a 3-month interval have been required in some patients to normalize the vitamin A level, as well as resolving the symptom of night blindness.
At the last group meeting, there were several questions whether vitamin D and other vitamins would be absorbed via patch (transdermal) and spray (buccal/sublingual) routes. After reviewing several resources, the only article I could find was for transdermal Vitamin D absorption. However, if we look at the mechanism for each route we can make an educated assumption.
Transdermal route of absorption (without additional absorption enhancers) (ref) requires a molecular mass less than 500 g/mole, high lipophilicity (affinity to fat or lipids), and low required daily dose (less than 2mg). The fat-soluble vitamins are definitely lipophilic, all of them have molecular weights less than 500 g/mole and daily dose is under 2mg. It seems that hydrophilic medications (that have an affinity to water) may have less ability to be absorbed with this route unless a chemical enhancer is added to the product. Most vitamins and minerals have lower molecular weights except Vitamin B12 which has too high of a molecular weight unless an enhancer is added. The transdermal route has slower absorption than buccal (oral mucosa) but faster than usual tablet oral route. The down side to transdermal route is possible skin issues due to medication, adhesives, and also different rates of absorption due to skin thickness and condition.
Buccal/sublingual route of absorption is dependent on lipid solubility, oil to water partition coeffincient, saliva pH, small to moderate molecular weight, and oral mucosa thickness. The mechanism of action is osmosis, which means items that readily dissolve in water are easily absorbed. Unlike orally ingested medicates, that take time to absorb and need to be filtered and/or processed in the liver, sublingual route is fast absorbing and the liver is bypassed. The down side to this route is it disrupts eating and drinking and is not efficient with smoking due to vasoconstriction.
An e-mail was sent to the companies inquiring about the outcomes of their products with people with malabsorption issues. No response was received from the spray vitamin companies.A request was also sent to obtain any research articles they may have but a response has not been received at this time. The following is the response I received from the maker of Patch MD.
“I am the president and founder of Patch MD. We design Patch MD to help people that have digestive issues and malabsorption. Our whole premise is to avoid the digestive track, by doing so we avoid dealing with conditions such as short bowel syndrome, acid reflux, and bariatric surgery to name a few. People also with Crohn’s disease and iliac disease are challenged with digestion and absorption every day of their life. Our patches are designed specifically to pass nutrition through the skin into the bloodstream. We get letters every day from people that have had bariatric surgery and were unable to get vitamin D, calcium, the B’s and Vitamin A and K, our product works because we use the skin as our delivery system, absorption is through the skin, avoiding all digestive potential issues. The only problem that we may have is we tell our customers to use no lotions or cream in the patch application area, as you may understand it will prevent absorption. We are going to be at a national convention this weekend in Manhattan Beach California to take part and display our products at the ObesityHelp conference. They ask us to take part as they were getting great reviews from their members that are using the patch. All were improving their blood work after taking Patch MD patches.”
Earl Hailey, President Patch MD
In light of the review of data, it would seem that the transdermal route would be beneficial to people who are having issues maintaining blood levels of fat-soluble vitamin levels. The other vitamins also have a good prospect of absorption via transdermal route. Buccal or sublingual (sprays) would seem to have a better outcome for water-soluble vitamins unless there is an additive added to the product to increase the solubility of the fat-soluble vitamins and make them water miscible. We must realize that there is no data for Duodenal Switch patients and very little data regarding these routes of absorption with vitamins specifically. If you are going to try these types of vitamins you should be extremely diligent in following your laboratory studies for vitamin levels with greater frequency until it is determined they are maintaining your blood levels.
Also, it should be noted that water miscible (dry) Vitamin A, D, E, K are the only type of these vitamins a DS patients should be taking. Over the counter Vitamin A, D, E, K are fat-soluble and due to the fat malabsorption after DS these type of vitamins are not appropriate to maintain blood levels. Water miscible (dry) vitamins should NOT be taken with fatty or oily foods and should also be taken 30 minutes prior or 30 minutes after eating. The water miscibility makes them water soluble and therefore will not have optimal absorption if taken with fat. Fat also increases the rate of digestion through the small bowel after DS and decreases the amount of time the vitamin has in the bowel and therefore, decreases absorption. They are best absorbed when taken on their own.
The good news patches and spray routes of administering medications and supplements is an up and coming area of research. There are several ongoing research studies and new developments on the horizon for increasing absorbability of transdermal route with different types of additives and techniques.