IngredientsShark liver oil (SLO) is the crude or refined lipid fraction extracted from the livers of sharks, primarily deep-sea species. It is not a single chemical entity but rather a complex mixture of lipid classes. The primary source species include Centrophorus squamosus (deep-sea shark), Cetorhinus maximus (basking shark), and Squalus acanthias (dogfish shark). The composition of SLO differs among shark species and depends on the size of the shark — the liver constitutes about 25% of the total shark body weight — as well as diet, gender, growth rate, swimming depth, and reproduction.
The two principal and most pharmacologically studied constituents are:
SLO contains alkylglycerols (AKGs), squalene, pristane, vitamins A and D, esters of fatty acids, glycerol ethers, triglycerides, cholesterol, and fatty acids. Shark liver oils are rich in alkylglycerols and squalene, but contain relatively low amounts of n-3 polyunsaturated fatty acids. The quantitative proportions vary considerably with species and processing method. Chemical analysis of one preparation revealed it to be almost free of n-3 long-chain fatty acids and mainly composed (w/w) of squalene (38.8%) and alkylglycerols (43.6%). In Centrophorus species, the oil can contain glycerol esters and 60% unsaponifiable matter, including squalene (45%) and cholesterol (4.5%).
Squalene is sourced predominantly from shark liver oils and to a lesser extent from plants such as olives, and is used for the production of surfactants, dyes, sunscreen, and cosmetics. The economic value of shark liver oil is directly related to its squalene content, which is highly variable and species-dependent. Later, squalene was also found in a variety of vegetable oils, including olive, palm, wheat-germ, and rice bran oils.
Alkylglycerols are not exclusive to shark liver. These ether lipids are found in hematopoietic organs of mammals, especially in the bone marrow and in human breast milk.
The oil has a dark yellow to brown shade and pungent aroma and taste. It is found in liquid or capsule form, or as an ingredient in skin creams and lip balms. Purified preparations enriched specifically in alkylglycerols, such as the commercial product Alkyrol®, are available in which squalene and other potentially undesirable components have been largely removed. Alkyrol® has been purified to enrich for alkylglycerols and to remove contaminants and unwanted substances such as polychlorinated biphenyls, pesticides, heavy metals, fatty substances including cholesterol, squalene, and excessive amounts of vitamins A and D. A preparation known as Ecomer has also been used in clinical and observational studies.
SLO is an ancient remedy among the fishermen along the west coast of Norway and Sweden. Scandinavian folk medicine used shark liver oil for the treatment of cancers and other ailments based on the rarity of tumors in sharks and their ability to resist infections. 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. Initially, SLO was employed by Scandinavian fishermen to treat skin conditions, respiratory ailments, and certain cancers. The oil has been historically used to treat what was referred to as glandular disease, which today most likely would be identified as lymphadenopathy.
Shark liver oil was used for centuries in Scandinavian countries, particularly by fishermen, as a remedy for slow-healing wounds and against irritation of the respiratory organs. In the 19th century, the use of shark liver oil almost died out, surviving only in a few fishing communities. It was to take more than a century before the use was revived, following the publication of scientific documentation regarding its beneficial effects.
SLO has been traditionally used by Scandinavian fishermen for the treatment of a variety of ailments, including wounds, heart disease, and infertility.
Its use increased during World War II as a vitamin A source amid shortages of alternatives like cod liver oil.
In 1952, a young Swedish physician, Astrid Brohult, M.D., discovered that marrow from fresh calf bones given to children with leukemia stimulated their white cell production. Brohult and Holmberg, using the unsaponifiable portion of different bone marrow fats as well as preparations containing esters of alkylglycerols in child leukemia, observed a pro-differentiating effect on white blood cells leading to clinical administration of AKGs in actinic leukopenia. In the early 1950s, Astrid Brohult began experimenting with AKGs from calf marrow in children with leukemia, highlighting their ability to stimulate white blood cell production; later, in 1963, she published a thesis on AKGs and their use in irradiated uterine cancer patients, demonstrating that AKG administration during radiation exposure reduced the bone marrow-induced leukopenia following radiation therapy for uterine cervix carcinoma.
The active ingredients in shark liver oil were found to be a group of ether-linked glycerols known as alkylglycerols. Initial clinical use was for treating leukemias, and later to prevent radiation sickness from cancer x-ray therapy.
In 1922, Tsujimoto and Toyama found alkylglycerols in SLO, and Sir Robert Robinson, a Nobel laureate, first synthesized them in 1930.
Natural 1-O-alkylglycerols (alkyl-Gro) are bioactive ether lipids present in body cells and fluids. They are precursors of ether phospholipids, which participate in structures and functions of membranes in certain cells such as white blood cells or macrophages. Shark liver oil from Centrophorus squamosus (SLO), or alkyl-Gro mix from this source, has several in vivo biological activities including stimulation of hematopoiesis and immunological defences, sperm quality improvement, and anti-tumor and anti-metastasis activities. Several mechanisms are suggested for these multiple activities, resulting from incorporation of alkyl-Gro into membrane phospholipids and lipid signaling interactions.
With respect to immune modulation, AKGs may control immune response possibly through modification of platelet-activating factor (PAF) and diacylglycerol (DAG) production. The level of natural alkylglycerols rises within tumor cells, apparently in an effort to control cell growth. Recent studies indicate that the activation of protein kinase C, an essential step in cell proliferation, can be inhibited by alkylglycerols — an action suggesting competitive inhibition of 1,2-diacylglycerol by alkylglycerols.
Literature reports show that alkylglycerols enhance Fc-receptor mediated phagocytosis, increase humoral immune response, and delay hypersensitivity reactions.
Shark liver oil is a rich source of alkylglycerols that can be metabolized into plasmalogens. Plasmalogens are critical for human health and have established roles in neuronal development, the immune response, and as endogenous antioxidants. However, the mechanistic bases of these and other biological functions of plasmalogens are not well defined.
Regarding blood-brain barrier permeability, synthetic short-chain alkyl-Gro such as 1-O-pentyl-sn-glycerol are interesting compounds that transiently open the blood-brain barrier (BBB), allowing increased crossing of the BBB by therapeutic molecules. Parenteral 1-O-decyl-sn-glycerol may also increase carbamazepine crossing through the BBB. This effect has been demonstrated primarily in animal models.
Chemically, squalene is a polyprenyl compound, having structural similarity with β-carotene, coenzyme Q10, and vitamins A, E, and K. Squalene, an intermediate for cholesterol biosynthesis, has been proposed to act similarly to statins via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the liver. However, this possibility is challenged by a substantial number of existing in vitro and in vivo studies demonstrating that exogenous squalene exhibits feedback inhibition of HMG-CoA reductase, a key enzyme functioning in cholesterol biosynthesis.
Squalene enhances antigen presentation and induction of the inflammatory response. Squalene has also been discovered to possess a wide spectrum of biological functions such as preventing cell deterioration, being anti-senescence, and improving immunity as well as sexual function.
Squalene is also a natural component of human skin sebum. 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.
A total of 16 articles meeting inclusion criteria — including human studies and in vivo animal models with various baseline health conditions — indicated that SLO has a broad yet selective immunomodulatory effect that shows an adaptive response depending on context, such as inflammatory conditions, cancer, or infection. The inconsistencies in results highlighted the biological complexity and the context-dependent role of SLO in the immune system. Despite this, alkylglycerols (AKG) emerge as a key bioactive component, with some studies suggesting potential dose-dependent effects and exploring the structure-activity relationship of different AKG forms in modulating the immune response.
In a human study examining perioperative use, an open spontaneous study was conducted on 40 very elderly surgical patients pre-operatively treated with alkylglycerols (500 mg twice a day for 4 weeks), in order to reduce the risks of surgery by counteracting postoperative inflammatory and anergic conditions. The onset of complications was reduced in the alkylglycerol-treated group and compliance was excellent without any serious adverse effect. Specifically, WBC count and IgG increased significantly (p <0.05 and p <0.001, respectively), which may explain some protection against infectious agents and wound repair adverse events. Lymphocyte concentration also increased significantly in the AKG-treated group (p <0.001), while neutrophils significantly decreased in the AKG-treated group (p <0.001), indicating resolution of infection and re-establishment of physiologic state.
In a 4-week study of high-dose SLO in 13 adults, clinical, immunological, and biochemical effects were examined. The experiment was based on consumption of 3.6 g of squalene, 3.6 g of alkylglycerols, and 750 mg of n-3 polyunsaturated fatty acids per day for 4 weeks. Results showed increased response of neutrophils toward bacteria, increased level of C4 complement component in blood, rise of total antioxidant status of serum, and predominance of Type I cytokine IFN-gamma, TNF-alpha, and IL-2 production by peripheral blood mononuclear cells after shark liver oil intake.
Evidence strength: Preliminary. Most data come from small, uncontrolled, or non-randomized human studies and animal models. Larger randomized controlled trials are lacking.
Alkylglycerols have been studied as anti-cancer agents in several clinical trials and have been investigated for the treatment of radiation-induced side effects and for their ability to boost the immune system.
In the early 1950s, Astrid Brohult demonstrated that AKG administration during radiotherapy exposure reduced the bone marrow-induced leukopenia following radiation therapy for uterine cervix carcinoma. AKG-treated patients showed a reduced complication rate and a 47% reduction in fistula incidence when AKG had been administered prior to radiation treatment.
The first clinical studies using SLO supplementation were for the treatment of leukemia and as a complementary agent administered to uterine cervix cancer patients submitted to x-ray therapy. In such approaches, SLO supplementation was able to avoid leukopenia and thrombocytopenia usually caused by radiation.
Animal model data on anti-tumor activity include: tumor growth inhibition in 3LL-grafted carcinoma was similar between mice treated with SLO (−29 ± 3% compared with control) and alkyl-Gro (−26% ± 3%). SLO appeared to decrease pulmonary metastasis by 31 ± 8% below control, and alkyl-Gro reduced it by 64 ± 8%. Five days of treatment with alkyl-Gro was associated with a 26 ± 9% reduction in the tumor blood vessel endothelial marker compared with the control group. The authors concluded that alkyl-Gro and SLO seemed to exhibit antitumor and antiangiogenesis effects.
Furthermore, in the context of individual alkylglycerol species tested in mouse models, six prominent constituents of natural alkyl-Gro mix — 12:0, 14:0, 16:0, 18:0, 16:1 n-7, and 18:1 n-9 — were synthesized and tested for anti-tumor and anti-metastatic activities. 16:1 and 18:1 alkyl-Gro showed strong activity in reducing lung metastasis number, while saturated alkyl-Gro had weaker (16:0) or no (12:0, 14:0, 18:0) effect.
Evidence strength: Clinical radiation protection data (Brohult) are from non-randomized, older trials with methodological limitations by contemporary standards. Anti-tumor data are largely preclinical (animal models). Human clinical evidence is insufficient to draw firm efficacy conclusions.
The effect of SLO and squalene on cholesterol levels has produced mixed findings across study designs and populations.
In a randomized, double-blind, placebo-controlled crossover study (2021), designed to evaluate the impact of SLO supplementation on endogenous plasmalogen levels, ten overweight or obese males received 4 g of Alkyrol® (purified SLO) or placebo per day for 3 weeks followed by a 3-week washout phase and then crossed over. SLO supplementation led to significant changes in plasma and circulatory white blood cell lipidomes, notably increased levels of plasmalogens and other ether lipids. In addition, SLO supplementation significantly decreased the plasma levels of total free cholesterol, triglycerides, and C-reactive protein. These findings suggest that SLO supplementation can enrich plasma and cellular plasmalogens and this enrichment may provide protection against obesity-related dyslipidemia and inflammation.
In an 8-week, placebo-controlled Japanese study in middle-aged and elderly males, supplementation with SLO at 1,500 mg daily (582 mg as squalene) was compared with placebo on indexes of central arterial stiffness and peripheral microvascular function. Supplementation with SLO and thus squalene did not show clinically significant effects on weight, blood pressure, heart rate, or serum levels of lipids, glucose, or any other laboratory test parameters.
A short-term study in young healthy women found that 6 weeks of SLO supplementation led to a significant decrease in C-reactive protein levels in sera and intracellular cholesterol levels in peripheral blood mononuclear cells.
A high-dose, 4-week study of 13 adults reported contrasting results: an increase of total cholesterol level from 182.92 ± 29.290 mg/dL before oil consumption to 224.46 ± 62.198 mg/dL after the diet rich in oil, and a decrease in the HDL fraction, were noted. However, lipid metabolism normalized spontaneously after the end of the experiment in all individuals.
Animal data are also inconsistent: a study testing hypercholesterolemic activities of pure squalene and SLO in hamsters found that serum total cholesterol was elevated by 32% in the 0.05% squalene group, 23% in the 0.10% squalene group, 35% in the 0.5% squalene group, and 19% in the 0.05% SLO group when compared with the control group. Conversely, rat supplementation with squalene has also shown increases in HDL cholesterol in some animal studies.
Evidence strength: Mixed. Small human trials at purified, lower doses tend to show lipid-lowering or neutral effects, while high-dose regimens have transiently elevated cholesterol. Larger and longer RCTs are needed before clinical recommendations can be made.
Plasmalogens are membrane glycerophospholipids with diverse biological functions. Reduced plasmalogen levels have been observed in metabolic diseases; hence, increasing their levels might be beneficial in ameliorating these conditions. Shark liver oil is a rich source of alkylglycerols that can be metabolized into plasmalogens. Lipidomic studies have characterized reduced levels of plasmalogens in a number of disease states, including neurodegenerative and cardiometabolic disease, highlighting the potential of plasmalogen modulation as a therapeutic strategy. The 2021 Journal of Lipid Research crossover study (Paul et al.) noted that SLO supplementation modulated plasmalogens and other ether lipids in human plasma and white blood cells. These changes, together with small but significant improvements in clinically important markers of dyslipidemia and inflammation, provide a strong rationale for larger trials examining the impact of SLO supplementation on metabolic diseases.
Evidence strength: Preliminary but mechanistically coherent. The placebo-controlled crossover design of the 2021 study represents the strongest contemporary human evidence to date; however, the sample (n=10) was small and findings require replication in larger cohorts.
There is no specific and effective treatment for recurrent aphthous stomatitis (RAS), which is connected with its unexplained etiology. In a study designed to determine the clinical efficiency and immunomodulation of shark liver oil in treatment of RAS, 25 patients with severe disease received treatment with shark liver oil during a three-month period. The frequency of occurrence of RAS decreased from 1.56 before treatment to 0.95 after treatment, and the number of lesions per month was significantly reduced during the third month of treatment and two months after treatment. During the two months after treatment, 4 patients had no ulcers, and an improvement was exhibited in all except 3 of the remaining patients.
Evidence strength: Very limited. This is a single, small, uncontrolled study; no placebo-controlled replications have been identified.
SLO has been used for wound healing, inflammatory lung and alimentary tract diseases, lymphadenopathy, cancer, and dermatitis. Preliminary qualitative screening for shark liver oil discovered that squalene and alkylglycerols play a significant role in promoting wound healing via multiple mechanisms. Topical applications have also been studied; SLO marketed under the name Isolutrol has been studied in a clinical trial of acne at a topical concentration of 0.15 g per 100 mL.
Evidence strength: Mainly traditional use and preclinical. Formal human clinical trial evidence for wound healing is very limited.
Alkylglycerols may serve as precursors for a platelet-activating factor that has been linked in animal studies with sperm motility. In vivo studies in boars showed that oral intake of SLO (40 g/day, 28 days) improved sperm motility and velocity, together with an increase in the levels of alkyl-Gro in sperm. The possibility of improving fertility by oral SLO supplementation is suggested by these data; however, confirmation is needed.
Evidence strength: Animal data only. No well-controlled human trials on sperm quality have been identified.
SLO is available commercially in oral capsule, softgel, and liquid forms. Purified alkylglycerol-enriched preparations (e.g., Alkyrol®, Ecomer) are also available.
There is no standardized dose for shark liver oil.
In a clinical study, 29% of subjects taking the SLO supplement reported minor adverse events (P=0.469 compared to placebo), the most common being gastrointestinal upset with or without eruption. There was no intervention-related untoward side-effect with clinical significance, and no abnormality in routine laboratory test parameters was found in any subject in either group. SLO supplements may have an unpleasant taste and/or odor.
A case of acute toxic hepatitis was reported in a 31-year-old female who became symptomatic with malaise and abdominal discomfort one week after starting shark liver oil supplementation, soon progressing to jaundice and pruritus. Upon admission, she had been taking shark liver oil capsules twice daily for 2 weeks. No family history, environmental, or infectious risk factors for hepatotoxicity were identified. Immediate improvement in symptoms was seen upon discontinuation of the supplement, with liver enzymes normalizing within 8 weeks. In Sweden, a SLO product (Ecomer) was prohibited for use by the National Board of Health and Welfare because of suspected adverse effects.
Non-purified or semi-purified SLO could have deleterious effects on the liver and other major organs because of the presence of substantial amounts of squalene and other undesirable components. Therefore, SLO should be consumed with caution.
Shark liver oil contains vitamin A, which can be toxic in excessive amounts. Symptoms of vitamin A toxicity include dizziness, nausea, and, in severe cases, liver damage.
Pollutants such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) have been identified in raw, cold-processed (essentially unrefined) SLO products. As a marine product, shark liver oil may contain contaminants like mercury and PCBs.
Shark liver oil supplementation at high doses markedly affected lipid metabolism and cholesterol balance, including an increase in total cholesterol and a decrease in HDL fraction. However, lipid metabolism normalized spontaneously after the end of the experiment. As neither SLO nor squalene have been extensively studied in humans, information on their toxicity and side effects is limited.
There have been reports of SLO-induced pneumonia in humans and pigs.
Despite the popularity of SLO, there is little published toxicology data on alkoxyglycerols. The toxicity of a supercritical fluid extract of shark liver oil (AKG-1 extract) was evaluated in acute and repeated-dose (28-day) oral toxicity studies in rats at doses 200 and 100 times the maximum recommended dose by supplement manufacturers in humans, respectively. A single oral gavage dose of 2,000 mg/kg body weight resulted in no adverse events or mortality. A daily dose of 1,000 mg/kg body weight for 28 days by gavage resulted in no adverse effects or mortality.
Shark liver oil may interact with certain medications, including blood thinners and immunosuppressants. The immunostimulatory properties of AKGs theoretically represent a pharmacodynamic concern in patients receiving immunosuppressive therapy. No formal pharmacokinetic interaction studies in humans have been identified in the peer-reviewed literature. Formal contraindications have not been identified; however, information regarding safety and efficacy in pregnancy and lactation is lacking.
Health conditions that Shark liver oil may help support.
Body systems that Shark liver oil may help support.
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