Squalene

Squalene is a compound found in Olive Oil and in high amounts in shark oil. It was touted as the reason sharks don't get cancer, until it was found that sharks can get cancer. Squalene however, remains an anti-cancer compound, is fairly healthy, and benefits cholesterol levels.

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Squalane is a nutritional compound found mostly in Olive Oil and shark oil, and to a lesser extent in wheat germ and rice bran. It can be consumed at high levels through the diet alone if consideration is paid, although supplementation can also help.

It helps protect the body against cancer and the effects of aging, and is generally well tolerated and safe.

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Things to Note

Squalene is non-stimulatory

A typical preventative dose to alleviate cancer risk would be in the range of 300mg a day, to mimic the dosages found in the mediterranean diet.

Dosages above this are well-tolerated.


Table of Contents:


Edit1. Structure and Sources

Squalene is a Triterpenoid compound[1] that is synthesized in vivo by human livers as a precursor to cholesterol synthesis. Like many terpene compounds, squalene is fat-soluble.[2] Like cholesterol, it is secreted through the skin[3] and is important in the Skin Surface Lipid (SSL) film that protects the body from the external environment.[4]

It is widespread in nature, but most commonly found in Olive Oil, Shark Oil, Wheat Germ, and Rice Bran.[2] The squalene content of olive oil is variable between 3.6-9.6mg per gram of extra virgin olive oil.[5][6] The squalene content appears to be unaffected by heat processing.[7]

Shark liver oil appears to be 40% Squalene by weight.[8][2] 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.[2]


Edit2. 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.[9] Due to squalene synthesis being downstream of HMG-CoA, statins (HMG-CoA) can inhibit in vivo squalene production.[10]

After synthesis (in the skin and liver), it is either secreted by sebaceous glands in the skin[11] or bound to LDL and vLDL for transport.[2]

If ingested, approximately 20% of squalene is cyclized into sterols and ejected back into the gut without being effectively taken up into systemic circulation.[12][13] Despite this, approximately 60-85% of orally ingested squalene is distributed to body tissues.[14][15]


Edit3. 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[8][2] as well as possibly playing a significant role in lower cancer rates found with the Mediterranean Diet.[16][17]

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.[5] A mechanism which has been suggested to reduce cancer risk without drastically altering the normal biochemicular pathway.[2][5]

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.[5][18] 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[18] and seems to enhance the anti-carcinogenic effect of co-ingested drug treatments.[19][20] and shows synergism against cancer with oleic acid, another constituent of olive oil.[21]

Squalene, via scavenging toxic metabolites, also show some promise in alleviating chemotherapy induced side-effects; although no applied trials have been conducted.[22][23]


Edit4. 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[5], and it exhibiting antiradioactive and antioxidative properties[24] as well as shark oil being used with efficacy in treating some select skin conditions.[25]|published=2007 Apr|authors=Nowicki R, BaraƄska-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.[26] And despite squalene inducing an oxygenating effect in cells (incorporating more oxygen for cellular reactions) it exerts an overall anti-oxidative effect.[2][27]


Edit5. 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[28]) as a squalene-in-water solution stabilized with polysorbate 80; it has been proven to be effective as an adjuvant with good chemicular stability.[29][30][31]


Edit6. 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.[2][32]

References

  1. Connolly JD, Hill RA. Triterpenoids. Nat Prod Rep. (2010)
  2. Reddy LH, Couvreur P. Squalene: A natural triterpene for use in disease management and therapy. Adv Drug Deliv Rev. (2009)
  3. Nikkari T, Schreibman PH, Ahrens EH Jr. In vivo studies of sterol and squalene secretion by human skin. J Lipid Res. (1974)
  4. De Luca C, Valacchi G. Surface lipids as multifunctional mediators of skin responses to environmental stimuli. Mediators Inflamm. (2010)
  5. Newmark HL. Squalene, olive oil, and cancer risk. Review and hypothesis. Ann N Y Acad Sci. (1999)
  6. Murkovic M, et al. Analysis of minor components in olive oil. J Biochem Biophys Methods. (2004)
  7. Allouche Y, et al. How heating affects extra virgin olive oil quality indexes and chemical composition. J Agric Food Chem. (2007)
  8. Mathews J. Sharks still intrigue cancer researchers. J Natl Cancer Inst. (1992)
  9. Kelly GS. Squalene and its potential clinical uses. Altern Med Rev. (1999)
  10. Abe I, et al. Inhibitors of squalene biosynthesis and metabolism. Nat Prod Rep. (1994)
  11. Sebaceous gland lipids
  12. Tilvis RS, Miettinen TA. Absorption and metabolic fate of dietary 3H-squalene in the rat. Lipids. (1983)
  13. Strandberg TE. Sterol synthesis from biliary squalene in the jejunal mucosa of the rat in vivo. Lipids. (1983)
  14. Serum concentration and metabolism of cholesterol during rapeseed oil and squalene feeding
  15. Gylling H, Miettinen TA. Postabsorptive metabolism of dietary squalene. Atherosclerosis. (1994)
  16. Owen RW, et al. Olives and olive oil in cancer prevention. Eur J Cancer Prev. (2004)
  17. Waterman E, Lockwood B. Active components and clinical applications of olive oil. Altern Med Rev. (2007)
  18. Smith TJ. Squalene: potential chemopreventive agent. Expert Opin Investig Drugs. (2000)
  19. Nakagawa M, et al. Potentiation by squalene of the cytotoxicity of anticancer agents against cultured mammalian cells and murine tumor. Jpn J Cancer Res. (1985)
  20. Pimm MV, Baldwin RW, Lederer E. Suppression of an ascitic rat hepatoma with cord factor and Nocardia cell wall skeleton in squalene emulsions. Eur J Cancer. (1980)
  21. Van Duuren BL, Goldschmidt BM. Cocarcinogenic and tumor-promoting agents in tobacco carcinogenesis. J Natl Cancer Inst. (1976)
  22. Attenuation of cyclophosphamide induced toxicity by squalene in experimental rats
  23. Senthilkumar S, et al. Effect of squalene on cyclophosphamide-induced toxicity. Clin Chim Acta. (2006)
  24. Hashim YZ, et al. Components of olive oil and chemoprevention of colorectal cancer. Nutr Rev. (2005)
  25. [Shark liver oil as a supporting therapy in atopic dermatitis
  26. Buddhan S, et al. Protective effect of dietary squalene supplementation on mitochondrial function in liver of aged rats. Prostaglandins Leukot Essent Fatty Acids. (2007)
  27. Sabeena Farvin KH, et al. Effect of squalene on tissue defense system in isoproterenol-induced myocardial infarction in rats. Pharmacol Res. (2004)
  28. Challenges facing adjuvants for cancer immunotherapy
  29. Safety and Immunogenicity of a Genetically Engineered Immunodeficiency Virus Vaccine
  30. Allison AC, Byars NE. An adjuvant formulation that selectively elicits the formation of antibodies of protective isotypes and of cell-mediated immunity. J Immunol Methods. (1986)
  31. Edelman R. Vaccine adjuvants. Rev Infect Dis. (1980)
  32. Sotiroudis TG, Kyrtopoulos SA. Anticarcinogenic compounds of olive oil and related biomarkers. Eur J Nutr. (2008)

(Common misspellings for Squalene include squaline, scalene, sqalene, squalen)

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