BioActive Lipids 120c

Orthoplex

Here at Orthoplex, we have a mission to remove every excipient or additive that is not 100% essential to the formulation. Orthoplex BioActive Lipids has taken testing for purity to a new unprecedented level, a level we believe should be the new minimum standard. By independently third-party testing for over 460 environmental contaminants, including almost 200 pesticides, 30 common plasticisers and 3 radioactive isotopes, our aim is that everything that can be tested has been tested.

This product has been batch tested by HASTA for over 250 WADA prohibited substances. HASTA is the Australian sports supplement drug testing specialist, a division of Racing Analytical Services Limited (RASL), Australia's largest independent sports drug testing laboratory.

Gluten Free
Egg Free
Dairy Free
Soy Protein Free
Corn Free
    Product Details

    Pack Size
    120 Capsule

    Adult Dose
    Adult and Elderly Dose: Take 1-2 capsules two or three times per day, or as recommended by your registered healthcare practitioner.

    Storage
    Store below 25°C in a cool, dry place, away from direct sunlight. REFRIGERATE AFTER OPENING

    Indications

      • Supports healthy mood balance, cognitive function and stress response
      • Supports brain health and function
      • Supports omega-3 levels in the body in children
      • Supports healthy pregnancy and foetal development

    Excipients
    Manufacturing Excipients: D-alpha-tocopherol (non-GMO certified from sunflower oil), gelatin, glycerol, lemon oil distilled, purified water. Incidental Excipients: Sunflower oil.

    Warning
    If you are concerned about the health of yourself or your baby, talk to your health professional. Advise your doctor of any medicine you take during pregnancy, particularly in your first trimester. Keep out of reach of children. This health supplement is not to be used as a substitute for a varied diet. This product is exclusively a HEALTH SUPPLEMENT and NOT INTENDED TO DIAGNOSE, TREAT, CURE OR CORRECT ANY DISEASE. Contains Fish and Sulfites.

    Ingredients

    Each softgel capsule contains:

    Concentrated fish omega-3 triglycerides 1000.0mg
    equiv. Eicosapentaenoic acid (EPA) 360.0mg
    equiv. Docosahexaenoic acid (DHA) 240.0mg
    Drug Interactions
    Significance
    Ingredient
    Interaction Descriptions
    Moderate
    DOCOSAHEXAENOIC ACID (DHA)
    (Docosahexaenoic acid (DHA))
    Be cautious with this combination.
    View Interactions:
    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Severity: high
    Occurrence: unlikely
    Level of Evidence: B

    Theoretically, DHA may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.<br> Although some clinical evidence suggests that DHA might reduce collagen-stimulated platelet aggregation and thromboxane release, most clinical evidence suggests that DHA alone does not affect blood clotting (11112,11113,48020). However, theoretically, when given in combination with EPA as fish oil, concomitant use with anticoagulant or antiplatelet drugs (including aspirin) might increase risk of bleeding.

    References

    48020

    Woodman, R. J., Mori, T. A., Burke, V., Puddey, I. B., Barden, A., Watts, G. F., and Beilin, L. J. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis 2003;166(1):85-93.

    11112

    Leng GC, Smith FB, Fowkes FG, et al. Relationship between plasma essential fatty acids and smoking, serum lipids, blood pressure and haemostatic and rheological factors. Prostaglandins Leukot Essent Fatty Acids 1994;51:101-8.

    11113

    Nelson GJ, Schmidt PS, Bartolini GL, et al. The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids 1997;32:1129-36.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Theoretically, taking DHA with antihypertensive drugs might increase the risk of hypotension.<br> Fish oils containing DHA can lower blood pressure and might have additive effects in patients treated with antihypertensives (1001,1020,1030,1033,47944,48013,48020,48163); use with caution.

    References

    1001

    Prisco D, Paniccia R, Bandinelli B, et al. Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res 1998;1:105-12.

    1020

    Toft I, Bonaa KH, Ingebretsen OC, et al. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med 1995;123:911-8.

    1030

    Sacks FM, Hebert P, Appel LJ, et al. Short report: the effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the trials of hypertension prevention. J Hypertens 1994;12:209-13.

    1033

    Vandongen R, Mori TA, Burke V, et al. Effects on blood pressure of omega 3 fats in subjects at increased risk of cardiovascular disease. Hypertension 1993;22:371-9.

    47944

    Mori, T. A., Bao, D. Q., Burke, V., Puddey, I. B., and Beilin, L. J. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension 1999;34(2):253-260.

    48013

    Nestel, P., Shige, H., Pomeroy, S., Cehun, M., Abbey, M., and Raederstorff, D. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am.J.Clin.Nutr. 2002;76(2):326-330.

    48020

    Woodman, R. J., Mori, T. A., Burke, V., Puddey, I. B., Barden, A., Watts, G. F., and Beilin, L. J. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis 2003;166(1):85-93.

    48163

    Theobald, H. E., Goodall, A. H., Sattar, N., Talbot, D. C., Chowienczyk, P. J., and Sanders, T. A. Low-dose docosahexaenoic acid lowers diastolic blood pressure in middle-aged men and women. J Nutr 2007;137(4):973-978.

    Moderate

    ANTIDIABETES DRUGS

    Be cautious with this combination.

    Moderate

    ANTIDIABETES DRUGS

    Be cautious with this combination.

    Moderate

    ANTIDIABETES DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: possible
    Level of Evidence: B

    Theoretically, taking DHA with antidiabetes drugs might reduce the effects of these medications. <br> In people with type 2 diabetes, including those taking oral hypoglycemic medications, DHA seems to increase fasting blood glucose levels (10321).

    References

    10321

    Woodman RJ, Mori TA, Burke V, et al. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 2002;76:1007-15..

    Moderate
    EICOSAPENTAENOIC ACID (EPA)
    (Eicosapentaenoic acid (EPA))
    Be cautious with this combination.
    View Interactions:
    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Theoretically, taking EPA with antihypertensive drugs might increase the risk of hypotension.<br> Fish oils containing EPA can lower blood pressure and might have additive effects in patients treated with antihypertensives (1001,1020,1030,1033); use with caution.

    References

    1001

    Prisco D, Paniccia R, Bandinelli B, et al. Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res 1998;1:105-12.

    1020

    Toft I, Bonaa KH, Ingebretsen OC, et al. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med 1995;123:911-8.

    1030

    Sacks FM, Hebert P, Appel LJ, et al. Short report: the effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the trials of hypertension prevention. J Hypertens 1994;12:209-13.

    1033

    Vandongen R, Mori TA, Burke V, et al. Effects on blood pressure of omega 3 fats in subjects at increased risk of cardiovascular disease. Hypertension 1993;22:371-9.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Moderate

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be cautious with this combination.

    Severity: high
    Occurrence: possible
    Level of Evidence: B

    Theoretically, EPA may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.<br> In human research, taking EPA has been shown to inhibit platelet aggregation (9930).

    References

    9930

    Terano T, Hirai A, Hamazaki T, et al. Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects. Atherosclerosis 1983;46:321-31..

    Moderate
    FISH OIL
    (Omega-3 marine triglycerides, Concentrated fish omega-3 triglycerides, Fish Oil – natural)
    Be cautious with this combination.
    View Interactions:
    Moderate

    CYCLOSPORINE (Neoral, Sandimmune)

    Be cautious with this combination.

    Moderate

    CYCLOSPORINE (Neoral, Sandimmune)

    Be cautious with this combination.

    Moderate

    CYCLOSPORINE (Neoral, Sandimmune)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Taking fish oil with cyclosporine might increase levels and adverse effects of cyclosporine.<br> In kidney transplant recipients on a general immunosuppressive regimen, taking omega-3 fatty acids daily seems to increase peak blood levels of cyclosporine when compared with placebo. This increase was as much as 20% after one month. However, the area under the curve was not significantly affected (66472).

    References

    66472

    Busnach, G., Stragliotto, E., Minetti, E., Perego, A., Brando, B., Broggi, M. L., and Civati, G. Effect of n-3 polyunsaturated fatty acids on cyclosporine pharmacokinetics in kidney graft recipients: a randomized placebo- controlled study. J Nephrol. 1998;11(2):87-93.

    Moderate

    TACROLIMUS (Prograf)

    Be cautious with this combination.

    Moderate

    TACROLIMUS (Prograf)

    Be cautious with this combination.

    Moderate

    TACROLIMUS (Prograf)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Taking fish oil with tacrolimus might increase levels and adverse effects of tacrolimus. <br> In a small group of patients, taking fish oil 2.6 grams (Omacor) daily for 4 weeks increased the 8-hour area under the curve of tacrolimus by 25% when compared with baseline. Peak levels were increased by approximately 22% (105212). Researchers hypothesize that this may be due either to an increase in bioavailability or to inhibition of cytochrome P450 3A4 (CYP3A4) by fish oil, although this has not been confirmed in clinical research.

    References

    105212

    Robertsen I, Åsberg A, Jenssen TG, et al. Increased systemic exposure of once daily tacrolimus in renal transplant recipients on marine omega-3 fatty acid supplementation. Transpl Int. 2021.

    Moderate

    ORLISTAT (Xenical, Alli)

    Be cautious with this combination.

    Moderate

    ORLISTAT (Xenical, Alli)

    Be cautious with this combination.

    Moderate

    ORLISTAT (Xenical, Alli)

    Be cautious with this combination.

    Severity: mild
    Occurrence: probable
    Level of Evidence: D

    Theoretically, taking fish oil with orlistat might decrease the absorption of fish oil fatty acids. <br> Orlistat binds lipase in the gastrointestinal tract and reduces fat absorption. Theoretically, taking fish oil with orlistat might decrease absorption of fish oil fatty acids. To avoid this potential interaction, recommend separating administration of orlistat and fish oil by at least 2 hours.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Moderate

    ANTIHYPERTENSIVE DRUGS

    Be cautious with this combination.

    Severity: mild
    Occurrence: probable
    Level of Evidence: B

    Theoretically, taking fish oil with antihypertensive drugs might increase the risk of hypotension. <br> Clinical evidence indicates that fish oils can modestly lower blood pressure and might have additive effects in patients treated with antihypertensives (1001,1020,1030,1033,66095,66100,66215,66331,66358,66379,66385).

    References

    1001

    Prisco D, Paniccia R, Bandinelli B, et al. Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res 1998;1:105-12.

    1020

    Toft I, Bonaa KH, Ingebretsen OC, et al. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med 1995;123:911-8.

    1030

    Sacks FM, Hebert P, Appel LJ, et al. Short report: the effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the trials of hypertension prevention. J Hypertens 1994;12:209-13.

    1033

    Vandongen R, Mori TA, Burke V, et al. Effects on blood pressure of omega 3 fats in subjects at increased risk of cardiovascular disease. Hypertension 1993;22:371-9.

    66095

    Bonaa, K. H., Bjerve, K. S., Straume, B., Gram, I. T., and Thelle, D. Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension. A population-based intervention trial from the Tromso study. N Engl J Med 3-22-1990;322(12):795-801.

    66100

    Singer, P., Melzer, S., Goschel, M., and Augustin, S. Fish oil amplifies the effect of propranolol in mild essential hypertension. Hypertension 1990;16(6):682-691.

    66215

    Knapp, H. R. and FitzGerald, G. A. The antihypertensive effects of fish oil. A controlled study of polyunsaturated fatty acid supplements in essential hypertension. N Engl J Med 4-20-1989;320(16):1037-1043.

    66331

    Lungershausen, Y. K., Abbey, M., Nestel, P. J., and Howe, P. R. Reduction of blood pressure and plasma triglycerides by omega-3 fatty acids in treated hypertensives. J Hypertens. 1994;12(9):1041-1045.

    66358

    Appel, L. J., Miller, E. R., III, Seidler, A. J., and Whelton, P. K. Does supplementation of diet with 'fish oil' reduce blood pressure? A meta-analysis of controlled clinical trials. Arch Intern Med 6-28-1993;153(12):1429-1438.

    66379

    Morris, M. C., Sacks, F., and Rosner, B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation 1993;88(2):523-533.

    66385

    Morris, M. C., Taylor, J. O., Stampfer, M. J., Rosner, B., and Sacks, F. M. The effect of fish oil on blood pressure in mild hypertensive subjects: a randomized crossover trial. Am J Clin Nutr 1993;57(1):59-64.

    Moderate

    CONTRACEPTIVE DRUGS

    Be cautious with this combination.

    Moderate

    CONTRACEPTIVE DRUGS

    Be cautious with this combination.

    Moderate

    CONTRACEPTIVE DRUGS

    Be cautious with this combination.

    Severity: mild
    Occurrence: probable
    Level of Evidence: B

    Theoretically, taking fish oil with contraceptive drugs might decrease the triglyceride-lowering effects of fish oil. <br> There is some evidence that contraceptive drugs might interfere with the triglyceride lowering effects of fish oils (8694).

    References

    8694

    Deutch B, Jorgensen EB, Hansen JC. n-3 PUFA from fish or seal oil reduce atherogenic risk indicators in Danish women. Nutr Res 2000;20:1065-77.

    Moderate

    SIROLIMUS (Rapamune)

    Be cautious with this combination.

    Moderate

    SIROLIMUS (Rapamune)

    Be cautious with this combination.

    Moderate

    SIROLIMUS (Rapamune)

    Be cautious with this combination.

    Severity: moderate
    Occurrence: probable
    Level of Evidence: B

    Taking fish oil with sirolimus might increase levels and adverse effects of sirolimus.<br> Pharmacokinetic research shows that omega-3 fatty acids increase exposure to sirolimus in kidney transplant patients on a calcineurin inhibitor-free immunosuppressive regimen. A 25% dose reduction in sirolimus was required to keep patients within the expected trough-concentration window (105232). Researchers hypothesize that this may be due to inhibition of cytochrome P450 3A4 (CYP3A4) by fish oil, although this has not been confirmed in clinical research.

    References

    105232

    Cortinovis M, Gotti E, Remuzzi G, Perico N, Cattaneo D, Baldelli S. Omega-3 polyunsaturated fatty acids affect sirolimus exposure in kidney transplant recipients on calcineurin inhibitor-free regimen. Transplantation. 2010;89(1):126-7.

    Minor

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be watchful with this combination.

    Minor

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be watchful with this combination.

    Minor

    ANTICOAGULANT/ANTIPLATELET DRUGS

    Be watchful with this combination.

    Severity: moderate
    Occurrence: unlikely
    Level of Evidence: B

    Fish oil may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, evidence is conflicting. <br> While fish oil may not be a potent inhibitor of platelet function, high doses of fish oil might have antiplatelet effects. Theoretically, concomitant use of fish oil with anticoagulant or antiplatelet drugs may increase the risk of bleeding (8671,8679,8696,13769,21223,21224,66258). However, the most rigorous research shows that short-term doses of fish oil 10 grams daily or long-term doses of 1.5 grams daily for up to 52 weeks does not increase the risk of bleeding or affect coagulation parameters in chronically ill and vulnerable patients (97180). Other controlled research shows that fish oil does not affect platelet function or increase the risk of bleeding (17990,17996,66105,66267,89374,107180). Some research even suggests that perioperative fish oil use decreases bleeding risk (89352). Some research suggests fish oil does not have additive antiplatelet effects when combined with aspirin (13769), but other clinical evidence suggests that adding fish oil to low-dose aspirin treatment increases antiplatelet effects in patients who are aspirin-resistant (21226). Also, some clinical research seems to show that fish oil has additive antiplatelet effects when used with aspirin and clopidogrel compared to aspirin and clopidogrel alone (21225).

    References

    8671

    Leaf A. On the reanalysis of the GISSI-Prevenzione. Circulation 2002;105:1874-5.

    8679

    Connor WE. n-3 Fatty acids from fish and fish oil: panacea or nostrum? Am J Clin Nutr 2001;74;415-6.

    8696

    Calder PC. N-3 polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled waters or another fishy tale? Nutr Res 2001;21:309-41.

    66267

    Demke, D. M., Peters, G. R., Linet, O. I., Metzler, C. M., and Klott, K. A. Effects of a fish oil concentrate in patients with hypercholesterolemia. Atherosclerosis 1988;70(1-2):73-80.

    13769

    Svaneborg N, Kristensen SD, Hansen LM, et al. The acute and short-time effect of supplementation with the combination of n-3 fatty acids and acetylsalicylic acid on platelet function and plasma lipids. Thromb Res 2002;105:311-6.

    17990

    Kwak SM, Myung SK, Lee YJ, Seo HG. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med 2012;172:686-94.

    17996

    Armaganijan L, Lopes RD, Healey JS, et al. Do omega-3 fatty acids prevent atrial fibrillation after open heart surgery? A meta-analysis of randomized controlled trials. Clinics (Sao Paulo) 2011;66:1923-8.

    21223

    von Houwelingen R, Nordøy A, van der Beek E, et al. Effect of a moderate fish intake on blood pressure, bleeding time, hematology, and clinical chemistry in healthy males. Am J Clin Nutr. 1987 Sep;46(3):424-36.

    21224

    Goodnight SH Jr, Harris WS, Connor WE. The effects of dietary omega 3 fatty acids on platelet composition and function in man: a prospective, controlled study. Blood. 1981 Nov;58(5):880-5.

    21225

    Gajos G1, Rostoff P, Undas A, et al. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol. 2010 Apr 20;55(16):1671-8.

    21226

    Lev EI, Solodky A, Harel N, et al. Treatment of aspirin-resistant patients with omega-3 fatty acids versus aspirin dose escalation. J Am Coll Cardiol. 2010 Jan 12;55(2):114-21.

    66105

    Salvig, J. D. and Lamont, R. F. Evidence regarding an effect of marine n-3 fatty acids on preterm birth: a systematic review and meta-analysis. Acta Obstet.Gynecol.Scand. 2011;90(8):825-838.

    66258

    Zucker, M. L., Bilyeu, D. S., Helmkamp, G. M., Harris, W. S., and Dujovne, C. A. Effects of dietary fish oil on platelet function and plasma lipids in hyperlipoproteinemic and normal subjects. Atherosclerosis 1988;73(1):13-22.

    89352

    Mozaffarian D, Wu JH, de Oliveira Otto MC, Sandesara CM, Metcalf RG, Latini R, Libby P, Lombardi F, O'Gara PT, Page RL, Silletta MG, Tavazzi L, Marchioli R. Fish oil and post-operative atrial fibrillation: a meta-analysis of randomized controlled trials. J Am Coll Cardiol 2013;61(21):2194-6.

    89374

    Xin W, Wei W, Lin Z, Zhang X, Yang H, Zhang T, Li B, Mi S. Fish oil and atrial fibrillation after cardiac surgery: a meta-analysis of randomized controlled trials. PLoS One 2013;8(9):e72913.

    97180

    Jeansen S, Witkamp RF, Garthoff JA, van Helvoort A, Calder PC. Fish oil LC-PUFAs do not affect blood coagulation parameters and bleeding manifestations: Analysis of 8 clinical studies with selected patient groups on omega-3-enriched medical nutrition. Clin Nutr. 2018;37(3):948-957.

    107180

    Fradet S, Pelletier JF, Singbo N, et al. Effects of omega-3 fatty acids supplementation on perioperative blood loss and complications after radical prostatectomy. Clin Nutr ESPEN 2022;47:221-226.

    Minor

    WARFARIN (Coumadin)

    Be watchful with this combination.

    Minor

    WARFARIN (Coumadin)

    Be watchful with this combination.

    Minor

    WARFARIN (Coumadin)

    Be watchful with this combination.

    Severity: moderate
    Occurrence: unlikely
    Level of Evidence: B

    Fish oil may have antiplatelet effects and might increase the risk of bleeding if used with warfarin. <br> Fish oil has antiplatelet effects at high doses. Case reports show elevated INR in patients taking warfarin and fish oil 1-2 grams daily (21222,21223). However, some clinical research shows that taking fish oil 3-6 grams daily does not significantly increase INR in patients taking warfarin (8801).

    References

    8801

    Bender NK, Kraynak MA, Chiquette E, et al. Effects of marine fish oils on the anticoagulation status of patients receiving chronic warfarin therapy. J Thromb Thrombolysis 1998;5:257-61..

    21222

    Jalili M, Dehpour AR. Extremely prolonged INR associated with warfarin in combination with both trazodone and omega-3 fatty acids. Arch Med Res. 2007 Nov;38(8):901-4.

    21223

    von Houwelingen R, Nordøy A, van der Beek E, et al. Effect of a moderate fish intake on blood pressure, bleeding time, hematology, and clinical chemistry in healthy males. Am J Clin Nutr. 1987 Sep;46(3):424-36.

    Minor

    PLATINUM AGENTS

    Be watchful with this combination.

    Minor

    PLATINUM AGENTS

    Be watchful with this combination.

    Minor

    PLATINUM AGENTS

    Be watchful with this combination.

    Severity: moderate
    Occurrence: unlikely
    Level of Evidence: D

    Theoretically, taking fish oil with platinum agents can cause resistance to platinum agents, potentially decreasing their effectiveness. <br> Platinum-induced fatty acids (PIFAs) are fatty acids secreted from human and mouse stem cells when exposed to platinum-based chemotherapy. Animal research suggests that PIFAs cause resistance to chemotherapy by stimulating lysophospholipid production in the spleen, which interferes with the DNA damage caused by certain chemotherapy drugs (92076). One PIFA, known as 16:4(n-3), has been found in both raw fish and some commercially available fish oil products. Mackerel and herring have high PIFA concentrations, while salmon and tuna have low PIFA concentrations. Levels of PIFA in commercial fish oil products ranged from 0.2- 5.7 microMol. Animal research shows that PIFA-containing fish oil products cause resistance to cisplatin, fluorouracil, irinotecan, and oxaliplatin (91250,92075). It is unclear if all commercially available fish oil products contain PIFAs. Additionally, it is argued that levels of PIFA found in some fish oil products are too low to be of clinical concern. Furthermore, a lack of chemotherapy resistance in countries with high fish intake, such as Greenland, Japan, and Norway, suggest that this interaction may not be clinically significant (91288,91289).

    References

    91289

    Baracos V. Let them eat fish. JAMA Oncol 2015;1(6):840-1.

    91250

    Daenen LG, Cirkel GA, Houthuijzen JM, et al. Increased plasma levels of chemoresistance-inducing fatty acid 16:4(n-3) after consumption of fish and fish oil. JAMA Oncol 2015;1(3):350-8.

    91288

    Mazurak VC, Calder PC, van der Meij BS. Let them eat fish. JAMA Oncol 2015;1(6):840.

    92075

    Roodhart JM, Daenen LG, Stigter EC, et al. Mesenchymal stem cells induce resistance to chemotherapy through the release of platinum-induced fatty acids. Cancer Cell 2011;20(3):370-83.

    92076

    Houthuijzen JM, Daenen LG, Roodhart JM, et al. Lysophospholipids secreted by splenic macrophages induce chemotherapy resistance via interference with the DNA damage response. Nat Commun 2014;5:5275.


    Full Reference List

    105232
    Cortinovis M, Gotti E, Remuzzi G, Perico N, Cattaneo D, Baldelli S. Omega-3 polyunsaturated fatty acids affect sirolimus exposure in kidney transplant recipients on calcineurin inhibitor-free regimen. Transplantation. 2010;89(1):126-7.
    91289
    Baracos V. Let them eat fish. JAMA Oncol 2015;1(6):840-1.
    91250
    Daenen LG, Cirkel GA, Houthuijzen JM, et al. Increased plasma levels of chemoresistance-inducing fatty acid 16:4(n-3) after consumption of fish and fish oil. JAMA Oncol 2015;1(3):350-8.
    91288
    Mazurak VC, Calder PC, van der Meij BS. Let them eat fish. JAMA Oncol 2015;1(6):840.
    92075
    Roodhart JM, Daenen LG, Stigter EC, et al. Mesenchymal stem cells induce resistance to chemotherapy through the release of platinum-induced fatty acids. Cancer Cell 2011;20(3):370-83.
    92076
    Houthuijzen JM, Daenen LG, Roodhart JM, et al. Lysophospholipids secreted by splenic macrophages induce chemotherapy resistance via interference with the DNA damage response. Nat Commun 2014;5:5275.
    8801
    Bender NK, Kraynak MA, Chiquette E, et al. Effects of marine fish oils on the anticoagulation status of patients receiving chronic warfarin therapy. J Thromb Thrombolysis 1998;5:257-61..
    21222
    Jalili M, Dehpour AR. Extremely prolonged INR associated with warfarin in combination with both trazodone and omega-3 fatty acids. Arch Med Res. 2007 Nov;38(8):901-4.
    21223
    von Houwelingen R, Nordøy A, van der Beek E, et al. Effect of a moderate fish intake on blood pressure, bleeding time, hematology, and clinical chemistry in healthy males. Am J Clin Nutr. 1987 Sep;46(3):424-36.
    8694
    Deutch B, Jorgensen EB, Hansen JC. n-3 PUFA from fish or seal oil reduce atherogenic risk indicators in Danish women. Nutr Res 2000;20:1065-77.
    1001
    Prisco D, Paniccia R, Bandinelli B, et al. Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res 1998;1:105-12.
    1020
    Toft I, Bonaa KH, Ingebretsen OC, et al. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med 1995;123:911-8.
    1030
    Sacks FM, Hebert P, Appel LJ, et al. Short report: the effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the trials of hypertension prevention. J Hypertens 1994;12:209-13.
    1033
    Vandongen R, Mori TA, Burke V, et al. Effects on blood pressure of omega 3 fats in subjects at increased risk of cardiovascular disease. Hypertension 1993;22:371-9.
    66095
    Bonaa, K. H., Bjerve, K. S., Straume, B., Gram, I. T., and Thelle, D. Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension. A population-based intervention trial from the Tromso study. N Engl J Med 3-22-1990;322(12):795-801.
    66100
    Singer, P., Melzer, S., Goschel, M., and Augustin, S. Fish oil amplifies the effect of propranolol in mild essential hypertension. Hypertension 1990;16(6):682-691.
    66215
    Knapp, H. R. and FitzGerald, G. A. The antihypertensive effects of fish oil. A controlled study of polyunsaturated fatty acid supplements in essential hypertension. N Engl J Med 4-20-1989;320(16):1037-1043.
    66331
    Lungershausen, Y. K., Abbey, M., Nestel, P. J., and Howe, P. R. Reduction of blood pressure and plasma triglycerides by omega-3 fatty acids in treated hypertensives. J Hypertens. 1994;12(9):1041-1045.
    66358
    Appel, L. J., Miller, E. R., III, Seidler, A. J., and Whelton, P. K. Does supplementation of diet with 'fish oil' reduce blood pressure? A meta-analysis of controlled clinical trials. Arch Intern Med 6-28-1993;153(12):1429-1438.
    66379
    Morris, M. C., Sacks, F., and Rosner, B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation 1993;88(2):523-533.
    66385
    Morris, M. C., Taylor, J. O., Stampfer, M. J., Rosner, B., and Sacks, F. M. The effect of fish oil on blood pressure in mild hypertensive subjects: a randomized crossover trial. Am J Clin Nutr 1993;57(1):59-64.
    105212
    Robertsen I, Åsberg A, Jenssen TG, et al. Increased systemic exposure of once daily tacrolimus in renal transplant recipients on marine omega-3 fatty acid supplementation. Transpl Int. 2021.
    66472
    Busnach, G., Stragliotto, E., Minetti, E., Perego, A., Brando, B., Broggi, M. L., and Civati, G. Effect of n-3 polyunsaturated fatty acids on cyclosporine pharmacokinetics in kidney graft recipients: a randomized placebo- controlled study. J Nephrol. 1998;11(2):87-93.
    8671
    Leaf A. On the reanalysis of the GISSI-Prevenzione. Circulation 2002;105:1874-5.
    8679
    Connor WE. n-3 Fatty acids from fish and fish oil: panacea or nostrum? Am J Clin Nutr 2001;74;415-6.
    8696
    Calder PC. N-3 polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled waters or another fishy tale? Nutr Res 2001;21:309-41.
    66267
    Demke, D. M., Peters, G. R., Linet, O. I., Metzler, C. M., and Klott, K. A. Effects of a fish oil concentrate in patients with hypercholesterolemia. Atherosclerosis 1988;70(1-2):73-80.
    13769
    Svaneborg N, Kristensen SD, Hansen LM, et al. The acute and short-time effect of supplementation with the combination of n-3 fatty acids and acetylsalicylic acid on platelet function and plasma lipids. Thromb Res 2002;105:311-6.
    17990
    Kwak SM, Myung SK, Lee YJ, Seo HG. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med 2012;172:686-94.
    17996
    Armaganijan L, Lopes RD, Healey JS, et al. Do omega-3 fatty acids prevent atrial fibrillation after open heart surgery? A meta-analysis of randomized controlled trials. Clinics (Sao Paulo) 2011;66:1923-8.
    21224
    Goodnight SH Jr, Harris WS, Connor WE. The effects of dietary omega 3 fatty acids on platelet composition and function in man: a prospective, controlled study. Blood. 1981 Nov;58(5):880-5.
    21225
    Gajos G1, Rostoff P, Undas A, et al. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol. 2010 Apr 20;55(16):1671-8.
    21226
    Lev EI, Solodky A, Harel N, et al. Treatment of aspirin-resistant patients with omega-3 fatty acids versus aspirin dose escalation. J Am Coll Cardiol. 2010 Jan 12;55(2):114-21.
    66105
    Salvig, J. D. and Lamont, R. F. Evidence regarding an effect of marine n-3 fatty acids on preterm birth: a systematic review and meta-analysis. Acta Obstet.Gynecol.Scand. 2011;90(8):825-838.
    66258
    Zucker, M. L., Bilyeu, D. S., Helmkamp, G. M., Harris, W. S., and Dujovne, C. A. Effects of dietary fish oil on platelet function and plasma lipids in hyperlipoproteinemic and normal subjects. Atherosclerosis 1988;73(1):13-22.
    89352
    Mozaffarian D, Wu JH, de Oliveira Otto MC, Sandesara CM, Metcalf RG, Latini R, Libby P, Lombardi F, O'Gara PT, Page RL, Silletta MG, Tavazzi L, Marchioli R. Fish oil and post-operative atrial fibrillation: a meta-analysis of randomized controlled trials. J Am Coll Cardiol 2013;61(21):2194-6.
    89374
    Xin W, Wei W, Lin Z, Zhang X, Yang H, Zhang T, Li B, Mi S. Fish oil and atrial fibrillation after cardiac surgery: a meta-analysis of randomized controlled trials. PLoS One 2013;8(9):e72913.
    97180
    Jeansen S, Witkamp RF, Garthoff JA, van Helvoort A, Calder PC. Fish oil LC-PUFAs do not affect blood coagulation parameters and bleeding manifestations: Analysis of 8 clinical studies with selected patient groups on omega-3-enriched medical nutrition. Clin Nutr. 2018;37(3):948-957.
    107180
    Fradet S, Pelletier JF, Singbo N, et al. Effects of omega-3 fatty acids supplementation on perioperative blood loss and complications after radical prostatectomy. Clin Nutr ESPEN 2022;47:221-226.
    9930
    Terano T, Hirai A, Hamazaki T, et al. Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects. Atherosclerosis 1983;46:321-31..
    10321
    Woodman RJ, Mori TA, Burke V, et al. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 2002;76:1007-15..
    47944
    Mori, T. A., Bao, D. Q., Burke, V., Puddey, I. B., and Beilin, L. J. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension 1999;34(2):253-260.
    48013
    Nestel, P., Shige, H., Pomeroy, S., Cehun, M., Abbey, M., and Raederstorff, D. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am.J.Clin.Nutr. 2002;76(2):326-330.
    48020
    Woodman, R. J., Mori, T. A., Burke, V., Puddey, I. B., Barden, A., Watts, G. F., and Beilin, L. J. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis 2003;166(1):85-93.
    48163
    Theobald, H. E., Goodall, A. H., Sattar, N., Talbot, D. C., Chowienczyk, P. J., and Sanders, T. A. Low-dose docosahexaenoic acid lowers diastolic blood pressure in middle-aged men and women. J Nutr 2007;137(4):973-978.
    11112
    Leng GC, Smith FB, Fowkes FG, et al. Relationship between plasma essential fatty acids and smoking, serum lipids, blood pressure and haemostatic and rheological factors. Prostaglandins Leukot Essent Fatty Acids 1994;51:101-8.
    11113
    Nelson GJ, Schmidt PS, Bartolini GL, et al. The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids 1997;32:1129-36.

    Rating System Description

    Level of Significance: Stop‑Light Rating System Occurrence/Severity
    Major

    Do not use combination; contraindicated; strongly discourage patients from using this combination; a serious adverse outcome could occur.

    Moderate

    Use cautiously or avoid combination; warn patients that a significant interaticon or adverse outcome could occur.

    Minor

    Be aware that there is a chance of an interaction; advise patients to watch for warning signs of a potential interaction.

    Likelihood of Occurrence

    Likely: Well‑controlled human studies have demonstrated existence of this interaction.

    Probable: Interaction has not been documented in well‑controlled studies, however interaction has been demonstrated in human studies or in controlled animal studies plus multiple case reports.

    Possible: Interaction has been documented in animal or in vitro research, or interaction has been documented in humans but is limited to case reports or conflicting clinical research.

    Unlikely: Interaction has been demonstrated in animal or in vitro research but has been shown not to occur in humans.

    Severity

    High: Life threatening or requires medical intervention to prevent a serious adverse event.

    Moderate: Worsened clinical status and/or requires medication adjustment.

    Mild: May cause minor clinical side effects. Unlikely to require medication adjustment.

    Insignificant: Drug or supplement levels may be affected but will not cause clinical effects.

    Level of Evidence

    A: High-quality randomized controlled trial(RCT).

    A: High-quality meta-analysis (quantitative systematic review)

    B: Nonrandomized clinical trial

    B: Nonquantitative systematic review

    B: Lower quality RCT

    B: Clinical cohort study

    B: Case-control study

    B: Historical control

    B: Epidemoilogic study

    C: Consensus

    C: Expert opinion

    D: Acecdotal evidence

    D: In vitro or animal study

    D: Theoretical based on pharmacology


    © 2019 TRC is a registered trademark of Therapeutic Research Center.
    TRC and all associated names and service marks including TRC are restricted and reserved for Therapeutic Research Center use.
    Natural Medicines™ and associated Natural Medicines product marks are trademarks of Therapeutic Research Center.

    Disclaimer: This information on interactions is licensed from the TRC Natural Medicines Database. Neither Bio Concepts nor TRC are providing medical, clinical or other advice and nothing should be interpreted as constituting such advice. Currently this does not check for drug-drug or supplementsupplement interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgement is necessary.

    Factsheets Pregnancy & Lactation

    Contraindications*:

    Pregnancy & Lactation: None reported at 1 capsule/day

    *Information taken from Natural Medicines Database regarding “Major” contraindications related to active ingredients only and accurate as of May 2022. Please refer to Natural Medicines Database for more information.