Hydrogen Sulfide Reduces Mast Cell Activity
Dietary Sources of Hydrogen Sulfide Precursors
I have written several articles that deal with the mast cell hyperactivity that is a part of the Long-Covid syndrome… the evidence is that long covid patients as a group have all the hallmarks of Mast Cell Activation Syndrome (MCAS). So treating that may provide real relief (although there may be other issues). Here is another mechanism that holds potential for turning down mast cell excesses: hydrogen sulfide. There are foods and dietary supplements that can increase hydrogen sulfide production in the body.
What is hydrogen sulfide?
If you have smelled that peculiar smell that can come from rotten eggs (or sewer gas or other anaerobic rotting organic matter), then you have smelled hydrogen sulfide. It is a small, simple gas molecule with the formula H2S.
Hydrogen Sulfide can be toxic at higher levels, but it is also produced by the body in small amounts, and it serves many vital roles. The discovery of H2S as a signaling molecule in the body is relatively recent (1996), but it has gotten a fair amount of attention due to the many potential benefits of boosting H2S when it is low.
Hydrogen sulfide acts fairly rapidly to open up blood vessels and may be beneficial in lowering blood pressure. In the medium to long term, H2S is angiogenic - it encourages the formation of new microscopic blood vessels. The gas can reduce the formation of atherosclerotic plaque that causes heart disease. Higher levels of H2S can protect the brain, heart and kidneys in situations where they are cut off from blood and oxygen (ischemia). 1
And hydrogen sulfide is a mast cell stabilizer - it makes those immune cells less willing to drop their bombs loaded with histamine and proteases and other inflammatory compounds. When there is an active infection, mast cell inflammation is called for. But if the microbe invader is conquered but the mast cells keep firing, the body will make itself sick for no good reason.
Research Showing A Stabilizing Effect on Mast Cells
There is a solid body of research that shows that hydrogen sulfide can stabilize mast cells. Here are a few representative articles:
“Hydrogen sulfide: An endogenous regulator of the immune system.” Pharmacological Research, Nov 2020. https://pubmed.ncbi.nlm.nih.gov/32781284/
“Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice.” Pharmacological Research, Jan 2017. https://pubmed.ncbi.nlm.nih.gov/27840098/
“Nutraceutical Aid for Allergies - Strategies for Down-Regulating Mast Cell Degranulation.” Journal of Asthma and Allergy, 27 Oct 2021, https://pubmed.ncbi.nlm.nih.gov/34737578/.
“Hydrogen sulfide inhalation ameliorates allergen induced airway hypereactivity by modulating mast cell activation.” Pharmacological Research, Oct 2015, https://pubmed.ncbi.nlm.nih.gov/26241177/.
(Note: generating H2S to inhale as the last article above discusses poses a risk of toxic overdose and should not be considered outside of a medical environment.) Consumption of modest amounts of garlic or amino acids poses relatively few risks and presents a reasonable way to biohack the hydrogen sulfide pathways in the body.)
Some Precursors and their Effects
In theory, any form of Sulfur that is absorbed into the body might get turned into hydrogen sulfide - eventually. Amino acids are one source of sulfur in our diet. Methionine and cysteine are found in the proteins in many different foods. Taurine is an ‘amino acid’ that is not used to make proteins, but it can be found in some foods (especially fish). Epsom salt (magnesium sulfate) contains sulfur, and that can ultimately be transformed into hydrogen sulfide (although it takes several steps, and may not be the most efficient way to boost H2S).
But some forms of sulfur are more likely to have a noticeable boost on H2S than others. The most direct precursor or building block for hydrogen sulfide is the amino acid cysteine. Ordinary cysteine found in proteins in our food is known as l-cysteine or just plain cysteine. Another form of cysteine amino acid is n-acetyl-cysteine (or NAC).
NAC is a popular dietary supplement is created essentially by boiling vinegar (or acetic anhydride) and cysteine together. The acetyl group from vinegar attaches to the amino acid, and this makes the amino acid more water soluble, more absorbable, and it changes some of the other properties a bit. This is similar to how aspirin (acetylsalicylic acid) is created by taking salicylic acid (originally from Salix or willow trees) and linking it to an acetyl group.
Garlic, onions, and the cabbage family contain some interesting sulfur compounds. In the case of garlic and onions, these sulfur compounds are rather stinky, and include diallyl disulfide, diallyl trisulfide, and diallyl tetrasulfide. In the case of cabbage, broccoli, and other crucifer vegetables, the sulforaphanes may be less odiferous, but they still have a sharp taste, and they contribute to the healthy properties of those veggies.
Sodium thiosulfate is a commonly used mineral compound that has a variety of industrial uses. It was widely used as the ‘fixative’ in black and white photography - it permanently stops silver photographic film from being sensitive to light. It also is used in hospital emergency rooms in an intravenous solution as a treatment for cyanide poisoning, where it acts as a source of hydrogen sulfide.
Sulfide vs Sulfite
Those two words look very similar, but they represent two very different types of sulfur compounds. Sulfide is sulfur in a chemically reduced form; sulfite is an oxidized form. And sulfite (in the form of sodium sulfite or potassium metabisulfite) has potentially unwanted effects in the body: Sulfite stimulates mast cell activity. People who are sulfite-sensitive experience rashes, asthma, and other allergic responses after consuming this preservative.
“Effect of sodium sulfite on mast cell degranulation and oxidant stress.” Annals of Allergy, Asthma, and Immunology, Apr 2006, PMID 16680925.
“Sodium Sulfite-Induced Mast Cell Pyroptosis and Degranulation.” Journal of Agricultural and Food Chemistry, 14 Jul 2021. PMID 34191510.
“Clonal mast cell activation syndrome with anaphylaxis to sulfites.” International Archives of Allergy and Immunology, Jun 2013, PMID 23816954.
NAC vs Cysteine
NAC has become more popular during the pandemic, and between increased demand and supply chain disruptions, the price for NAC has risen. The price of NAC tablets is somewhere around 40 cents per 1000 mg (per gram). Ordinary cysteine (l-cysteine) powder can be much less expensive - around 5 cents per gram. But is it as effective?
Both NAC and l-cysteine can be turned into hydrogen sulfide in the body. NAC is actually first broken down into l-cysteine, and then turned into hydrogen sulfide.
There might be some differences in terms of absorption or bioavailability that favor NAC. But for most people, the less costly basic amino acid does work.
This article compared the effects of NAC, l-cysteine, and hydrogen sulfide:
“N-acetylcysteine (NAC) differentially affects arterial medial calcification and bone formation: The role of l-cysteine and hydrogen sulphide.” Cell Physiology, Jan 2022, PMID 34658034.
The study found that direct treatment with hydrogen sulfide was not as effective as treatment with either NAC or l-cysteine. One possibility is that the hydrogen sulfide did not distribute itself to all tissues; another is that the amino compounds NAC and cysteine also were used in other reactions in the body (like the production of glutathione, an important molecule involved in antioxidant and detoxification processes).
The Life Enhancement nutritional blog prefers l-cysteine over NAC. They recommend taking twice as much vitamin C as cysteine, to prevent the cysteine from being converted to cystine (which increases the risk of kidney stones). They also note that NAC (like aspirin) acts as a blood thinner by increasing acetylation of blood platelets and increasing the prothrombin time; this effect of NAC might be desirable or undesirable (depending on a person’s particular situation). If a person is already on a blood thinner, cysteine might be preferable.
The Bottom Line
In terms of rationale, cysteine and acetyl-cysteine both boost hydrogen sulfide, which reduces mast cell activation (a hallmark of Long Covid). Both compounds have been widely used with minor but real safety concerns - cysteine is present in small amounts in most protein-rich foods. The moderate use of garlic or garlic extracts presents a parallel course of action for biohackers to boost endogenous hydrogen sulfide. In terms of cost, the plain amino acid form of cysteine is much less expensive — but a daily dose of any of the hydrogen sulfide precursors can be had for under $1.
“Chapter Six - Medical Functions of Hydrogen Sulfide.” In Advances in Clinical Chemistry, Vol. 74, 2016, Pages 195-210. https://doi.org/10.1016/bs.acc.2015.12.007