Omega-3 Benefits: Omega-3 in Hematology

Omega-3 benefits in hematology

Chronic consumption of fish oil favours renewal of haematopoietic stem cells and extramedullary hematopoiesis (1).

Anaemias and omega-3

Iron deficiency and omega-3

In young women with iron deficiency, greater fish oil consumption increases insulin sensitivity and HDL-cholesterol levels compared to greater red-meat consumption (2).

In South Africa, iron supplementation (required in malaria-free areas to avoid infection) has been shown to increase respiratory morbidity, but this secondary effect is prevented by the joint administration of omega-3 long-chain polyunsaturated fatty acids (omega-3 LC-PUFA) (3).

Ribavirin and pegylated interferon-induced anaemia and omega-3

Ribavirin and pegylated interferon-induced anaemia can require a reduction in dose or even interruption of treatment. These consequences can be prevented by supplementation with eicosapentaenoic acid (omega-3 EPA), which significantly improves haemoglobin levels in these patients (4,5).

Cycle-cell anaemia and omega-3

Known characteristics of cycle-cell anaemia are: significantly lower omega-3 EPA and docosahexaenoic acid (DHA) plasma levels compared to healthy controls (6-8) and chronic inflammation (7).

Treatment with omega-3 LC-PUFA has significantly reduced vaso-occlusive crises, cases of severe anaemia and blood transfusions, improved leukocyte count and cut time off school due to the disease, all of which are adverse effects (8).

The higher the blood levels of omega-3 EPA and DHA, the fewer the complications in cycle-cell anaemia (number of vaso-occlusive crises, among others) and the higher the stable haemoglobin level (9).

Haematological neoplasms and omega-3

Leukaemia and lymphomas and omega-3

Development of leukaemia and lymphomas is related to a rise in inflammation modulators. Different T-cells have different functions in the neoplastic environment: some have anti-tumour activity, while others have pro-tumour activity. At the same time, the inflammatory process favours production of lipid mediators, which are also involved in the inflammatory response. Omega-3 EPA and DHA reduce arachidonic acid (AA) production, so that most of the lipid mediators produced are less inflammatory; furthermore, they also influence cytokine production (10).

It has been shown that when most energy and fat intake comes from fish, the risk of developing leukaemia, multiple myeloma and non-Hodgkin lymphoma is lower (11).

Both omega-3 EPA and DHA reduce Th2 cytokine expression in RBL-2H3 basophilic leukaemia cells, thus reducing slanted allergic immune responses (122).

Omega-3 DHA potentiates the apoptotic action of arsenic trioxide on HL-60 cells, indicating that the combination of both could be applicable to the treatment of leukaemia (13).

Acute myeloid leukaemia

Omega-3 DHA may have a role as adjuvant treatment (which is well tolerated) in acute myeloid leukaemia (AML), as it induces death in an early undifferentiated subtype of AML cell line with no harmful effects on normal haematopoiesis (14, 15).

Chronic myeloid leukaemia

In mouse models, Δ(12)-PGJ3, an omega-3 EPA metabolite already shown to act on leukaemia stem cells (in the bone marrow and spleen) without affecting normal haematopoietic stem cells, has produced results that make it a promising candidate for treating chronic myeloid leukaemia (16, 17).

Chronic lymphocytic leukaemia

The nuclear factor kappa B (NFκB) pathway has been proposed as a therapy for chronic lymphocytic leukaemia. Omega-3 LC-PUFA supplementation in patients with Rai stage 0-1 chronic lymphocytic leukaemia had the following effects: increased plasma omega-3 LC-PUFA; reduced NFκB activation in lymphocytes, increased in vitro lymphocyte sensitivity to doxorubicin; and significantly reduced gene 32 expression in lymphocytes (18).

Non-Hodgkin’s Lymphoma

According to a study performed in conjunction with various departments of the Mayo Clinic, diets high in omega-3 LC-PUFA and foods of marine origin inversely correlate to the risk of suffering non-Hodgkin lymphoma (19).

Multiple myeloma

Omega-3 EPA and DHA induce selective cytotoxic effects in multiple myeloma (cells L363, OPM-1, OPM-2 and U266) and increase sensitivity to bortezomib, without affecting normal peripheral mononuclear cells (20).

Bone-marrow transplantation and Omega-3

Supplementation with omega-3 EPA has been shown to significantly reduce complications after bone-marrow transplants, compared to lack of supplementation; patients who undergo transplantation show (significantly) lower levels of leukotriene B4, thromboxane A2, prostalgandin I2, tumour necrosis factor-alpha, interferon gamma, interleukin-10, thrombomodulin and plasminogen activator inhibitor-1; in addition, the survival rate is higher (also significantly so). This may mean that systemic inflammatory response syndrome underlies complications in bone-marrow transplants (21).

Chemotherapy-induced leukopaenia and omega-3

In the murid model, diets rich in omega-3 LC-PUFA increased levels of stem-cell factor and fibroblast growth factor-1 and reduced chemotherapy-induced leukopenia (with intraperitoneal cisplatin) (22).

Porphyria and omega-3

The diet of patients with porphyria has been seen to be deficient in omega-3 LC-PUFA (23).



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Effect of omega-3 (n-3) fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2013 Jan;97(1):37-44. doi: 10.3945/ajcn.112.036319. Epub 2012 Nov 28.// 9 Okpala I, Ibegbulam O, Duru A et al. Pilot study of omega-3 fatty acid supplements in sickle cell disease. APMIS. 2011 Jul;119(7):442-448. doi: 10.1111/j.1600-0463.2011.02751.x. Epub 2011 Apr 17. // 10 Betiati Dda S, de Oliveira PF, Camargo Cde Q et al. Effects of omega-3 fatty acids on regulatory T cells in hematologic neoplasms. Rev Bras Hematol Hemoter. 2013;35(2):119-125. doi: 10.5581/1516-8484.20130033. // 11 Fritschi L, Ambrosini GL, Kliewer EV et al. Dietary fish intake and risk of leukaemia, multiple myeloma, and non-Hodgkin lymphoma. Canadian Cancer Registries Epidemiologic Research Group. Cancer Epidemiol Biomarkers Prev. 2004 Apr; 13(4):532-537. // 12 Jin M, Park S, Park BK et al. Eicosapentaenoic acid and docosahexaenoic acid suppress Th2 cytokine expression in RBL-2H3 basophilic leukemia cells. J Med Food. 2014 Feb;17(2):198-205. doi: 10.1089/jmf.2013.2935. Epub 2014 Jan 24. // 13. Sturlan S, Baumgartner M, Roth E et al. Docosahexaenoic acid enhances arsenic trioxide-mediated apoptosis in arsenic trioxide-resistant HL-60 cells. Blood. 2003 Jun 15;101(12):4990-4997. Epub 2003 Feb 27. // 14. Yamagami T, Porada CD, Pardini RS et al. Docosahexaenoic acid induces dose dependent cell death in an early undifferentiated subtype of acute myeloid leukemia cell line. Cancer Biol Ther. 2009 Feb;8(4):331-337. Epub 2009 Feb 3. // 15 Quesenberry PJ, Butera JN. An interesting fishing expedition. Cancer Biol Ther. 2009 Feb;8(4):338-9. Epub 2009 Feb 12. // 16 Kudva AK, Kaushal N, Mohinta S et al. Evaluation of the stability, bioavailability, and hypersensitivity of the omega-3 derived anti-leukemic prostaglandin: Δ(12)-prostaglandin J3. 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Omega-3 fatty acids, EPA and DHA induce apoptosis and enhance drug sensitivity in multiple myeloma cells but not in normal peripheral mononuclear cells. J Nutr Biochem. 2014 Dec;25(12):1254-1262. doi: 10.1016/j.jnutbio.2014.06.013. Epub 2014 Sep 6. // 21 Takatsuka H, Takemoto Y, Iwata N et al. Oral eicosapentaenoic acid for complications of bone marrow transplantation. Bone Marrow Transplant. 2001 Oct;28(8):769-774. // 22 Murakami K, Miyata H, Miyazaki Y et al. ω-3 Fatty Acids Reduce Chemotherapy-Induced Hematological Toxicity by Bone Marrow Stimulation in Mice. JPEN J Parenter Enteral Nutr. 2015 Jul 28. pii: 0148607115597887. [Epub ahead of print]. // 23 Romaguera D, Puigros MA, Palacin D et al. Nutritional assessment of patients affected by Porphyria variegata. Ann Nutr Metab 2006;50:442-449.