Squalene is absorbed through several routes of administration, depending on the species (Final Report, 1982). In mice, squalene penetrates slowly and poorly through the skin at a rate of 0.12 nmol/cm2 per minute (Final Report, 1982). Subcutaneous administration in rabbits leads to increases of stored squalene in liver, muscle, and skin (Final Report, 1982). Virtually all squalene administered orally to rats (96–100 percent) is unabsorbed (Albro and Thomas, 1970).

In humans, about 60 percent of dietary squalene is absorbed through the gastrointestinal tract, with the remainder excreted in feces (Strandberg et al., 1990). A significant fraction of absorbed squalene is converted into cholesterol. Squalene is distributed throughout human tissues, with greatest concentrations in skin and fat (Kelly, 1999). Squalene in human serum comes from endogenous cholesterol synthesis and from diet (Strandberg et al., 1990; Kelly, 1999). Peak serum levels are attained 9–12 hours after ingestion (Gylling and Miettinen, 1994).

Animal Studies

There are few published studies of squalene toxicity in animals or humans (Kelly, 1999). Kamimura and colleagues (1989) examined subacute toxicity in dogs after a single oral squalene dose of 1,200 mg/kg. Over the next 3 months, accumulation was noted in several tissues, especially liver, but there were no signs of toxicity based on testing of serum and liver function. In contrast to humans, who absorb 60 percent of ingested squalene, this study reported that dogs absorb a relatively small percentage and excrete most in feces (83 percent). Thus, the relevance of this study to humans is unclear.

Squalene’s toxicity is considered low, with an oral LD50 (median lethal dose) in mice at greater than 50 ml/kg (Final Report, 1982). No toxic responses were noted after subcutaneous and intramuscular injections of 0.5 ml per 20g mouse (25 ml/kg) of squalane (C30H62), a saturated and more stable version of squalene.

In a neuropathology study, squalene was administered subcutaneously to 10 rats (and 5 control rats) at a dose of 20 g/kg body weight for 4 consecutive days (Gajkowska et al., 1999). The rats’ peripheral and central nervous systems were examined via electron microscopy 7 or 30 days from initiation of the experiment. After 7 days, disturbances in the myelin sheath were observed; these disturbances were more pronounced at 30 days. There was some swelling of Schwann cells in the peripheral nervous system. Fibroblasts were activated and showed signs of increased collagen production. In the central nervous system, squalene triggered swelling of astrocytes in white matter and in the hippocampus, especially near blood vessels. Lipid droplets accumulated in myelin in both the central and the peripheral nervous systems.

The pertinence of this neuropathology study is difficult to gauge because the dose was extremely high and the report provided minimal information about the study’s methodology (especially handling of controls). Additionally, it is not uncommon to detect occasional astrocytic or neuronal swelling or mitochondrial swelling in electron micrographs of normal tissue. Further, damage appeared to be localized, not global, targeting, for example, a single myelin fiber or axon.



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