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Glutathione and MTHFR

The “Master Antioxidant” And What That Means For The Rest Of Us.

Generally, in medicine it takes a lot for a substance to get such a high-flying label as the “master antioxidant” but glutathione has managed it. Naturally, since it’s so vital, the MTHFR polymorphism messes with it.

What Is Glutathione?

Glutathione is a very small protein that is present in high levels in every cell in your body. It is just as common in your cells as glucose (which is absolutely vital for cellular function). It is made of three amino acids, glycine, cysteine, and glutamic acid. At the most basic level, glutathione is an antioxidant, but it is also the antioxidant of the antioxidants, the ONLY antioxidant of antioxidants.

Glutathione and MTHFR - this is how free radicals do damage in the body, and why antioxidants are so important.
Glutathione and MTHFR – this is how free radicals do damage in the body, and why antioxidants are so important.

Functions of Glutathione

  1. Direct antioxidant action – meaning it binds to and neutralizes free radicals and other reactive oxygen species. Lots of other compounds do this like vitamin C, E, and A, alpha-lipoic acid, melatonin, and a host of compounds from fruits, green tea, red wine, and the like.
  2. Regenerates other antioxidants – glutathione can donate electrons back to vitamins C and E, allowing them to work again.
  3. Activates antioxidant enzymes – glutathione acts as a cofactor for some antioxidant enzymes, which cannot function without it.
  4. Takes mercury out of cells and your brain – glutathione actively transports the heavy metal mercury out of cells, including brain cells. This is a big deal for neurodegenerative disorders like Alzheimer’s and Parkinson’s.
  5. Helps eliminate some toxins from the body – specifically mercury and persistent organic pollutants (POPs).
  6. Key detox reaction – glutathione conjugation is one of the seven Phase II liver reactions that help to eliminate toxins, thereby preventing them from roaming around your body doing damage..
  7. Regulates cell duplication and death – glutathione helps to determine when cells reproduce and also when they die, both of which are vital in cancer prevention.
  8. Vital for mitochondrial function – your mitochondria are your cellular powerhouses and arguably the source of most of your energy as a human. You want them to be working.

Because glutathione is involved in so many critical body processes it is also a key factor in many diseases, and may potentially be useful in the treatment of some. Also, I’ve highlighted in red the conditions which are also associated with MTHFR mutations. This is no coincidence. Also, if it’s a less-known disease association with MTHFR, I’ve included reference links. For more known associations, you could read this article.

Diseases Associated With Low Glutathione

Neurodegenerative disorders – Alzheimer’s, Parkinson’s, Friedrich’s Ataxia, Huntington’s disease, ALS (Lou Gehrig’s disease).

Lung disorders asthma (article showing MTHFR association here), COPD, acute respiratory distress syndrome

Immune disease – HIV, autoimmune disease including psoriasis, lupus, Sjogren’s, Behcet’s, and multiple sclerosis.

Heart disease – high blood pressure, heart attack, high cholesterol, coronary artery disease, preeclampsia. stroke.

Diseases of Agingcataracts (see this research), hearing loss (this article), macular degeneration (this research), glaucoma (this article).

Liver disease non-alcoholic fatty liver,

Cancer

Cystic Fibrosis (see this article for more).

Aging Itself

Autism and spectrum disorders

Obviously, Glutathione and MTHFR mutations don’t get along.

This is exactly right. It could be because glutathione production is lower, or it could be because glutathione use is higher.

The methylation pathway showing vitamins for MTHFR. Also glutathione and MTHFR
The methylation pathway showing B vitamin cofactors. Look to the bottom left for the little glutathione tie-in.

With MTHFR Issues Less Glutathione is Produced, Also, More Might Be Used.

The cycle above shows glutathione hanging out in the lower-left area, an offshoot of the methionine cycle. Less glutathione production is a bummer on its own, but a case can also be made for more glutathione use. When any metabolic process is out of balance, there is usually some tangible fall-out. A waste-product building up here, some damage going unmanaged there. This is no exception. Homocysteine can be notoriously high in MTHFR folks and it by itself is an inflammatory particle. Chronic inflammation depletes glutathione in even the hardiest of folks. Also, if detoxification is log-jammed somewhere, there is a corresponding build-up of reactive oxygen species.

With MTHFR mutation, glutathione production is lower and glutathione use is higher.

– Amy Neuzil – tohealthwiththat.com

Other Factors That Can Reduce Glutathione

  • Smoking. High intake of toxins, increased inflammation, and draining of the wallet. Not that the last bit has anything to do with glutathione, but still. Smokers are often the subjects in glutathione research because we can safely assume their levels are depleted.
  • Chronic Inflammation of any type.
  • Antacid use, medications for reflux, or poor digestion in aging. (Anything that interferes with protein absorption because you need amino acids from protein to make glutathione.)
  • Chronic Disease of any type.
  • Aging
  • High toxin exposure from pollution, heavy metals in the workplace, etc…
  • SNPs directly related to glutathione synthesis – including GSTM1, GSTP1, and GSTT1.

Boost Your Glutathione Naturally

Glutathione is generally not very bioavailable when you take it orally, because it’s a try-peptide. A try-peptide is essentially a tiny protein with three amino acids that will just break down like any other protein you eat. In spite of this, there are some very effective ways to boost your levels (see this review article for links to research references for all of these factors).

Boost glutathione naturally - glutathione and MTHFR
Boost glutathione naturally!
  • Liposomal glutathione – this is a drug-dosing method that helps to boost absorption in difficult scenarios. Research shows this form does absorb and impact body stores of glutathione. This is, however, reflected in the price of the product.
  • NAC – N-Acetylcysteine is a supplement you can find in even the most basic of health food stores that delivers cysteine, the rate-limiting step in glutathione production. It should be taken on an empty stomach so as to not have to compete with other proteins you are eating at that moment. NAC is gaining popularity for use in conventional medicines, especially to treat damaged livers.
  • Whey protein – whey protein, which is also widely available, is a great source of cysteine and can boost your glutathione production in an easy and cost-effective way. This is a dairy product, so it may not be appropriate in dairy sensitivities.
  • Omega 3 Fatty Acids – by dint of decreasing inflammation, these good fats help to boost available glutathione.
  • Other Antioxidants – Vitamin C, vitamin E, and Alpha-lipoic acid have all been shown to increase the available glutathione levels – presumably by taking some of the burdens off of the system in their own action as antioxidants.
  • B vitamins – specifically riboflavin (which you’ll notice in the picture above is actually a cofactor in glutathione synthesis). Also, Folate, B12, and B5 have been shown to boost glutathione. In any event, you should be taking the B vitamins together, and if you’re unclear about why read this article.
  • Sulfur-rich fruits and veggies – In theory, because cysteine is a sulfur-containing amino acid. Also, in a quirky twist of near-inconceivable coincidence, these happen to be high folate foods as well. Think Asparagus, avocado, spinach, mango, and green beans. For more high-folate foods, read here.
  • Selenium – this trace mineral is often deficient in our western diet and is crucial to glutathione production. You can get your daily dose from three Brazil nuts.
  • Broccoli and other Brassica veggies – If there is a superfood, broccoli is it. The brassica family includes broccoli, cauliflower, kale, Brussel’s sprouts, and cabbage. They are all rich sources of sulforophane, which boosts glutathione along with doing a host of other amazing health things. For best results eat the vegetable raw or lightly steamed, don’t store them in the freezer or buy frozen varieties, and a tad of powdered mustard seed during heating can boost the sulforophane content.
  • Other things – turmeric, which is a potent anti-inflammatory, and green tea, a potent anti-oxidant, have both been shown to increase glutathione levels. Also, rosemary, Ginkgo biloba, milk thistle, and fresh fruit and vegetable juices have shown some impact.
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