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Does Supplementation of Diet With 'Fish Oil' Reduce Blood Pressure?: A Meta-analysis of Controlled Clinical Trials

Does Supplementation of Diet With 'Fish Oil' Reduce Blood Pressure?: A Meta-analysis of... Abstract Background: Several lines of evidence suggest that supplementation of diet with omega-3 polyunsaturated fatty acids (ω-3) PUFA), commonly referred to as fish oils, may reduce blood pressure (BP). However, most clinical trials of ω-3 PUFA supplementation have been of insufficient size to detect relevant BP changes. Methods: We conducted a meta-analysis of 17 controlled clinical trials of ω-3 PUFA supplementation. To estimate an overall effect of ω-3 PUFA supplementation on BP, we calculated the net BP change in each trial (BP A in ω-3 PUFA group minus BP A in control group), which was then weighted according to the inverse of the variance. Results: In the 11 trials that enrolled normotensive individuals (n=728), ω-3 PUFA supplementation led to significant reductions of systolic BP (SBP) and diastolic BP (DBP) in two and one trials, respectively. In the six studies that enrolled untreated hypertensives (n=291), significant reductions of SBP and DBP were present in two and four trials, respectively. Weighted, pooled estimates of SBP and DBP change (mm Hg) with 95% confidence intervals were —1.0 (—2.0 to 0.0) and —0.5 (—1.2 to +0.2) in the trials of normotensives, and —5.5 (—8.1 to —2.9) and —3.5 (—5.0 to —2.1) in the trials of untreated hypertensives. In 13 of 17 studies, trial duration was less than 3 months. Doses of ω-3 PUFA tended to be high (average dose >3 g/d in 11 trials). The magnitude of BP reduction was greatest at high BP but was not significantly associated with dose of ω-3 PUFA. Side effects, most commonly eructation and a fishy taste, occurred more frequently in ω-3 PUFA participants than in control participants (28% vs 13%, P<.001). Conclusions: Our analyses indicate that diet supplementation with a relatively high dose of ω-3 PUFA, generally more than 3 g/d, can lead to clinically relevant BP reductions in individuals with untreated hypertension. However, use of ω-3 PUFA as antihypertensive therapy will require demonstration of long-term efficacy and patient acceptability of lower doses.(Arch Intern Med. 1993;153:1429-1438) References 1. Bang HO, Dyerberg J, Sinclair HM. The composition of the Eskimo food in north western Greenland . Am J Clin Nutr. 1980;33:2657-2661. 2. Kagawa Y, Nishizawa M, Suzuki M, et al. Eicosapolyenoic acids of serum lipids of Japanese islanders with low incidence of cardiovascular diseases . J Nutr Sci Vitaminol (Tokyo) . 1982;28:441-453.Crossref 3. Kromhout D, Bosschieter EB, Coulander CDL. The inverse relation between fish consumption and 20-year mortality from coronary heart disease . N Engl J Med. 1985;312:1205-1209.Crossref 4. Shekelle RB, Missell LV, Paul 0, Shryock AM, Stamler J. Fish consumption and mortality from coronary heart disease . N Engl J Med. 1985;313:820.Crossref 5. Norell SE, Ahlbom A, Feychting M, Pedersen NL. Fish consumption and mortality from coronary heart disease . BMJ . 1986;293:426.Crossref 6. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART) . Lancet . 1989;2:757-761.Crossref 7. Simopoulos AP. Omega-3 fatty acids in health and disease and in growth and development . Am J Clin Nutr. 1991;54:438-463. 8. Bonaa K. Epidemiological and intervention studies on the effect of marine polyunsaturated fatty acids on blood pressure . J Intern Med. 1989;225( (suppl 1) ): 105-110.Crossref 9. Radack K, Deck C. The effects of omega-3 polyunsaturated fatty acids on blood pressure: a methodologic analysis of the evidence . J Am Coll Nutr. 1989;8: 376-385.Crossref 10. Greenland S. Quantitative methods in the review of epidemiologic literature . Epidemiol Rev. 1987;9:1-30. 11. Gill JS, Zezulka AV, Beevers DG, Davies P. Relationship between initial blood pressure and its fall with treatment . Lancet . 1985;1:567-569.Crossref 12. Wing LMH, Nestel PJ, Chalmers JP, et al. Lack of effect of fish oil supplementation on blood pressure in treated hypertensives . J Hypertens. 1990;8: 339-343.Crossref 13. Singer P, Melzer S, Goschell M, Augustin S. Fish oil amplifies the effect of propranolol in mild essential hypertension . Hypertension . 1990;16:682-691.Crossref 14. Margolin G, Huster G, Glueck CJ, et al. Blood pressure lowering in elderly subjects: a double-blind crossover study of ω-3 and ω-6 fatty acids . Am J Clin Nutr. 1991;53:562-572. 15. Sanders TAB, Vickers M, Haines AP. Effect on blood lipids and haemostasis of a supplement of cod-liver oil, rich in eicosapentaenoic and docosahexaenoic acids, in healthy young men . Clin Sci. 1981;61:317-324. 16. Lorenz R, Spengler U, Fischer S, Duhm J, Weber PC. Platelet function, thromboxane formation and blood pressure control during supplementation of the western diet with cod liver oil . Circulation . 1983;67:504-511.Crossref 17. Hamazaki T, Nakazawa R, Tateno S, et al. Effects of fish oil rich in eicosapentaenoic acid on serum lipid in hyperlipidemic hemodialysis patients . Kidney Int. 1984;26:81-84.Crossref 18. Olivieri O, Negri M, De Gironcoli M. Effects of dietary fish oil on malondialdehyde production and glutathione peroxidase activity in hyperlipidemic patients . Scand J Clin Lab Invest. 1988;48:659-665.Crossref 19. Urakaze M, Hamazaki T, Yano S. Fish oil and hypertension . J Hum Hypertens. 1989;3:277-278. 20. Singer P, Jaeger W, Wirth M, et al. Lipid and blood pressure-lowering effect of mackerel diet in man . Atherosclerosis . 1983;49:99-108.Crossref 21. Singer P, Wirth M, Berger I, et al. Influence on serum lipids, lipoproteins and blood pressure of mackerel and herring diet in patients with type IV and V hyperlipoproteinemia . Atherosclerosis . 1985;56:111-118.Crossref 22. Singer P, Wirth M, Voigt S, et al. Blood pressure- and lipid-lowering effect of mackerel and herring diet in patients with mild essential hypertension . Atherosclerosis . 1985;56:223-235.Crossref 23. Kristensen SD, Schmidt EB, Anderson HR, Dyerberg J. Fish oil in angina pectoris . Atherosclerosis . 1987;64:13-19.Crossref 24. Kasim SE, Stern B, Khilnani S, McLin P, Baciorowski S, Jen KLC. Effects of omega-3 fish oils on lipid metabolism, glycemic control, and blood pressure in type II diabetic patients . J Clin Endocrinol Metab. 1988;67:1-5.Crossref 25. Jensen T, Stender S, Goldstein K, Holmer G, Deckert T. Partial normalization by dietary cod-liver oil of increased microvascular albumin leakage in patients with insulin-dependent diabetes and albuminuria . N Engl J Med. 1989;321: 1572-1577.Crossref 26. Mehta JL, Lopez LM, Lawson D, Wargovich TJ, Williams LL. Dietary supplementation with omega-3 polyunsaturated fatty acids in patients with stable coronary heart disease . Am J Med. 1988;84:45-52.Crossref 27. Urakaze M, Hamazaki T, Yano S, Kashiwabara H, Oomori K, Yokoyama T. Effect of fish oil concentrate on risk factors of cardiovascular complications in renal transplantation . Transplant Proc. 1989;21:2134-2136. 28. Gans ROB, Bilo HJG, Weersink EGL, et al. Fish oil supplementation in patients with stable claudication . Am J Surg. 1990;160:490-495.Crossref 29. Homan van der Heide JJ, Bilo HJG, Tegzess AM, Donker AJM. The effects of dietary supplementation with fish oil on renal function in cyclosporine-treated renal transplant recipients . Transplantation . 1990;49:523-527.Crossref 30. Bairati I, Roy L, Meyer F. Effects of a fish oil supplement on blood pressure and serum lipids in patients treated for coronary artery disease . Can J Cardiol. 1992; 8:41-46. 31. Norris PG, Jones CJH, Weston MJ. Effect of dietary supplementation with fish oil on systolic blood pressure in mild essential hypertension . BMJ . 1986;293: 104-105.Crossref 32. Bach R, Schmidt U, Jung F, et al. Effects of fish oil capsules in two dosages on blood pressure, platelet functions, haemorrheological and clinical chemistry parameters in apparently healthy subjects . Ann Nutr Metab. 1989;33:359-367.Crossref 33. Hughes GS, Ringer TV, Watts KC, DeLoof JJ, Francom SF, Spillers CR. Fish oil produces an atherogenic lipid profile in hypertensive men . Atherosclerosis . 1990; 84:229-237.Crossref 34. Cobiac L, Nestel PJ, Wing LMH, Howe PRC. Effects of dietary sodium restriction and fish oil supplements on blood pressure in the elderly . Clin Exp Pharmacol Physiol. 1991;18:265-268.Crossref 35. Mortensen JZ, Schmidt EB, Nielsen AH, Dyerberg J. The effect of N-6 and N-3 polyunsaturated fatty acids on hemostasis, blood lipids and blood pressure . Thromb Haemost. 1983;50:543-546. 36. Bruckner G, Webb P, Greenwell L, Chow C, Richardson D. Fish oil increases peripheral capillary blood cell velocity in humans . Atherosclerosis . 1987;66: 237-245.Crossref 37. Rogers S, James KS, Butland BK, Etherington MD, O'Brien JR, Jones JG. Effects of a fish oil supplement on serum lipids, blood pressure, bleeding time, haemostatic and rheological variables . Atherosclerosis . 1987;63:137-143.Crossref 38. Van Houwelingen R, Nordoy A, van der Beek E, Houtsmuller U, de Metz M, Hornstra G. Effect of a moderate fish intake on blood pressure, bleeding time, hematology, and clinical chemistry in healthy males . Am J Clin Nutr. 1987; 46:424-436. 39. Demke DM, Peters GR, Linet 01, Metzler CM, Klott KA. Effects of a fish oil concentrate in patients with hypercholesterolemia . Atherosclerosis . 1988;70: 73-80.Crossref 40. Blonk MC, Bilo HJG, Nauta JJP, Popp-Snijders C, Mulder C, Donker AJM. Dose-response effects of fish-oil supplementation in healthy volunteers . Am J Clin Nutr. 1990;53:120-127. 41. Flaten H, Hostmark AT, Kierulf P, et al. Fish-oil concentrate: effects on variables related to cardiovascular disease . Am J Clin Nutr. 1990;52:300-306. 42. Kestin M, Clifton P, Belling GB, Nestel PJ. n-3 Fatty acids of marine origin lower systolic blood pressure and triglycerides but raise LDL cholesterol compared with n-3 and n-6 fatty acids from plants . Am J Clin Nutr. 1990;51:1028-1034. 43. Cobiac L, Clifton PM, Abbey M, Belling GB, Nestel PJ. Lipid, lipoprotein, and hemostatic effects of fish vs fish-oil n-3 fatty acids in mildly hyperlipidemic males . Am J Clin Nutr. 1991;53:1210-1216. 44. Oh SY, Ryue J, Hsieh CH, Bell DE. Eggs enriched in ω-3 fatty acids and alterations in lipid concentrations in plasma and lipoprotein and in blood pressure . Am J Clin Nutr. 1991;54:689-695. 45. The Trials of Hypertension Prevention Collaborative Research Group (TOHP). The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels: results of the Trials of Hypertension Prevention, phase 1 . JAMA . 1992;267:1213-1220.Crossref 46. Singer P, Berger I, Luck K, Taube C, Naumann E, Godicke W. Long-term effect of mackerel diet on blood pressure, serum lipids and thromboxane formation in patients with mild essential hypertension . Atherosclerosis . 1986;62:259-265.Crossref 47. Knapp HR, Fitz-Gerald GA. The antihypertensive effects of fish oil: a controlled study of polyunsaturated fatty acid supplements in essential hypertension . N Engl J Med. 1989;320:1037-1043.Crossref 48. Meland E, Fugelli P, Laerum E, Ronneberg R, Sandivk L. Effect of fish oil on blood pressure and blood lipids in men with mild to moderate hypertension . Scand J Prim Health Care. 1989;7:131-135.Crossref 49. Bonaa KH, Bjerve KS, Straume B, Gram IT, Thelle D. Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension . N Engl J Med. 1990;322:795-801.Crossref 50. Levinson PD, Iosiphidis AH, Saritelli AL, Herbert PN, Steiner M. Effects of n-3 fatty acids in essential hypertension . Am J Hypertens. 1990;3:754-760. 51. Radack K, Deck C, Huster G. The effects of low doses of n-3 fatty acid supplementation on blood pressure in hypertensive subjects . Arch Intern Med. 1991;151:1173-1180.Crossref 52. Cutler JA, Follmann D, Elliott P, Suh I. An overview of randomized trials of sodium reduction and blood pressure . Hypertension . 1991;17( (suppl 1) ):127-133.Crossref 53. Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? Ill: analysis of data from trials of salt reduction . BMJ . 1991; 302:819-824.Crossref 54. MacMahon S, Cutler J, Brittain E, Higgins M. Obesity and hypertension: epidemiological and clinical issues . Eur Heart J. 1987;8:57-70.Crossref 55. Cutler JA. Randomized clinical trials of weight reduction in nonhypertensive persons . Ann Epidemiol. 1991;1:363-370.Crossref 56. Hepburn FN, Exler J, Weihrauch JL. Provisional tables on the content of omega-3 fatty acids and other fat components of selected foods . J Am Diet Assoc. 1986;86:788-793. 57. The Medical Letter Inc. Fish oil for the heart . Med Lett. 1987;29:7-9. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Does Supplementation of Diet With 'Fish Oil' Reduce Blood Pressure?: A Meta-analysis of Controlled Clinical Trials

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Publisher
American Medical Association
Copyright
Copyright © 1993 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1993.00410120017003
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Abstract

Abstract Background: Several lines of evidence suggest that supplementation of diet with omega-3 polyunsaturated fatty acids (ω-3) PUFA), commonly referred to as fish oils, may reduce blood pressure (BP). However, most clinical trials of ω-3 PUFA supplementation have been of insufficient size to detect relevant BP changes. Methods: We conducted a meta-analysis of 17 controlled clinical trials of ω-3 PUFA supplementation. To estimate an overall effect of ω-3 PUFA supplementation on BP, we calculated the net BP change in each trial (BP A in ω-3 PUFA group minus BP A in control group), which was then weighted according to the inverse of the variance. Results: In the 11 trials that enrolled normotensive individuals (n=728), ω-3 PUFA supplementation led to significant reductions of systolic BP (SBP) and diastolic BP (DBP) in two and one trials, respectively. In the six studies that enrolled untreated hypertensives (n=291), significant reductions of SBP and DBP were present in two and four trials, respectively. Weighted, pooled estimates of SBP and DBP change (mm Hg) with 95% confidence intervals were —1.0 (—2.0 to 0.0) and —0.5 (—1.2 to +0.2) in the trials of normotensives, and —5.5 (—8.1 to —2.9) and —3.5 (—5.0 to —2.1) in the trials of untreated hypertensives. In 13 of 17 studies, trial duration was less than 3 months. Doses of ω-3 PUFA tended to be high (average dose >3 g/d in 11 trials). The magnitude of BP reduction was greatest at high BP but was not significantly associated with dose of ω-3 PUFA. Side effects, most commonly eructation and a fishy taste, occurred more frequently in ω-3 PUFA participants than in control participants (28% vs 13%, P<.001). Conclusions: Our analyses indicate that diet supplementation with a relatively high dose of ω-3 PUFA, generally more than 3 g/d, can lead to clinically relevant BP reductions in individuals with untreated hypertension. However, use of ω-3 PUFA as antihypertensive therapy will require demonstration of long-term efficacy and patient acceptability of lower doses.(Arch Intern Med. 1993;153:1429-1438) References 1. Bang HO, Dyerberg J, Sinclair HM. The composition of the Eskimo food in north western Greenland . Am J Clin Nutr. 1980;33:2657-2661. 2. Kagawa Y, Nishizawa M, Suzuki M, et al. Eicosapolyenoic acids of serum lipids of Japanese islanders with low incidence of cardiovascular diseases . J Nutr Sci Vitaminol (Tokyo) . 1982;28:441-453.Crossref 3. Kromhout D, Bosschieter EB, Coulander CDL. The inverse relation between fish consumption and 20-year mortality from coronary heart disease . N Engl J Med. 1985;312:1205-1209.Crossref 4. Shekelle RB, Missell LV, Paul 0, Shryock AM, Stamler J. Fish consumption and mortality from coronary heart disease . N Engl J Med. 1985;313:820.Crossref 5. Norell SE, Ahlbom A, Feychting M, Pedersen NL. Fish consumption and mortality from coronary heart disease . BMJ . 1986;293:426.Crossref 6. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART) . Lancet . 1989;2:757-761.Crossref 7. Simopoulos AP. Omega-3 fatty acids in health and disease and in growth and development . Am J Clin Nutr. 1991;54:438-463. 8. Bonaa K. Epidemiological and intervention studies on the effect of marine polyunsaturated fatty acids on blood pressure . J Intern Med. 1989;225( (suppl 1) ): 105-110.Crossref 9. Radack K, Deck C. The effects of omega-3 polyunsaturated fatty acids on blood pressure: a methodologic analysis of the evidence . J Am Coll Nutr. 1989;8: 376-385.Crossref 10. Greenland S. Quantitative methods in the review of epidemiologic literature . Epidemiol Rev. 1987;9:1-30. 11. Gill JS, Zezulka AV, Beevers DG, Davies P. Relationship between initial blood pressure and its fall with treatment . Lancet . 1985;1:567-569.Crossref 12. Wing LMH, Nestel PJ, Chalmers JP, et al. Lack of effect of fish oil supplementation on blood pressure in treated hypertensives . J Hypertens. 1990;8: 339-343.Crossref 13. Singer P, Melzer S, Goschell M, Augustin S. Fish oil amplifies the effect of propranolol in mild essential hypertension . Hypertension . 1990;16:682-691.Crossref 14. Margolin G, Huster G, Glueck CJ, et al. Blood pressure lowering in elderly subjects: a double-blind crossover study of ω-3 and ω-6 fatty acids . Am J Clin Nutr. 1991;53:562-572. 15. Sanders TAB, Vickers M, Haines AP. Effect on blood lipids and haemostasis of a supplement of cod-liver oil, rich in eicosapentaenoic and docosahexaenoic acids, in healthy young men . Clin Sci. 1981;61:317-324. 16. Lorenz R, Spengler U, Fischer S, Duhm J, Weber PC. Platelet function, thromboxane formation and blood pressure control during supplementation of the western diet with cod liver oil . Circulation . 1983;67:504-511.Crossref 17. Hamazaki T, Nakazawa R, Tateno S, et al. Effects of fish oil rich in eicosapentaenoic acid on serum lipid in hyperlipidemic hemodialysis patients . Kidney Int. 1984;26:81-84.Crossref 18. Olivieri O, Negri M, De Gironcoli M. Effects of dietary fish oil on malondialdehyde production and glutathione peroxidase activity in hyperlipidemic patients . Scand J Clin Lab Invest. 1988;48:659-665.Crossref 19. Urakaze M, Hamazaki T, Yano S. Fish oil and hypertension . J Hum Hypertens. 1989;3:277-278. 20. Singer P, Jaeger W, Wirth M, et al. Lipid and blood pressure-lowering effect of mackerel diet in man . Atherosclerosis . 1983;49:99-108.Crossref 21. Singer P, Wirth M, Berger I, et al. Influence on serum lipids, lipoproteins and blood pressure of mackerel and herring diet in patients with type IV and V hyperlipoproteinemia . Atherosclerosis . 1985;56:111-118.Crossref 22. Singer P, Wirth M, Voigt S, et al. Blood pressure- and lipid-lowering effect of mackerel and herring diet in patients with mild essential hypertension . Atherosclerosis . 1985;56:223-235.Crossref 23. Kristensen SD, Schmidt EB, Anderson HR, Dyerberg J. Fish oil in angina pectoris . Atherosclerosis . 1987;64:13-19.Crossref 24. Kasim SE, Stern B, Khilnani S, McLin P, Baciorowski S, Jen KLC. Effects of omega-3 fish oils on lipid metabolism, glycemic control, and blood pressure in type II diabetic patients . J Clin Endocrinol Metab. 1988;67:1-5.Crossref 25. Jensen T, Stender S, Goldstein K, Holmer G, Deckert T. Partial normalization by dietary cod-liver oil of increased microvascular albumin leakage in patients with insulin-dependent diabetes and albuminuria . N Engl J Med. 1989;321: 1572-1577.Crossref 26. Mehta JL, Lopez LM, Lawson D, Wargovich TJ, Williams LL. Dietary supplementation with omega-3 polyunsaturated fatty acids in patients with stable coronary heart disease . Am J Med. 1988;84:45-52.Crossref 27. Urakaze M, Hamazaki T, Yano S, Kashiwabara H, Oomori K, Yokoyama T. Effect of fish oil concentrate on risk factors of cardiovascular complications in renal transplantation . Transplant Proc. 1989;21:2134-2136. 28. Gans ROB, Bilo HJG, Weersink EGL, et al. Fish oil supplementation in patients with stable claudication . Am J Surg. 1990;160:490-495.Crossref 29. Homan van der Heide JJ, Bilo HJG, Tegzess AM, Donker AJM. The effects of dietary supplementation with fish oil on renal function in cyclosporine-treated renal transplant recipients . Transplantation . 1990;49:523-527.Crossref 30. Bairati I, Roy L, Meyer F. Effects of a fish oil supplement on blood pressure and serum lipids in patients treated for coronary artery disease . Can J Cardiol. 1992; 8:41-46. 31. Norris PG, Jones CJH, Weston MJ. Effect of dietary supplementation with fish oil on systolic blood pressure in mild essential hypertension . BMJ . 1986;293: 104-105.Crossref 32. Bach R, Schmidt U, Jung F, et al. Effects of fish oil capsules in two dosages on blood pressure, platelet functions, haemorrheological and clinical chemistry parameters in apparently healthy subjects . Ann Nutr Metab. 1989;33:359-367.Crossref 33. Hughes GS, Ringer TV, Watts KC, DeLoof JJ, Francom SF, Spillers CR. Fish oil produces an atherogenic lipid profile in hypertensive men . Atherosclerosis . 1990; 84:229-237.Crossref 34. Cobiac L, Nestel PJ, Wing LMH, Howe PRC. Effects of dietary sodium restriction and fish oil supplements on blood pressure in the elderly . Clin Exp Pharmacol Physiol. 1991;18:265-268.Crossref 35. Mortensen JZ, Schmidt EB, Nielsen AH, Dyerberg J. The effect of N-6 and N-3 polyunsaturated fatty acids on hemostasis, blood lipids and blood pressure . Thromb Haemost. 1983;50:543-546. 36. Bruckner G, Webb P, Greenwell L, Chow C, Richardson D. Fish oil increases peripheral capillary blood cell velocity in humans . Atherosclerosis . 1987;66: 237-245.Crossref 37. Rogers S, James KS, Butland BK, Etherington MD, O'Brien JR, Jones JG. Effects of a fish oil supplement on serum lipids, blood pressure, bleeding time, haemostatic and rheological variables . Atherosclerosis . 1987;63:137-143.Crossref 38. Van Houwelingen R, Nordoy A, van der Beek E, Houtsmuller U, de Metz M, Hornstra G. Effect of a moderate fish intake on blood pressure, bleeding time, hematology, and clinical chemistry in healthy males . Am J Clin Nutr. 1987; 46:424-436. 39. Demke DM, Peters GR, Linet 01, Metzler CM, Klott KA. Effects of a fish oil concentrate in patients with hypercholesterolemia . Atherosclerosis . 1988;70: 73-80.Crossref 40. Blonk MC, Bilo HJG, Nauta JJP, Popp-Snijders C, Mulder C, Donker AJM. Dose-response effects of fish-oil supplementation in healthy volunteers . Am J Clin Nutr. 1990;53:120-127. 41. Flaten H, Hostmark AT, Kierulf P, et al. Fish-oil concentrate: effects on variables related to cardiovascular disease . Am J Clin Nutr. 1990;52:300-306. 42. Kestin M, Clifton P, Belling GB, Nestel PJ. n-3 Fatty acids of marine origin lower systolic blood pressure and triglycerides but raise LDL cholesterol compared with n-3 and n-6 fatty acids from plants . Am J Clin Nutr. 1990;51:1028-1034. 43. Cobiac L, Clifton PM, Abbey M, Belling GB, Nestel PJ. Lipid, lipoprotein, and hemostatic effects of fish vs fish-oil n-3 fatty acids in mildly hyperlipidemic males . Am J Clin Nutr. 1991;53:1210-1216. 44. Oh SY, Ryue J, Hsieh CH, Bell DE. Eggs enriched in ω-3 fatty acids and alterations in lipid concentrations in plasma and lipoprotein and in blood pressure . Am J Clin Nutr. 1991;54:689-695. 45. The Trials of Hypertension Prevention Collaborative Research Group (TOHP). The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels: results of the Trials of Hypertension Prevention, phase 1 . JAMA . 1992;267:1213-1220.Crossref 46. Singer P, Berger I, Luck K, Taube C, Naumann E, Godicke W. Long-term effect of mackerel diet on blood pressure, serum lipids and thromboxane formation in patients with mild essential hypertension . Atherosclerosis . 1986;62:259-265.Crossref 47. Knapp HR, Fitz-Gerald GA. The antihypertensive effects of fish oil: a controlled study of polyunsaturated fatty acid supplements in essential hypertension . N Engl J Med. 1989;320:1037-1043.Crossref 48. Meland E, Fugelli P, Laerum E, Ronneberg R, Sandivk L. Effect of fish oil on blood pressure and blood lipids in men with mild to moderate hypertension . Scand J Prim Health Care. 1989;7:131-135.Crossref 49. Bonaa KH, Bjerve KS, Straume B, Gram IT, Thelle D. Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension . N Engl J Med. 1990;322:795-801.Crossref 50. Levinson PD, Iosiphidis AH, Saritelli AL, Herbert PN, Steiner M. Effects of n-3 fatty acids in essential hypertension . Am J Hypertens. 1990;3:754-760. 51. Radack K, Deck C, Huster G. The effects of low doses of n-3 fatty acid supplementation on blood pressure in hypertensive subjects . Arch Intern Med. 1991;151:1173-1180.Crossref 52. Cutler JA, Follmann D, Elliott P, Suh I. An overview of randomized trials of sodium reduction and blood pressure . Hypertension . 1991;17( (suppl 1) ):127-133.Crossref 53. Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? Ill: analysis of data from trials of salt reduction . BMJ . 1991; 302:819-824.Crossref 54. MacMahon S, Cutler J, Brittain E, Higgins M. Obesity and hypertension: epidemiological and clinical issues . Eur Heart J. 1987;8:57-70.Crossref 55. Cutler JA. Randomized clinical trials of weight reduction in nonhypertensive persons . Ann Epidemiol. 1991;1:363-370.Crossref 56. Hepburn FN, Exler J, Weihrauch JL. Provisional tables on the content of omega-3 fatty acids and other fat components of selected foods . J Am Diet Assoc. 1986;86:788-793. 57. The Medical Letter Inc. Fish oil for the heart . Med Lett. 1987;29:7-9.

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Jun 28, 1993

References