Library: Squalene

Squalene

Squalene is a natural lipid substance found in olive, amaranth, and shark liver oil. It is an intermediate product of cholesterol synthesis in the body [3]. It is also the main component of unsaturated lipids in human skin surface sebum [3]. Its name comes from the shark genus (Squalus). It was first identified in shark liver oil [1]. Cosmetic manufacturers purchase it as an emollient. Vaccine manufacturers purchase it as an adjuvant. Supplement manufacturers purchase it as a capsule ingredient. Its hydrogenated derivative squalane is a separate substance. The two are often confused.

Where does it come from, and how much is there?

The richest natural source is the liver oil of deep-sea sharks [2], [3]. One study considers shark squalene unethical for cosmetics [2]. For this reason, a "plant-based" claim must be verified.

Prominent plant sources include olive oil refining residues and amaranth seed oil [3], [6]. Squalene is also found in palm, wheat germ, and rice bran oils [3]. A study screening grains, seeds, and legumes found squalene in all of them [11]. The highest value was in pumpkin seeds (89 mg/100 g) [11]. Amaranth seed oil has one of the highest squalene levels among vegetable oils. Hexane-extracted amaranth oil showed 7.0% to 7.1% squalene [12]. A study comparing four species and eleven genotypes found 3.6% to 6.1% squalene in total oil [14]. The same group reported up to 15.3% squalene in fractions obtained with supercritical CO₂ [15]. Supercritical CO₂ is carbon dioxide that behaves like a liquid under pressure. The ratio varies by seed, variety, and process. The squalene content of an oil is determined by measurement, not the plant name.

Squalene or squalane: what is the difference?

MoleculeCASFormulaMolar mass (g/mol)XLogPPubChem
Squalene111-02-4C₃₀H₅₀410.711.6638072
Squalane111-01-3C₃₀H₆₂422.814.78089

Values are taken from PubChem. XLogP indicates whether the substance is closer to oil or water. A higher value indicates higher lipophilicity. Both are insoluble in water and soluble in oil.

One letter, two substances. Squalene has six double bonds in its structure that react easily with atmospheric oxygen. Therefore, it degrades with light, air, and heat. Squalane is the form where these bonds are saturated with hydrogen. It is resistant to degradation. A study reviewing hydrogenation methods describes squalane as the best emollient known to the cosmetic industry [7]. If a document states squalene, it refers to the natural, degradable substance. If it states squalane, it refers to the hydrogenated, stable derivative. This is the first thing to check when reading certificates and labels.

What is it used for?

Cosmetics. Squalene is used as an emollient because it is compatible with skin sebum. It is a raw material in creams, emulsions, and dermal carrier systems [3]. A study measuring skin surface lipids in 100 volunteers reported key findings [13]. Squalene, vitamin E, and coenzyme Q10 levels increased from childhood to adulthood. They dropped significantly in older age [13]. In 1982, the Cosmetic Ingredient Review (CIR) expert panel found squalene and squalane safe as used [9]. They saw no need to reopen the safety assessment in 2001 [9]. According to the same report, 2001 cosmetic formulation records listed squalane in 595 products and squalene in 29 [9]. The industry selects squalane for stability [7], [9].

Pharmaceuticals: vaccine adjuvant. Squalene and squalane emulsions with very fine droplets are used in vaccines to enhance immune response. A review reported that these emulsions induce both antibody and cellular responses [8]. They remain stable at room temperature for years [8]. They show very low toxicity without additional stimulant additives [8]. These products are subject to pharmaceutical regulations. They are not the same as cosmetic or food-grade squalene.

Food and supplements. Squalene is found in measurable levels across grains, seeds, and legumes [11]. Degradation by air reduces its value in food [10]. Shark liver oil and plant squalene capsules are sold as supplements.

Which source, which purity: which form?

Squalene is available on the market in four forms. Source and purity determine the price.

FormSourceSqualeneAssociated components
Shark liver oilshark liverrichest natural source [3]fish oil, source claim must be verified [2]
Olive-derived concentrateolive oil refining residueup to 90% in CO₂ fractionation [6]sterols, fatty alcohols
Amaranth seed oil and CO₂ extractamaranth seedapproximately 7% in oil [12], up to 15.3% in CO₂ fractions [15]vitamin E group (tocopherols), fatty acids [5]
High-purity squalene and squalaneolive, amaranth, or sharkup to 98% in laboratory fractionation [14]none

Supercritical CO₂ extraction can produce amaranth seed oil. In one study, temperature, pressure, and seed pretreatment changed the yield [4]. Adding ethanol to CO₂ extracts squalene and vitamin E together [5]. In hexane extraction, heat did not change the squalene ratio (7.0% to 7.1%) [12]. Trans fatty acids increased with heat but stayed below 0.5 g/100 g [12].

The choice depends on four questions.

  • Shark or plant? Label and market policies determine this. The claim can be verified in the laboratory (see "How to read an analysis report?").
  • Squalene or squalane? Select squalene if a natural, degradable substance is required. Select squalane if shelf life is the priority.
  • What comes with it? Amaranth oil contains vitamin E and fatty acids [5]. Vitamin E slows squalene degradation [10]. This determines if additional antioxidants are needed in the formulation.
  • Price. Compare the price per kilogram of squalene, not per kilogram of oil. For 1 kg of squalene, 14 kg of 7% oil or 1.02 kg of 98% concentrate is needed. These figures are examples.

How to read an analysis report?

Method. Squalene in oils is measured by gas chromatography (GC). Liquid chromatography (HPLC) is also used [11]. Both separate the mixture into its components. They quantify each separately. The certificate must state the method name.

Plant or shark? The origin of a squalene sample is determined in the laboratory. Carbon has two natural isotopes. Plants and animals incorporate them into their tissue at slightly different ratios. That ratio remains in the molecule. It acts like a fingerprint of the source. This measurement distinguishes olive squalene from shark squalene [2]. Shark squalene added to a product sold as "plant-based" was detected at additions from 10% upward [2]. If the plant-based claim matters, request this analysis report from the supplier.

Degradation indicators. Squalene degrades easily with air (oxidation). One study showed that light-induced degradation and spontaneous radical-induced degradation yield different products [10]. β-Carotene slowed the light pathway. Vitamin E slowed the radical pathway [10]. The peroxide value (measure of degradation) and production date must be on the certificate.

Specification and measured value are separate things. The specification is the manufacturer commitment. The measured value is the result of that specific lot. The technical data sheet (TDS) is a general document. The certificate of analysis (CoA) belongs to the lot.

What indicates quality?

Source and process. Squalene content varies by seed, variety, and process [14], [15]. Solvent residues depend on the solvent used for extraction. The certificate must show the residue limit for hexane-extracted oil. The same question applies when a co-solvent such as ethanol is added during CO₂ extraction [5].

Degradation status. Evaluate the peroxide value and vitamin E content together. Vitamin E slows degradation [10].

Required items on the certificate. Squalene content and test method, peroxide value, fatty acid profile, heavy metals, and microbiology. Pesticides, aflatoxins, and benzo(a)pyrene for plant raw materials. Source declaration and, if necessary, source verification report [2].

How does it behave in formulations?

Feel and solubility. Squalene and squalane are oil-soluble and water-insoluble. Both spread easily on skin and are compatible with skin sebum [3], [7].

Degradation and storage. Squalene degrades with light, air, and heat. Antioxidants such as vitamin E and β-carotene slow this down [10]. Store in a cool, dark, sealed container, preferably under nitrogen. Squalane is resistant to degradation [7].

Safety and labeling. The CIR panel found squalene and squalane safe under conditions of use [9]. Details are in the product safety data sheet (SDS). Cosmetic ingredient names (INCI) are Squalene and Squalane. The label identifier depends on product classification and regulations.

References

  1. Tsujimoto M. (1920). Squalene: A Highly Unsaturated Hydrocarbon in Shark Liver Oil. Journal of Industrial & Engineering Chemistry. https://doi.org/10.1021/ie50121a020
  2. Camin F., Bontempo L. et al. (2010). Stable isotope ratios of carbon and hydrogen to distinguish olive oil from shark squalene-squalane. Rapid Communications in Mass Spectrometry. https://doi.org/10.1002/rcm.4581
  3. Huang Z., Lin Y. et al. (2009). Biological and Pharmacological Activities of Squalene and Related Compounds: Potential Uses in Cosmetic Dermatology. Molecules. https://doi.org/10.3390/molecules14010540
  4. Westerman D., Santos R. et al. (2006). Extraction of Amaranth seed oil by supercritical carbon dioxide. The Journal of Supercritical Fluids. https://doi.org/10.1016/j.supflu.2005.06.012
  5. Kraujalis P., Venskutonis P. (2013). Supercritical carbon dioxide extraction of squalene and tocopherols from amaranth and assessment of extracts antioxidant activity. The Journal of Supercritical Fluids. https://doi.org/10.1016/j.supflu.2013.04.005
  6. Vázquez L., Torres C. et al. (2007). Recovery of squalene from vegetable oil sources using countercurrent supercritical carbon dioxide extraction. The Journal of Supercritical Fluids. https://doi.org/10.1016/j.supflu.2006.04.012
  7. Ciriminna R., Pandarus V. et al. (2014). Catalytic Hydrogenation of Squalene to Squalane. Organic Process Research & Development. https://doi.org/10.1021/op5002337
  8. Allison A. (1999). Squalene and Squalane Emulsions as Adjuvants. Methods. https://doi.org/10.1006/meth.1999.0832
  9. Cosmetic Ingredient Review Expert Panel (2003). Squalene and Squalane. International Journal of Toxicology. https://doi.org/10.1177/1091581803022s112
  10. Shimizu N., Ito J. et al. (2018). Oxidation of squalene by singlet oxygen and free radicals results in different compositions of squalene monohydroperoxide isomers. Scientific Reports. https://doi.org/10.1038/s41598-018-27455-5
  11. Ryan E., Galvin K. et al. (2007). Phytosterol, Squalene, Tocopherol Content and Fatty Acid Profile of Selected Seeds, Grains, and Legumes. Plant Foods for Human Nutrition. https://doi.org/10.1007/s11130-007-0046-8
  12. Ortega J., Martínez Zavala A. et al. (2012). Analysis of trans fatty acids production and squalene variation during amaranth oil extraction. Open Chemistry. https://doi.org/10.2478/s11532-012-0104-4
  13. Passi S., De Pità O. et al. (2002). Lipophilic Antioxidants in Human Sebum and Aging. Free Radical Research. https://doi.org/10.1080/10715760290021342
  14. He H., Cai Y. et al. (2002). Extraction and Purification of Squalene from Amaranthus Grain. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/jf010918p
  15. He H., Corke H. et al. (2003). Supercritical Carbon Dioxide Extraction of Oil and Squalene from Amaranthus Grain. Journal of Agricultural and Food Chemistry. https://doi.org/10.1021/jf030488y