The March 2021 EMM Editor’s Choice article is “Exogenous exposure to dihydroxyacetone mimics high fructose induced oxidative stress and mitochondrial dysfunction,” (https://onlinelibrary.wiley.com/doi/10.1002/em.22425) by Raj Mehta, Manoj Sonavane, Marie E. Migaud, and Natalie R. Gassman.
Dihydroxyacetone (DHA) is a simple ketone sugar behind the “browning” effect associated with sunless tanning lotions. DHA is also produced in aerosols from electronic cigarettes (e-cigarettes). As exposure to DHA increases through skin absorption in sunless tanning lotions and inhalation and absorption through mucous membranes from e-cigarettes, there has been cause for concern as DHA effects are not fully understood. Several studies have shown that DHA is cytotoxic and genotoxic, however the mechanisms for these outcomes of DHA exposure are still under investigation.
Studies have shown that the phosphorylated form of DHA, dihydroxyacetone phosphate (DHAP), is rapidly absorbed into cells and can integrate into nine different metabolic pathways. DHAP is produced from the breakdown of fructose, a sugar found in fruits and honey. A diet high in fruits causes increased DHAP production which is linked to increased DNA and RNA damage, changes in metabolic profile, and reduced mitochondrial function. Also, elevated levels of DHAP contributes to the development of insulin resistance as seen in type 2 diabetes. Given the deleterious effects of DHAP, the authors believe examination of fructose exposure may provide the much-needed insight on the cytotoxic and genotoxic effects of the parent compound DHA.
The authors state that potential exposure effects of systemic DHA could place significant stress on cellular reduction and oxidation pathways, mitochondrial function, and metabolism. Chronic, long-term DHA exposure may act similarly to high fructose diets and induce metabolic reprogramming that reduces glucose uptake, changes glucose tolerance, and alters metabolic dependence of tissues. Also, DHAP produced from DHA exposure can impair lipid metabolism, similar to fructose exposures, and contribute to increased adipose tissue content, higher body weights, blood pressures, and plasma triglyceride concentrations in exposed individuals. Such DHA exposure outcomes can possibly impact the development of chronic illnesses like insulin resistance. The authors conclude that DHA exposure can occur through use of sunless tanning products and e-cigarettes, and millimolar doses of the compound are genotoxic, cytotoxic and can induce metabolic reprogramming.