Glutathione Skin Whitening: Facts and Fiction



Skin lightening has a controversial background. Ideas equating skin lightness with desirability, beauty and even class/caste are prevalent in some cultures. Shadeism (or colorism) is a term used to describe discrimination based on skin tone within a community, with lightness being perceived as more desirable. The marketing of skin lightening products is widespread, as is their use. Worldwide, this is a billion-dollar industry, one with a lot of critics. I’m not going to comment on the appropriateness of skin lightening, the social context, or the ethical issues these products present.

I’ve never recommended or endorsed the use any particular skin lightening product. But if given a question about glutathione from a patient, I would first seek to understand their rationale – is it simply to lighten one’s complexion? Or are there other skin issues of concern? I’d then turn to the medical literature, understanding the scientific evidence, the risks and the unanswered questions. I’d also look at costs to help the patient evaluate the value-for-money. It should be acknowledged that a lightening product that is safe and effective could be significantly better for consumers than the widely marketed creams and lotions that are the more traditional approaches to lightening.


Aggressive media campaigns about its exaggerated effects as a “skin lightening” agent and  over-the-counter availability of this drug have resulted in consumption of improper doses and schedules. These consumers, as well as dermatologists who prescribe oral glutathione for general skin lightening or as an adjuvant for disorders of hyperpigmentation, are often oblivious about its efficacy, dosing and adverse effects. Dermatologists frequently encounter patients who are inclined to self-medicate with glutathione, enticed by the manufacturers’ claims.



Glutathione (γ-glutamyl-cysteinylglycine) is a small, lowmolecular weight, water-soluble thiol-tripeptide formed by three amino acids (glutamate, cysteine and glycine). Glutathione is an antioxidant that is naturally synthesized in the body. It is involved with numerous biochemical pathways and may have some role in different diseases.

Glutathione exists in two interconvertible forms, reduced glutathione (GSH) and oxidized glutathione (GSSG). GSH is the predominant intracellular form, which acts as a strong antioxidant and defends against toxic compounds and xenobiotics. In this process, GSH is constantly oxidized to GSSG by the enzyme glutathione peroxidase. To maintain the intracellular redox balance, GSH is replenished through the reduction of GSSG by glutathione reductase enzyme.

Extensive research in various specialties has shown that many human diseases are associated with low glutathione levels. These conditions and causes include emphysema, asthma, allergic disorders, drug toxicity, metabolic disorders, cancer, chemotherapy and human immunodeficiency virus-acquired immune deficiency syndrome, among others.


Melanin in human skin is a polymer of various indole compounds synthesized from L-tyrosine. With tyrosinase being the rate limiting enzyme. The ratio of the two different types of melanin found in skin, black-brown colored eumelanin and yellow-red pheomelanin, determines the skin colour. An increased proportion of pheomelanin is associated with lighter skin colour.

Exposure to ultraviolet radiation is the most important factor that causes undesirable hyperpigmentation.  The crucial cellular event is enhanced tyrosinase activity. Exposure to ultraviolet radiation results in generation of excessive amounts of reactive oxygen and nitrogen species within the cells.  Oral antioxidants partially reduce melanogenesis by suppressing these free radicals.

The role of glutathione as a skin-lightening agent was an accidental discovery when skin lightening was noticed as a side effect of large doses of glutathione used to combat side effects of chemotherapy.

Proposed mechanisms of action of Glutathione

(a) Direct inactivation of the enzyme tyrosinase by binding with the copper-containing active site of the enzyme.

(b) Mediating the switch mechanism from eumelanin to phaeomelanin production.

(c) Quenching of free radicals and peroxides that contribute to tyrosinase activation and melanin formation.

  1. d) Modulation of depigmenting abilities of melanocytotoxic agents.

Glutathione has potent antioxidant properties. The free radical scavenging effect of glutathione blocks the induction of tyrosinase activity caused by peroxides. Glutathione has been shown to scavenge ultraviolet radiation induced reactive oxygen species generated in epidermal cells.

Natural dietary sources of glutathione

Fresh fruits, vegetables, and nuts are natural sources of glutathione. Tomatoes, avocados, oranges, walnuts and asparagus are some of the most common edibles that help to increase levels of glutathione in the body. Whey protein is another rich source of glutathione and has been used to enhance systemic glutathione levels in cystic fibrosis.


Glutathione is primarily available as oral formulations (pills, solutions, sublingual tablets, syrups and sprays) and parenteral formulations (intravenous and intramuscular). It has been administered by intranasal and intrabronchial routes as well. The three major routes of administration used for skin lightening are topical (creams, face washes), oral (capsules and sublingual/buccal tablets) and intravenous injections.

Topical glutathione

Glutathione is commercially available as face washes and creams. A randomized, double-blind, placebo-controlled clinical trial conducted in 30 healthy Filipino women aged 30–50 years has provided some evidence favouring the efficacy of topical 2% GSSG lotion in temporary skin lightening. Patients were randomized to apply glutathione as 2% GSSG lotion and a placebo lotion in a split-face protocol, twice daily for ten weeks. GSSG was preferred over GSH, as GSH is unstable in aqueous solutions. GSSG eventually generates GSH after cutaneous absorption.The reduction of the melanin index with glutathione was statistically significant when compared to placebo.



“Reduced Glutathione( GSSG) in face lotion or soaps are effective to some extent. But choosing the right brand in an market flooded with cheap and fake products is challenging. Considering the High cost of quality Glutathione soaps. The value for money must be considered.”


Oral glutathione

Pharmacokinetics and metabolism of orally administered glutathione

Oral glutathione is derived from torula yeast (Candida utilis). It is marketed as a food or dietary supplement, either alone, or in combination with vitamin C, alpha lipoic acid and other antioxidants.The fate of orally administered glutathione has been studied in animal models and human volunteers. The principal site of absorption is the upper jejunum.

Circulating glutathione is primarily cleared by the kidney. After absorption into plasma, glutathione needs to be broken down into amino acids and re-synthesized intracellularly. The bioavailability of oral glutathione in humans is a controversial subject. Most studies have shown no raise in plasma levels of glutathione following oral administration. EVIDENCE 1 2  3 The inadequate absorption of glutathione in humans compared to that in rats has been attributed to a higher hepatic gamma-glutamyl transferase activity in humans. This results in increased hydrolysis of glutathione with resultant low serum levels.

In summary, human trials performed have shown that over-the-counter oral glutathione supplementation has a negligible effect on raising plasma levels in humans.

Manufacturing high dose glutathione pills is technically difficult as GSH has a very high electrostatic charge which makes processing and encapsulating higher strengths of glutathione very difficult. Addition of crystalline ascorbic acid dissipates this electrostatic charge and allows packaging of pills with up to 750 mg of the drug. However, oral formulations may have a combination of vitamin C, vitamin E, alpha-lipoic acid, N-acetyl cysteine, grape seed extract, etc. Alpha lipoic acid is a glutathione replenishing disulfide that increases whole blood and intracellular GSH levels.

Gutathione capsules

Oral glutathione is also available as sublingual tablets and solutions. While sublingual preparations contain very low doses (50–100 mg), oral suspensions and solutions have a foul sulfurous taste and need to be freshly prepared.



Dose: 20-40 mg/kg body weight per day (i.e. 1-2 grams GSH per day) divided into two doses, for skin lightening effects

Time duration required for the skin lightening effects: May become visible within four weeks; although a signifi  cant effect may need 1-3 months, 3-6 months, 6-12 months, and 2 years (or more) in medium brown skin, dark brown skin, very dark skin, and black skin, respectively

Maintenance dose: After attaining the ‘desired’ skin colour, a maintenance dose of 500mg/day for an indefinite duration has been suggested.



 “Glutathione Works as Skin Lightning agent and Lozenges Form are effective. Oral Form high doses in combination with vitamin C, vitamin E, alpha-lipoic acid, N-acetyl cysteine are effective.Cheap and non standerdized manufacturing of Plain Gtutathione capsules is ineffective.”

Intravenous glutathione

Due to the low bioavailability of oral glutathione, intravenous injections are being promoted to provide desired therapeutic levels in the blood and skin and to produce “instant” skin-lightening. Interestingly, intravenous injections of glutathione have been used for years but there is not even a single clinical trial evaluating its efficacy. Manufacturers of intravenous glutathione injections recommend a dose of 600–1200 mg for skin lightening, to be injected once to twice weekly. The duration for which they should be continued is not specified. Intravenous administration is expected to deliver 100% bioavailability of glutathione, much more compared to that achieved by oral administration. However, there are no studies to support this hypothesis. Although intravenous glutathione delivers a much higher therapeutic dose that enhances its efficacy, it also provides a narrower margin of safety due to the possibility of overdose toxicity.


I could locate no published evidence that demonstrates that intravenous glutathione is an effective skin-lightening agent. I could locate no clinical trials that have studied the injection or established that it is effective for this purpose.  Human studies in which parenteral glutathione was administered for male infertility (600 mg/day glutathione intramuscularly for two months), or given to enhance insulin secretion in people with impaired glucose tolerance, did not report any significant adverse effects. Proponents of intravenous glutathione suggest that these adverse effects may be attributed to other additives present in the glutathione injection vials and the risk is minimized if pure glutathione is used instead.

Another issue pertaining to pure and high-quality intravenous glutathione solution is the extremely high cost. The cheaper versions may be counterfeit, with the risk of life-threatening events.

Adverse effects reported with intravenous glutathione injection by the Food and Drug Administration of the Philippines

“The alarming increase in the unapproved use of glutathione administered intravenously as a skin-whitening agent at very high doses is unsafe and may result in serious consequences to the health of users. There is inadequate safety documentation on the use of high doses of glutathione administered at 600 mg to 1.2 grams once weekly and even up to twice weekly. The only approved indication of the intravenous format of glutathione is as an adjunctive treatment to reduce neurotoxicity associated with cisplatin chemotherapy.”

Adverse drug reactions resulting from the use of glutathione IV for skin whitening have been reported and include the following:
1. Reports of adverse drug reactions ranging from skin rashes to the serious and potentially fatal Steven Johnsons Syndrome and Toxic Epidermal Necrolysis.
2. Derangements in the thyroid function
3. Suspected kidney dysfunction potential resulting in kidney failure.
4. Severe abdominal pain in a patient receiving twice-weekly glutathione administered intravenously had been reported.
5. Incorrect technique in intravenous administration especially in association with administration by untrained persons can result in the following:

Introduction of harmful microorganisms that can result in serious infections including potential fatal sepsis.
Injection of air can lead to embolus which is also potentially fatal.
Unsafe use of needles (recycling, sharing) can result in the transmission of hepatitis B and even HIV.
Counterfeiting of glutathione has been reported and may lead to use of non-sterile preparations which could lead to serious infections.

Other potential adverse effects of high dose and long-term glutathione supplementation include:

Lightening of hair colour

Hypopigmented patches, especially on sun-exposed areas have been observed after 10–12 doses of intravenous injection by practitioners (unpublished observations). Their experience suggested that the patchy hypopigmentation tended to resolve after 30-40 doses due to the evolution of a uniform skin-lightening effect

Depletion of natural hepatic stores of glutathione: Hypothetically, long-term supplementation with any external synthetic compound may signal the body to stop its own production resulting in dependence on synthetic supplements.

Exacerbation of  Helicobacter pylori  associated peptic ulcers:  Helicobacter  pylori is known to feed on macrophages and neutrophils abundant at the site of inflammation caused by the ulcer. As glutathione can improve the numbers and activity of macrophages, peptic ulcers may be exacerbated.


“Based on overall mechanism of action of Glutathione in skin Whitening, Intravenous Gutathione manufactured with strict quality standards with no additive may be more efficacious than Lozenges form. Dosage and duration needs to be standardized.” 


There is very little evidence that establishes either the safety or efficacy of glutathione injections for skin lightening. Based on the limited information that exists, glutathione’s effects on skin tone are plausible, but haven’t been well established. The same can be said for safety: There’s a lack of good safety information when used for this purpose and some international reports of serious harms. Given this product appears to be prepared by naturopaths directly, ensuring the final product is sterile and of high quality is essential, but may be difficult for consumers to confirm. Given the unclear benefits, risks of harm, and the overall lack of medical need  recommend consumers think carefully before undertaking skin lightening with glutathione injections.

4 thoughts on “

  1. Vijay kumar says:

    This was quite informative … thanks

  2. Osman says:

    Thanks for this nice information

  3. Osman says:

    Thanks alot

  4. Vidya says:

    Tq a lot nice information i will go for natural home remdies.

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