Squalene

    Written by:
    Kamal Patel
    Last Updated: August 28, 2025

    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.



    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.[2][8] 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[2][8] 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

    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]

    6.

    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 RATriterpenoidsNat Prod Rep.(2010 Jan)
    2. ^Reddy LH, Couvreur PSqualene: A natural triterpene for use in disease management and therapyAdv Drug Deliv Rev.(2009 Dec 17)
    3. ^Nikkari T, Schreibman PH, Ahrens EH JrIn vivo studies of sterol and squalene secretion by human skinJ Lipid Res.(1974 Nov)
    4. ^De Luca C, Valacchi GSurface lipids as multifunctional mediators of skin responses to environmental stimuliMediators Inflamm.(2010)
    5. ^Newmark HLSqualene, olive oil, and cancer risk. Review and hypothesisAnn N Y Acad Sci.(1999)
    6. ^Murkovic M, Lechner S, Pietzka A, Bratacos M, Katzogiannos EAnalysis of minor components in olive oilJ Biochem Biophys Methods.(2004 Oct 29)
    7. ^Allouche Y, Jiménez A, Gaforio JJ, Uceda M, Beltrán GHow heating affects extra virgin olive oil quality indexes and chemical compositionJ Agric Food Chem.(2007 Nov 14)
    8. ^Mathews JSharks still intrigue cancer researchersJ Natl Cancer Inst.(1992 Jul 1)
    9. ^Kelly GSSqualene and its potential clinical usesAltern Med Rev.(1999 Feb)
    10. ^Abe I, Tomesch JC, Wattanasin S, Prestwich GDInhibitors of squalene biosynthesis and metabolismNat Prod Rep.(1994 Jun)
    11. ^Sebaceous gland lipids
    12. ^Tilvis RS, Miettinen TAAbsorption and metabolic fate of dietary 3H-squalene in the ratLipids.(1983 Mar)
    13. ^Strandberg TESterol synthesis from biliary squalene in the jejunal mucosa of the rat in vivoLipids.(1983 Aug)
    14. ^Serum concentration and metabolism of cholesterol during rapeseed oil and squalene feeding
    15. ^Gylling H, Miettinen TAPostabsorptive metabolism of dietary squaleneAtherosclerosis.(1994 Apr)
    16. ^Owen RW, Haubner R, Würtele G, Hull E, Spiegelhalder B, Bartsch HOlives and olive oil in cancer preventionEur J Cancer Prev.(2004 Aug)
    17. ^Waterman E, Lockwood BActive components and clinical applications of olive oilAltern Med Rev.(2007 Dec)
    18. ^Smith TJSqualene: potential chemopreventive agentExpert Opin Investig Drugs.(2000 Aug)
    19. ^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)
    20. ^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)
    21. ^Van Duuren BL, Goldschmidt BMCocarcinogenic and tumor-promoting agents in tobacco carcinogenesisJ Natl Cancer Inst.(1976 Jun)
    22. ^Attenuation of cyclophosphamide induced toxicity by squalene in experimental rats
    23. ^Senthilkumar S, Devaki T, Manohar BM, Babu MSEffect of squalene on cyclophosphamide-induced toxicityClin Chim Acta.(2006 Feb)
    24. ^Hashim YZ, Eng M, Gill CI, McGlynn H, Rowland IRComponents of olive oil and chemoprevention of colorectal cancerNutr Rev.(2005 Nov)
    25. ^Roman Nowicki, Wioletta Barańska-RybakShark liver oil as a supporting therapy in atopic dermatitisPol Merkur Lekarski.(2007 Apr)
    26. ^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)
    27. ^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)
    28. ^Mesa C, Fernández LEChallenges facing adjuvants for cancer immunotherapyImmunol Cell Biol.(2004 Dec)
    29. ^Safety and Immunogenicity of a Genetically Engineered Immunodeficiency Virus Vaccine
    30. ^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)
    31. ^Edelman RVaccine adjuvantsRev Infect Dis.(1980 May-Jun)
    32. ^Sotiroudis TG, Kyrtopoulos SAAnticarcinogenic compounds of olive oil and related biomarkersEur J Nutr.(2008 May)