Scientific Research on Squalene

Structure and Sources

Squalene is a Triterpenoid compount that is synthesized in vivo by human livers as a precursor to cholesterol synthesis. Like many terpene compounds, squalene is fat-soluble. Like cholesterol, it is secreted through the skin and is important in the Skin Surface Lipid (SSL) film that protects the body from the external environment.

It is widespread in nature, but most commonly found in Olive Oil, Shark Oil, Wheat Germ, and Rice Bran. The squalene content of olive oil is variable between 3.6-9.6mg per gram of extra virgin olive oil. The squalene content appears to be unaffected by heat processing.

Shark liver oil appears to be 40% Squalene by weight. The standard intake of squalene is 30mg per day with the Standard North American diet and up to 200-400mg a day in those who consume liberal amounts of olive oil or practitioners of the Mediterranean diet.

Metabolism and Pharmacology

Squalene is a 6-isoprenoid unit containing triterpenoid. It is produced in vivo by (1) the conversion of Acetyl-CoA into HMG-CoA, the (2) reduction of HMG-CoA into mevalonate via HMG-CoA reductase, the (3) phosphrylation and decarboxylation of mevalonate to form delta 3-isopentenyl diphosphate, which is the donor molecule for polyprenyl compounds. D3IDP then (4) adds phenyl groups to form farnesyl diphosphate, and then (5) two farnesyl diphosphate molecules undergo a reactive coupling to form a single squalene molecule. Due to squalene synthesis being downstream of HMG-CoA, statins (HMG-CoA) can inhibit in vivo squalene production.

After synthesis (in the skin and liver), it is either secreted by sebaceous glands in the skin or bound to LDL and vLDL for transport.

If ingested, approximately 20% of squalene is cyclized into sterols and ejected back into the gut without being effectively taken up into systemic circulation. Despite this, approximately 60-85% of orally ingested squalene is distributed to body tissues.

Squalene and Cancer risk

Squalane initially interested cancer researchers with the observed correlation between a high amount of squalene in shark fatty tissues and the absence of cancer in this species as well as possibly playing a significant role in lower cancer rates found with the Mediterranean Diet.

It has been theorized that the mechanism of action by which squalene exerts anti-carcinogenic effects is through decreasing farnesyl pyrophosphate levels in cells, of which prenylation of FPP is required for oncogene activation. A mechanism which has been suggested to reduce cancer risk without drastically altering the normal biochemicular pathway.

The mechanism by which Squalene has been hypothesized to act is via increasing squalene levels in the body, sending inhibition via negative feedback to the HMG-CoA enzyme, and thus creating less synthesis of FPP. This mechanism would mean protection for for breast, pancreatic, colon carcinomas, and similar tumors associated with oncogene mutations.

Beyond the main mechanisms, Squalene can also act as a free radical scavenger and seems to enhance the anti-carcinogenic effect of co-ingested drug treatments. and shows synergism against cancer with oleic acid, another constituent of olive oil.

Squalene, via scavenging toxic metabolites, also show some promise in alleviating chemotherapy induced side-effects; although no applied trials have been conducted.

Non-cancer uses of Squalene

Squalene can potentially protect the skin against oxidation and ultraviolet radiation. Its importance is illustrated by having 12% of overall bodily squalene content secreted from the skin, and it exhibiting antiradioactive and antioxidative properties as well as shark oil being used with efficacy in treating some select skin conditions.|published=2007 Apr|authors=Nowicki R, Barańska-Rybak W|journal=Pol Merkur Lekarski]

Squalene can also be seen as anti-aging due to its protection of the skin (one symptom of aging) as well as enhancing the efficacy of the mitochondria. And despite squalene inducing an oxygenating effect in cells (incorporating more oxygen for cellular reactions) it exerts an overall anti-oxidative effect.

Squalene and Medicinal sciences

Squalene is commonly used as an adjuvant (a substance employed to increase or to modulate the immune response against an antigen as a squalene-in-water solution stabilized with polysorbate 80; it has been proven to be effective as an adjuvant with good chemicular stability.

Safety Profile

Although no acute toxicity has been reported with Squalene, there is no long term evidence for squalene consumption above the doses commonly found in foods.