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Lipid Disorders and Essential Fatty Acids

Written by ColleenO, FoundHealth.

Fish oil has shown distinct promise for treating high triglycerides. When taken in combination with stanols and sterols, fish oil helps lower total cholesterol, LDL cholesterol, and triglycerides, while increasing HDL cholesterol.

Fish oil supplementation should be considered for patients on statin drugs. Fish oil can enhance the effects of statins and help decrease potentially severe side-effects of the drugs.

Krill are tiny shrimp-like crustaceans that flourish in the Antarctic Ocean and provide food for numerous aquatic animals. Krill oil is similar but not identical to fish oil and may improve cholesterol profile.

A slightly modified form of fish oil (ethyl-omega-3 fatty acids) has been approved by the FDA as a treatment for high triglycerides.33 This specially processed product, sold under the trade name Omacor, is widely advertised as more effective than ordinary fish oil. However, it should be noted that Omacor has undergone relatively little study itself; the physician prescribing information notes only two small trials to support its effectiveness for this use. This is far less evidence than usually required for drug approval, and also substantially less than the body of evidence supporting standard fish oil as a treatment for high triglycerides.

Effect of Essential Fatty Acids on Lipid Disorders

Fish oil has a number of effects on cardiovascular processes and conditions, including reducing triglycerides and increasing HDL ("good") cholesterol.

Read more details about Essential Fatty Acids.

Research Evidence on Essential Fatty Acids

Fish oil has been shown to have a favorable effect on fats in the blood, in particular triglycerides. A study investigating the possible benefit of combining sterols with fish oil found that together they significantly lowered total cholesterol, LDL-cholesterol and triglycerides, and raised HDL-cholesterol in subjects with undesirable cholesterol profiles.286

Fish oil has shown distinct promise for treating high triglycerides. More than 2,000 people have participated in well-designed studies of fish oil for reducing triglyceride levels.1 Most studies ran from about 7 to 10 weeks.

It appears that fish oil supplements can reduce triglycerides by about 25% to 30%. Although not all studies have been positive, in a detailed review of 47 randomized trials, researchers concluded that fish oil is capable of significantly reducing triglyceride levels with no change in total cholesterol levels and only slight increases in HDL (“good”) cholesterol and LDL (“bad”) cholesterol.35 Fish oil has been studied for reducing triglyceride levels specifically in people with diabetes, and it appears to do so safely and effectively.3 It should be noted that in some studies, use of fish oil has markedly raised LDL cholesterol, which might offset some of the benefit.

The most important omega-3 fatty acids found in fish oil are named EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). According to some, but not all, studies, EPA may be more important than DHA for reducing triglyceride levels.5-10,32

Fish oil may enhance the effectiveness of drugs in the statin family.252,264 EPA, a constituent of fish oil, may help prevent severe heart complications in people with high cholesterol already taking statins.254

Krill oil is made from shrimp-like crustaceans. It is similar but not identical to fish oil and may improve cholesterol profile.204

How to Use Essential Fatty Acids

Typical dosages of fish oil are 3 g to 9 g daily, but this is not the upper limit. In one study, participants ingested 60 g daily.

The most important omega-3 fatty acids found in fish oil are called eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In order to match the dosage used in several major studies, you should take enough fish oil to supply about 2 g to 3 g of EPA (2,000 mg to 3,500 mg) and about 1.0 g to 2.5 g of DHA daily (1,000 mg to 2,500 mg). Far higher doses have been used in some studies; conversely, one study found blood-pressure lowering effects with a very low daily dosage of DHA—0.7 g.238

DHA and EPA are not identical and might not have identical effects. Some evidence hints that DHA may be more effective than EPA for thinning the blood 176 and reducing blood pressure.105 The reverse may be true for reducing triglyceride levels, but study results are conflicting.160-165,235

Some manufacturers add vitamin E to fish oil capsules to keep the oil from becoming rancid. Another method is to remove all the oxygen from the capsule.

If possible, purchase fish oil products certified as free of significant levels of mercury, toxic organochlorines, and PCBs (see Safety Issues).

Flaxseed oil also contains omega-3 fatty acids, although of a different kind. It has been suggested as a less smelly substitute for fish oil. However, it is far from clear whether flaxseed oil is therapeutically equivalent to fish oil.1,200

Types of Professionals That Would Be Involved with This Treatment

  • Integrative MD
  • Naturopathic doctor
  • Clinical nutritionist or registered dietitian

Safety Issues

Fish oil appears to be generally safe. The most common problem is fishy burps. However, there are some safety concerns to consider.

For example, it has been suggested that some fish oil products contain excessive levels of toxic substances such as organochlorines and PCBs. 1 If possible, try to purchase fish oil products certified not to contain significant levels of these contaminants. Note:Various types of fish contain mercury, but this has not been a problem with fish oil supplements, according to reports on Consumerlab.com.

Fish oil has a mild blood-thinning effect; 2 in one case report, it increased the effect of the blood-thinning medication warfarin (Coumadin). 3 Fish oil does not seem to cause bleeding problems when it is taken by itself 4 or with aspirin. 5 Nonetheless, people who are at risk of bleeding complications for any reason should consult a physician before taking fish oil.

Fish oil does not appear to raise blood sugar levels in people with diabetes. 6 Nonetheless, if you have diabetes, you should not take any supplement except on the advice of a physician.

Fish oil may modestly increase weight and lower total cholesterol and HDL (“good”) cholesterol levels. 7 It may also raise the level of LDL ("bad") cholesterol; however, this effect may be short-lived. 8 If you decide to use cod liver oil as your fish oil supplement, make sure you do not exceed the safe maximum intake of vitamin A and vitamin D . These vitamins are fat soluble, which means that excess amounts tend to build up in your body, possibly reaching toxic levels. The official maximum daily intake of vitamin A is 3,000 mcg for pregnant women as well as other adults. Look at the bottle label to determine how much vitamin A you are receiving. (It is less likely that you will get enough vitamin D to produce toxic effects.)

Interactions You Should Know About

If you are taking warfarin (Coumadin) or heparin , do not take fish oil except on the advice of a physician.

References

  1. Jacobs MN, Santillo D, Johnston PA, Wyatt CL, French MC. Organochlorine residues in fish oil dietary supplements: comparison with industrial grade oils. Chemosphere. 37(9-12):1709-21.
  2. Emsley R, Niehaus DJ, Oosthuizen PP, Koen L, Ascott-Evans B, Chiliza B, van Rensburg SJ, Smit RM. Safety of the omega-3 fatty acid, eicosapentaenoic acid (EPA) in psychiatric patients: results from a randomized, placebo-controlled trial. Psychiatry Res. 161(3):284-91.
  3. Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother. 38(1):50-2.
  4. Harris WS. Dietary fish oil and blood lipids. Curr Opin Lipidol. 7(1):3-7.
  5. Leaf A, Jorgensen MB, Jacobs AK, Cote G, Schoenfeld DA, Scheer J, Weiner BH, Slack JD, Kellett MA, Raizner AE. Do fish oils prevent restenosis after coronary angioplasty? Circulation. 90(5):2248-57.
  6. Harris WS. Dietary fish oil and blood lipids. Curr Opin Lipidol. 7(1):3-7.
  7. Emsley R, Niehaus DJ, Oosthuizen PP, Koen L, Ascott-Evans B, Chiliza B, van Rensburg SJ, Smit RM. Safety of the omega-3 fatty acid, eicosapentaenoic acid (EPA) in psychiatric patients: results from a randomized, placebo-controlled trial. Psychiatry Res. 161(3):284-91.
  8. 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. 53(5):1210-6.
  1. Harris WS. N-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(suppl 5 ):S1645-S1654.
  2. van Dam M, Stalenhoef AF, Wittekoek J, et al. Efficacy of concentrated n-3 fatty acids in hypertriglyceridaemia: a comparison with gemfibrozil. Clin Drug Invest. 2001;21:175-181.
  3. Montori VM, Farmer A, Wollan PC, et al. Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care. 2000;23:1407-1415.
  4. Durrington PN, Bhatnagar D, Mackness MI, et al. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544-548.
  5. Mori TA, Burke V, Puddey IB, et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr. 2000;71:1085-1094.
  6. Rambjor GS, Walen AI, Windsor SL. Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans. Lipids. 1996;31(Suppl):S45-S49.
  7. Agren JJ, Hanninen O, Julkunen A, et al. Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels. Eur J Clin Nutr. 1996;50:765-771.
  8. Childs MT, King IB, Knopp RH. Divergent lipoprotein responses to fish oils with various ratios of eicosapentaenoic acid and docosahexaenoic acid. Am J Clin Nutr. 1990;52:632-639.
  9. Davidson MH, Maki KC, Kalkowski J, et al. Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial. J Am Coll Nutr. 1997;16:236-243.
  10. Leigh-Firbank EC, Minihane AM, Minihane AM, et al. Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses. Br J Nutr. 2002;87:435-445.
  11. Schwellenbach LJ, Olson KL, McConnell KJ, et al. The triglyceride-lowering effects of a modest dose of docosahexaenoic acid alone versus in combination with low-dose eicosapentaenoic acid in patients with coronary artery disease and elevated triglycerides. J Am Coll Nutr. 2006;25:480-5.
  12. McKenney JM, Sica D. Prescription omega-3 fatty acids for the treatment of hypertriglyceridemia. Am J Health Syst Pharm. 2007;64:595-605.
  13. Meyer BJ, Hammervold T, Rustan AC, et al. Dose-dependent effects of docosahexaenoic acid supplementation on blood lipids in statin-treated hyperlipidaemic subjects. Lipids. 2007;42:109-15.
  14. Eslick GD, Howe PR, Smith C, et al. Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol. 2008 Sep 5.
  15. Mori TA, Bao DQ, Burke V, et al. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension. 1999;34:253-260.
  16. Mori TA, Burke V, Puddey IB, et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr. 2000;71:1085-1094.
  17. Rambjor GS, Walen AI, Windsor SL Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans. Lipids. 1996;31(suppl):45-49.
  18. Agren JJ, Hanninen O, Julkunen A, et al. Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels. Eur J Clin Nutr. 1996;50:765-771.
  19. Childs MT, King IB, Knopp RH. Divergent lipoprotein responses to fish oils with various ratios of eicosapentaenoic acid and docosahexaenoic acid. Am J Clin Nutr. 1990;52:632-639.
  20. Davidson MH, Maki KC, Kalkowski J, et al. Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial. J Am Coll Nutr. 1997;16:236-243.
  21. Leigh-Firbank EC, Minihane AM, Minihane AM, et al. Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses. Br J Nutr. 2002;87:435-445.
  22. Harper CR, Edwards MJ, Defilipis AP, et al. Flaxseed Oil Increases the Plasma Concentrations of Cardioprotective (n-3) Fatty Acids in Humans. J Nutr. 2005;136:83-87.
  23. Mozaffarian D, Geelen A, Brouwer IA, et al. Effect of fish oil on heart rate in humans. A meta-analysis of randomized controlled trials. Circulation. 2005 Sep 19. [Epub ahead of print]
  24. Murkovic M, Abuja PM, Bergmann AR, et al. Effects of elderberry juice on fasting and postprandial serum lipids and low-density lipoprotein oxidation in healthy volunteers: a randomized, double-blind, placebo-controlled study. Eur J Clin Nutr. 2004;58:244-249.
  25. Schwellenbach LJ, Olson KL, McConnell KJ, et al. The triglyceride-lowering effects of a modest dose of docosahexaenoic acid alone versus in combination with low-dose eicosapentaenoic acid in patients with coronary artery disease and elevated triglycerides. J Am Coll Nutr. 2006;25:480-485.
  26. Theobald HE, Goodall AH, Sattar N, et al. Low-dose docosahexaenoic acid lowers diastolic blood pressure in middle-aged men and women. J Nutr. 2007;137:973-978.
  27. Meyer BJ, Hammervold T, Rustan AC, et al. Dose-dependent effects of docosahexaenoic acid supplementation on blood lipids in statin-treated hyperlipidaemic subjects. Lipids. 2007;42:109-115.
  28. Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369:1090-1098.
  29. Davidson MH, Stein EA, Bays HE, et al. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354-1367.
  30. Micallef MA, Garg ML. The lipid-lowering effects of phytosterols and (n-3) polyunsaturated fatty acids are synergistic and complementary in hyperlipidemic men and women. J Nutr. 2008;138:1086-1090.

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