Disorders of Lipid Metabolism

DLM: Elevated Triglycerides and Omega-3 Fatty Acids (2007)

• Intervention
  What effect does EPA/DHA taken as a fish oil supplement have on triglycerides in hypertriglyceridemic patients who are taking cholesterol lowering medication (statins)?

  • Conclusion

    The triglyceride lowering benefit of EPA/DHA fish oil with HMG-Co A reductase inhibitors (statins) was reported in three studies of varied patient populations. Studies provided 1.68-3.2g EPA/DHA daily for 5-48 weeks in patients receiving statin therapy with diet and lifestyle changes. This resulted in a 0-35% reduction in triglycerides vs. baseline values. Two of the studies found a 32-35% reduction and one study found no reduction in triglycerides. In these three studies there appears to be no dose response. No dietary adherence data were reported.

  • Grade: III
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: What is the role of omega-3 fatty acids in triglyceride lowering?
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      •  Calabresi L, Donati D, Pazzucconi F, Sirtori CF, Franceschini G. Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses. Atherosclerosis. 2000;148:387-396.
        
      •  Durrington PR, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acide concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548.
      • Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovascular Risk. 1997;r:385-391.
      • Hong H, Xu Z, Pang B, Cui L, Wei Y, Guo W, Mao Y, Yang X. Effects of simvastatin combined with omega-3 fatty acids on high sensitive C-reactive protein, lipidemia, and fibrinolysis in patients with mixed dyslipidemia. Chin Med Sci J. 2004;19:145-149.
      • Maki K, Van Elswyk ME, McCarthy D, Seeley MA, Veith PE, Hess SP, Ingram KA, Halvorson JJ, Calaguas EM, Davidson MH.  Lipid Responses in Mildly Hypertriglyceridemic Men and Women to Consumption of Docosahexaenoic Acid- Enriched Eggs. Int. J. Vitam, Nutr. Res. 2003; 73(5), 357-368.
      •  Nordøy A, Hansen JB, Brox J, Svensson B. Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia. Nutr Metab Cardiovasc Dis. 2001;11:7-16.
      • Otto C, Ritter MM, Soennichsen AC, Schwandt P, Richter WO. Effects of n-3 fatty acids and fenofibrate on lipid and hemorrheological parameters in familial dysbetalipoproteinemia and familial hypertriglyceridemia. Metabolism. 1996;45:1305-1311.
      • Silva JM, Souza I, Silva R, Tavares P, Teizeira F, Silva PS.  The triglceride lovering effect of fish oils is affected by fish consumption. Int J of Caridiology 57 (1996)75-80. 
      • Sirtori CR, Paoletti R, Mancini M, Crepaldi G, Manzato E, Rivellese A, Pamparana, F, Stragliotto E on behalf ot eh The Italian Fish Oil  Multicenter Study. n-3 Fatty acids do not lead to an increased diabertic rish in patients with hyperlipidemia and abnormal glucose tolerance. Am J Clin Nutr 1997:65:1874-81.
      • Sirtori CR, Crepaldi G, Manzato E, Mancini M, Rivellese A, Paoletti R, Pazzucconi F, Pamparana F, Stragliotto. One-year treatment with ethyl esters of n-3 fatty acids in patients with hypertriglyceridemia and glucose intolerance Reduced triglyceridemia, total cholesterol and increased HDL-C without glycemic alterations. Atherosclerosis 1998;137: 419-427.
      •  Wohl DA, Tien HC, Busby M, Cunningham C, MacIntosh B, Napravnik S, Danan E, Donovan K, Hossenipour M, Simpson RJ. Randomized study of the safety and efficacy of fish oil (omega-3 fatty acid) supplementation with dietary and exercise counseling for the treatment of antiretroviral therapy-associated hypertriglyeridemia. Clinical Infectious Disease. 2005;41:1498-1504.
  • Search Plan and Results: Omega-3 Fatty Acids and Triglyceride Lowering 2006
     
  What effect does EPA/DHA taken as a fish oil supplement have on triglycerides in hypertriglyceridemic patients who are not taking cholesterol lowering medications?

  • Conclusion

    Subjects with elevated triglycerides (mean values ranged 250-919 mg/dL) taking 2.6-3.6g of commercial EPA/DHA fish oil (approximately 48-60% EPA/ 33-40% DHA) with varied dietary intakes without cholesterol lowering medicines, for 6 weeks to 1 year* had 22-45% reductions in triglyceride values compared to baseline values. Lower doses of fish oil (1.72g; 59% EPA/41% DHA) also resulted in 22-25% reductions in triglycerides vs. baseline values after 6 months to 1 year.

    *One study was of 1 year duration and was a 6-month open label extension of a 6 month study.

  • Grade: II
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: What is the role of omega-3 fatty acids in triglyceride lowering?
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      •  Calabresi L, Donati D, Pazzucconi F, Sirtori CF, Franceschini G. Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses. Atherosclerosis. 2000;148:387-396.
        
      •  Durrington PR, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acide concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548.
      • Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovascular Risk. 1997;r:385-391.
      • Hong H, Xu Z, Pang B, Cui L, Wei Y, Guo W, Mao Y, Yang X. Effects of simvastatin combined with omega-3 fatty acids on high sensitive C-reactive protein, lipidemia, and fibrinolysis in patients with mixed dyslipidemia. Chin Med Sci J. 2004;19:145-149.
      • Maki K, Van Elswyk ME, McCarthy D, Seeley MA, Veith PE, Hess SP, Ingram KA, Halvorson JJ, Calaguas EM, Davidson MH.  Lipid Responses in Mildly Hypertriglyceridemic Men and Women to Consumption of Docosahexaenoic Acid- Enriched Eggs. Int. J. Vitam, Nutr. Res. 2003; 73(5), 357-368.
      •  Nordøy A, Hansen JB, Brox J, Svensson B. Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia. Nutr Metab Cardiovasc Dis. 2001;11:7-16.
      • Otto C, Ritter MM, Soennichsen AC, Schwandt P, Richter WO. Effects of n-3 fatty acids and fenofibrate on lipid and hemorrheological parameters in familial dysbetalipoproteinemia and familial hypertriglyceridemia. Metabolism. 1996;45:1305-1311.
      • Silva JM, Souza I, Silva R, Tavares P, Teizeira F, Silva PS.  The triglceride lovering effect of fish oils is affected by fish consumption. Int J of Caridiology 57 (1996)75-80. 
      • Sirtori CR, Paoletti R, Mancini M, Crepaldi G, Manzato E, Rivellese A, Pamparana, F, Stragliotto E on behalf ot eh The Italian Fish Oil  Multicenter Study. n-3 Fatty acids do not lead to an increased diabertic rish in patients with hyperlipidemia and abnormal glucose tolerance. Am J Clin Nutr 1997:65:1874-81.
      • Sirtori CR, Crepaldi G, Manzato E, Mancini M, Rivellese A, Paoletti R, Pazzucconi F, Pamparana F, Stragliotto. One-year treatment with ethyl esters of n-3 fatty acids in patients with hypertriglyceridemia and glucose intolerance Reduced triglyceridemia, total cholesterol and increased HDL-C without glycemic alterations. Atherosclerosis 1998;137: 419-427.
      •  Wohl DA, Tien HC, Busby M, Cunningham C, MacIntosh B, Napravnik S, Danan E, Donovan K, Hossenipour M, Simpson RJ. Randomized study of the safety and efficacy of fish oil (omega-3 fatty acid) supplementation with dietary and exercise counseling for the treatment of antiretroviral therapy-associated hypertriglyeridemia. Clinical Infectious Disease. 2005;41:1498-1504.
  • Search Plan and Results: Omega-3 Fatty Acids and Triglyceride Lowering 2006
     
  What effect does EPA/DHA taken as a fish oil supplement have on LDL-cholesterol in hypertriglyceridemic patients?

  • Conclusion

    In studies of patients with high triglycerides, not following specific dietary advice and not on concurrent statin therapy, fish oil was associated with a 8-44% increase in LDL-C. In studies of people taking fish oil capsules and statins, LDL-C decreased 0-20%. 

  • Grade: III
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: What is the role of omega-3 fatty acids in triglyceride lowering?
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      •  Calabresi L, Donati D, Pazzucconi F, Sirtori CF, Franceschini G. Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses. Atherosclerosis. 2000;148:387-396.
        
      •  Durrington PR, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acide concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548.
      • Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovascular Risk. 1997;r:385-391.
      • Hong H, Xu Z, Pang B, Cui L, Wei Y, Guo W, Mao Y, Yang X. Effects of simvastatin combined with omega-3 fatty acids on high sensitive C-reactive protein, lipidemia, and fibrinolysis in patients with mixed dyslipidemia. Chin Med Sci J. 2004;19:145-149.
      • Maki K, Van Elswyk ME, McCarthy D, Seeley MA, Veith PE, Hess SP, Ingram KA, Halvorson JJ, Calaguas EM, Davidson MH.  Lipid Responses in Mildly Hypertriglyceridemic Men and Women to Consumption of Docosahexaenoic Acid- Enriched Eggs. Int. J. Vitam, Nutr. Res. 2003; 73(5), 357-368.
      •  Nordøy A, Hansen JB, Brox J, Svensson B. Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia. Nutr Metab Cardiovasc Dis. 2001;11:7-16.
      • Otto C, Ritter MM, Soennichsen AC, Schwandt P, Richter WO. Effects of n-3 fatty acids and fenofibrate on lipid and hemorrheological parameters in familial dysbetalipoproteinemia and familial hypertriglyceridemia. Metabolism. 1996;45:1305-1311.
      • Silva JM, Souza I, Silva R, Tavares P, Teizeira F, Silva PS.  The triglceride lovering effect of fish oils is affected by fish consumption. Int J of Caridiology 57 (1996)75-80. 
      • Sirtori CR, Paoletti R, Mancini M, Crepaldi G, Manzato E, Rivellese A, Pamparana, F, Stragliotto E on behalf ot eh The Italian Fish Oil  Multicenter Study. n-3 Fatty acids do not lead to an increased diabertic rish in patients with hyperlipidemia and abnormal glucose tolerance. Am J Clin Nutr 1997:65:1874-81.
      • Sirtori CR, Crepaldi G, Manzato E, Mancini M, Rivellese A, Paoletti R, Pazzucconi F, Pamparana F, Stragliotto. One-year treatment with ethyl esters of n-3 fatty acids in patients with hypertriglyceridemia and glucose intolerance Reduced triglyceridemia, total cholesterol and increased HDL-C without glycemic alterations. Atherosclerosis 1998;137: 419-427.
      •  Wohl DA, Tien HC, Busby M, Cunningham C, MacIntosh B, Napravnik S, Danan E, Donovan K, Hossenipour M, Simpson RJ. Randomized study of the safety and efficacy of fish oil (omega-3 fatty acid) supplementation with dietary and exercise counseling for the treatment of antiretroviral therapy-associated hypertriglyeridemia. Clinical Infectious Disease. 2005;41:1498-1504.
  • Search Plan and Results: Omega-3 Fatty Acids and Triglyceride Lowering 2006
     
  What effect does DHA consumed as DHA-enriched eggs have on triglycerides in hypertriglyceridemic patients?

  • Conclusion

    Based on one study (n=150), ten DHA-rich eggs per week (209mg DHA per day) given for 6 weeks did not lower triglycerides and increased LDL-C.

  • Grade: III
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: What is the role of omega-3 fatty acids in triglyceride lowering?
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      •  Calabresi L, Donati D, Pazzucconi F, Sirtori CF, Franceschini G. Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses. Atherosclerosis. 2000;148:387-396.
        
      •  Durrington PR, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acide concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548.
      • Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovascular Risk. 1997;r:385-391.
      • Hong H, Xu Z, Pang B, Cui L, Wei Y, Guo W, Mao Y, Yang X. Effects of simvastatin combined with omega-3 fatty acids on high sensitive C-reactive protein, lipidemia, and fibrinolysis in patients with mixed dyslipidemia. Chin Med Sci J. 2004;19:145-149.
      • Maki K, Van Elswyk ME, McCarthy D, Seeley MA, Veith PE, Hess SP, Ingram KA, Halvorson JJ, Calaguas EM, Davidson MH.  Lipid Responses in Mildly Hypertriglyceridemic Men and Women to Consumption of Docosahexaenoic Acid- Enriched Eggs. Int. J. Vitam, Nutr. Res. 2003; 73(5), 357-368.
      •  Nordøy A, Hansen JB, Brox J, Svensson B. Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia. Nutr Metab Cardiovasc Dis. 2001;11:7-16.
      • Otto C, Ritter MM, Soennichsen AC, Schwandt P, Richter WO. Effects of n-3 fatty acids and fenofibrate on lipid and hemorrheological parameters in familial dysbetalipoproteinemia and familial hypertriglyceridemia. Metabolism. 1996;45:1305-1311.
      • Silva JM, Souza I, Silva R, Tavares P, Teizeira F, Silva PS.  The triglceride lovering effect of fish oils is affected by fish consumption. Int J of Caridiology 57 (1996)75-80. 
      • Sirtori CR, Paoletti R, Mancini M, Crepaldi G, Manzato E, Rivellese A, Pamparana, F, Stragliotto E on behalf ot eh The Italian Fish Oil  Multicenter Study. n-3 Fatty acids do not lead to an increased diabertic rish in patients with hyperlipidemia and abnormal glucose tolerance. Am J Clin Nutr 1997:65:1874-81.
      • Sirtori CR, Crepaldi G, Manzato E, Mancini M, Rivellese A, Paoletti R, Pazzucconi F, Pamparana F, Stragliotto. One-year treatment with ethyl esters of n-3 fatty acids in patients with hypertriglyceridemia and glucose intolerance Reduced triglyceridemia, total cholesterol and increased HDL-C without glycemic alterations. Atherosclerosis 1998;137: 419-427.
      •  Wohl DA, Tien HC, Busby M, Cunningham C, MacIntosh B, Napravnik S, Danan E, Donovan K, Hossenipour M, Simpson RJ. Randomized study of the safety and efficacy of fish oil (omega-3 fatty acid) supplementation with dietary and exercise counseling for the treatment of antiretroviral therapy-associated hypertriglyeridemia. Clinical Infectious Disease. 2005;41:1498-1504.
  • Search Plan and Results: Omega-3 Fatty Acids and Triglyceride Lowering 2006
     
  What effect does EPA/DHA taken as a fish oil supplement have on triglycerides in hypertriglyceridemic patients when combined with medical nutrition therapy provided by a Registered Dietitian?

  • Conclusion

    Fish oil capsule intake in addition to MNT according to current evidence-based nutrition practice guidelines provided by an RD has not been evaluated in the hypertriglyceridemic patient.

  • Grade: V
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Search Plan and Results: Omega-3 Fatty Acids and Triglyceride Lowering 2006