Squalene

Squalene is a specific type of organic compound known as a triterpene. It has the chemical formula C30H50. In its pure form, it is a colorless oil. However, samples that are not pure often appear yellow. This substance is found throughout the natural world in many different forms. Most plants, fungi, and animals produce it through biological processes. It even exists within the human body. For example, about 12% of the sebum, or skin oil, in humans is made of squalene. This oil plays a vital role in lubricating and protecting the skin.

Squalene acts as a biochemical precursor in many different systems. A precursor is a starting molecule that helps build more complex substances. In many bacteria, squalene is an intermediate used to make hopanoids. In many eukaryotes, which are complex organisms, it is used to build sterols. The process for making sterols begins with a specific chemical change called oxidation. An enzyme called squalene monooxygenase acts on one of the terminal double bonds of the squalene molecule. This reaction creates a new substance called 2,3-oxidosqualene.

From there, the molecule undergoes a process called enzyme-catalyzed cyclization. This means an enzyme helps the molecule fold into a ring shape to create lanosterol. Lanosterol is a key building block for many other steroids. Through a multistep process, lanosterol can be changed into cholesterol or steroid hormones in humans. This process involves removing three methyl groups and moving a double bond. It also involves the reduction of another double bond using NADPH. In many plants, this pathway leads to the creation of stigmasterol. In many fungi, the pathway produces ergosterol.

Nature produces squalene through a process called biosynthesis. This happens when two molecules of farnesyl pyrophosphate are coupled together. This condensation process requires a specific enzyme called squalene synthase and a substance called NADPH. While nature uses these biological paths, humans have learned to produce squalene in other ways. Commercially, synthetic squalene can be prepared from a substance called geranylacetone. Scientists also use genetically engineered yeast or bacteria to grow it. This modern method is important for conservation efforts.

Historically, squalene was obtained from the liver oil of sharks. Its name comes from the shark genus known as Squalus. However, using shark oil has caused significant environmental concerns. In 2020, conservationists worried that sharks might be slaughtered to obtain squalene for COVID-19 vaccines. Because of these concerns, researchers moved toward using other sources. This shift helps protect shark populations while still providing the oil needed for medicine and industry.

Squalene is also a key ingredient in certain vaccine adjuvants. An adjuvant is a substance added to a vaccine to stimulate the immune system. While squalene is not an adjuvant by itself, it is used with surfactants in special formulations. One famous example is the MF59 adjuvant, which was developed in the 1990s. Researchers at Ciba-Geigy and Chiron originally developed it. These companies were later acquired by Novartis. Today, the influenza vaccine business of Novartis is managed by a company called Seqirus.

MF59 is used in influenza vaccines to make them more immunogenic. This means it helps the vaccine create a stronger immune response. Specifically, it helps the body produce CD4 memory cells. The FLUAD vaccine, which uses MF59, was approved in the United States for people aged 65 and older starting in the 2016–2017 season. Scientists are still studying exactly how MF59 works. They do not yet know the exact mechanism of action or which receptors it responds to. One theory is that it changes lipid metabolism by causing cells to accumulate neutral lipids.

Safety is a major topic regarding the use of squalene. Toxicology studies show that squalene has low acute toxicity in cosmetic concentrations. It is generally not a significant irritant or allergen for the skin. The World Health Organization has noted that squalene is naturally occurring in things like human fingerprints. Since 1997, over 22 million flu vaccines containing squalene have been used in Europe. These vaccines have not been linked to significant adverse events. Additionally, scientific studies have debunked attempts to link squalene to Gulf War syndrome.