1.
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]
2.
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]
3.
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]
4.
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]
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]
5.
Squalene and Medicinal sciences
References
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- ^Nikkari T, Schreibman PH, Ahrens EH JrIn vivo studies of sterol and squalene secretion by human skinJ Lipid Res.(1974 Nov)
- ^De Luca C, Valacchi GSurface lipids as multifunctional mediators of skin responses to environmental stimuliMediators Inflamm.(2010)
- ^Newmark HLSqualene, olive oil, and cancer risk. Review and hypothesisAnn N Y Acad Sci.(1999)
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- ^Mathews JSharks still intrigue cancer researchersJ Natl Cancer Inst.(1992 Jul 1)
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- ^Abe I, Tomesch JC, Wattanasin S, Prestwich GDInhibitors of squalene biosynthesis and metabolismNat Prod Rep.(1994 Jun)
- ^Sebaceous gland lipids
- ^Tilvis RS, Miettinen TAAbsorption and metabolic fate of dietary 3H-squalene in the ratLipids.(1983 Mar)
- ^Strandberg TESterol synthesis from biliary squalene in the jejunal mucosa of the rat in vivoLipids.(1983 Aug)
- ^Serum concentration and metabolism of cholesterol during rapeseed oil and squalene feeding
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- ^Owen RW, Haubner R, Würtele G, Hull E, Spiegelhalder B, Bartsch HOlives and olive oil in cancer preventionEur J Cancer Prev.(2004 Aug)
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- ^Nakagawa M, Yamaguchi T, Fukawa H, Ogata J, Komiyama S, Akiyama S, Kuwano MPotentiation by squalene of the cytotoxicity of anticancer agents against cultured mammalian cells and murine tumorJpn J Cancer Res.(1985 Apr)
- ^Pimm MV, Baldwin RW, Lederer ESuppression of an ascitic rat hepatoma with cord factor and Nocardia cell wall skeleton in squalene emulsionsEur J Cancer.(1980 Dec)
- ^Van Duuren BL, Goldschmidt BMCocarcinogenic and tumor-promoting agents in tobacco carcinogenesisJ Natl Cancer Inst.(1976 Jun)
- ^Attenuation of cyclophosphamide induced toxicity by squalene in experimental rats
- ^Senthilkumar S, Devaki T, Manohar BM, Babu MSEffect of squalene on cyclophosphamide-induced toxicityClin Chim Acta.(2006 Feb)
- ^Hashim YZ, Eng M, Gill CI, McGlynn H, Rowland IRComponents of olive oil and chemoprevention of colorectal cancerNutr Rev.(2005 Nov)
- ^Roman Nowicki, Wioletta Barańska-RybakShark liver oil as a supporting therapy in atopic dermatitisPol Merkur Lekarski.(2007 Apr)
- ^Buddhan S, Sivakumar R, Dhandapani N, Ganesan B, Anandan RProtective effect of dietary squalene supplementation on mitochondrial function in liver of aged ratsProstaglandins Leukot Essent Fatty Acids.(2007 Jun)
- ^Sabeena Farvin KH, Anandan R, Kumar SH, Shiny KS, Sankar TV, Thankappan TKEffect of squalene on tissue defense system in isoproterenol-induced myocardial infarction in ratsPharmacol Res.(2004 Sep)
- ^Mesa C, Fernández LEChallenges facing adjuvants for cancer immunotherapyImmunol Cell Biol.(2004 Dec)
- ^Safety and Immunogenicity of a Genetically Engineered Immunodeficiency Virus Vaccine
- ^Allison AC, Byars NEAn adjuvant formulation that selectively elicits the formation of antibodies of protective isotypes and of cell-mediated immunityJ Immunol Methods.(1986 Dec 24)
- ^Edelman RVaccine adjuvantsRev Infect Dis.(1980 May-Jun)
- ^Sotiroudis TG, Kyrtopoulos SAAnticarcinogenic compounds of olive oil and related biomarkersEur J Nutr.(2008 May)