What is cysteamine? Does it work for melasma?

Cysteamine is a chemical present in the human body, a product of degradation of Coenzyme A.

Figure. Cysteamine

Re. “Does it work for melasma” question, we should first answer this one: do we need another active to treat melasma?

Answer: Yes. Melasma is a problem for many people with no great or satisfactory solutions.

Second. How to choose a new active?

The answer should be: add a new active if it is safer and better than what’s in the market. Even if it doesn’t help everybody, does it work for some people better than what’s available? Especially since old actives, still used, include hydroquinone, which is irritating, photosensitive and citotoxic.

Third: Does cysteamine justify its introduction to skincare? Not in my opinion, and here is why.

Cysteamine. What is it good for?

People with cystinosis lack a functioning transporter which transports cystine from the lysosome to the cytosol. This ultimately leads to buildup of cystine in lysosomes, where it crystallizes and damages cells. Cysteamine enters lysosomes and converts cystine into cysteine and cysteine-cysteamine, both of which can exit the lysosome. This is an effective solution for a very specific problem.

Concentrations of 10–4 M levels of cysteamine kill cells by apoptosis.

Cysteamine is a very potent inducer of duodenal ulcers, and a cysteamine-induced duodenal ulcers model is now used to study the antiulcer activity of drugs. Cysteamine gets to the duodenum and its cytotoxic effect depends on the generation of H2O2 in the presence of transition metals. Its ulcerogenic effect may be due to the generation of ROS, the decreasing defense activity of SOD and increasing duodenal endothelin-1 (a potent vasoconstrictor) concentration, which are all associated with decreased duodenal mucosal blood flow and causes tissue ischemia and hypoxia.

How about topical cysteamine?

The strong unpleasant odor of cysteamine has kept skincare companies away, but now there is a cysteamine out for sale, including many fragrances (listed as fragrance, hexyl cinnamal, linalool, geraniol) to distract the nose from the disagreeable odor. Advertising asserts that cysteamine is a safe and potential asset for treating resistant melasma.  Although the advert presents several theories for its action mechanism, there is no data. This is worrying because we don’t have information about possible side effects either.

My recommendation

Wait. Stay with what’s proven to be safe and effective.

Avoid cysteamine, unless used for the treatment of cystinosis. There is evidence of allergy to cysteamine in Japan, where it is used by hair stylists in permanent hair waving. Its use to produce experimental duodenal ulcers suggests it may be cytotoxic for other tissues. It’s true that cysteamine is produced in the human body, but nothing near the 5%used in the cream. Research supported by the company that sells the product (Scientis) should be taken with a pinch of salt. I would like to see more data and research on the mechanism of action of cysteamine, both in hyperpigmentation and in citotoxicity.

Advertising online can give the wrong idea to potential users. Cysteamine does not have a long history of topical use, and the publications that support its use are relatively new and include few cases. On the other hand, we have indications that it can be topically allergenic and cytotoxic for internal use. Stay with what we know.

References

Chavin W, Schlesinger W. A new series of depigmentational agents in the black goldfish. (1966) Naturwissenschaften. 53:163.

Desai S, Hartman C, Grimes P, Shah S. Topical stabilized cysteamine as a new treatment for hyperpigmentation disorders: Melasma, post-inflammatory hyperpigmentation, and lentigines. J Drugs Dermatol. 2021;20(12):1276-1279. doi:10.36849/jdd.6367

Dos Santos-Neto AG, da Silva ÍCV, Melo CR, Santana AAM, de Albuquerque-Junior RLC. Is cysteamine use effective in the treatment of melasma? A systematic review and meta-analysis. Dermatol Ther. 2022 Dec;35(12):e15961. doi: 10.1111/dth.15961. Epub 2022 Nov 2. PMID: 36285354.

Frenk E, Pathak MA, Szabó G, Fitzpatrick TB. Selective action of mercaptoethylamines on melanocytes in mammalian skin: experimental de-pigmentation. (1968) Arch Dermatol. 97:465-477.

Jeitner TM, Lawrence DA. Mechanisms for the cytotoxicity of cysteamine. Toxicol Sci. 2001 Sep;63(1):57-64. doi: 10.1093/toxsci/63.1.57. PMID: 11509744.

Karrabi M, Mansournia MA, Sharestanaki E, Abdollahnejad Y, Sahebkar M. Clinical evaluation of efficacy and tolerability of cysteamine 5% cream in comparison with tranexamic acid mesotherapy in subjects with melasma: a single-blind, randomized clinical trial study. (2020) Arch Dermatol Res. 313(7):539-547.