History Sharkliveroil l What is squalene? l The Role of Squalene in Health  l  Dr. Carl A. Luer

Dr. William Lane interview by dr. Passwater  Dr. William Lane  l  Dr. Bikul Das  l  G.S. Kelly Clinical uses

Role of Squalene in Health

The Role of Squalene in Health
Squalene is a polyunsaturated hydrocarbon that is widely distributed in nature. Although very little is found in common foodstuffs such as plant oils such as olive oil and palm oil, meats, wheat-germ oil and some fish oils as well as in human sebum, it is found in large quantities in liver oil of deep-sea sharks living at the depth of 150-1,000 meters. According to the USDA survey taken in 1965, the daily intake of Squalene in the average U. S. diet ranged from 24 to 38/mg per 2,000 calories from various foodstuffs. As the principal hydrocarbon of human surface lipids, it constitutes up to 1 1% of total surface fat and approximately 5% of adult surface sebum. Squalene was first documented in 1916 by Dr. Tsujimoto, a Japanese marine oil chemist who had discovered a large quantity of Squalene in the liver oil of deep-sea shark belonging to the family of Squalidae, a fatty shark. In this species, the liver weight accounts for approximately 1/4 of their body weight, and about 80% of the liver weight is composed of oil. Since approximately 90% of the liver oil is Squalene, it actually accounts for roughly 20% of the body weight of deep-sea sharks. Although ecological conditions of sharks living in the deep sea where the sunlight hardly reaches are not fully known, oxygen is scarce and the water pressure is high (1 atm/lOin depth). Squalene is not present in liver oil of sharks living in shallow sea. The fact that deep-sea sharks contain large quantities of Squalene may be regarded as playing an important role for maintaining buoyancy under high water pressure and for channeling oxygen in an unknown mechanism.

Sharks have an amazing ability to resist cancer. Seven cases of tumors in sharks have been documented worldwide since the Smithsonian Institution began keeping such statistics twenty years ago, and only two of these tumors were considered malignant. By contrast, thousands of tumors are regularly reported in other fish by both scientists and fisherman. Dr. Carl Luer, a marine biologist at the Motte Marine Laboratory in Sarasota, FL, has fed 200 nurse sharks with diets containing Alphatoxin-B for seven years and found none of them has developed cancer. Comparable dosages to rainbow trout produce massive tumors within six months. Dr. Luer has reported that shark livers do not activate Alphatoxin-B into a cancer causing form. Not only free from cancer, sharks appear to be free of most all infectious diseases.

Squalene is an excellent quencher of thermodynamically active singlet oxygen and effectively binds free oxygen molecules. Direct measurements of Squalene oxidation products show that it is capable of binding with approximately 25% of its weight with oxygen. Squalene also appears to scavenge oxygen free radicals, such as the hydroxy radical (OH) and the supper-oxide radical (02) When molecular oxygen becomes electronically excited by some chemical physical processes, singlet oxygen is produced. Singlet oxygen is in the highest energy state and therefore initiates a variety of harmful reactions such lipid peroxidation. Photosensitive compounds such as pigments (chlorophyll) and carcinogenic aromatic hydrocarbons (anthracenes) are effective promoters for singlet oxygen. Various studies have demonstrated that the pervasiveness of singlet oxygen is the atmosphere by sunlight irradiation of various air-borne pollutants, direct photolysis of ozone and industrial waste products such as phorbol esters, ether, alcohol, and pigments. Singlet oxygen resulting from atmospheric pollution may be involved in numerous negative reactions affecting plants, animals, and humans.

Oxygen free radicals such as the hydroxy radical (OH) and the superoxide radical(02) are generated from not only ionizing radiation and intermediates in the metabolism of chemical carcinogens, but also normal metabolic reactions within the cells in human bodies. These reactive oxygen species are implicated in oxidation damages to cytoplasmic organelles of the cell, cellular membranes and nucleus material. The reactive oxygen species inside the nucleus may damage DNA, causing genetic mutations or even cell death.

The chemical function of Squalene apparently resides with its superior antioxidant effect. Experiments with animals have shown that Squalene given to animals as a dietary supplement has preventative effects against carcinogenesis. Highly purified Squalene extracted from deep-sea shark liver oil exhibited stimulation of the reticuloendothelial system, which scavenges invading foreign organisms. And several scientists reported antitumor activity of highly purified Squalene against transplanted tumors. The number of the 1gM antibody forming cell was also increased by Squalene administration in the tumor-bearing and the healthy mice. Delayed hypersensitivity reaction against measuring swelling of the foot pads of mice was also stimulated by administration of Squalene. On the other hand, the highly purified Squalene did not exhibit a direct cytotoxic activity on the tumor cell both in vitro and in vivo.

In cancer immunotherapy, augmentation of the tumor specific as well as non- specific immunity is critical and important. The immunostimulating effect and the anti- tumor activity of highly purified Squalene are very significant. This is particularly true because Squalene is a natural supplement. The nature of radiation toxicity to living bodies is not well comprehended by lay people. Ionizing bodies actually generates profuse amounts of oxygen free radicals. Radiation induced toxicity and injury are attributed to the oxidative damages of cell membranes as well as the genes in the cell nucleus by the reactive oxygene species. An animal experiment with mice was recently conducted to determine whether Squalene protects animal bodies from radiation toxicity and injury. For this, 90 mice were divided into two groups. One was fed a diet supplemented with 2% of Squalene while the other received a control diet for two weeks. Both groups were also exposed to an intermediate dosage of Gamma Radiation (600 Roentgens). All animals whose diet included Squalene survived for 30 days, whereas half of the non-squalene group died within 21 days after the radiation exposure. Animals treated with Squalene had 30% more total white blood cells than mice which received no Squalene. The data clearly showed that Squalene protected the animals against the toxicity of ionizing radiation. The final report on the Safety Assessment of Squalene by the American Toxicology Society in 1982 concluded that the acute toxicity of Squalene in animals by all routes is very low regardless of dosage. Squalene is an non-irritant even at 100% concentration.

In humans Squalene is transported by the Very Low-Density lipoproteins in blood. Distribution of Squalene in human tissues is ubiquitous, with greatest concentrations in the intestinal mucosa followed by the skin, adipose tissues, and all other tissues. Squalene readily enters cell membranes owing to its hydrophobic properties and can be transported into the cell by Squalene carrier proteins that are synthesized in the liver. Therefore, Squalene plays an important versatile role as an antioxidant in the cell membranes as well as intracellular organelles including the nucleus.
What is Squalene?
Squalene is an individually resolved component of Aizame shark liver oil.
This ubiquitous compound (C30H50) is a metabolite of sterol synthesis and is also found in human tissues and plasma.’ Shark’s have a highly active immune system. Researchers have long been interested in the apparent resistance of elasmobranchs to neoplasia.2 Studies conducted at the University of Miami School of Medicine have shown that shark serum contains a unique variety of antibodies that can destroy different types of cancer cells.3 Cancer in sharks is practically nonexistent. In fact, only six cases of tumors in sharks have been documented in studies exposing these fish to a wide variety of man-made 4 toxins.

Even in cases where sharks are exposed to Alfatoxin-B1, the most potent, naturally acquiring liver cancer-causing agent known, they still do not get cancer. In most animals exposed to Alfatoxin-B 1, the liver changes into a cancer causing form.5 Carl Luer, of the Mote Marine Laboratory in Sarasota, FL is another research scientist whohas studied tumor formation in sharks. The focus of his research concerns the action of the liver enzymes known to be involved in detoxification of environmental carcinogens. These mixed function oxidase offer the first line of defense against cancer causing chemicals. Squalene also activates the key antioxidant enzyme, glutathione transferase.6 Activation of these enzymes have important clinical applications in human subjects.

The relatively high Phase-Il activity in conjunction with pro-carcinogen activation capability of shark liver preparations would appear to play a role in resistance of elasmobranchs to chemical carcinogenesis. In studies measured by the Ames Mutagenicity Test, it was found that shark and skate liver microsomes possess very low activity converting Aflatoxin-B 1 to the carcinogenic AFB- 1 epoxide. This partly explains why sharks exposed to these potent carcinogens do not develop cancer.7
Lipids derived from shark liver have been reported to stimulate the endothelial 8 system. Other reports have been described as an enhancement of anti-tumor activities of cell wall skeleton and mycobacterial components emulsified with Squalene. This oil also stimulates host resistance against bacterial infection as well as transplantable tumor challenge by the combined use of the respective antigen.9 Squalene has also been examined for its ability to potentiate the cytotoxicity and antitumor activity of anticancer agents, such as adnamycin, 5FU and cis-platinum in vivo and vitro. The antitumor activities of these anticancer agents combined with Squalene were tested against sarcoma 180 ascite cells.’0 The combination of anticancer agents with membrane-active agents is useful because it can overcome drug resistance and inhibit the development of drug resistant tumors. In other studies performed by Robert Langer at M.I.T., Squalene strongly inhibited tumor-induced neovascularization.3 Recently Nakagawa and co-workers have reported antitumor activity of highly purified squalene immune transplantable tumor systems. In cancer immunotherapy, augmentation of the tumor-specific as well as nonspecific immunity is critically important.”

Squalene also has some antifungal properties which make it effective in candidiasis and has been shown to enhance the effects of Amphotericin-B (Fungizone) against a variety of candida species.’12
Acute and chronic toxicity tests orally and intraperitoneally establish squalene as an extremely safe compound. Because of its low or absent toxicity, squalene may be useful in combination therapy with other agents, particularly if it can overcome drug resistance in tumors. 13,14.As a nutritional immunostimulant, squalene is a valuable adjunct in other less severe conditions and may be prescribed prophylactically in immunocompromised individuals.

Why is shark liver oil especially recommended as a preventive for children, pregnant women aged people;
how and which substance from shark liver oil effects the complexion, fresh look, fading of wrinkles, vitality…;
Why had the benefits of shark liver oil been kept a secret in the countries of the Far East and Scandinavia;
What are the most common diseases caused by radiation and what do doctors and scientists recommend a protection against its effects after they have emerged;Which diseases emerge as the result of immunity loss; “A moving story of a Spanish pilot, Luis de la Hoza, about a massacre of an entire nation: …
They were bombed with new types of weapon, poisonous gases that weaken the immune system, bombs that pollute the soil, field poison, bombs causing sterility…

After the dreadful bombing campaigne in Kosovo and some towns in Serbia (Bor, Kragujevac, Pancevo, Novi Sad, Niš) with the uranium ammunition there has been reported terrifying radiation.

Today, when scientists and doctors have completely investigated the miraculous effects of shark liver oil in the treatments of various diseases, the fantastic strenghtener of the human immune system and as a preventive against various diseases, shark liver oil has gained recognition on the revolutionary field of natural medicine, especially when taken into account the already existing therapies in the official medicine for certain diseases which may bring unwanted effects, and which are sometimes more destructive that the illness itself. The prediction of physicists that by year 2000 every other man in the USA is going to suffer from cancer, caused panic among the researchers who are trying to find a cure, and even rather a preventive for healthy people for this disastrous sisease. Since 1986 shark liver oil has been used in Germany as an unavoidable means for treating cases of oncological lung diseases.
Find out why this may be the most important book on your health you will read this year.

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Sources and references Squalene and haaienleverolie

1. Berger S.M.: 'Forever Young', 1ste ed., 1989.

2. Tsjujimoto M., Toyam Y., 1992: ' Unsaponifiable Constituents (higher alcohol) of the liver oil of the sharks and rays'. Chem Umschau 29: 27 - 29, 43 - 45

3. Dr. Conrado O. Venzon, 'The Precious Oil of the Deep-Sea Shark', Worldwide Publ.Services Quezon City, Philippines.

4. 'The Healer Shark', Neil Solomons MD.Ph.D. and Richard Passwater, Ph.D. 1998

5. Brohult, Astrid, 1963: 'Alkylglycerols and their use in Radiation Treatment', Acta. Radiol. Suppl. 223: 7 - 99, Stockholm.

6. Dr. William Lane Comac, 'Sharks don't Get Cancer', 1992.

7. ' Fish Oil May Ease Arthritis Pain'. Med. World News July 14, 1986, p. 9.

8 Glausinz: 'The Secret Healing Power of Sharks', The Medicine Discoverer Magazine, January 1994.

9. Prof. dr. J. de Vries, Hart- en vaatziekten vormen samen met kanker de belangrijkste doodsoorzaak in de westerse wereld. Studies wijzen uit dat visolie unieke vetzuren bevat die preventief werken. Waar blijven de aanbevelingen van volksgezondheid? Natuur en techniek 65, 12 1997

10. Kromhout, Daan, Bosschieter, Edward B. and Coulander, Cor de Lezenne, 1985: 'The Inverse relationship Between Fish Oil Consumption and 20-Year old Mortality from Coronary Health Diseases'.

11. Takashi Yokota M.D., 'The Miracle of Squalene (Cures Cancer & Modern Diseases)'

The Medicine Discoverer, January 1994, 'The Secret Healing Power of Sharks'.

13. Martin-Moreno JM, Willett WC, Gorgojo L et al. Dietary fat, olive oil intake and breast cancer risk. Int.J Cancer 1994;58:

14. Trichopoulou A, Katsouyanni K, Stuver S et al. Consumption of olive oil and specific food groups in relation to breast cancer risk in Greece. J Natl.Cancer Inst. 1995;87:110-6.

15. Landa MC, Frago N, Tres A. Diet and the risk of breast cancer in Spain. Eur.J Cancer Prev. 1994;3:313-20.

16. Franceschi S, Favero A, Decarli A et al. Intake of macronutrients and risk of breast cancer. Lancet 1996;347:1351-6.

17. La Vecchia C, Negri E. Fats in seasoning and the relationship to pancreatic cancer. Eur.J Cancer Prev. 1997;6:370-3.

18. Porter, Ph.D. Squalene Monooxygenase, University of Kentucky

19. Newmark HL. Squalene, olive oil, and cancer risk: a review and hypothesis. Cancer Epidemiol Biomarkers Prev 1997

20. Rao CV, Newmark HL, Reddy BS. Chemopreventive effect of squalene on colon cancer. Carcinogenesis 1998;19:287-290

21. Nakagawa M, Yamaguchi T, Fukawa H, et al. Potentiation by squalene of the cytotoxicity of anticancer agents against culture mammalian cells and murine tumor. Jpn J Cancer Res 1985;76:315-320.

22. Asnis DS, Saltzman HP, Melchert A. Shark oil pneumonia. An overlooked entity. Chest 1993;103:976-977.

23. Yamaguchi T, Nakagawa M, Hidaka K et al. Potentiation by squaleen of antitumor effect of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-nitros ourea in a murine tumor system. Jpn.J Cancer Res. 1985;76:1021-6.

24. Smith TJ, Yang GY, Seril DN, Liao J, Kim S. Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis by dietary olive oil and squaleen. Carcinogenesis 1998;19:703-6.

25. Smith, T. J., Kim, S., Lee, M. J., Yang, G. Y., Newmark, H. L., and Yang, C. S. Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK)-induced lung tumorigenesis and DNA oxidation by dietary squaleen. Proceedings of the American Association for Cancer Research 40, 262. 1999. Ref Type: Journal (Full)

26. Dr. Bikul Das. The Science behind Squalene. The Human Antioxidant. 2000. Toronto Canada

27. Kelly GS. Squaleen and its potential clinical uses. Altern.Med Rev. 1999;4:29-36.

28. Fliesler SJ, Keller RK. Isoprenoid metabolism in the vertebrate retina. Int.J Biochem.Cell Biol. 1997;29:877-94.

29. Strandberg TE, Tilvis RS, Miettinen TA. Metabolic variables of cholesterol during squaleen feeding in humans: comparison with cholestyramine treatment. J Lipid Res. 1990;31:1637-43.

30. Kohno Y, Egawa Y, Itoh S, Nagaoka S, Takahashi M, Mukai K. Kinetic study of quenching reaction of singlet oxygen and scavenging reaction of free radical by squaleen in n-butanol. Biochim.Biophys.Acta 1995;1256:52-6.

31. Miettinen TA, Vanhanen H. Serum concentration and metabolism of cholesterol during rapeseed oil and squaleen feeding. Am J Clin.Nutr. 1994;59:356-63.

32. Chan P, Tomlinson B, Lee CB, Lee YS. Effectiveness and safety of low-dose pravastatin and squaleen, alone and in combination, in elderly patients with hypercholesterolemia. J Clin.Pharmacol. 1996;36:422-7.

33. Smith TJ. Squaleen: Potential chemopreventive agent by squalene. Expert.Opin.Investig.Drugs 2000;9:1841-8.

34. Martin-Moreno JM, Willett WC, Gorgojo L et al. Dietary fat, olive oil intake and breast cancer risk. Int.J Cancer 1994;58:

35. Luer, C. A. et al: (In Vitro Metabolism Of The Proximate Carcinogen Aflatoxin-B 1 By Liver Portions Of The Calf, Nurse Shark And Clearnose Skate) Fed. Froc. 46:2 290, 1987
36. Trichopoulou A, Katsouyanni K, Stuver S et al. Consumption of olive oil and specific food groups in relation to breast cancer risk in Greece. J Natl.Cancer Inst. 1995;87:110-6.

37. Paul Terry, Paul Lichtenstein, Maria Feychting, Anders Ahlbom, Alicja Wolk, Vol 357, June 2, 2001 The Lancet

38. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors a and g . Steven A. Kliewer, Scott Sundseth et al. Nat. Academy of Sciences of the USA 1997

39. Joseph Vamecq, Norbert Latruffe, Vol 354, July 10, 1999 The Lancet

40. E. Mueller, P. Sarraf , …… Bruce M. Spiegelman. Molecular Cell. Vol 1, 465-470, February, 1998

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