This article talks about Glutathione (GSH)
There are many cosmetic ingredients that have excellent properties, but are not widely used for a variety of reasons, some because the color is not very pleasant (such as tea extract), some because the smell is not pleasant enough (such as sulfur), and quite a few because it is too delicate, too easy to degrade or deteriorate, such as vitamin C, many peptides, etc. The formulators love and hate it at the same time.
1, Background of glutathione
Glutathione is a short peptide that can be naturally produced by human cells and is composed of three amino acid residues, namely glutamic acid, cystine and glycine. The structural formula is shown in Figure 1. Wheat germ is rich in glutathione.
The main functional group of glutathione is sulfhydryl (-SH), which can be oxidized into S-S-bond (disulfide bond), and S-S-S-bond is converted into sulfhydryl group by reduction. This property has a significant impact on many enzymes of the organism, especially the enzyme activity related to protein transformation, so it has a wide range of biological activities and important physiological significance.
We already know that the life activities of the human body constantly carry out oxidation and reduction reactions, and oxidation reactions will produce free radicals, too much free radicals will damage the body, but also an important factor leading to aging.
In order to remove excessive free radicals, the body has a set of antioxidant networks, which are composed of vitamins C, vitamin E, GSH, ubiquinone (Co. Q10), lipoic acid, niacinamide, etc.
The network synergy between them is shown in Figure 2.
The explanation in Figure 2 is as follows: The red arrow shows the oxidation reaction (RO●→RO), scavenging oxygen free radicals (RO●);
The green arrow indicates the antioxidant regeneration reaction.
The arrows are connected to reactions that occur directly.
(1) The RO● free radical in the cell membrane is quenched by the combination of vitamin E to form a vitamin E oxygen free radical, which can be quenched (cleared) by ascorbic acid (vitamin C) at the plasmic junction of the cell membrane.
(2) The RO● free radical in the cytoplasm is directly quenched by ascorbic acid to produce dehydroascorbic acid, which can then be converted into ascorbic acid again by glutathione (GSH).
Both α-lipoic acid and DHLA can quench oxygen free radicals directly.
DHLA itself is a strong reducing agent, which can reduce oxidized vitamin C, vitamin E and oxidized glutathione (GSSG).
If you think the above paragraph is too much of a mouthful, we can summarize it in two simple sentences: Vitamin E after clearing free radicals, becomes oxidized vitamin E, and vitamin C can make vitamin E regenerate.
After regeneration, vitamin C becomes dehydroascorbic acid, and GSH can turn dehydroascorbic acid into vitamin C, that is, vitamin C can also be regenerated by GSH.
It can be seen that if GSH is not enough, it will affect the regeneration of vitamin C, if the amount of vitamin C is not enough, it will affect the regeneration of vitamin E, if vitamin E is not enough, then the cell membrane will suffer – the so-called one glory, one loss, this is the meaning.
Glutathione plays a vital role in the body’s antioxidant system, and since antioxidants involved in a variety of processes, including aging, melanin synthesis, cell damage, and inflammation, it is not surprising that glutathione has a wide range of physiological effects, as do many other antioxidants.
For such a versatile player, the cosmetics industry is of course extremely welcome, so it has also carried out a more in-depth study from all aspects.
In fact, glutathione is probably the most studied for its protective effects on the liver, not the skin.
To inquire about the studies related to glutathione and liver protection and liver detoxification, the papers are too many to read.
In addition, it plays a role in many fields such as cardiovascular and kidney diseases.
We are concerned with the skin, so here is a brief overview of the studies on glutathione and skin.
2, The effect of glutathione on the skin
Glutathione has important effects on the skin and a variety of cells in the skin.
Telorack et al. found through mouse experiments that a low concentration of GSH was sufficient to maintain the growth of keratinocytes and wound healing.
In mice deficient in vitamin A, which is also an important antioxidant, GSH plays an important role as an antioxidant.
The higher the levels of GSH in the mice’s skin, the lower the levels of ROS (reactive oxygen species clusters).
Antioxidants and whitening are related. In an open trial in the Philippines, type VI and V women who took lozenges containing GSH for eight weeks were able to see a reduction in melanin after two weeks, with no adverse effects.
In a double-blind, randomized controlled trial in Thailand, subjects took GSH (250mg/ day) or GSSH (250mg/ day) or placebo for 12 weeks to test skin melanin index, wrinkles and other physiological indicators, and found that both the GSH group and the GSSG group had a tendency to reduce melanin and improve wrinkles. The improvement of wrinkles in GSH group was more significant.
Skin elasticity also improved in both groups. No serious adverse effects were found in the study.
(Here’s a friendly tip: one of the main ingredients in many whitening pills is GSH)
A very interesting study was done BY Chung By et al. They used in vitro cell tests and found that extracellular GSH itself did not inhibit melanin synthesis, but extracellular GSH monoethyl ester could significantly inhibit melanin synthesis.
Therefore, GSH may converted into monoethyl ester in the body and then play a role, or directly, or through other ways to play the role of whitening, it necessary to further confirm, because other studies have found that GSH can inhibit the synthesis of melanin by melanoma cells, and the results of this study need to repeated.
However, the role of GSH in scavenging free radicals, as well as the role of intracellular GSH in inhibiting melanin synthesis, well established.
GSH may also associated with allergies.
SirjeKaur et al. examined changes in iron levels and various forms of GSH in the skin of patients with allergic contact dermatitis and found that oxidized GSH (i.e., GSSG) elevated, suggesting that GSH may reduced due to scavenging free radicals produced in allergies.
Coincidentally, Chinese researcher Zhao Xinling et al. tested the anti-allergic activity of GSH in vitro, and found that GSH can anti-allergy, its effects include inhibiting hyaluronidase and inhibiting delayed allergic reactions, and its effect can be comparable to that of Pramine at a concentration of 5mg/ml, suggesting that GSH has a promising application prospect in allergic skin problems.
FaribaIraji et al. conducted a comparative study, in which tranexamic acid (i.e., thrombotic acid) + vitamin C, plus GSH or no GSH, and methyloplastic therapy (30-needle dot injection microneedles) injected into the skin 1mm, respectively, to treat the left and right face melasma, once every 2 weeks, for a total of 12 weeks, to evaluate the improvement of both sides of the melasma.
The results showed that both sides of melasma significantly improved, and the improvement effect of GSH better than that of no GSH, indicating that GSH had an enhanced effect on tranexamic acid (i.e., thrombotic acid) and vitamin C.
This may partly because in the skin of melasma, oxidative stress increased (or the increase of free radicals), and GSH has a strong antioxidant capacity, plus it is itself an endogenous substance, so it can safely and effectively help improve melasma.
The study found that GSH even had antibacterial effects. When the concentration is 50mM, pH<4.0, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and pseudomonas aeruginosa isolated from the skin can be completely inhibited, and in vitro experiments found that even when the concentration is used up to 160mM, it will not cause toxicity to murine cells.
Irradiating keratinocytes and fibroblasts with UVA can significantly reduce the amount of GSH in the cells, which further indicates that the role of UVA on aging cannot ignored.
The addition of GSH may help to reduce the aging caused by UVA, and also reminds us once again that sun protection is an important basis for anti-aging.
3, The application problem of glutathione
Glutathione is so good, but application has been a big problem. Aside from the special smell of sulfur, stability is enough to cause headaches, because as a peptide, it is naturally unstable, and it is extremely easy to decompose in water and lose its effectiveness, how to keep it effective during production, transportation, storage, is the goal of formulators.
Khan et al. first dissolved GSH in the oil phase, and then used non-ionic emulsifiers to prepare oil-in-water nanoemulsion. After 90-day stability test, glutathione could remain stable.
Duge of Jiangnan University used gelatin and gum Arabic as wall materials, and embedded glutathione in the form of water-in-oil emulsion as core material to prepare glutathione microcapsules.
Dry microcapsules have low moisture content, are easy to store and have good fluidity. Microcapsule storage is stable under low humidity conditions (relative humidity 33%, 58%),
but when relative humidity is 80%, glutathione microcapsule storage is stable.
The stability of microcapsules significantly reduced, so this technology may more suitable for making oral glutathione products that are not yet available in cosmetics.
The United States Central Pharmacy used low-moisture cyclodextrin inclusion technology to maintain glutathione activity,
and prepared a subol glutathione brightening gel, and has been clinically verified at the Air Force General Hospital, with the effect of inhibiting pigmentation.
I also carried out DPPH free radical scavenging experiment on it in the laboratory, and confirmed that it has efficient free radical scavenging ability (directly using the product test, the DPPH free radical scavenging rate is >90% when the dosage is 0.4%).
The tested product has stored for almost one year. Therefore, it can confirmed that this cyclodextrin inclusion technology can maintain the stability and activity of glutathione well.
4, Future outlook
The main problem with the application of glutathione is stability.
In aqueous solutions, GSH lost within a few days, and there no good solution to this problem,
which greatly limits the application of glutathione in cosmetic skin.
At present, there many skin care products on the market that claim to contain GSH,
but if the corresponding “preservation” technology not used, or just a symbolic addition, its stability and effect are doubtful.
In the future, it is likely to be necessary to use new preparations, such as encapsulation,
freeze-drying technology, dry and wet separation packaging technology, and so on. I suspect these goals could achieved in the next few years.
Glutathione also has a particular sulfur odor that some people may not like. In the future, it may be possible to stabilize the sulfhydryl group and avoid too strong an odor by adding some modifying groups.
It is not possible to completely eliminate the smell of sulfur because all things containing sulfur have a special smell,
from foods (such as garlic, radishes) to organic compounds containing sulfur.
Glutathione injections for whole-body whitening have become increasingly popular around the world in recent years.
But there may be some problems with that,
First, many of them carried out by non-medical institutions, which may have loopholes in health safety;
The second that the injected things not necessarily only GSH, there may other substances,
such as vitamins, grape seed extract, etc., and it not necessarily guaranteed that each substance is safe;
Third, there is a lack of research and guidance on effectiveness, safety, dosage, etc., and generally it is still in a state of disorder.
Ok, that’s all, let’s make a summary:
Glutathione is a tripeptide, has a strong antioxidant effect, is one of the core members of the antioxidant network in the body,
has a wide range of physiological activities, so it can used for anti-aging, whitening, anti-allergy, liver protection and so on.
Glutathione is more effective than tranexamic acid and vitamin C alone when used in Meplastic therapy.
A major disadvantage of glutathione is that it is unstable in aqueous solution and needs to solved with special preparations,
such as nanoemulsion or cyclodextrin inclusion.
In the future, it may necessary to solve the stability problem with the packaging technology of dry and wet separation,
encapsulation technology, lyophilization technology, molecular modification, etc. These problems expected to solved in the next few years.
Oral glutathione whitening has preliminary clinical research evidence,
there is still a lack of large-scale clinical trial evidence, but I believe that conditions allow the case may wish to eat.
The use of glutathione injections for whitening is increasing globally, but there are currently some issues, including the safety of sanitary conditions,
insufficient evidence, lack of guidelines, and even if adverse effects are rare, it is still worthy of attention.
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