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).
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).
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).
1. Xia S, Li XP, Cheng L et al. Fish Oil Rich Diet Promotes Hematopoiesis and Alters Hematopoietic Niche. Endocrinology. 2015 Jun 10:en20151258. [Epub ahead of print] // 2 Navas-Carretero S, Pérez-Granados AM, Schoppen S et al. An oily fish diet increases insulin sensitivity compared to a red meat diet in young iron-deficient women. Br J Nutr. 2009 Aug;102(4):546-553. doi: 10.1017/S0007114509220794. Epub 2009 Feb 12. // 3 Malan L, Baumgartner J, Calder PC et al. n-3 Long-chain PUFAs reduce respiratory morbidity caused by iron supplementation in iron-deficient South African schoolchildren: a randomized, double-blind, placebo-controlled intervention. Am J Clin Nutr. 2015 Mar;101(3):668-679. doi: 10.3945/ajcn.113.081208. Epub 2014 Dec 31. // 4 Suzuki M, Inage E, Minowa K et al. Prophylaxis for ribavirin-related anemia using eicosapentaenoic acid in chronic hepatitis C patients. Pediatr Int. 2012 Aug;54(4):528-531. doi: 10.1111/j.1442-200X.2012.03603.x. Epub 2012 Apr 19. // 5 Takaki S, Kawakami Y, Imamura M et al. Eicosapentaenoic acid could permit maintenance of the original ribavirin dose in chronic hepatitis C virus patients during the first 12 weeks of combination therapy with pegylated interferon-alpha and ribavirin. A prospective randomized controlled trial. Intervirology. 2007;50(6):439-446. doi: 10.1159/000114718. Epub 2008 Feb 4. // 6 Aslan M, Celmeli G, Ozcan F et al. LC-MS/MS analysis of plasma polyunsaturated fatty acids in patients with homozygous sickle cell disease. Clin Exp Med. 2014 Jun 13. [Epub ahead of print]. // 7 Daak AA, Elderdery AY, Elbashir LM et al. Omega 3 (n-3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease. Blood Cells Mol Dis. 2015 Jun;55(1):48-55. doi: 10.1016/j.bcmd.2015.03.014. Epub 2015 Mar 31. // 8 Daak AA, Ghebremeskel K, Hassan Z et al. 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. PLoS One. 2013 Dec 2;8(12):e80622. doi: 10.1371/journal.pone.0080622. eCollection 2013. // 17 Hegde S, Kaushal N, Ravindra KC et al. Δ12-prostaglandin J3, an omega-3 fatty acid-derived metabolite, selectively ablates leukemia stem cells in mice. Blood. 2011 Dec 22;118(26):6909-19. doi: 10.1182/blood-2010-11-317750. Epub 2011 Oct 3. // 18 Fahrmann JF, Ballester OF, Ballester G et al. Inhibition of nuclear factor kappa B activation in early-stage chronic lymphocytic leukemia by omega-3 fatty acids. Cancer Invest. 2013 Jan;31(1):24-38. doi: 10.3109/07357907.2012.743553. Epub 2012 Nov 29. // 19 Charbonneau B, O'Connor HM, Wang AH et al. Trans fatty acid intake is associated with increased risk and n3 fatty acid intake with reduced risk of non-hodgkin lymphoma. J Nutr. 2013 May;143(5):672-681. doi: 10.3945/jn.112.168658. Epub 2013 Mar 13. // 20 Abdi J, Garssen J, Faber J et al. 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.