Fish oils are highly effective anti-cancer agents
Fish Oils are connected with low cancer risk:
"n-3 long-chain PUFA's, eicosapentaenoic and docosahexaenoic acids, were the most effective fatty acids in arresting the cell growth." from breast cancer study above
"high levels of dietary n-3 fatty acids from fish/shellfish (marine n-3 fatty acids) were significantly associated with reduced risk. Relative to the lowest quartile of intake, individuals in the higher three quartiles exhibited a 26% reduction in risk." Singapore Chinese Health Study
Each additional daily intake of 0.5 g of marine fatty acid from food was associated with a 24% decreased risk of metastatic cancer." Study of fish and prostate cancer (pdf)
"It is proposed that incorporation of DHA makes tumor plasma membranes substantially more permeable, which may explain, in part, its anti-tumor properties." DHA increases permeability of lipid vesicles and tumor cells
From a prostate cancer and fatty fish study from Sweden: Consumption of fatty fish might reduce the risk of prostate cancer, although epidemiological studies of fish consumption are rare. We studied the association between fish consumption and prostate cancer in a population-based prospective cohort of 6272 Swedish men. During 30 years of follow-up, men who ate no fish had a two-fold to three-fold higher frequency of prostate cancer than those who ate moderate or high amounts did. Our results suggest that fish consumption could be associated with decreased risk of prostate cancer.
In an Italian study looking at fish consumption (pdf), they concluded: "the results of this study suggest that, in addition
to the potential beneficial effect of fish consumption on cardiovascular
disease risk, the intake of even relatively small amounts
of fish is a favorable indicator of the risk of several digestive tract
cancers, notably colon and rectal cancer"
In a large review of omega3 oils and cardiovascular disease (pdf),"Evidence from prospective secondary prevention studies suggests that EPADHA supplementation
ranging from 0.5 to 1.8 g/d (either as fatty fish or supplements)
significantly reduces subsequent cardiac and all-cause mortality."
Fish Oils are shown repeatedly to kill cancer cells, and DHA is more effective than EPA:
"Conjugated eicosapentaenoic acid (CEPA) and conjugated docosahexaenoic acid (CDHA) ... showed intensive cytotoxicity with LD(50) at 12 and 16 microM, respectively, in DLD-1 cells (colorectal adenocarcinoma), while they had no effect on normal human fibroblast cell lines..." Study of EPA and DHA and apoptosis
showed that all fatty acids inhibited cell growth, whereas
only DHA induced cell apoptosis." DHA induces apoptosis in pancreatic cancer cells (pdf)
DHA must be incorporated into the cancer cell membrane to be effective. "The results indicate that uptake of DHA into tumour cells results in altered tumour cell membrane characteristics and a decreased ability to metastasize". Inhibitory effects of DHA on metastasis to the lung
"Fish oil significantly decreases certain markers of cell proliferation, as previously reported by others, but its greatest effect is on the maintenance of higher levels of apoptosis in the presence of carcinogen." Fish Oil Blocks Azoxymethane-Induced Rat Colon Tumorigenesis by Increasing Cell Differentiation and Apoptosis Rather Than Decreasing Cell Proliferation (pdf)
In a study on tumor growth and metastasis to the liver in mice, carp oil (0.1 or 0.2 mL per mouse) significantly reduced tumor growth and metastasis to the liver. Linoleic acid and linolenic acid had no effect on tumor growth or metastasis to the liver. Carp Oil but Not Linolenic Acid Inhibits Tumor Growth and Metastasis in Mice.pdf
In a study of human pancreatic cancer cells, both alpha linolenic acid and DHA inhibited cell growth but only DHA induced apoptosis.
"It is concluded from the results of the present study that the anti-tumoral effect of EPA is related mainly to its inhibition of cell proliferation, whereas that of DHA corresponds with its induction of apoptosis." Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: Effects on proliferation and apoptosis
"DHA was more potent than EPA in inhibiting the growth of MDA-MB-231 (breast cancer) cells "Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells
A case of a remission based on high consumption of fish oils:
he " consumed 15 g of the long-chain omega-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) per day" Nutritional Intervention With Omega-3 Fatty Acids in a Case of Malignant Fibrous Histiocytoma of the Lungs (thanks to Blake Frederick for sending us this article)
Fish oils and some specific cancers:
Fish oils help pancreatic cancer patients gain weight (see also pancreatic article above)
"there was a significant dose-response for risk of leukemia and NHL." Dietary Fish Intake and Risk of Leukemia, Multiple
Myeloma, and Non-Hodgkin Lymphoma (pdf)
DHA inhibits the growth of cultured metastatic melanoma cells. Cell Cycle Arrest and Apoptosis of Melanoma Cells by Docosahexaenoic Acid Association with Decreased pRb Phosphorylation
Lymphoma in dogs (pdf)
For an example of a patient response to DHA, see the article about Sam Hutchinson. If the link is broken, click here. "But the omega-3 seemed to pay off. Within weeks, the Hutchisons say Sam's hair and eyebrows began to grow back and they noticed he had more energy"
Fish Oil and DHA synergize other therapies also:
"In the present study, incorporation of 3% FOC in the diet, even without DOX chemotherapy, was as effective at suppressing tumor growth as was a course of DOX chemotherapy in mice that were consuming the 5% CO diet." and "These positive results justify clinical testing of FOC (fish oil concentrate) in conjunction with cancer chemotherapy." Three Percent Dietary Fish Oil Concentrate Increased Efficacy of Doxorubicin Against MDA-MB 231 Breast Cancer Xenografts
DHA helps arsenic trioxide fight leukemia: " Our data provide the first evidence that DHA may help to extend the therapeutic spectrum of As2O3 and suggest that the combination of As2O3 and DHA could be more broadly applied in leukemia therapy" .Docosahexaenoic acid enhances arsenic trioxide–mediated apoptosis in arsenic trioxide–resistant HL-60 cells
For a review of how butyrate and DHA synergize, click here
Vitamins E and C counter the effects of DHA
"An oxidative process was implicated in apoptosis induced by DHA because butylated hydroxytoluene" and "vitamin E prevented lipid peroxidation and reversed apoptosis"
and "We observed that pretreatment of PaCa-44 cells with the antioxidants BHT (10 μM) or vitamin E (40 μM) reversed the apoptosis induced by DHA (200 μM. We also observed that treatment of PaCa-44 cells with DHA induced an increase in MDA (Malondialdehyde) concentration that was strongly inhibited by pretreatment of cells with BHT or vitamin E " . Docosahexaenoic Acid Induces Apoptosis in the Human PaCa-44 Pancreatic Cancer Cell Line by Active Reduced Glutathione Extrusion and Lipid Peroxidation
"these results provide evidence that dietary FO (Fatty Oils) can significantly suppress growth of human breast carcinoma..." and " In conclusion, dietary FO induced suppression of human breast carcinoma growth is a function, at least in part, of an accumulation of lipid peroxidation products in the tumor tissues." Dietary fish oil inhibits human breast carcinoma growth: A function of increased lipid peroxidation
Besides showing a correlations between the number of fatty acid double bonds and the proportion of cells undergoing apoptosis (meaning DHA > flaxseed oil), this paper shows that PUFA-induced apoptosis was oxidative (via lipid peroxidation) and was blocked by vitamin E acetate. Apoptotic death of pancreatic cancer cells induced by polyunsaturated fatty acids varies with double bond number and involves an oxidative mechanism This double bond issue is supported by "Overall our data suggest that the number of double bonds in the carbon atom chain of the fatty acid is more important for the anti-proliferative and cytotoxic effects of n-3 and n-6 fatty acids in our in vitro system than the place of the double bond." The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE2 synthesis and cytotoxicity in human colorectal carcinoma cell lines
"In mammary tumours, it is observed that long-chain FA not only increase apoptosis, but also increase lipid peroxidation, and the apoptotic effect can be reversed by antioxidants." n-3 Fatty acids and lipid peroxidation in breast cancer inhibition
"The addition of Vitamin E to cancer cells ... almost completely restored cell growth.
Our data indicate that PUFA's significantly interfere with cell proliferation of breast cancer cells in vitro due to the formation of oxidation products." Influence of n-3 fatty acids on the growth of human breast cancer cells in vitro: Relationship to peroxides and Vitamin-E
"Inhibition of A549 or B16 cell growth by TGF-ß 1 in the presence of PUFAs was almost completely reversed by the antioxidant vitamin E, suggesting a role for lipid peroxidation in this process." Inhibition of Carcinoma and Melanoma Cell Growth by Type 1 Transforming Growth Factor ß is Dependent on the Presence of Polyunsaturated Fatty Acids
"In conclusion, some effects of the fish oil, especially on triglycerides and fibrinogen, were clearly
more pronounced when the oil was adequately supplemented with vitamin E. This is probably due to
the antioxidant effect of vitamin E, which leads to
efficient inhibition of fatty acid peroxidation, less
formation of MDA and larger amounts of active (n-3)
fatty acids at their sites of action in the liver. The end
result is pronounced decrease in the synthesis of tri
glycerides and fibrinogen." from The Effects of Fish Oil on Triglycerides etc in Humans Supplemented with Vitamin E (pdf)
Taking high doses of fish oil without Vitamin E supplementation is not recommended for healthy people. It subjects you to potentially greater free radical attack. Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women.
Rats burdened with tumors on a diet of polyunsaturated fatty acids did better without vitamin E. Suppression of the promoter effect of polyunsaturated fatty acids by the absence of dietary vitamin E in experimental mammary carcinoma.
"DHA was associated with increased production of intracellular ROS (reactive oxygen species) and toxic lipid peroxidation products and was abolished by the antioxidant vitamin E or when oleic acid (a
nonperoxidizable fatty acid) was used in place of DHA." Docosahexaenoic acid enhances arsenic trioxide–mediated apoptosis in arsenic trioxide–resistant HL-60 cells
"Both inhibition of the COX pathway by indomethacin as well as inhibition of direct lipid peroxidation by antioxidants such as vitamin E and C diminished the anti-proliferative effects of AA as well as EPA. Also, malondialdehyde, a product of lipid peroxidation and COX-activity was decreased by addition of vitamin E and partially decreased by indomethacin. These data support the hypothesis that growth inhibitory and cytotoxic effects of PUFAs with methylene-interrupted double bonds such as AA and EPA are due to peroxidation products that are generated during lipid peroxidation and COX activity." The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE2 synthesis and cytotoxicity in human colorectal carcinoma cell lines
Fish Oil Can Reduce Peripheral Neuropathy
"Moreover, a preventive effect of fish oil was observed on nerve histological damage [endoneurial edema, axonal degeneration (by 10-15%) with demyelination]. Moreover, the normal bimodal distribution of the internal diameter of myelinated fibers was absent in the DO group and was restored in the DM group. These data suggest that fish oil therapy may be effective in the prevention of diabetic neuropathy. " from Fish Oil Supplementation Prevents Diabetes-Induced Nerve Conduction Velocity and Neuroanatomical Changes in Rats
Fish Oil Dosage and Toxicity
"The maximum tolerated dose was found to be 0.3 g/kg per day of this preparation. This means that a 70-kg patient can generally tolerate up to 21 1-g capsules/day containing 13.1 g of eicosapentaenoic acid docosahexaenoic acid, the two major v-3 fatty acids. Dose-limiting toxicity was gastrointestinal, mainly diarrhea, and a poorly described toxicity designated as “unable to tolerate in esophagus or stomach.” Phase I Clinical Study of Fish Oil Fatty Acid Capsules for Patients with Cancer Cachexia: Cancer and Leukemia (pdf) to highlight a lengthy discussion on previous studies, discussed in this paper, click here.
18 grams a day of EPA was well tolerated in this study .Tolerance and incorporation of a high-dose eicosapentaenoic acid diester emulsion by patients with pancreatic cancer cachexia
There seems to be no long-term issues with taking DHA. Note this study used a dose of 400 mg/day, which is less than a cancer patient would take per day.
In a four year study of patients on DHA, "There was a trend toward lower mean vitamin E concentrations in the docosahexaenoic acid–supplemented group after 4 years. Docosahexaenoic acid supplementation did not compromise plasma antioxidant capacity, platelet aggregation, liver function enzyme activity, or plasma lipoprotein lipid content in patients with XLRP. Conclusion Long-term docosahexaenoic acid supplementation to patients with XLRP was associated with no identifiable safety risks in this 4-year clinical trial." Biological Safety Assessment of Docosahexaenoic Acid Supplementation in a Randomized Clinical Trial for X-Linked Retinitis Pigmentosa
Does any fish oil or DHA work? Probably not. We need this fish oil to be unoxidized.
The key to fish oil success lies in the numerous double bonds they have. DHA has 6 of them. EPA has 5. These oils are very susceptible to oxidation. Once they are exposed to air, oxidation begins. Their value in fighting cancer is their oxidizing in our bodies, not in the air. Any oxidation prior to consumption diminishes their value.
" The primary (n-3) fatty acids in fish oil, eicosapentaenoic acid [20:5(n-3)] and docosahexaenoic acid [22:6(n-3)] have up to 3 times as many double bonds per molecule than the (n-6) fatty acids found in corn oil, such as linoleic acid [18:2(n-6)]. This increases the opportunity for oxidant attack and can contribute to the propagation of ROS"
"Furthermore, we have shown dietary (n-3) PUFA to be readily incorporated into the mitochondrial membrane (38), predisposing the mitochondria to enhanced lipid peroxidation and membrane damage and contributing to the propagation of ROS generated by the mitochondrial electron transport system (36)."
" It is likely that many of the fatty acids consumed in these experimental diets maintained a high degree of unsaturation because the diets were kept at 80°C to prevent fatty acid oxidation. However, these conditions may not be practical outside of the laboratory setting, and less than optimal storage may enhance the degree of fatty acid oxidation before consumption. This may have a substantial impact on the physiologic effects of dietary lipid and definitely
warrants further attention." An Increase in Reactive Oxygen Species by Dietary Fish Oil Coupled with the Attenuation of Antioxidant Defenses by Dietary Pectin Enhances Rat Colonocyte Apoptosis
The challenge is getting these oils in a state of near zero oxidation. The ideal is to get a high quality product that does not contain anti-oxidants. This would require shipping and storage of the fish oils at very low temperatures. The best we can do now is use what products are available. Some vitamin E in the oil is unavoidable for fish oils sold in health food stores, as they are needed to stabilize the oils. You have to go with what you can get.
Fish oil, particularly DHA, has some other great benefits.Here are some quick references:
1. Reduced risk of Alzheimer's: risk, risk2
2. Lowered risk of Childhood diabetes
3. Lowered risk of heart attack: (Among women, higher consumption of fish and omega-3 fatty acids is associated with a lower risk of CHD, particularly CHD deaths)
4. Lowered risk of macular degeneration (A high intake of fish may reduce the risk of AMD)
A great source of DHA is www.martek.com. They are a major provider of DHA for the baby formula market, for example.
Questions? Need Help? email Jim T