The Supplements

What Vitamin A Does

Vitamin A helps us see, supports the immune system and helps the cells covering our skin and internal organs do their jobs. Researchers worked out these roles over many years. In 1913, experiments showed that certain foods contained a small amount of something needed for normal growth. That substance later became known as vitamin A.

Vitamin A is called fat-soluble because it dissolves in fat. During digestion, it is absorbed mainly in the small intestine with help from the processes that handle dietary fat. Unlike a nutrient that the body quickly gets rid of, vitamin A can be stored and used later.

The liver holds most of that stored vitamin A and releases it as the body needs it. Some comes from animal foods in forms the body can use as vitamin A. Some comes from plant pigments that the body first has to convert. These different forms are explained in the next cards.

The connection to the stomach is the health of its lining cells. These cells have to keep doing their normal jobs while worn or damaged cells are replaced. The body turns some vitamin A into retinoic acid, a substance that helps cells respond to instructions about growth and function. That gives us a reason to study vitamin A in the stomach; it does not mean that taking extra vitamin A automatically heals gastritis.

The Stomach’s Protective Lining

Your stomach makes acid to help digest food, but its own surface needs protection from that acid. Mucus forms a wet gel over the lining. Large proteins called mucins help the gel hold water. Mixed into it is bicarbonate, a substance that neutralizes acid close to the cells. Underneath sits a closely joined sheet of lining cells, called epithelial cells. Their connections help keep stomach contents out of the tissue below, while blood brings oxygen and nutrients needed for maintenance and repair.

Gastritis means inflammation of the stomach lining: an immune response involving changes in the tissue and the activity of immune cells. It does not always mean that the mucus has disappeared or that an ulcer has formed. One common cause is infection with Helicobacter pylori, usually shortened to H. pylori. Another is the immune system mistakenly attacking the stomach’s own cells. Medicines such as ibuprofen can also damage the lining, sometimes with relatively little inflammation; that kind of damage is called gastropathy.

Healing depends on what caused the problem and how much damage there is. Medicines that reduce acid can give injured tissue a better chance to heal, while treatment also addresses causes such as H. pylori. Vitamin A belongs in this discussion because lining cells use it to make retinoic acid, a substance involved in communication between cells. Nutrition helps the body maintain its tissues, but neither vitamin A nor sea buckthorn oil has been shown to supply everything needed to repair every case of gastritis.

Different Forms of Vitamin A

When a food label or a study says vitamin A, it helps to check which form it means. Vitamin A is a group of related substances. The form in a carrot, the form stored in the liver and the form used for certain signals inside a cell are not all the same.

Retinol is one form of vitamin A found in animal foods. Liver, eggs, dairy products and some fish can provide it, although amounts vary. It is called preformed vitamin A because the body does not have to make it from a plant pigment first. It can still need further changes before it does a particular job, such as helping vision or supplying a signal inside a cell.

Retinyl esters are forms in which retinol is joined to another molecule, usually a fatty acid. This makes a form suited to storage. The body can separate that attachment to release retinol. Retinyl palmitate and retinyl acetate are names you may see on supplement labels. They are forms of preformed vitamin A, rather than beta-carotene or ready-made retinoic acid.

Beta-carotene is a pigment that gives foods such as carrots and sweet potatoes their orange color. It is also found in dark-green vegetables, where the green pigment hides its color. Beta-carotene belongs to a larger group of plant pigments called carotenoids. The body can turn some carotenoids into vitamin A, which is why they are called provitamin A: they can provide the starting material.

The conversion happens in steps. The body first splits beta-carotene to make retinal. Retinal can then become retinol, or it can be changed into retinoic acid. Retinol can also be changed to retinal. Retinal is involved in vision, while retinoic acid helps control how certain cells grow and work. Similar names can make this confusing, but each substance has its own place in the process.

People differ in how efficiently they use beta-carotene. An enzyme—a protein that helps a chemical change happen—carries out the first conversion step. In a study published in 2012, Lietz and colleagues found that small differences in the gene for this enzyme affected conversion in female volunteers. Food preparation, absorption and a person’s vitamin A status also matter. These differences do not establish that people with gastritis generally cannot use beta-carotene properly.

Retinoic acid is the form involved in many of the cell-signaling experiments discussed here. One version, all-trans retinoic acid, is often shortened to ATRA. It is also used as a prescription medicine for a particular type of leukemia. Adding retinoic acid directly to cells in a laboratory is different from eating food containing vitamin A or taking a retinol supplement. Findings from one form should not be treated as proof that every other form will produce the same result.

How Cells Use Vitamin A Signals

Cells need instructions about what to make and how to work. Some of those instructions come from DNA, the material that holds the body’s genetic information. A gene is a section of DNA with instructions for making a particular product, often a protein. Proteins do many jobs, from giving a cell structure to helping it receive messages.

Most of a cell’s DNA is kept in a compartment called the nucleus. Retinoic acid, a substance the body makes from vitamin A, can affect how certain genes are used there. This is called gene expression. In everyday terms, it changes how much of a gene’s product the cell makes; it does not rewrite the DNA itself.

Retinoic acid works through proteins called receptors. A receptor recognizes a particular substance and helps the cell respond to it. Two related groups involved in vitamin A signaling are retinoic acid receptors, shortened to RAR, and retinoid X receptors, shortened to RXR. Each group has three versions. Alpha, beta and gamma are simply names used to tell those versions apart:

• Retinoic acid receptors: RAR-alpha, RAR-beta and RAR-gamma.
• Retinoid X receptors: RXR-alpha, RXR-beta and RXR-gamma.

An RAR usually works with an RXR as a pair. All-trans retinoic acid binds to the RAR part. The pair can bind to particular places on the DNA and affect nearby genes. The receptors are not carrying retinoic acid to the DNA like a delivery service; they are part of the system that connects a chemical signal to the use of genetic instructions.

The result depends on the cell receiving the signal and the other messages around it. A stomach cell and an immune cell have different jobs, so they do not necessarily respond in the same way. Having a receptor shows that a cell has part of the machinery for a response. It does not tell us that more vitamin A will always be helpful.

In 1999, Jiang and colleagues examined samples of human stomach tissue. They looked for messenger RNA, or mRNA: temporary copies of genetic instructions used to make proteins. They found messages for five receptor versions—RAR-alpha, RAR-beta, RAR-gamma, RXR-alpha and RXR-beta—in most cell types in normal stomach lining. The study examined tissue rather than giving vitamin A to people with gastritis.

The researchers also found less RAR-alpha mRNA in tissue with certain abnormal changes. One was intestinal metaplasia, where some stomach cells take on features of intestinal cells. Another was dysplasia, where cells look and develop abnormally. Neither term means that cancer is certain. The study found a difference between tissue samples; it did not prove that a shortage of vitamin A caused those changes or that supplements would reverse them.

These findings help explain why researchers study retinoic acid in the stomach: the lining contains the receptors associated with its signals. They do not establish a treatment. Finding the messages used to make a receptor is different from measuring how well the whole signaling process works, and different again from showing that a person’s symptoms or stomach damage improve.

In 2015, Bimczok and colleagues studied human stomach lining cells and found that they could turn retinol into retinoic acid. They used enzymes, proteins that help chemical changes happen, to carry out the conversion. In laboratory experiments, the lining cells also increased the ability of immune cells grown alongside them to make retinoic acid. The stomach cells were using vitamin A supplied to them, rather than making vitamin A from nothing.

The same research found changes in this retinoic-acid-making system in stomach tissue infected with H. pylori. That suggests the infection can interfere with local cell communication. It does not show that taking a vitamin A capsule restores the system, removes the infection or heals gastritis. The finding is about how human stomach cells work and how infection may disturb that process.

Th17 and Treg Cells

When the stomach is inflamed, immune cells are part of what is happening. Their job is to deal with threats and damage, but their response also needs limits. A response that is too weak may leave an infection in place. A response that continues too strongly can damage the body’s own tissue.

T cells are one family of immune cells. Different kinds help organize a response, attack infected cells or limit other immune activity. A naive T cell is a mature cell that has not yet met the particular target it recognizes. Signals around it help shape what role it takes on when it becomes active.

One group is called Th17 cells. These cells help the body respond to certain bacteria and fungi, especially around surfaces such as the intestinal lining. They can be useful during infection. In some conditions, though, continued Th17 activity contributes to inflammation and tissue damage. Their name is not a label for a cell that is always harmful.

Immune cells communicate by releasing small proteins called cytokines. Th17 cells are known for making a cytokine called interleukin-17, usually written as IL-17. It helps call other defenses into action. Some Th17 cells also make IL-22, which can affect the health and defenses of lining cells. What these messages do depends on the tissue, the infection and the other signals present.

Another group is called regulatory T cells, or Treg cells. They help limit immune responses and reduce the chance of attacks on the body’s own tissues or harmless material. This ability to avoid unnecessary attacks is called immune tolerance. Treg cells can act through contact with other cells and through chemical messages that change how those cells respond.

Many Treg cells contain a protein called Foxp3. Foxp3 helps control genes, the instructions a cell uses to make products such as proteins. In Treg cells, some of those products support the job of regulating immune responses. This is why researchers measure Foxp3 when studying these cells. Measuring it alone does not tell us how well a person’s immune response is controlled or whether their stomach is healing.

More immune suppression is not always better. Limiting an excessive response can protect tissue, but suppressing a response too much can make an infection harder to clear. In the stomach, H. pylori can remain despite an ongoing immune response. The useful question is how the whole response behaves, rather than whether one cell group can always be increased or another always reduced.

In 2007, Mucida and colleagues studied retinoic acid, the signaling substance made from vitamin A, in experiments involving mouse T cells and intestinal immune cells. Under the conditions they tested, it encouraged the development of Treg cells and reduced the development of Th17 cells. A message called TGF-beta helped shape this response. TGF-beta is a protein that affects cell growth and immune behavior, and its effects depend on the other signals around it.

In 2008, Xiao and colleagues looked more closely at that process. In cell experiments, retinoic acid strengthened part of the response to TGF-beta and increased Foxp3. It also reduced the amounts of receptors for IL-6 and IL-23, messages that help support Th17 development or activity. Receptors are the proteins cells use to receive those messages. But in the researchers’ mouse model of ongoing autoimmune inflammation, retinoic acid did not increase the proportion of Treg cells. The laboratory result did not apply in every setting.

Elias and colleagues also reported experiments in 2008 using all-trans retinoic acid and substances that activate or block vitamin A receptors. Activating the RAR-alpha receptor favored Foxp3 production and reduced Th17 development under the tested conditions; blocking retinoic acid signaling reduced the Foxp3 response to TGF-beta. These were experiments about how T cells develop. They were not trials showing that a vitamin A supplement treats an inflamed stomach.

A different kind of evidence came from Lounder and colleagues in 2017. They followed 114 children after donor stem-cell transplants, which replace the cells that produce blood and immune cells. Lower blood vitamin A levels 30 days after transplant were associated with more later graft-versus-host disease, including disease involving the gut. In this condition, immune cells from the donor attack the recipient’s tissues. This was an association, not a trial of vitamin A treatment, and it concerned transplant patients rather than people with ordinary gastritis.

For gastritis, the cause still matters. H. pylori is a bacterial infection. Autoimmune gastritis involves the immune system attacking the stomach’s own cells. Learning how retinoic acid affects T cells helps researchers ask questions about these conditions, but the studies above do not show that vitamin A clears H. pylori, improves antibiotic treatment or treats autoimmune gastritis.

What I take from this research is that vitamin A participates in the way immune responses are organized. That supports its place in normal nutrition. It does not give us a formula in which more vitamin A means more Treg cells, less inflammation and a healed stomach. The form used, the tissue being studied and the other immune signals all matter.

IgA Antibodies

Antibodies are proteins made by the immune system that recognize particular targets, such as parts of a bacterium. There are several kinds. One is immunoglobulin A, usually called IgA. A form released onto moist body surfaces, called secretory IgA, is found in places such as the digestive tract and airways. These surfaces are often called mucous membranes because they have a lining kept moist by secretions.

IgA can bind to microbes and their products, help gather them together and limit their contact with lining cells. This gives the body a way to handle some threats at the surface. It does not make the surface sterile or guarantee that every infection will be stopped. Having IgA in stomach secretions does not, by itself, mean H. pylori cannot remain there.

B cells are immune cells that can develop into cells that release antibodies. They can also change the kind of antibody they make while keeping the same target. That change is called class switching. In a 2013 study, Seo and colleagues found that retinoic acid encouraged switching toward IgA in cell experiments and affected intestinal IgA production in mice. Combining it with TGF-beta, another protein message that changes cell behavior, strengthened several parts of the response. This was laboratory and mouse research, rather than a study of human stomach healing.

In 2006, Mora and colleagues studied intestinal dendritic cells, immune cells that collect information about nearby material and help organize other immune cells. Retinoic acid helped B cells acquire the ability to travel to the intestine, a process called gut homing. In those experiments, retinoic acid alone did not make the cells release IgA; other messages from the dendritic cells were also needed. Mice lacking vitamin A had far fewer IgA-releasing cells in the small intestine. The study shows why both the nutrient supply and the surrounding signals matter.

Yang and colleagues examined vitamin A deficiency in a rat study published in 2011. Rats receiving a diet without vitamin A were compared with rats receiving vitamin A, and some were infected with Salmonella, a bacterium that can cause intestinal illness. The deficient animals had lower secretory IgA and more intestinal damage after infection. This was a study of deficiency and intestinal infection in rats, not H. pylori infection in the human stomach.

Together, these studies connect vitamin A and retinoic acid with some of the steps involved in intestinal IgA defenses. They do not establish how much IgA a person with gastritis will make after taking a supplement. They also do not show that vitamin A prevents H. pylori from attaching to stomach cells or protects against reinfection. Those would need to be tested directly in people.

Repairing the Lining

The stomach lining is living tissue, so maintaining it includes replacing cells. Its surface cells are called epithelial cells. New cells come from cells able to divide, including stem cells in the stomach’s glands. Stem cells can help maintain their own supply and produce cells that develop into more specialized types, such as mucus-producing cells. This development is called differentiation. Different parts of the lining renew at different speeds; the whole stomach lining is not replaced every three to five days.

Some early vitamin A research concerned skin wounds. In 1969, Hunt and colleagues reported that vitamin A treatment could counter the slowing of open-wound healing caused by cortisone, a steroid medicine. Their paper included animal experiments and human wound observations. That helped establish interest in vitamin A and tissue repair, but it concerned skin wounds under particular treatment conditions. It did not test retinoic acid as a treatment for gastritis or show that an ordinary vitamin A supplement repairs the stomach.

In 1984, Levenson and colleagues studied rats exposed to whole-body radiation, which can injure tissues and interfere with healing. The rats received additional vitamin A in their diet before or after the radiation. The researchers reported less impairment of skin-wound repair and less stomach ulceration, along with other improvements. This includes a stomach finding, but radiation injury is a very different situation from H. pylori infection or autoimmune gastritis, and the experiment does not establish a treatment for those conditions.

In 2004, Yuen and Stratford studied pieces of the ileum, the last part of the small intestine, taken from young piglets and kept alive in laboratory conditions. After chemically injuring the tissue, they added all-trans retinol. The treated samples recovered a more normal tissue structure and showed activation of TGF-beta1, a protein signal involved in growth and repair. The authors suggested that this signal explained part of the improvement. The experiment concerned piglet intestinal tissue, rather than a living person’s stomach, and did not prove that retinol works through the same process in gastritis.

In 2022, Vins and colleagues studied mice fed a vitamin-A-deficient diet from weaning. After months on that diet, the stomach lining showed changes, including surface damage and reduced cell division. It also showed more surface mucus, which is a useful reminder that more mucus does not necessarily mean a healthier lining. This was a study of long-term deficiency during growth. It did not test whether extra vitamin A heals an already inflamed human stomach.

For me, the useful point is that repair requires cells to replace damage and develop into the right kinds of cells. Vitamin A is involved in processes that help tissues do this, and a serious shortage can cause problems. But skin wounds, injured piglet intestine, radiation damage and mouse stomach changes are different kinds of evidence. They support further research; they do not establish that extra vitamin A heals human gastritis when vitamin A intake is already adequate.