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.

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

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.

Food sources of Vitamin U

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.

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.

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/