Vitamin U complements H2 blockers

Summary - H2 blockers are drugs used to reduce stomach acid in people who have pain due to stomach ulcers. Vitamin U in the form of fresh vegetable juice or supplements can be used alongside H2 blockers to speed up the restoration of the protective mucous bilayer.

The human stomach is a very acidic environment. The pH of a correctly-functioning stomach is 1.5 - 3. The acidity of gastric juice is due to hydrochloric acid (HCl), which is produced by parietal cells in the upper parts of the stomach (fundus and cardia). Parietal cells produce acid using enzymes called proton pumps (H+/K+ ATPase), which use the energy derived from the hydrolysis of ATP to pump H+ into the stomach. It is the protons (H+) that cause acidity. 

The parietal cells pump acid into the stomach in response to signal molecules binding receptors. There are numerous kinds of receptors that respond to different stimuli, either positively or negatively. The most important for acid production are the H2 histamine receptors. Protein in food is broken down in the stomach by acid and the enzyme pepsin to form peptides. These peptides stimulate the release of the hormone gastrin from G cells in the stomach and duodenum. Gastrin stimulates the release of histamine from ECL cells. Histamine binds receptors in the base of parietal cells where it stimulates the movement of proton pumps to the apical surface, where they pump acid into the stomach cavity (lumen). This acid accelerates this whole cycle, breaking down more proteins in food by hydrolysis as well as activating pepsin.

H2 blockers bind to the H2 receptors, which stops histamine from binding. If histamine can't bind, the levels of acid in the stomach remain fairly low and the corresponding pH relatively high. (H2 blockers are often referred to as H2 antagonists because they block the binding of histamine without itself stimulating the function of the receptor, an important distinction from agonists). 

H2 blockers were invented in the 1960s and have to a large extent been superseded by proton pump inhibitors due to the latter's more potent acid-suppressing abilities. Commonly used H2 blockers include omeprazole (e.g. Prilosec), famotidine (e.g. Pepcid) and cimetidine (e.g. Tagamet). Ranitidine (e.g. Zantac) was the most prescribed drug in the US during the 1980s, but the FDA has recently banned its sale due to carcinogenic impurities. 

Stomach ulcers and gastroesophageal reflux (GERD) are conditions characterized by pain caused by stomach acid coming into direct contact with the lining of the stomach and esophagus, respectively. Contrary to popular opinion, these conditions are rarely caused by excessive production of stomach acid. In fact, the acidity in the stomach of those with stomach ulcers is typically low (i.e. relatively high pH). GERD is caused by normal stomach acid coming into contact with the esophagus, an organ that is not designed to withstand such exposure. Unlike the stomach, the esophagus is not coated with a protective alkaline mucous bilayer and is very sensitive to contact from even small amounts of gastric juice.

One unfortunate problem with taking H2 blockers for stomach ulcers is that they reduce the secretion of mucin (Ichikawa et al., Diebel et al). So while they reduce pain by reducing the amount of acid produced, they also increase the risk of pain by weakening the mucous bilayer. 

Vitamin U is a nutrient abundant in vegetables and fruit that stimulates the secretion of mucin in the stomach. As fresh vegetables and fruit have been a major component of our diet for a very long time, it is reasonable to conclude that dietary Vitamin U plays an important role in the maintenance of optimal stomach function. 

Can Vitamin U be combined with H2 blockers? 

Considering Vitamin U stimulates mucin secretion and H2 blocker reduce it, one may wonder whether Vitamin U can be taken with H2 blockers to negate the negative effects. The evidence suggests yes. In 2009, Ichikawa et al. showed that co-administration of Vitamin U with famotidine reversed the mucin-blocking effects of famotidine without affecting the acid-suppression effects. These results suggest that Vitamin U can add another level of protection to the gut in those taking H2 blockers.

Considering these findings, drinking fresh vegetable juice daily or taking Vitamin U supplements may help restore your mucous bilayer, ease discomfort and heal your ulcers.

High salt consumption may cause stomach ulcers

Summary - High salt consumption is a risk factor for the development of gastritis, gastric ulcers and gastric adenocarcinoma. If you have a stomach ulcer and your salt consumption is high, reducing the amount of salt you eat might help heal your ulcer, especially in combination with other treatments like antibiotics and Vitamin U. Talk to you doctor about your options.

(For clarification, "peptic ulcer" usually refers to ulcers in either the stomach or the duodenum. A "gastric ulcer" is another name for a stomach ulcer.)

The two most cited risk factors for the development of stomach ulcers are infection with Helicobacter pylori and taking NSAIDs (Mayo Clinic, 2020a). High dietary salt is another risk factor that is lesser known, though it has long been considered a risk factor in the development of stomach cancer (Mayo Clinic, 2020b; Cromer et al, 1949). Stomach ulcers and stomach cancer are two different conditions, and ulcers do not automatically lead to stomach cancer. However, these two conditions result from a similar set of risk factors, include high salt intake. What determines whether you develops ulcers or cancer may lie in genetics, diet, and to a certain extent, luck.

 

It has been long noted that at times when salt consumption within a population is low, stomach ulcers are rare (Sonnenberg 1986 and references within). For example, prior to the French Revolution, salt was heavily taxed in France as a means of raising crown revenue. Salt consumption was light among the general population. and the incidence of stomach ulcers was low. As salt taxes were repealed, salt consumption especially via its use as a food preservative increased. Salt consumption in the Western world peaked in the early 20th century, declining with the invention of alternative forms of preservation like canning and refrigeration. Throughout this period, mortality due to stomach ulcers rose, peaked, then declined in lockstep with salt use. 

Another way to show a relationship between salt intake and stomach ulcer prevalence is to look at these factors in different countries at a given time. Countries in which salt intake is high (e.g. Japan, Portugal, Spain) tend to have higher mortalities from stomach ulcers than those in which salt intake is low (Sonnenberg 1986). 

Does this mean your stomach ulcer is caused by eating too much salt? On the one hand, your ulcer is caused by something, and if your diet is heavy in salt, it might be a contributing factor. On the other hand, while the evidence is quite suggestive, it's important to take these findings with a grain of salt (so to speak). If you have a stomach ulcer and eat a lot of salt, reducing dietary salt for a couple of weeks and seeing whether the pain goes away might be worth trying. Even better, talk to your doctor as a combination of reduced salt intake and other treatments might be even more effective.

How does a high-salt diet cause stomach ulcers? 

By itself, high salt intake can cause a non-inflammatory atrophic gastritis (Bergin et al, 2003). Concentrated salt strips off the mucous bilayer by inducing edema, increasing the percentage of replicating cells susceptible to mutagenesis, and exposing the underlying epithelial cells to damaging stomach acid (Charnley and Tannenbaum, 1985). The heightened cell turnover especially in combination with mutagens increases the chances of a cancer-causing mutation occurring. Acidic damage reduces production of mucus and acid required for digestion, with chronic damage resulting in low stomach acid (hypochlorhydria) (Cromer et al, 1949) and predisposes to ulcer formation. 

Like salt, H. pylori can induce atrophic gastritis in and of itself, while also inducing an inflammatory response. However, it seems that a combination of H. pylori infection and a high-salt environment leads to a much greater chance of developing stomach ulcers and/or cancer. Damaging the mucous bilayer with salt enables H. pylori to directly contact the epithelial cells. Low stomach acid allows H. pylori to more easily survive in the stomach, especially in parts prone to ulceration/cancer such as the corpus. Inflammation generates reactive oxygen species that damage the DNA of epithelial cells, resulting in immediate reduction in function as well as debilitating mutations. Reactive oxygen species generate mutations in the cells lining the stomach that are then enriched by heightened cell turnover. Most mutations result in reduced cell function, which often shows up as cells that produce less mucus or less gastric acid on a permanent basis. However, some mutations are in genes that when damaged result in the cells reproducing at an inappropriately increased rate, oftentimes producing cancer. 

A high-salt environment also seems to induce physiological changes in H. pylori that enable the bacterium to survive under the unusual conditions. When the salt concentration in the stomach increases above a certain level, H. pylori becomes stressed and its growth slows. It changes its shape from its regular spiral to an elongated filamentous form (Gancz et al, 2008). Virulence factors (e.g. cagA, vacA, adherins) may be induced depending on the strain of H. pylori present, which enable the bacterium to invade the cells lining the stomach (Loh et al, 2007).

What constitutes high salt? Charnley and Tannenbaum (1985) stated that frequent consumption of foods rich in salt such as soy sauce (18%), dried fish (20%), and pickles (13-25%) would probably lead to increased gastric cell proliferation. Chips and pretzels are similarly salt-rich, and in large and regular amounts would be expected to have similar effects on the gastric lining. The best measure of whether you are taking in too much salt is by having your doctor measure your 24 h urinary sodium output (Sonnenberg 1986).

Stomach ulcers result from an imbalance between destructive factors such as high salt intake and H. pylori infection, and constructive factors such as the mucus-stimulating ability of prostaglandin E2 and Vitamin U. Taking Vitamin U in the form of fresh vegetable juice or supplements will to some extent counteract the negative effects resulting from high salt consumption by rebuilding the protective mucous bilayer lining the stomach. Recall the pioneering cabbage juice studies of Cheney from 70 years ago (more). The role of H. pylori infection was unknown at the time, yet cabbage juice in the absence of supporting antibiotics was effective in healing peptic ulcers. 

Whatever means you take to treat your stomach ulcer, it would be wise to reduce exposure to the causative agent(s), whether that be infection with Helicobacter pylori, NSAIDs, a stressful job, the morning donuts, or in this case, a high-salt diet. If you have stomach issues but are not sure what condition you have, visit your doctor for a diagnosis. 

Please don't treat stomach cancer with vegetable juice or Vitamin U supplements. The primary role of nutrients is to promote good health and reduce the risk of developing cancer in the first place. Once a cancer has formed, it should be treated with chemotherapy, radiation and/or surgery. 

Vitamin U is a mucin secretagogue

Summary - Vitamin U is a nutrient abundant in vegetables and fruit whose main function is to stimulate the secretion of mucin and enable the formation of the mucous bilayer that protects the stomach from acid and Helicobacter pylori.

In the human body, Vitamin U heals and protects against peptic ulcers. It does so by stimulating the secretion of mucins onto the walls of the digestive tract, acting as a precursor to the biosynthesis of the master antioxidant glutathione, and supplies methyl groups for gene regulation, polyamine biosynthesis and a range of other molecules. Of these three functions, stimulating mucin secretion is the most direct way in which Vitamin U works.

In the stomach, there is an alkaline mucous bilayer gel that protects the stomach from gastric acid, pepsin digestion and bacterial infection. Mucus consists of two layers - a deep gel-like layer attached to cells and a superficial loosely-attached layer on top. The proteins that make up mucus are called mucins (MUC1, MUC5AC, MUC6), which are heavily-glycosylated proteins that attract water, thereby forming a gel. Mucins are made in foveolar cells lining the stomach and are stored in vesicles awaiting summons to the lumen. At the surface, some mucins stay attached to the cells and act as an anchor for the loosely-bound mucins to attach by disulfide bonds. When this mucous bilayer is disrupted, gastric juice can reach the lining of the stomach causing irritation and inflammation. Left long enough, a peptic ulcer may form.

Your body has a number of different ways to stimulate the secretion of mucin. The molecules that trigger secretion are called mucin secretagogues. The prime mucin secretagogue is prostaglandin E2, a hormone-like molecule that has many functions in the human body. It has a protective role in stomach function, suppressing production of gastric acid and pepsin, while at the same time promoting secretion of mucin and the alkaline molecule bicarbonate (Park et al). NSAIDs reduce prostaglandin E2 synthesis by inhibiting COX-1, leading to less mucin, less protection and a greater risk of ulcers.

Vitamin U (S-methylmethionine) is a nutrient found in all vegetables and fruit, and especially members of the cabbage family. Vitamin U protects the digestive tract by stimulating the secretion of mucin from the foveolar cells. In 1996, Watanabe et al. showed that exposing gastric mucous cells to L-cysteine or methylmethionine sulfonium chloride (MMSC or Vitamin U) prevented the formation of stomach ulcers caused by exposure to 50% ethanol. They demonstrated that Vitamin U and cysteine work in a similar manner via a sulfhydryl group. Interestingly, Vitamin U does not have a sulfhydryl group, but rather a sulfonium group. Consequently, Vitamin U is usually described as a latent sulfhydryl. The fact that Vitamin U and L-cysteine activities were inhibited by the pre-administration of the sulfhydryl inhibitor N-ethylmaleimide suggests that Vitamin U is active as a sulfhydryl. Vitamin U is stable at acid pH, so activation probably takes place in foveolar cells. 

In a follow up study, Watanabe et al. (2000) found that Vitamin U and cysteine induced the transport of vesicles containing mucin from deep within the cytosol to the cell surface for release into the stomach lumen, thereby forming a protective barrier. Interestingly, the movement they observed was independent of Ca2+ and cAMP. When signal transduction occurs via an endogenous molecule like prostaglandin-E2, there is a rise in the concentration of cAMP. When the P2 purinergic receptor is activated by ATP, there is an accompanying rise in Ca2+. Yet sulfhydryl-instigated movement did not induce a change in Ca2+ or cAMP levels. The authors suggested sulfhydryls promote mucus movement by a non-receptor mediated process.

Irrespective of how Vitamin U works, there's good evidence that drinking fresh vegetable juice or taking Vitamin U supplements may help restore your mucous bilayer, ease discomfort and heal your ulcers.