Shark Liver Oil and Alkylglycerols

In traditional folk medicine in Scandinavia, shark liver oil was used as an aid in wound healing, treatment of respiratory and digestive tract irritation, and lymphadenopathy. Fishermen on the western coast of Norway and Sweden traditionally used this oil. Even more interestingly, in Scandinavian traditional medicine, it was an essential part of cancer therapy. This traditional medical approach was based on early “folk” observations that sharks rarely suffer from tumors and successfully resist numerous infections. It is clear that this observation was simplistic and incorrect, as the incidence of cancer in sharks is multifactorial and requires careful evaluation, which has later been proven, as sharks can indeed develop cancer. Nevertheless, shark liver oil has shown potential benefits in the treatment of conditions caused by inadequate immune responses and in the therapy of several types of tumors.

Composition of Shark Liver Oil

Fish oils contain several biologically active factors that modify cellular activity and influence various physiological functions. Unlike typical fish oil known for its high content of omega-3 polyunsaturated fatty acids (EPA and DHA), shark liver oil has a relatively low concentration of these fatty acids. However, what sets this oil apart is its rich content of alkylglycerols and squalene.

Squalene

Squalene is a triterpene that serves as an intermediate in cholesterol biosynthesis and is also a major component of surface polyunsaturated lipids in the skin, acting as both an emollient and an antioxidant. It possesses hydrating and antitumor properties.

Alkylglycerols

These molecules are the primary constituents of the potential action of shark liver oil and are chemically classified as alkyl ethers of glycerol. They naturally occur in hematopoietic organs such as bone marrow, spleen, and liver, as well as in white blood cells (neutrophils) and in human and cow’s milk. In terms of alkylglycerol concentration, colostrum from human milk contains a higher concentration of unsubstituted glycerol ethers compared to mature milk; human milk contains 10 times higher concentrations than cow’s milk and 2 times higher than sheep’s milk. The highest concentration of alkylglycerols in neutral lipids is found in human bone marrow and in cervical cancer cells. Although alkylglycerols were first discovered in shark liver oil by Japanese scientists Tsujimoto and Toyama in 1922, the first synthesis of these compounds was accomplished in 1930 by Nobel laureate Robert Robinson. Given its traditional use and researched mechanisms of action, despite the presence of squalene, shark liver oil is considered to have its primary biological effects attributed to alkylglycerols. These compounds are believed to have beneficial effects on human health. Research on alkylglycerols mainly focuses on their modulation of the immune system and their potential benefits following radiation-induced biological damage. Alkylglycerols have been studied for decades using various research designs, including clinical studies. Experimental research has shown that these molecules have the ability to cross the blood-brain barrier, which could be advantageous for enhancing the delivery of methotrexate in therapies for central nervous system diseases.

Mechanism

Alkylglycerols likely control the immune response through mechanisms involving the modulation of platelet activation factors and the production of diacylglycerols. Ultimately, they seem to positively affect the maturation of leukocytes and antibodies as well as the final production of cytokines.
Squalene, on the other hand, enhances antigen presentation and the induction of the inflammatory response. Some studies have shown that both alkylglycerols and squalene possess antitumor activity through various cellular mechanisms: inhibiting angiogenesis, inducing apoptosis in neoplastic cells, promoting transmembrane transport of cytotoxic agents, and suppressing signal transduction.

Application: Cancers, Tumors, and Immunity

In the early 1950s, initial research was conducted on alkylglycerols and their potential use in children diagnosed with leukemia. Although alkylglycerols were then isolated from bovine bone marrow, the first results were notably favorable due to the resulting stimulation of white blood cell production. This led to the well-known publication on the use of alkylglycerols for diagnoses and biological damage caused by radiation. Later studies showed that in patients with cervical cancer, there was a lesser decrease in leukocytes and platelets after radiation when alkylglycerols were used concurrently. It was also observed that the incidence of radiation-induced injuries was significantly lower, and the frequency of fistulas was reduced by as much as 47% if patients used alkylglycerols before radiation. Experimental studies have shown an increased immune response of neutrophils to bacteria, as well as an enhanced antioxidant status in the serum. One study showed a favorable effect on cytokines IFN-gamma and TNF-alpha and the production of interleukin IL-2 in peripheral blood cells following oil administration. Another month-long study with 10 healthy participants demonstrated that alkylglycerol administration resulted in a nearly 40% increase in the CD4/CD8 ratio and increased cytokine production by lymphocytes towards a favorable Th1 response, making this intervention safe with no significant side effects observed. The content of polyunsaturated omega-3 fatty acids is significantly lower in shark liver oil compared to fish oil, which is known for its anti-inflammatory and anti-cachectic effects. In one in vivo experimental study, the anti-cachectic effect of fish oil was compared to that of shark liver oil. After 14 days of shark liver oil administration, stabilization of anti-cachectic parameters was achieved to the level of the control group. Additionally, combining fish oil and shark liver oil did not result in an additional anti-cachectic effect. Although the anti-cachectic effect of shark liver oil is less pronounced compared to fish oil, its antitumor properties, primarily due to the presence of alkylglycerols, are noteworthy. Therefore, it could be an interesting option for adjuvant therapy in oncology patients. It would certainly be valuable to see well-designed clinical studies comparing the anti-cachectic effects of fish oil and shark liver oil.

Conclusion

In concluding the potential antitumor effects of shark liver oil, specifically alkylglycerols, it can be stated that the mechanism of action is based on the modulation of immune system activity. Specifically, it involves the activation of macrophages and an increase in the production of cytokines such as interleukin (IL-12) and IFN-gamma, which ultimately enhances the cytotoxic activity of NK cells, T-lymphocytes, and the proliferation of preactivated T-cells and NK cells. Due to preliminary evidence regarding the mechanism of alkylglycerols crossing the blood-brain barrier, the use of short-chain alkylglycerol molecules is being considered as a potentially beneficial strategy for primary and secondary brain tumor diagnoses. A useful outcome of this intervention could be the improved delivery of cytotoxic drugs to tumor cells in distant regions of the brain. However, given the specificity of different types of tumors, it is essential to further investigate the effects and utility of this treatment across various oncological diagnoses. Considering the good tolerability of alkylglycerol application from shark liver oil observed so far, as well as encouraging data on its use, adjuvant therapy with alkylglycerols currently appears to be one of the promising strategies for adjuvant therapy in oncology diagnoses. LITERATURE

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