IngredientsStructurally, alkylglycerols are alkyl ethers of glycerol. More precisely, 1-O-alkylglycerol (AKG) is an ether glycerolipid characterized by an alkyl chain attached to the glycerol sn-1 position via an ether linkage. Natural AKG typically features saturated (C16:0, C18:0) and monounsaturated (C18:1) alkyl chains, and in its natural form predominantly exists as a diacylglyceryl ether with fatty acids esterified at the sn-2 and sn-3 positions. They are also referred to in the scientific literature as alkoxyglycerols, glyceryl ethers, ether lipids, or 1-O-alkylglycerols. In natural sources, they are always found esterified with fatty acids.
The principal alkylglycerols include chimyl (hexadecyl), batyl (octadecyl), and selachyl (octadecenyl) ethers. Three major natural alkylglycerols obtained from the Greenland shark are batyl alcohol, chimyl alcohol, and selachyl alcohol. Although chimyl and batyl alcohol are saturated chains, selachyl alcohol contains one unsaturated bond. In addition to these unsubstituted forms, 1-O-(2-hydroxyalkyl) glycerols, 1-O-(2-methoxyhexadecyl)-glycerol, 1-O-(2-methoxy-4-hexadecenyl)-glycerol, and 1-O-(2-methoxy-4-octadecenyl)-glycerol have been isolated from Greenland shark liver oil.
Marine sources of alkyl-Gro such as the liver oil of certain shark species or ratfish (elasmobranch fishes) contain high levels of these compounds as a mixture of few species varying by length and unsaturation of the alkyl chain. One of the major sources of natural alkylglycerols is obtained from the Greenland shark, Somniosus microcephalus, which contains up to 50% of alkylglycerols. Other sources include the elasmobranch fish, such as the small shark, Chimaera monstrosa, and the dogfish, Squalus acanthias. Cod liver oil and certain mollusks are additional sources of alkylglycerols.
Marine products such as deep-sea squid liver and shark liver oils are the major sources of diacylglyceryl ether, while benthic organisms, including starfish and sea cucumbers, also exhibit high lipid content, accounting for 40–70% of their total lipids.
The usual composition of alkyl chains in alkyl-Gro from Greenland shark (Centrophorus squamosus) liver oil is: 12:0, 1–2%; 14:0, 1–3%; 16:0, 9–13%; 16:1n-7, 11–13%; 18:0, 1–5%; 18:1n-9, 54–68%; 18:1n-7, 4–6%, and minor species.
Alkylglycerols are also found endogenously in the human body. AKG are glycerol ether lipids that are naturally occurring in hematopoietic (blood-forming) organs such as bone marrow, spleen, and liver, but they can also be found in neutrophils and in human and cow milk. Human colostrum contains about 0.19% AKGs, while cow milk contains only 0.01% AKGs, which accounts for approximately 1/20 of those in human milk. The highest concentration of alkylglycerols in neutral lipids is found in human bone marrow and in cervical cancer cells.
The composition of shark liver oil differs among shark species and depends on the size of the shark, diet, gender, growth rate, swimming depth, and reproduction.
Alkylglycerols are commercially available primarily as shark liver oil (SLO) supplements. SLO contains alkylglycerols (AKGs), squalene, pristane, vitamins A and D, esters of fatty acids, glycerol ethers, triglycerides, cholesterol, and fatty acids. The oil is available in both oral and topical preparations. 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. Analytical characterization of these compounds uses GC-MS primarily for characterizing the total composition and content of alkylglycerols, and LC-MS mainly for characterizing the esterified alkylglycerol molecular species.
Shark liver oil contains both alkylglycerols (AKG) and squalene and is an ancient remedy among the fishermen along the west coast of Norway and Sweden. It has been used for wound healing, the treatment of irritations of the respiratory and alimentary tracts, and lymphadenopathy.
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. Fishermen on the western coast of Norway and Sweden traditionally used this oil. 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.
In Japan, shark liver oil was consumed for its believed ability to boost vitality and protect against infections.
In 1922, Tsujimoto and Toyama found AKG in shark liver oil, and Sir Robert Robinson, a Nobel laureate, first synthesized them in 1930.
The discovery of alkylglycerols in a clinical context dates back to the 1950s, when Swedish Dr. Astrid Brohult found that administering calf bone marrow helped in the recovery of white blood cells in children undergoing radiotherapy for leukemia. The isolated active ingredient was identified as alkylglycerols.
Brohult and Holmberg, using the unsaponifiable portion of different bone marrow fats as well as preparations containing esters of AKG in child leukemia, observed a maturing effect on the white blood cells leading to experiments employing AKG in irradiation-induced leukopenia. In the early 1950s, Brohult performed experiments on children with leukemia, used extracts isolated from calf marrow, and observed that they were able to stimulate the production of white blood cells. These findings led, in 1963, to the publication of a thesis on AKG and their use in radiation treatment, which showed that the decrease in white cells and thrombocytes which usually occurs during radiation treatment is less pronounced if AKG are administered.
Initial clinical use was for treating leukemias, and later to prevent radiation sickness from cancer x-ray therapy.
AKGs in shark liver oil include such substances as batyl alcohol (AKG18:0), chimyl alcohol (AKG16:0), and selachyl alcohol (AKG18:1). They are precursors of ether phospholipids, which participate in structures and functions of membranes in certain cells such as white blood cells or macrophages.
Studies indicate that the activation of protein kinase C (PKC), an essential step in cell proliferation, can be inhibited by alkylglycerols. This action suggests a competitive inhibition of 1,2-diacylglycerol by alkylglycerols. Treatment of cells with 1-O-dodecyl-sn-glycerol resulted in a decrease in the activity of membrane-associated PKC activity and inhibited phorbol ester-stimulated translocation of PKC from the cytosol to the membrane fraction. Alkylglycerol was also shown to inhibit the activity of purified PKC in vitro when present at levels similar to that of the diacylglycerol activator.
AKG may control immune response possibly through modification of platelet-activating factor (PAF) and diacylglycerol (DAG) production. Their role in increasing PAF precursor and amplifying PAF production could explain effects related to PAF activities. These activities include inflammation and sperm functions, but also immune-regulation.
AKG and alkyl lysophospholipids significantly activate cytotoxic macrophages, leading to enhanced Fc-receptor-mediated phagocytosis and increased humoral immune response and delayed hypersensitivity reaction. Further studies on the immunostimulatory action of alkylglycerols suggest a primary action on the macrophage. The process of macrophage activation has been demonstrated with both synthetic and natural alkylglycerols. While the exact mechanism has not been found, both an autocrine and paracrine system have been suggested.
AKG have been shown to stimulate hematopoiesis, erythropoiesis, thrombocytosis, and granulocytosis in animals. Since alkyl-Gro are found in hematopoietic organs such as bone marrow, one may hypothesize that they have an important role in hematopoiesis, and could behave as precursors of PAF, which has stimulating functions in bone marrow cell lines.
Mechanisms of anti-tumor effects could also be related to anti-angiogenic activities, since both unsaturated alkyl-Gro reduced endothelial proliferation, which is involved in neo-angiogenesis. This was corroborated in animal models: a 5-day treatment with alkylglycerols curtailed the presence in tumors of von Willebrand factor, a marker of endothelial cells. This result suggested an anti-angiogenic effect of alkylglycerols. In summary, alkylglycerols were shown to decrease the growth, vascularization, and dissemination of Lewis lung carcinoma tumors in mice.
Several experimental studies have shown the ability of alkylglycerols to open the blood-brain barrier to facilitate the access of therapeutic drugs to the central nervous system. Of particular research interest is the increased transport of drugs across the blood-brain barrier (BBB) that has been reported in the presence of alkylglycerols. The mechanism appears to involve the amphipathic properties of these lipids acting on barrier membranes: non-ionic, amphipathic molecules form vesicles, and this property correlates with the disruption of membranes. High millimolar concentrations of certain short-chain alkylglycerols have been shown to cause enhanced drug transport into brain via disruption of the blood-brain barrier.
Metabolically, AKG is converted into alkyl- and alkenyl-phospholipids, which are key components of the cell membrane and play essential roles in maintaining membrane homeostasis and cellular functions. AKGs are involved in the synthesis of 1-O-alkylcerophosphocholine, the precursor of platelet-activating factor (PAF), and increase the production of ether analogues of DAG in monocyte cell lines. However, the ether analogue of DAG originated from AKGs has been demonstrated to have inhibiting activity on PKC in endothelial cells. Thus, the mechanism of action of AKGs remained particularly unclear.
The mechanisms of action of AGs are not fully understood. Several biochemical mechanisms could be involved in the multiple activities of alkyl-Gro.
This is the area with the longest clinical history and the strongest body of human evidence, derived primarily from the Brohult research group in Sweden, though the studies are now decades old and by modern standards lack some methodological rigor.
In patients with uterine cancer, it was shown that the decrease in white cells and thrombocytes which usually occurs during radiation treatment is less pronounced if alkylglycerols are administered during this treatment. In experiments on irradiated rats, it was shown that alkylglycerols or their esters inhibit, to a certain extent, the decrease of both megakaryocytes and nucleated cells in the bone marrow in connection with irradiation.
In 1977 it was shown that the incidence of injuries following radiation therapy for carcinoma of the uterine cervix was significantly decreased when the patients were treated with alkylglycerols. In 1979, it was shown that the frequency of severe fistulas (recto-vaginal and vesico-vaginal) was reduced by 47% when alkylglycerols were administered prior to radiation treatment.
When the results of Brohult's early investigations were analyzed, it was found that patients given alkyldiacylglycerols had a higher survival rate than the controls. After 3 years, the group treated with alkyldiacylglycerols showed a higher survival rate than the controls, and after 5 years the survival rate was still higher, and the difference was significant (p <0.05). The survival rate was higher for all tumor stages in patients treated with ether lipids than in the corresponding control groups.
Since the duration of radiation treatment varied between two and eleven weeks, there was a considerable variation in the amount of alkylglycerols given. The Brohults took advantage of this by ranking patients in the prophylactic group according to total dosage received and dividing them into two equal-sized groups, with the high-dosage subgroup receiving an average of 95 grams and the low-dosage subgroup receiving an average of 65 grams.
Dr. Astrid Brohult's initial research demonstrated that alkylglycerols could stimulate the production of white blood cells (leukocytes) and platelets (thrombocytes), and this hematopoietic effect was particularly significant in the context of radiation therapy for cancer.
Evidence strength: The overall quality and quantity of evidence is limited. Research — primarily from animal studies and some small-scale human trials — suggests that AKGs may modulate immune function. The Brohult studies are historically significant clinical investigations, but they predated modern controlled trial standards and have not been substantially replicated in large, randomized controlled trials.
AKGs are considered to be important immune-stimulating factors and are able to increase the number of leukocytes, lymphocytes, and platelets.
Administration of AGs increased the level of leukocytes and lymphocytes in aged rats. White blood cell count, IgG, and lymphocytes significantly increased, while neutrophils significantly decreased in aging patients after surgical and AGs treatment at a dose of 500 mg twice a day over 4 weeks.
A few clinical trials in humans, mostly from Scandinavian countries, reported positive effects of AKG supplementation on immune parameters, such as increased leukocyte counts and improved recovery after chemotherapy. However, these studies are often small, lack rigorous controls, and have not been widely replicated or confirmed in larger, high-quality clinical trials. Despite promising preliminary data, there is insufficient robust scientific evidence to strongly endorse AKGs for immune support.
In pigs, oral SLO increased both hematopoiesis and immunoglobulin production.
Evidence strength: While there is some scientific rationale for their use, the current evidence remains weak to moderate.
AKG and squalene have antitumor activity that may be based on different mechanisms, including induction of apoptosis of neoplastic cells, suppression of signal transduction, inhibition of angiogenesis, and promotion of transmembrane transport of cytotoxic agents.
In animal models: A mouse model was used to investigate the antitumor effects of SLO and of alkylglycerols purified from the same source, both administered orally. Either pure alkylglycerols or SLO reduced tumor growth in a similar manner, suggesting that alkylglycerols were involved in this effect. In alkylglycerol-treated mice, metastasis dissemination was reduced by 64 ± 8%, whereas SLO effect was 30 ± 9% below control.
Claims about the anticancer and immunostimulant properties of shark liver oil supplements are mainly based on in vitro or animal studies. Some authors nevertheless conclude that the alkylglycerols from shark liver oil may be useful as an adjunct to conventional cancer treatments and as a prophylactic. One study showed inhibition of tumor growth and a decrease in the number of radiation treatments and of complex lesions when alkylglycerol was administered before radiation therapy in patients with cervical cancer.
During the last century, initial clinical use of the SLO mixture was for treating leukemias and later preventing radiation sickness from cancer x-ray therapy. Selachyl alcohol is one of the most abundant AKGs in the SLO mixture and displayed strong activity in reducing lung metastasis number in a model of grafted tumor in mice (Lewis lung carcinoma cells).
Evidence strength: The preclinical (in vitro and animal) evidence is substantial and mechanistically plausible. Human clinical evidence in oncology is limited primarily to the historical Brohult studies of cervical cancer and radiation adjuvant therapy. These were not placebo-controlled randomized trials by contemporary standards. Claims about anticancer and immunostimulant properties of shark liver oil supplements are mainly based on in vitro or animal studies. Some authors nevertheless conclude that alkylglycerols from shark liver oil may be useful as an adjunct to conventional cancer treatments and as a prophylactic.
Several experimental studies have shown the ability of alkylglycerols to open the blood-brain barrier to facilitate the access of therapeutic drugs to the central nervous system. This has been investigated as a potential strategy to enhance delivery of chemotherapeutic agents to brain tumors. The evidence in this area is derived from animal and in vitro studies; no robust human clinical trials establishing this effect have been reported in the reviewed literature.
One Russian study indicated improvements in clinical status, anthropometric levels, lipids, and immunological status in patients with ischemic heart disease and hypertension who consumed SLO. SLO-enriched diets administered to rats with ischemic heart disease and hypertension improved clinical symptoms, anthropometric levels, lipidemic profile, and immunological status.
An in vitro study found that alkyl-Gro partially inhibited platelet-activating factor–induced serotonin release in rabbit platelets, though no impact on the spontaneous release of serotonin was noted. Limited data are available regarding the use of SLO on cardiovascular parameters in humans.
Evidence strength: Preliminary, primarily based on animal studies and very limited human observational data. No large clinical trials are documented in this area.
Shark liver oil has been used to help treat cancer, skin conditions, and respiratory ailments, as well as to reduce recurrent aphthous stomatitis and prevent radiation sickness. However, limited clinical data are available.
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. The protective action of SLO from bacterial and fungal infections has also been emphasized, and it has been recommended for patients suffering from atopic dermatitis. These reports are based on limited evidence and require further controlled study.
Research has highlighted the protective action of SLO from bacterial and fungal infections, recommending it for patients suffering from atopic dermatitis. This evidence is largely derived from observational and animal data, with no substantial randomized controlled human trials identified in the reviewed literature.
AKG exhibits several biological activities, including anti-cancer effects, the enhancement of sperm motility, and the stimulation of the immune system and hematopoiesis. Animal data suggest SLO may improve fertility. No human clinical trials in this area are documented in the reviewed sources.
Administration of AGs increased the level of leukocytes and lymphocytes in aged rats and lymphocytes in a rat chronic stress model (200 mg/kg during 6 weeks). The greatest increase in the number of leukocytes was obtained at a separate use of AGs or AGs in combination with n-3 PUFAs. In contrast, lymphocytes showed a stronger response to an AGs-enriched diet. Therefore, AGs must be the substances with direct and indirect pathways that participate in the processes associated with immunity. These findings come from animal studies and small human series and are considered preliminary.
Alkylglycerols are available primarily in the form of shark liver oil, in both oral (capsule or liquid) and topical preparations. The following dosages have been reported in sources:
There is no standardized dose for alkylglycerols.
Few toxic effects have been reported. SLO supplements may have an unpleasant taste and/or odor.
There have been reports of SLO-induced pneumonia in humans and pigs. This refers to lipoid (exogenous lipoid) pneumonia, a known adverse effect of oily substances when aspirated rather than properly swallowed. This is a documented, factual risk with oily supplements in general.
No adverse reactions or effects on mortality were noted in rats receiving short- and long-term doses of a supercritical fluid extract of SLO at doses 100 to 200 times that of normal human consumption.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Contraindications have not been identified. No drug interactions are well documented. However, given their modulation of PKC and PAF pathways — both of which are involved in platelet function and inflammatory signaling — interactions with anticoagulant or antiplatelet medications are biologically plausible but have not been systematically studied in humans.
SLO contains vitamins A and D among its constituents, and because SLO is taken in addition to other supplements, there is a theoretical risk of hypervitaminosis A with prolonged high-dose use, though this is not specifically documented in the reviewed literature.
High or prolonged doses of shark liver oil may be associated with acne or oily skin in sensitive individuals. This is noted in the reviewed sources but without rigorous clinical documentation establishing causality or dose thresholds.
Health conditions that Alkylglycerols may help support.
Body systems that Alkylglycerols may help support.
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