Thread by @siimland

Glutathione is called the body's master antioxidant:
- protects against oxidative stress
- has anti-inflammatory effects
- supports liver detoxification

Deficient glutathione underlies the oxidative stress in aging

Here's how to make enough glutathione⬇️⬇️

Image PMID: 34439468

Glutathione is made of primarily glutamine, cysteine, and glycine, which are amino acids

Glutathione synthesis is rate-limited by glycine (PMID: 29559876)

Taking N-acetylcysteine (NAC) and glycine has been shown to increase glutathione levels (PMID: 17602868; PMID: 21795440)

A 2023 randomized clinical trial found that supplementing glycine + NAC (GlyNAC) for 16 weeks in older adults improved glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, physical function, and 7 hallmarks of aging (PMID: 35975308)

The authors claimed: "Only GlyNAC supplementation in older adults resulted in significantly improved (a) glutathione concentrations by 121% after 2 weeks, and by 164% after 16 weeks to levels not different from younger adults"

With age, you see a decrease in glutathione, and correcting glutathione deficiency with Glynac improves health status and hallmarks of aging (PMID: 21795440)

The decrease in glutathione is what underlies a lot of the higher oxidative stress and inflammation levels seen in aging

Besides higher glutathione levels, glycine also helps to combat reactive oxygen species by inhibiting NADPH oxidase (NOX), which is the main source of superoxide radicals in the body, thereby raising NADPH levels and lowering oxidative stress

PMID: 30696582

In patients with metabolic syndrome, 15 grams of glycine per day in 3 divided doses (5 grams three times daily) reduces oxidative stress and improves systolic blood pressure

PMID: 24144057

Glutathione is synthesized in the liver – the central organ of detoxification

Glycine has many liver protective effects by stimulating glucagon-like peptide 1 (GLP-1) and glucagon, which then helps to prevent liver fat storage through AMPK and cAMP

PMID: 25332814

A short pitstop about the amino acids needed for glutathione synthesis:

- glutamine you can get from protein
- cysteine you can get from protein
- glycine you can get from collagenous proteins and gelatin

Supplementing glycine and NAC is an effective way to boost glutathione

You also need several minerals for glutathione synthesis, namely selenium and sulfur

Sulfur is a glutathione precursor, whereas glutathione peroxidase is one of the main selenoproteins that regulates thyroid hormones

The sulfur amino acids (SAA) methionine and cysteine promote protein synthesis as well as glutathione synthesis

Eating a sulfur-rich diet in humans increases glutathione levels and reduces oxidative stress

PMID: 21559038
PMID: 8200071
PMID: 17617661

Some of the highest sulfur-containing foods are:
- scallops
- eggs
- meat
- seafood
- Cruciferous vegetables like broccoli and cauliflower
- red onions
- garlic
- dairy
- leeks
- peanuts

Vitamin D3 sulfate is a water-soluble form of vitamin D3 that can travel the blood more freely without needing LDL cholesterol

The precursors for that are sunlight hitting the skin and cholesterol sulfate, which requires sulfur

PMID: 4054307

List of other sulfur-containing compounds:
- Glucosamine sulfate
- Chondroitin sulfate
- Glutathione
- Cysteine and NAC
- Taurine
- Alpha-lipoic acid (ALA)
- Dimethyl Sulfoxide (DMSO)
- Methyl-sulfonyl-methane (MSM)
- S-adenosylmethionine (SAMe)
- Methionine

Moving on with selenium

Glutathione peroxidase (GPx) is a selenoenzyme that regulates thyroid hormone synthesis (PMID: 4736708)

Selenium deficiency reduces glutathione peroxidase levels (PMID: 25695036)

Selenium has detoxifying effects on several heavy metals, such as cadmium, mercury, and lead (PMID: 996880; PMID: 934997; PMID: 6683195)

The mechanisms are mediated by glutathione peroxidases and other antioxidants that help to eliminate these toxic compounds

Highest selenium-containing foods:
- Brazil nuts
- Kidney
- Tuna
- Mussels
- Halibut
- Sardines
- Shrimp

Glutathione reductase is the one that converts oxidized glutathione into its reduced form by NADPH

This conversion requires riboflavin or vitamin B2

Patients of rheumatoid arthritis with B2 deficiency show higher inflammation levels and report higher pain scores (PMID: 8976642)

Riboflavin deficiency has been associated with higher oxidative stress and low glutathione levels (PMID: 10466188; PMID: 6619991)

During riboflavin deficiency, the body might be able to make glutathione from the other precursor amino acids as a compensatory action PMID: 9875552

Highest riboflavin-containing foods:
- beef
- milk
- tofu
- salmon
- pork
- eggs

To sum it up, glutathione is one of your main antioxidant shields against aging and oxidative stress

You need glutamine, cysteine and glycine as the main precursors, but there are many other nutrients needed, such as sulfur, selenium, B2 and amino acids

If you want to learn more about glutathione then check out my books with @drjamesdinic The Collagen Cure AND The Mineral Fix for info on sulfur and selenium





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