Glutathione Injections for Skin Lightening? A Waste of Money? Part 2

This is Part 2 of the “Glutathione Injections for Skin Lightening? Effective or Waste of Money?” discussion.

Glutathione Injections for Skin Lightening

Glutathione Injections are believed to lighten skin by many people.  The goal of this discussion is to understand whether Glutathione Injections for Skin lightening is a waste of money.  While the hype and user enthusiasm is high, there are no scientific studies which validate this assertion as being completely true.  That being said, many people swear by them.  The skin lightening protocol for Glutathione is as follows: 600-1200 mg of Glutathione with Vitamin C is administered intravenously 2-3 times per week, for a period of 3 months.  For the darkest individuals, the time necessary to lighten the skin color will take from 6 -12 months or longer.

 

Reportedly, over this period of time, a lightening of skin color 1-2 on the Fitzpatrick scale can occur.

 

The injections are very expensive.  A price of $200-400 is typical, but in major markets it may exceed $500 for each injection session.  Because this is not economical for the average person, some have obtained the Glutathione and Vitamin C vials from overseas vendors and have administered the injections to themselves.  Doing it this way lowers the total cost down to about $150 or less for a 5-week supply.  This is less than one-half or equal to the cost of having one injection done in a clinical or med spa setting.

Obviously, the average person is not trained to perform venipuncture or injections.  Without the proper training and experience in administering IV medications, the opportunity for a serious complication is present.  They can range from hematomas and bruising to air embolus (air in the veins which travel to the heart and lungs) to sepsis (blood infection) the most severe infection, including deadly those which travel to the heart and heart valves (Endocarditis).

It is doubtful that most people who administer Glutathione to themselves run into serious complications with deadly consequences, but people need to understand the potential risks when embarking on this endeavor.  It is not something I would recommend or encourage.

Do Glutathione Injections work? Or the other delivery options?

It depends on who you ask.  As I have stated, many swear by it.  Celebrities who have undergone a lightening of their skin aren’t discussing it, from which positive inferences can be drawn.  Unless countries, like the Philippines have banned it, these injections tend to be not only accessible and reasonably affordable for many people, but popular.  Popularity, however, cannot be sustained for an expensive procedure with hype alone.  There must be compelling evidence out there. Truth be told, the individuals who are undergoing Glutathione injections for skin lightening and skin brightening are likely using other methods to lighten the skin too, such as the topical creams, body scrubs, and skin lightening serum applied after micro needling treatment.

But based on scientific and theoretical perspectives, it should lighten skin.  Tyrosinase, the enzyme which synthesizes Melanin contains symmetric Copper ions in its active or catalytic site.   These Copper ions are metal ions which can change between oxidation states.

 

This is the feature that facilitates the specific substrate oxidation change and reaction converting the substrate to product by the enzyme.  Reduced Glutathione can bind the copper of tyrosinase and inhibit its function.  That is the direct mechanism it may use to alter skin color.

Also, since Glutathione conjugation is essential for the synthesis of the yellow pigment and red pigment, its presence in the melanin-producing cell steers production away from the darker brown-black melanin pigment (eumelanin) pathway towards the lighter red-yellow melanin (pheomelanin & benzothiazides) pathway.  This is the second, indirect way Glutathione functions to change skin color to a brighter hue or closer to yellow/orange.

 

What do Scientific Studies say about Glutathione and Skin Lightening?

There are only a few published studies that have evaluated the efficacy of oral, sublingual, topical, and Intravenous (parenteral) glutathione as a skin-whitening agent.

Oral Glutathione

The two trials on oral GSH. One was conducted in population of Thai medical students by Arjinpathana and Asawanonda.  Another used Filipino female subjects and was conducted by Handog et al.   The trials involved administering 500 mg per day of GSH in two divided doses.  The Handog study differed from the first study in the use of a buccal/sublingual lozenge (instead of oral capsules) in the latter study to enhance systemic absorption of glutathione.

The trials evaluated the pre-treatment and post-treatment melanin indices, using a machine (Mexameter MX 18) to evaluate skin color change quantitatively.

The randomized, placebo-controlled study by Arjinpathana and Asawanonda showed a consistent reduction in the melanin indices at all the six sites evaluated in the GSH group subjects, with a statistically-significant reduction in the melanin index over placebo at 2 body sites.

The study conducted by Handog et al. in 30 healthy Filipino women using buccal lozenges instead of capsules of GSH, reported significant reduction in melanin index at both sun-exposed and sun-protected sites in all the subjects.  There was also considerable skin lightening observed by 90% of the subjects.

Although these studies seem to conclude positive results with regard to skin lightening, the studies suffer from very low subject numbers and significant flaws in the design of the studies including short follow-up evaluation times and intervals, the absence of statistical analysis.  This does not mean the conclusions are false.  But it does suggest the results are not conclusive or reliable to make a recommendation regarding the use of Glutathione for skin lightening.

Topical Glutathione

A randomized, double-blind, placebo-controlled clinical trial by Watanabe et al., conducted in 30 healthy middle-aged Filipino women was also conducted.  This study used a split-face model where topical GSSG 2% lotion was applied to one side of the face twice daily for 10 weeks.  The results showed temporary skin whitening that was statistically significant.  There was a clear reduction of skin melanin index compared to placebo. While promising, the results have to be interpreted with caution owing to limitations in the study design.  And even if the evidence is to be believed, the results are only temporary.

Glutathione Suppositories and Inhaled Glutathione

There are no studies I can find that reveal or suggest efficacy with these types of delivery method.  It seems likely or at least possible that the results would mimic those of buccal/sublingual administration.

 

IV Glutathione Injections

Zubair et al. studied the efficacy and safety of IV GSH for skin tone lightening in 25 subjects.  The patients were from Pakistani.  In this study, subjects were given 1,200 mg given IV twice a week for 6 weeks in the treatment group versus normal saline in control group.  There is no standard dosage for IV Glutathione for skin lightening.  When it is administered by a medical or beauty spa, the dose is simply random and without scientific basis.  It typically involves 600 mg to 1200 mg IV per treatment session.  This arbitrary dose for skin-lightening may have its basis in the fact that ampoules containing Glutathione for Cisplatin adjunctive treatment come in those doses.  The results of the Zubair study did not prove efficacy for IV glutathione as an effective or lasting treatment for skin tone lightening.  And like the other studies there were several limitations complicating any meaningful conclusion.  First being the minute sample size. Second, being the short period of follow up.  Med spas providing these treatments commonly tell patients that 3 to 6 months are needed to appreciate the change in skin color or tone.  Third, the use of a visual scale rather than analysis by a computer for the melanin index is inherently flawed because of observer bias.   Finally, one major adverse event was reported in the IV GSH treated group.  Interestingly, it appeared to be “liver dysfunction”, which was neither qualified nor quantified.  This is surprising since IV Glutathione is a recognized therapy for Liver disease.

Conclusions

The available studies concerning the ability of Glutathione injections or other preparations to effect meaningful skin color changes are severely lacking.  The anecdotal evidence from what we believe to be the method of choice for certain celebrities who have clearly lightened their skin would suggest there can be benefit.  But like the insufficient evidence provided by the actual studies, we cannot know how they achieved skin lightening.   So, the issue as to whether or not Glutathione Injection of some other form, Glutathione lotion, Glutathione soap or Glutathione serum is worth the trouble.

Although the injections, oral and topical versions are being used heavily worldwide and in the US.  It appears not to have caused bad reactions or toxicity in most people.  The Philippine version of FDA and the US FDA caution against use of OFF-LABEL Glutathione IV injections because there are reports of bad reactions including severe allergic reactions (Stevens-Johnson and Toxic Epidermal Necrolysis) which can be potentially deadly emergencies or can cause severe kidney and thyroid dysfunction.  Med Spas and Beauty Spas know this, and they rarely mention the limitations of the science or disclose of the potential serious health consequences.  They hide behind Glutathione as “Wellness” therapy, more so than a skin-lightening therapy. And to their credit, an infusion of Glutathione, along with Vitamin C and B12 and other factors probably will make you feel good.  The DIY Youtubers who show you how to administer the IV Glutathione treatment yourself uniformly give a Disclaimer, because they are smart!   They understand there are risks. One has to evaluate for herself or himself whether the pursuit of lightening your skin with a method never proven to do it conclusively is worth losing 60% of your skin or ruining your kidneys or thyroid gland.  The risk is worth it if you are fighting cancer and Cisplatin is being used in your chemo.

Not sure if skin lightening is worth it?

As there are LESS EXPENSIVE, SAFER and much easier ways to achieve this goal, with little of the risks.  Visit Skinsurrection website,  Skinsurrection on Twitter,  Skinsurrection on Facebook or IG for some additional information and options.

Disclosure: I have used glutathione soaps and I did not find a lightening effect, but I did find a clarification effect of my skin, which I attribute to the soap.  I have used Glutathione serum after microneedling, and I believe it improved the quality of my skin and lightened.  The rational is that micro needling allows the Glutathione to enter the parts of the skin structure which can utilize it. The serum also contains several other compounds which lighten as well, so the entire contribution of the Glutathione alone cannot be judged.