Glutathione

Made of three amino acids joined together, glutathione occurs naturally inside almost all of the body's cells, where it helps guard against chemical damage and is often nicknamed the body's chief antioxidant. Its levels drop with age and under stress. Swallowing it barely survives digestion, so most direct research instead relies on an injected, intravenous, or intranasal form, alongside a separate line of work that compares glutathione already present in the body between people who have a health condition, such as Parkinson disease, and those who do not.

What it is

Three building blocks, the amino acids glutamate, cysteine and glycine, link together by an unusual chemical bond to form glutathione, a bond that shields it from being broken down by most of the body's ordinary protein-digesting enzymes. Because of this, it survives inside cells rather than being quickly dismantled, and that durability is a big part of why almost any cell you check keeps a working supply on hand.

Researchers describe its central role as neutralizing reactive, chemically unstable molecules before they can damage cells, a category of chemistry loosely called antioxidant activity, and as helping to regenerate other antioxidants, including vitamin C and vitamin E, once they have already been used up. It also plays a role in a liver detoxification pathway that helps prepare certain harmful substances for removal from the body. The amount of glutathione the body maintains on its own tends to decline with age and can be further reduced by stress, toxin exposure, and certain diseases.

How it is studied

Because glutathione taken by mouth is broken down heavily during digestion and does not raise blood levels, researchers studying its direct effects have mostly used injected, intravenous, or intranasal forms instead. A separate line of research looks at glutathione levels already present in the body, comparing people with a health condition such as Parkinson disease to people without it, rather than giving extra glutathione and observing an effect. Two small randomized trials have tested intranasal glutathione against placebo in people with Parkinson disease.

What studies report

In seven healthy volunteers given a single amount of glutathione by mouth, blood levels of glutathione, cysteine, and glutamate did not rise significantly afterward, showing that swallowed glutathione is broken down before it can meaningfully raise blood levels. [witschi-1992]
In brain tissue examined after death, glutathione levels in the substantia nigra, a brain area that degenerates in Parkinson disease, were about 40 percent lower in people who had Parkinson disease than in people without it, while nearby brain regions were not significantly different. [sian-1994]
In a small randomized trial in people with Parkinson disease, glutathione sprayed into the nose at either of two levels for three months was safe and well tolerated, with no meaningful difference in side effects compared with a placebo spray. [mischley-2015]
In a larger follow-up randomized trial, intranasal glutathione given for three months did not outperform placebo on a standard Parkinson disease symptom scale, even though the group getting the higher amount improved compared with their own starting scores; the placebo group also improved. [mischley-2017]

What is not known

How much of the lower glutathione level seen in Parkinson disease brain tissue reflects a cause of the disease, a result of it, or simply the loss of the affected brain cells themselves is not settled by this kind of after-death comparison. Because two small randomized trials of intranasal glutathione for Parkinson disease symptoms did not show a clear benefit over placebo, whether raising glutathione levels this way changes the course of the disease remains unresolved and would need larger, longer trials to answer. Whether intravenous glutathione behaves differently from the intranasal form studied in these trials, including how long it remains available in the body after injection, was not established by the sources reviewed for this profile.

Reported adverse findings

In the larger of the two intranasal glutathione trials in Parkinson disease, one participant in the higher-amount group developed cardiomyopathy, a disease of the heart muscle, during the study. [mischley-2017]

Regulatory status

Glutathione occurs naturally in food and in the body and is not itself subject to drug approval in the same way a novel compound would be, though injectable pharmaceutical glutathione products for specific medical uses do require regulatory approval in some countries. Regulators in some jurisdictions, including the Philippines, have issued public warnings specifically about high-strength intravenous glutathione marketed for cosmetic skin lightening.