Glutathione (GSH) is a tripeptide compound containing a thiol group, composed of glutamic acid, cysteine and glycine. Among them, cysteine is the rate-limiting substance for the production of glutathione. Supplementing sufficient cysteine can help increase the body’s glutathione.
Glutathione has important physiological activities in the human body, such as activating the REDOX system, activating sulfhydryl enzymes, and detoxification.
It is widely distributed in various organs of the human body and mainly plays a role in maintaining the biological functions of cells and protecting the integrity of cell membranes.
It is clinically applied in the treatment and adjuvant therapy of various diseases, including chemotherapy patients, radiotherapy patients, various hypoxemia, liver diseases and drug toxicity, etc.
Glutathione is an important antioxidant in cells.
During the oxidative phosphorylation process that occurs within the mitochondria of cells, the respiratory chain of ATP production leaks electrons, forming free radicals (ROS).
There are self-contained antioxidants within cells, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT).
Glutathione is constantly reoxidized and reduced within cells. Reduced glutathione (GSH) is converted into oxidized glutathione (GSSG) after exerting antioxidant effects within cells.
GSH is oxidized under the enzymatic action of glutathione peroxidase (GPx), and at the same time neutralizes the free radical H2O2 to form harmless water and oxygen molecules.
Under the action of glutathione reductase (GR), GSSG is rapidly reduced to GSH. The ratio of GSH/GSSG in cells indicates the oxidative stress state of the cells.
Due to the cytotoxicity of excessive GSSG, the GSSG that cannot be rapidly reduced is sent out of the cells, resulting in the reduction of glutathione within the cells. Increasing the reduced glutathione within cells helps reduce oxidative stress.
Oxidative stress is the result of an imbalance between the production and clearance of oxygen free radicals within cells, leading to human aging, metabolic diseases, autoimmune system disorders, and mental health issues, among others.
Glutathione works in synergy with other antioxidants to achieve antioxidant effects. For instance, vitamin E neutralizes lipid oxides, and the oxidized vitamin E reduced by vitamin C. Glutathione then reduces and oxidizes vitamin C, allowing vitamin C and vitamin E to recycled and produce antioxidant effects.
Although increasing vitamin C and vitamin E cannot directly increase GSH, they can share the antioxidant effect of glutathione, increase the ratio of GSH to GSSG, and achieve the effect of reducing oxidative stress.
The following text introduces whether oral glutathione effective, how effective its on commonly used whitening products, and what benefits supplementing the precursors of glutathione can bring, etc.
Supplement glutathione directly
Although glutathione is widely present in cells, the effect of oral administration of glutathione is not ideal.
Both the liver and cells have gamma-glutamyl transpeptidase (GGT). GGT can degrade glutathione. GGT degrades glutathione outside the cells, providing a substrate (cysteine) for the production of reduced glutathione inside the cells.
Therefore, whether glutathione administered orally or by injection, its inevitable that it will “eliminated” by GGT outside the cells. Not many GSH survived.
Oral GSH is more likely to be hydrolyzed in the intestines. As early as 1992, clinical studies had found that taking 3g of glutathione orally at one time could not increase the level of glutathione in the body.
If a single dose doesn’t work, so what if you take it every day?
In 2011, a double-blind control group test conducted to determine whether oral glutathione could increase the glutathione concentration in cells. Forty healthy subjects supplemented with 500mg x2 of glutathione every day for four consecutive weeks. The results showed that after the trial period, oxidative stress did not improve in the subjects, and neither reduced glutathione nor oxidized glutathione changed in the subjects’ bodies. The conclusion of the study is that oral glutathione has little effect on healthy adults.
If it doesn’t work for four weeks, what about six months?
A double-blind control group clinical study published in 2015 involved 61 healthy subjects who divided into 3 groups for the trial. The two intervention groups respectively orally supplemented with 250mg or 1g of glutathione every day for 6 consecutive months.
The results showed that supplementing 250mg daily did not cause any change in glutathione levels in the blood and cells during the trial period, while supplementing 1g daily could increase the levels of glutathione in the blood and cells.
It is worth noting that even though it is 1g per day, oral glutathione does not seem to have reached saturation after six months of supplementation, indicating that the effect of glutathione supplementation is not only proportional to the duration of supplementation, but also may take a relatively long time to develop.
In addition to direct oral administration of the common dosage form of glutathione, there are also special dosage forms. A cross-clinical study published in 2015 compared oral glutathione, oral NAC, and sublingual administration of glutathione. It found that although NAC better than oral glutathione, sublingual administration was more effective in increasing glutathione levels than both NAC and oral glutathione.
The study also tested the vitamin E levels of the subjects after the trial to evaluate the antioxidant effect of the subjects after the intervention. It found that sublingual glutathione could increase the vitamin E level, proving the antioxidant effect of the trial.
Changing the dosage form of glutathione can also enhance intestinal absorption. Among them, liposomes have frequently used as carriers for water-soluble nutrients in recent years, which can reduce the destruction of nutrients by gastric acid and increase cellular absorption.
A pilot clinical study published in 2018 found that 12 healthy subjects supplemented with 500mg and 1g of liposomal glutathione respectively every day.
It discovered that both doses of liposomal glutathione could effectively absorbed and increase the levels of glutathione in the blood and cells, reducing oxidative stress in the body.
After supplementation for 2 weeks, glutathione in cells and plasma could increased by 25% and 28% respectively, and the ratio of GSH/GSSG also increased by 20%.
Therefore, oral glutathione, if in the common dosage form, has a relatively low efficiency, requires a larger dose and a longer duration, but it can still be effective.
If a dosage form that is more easily absorbed is used, both absorption and effect will be better.
whitening effect of glutathione
Many people are concerned about whether glutathione can whiten the skin.
A meta-analysis published in 2019, which included five clinical studies, found that glutathione can improve melanin indicators in uncovered skin, but its of no help to skin that has not been exposed to the sun.
So glutathione does have a certain effect on whitening related to tanning.
Specifically, it can seen from clinical research. A double-blind control group clinical study published in 2012 involved 60 subjects. The intervention group took 500mg of oral glutathione every day.
After 4 weeks, the melanin index of the intervention group significantly decreased. The conclusion of the study was that oral glutathione could have a whitening effect on some subjects.
Is glutathione injection more effective than oral administration?
The control group clinical study published in 2016 involved 32 female subjects aged 25 to 47 who completed the trial. The intervention group received intravenous infusion of glutathione (1.2g) and vitamin C twice a week for 6 consecutive weeks.
After the trial period, 37.5% of the subjects in the intervention group showed significant improvement, and 18.7% of the subjects showed improvement but were not superior to the control group. After discontinuing glutathione, the whitening effect gradually disappeared. When followed up six months later, only one subject was still able to maintain the whitening effect.
It is worth noting that among the subjects (50 subjects registered), 8 developed liver dysfunction after receiving glutathione intervention and had to stop continuing the trial. Intravenous administration of glutathione is not safe.
A systematic analysis published in South Africa in 2016 concluded that long-term intravenous administration of glutathione for whitening purposes may not be safe, including increasing the risk of skin cancer. Its recommended that regulatory authorities assess the relevant risks as soon as possible to protect consumers.
A literature review published in 2020 included three clinical studies. One of them suggested that glutathione could not whiten the skin, while the other two clinical studies proved that glutathione only had a whitening effect on certain age groups and local skin.
The conclusion of the research is that glutathione has insufficient whitening effect, only whitening certain parts of the body’s skin, and the effect is not long-lasting.
So glutathione has a certain whitening effect on melanin caused by ultraviolet rays, but it has no effect on people with naturally dark skin. Moreover, even if there is an effect, it is only a local one. Once the use of glutathione is stopped, the effect will disappear.
Glutathione precursors and other nutrients
NAC (N-acetylcysteine) is an effective method for supplementing glutathione.
After oral administration of NAC, NAC is absorbed through the intestinal tract and metabolized in the liver to produce cysteine.
Cysteine is the rate-limiting substrate of glutathione. Unless liver function is impaired, supplementing NAC can effectively increase the level of glutathione in the body.
Excessive exercise can cause oxidative stress to body and reduce level of glutathione in it
A double-blind controlled clinical study published in 2018 divided the subjects into three groups according to the glutathione levels in their bodies: high-level, medium-level and low-level glutathione groups.
The subjects supplemented with 600mg x 2 of NAC every day for 30 consecutive days. After the trial period, it found that NAC could increase glutathione.
However, it only had a significant enhancing effect on the subjects in the low-level glutathione group.
The conclusion of the study is that NAC can increase the glutathione level in the population lacking glutathione, achieving the effect of reducing oxidative stress.
paracetamol is probably the most widely used OTC drug. We have colds, headaches, abdominal pains, toothaches… Basically, everyone uses paracetamol, and some people even use it for years on end.
But even doses of paracetamol that considered safe can put pressure on liver
In a double-blind control group clinical study in 2018,
healthy subjects used 1g x 4 paracetamol daily for 4 consecutive days. It found that the glutathione levels in the subjects’ bodies significantly reduced,
but supplementation with NAC could maintain the glutathione levels of the subjects unchanged.
In a clinical study conducted in 2005, after wrist strength exercises,
the intervention group supplemented with NAC(150mg/kg body weight), while the control group only had normal saline.
After repeating the wrist strength test, the fatigue of the NAC intervention group delayed by 30%,
the oxidation of glutathione also reduced, and the performance of the wrist strength test improved by 15%.
The conclusion of the study is that NAC improves athletic performance by enhancing glutathione homeostasis and delaying muscle fatigue.
In addition to glutathione precursors, supplementing NAD+ precursors can also increase glutathione levels
A clinical study of the control group in 2020 found that supplementing NR with the premise of NAD+ could increase the glutathione level of the subjects.
This trial involved two groups of subjects, namely young people and the older people.
It found that the oxidative stress of the older people higher and the level of glutathione lower.
After supplementing NR, the NAD levels of young people and the older people significantly increased,
but only the glutathione of the older people increased and only the oxidative stress of the older people significantly decreased. It was of little help to young people.
The conclusion of the study is that NR may only be helpful to people lacking antioxidants.
Clinical research has found that drinking four cups of green tea every day for eight consecutive weeks can increase the level of antioxidants in the blood and the level of glutathione in the blood.
Supplementing lipoic acid, selenium and Silymarin can all increase the level of glutathione in the body.
Improving the quality of diet can increase glutathione levels
Adding whole foods, such as vegetables and fruits, can increase glutathione levels.
Among them, foods containing organic sulfur antioxidants, such as asparagus, avocados, cucumbers, beans, spinach, and papayas, have the most significant effects.
However, heating can degrade organic sulfur antioxidants,
so eating them raw or lowering the heating temperature and reducing the heating time can be helpful.
Glutathione and anti-aging
In addition to having a certain effect on whitening, glutathione can also improve skin aging.
In a double-blind control clinical trial in 2017,
the intervention group divided into a group supplemented with 250mg of reduced glutathione (GSH) daily and a group supplemented with the same dose of oxidized glutathione (GSSG).
After 12 weeks of the trial period,
It found that both GSH and GSSG could improve the skin condition of the intervention group. Compared with the control group, all subjects had fewer dark spots caused by ultraviolet rays.
Some subjects had fewer skin wrinkles and increased elasticity after glutathione supplementation.
HIV patients may experience premature aging, and the results include aging conditions such as cognitive decline even among young people.
A clinical study published in 2020 found that HIV patients supplemented glutathione precursors for 12 consecutive weeks:
NAC and glycine. As a result, after the trial period,
the glutathione level of the subjects increased and the symptoms of cognitive decline improved.
A clinical study just published in 2021 May offer significant insights for future anti-aging research.
The subjects of this trial were genuine older people. Eight subjects aged 71 to 80 years old supplemented with 100mg of NAC and glycine per kilogram of body weight every day for 24 consecutive weeks. The results completely exceeded expectations.
The study compared the GSH levels of the subjects and the young control group and found that the GSH of the older people subjects was 76% lower than that of the young people,
while the oxidative stress state was 318% (F2-isoprostane) to 845% (TBARS) higher.
After supplementing NAC and glycine,
the intracellular glutathione level of the subjects increased by 200%, and oxidative stress decreased by 75%.
The inflammatory cytokines and indicators including IL-6, TNF-A and CRPIL-6 in the older people were higher than those in young people. Among them, IL-6 was 934% higher. After supplementing NAC and glycine,
all inflammatory cytokines decreased, and IL-6, TNF-A and CRP decreased by 77%, 57% and 49% respectively.
The cognitive function of the older people subjects improved significantly.
After the trial period, the cognitive score of the older people subjects increased by 9.4%,
which was the same as that of the young control group.
The BNDF increased by 54%, and there was no difference after the increase among the young subjects.
The average language ability increased by 21.1%, and there was no significant difference after the improvement in the young control group.
The walking speed increased by 50%, and there was no difference after the increase in the young control group.
Wrist strength increased by 11%, but it was still 24% lower than that of the young control group after the increase.
The waist circumference of the older people subjects was 12cm wider than that of the young control group, and it decreased by 4cm after the test period.
Fasting blood glucose decreased by 10%, and there was no difference after the reduction in the young control group. Insulin resistance HOMA-IR improved by 58%, but was still 176% higher than that of the younger control group.
Despite high doses of NAC and glycine, the liver function indicators such as AST,
ALT and creatinine of the subjects did not increase, indicating that liver function not affected.
However, after stopping the supplementation of NAC and glycine, all the improvement results basically disappeared.
The anti-aging effect of supplementing glutathione precursors can described as “astonishing”,
outperformed by all the clinical trial results of NAD+ precursors I have seen, including NR and NMN.
The samples of these clinical studies are not large and cannot over-interpreted. More and larger clinical studies needed for further verification, but the results indeed exciting.
Summary
Glutathione is an important antioxidant in body and has a significant effect on improving physical health
- 1. Oral administration of the common dosage form of glutathione is not very effective. However, if a higher dose is used every day consistently, there will be certain effects, but the effects will disappear after the use is stopped.
- 2. Glutathione has a certain whitening effect, but it only has a local and temporary effect on melanin caused by ultraviolet rays.
- 3. Glutathione in easily absorbed dosage forms can improve absorption and antioxidant effects.
- 4. NAC is the precursor of glutathione and may be a nutrient with a relatively high cost-effectiveness and good effect in supplementing glutathione.
- 5. Other ways to supplement glutathione include increasing the intake of fruits and vegetables rich in organic sulfide antioxidants, such as green tea, lipoic acid, selenium and silymarin.
- 6. Although adding other antioxidants such as vitamin C and E cannot directly increase glutathione, they can share the antioxidant effect and reduce the oxidative loss of glutathione.
- 7. Supplementing with glutathione precursors: NAC and glycine may be helpful in combating aging and related metabolic indicators.
