The Link Between Sulfur Dysregulation and MCAS

This post describes the link between sulfur dysregulation and MCAS for people who have sulfur issues.

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Some people have issues regulating sulfur

I have tried many different diets in search of relief from my MCAS symptoms. I’d always felt better when I ate an egg-free diet. But without a concrete reason to abstain from eggs, they always slipped back into my diet.

Since reading an article by Naturopathic doctor Greg Nigh I may have figured out part of the puzzle exacerbating my MCAS symptoms.

Sulfur is the most abundant mineral in the human body, and it’s an important part of the production of sulfate (one sulfur molecule joined to four oxygen molecules SO2−4.) You need sulfate for many body functions, from detoxification to collagen production to making sure your cells are properly hydrated.

However, some people experience sulfur dysregulation due to genetic factors, nutritional deficiencies, or toxins.

What is MCAS?

Mast Cell Activation Syndrome (MCAS) is a chronic condition that affects all organ systems. MCAS is serious and disabling and people with MCAS experience often significant and debilitating symptoms daily, including anaphylaxis, which can be fatal.MCAS is often found in combination with other chronic conditions such as Ehlers-Danlos Syndrome (EDS) and Postural Orthostatic Tachycardia Syndrome (POTS).

Frequently healthcare providers do not know about MCAS, and the tests for MCAS are problematic because they are not uniformly reliable. MCAS can be difficult to manage. Treatments include blocking mast cell mediators with anti-histamines and mast cell stabilizers, as well as avoiding triggers.

Check out this post on how to manage MCAS.

The bucket theory

The bucket theory offers a helpful analogy for understanding symptom reactions with MCAS.

Think of your body as an empty bucket you want to keep from overflowing. Different foods and activities fill your histamine bucket at different speeds but they combine to form the total level of histamine in your body (how full your bucket is). A fuller bucket means you have more histamine symptoms. When you manage triggers, reduce exposure to known triggers, and take medications and supplements to reduce histamine, you can manage the level of your bucket.

Know your typical symptom progression

Knowing your symptom progression in a symptom flare is the key to developing your rescue plan. In this post, I discuss how to determine your symptom progression. Once you know what typically happens in your symptom progression you can design a rescue plan to address those symptoms.

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Because histamine and gut health are so closely linked, histamine-producing bacteria are an important factor in MCAS.

Sulfur metabolism impairment can be a significant contributor to histamine intolerance, and a unique connection exists between sulfur dysfunction and histamine intolerance.

“Histamine and sulfur sensitivity appear to be closely linked, but in some cases, excess sulfur and sulfur metabolism impairment may lead to histamine sensitivity.” – source

Because the symptoms of sulfur and histamine intolerance, they are easily confused. An inability to properly process sulfur is linked to a downstream inability to efficiently regulate histamine.

Here are the common symptoms of both sulfur and histamine intolerance:

  • Headaches/Migraines
  • Flushing/Hives
  • Joint pain/Body pain
  • Itchiness
  • Palpitations/Sudden blood pressure changes
  • Inflammation
  • GI pain/Constipation/Diarrhea
  • Shortness of breath
  • Fatigue/Cognitive impairment

Your body typically uses sulfur in the body as sulfate. When the conversion of sulfur to sulfate is too slow or is compromised, sulfate concentrations in the body are depleted, while concentrations of sulfur and sulfite may be too high. – source

The role of sulfur in histamine levels

Mast cells have hydrogen sulfide receptors that help stabilize mast cells.  

Normal levels of hydrogen sulfide help regulate gut inflammation and motility, oxidative stress, ulcer healing, cell regeneration, vascular tone, and hormone secretion. Certain gut bacteria are involved in both processing sulfur and producing histamine.

When these bacteria become imbalanced, levels of sulfur and histamine can easily get out of control.

Sulfur and SIBO

Dr. Greg Nigh discusses the connection between sulfur and SIBO. He says that Hydrogen Sulfide SIBO is so hard to get rid of because the body is trying to produce sulfur compounds to aid detox.

In cases of candida overgrowth and SIBO, sulfate-reducing bacteria in the gut produce excess hydrogen sulfide gas when they ferment carbohydrates, further disrupting microbiome health, inducing an immune response, and increasing intestinal permeability and gut inflammation (Figliuolo et al., 2017).

People with candida overgrowth or SIBO often have an intolerance to sulfur-based medicines and foods, with symptoms that mirror those of histamine intolerance.

Intolerance to key sulfur-rich foods and supplements

Common foods and supplements that can often exacerbate a sulfur intolerance are garlic, alpha-lipoic acid (ALA), and MSM. These are healthful for most people, but for those whose sulfur pathways are already overwhelmed they can cause worsened symptoms.

One red flag for sulfur-sensitivity is an intolerance to glutathione, a sulfur-based antioxidant. When the body cannot properly break down glutathione, a side effect is an increased production of hydrogen sulfide gas, especially in cases of SIBO. Hydrogen sulfide causes the breakdown of the mucus barrier and reduces concentrations of the mineral molybdenum, which is crucial for the regulation of histamine.

Another common intolerance for those with sulfur issues is NAC or N-Acetyl-L-Cysteine. NAC is a key precursor for glutathione but those with sulfur dysregulation issues often find that they cannot tolerate NAC.

For years I never knew why I could not tolerate NAC, MSM, glutathione, chondroitin sulfate, and Betaine HCl. I read about these helpful supplements and wanted their benefits. But time after time I would react to them.

Why does this happen?

I read Dr. Greg Nigh’s article called “The Devil in the Garlic: The Paradoxical Roles of Sulfur in Human Physiology” in Wise Traditions (Summer 2022). Nigh discusses how some people run low on sulfur — not because they aren’t eating enough foods containing sulfur — but because their body can’t process it properly.

Genetic factors

One reason for this can be genetic. If you have a gene glitch with the SUOX gene you may experience symptoms of sulfur dysregulation.

The SUOX gene provides instructions for making an enzyme called sulfite oxidase, which helps break down protein building blocks (amino acids) that contain sulfur when they are no longer needed.

In addition, Nigh says, “The sulfation pathway is closely linked to the methylation cycle within cells. A number of genes and their polymorphisms have the potential to affect the flow of the methylation cycle, and can, consequently, affect sulfation as a downstream effect. These include MTHRF, BHMT, and others.”

Supplements for sulfur dysregulation

A second reason for sulfur dysregulation is nutrient deficiency, specifically molybdenum deficiency. Nigh recommends people in this situation take Biotics Mo-Zyme, a form of molybdenum.

Another helpful supplement, for people with sulfur issues is Butyrate. I recommend Healthy Gut Tributyrin-X for this need.

While hydroxycobalamin, which is a form of vitamin B-12 that oxidizes hydrogen sulfide, can be helpful as well, this is another supplement that I can’t tolerate.

Speak to your functional provider about whether these supplements might be helpful for your situation.

Toxins

A third way that you may not be getting the benefit of sulfur from your food is that certain environmental toxins may be interfering with sulfur metabolism.

Nigh says, “Glyphosate is a major toxicant that interferes with sulfur metabolism” by suppressing certain critical enzyme functions and depleting vitamins.

What helps with sulfur issues?

In addition to the supplements mentioned above, many people benefit from a short-term (5-14 days) low-sulfur diet. Your body needs sulfur to thrive, but it can be overwhelmed by sulfur and not able to process it fast enough.

Sulfur overwhelm can manifest as SIBO, inflammation, pain (like from gout), headaches, hot flashes, and excess mucous. If that’s the case, then temporarily stopping sulfur-rich foods can help reset your metabolism and bring your sulfur back into balance.

A low-sulfur diet means eliminating eggs, garlic, onions, cruciferous vegetables, and supplements high in sulfur (NAC, MSM, glutathione, ALA, etc.) which tend to exacerbate sulfur issues.

At the same time, Nigh recommends doing Epsom salt baths to give your body sulfates through the skin to reduce the need for the GI tract to produce sulfur compounds it needs right away. Epsom salt baths raise blood levels of sulfate and also help with detoxification in general.

Finally, Nigh recommends nervous system-regulating therapies, as I’ve discussed in this post and this post.

If you’d like to learn more about Nigh’s recommendations, I recommend his book!

To Recap

To summarize the issue of sulfur cycle dysregulation:

  • When you run short of sulfate in your body it causes serious problems and most of the sulfur from the foods we eat is not in the form of sulfate; we need to metabolize it;
  • You can overwhelm your sulfur pathways by eating too many high-sulfur foods;
  • The body works around this by extracting sulfur from the mucus lining in the GI tract and by overgrowing sulfur-fixing bacteria in the gut (causing SIBO symptoms), and by creating localized inflammation that helps to generate sulfate;
  • The localized inflammation causes gout attacks in areas of the body like joints that are more prone to inflammation anyway, which for me is my feet, knees, elbows, and shoulders, and where there is excess inflammation my mast cells are quick to mobilize and cause more inflammation;
  • A short-term low sulfur diet brings down the excess sulfur so your sulfur pathways come back into balance and your body no longer needs to pull sulfate from the GI tract, or cause your body to make it at sites of inflammation, so the gout is self-limiting and the pain stops.

This helped me!

I tried the low-sulfur diet last spring and noticed improvement after about a week. My migraines and hot flashes disappeared. I no longer had severe EMF sensitivity. My SIBO symptoms vanished. Joint pain and gout abated. And I was able to start exercising regularly after decades of painful joints.

Over the summer I inadvertently added higher-sulfur foods back into my diet, and I started taking NAC again. I briefly experimented with chondroitin sulfate to help with parasites, but immediately I experienced gout in almost all of my joints.

This fall I noticed that I’d started experiencing hot flashes and bloating again, and my gout returned. I did another week of the low-sulfur diet and again felt so much better.

For people like me who have trouble regulating sulfur, Nigh recommends following a short-term low-sulfur diet every quarter to keep your sulfur levels in check. And this is advice I’m incorporating into my MCAS maintenance plan.

Before I did the low-sulfur protocol:

– I could only tolerate a handful of foods;

– I experienced severely disordered sleep;

– I was unable to exercise regularly due to pain and tachycardia;

– I experienced debilitating neuropathy which triggered hot flashes and contributed to more disordered sleep;

– I had chronic pain and inflammation

– I had just undergone 2-month antibiotic treatment for SIBO but hadn’t seen much benefit to doing it

– I couldn’t sleep on my side due to constant neck pain

After the low-sulfur protocol:

– Within a week I was tolerating many more foods, sleeping much better, and was no longer experiencing gas and bloating

– My hot flashes diminished considerably. I began to be able to sleep on my side and that gave me more comfortable sleep.

– After two weeks I gradually began adding sulfur-containing foods back into my diet.

– I have been able to slowly increase my exercise regimen, adding biking, and then running after being unable to bike or run for about 10 years prior.

– I’ve been able to gradually resume eating many higher histamine foods without issues.

The sulfur-rich foods and supplements that I react to most

I’ve created the table below showing the sulfur-rich foods and supplements that seem to affect me the most, the symptoms I experience from them, and the likely reason for my negative reactions*.

Food/SupplementSymptomsLikely Cause
N-Acetyl L-CysteineWorsened sulfur issuesContains Sulfur
Magnesium Ascorbate (Vitamin C), Ascorbic Acid, Sodium AscorbateWorsened sulfur issuesAggravates sulfur cycle issues; makes it difficult to break down neurotransmitters?
Alpha Lipoic Acid (ALA)Worsened MCAS symptomsContains Sulfur
Chondroitin SulfateIntolerable gout painContains Sulfur
GlycineIntolerable insomniaFree-form amino acid; Contains Sulfur
SAM-EIntolerable insomniaContains Sulfur
CoffeeIntolerable insomniaContains Sulfur
Pantoghenic acid (B5)Worsened MCAS symptomsContains Sulfur
Collagen powder, Whey powderIncreased inflammationHigh in sulfur
Immune PRP Pro (Bovine IgG, IgA, IgM)Worsened pain and MCAS symptomsNot helpful
LegumesWorsened MCAS symptomsHigh in sulfur
EggsWorsened pain and inflammationHigh in sulfur
Betaine HClWorsened MCAS symptomsHigh in sulfur
SeleniumWorsened MCAS symptomsSeems to mimic sulfur-rich compounds known as “sulfur but more so”
Klaire Labs Advanced Inflammation Support (Stephania Extract, Stinging Nettle Extract, Holy Basil Extract,  Ginger Extract, Boswellia Extract, Green Tea, Perilla ExtractWorsened MCAS symptomsBoswellia and Perilla are high in sulfur compounds
Methionine, tryptophan, and cysteineWorsened symptomsSulfur-containing amino acids
It is a very reactive form of sulfurGallbladder painMeat highest in sulfur containing amino acids
GarlicWorsened MCAS symptomsVery reactive form of sulfur
CauliflowerGas, bloatingSulfur-rich
LentilsGas, bloating, inflammationIncompatible with B-positive blood type, which I have
Chia seedsInflammationContain sulfur
RiceInflammationSupposedly low in sulfur, but I can’t tolerate it
*For informational purposes only. Consult your healthcare provider before making changes to your diet.

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Disclaimer

The preceding material does not constitute medical advice. This information is for information purposes only and is not intended to be a substitute for professional medical advice, diagnosis, cure or treatment. Always seek advice from your medical doctor. 

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