Mouth ulcers and Vitamin U

Summary - Mouth ulcers result from a breach of the mucous layer that protects the lining of the mouth and an underlying inability to repair the mucous layer quickly. Taking Vitamin U in the form of fresh vegetable juice and/or supplements is a great way to naturally heal mouth ulcers. Talk to your doctor or dentist.

Mouth ulcers (aphthous ulcers or stomatitis) are small, painful, circular sores that form in the lining of the mouth. They are very common. Right this minute, 1-2% of people have a mouth ulcer. Over a lifetime, about half of the US population will get at least one if not many. They mainly afflict teenagers. Ulcers normally heal spontaneously in one to two weeks, although they can reoccur many times. Recurrent ulcers indicate an underlying health problem. Sores in the corner of the mouth or outside the mouth are not ulcers and should be treated differently.  

Why do I have a mouth ulcer? 

The lining of your mouth is covered by a thin layer of mucus. The main purposes of this mucus is to protect the lining of the oral cavity from physical and chemical damage, infection, and to help digest food. Mouth ulcers develop when the protective mucus layer is breached and the body shows a delayed repair response with non-specific oral bacteria infecting. The integrity of the mucus layer is a function of constructive vs destructive factors. 

Destructive factors

Biting your mouth while eating or from a nervous habit is probably the most common way ulcers start. Physical or chemical damage from food is another very common cause - 

• Crusty food like bread or toast
• Crispy food like chips
• Salty food like pretzels
• Sweet food like candy
• Sticky food like cookies
• Sour food like vinegar
• Hot food like coffee

Abrasive, salty and hot foods/drinks physically damage the mouth. Sour foods/drinks chemically burn the mouth instantly. Sweet and sticky foods burn slowly by feeding oral bacteria, which metabolize sugars to produce corrosive acids. 

Drugs are another destructive factor. Alcohol is oxidized by oral bacteria to acetaldehyde, which is toxic and a carcinogen (Tagaino et al, 2019). Some acetaldehyde is even produced from sugar by oral bacteria. Acetaldehyde is also found in cigarette smoke (Sprince et al, 1975). As with peptic ulcers, NSAIDs like aspirin inhibit prostaglandin E2 synthesis which reduces mucin secretion. People swishing aspirin in their mouth to quell inflammation are actually slowing down ulcer healing (Slomiany and Slomiany, 2000).

Poor dental hygiene is yet another destructive factor. Harsh brushing makes tiny holes through which corrosive agents can meet the cell surface. Ineffectual or nonexistent brushing leaves food and bacteria in position to generate more organic acids and acetaldehyde.

Constructive factors

The major factor protecting the mouth is mucus. There are five kinds of mucin produced in the mouth - MUC5B and MUC7 being the most important (Frenkel and Ribbeck, 2015). MUC5B is a very long protein rich in serine and threonine amino acids to which glycans attach. These glycans attract water to form a gel and gives your mouth that slippery feeling. The protein overall looks likes a bottle brush with one end attached to the cell. MUC7 is similar, but is unattached and therefore flows freely aiding in formation of the soft bolus from food. MUC5B proteins form polymers via disulfide bonds. Cysteine is unusually common in MUC5B and is essential for disulfide bond formation.

A shortage of many dietary factors have been suggested to cause mouth ulcers. Examples include vitamin B9 (folate), vitamin B12, vitamin C, vitamin E, selenium. All play a role in antioxidation, and it makes sense that these nutrients are low in ulcers as the environment shows signs of oxidative stress (elevated malondialdehyde and depressed glutathione)(Arikan et al, 2009). 

Despite this speculation, however, the evidence has been inconclusive. There are certainly some patients who respond well to supplementation with one or another of these micronutrients. However, many times mouth ulcers occur in people with no apparent deficiency and/or supplementation has no effect. Considering that some of these micronutrients work in some cases, it's possible that they help in an indirect way, or that chronic mouth ulcers are indicative of a systemic redox imbalance. For example, chronic ulcers are more prevalent in those with other problems in their digestive tract (Brailo et al, 2007).

Can Vitamin U help heal and prevent mouth ulcers?

The use of Vitamin U to treat or prevent mouth ulcers has undergone little investigation (Kato and Takayasu, 1961). Vitamin U has been shown to be a useful treatment for gum disease (Sulym, 2016), and sulfur compounds like cysteine are effective in quenching the damaging effects of acetaldehyde in the mouth, particularly when combined with vitamins B1 and C (Sprince et al, 1975; Syrjanen et al, 2016).

The fact that Vitamin U has been shown to heal and prevent peptic ulcers by stimulating the release of mucin suggests that it may also have this function in other parts of the digestive tract which also secrete mucin (Watanabe et al, 2000). One can't help but wonder whether mouth ulcers have a similar etiology to its more dangerous relatives. If this is indeed the case, one may speculate as to whether Vitamin U or a metabolic derivative could have this effect on the release of mucin from not only the mouth or other parts of the alimentary canal, but even other epithelial tissues, including the lungs, trachea, nose and eyes.  

Vitamin U may also support mucosal function in indirect ways. Firstly, Vitamin U yields cysteine, which is the rate-limiting component of glutathione, the master antioxidant that fights oxidative stress. Secondly, the relatively large amount of cysteine required to tether mucin to the epithelial tissue means that extra cysteine in the form of Vitamin U may prove useful. Thirdly, much of the glycans that attach to mucins are themselves sulfated, requiring more sulfur. 

Many people, especially those whose diet is low in the sulfur amino acids methionine and cysteine, have limited antioxidant capacity due to having low levels of glutathione. For those people, alternative sources of sulfur amino acids like Vitamin U are an important alternative source. Drinking freshly-made vegetable juice or taking Vitamin U supplements in combination with the cessation of destructive practices will probably help clear up your current mouth ulcer and help prevent future ulcers.

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 and acne, dandruff and eczema

Acne, dandruff and eczema are skin conditions the origins of which are often idiosyncratic and mysterious. However, one characteristic shared by all three conditions is low glutathione levels. Glutathione is by far the most important antioxidant in the human body, yet we absorb little of it from our food- that's why our body makes it. 

There are three main causes of low glutathione - 

1. A medical condition that drains large amounts of glutathione

2. A genetic block that prevents the biosynthesis or regeneration of glutathione

3. Not enough glutathione precursors in our diet

Identifying the root cause of your skin condition is an important first step in the healing process. However, this is easier said than done. Often we just don't know why these conditions happen. Sometimes they can break out suddenly and worsen quickly, particularly under stress. At other times, symptoms can persist chronically for years.

Irrespective of the root cause, restoring your glutathione levels is a vital part of this rebalancing act. Glutathione is a tripeptide comprised of cysteine, glutamate and glycine. Of these amino acids, cysteine is most commonly in short supply. If glutathione levels are low due to dietary factors, it is usually due to a shortage of cysteine. Cysteine is found in protein, especially that derived from animals. Cysteine is also made from methionine, again abundant in animal proteins. These sulfur amino acids are also plentiful in grain proteins. However, some people find that meat/dairy/grain are inflammatory for other reasons like hormones or allergens. 

Vitamin U is S-methylmethionine, a soluble nutrient abundant in vegetables and fruit that is converted into methionine by the enzyme BHMT2. There have not been any direct studies into whether Vitamin U has any effect on these three conditions, whether taken internally in the diet or as a supplement, or when applied topically as an active component of a lotion. However, taking Vitamin U can help restore glutathione levels which are low in the tissues affected by acne, dandruff and eczema, so it is quite likely that increasing your intake of Vitamin U will help with these conditions, especially in combination with the identification and removal of triggers of these conditions in you. 

A glass of freshly-made vegetable juice every day is an excellent way to boost your Vitamin U intake along with a slew of vitamins and minerals essential for good skin health.

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.

Celery Juice and Vitamin U

Recently, drinking celery juice has been promoted as a cure for a whole range of ailments. The original promoter Anthony William recommends drinking 16-32 oz of celery juice daily. He stipulates the juice should be fresh, not mixed with other ingredients and that juicing is better than blending. Williams has stated that the science behind the healing powers of celery juice have yet to be discovered. Hollywood types and regular people who get with the program report improved skin quality and gut function among other health improvements, though results are still pending on its effect on most conditions.

Nutritionists have responded that while celery juice can be part of a well-rounded diet, it should not be considered the cure-all being touted. Some are concerned by the removal of fiber. Some consider the positive effects result primarily from the water content rather than any nutrient in the juice. Others generally state that celery juice is nothing special and won't cure anything. There are also skeptics who question William's conflation of the scientifically-backed benefits of eating vegetables with the nonscientific rationale for how this improves health.

Drinking celery juice is most likely good for us. From a scientific standpoint, celery juice contains lots of vitamins, minerals and other nutrients that will improve our health if we are not getting enough from our regular diet. Celery juice is also low in calories, unlike most fruit juices. Celery juice might help people psychologically in helping people make healthy lifestyle choices like avoiding bad foods and getting regular exercise.

It is quite likely that some of the health benefits resulting from drinking celery juice daily can be ascribed to boosting one's intake of Vitamin U. For those unfamiliar with Vitamin U (S-methylmethionine), it was discovered as an anti peptic ulcer factor during the 1940s-1950s by Dr Garnett Cheney. Patients with peptic ulcer disease were cured by drinking 1 liter of fresh cabbage juice every day for 7-10 days. Cheney found that other vegetables like celery also worked and increased the palatability of the treatment. Later research found that all vegetables and fruit have Vitamin U, especially in the stalky part. One of its functions in plants is to facilitate the movement of methionine between roots and leaves/fruit. Being mostly stalk, celery makes large amounts of Vitamin U to function. 

Most people have chronically low levels of glutathione, which results in chronically high levels of inflammation. People differ in their susceptibility to inflammation according to their genetic makeup, their diet and lifestyle. Vitamin U in celery juice probably improves the function of every body part by helping to restore glutathione levels, thereby reducing inflammation.

Vitamin U - A possible natural alternative to N-acetylcysteine (NAC)

The current coronavirus pandemic has changed our lives forever. One of the hallmarks of coronavirus (COVID-19) infection is acute oxidative stress, and as a consequence, life-threatening damage to the endothelial cells lining our blood vessels. It has been proposed that to counter this oxidative stress one may take N-acetylcysteine (NAC) as part of an array of treatment options that may allay this frightening illness.

Dr Roger Seheult 

https://www.youtube.com/watch?v=Dr_6w-WPr0w

https://www.youtube.com/watch?v=kK-DNyKnb5c

Dr Chris Martenson 

https://youtu.be/lIkXmAI6A0olist=PLRgTUN1zz_oeQpnJxpeaEkFimDeepqyWf&t=1494

N-acetylcysteine (NAC) is a popular supplement invented in the 1960s used primarily to optimize glutathione levels. It is normally used in hospitals in emergency situations to treat overdoses of acetaminophen (e.g. Tylenol), which results in an acute and deadly shortage of glutathione in the liver. When acetaminophen is taken as directed, it is safely metabolized by the liver enzymatically. A small amount is oxidized to form N-acetyl-p-benzoquinone imine (NAPQI), which is highly toxic. NAPQI is detoxified in the liver by conjugation with glutathione. However, in overdoses of acetaminophen, NAPQI levels rise dramatically as the regular detoxification processes are overwhelmed. The liver literally cannot regenerate glutathione fast enough to quench the toxic NAPQI. Extensive liver damage and death often ensues. NAC helps by being quickly converted into cysteine, which enables the production of fresh glutathione.

NAC is also sold as a dietary supplement as a means of optimizing glutathione levels on an everyday basis. Glutathione is the master antioxidant in the human body, responsible for detoxifying compounds in the liver as well as reacting with reactive oxygen species that are harmful in large amounts. Glutathione differs significantly to other antioxidants (such as Vitamin C) in that it is made by humans. Our body makes glutathione from three amino acids - glutamate, cysteine and glycine. Levels can get low when our diet is short of these amino acids. The rate-limiting amino acid is usually cysteine, which the body can obtain from the diet following the digestion of protein, and also enzymatically from methionine. When cysteine levels in the diet are inadequate, glutathione levels in the body become inadequate, resulting in general inflammation. Most chronic illnesses are characterized as having low glutathione levels and restoring glutathione levels may help reduce inflammation, if not actually reverse the underlying problem. 

Vitamin U (S-methylmethionine) is a naturally abundant nutrient found in vegetables and fruits, especially cruciferous (e.g. cabbage, kale) and stalky vegetables (e.g. celery, asparagus). Like NAC, one of the functions of Vitamin U is to facilitate glutathione biosynthesis via its conversion to cysteine. Its use as an alternative to NAC in the treatment of acetaminophen overdose has been proposed and remains under investigation. One of the advantages of Vitamin U is that unlike NAC, Vitamin U is already found in many of the foods available in the fresh market, and is therefore unlikely to cause side effects. 

While Vitamin U should not be used in an emergency situation as its efficacy has not been tested, Vitamin U may serve as an alternative to NAC by those looking for a natural choice to boost their glutathione levels and restore their redox balance on an everyday basis. 

It should be emphasized that any possible overdose of paracetamol/acetaminophen should be treated at a hospital by a doctor and not self-treated with NAC or Vitamin U. 

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798828/

https://www.webmd.com/vitamins-supplements/ingredientmono-1018-N-ACETYL+CYSTEINE.aspx?activeIngredientId=101

Food sources of Vitamin U

Vitamin U is produced by all flowering plants (angiosperms). Pretty much any vegetable and fruit we eat comes from a flowering plant, so pretty much anything we eat that comes from a plant has some Vitamin U, at least before it is processed. In fact, the only plants or plant-like organisms that don't make Vitamin U are conifers, ferns, mosses, algae and fungi.

In general, vegetables belonging to the Brassicacea family are the best source of Vitamin U. This family includes cabbages, kale, broccoli, kohlrabi, collards and turnips. Other vegetables such as spinach, asparagus and celery also produce abundant amounts of Vitamin U. Fruit are also good sources, but not as good as vegetables. In general, there is more Vitamin U in the leaves and stalks than in the fruit, roots and seeds. Grains seem to have little when fresh, but Vitamin U is made during sprouting. Animal products have little to no Vitamin U as it is not synthesized nor stored in significant amounts in animals.

Several studies have measured the concentration of Vitamin U in various foods. Tables listing some of these results are included below. Many factors affect the amount of Vitamin U in a given vegetable. These factors include storage conditions, storage duration, harvest time, regional variations and species variations. For example, cabbages have more Vitamin U during spring and summer when freshly harvested, with the nutrient slowly degrading with storage. After six months in the fridge, the concentration drops by one third, with faster losses at room temperature. In contrast, when barley is germinated for making beer, the amount of Vitamin U rises over time, affecting the flavor of the end product. In some cases, there are varieties of fruit that produce less Vitamin U. Oranges that have been selected to produce less Vitamin U are used to make juice because Vitamin U breaks down with extended storage and pasteurisation to form dimethyl sulfide, a compound that negatively affects the taste of the product (Sakamoto et al https://pubmed.ncbi.nlm.nih.gov/8987599/.) 

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Song, Ji-Hoon, Hae-Rim Lee, and Soon-Mi Shim. 2016. “Determination of S-Methyl-L-Methionine (SMM) from Brassicaceae Family Vegetables and Characterization of the Intestinal Transport of SMM by Caco-2 Cells.” Journal of Food Science 82 (1): 36–43.

https://www.ncbi.nlm.nih.gov/pubmed/27883364

Food (Vitamin U concentration (mg/kg dry weight))

Radish (129-139)
Cabbage (535)
Kimchi cabbage (89-116)
Broccoli (150-350)

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Scherb, J., Kreissl, J., Haupt, S. & Schieberle, P. Quantitation of S-methylmethionine in raw vegetables and green malt by a stable isotope dilution assay using LC-MS/MS: comparison with dimethyl sulfide formation after heat treatment. J. Agric. Food Chem. 57, 9091–9096 (2009).

https://www.ncbi.nlm.nih.gov/pubmed/19754146

Food (Vitamin U concentration (mg/kg wet weight))

Celery (176)
Kohlrabi (124)
Leek (94)
Beetroot (89)
Cabbage (81)
White asparagus - Peru spears (161)
White asparagus - Peru stalks (86)
White asparagus - Germany spears (252)
White asparagus - Germany stalks (68)
White asparagus - Greece spears (113)
White asparagus - Greece stalks (101)
Green asparagus - Peru spears (234)
Green asparagus - Peru stalks (109)
Green asparagus - Germany spears (94)
Green asparagus - Germany stalks (53)
Green asparagus - Mexico spears (134)
Green asparagus - Mexico stalks (64)
Tomato (2.8)
Commercial orange juice (0.9)
Commercial strawberry juice (1.8)

Freshly-squeezed orange juice (1.2)
Barley - unprocessed (0.9)
Barley - after 4 days of germination (24)

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Kim, G.-H. Determination of Vitamin U in Food Plants. Food Sci. Technol. Res. 9, 316–319 (2003).

https://www.jstage.jst.go.jp/article/fstr/9/4/9_4_316/_pdf

Food (Vitamin U concentration (mg/100g dry weight))

Spinach (45.2)
Pak-choy (34.3)
Kale (23.4)

Sumssukbujaengi - a wild korean leafy vegetable (19.8)
Leaf mustard (19.6)
Bud of aralia (19.3)
Broccoli (18.9)
Asparagus (18.7)
Sanmanul - a wild garlic (14.4)
Crown daisy (11.1)
Burdock (11.0)
Celery (8.3)
Komchi (4.7)
Wasabi (4.7)
Chamchi - a wild korean plant (4.0)
Shepherd’s purse (3.4)
Garlic (2.8)
Onion (2.7)
Green onion (2.6)
Laver (2.2)
Nurukchi (0.8)
Green tea (0.1)
Ginger (not detected)
Seaweed (not detected)
Red chilli (not detected)
Miscellaneous wild korean vegetables (not detected)

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Kovatscheva, E. G. & Popova, J. G. [S-Methylmethionine content in plant and animal tissues and stability during storage]. Nahrung 21, 465–472 (1977).

https://www.ncbi.nlm.nih.gov/pubmed/927476

Food (Vitamin U concentration (mg/kg wet weight))

Cabbage (50-104)
Kohlrabi (81-110)

Turnip (51-72)
Tomato (45-83)

Celery (38-78)

Leeks (66-75)
Garlic leaves (44-64)

Beet (22-37)
Raspberries (27)
Strawberries (14-25)

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Other references

1. 100-600 mg/kg dry weight (Bourgis et al and references within.)

  

https://pubmed.ncbi.nlm.nih.gov/10449582/

How much Vitamin U do you need to heal ulcers?

Summary - Hospitalized peptic ulcer patients were cured by drinking cabbage juice containing 42-162 mg of Vitamin U per day for 7-10 days when eating a bland diet and getting bed rest.

A recommended dietary allowance (RDA) for Vitamin U has not been established by the US National Academy of Medicine. However, an estimate of how much Vitamin U you could try can be made by calculating the amount of Vitamin U used in Dr Cheney's studies. Cheney healed ulcer patients with 1 liter of cabbage juice per day over 7-10 days. At the time, Cheney didn't know exactly how much Vitamin U was in the juice. He just knew this much juice in combination with a bland diet and rest was enough. In more recent years, Vitamin U was identified as S-methylmethionine, and there have been several studies in which the amount of this amino acid has been quantified in cabbages. From these studies we can approximate how much supplemental Vitamin U is required to heal ulcers.

In 2003, Kim reported 26-46 mg/100 g of dry weight, which given that a cabbage is ~92% water, works out as 21-37 mg/kg of fresh cabbage. In 2009, Scherb and others found that cabbages have 81 mg of Vitamin U per kg of fresh cabbage. In 2017, Song et al determined that cabbages contain 50 mg/kg of Vitamin U. So we can estimate that there is roughly 21-81 mg Vitamin U per kg of cabbage.

Why this variation? There are several probable explanations. One possibility is that different parts of the cabbage were analyzed by the various researchers. Kim found that the concentration of Vitamin U in the core, middle and outside leaves varied by 2-fold, with the middle leaves having the most. Scherb found that vegetables grown in different countries had different amounts of Vitamin U, suggesting that some of the variation may be due to geography. Another possibility is that the cabbages were not all of equal freshness or picked at the same time of the year. In an older study, Kovatscheva and Popova noted that cabbages lose 62% of their Vitamin U during six months of storage without refrigeration and 34% with refrigeration. Cabbages harvested in spring /summer have the highest Vitamin U content. Finally, it is possible that the various extraction procedures used in the studies resulted in slightly different yields of Vitamin U. 

1 liter of juice is typically extracted from about 2 kg of cabbage. Cheney arrived at 1 liter from prior studies in which various volumes of cabbage juice were given to guinea pigs subjected to chemically-induced ulceration. 100% of the guinea pigs responded to the guinea-pig equivalent of 720 ml of juice. The volume used in the clinical study was rounded up to 1 liter to take into consideration variations in body weight and unexpected factors. 

Taking all this data together, it can be estimated that 1 litre of juice contains 42-162 mg of Vitamin U, which probably represents a maximum daily requirement.

Issues with drinking 1 liter of cabbage juice

In the 1940s and 1950s, Stanford doctor Garnett Cheney healed his peptic ulcer patients by having them drink 1 liter of cabbage juice daily for a couple of weeks. Cabbage juice is not only rich in Vitamin U, but is also rich in folate, vitamin C, vitamin K and potassium among other nutrients. It's well worth trying this treatment for peptic ulcers rather than taking supplements. However, there may be some drawbacks. 

Taste

Many people find cabbage juice to be distasteful. The chemicals responsible for this bitterness are called isothiocyanates. These compounds are produced in the cabbage when the leaves are physically damaged during chewing or juicing. Glucosinolates are enzymatically converted by myrosinases to form the bitter isothiocyanates. Some people are lucky in that can't taste isothiocyanates all that well so they can readily drink cabbage juice. One way to prevent the formation of isothiocyanates is by boiling unbroken cabbage leaves before juicing to kill the enzymes. That's why boiled cabbage has a mild taste compared to raw cabbage. However, the problem with this approach is that Vitamin U is also unstable to boiling, negating any beneficial effects. 

One solution is to drink the one liter of juice as 4 cups throughout the day instead of all at once. Another solution is to mix in better tasting vegetables that contain Vitamin U such as celery. Cheney used mixes containing a 3:1 cabbage-to-celery to good effect.


Gas

A second issue is gas. Cabbage has a significant amount of raffinose, a sugar that is notorious for producing gas when eaten. The human small intestine lacks the enzyme required for the digestion of raffinose. Unfortunately, some types of bacteria in our large intestine do have such an enzyme and will ferment raffinose quite readily to form gases. These gases produced in the colon have only one way out and will cause bloating and discomfort until discharged. Ingesting one liter of cabbage juice will cause problems for most people. In principle, a possible solution is to treat the cabbage juice with Beano before drinking it. Beano is basically alpha-galactosidase, an enzyme that will break down raffinose into sucrose and galactose, both of which we can easily break down and absorb. I'm not sure whether anyone has tested this idea, though taking Beano along with the juice as recommended should help. Drinking several cups spread throughout the day should also reduce bloating.


Smell

A third issue is smell. Fresh cabbage juice smells fine - old juice does not. Vitamin U is degraded to homoserine and dimethylsulfide by enzymes found in cabbage. Dimethylsulfide has a disagreeable sulfur odor a little like that found in rotten eggs, though without the toxicity. These enzymes don't work as quickly as myrosinases, but leaving cabbage juice sitting around for a few hours will allow plenty of time for dimethylsulfide to form. Putting the juice in the fridge will slow the reaction somewhat, but after 24 h the juice still tastes terrible. Even if a person could stomach the old juice, there would not be much point as by this stage most of the Vitamin U would have been degraded. Cabbages also have other compounds that contain sulfur that when broken down produce disagreeable odors. The solution is to drink cabbage juice fresh before it has had a chance to go off.

Cabbage Juice Heals Peptic Ulcers

In the 1940s and 1950s, Dr Garnett Cheney from Stanford discovered that having his peptic ulcer patients drink one liter of fresh cabbage juice every day healed their stomach and duodenal ulcers 3-6 times faster than a bland diet alone. Chronic ulcers disappeared in 1-2 weeks depending on their severity. Dr Cheney was of the opinion that peptic ulcers resulted from a deficiency of a nutritional factor he termed Vitamin U, later identified as the amino acid S-methylmethionine. While cabbages are a particularly rich source of Vitamin U, Cheney found that all raw vegetables, and to a lesser extent, fruit, contain Vitamin U. In addition to healing existing ulcers, Dr Cheney found that Vitamin U also prevented the formation of new ulcers.

Why do we get ulcers? Ulcers result from an imbalance in the digestive system between protective and destructive factors. An alkaline bilayer of mucus containing mucin protects the wall of the digestive tract from harsh elements such as stomach acid, infection by bacteria living in the digestive system, NSAIDs, and dietary factors like high salt and alcohol. In modern times, NSAIDs increasingly contribute to ulcer formation by inhibiting the mucus-stimulating function of our body's prostaglandins. When the mucus layer is depleted, these harsh elements irritate the epithelial cells lining the digestive tract causing inflammation and enabling deep infection. 

Ulcers are usually treated with proton pump inhibitors or H2 blockers to reduce acid production, antibiotics to treat bacterial infections (particularly Helicobacter pylori in the stomach), antacids to neutralize acid, and mucosal protectants such as prostaglandin mimics. Unfortunately, these only provide a temporary solution to the problem. Ulcers return soon after cessation of treatment. Excessive stomach acid is usually not the root problem, nor is H. pylori infection. Most people with ulcers produce a normal amount of stomach acid, and half the world's population has H. pylori yet remain ulcer-free. These facts indicate that while acid and infection contribute to the formation of ulcers, other factors are at play.

Given the findings of Dr Cheney, it's easy to see that eating a balanced diet rich in sources of Vitamin U is beneficial. But how does Vitamin U work? In later studies, it was shown that Vitamin U has three properties that help maintain a healthy gut.

1. Stimulating the release of mucin into the mucus layer, thereby protecting the walls from acid and bacterial infection (most important).
2. Reducing inflammation by acting as a precursor to glutathione, the master antioxidant of the human body via its conversion to cysteine.
3. Coordinating with other nutrients such as methionine, folate, B12, betaine, choline, SAMe and B6 to supply vital methyl groups required for optimal health.

Increasing the Vitamin U content of one's diet in combination with reducing the intake of foods that deplete the protective mucus layer has been shown to improve ulcerative conditions in the digestive system. A diet rich in fresh vegetables, vegetable juice and fruit, and low in salt, alcohol and sugars is a good approach for restoring the mucus bilayer in most patients.

References

https://www.ncbi.nlm.nih.gov/pubmed/18104715

https://www.ncbi.nlm.nih.gov/pubmed/10719747

https://pubs.acs.org/doi/pdf/10.1021/ja01630a032