Squalene

History

Squalene was first identified in 1906 by Japanese oil researcher Mitsumaru Tsujimoto. He found it in the unsaponifiable portion of kuroko-zame, a deep sea shark, though his initial formula was wrong. By 1916, using fractional vacuum distillation on various deep sea shark liver oils, he corrected the formula. The compound was most abundant in the liver oil of the Squalidae family, which inspired its name. In 1931, Karrer and Helfenstein synthesized squalene from farnesyl bromide, confirming its structure.

Role in triterpenoid synthesis

Squalene serves as a biochemical precursor to both steroids and hopanoids. For sterol synthesis, squalene monooxygenase oxidizes one terminal double bond to produce 2,3-oxidosqualene, which then undergoes enzyme-catalyzed cyclization to lanosterol. Lanosterol can be elaborated into cholesterol, ergosterol, or stigmasterol through removal of methyl groups and double-bond modifications. This biosynthetic pathway occurs in many bacteria and most eukaryotes but has not been found in Archaea.

Uses

Squalene is used in topical products for skin lubrication and in certain vaccine adjuvant formulations, though it is not itself an adjuvant. The proprietary adjuvant MF59, developed by researchers at Ciba-Geigy and Chiron in the 1990s, contains squalene and is added to influenza vaccines to stimulate immune response through production of CD4 memory cells. MF59 is an oil-in-water emulsion; its mechanism of action remains unknown, though it may affect cell behavior by inducing accumulation of neutral lipids.

The influenza vaccine FLUAD, using MF59, was approved in the US for people 65 and older starting with the 2016–2017 flu season. A 2009 meta-analysis of 64 clinical trials comparing MF59-adjuvanted influenza vaccines with non-adjuvanted vaccines found that adjuvanted vaccines were associated with slightly lower risks of chronic diseases and that neither type altered the rate of autoimmune diseases, supporting a good safety profile.

Safety

Squalene used in cosmetics is not very toxic, rarely causes skin irritation, and is unlikely to trigger allergic reactions. Both the World Health Organization and the U.S. Department of Defense have highlighted that squalene occurs naturally, including in the oils found on human fingerprints. Since 1997, over 22 million flu vaccines containing squalene have been administered in Europe without notable adverse effects. Although squalene was once suspected of causing Gulf War syndrome, that theory has been disproven, and the vaccines in question did not actually contain squalene.