Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Berry, E.M.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Berry, E.M.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


Are diets high in omega-6 polyunsaturated fatty acids unhealthy?

E.M. Berry*

Department of Human Nutrition and Metabolism, Hebrew University Hadassah Medical School, Jerusalem, Israel

* Correspondence: Elliot M. Berry, Department of Human Nutrition and Metabolism, Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem, Israel 91120.

Abstract

This article reviews the connection between dietary omega-6 fatty acids and atherosclerosis, carcinogenesis and insulin resistance. These polyunsaturated fatty acids (PUFAs) may be likened to ‘double-edged swords’: on one hand they are considered essential for membrane function and eicosanoid formation necessary for vascular, immune and inflammatory cell function, while on the other they lead to increased susceptibility to lipid oxidation, stimulating neoplastic cell growth in culture and impairing insulin activity. Omega-6 function should not be considered in isolation but as part of a complex of nutrient interactions together with omega-3 fatty acids (shared enzymatic pathways) and antioxidants. Insulin sensitivity might be the common factor relating disease to fatty acid metabolism — both within and between the fatty acid pathways. A high linoleate to arachidonate concentration occurs in insulin resistance, in diabetic complications and also in some tumours. Since the interaction between the omega-6 and omega-3 pathways in neither linear nor stochastic, specific dietary recommendations have to await clarification of these relationships. Adipose tissue fatty acid composition and function may be a suitable biomarker with which to study these questions. Current epidemiological and clinical evidence supports the regular consumption of cold-water fish as part of a balanced diet, in which attention to lifestyle and the quantities eaten (to prevent obesity and the insulin resistance syndrome) may be more critical than the nature of the fatty acids consumed.

Key Words: Polyunsaturated fatty acids • insulin resistance • heart disease • cancer • omega-6 fatty acids • omega-3 fatty acids

References

  1. Keys A, Parlin RW. Serum cholesterol response to changes in dietary lipids. Am J Clin Nutr. 1966;19:175–181[Abstract]
  2. Task Force of the European Society of Cardiology EAS, European Society of Hypertension. Prevention of coronary heart disease in clinical practice. Eur Heart J. 1994;15:130–131
  3. Yam D, Eliraz A, Berry EM. Diet and disease — the Israeli paradox: possible dangers of a high omega-6 polyunsaturated fatty acid diet. Isr J Med Sci. 1996;32:1134–1143[Web of Science][Medline]
  4. Reaven GM. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–1607[Abstract]
  5. Budowski P. Alpha-linolenic acid and the metabolism of arachidonic acid. Galli C, Simopoulos A. Dietary n-3 and n-6 Fatty Acids: Biological Effects and Nutritional Essentiality. New York: Plenum Press; 1988. p. 97–110
  6. Okuyama H, Kobayashi T, Watanabe S. Dietary fatty acids — the balance and chronic elderly diseases. Excess linoleic acid and relative n-3 deficiency syndrome seen in Japan. Prog Lipid Res. 1997;35:409–457[Web of Science]
  7. British Nutrition Foundation. Unsaturated Fatty Acids. London: Chapman & Hall; 1992.
  8. Lands WEM. Biochemistry and physiology of n-3 FAs. FASEB J. 1992;6:2530–2536[Abstract]
  9. Xu J, Nakamura MT, Cho HP, Clarke SD. Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. J Biol Chem. 1999;274:23577–23583[Abstract/Free Full Text]
  10. Alexander JW. Immunonutrition: the role of omega-3 fatty acids. Nutrition. 1998;14:627–633[CrossRef][Web of Science][Medline]
  11. Berry EM, Eisenberg S, Friedlander Y, et al. Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins — The Jerusalem Nutrition Study. I. High MUFA vs high PUFAs. Am J Clin Nutr. 1991;53:899–907[Abstract/Free Full Text]
  12. Jenkinson A, Franklin MF, Wahle K, Duthie GG. Dietary intakes of polyunsaturated fatty acids and indices of oxidative stress in human volunteers. Eur J Clin Nutr. 1999;53:523–528[CrossRef][Web of Science][Medline]
  13. Hodgson JM, Wahlqvist ML, Boxall JA, Balazs ND. Can linoleic acid contribute to coronary heart disease? Am J Clin Nutr. 1993;58:228–234[Abstract/Free Full Text]
  14. Gordon DJ, Probsfield TH, Gamson RJ, et al. HDL-cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989;74:8–15
  15. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Modifications of low density lipoprotein that increase the atherogenicity. N Engl J Med. 1989;320:24–40
  16. Berry EM, Eisenberg S, Friedlander Y, et al. Effects of diet rich in monounsaturated fatty acids on plasma lipoproteins — The Jerusalem Nutrition Study. III. Monounsaturated vs saturated fatty acids. Nutr Metab Cardiovasc Dis. 1995;5:55–62
  17. Harats D, Dabach Y, Hollander G, et al. Fish oil ingestion in smokers and nonsmokers enhances peroxidation of plasma lipoproteins. Atherosclerosis. 1991;90:127–139[CrossRef][Web of Science][Medline]
  18. GISSI—Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI—Prevenzione trial. Lancet. 1999;354:447–455[CrossRef][Web of Science][Medline]
  19. Umeda F, Kunisaki M, Inoguchi T, Nawata H. Modification of prostacyclin-stimulatory activity in sera by glucose, insulin, low density lipoprotein, linoleic acid and linoleic acid hydroperoxide. Diabetes Res Clin Pract. 1990;8:137–144[CrossRef][Web of Science][Medline]
  20. Harats D, Chevion S, Nahir M, Norman Y, Sagee O, Berry EM. Citrus fruit supplementation reduces lipoprotein oxidation in young men ingesting a high saturated fat diet — presumptive evidence for interaction between vitamins C and E in vivo. Am J Clin Nutr. 1998;68:240–245
  21. Berry EM, Dalmaso L, Franceschi S. Synergism between vitamins E and C: biological implications for future research. Int J Cancer. 1999;83:288[CrossRef][Web of Science][Medline]
  22. Li L, Kang JX, Leaf A. Differential effects of various eicosanoids on the production or prevention of arrhythmias in cultured neonatal rat cardiac myocytes. Prostaglandins. 1997;54:511–530[CrossRef][Web of Science][Medline]
  23. Kang JX, Leaf A. Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes. Proc Natl Acad Sci USA. 3rd edn. 1994. p. 9886–9890
  24. McLennan PL. Relative effects of dietary saturated, monounsaturated and polyunsaturated fatty acids on cardiac arrhythmias. Am J Clin Nutr. 1993;57:207–212[Abstract/Free Full Text]
  25. Sasaki T, Kanke Y, Kudoh K, Misawa Y, Shimuizu J, Takita T. Effects of dietary docosahexaenoic acid on surface molecules involved in T cell proliferation. Biochim Biophys Acta. 1999;1436:519–530[Medline]
  26. Jeffery NM, Sanderson P, Sherrington EJ, Newsholme EA, Calder PC. The ratio of n-6 to n-3 polyunsaturated fatty acids in the rat diet alters serum lipid levels and lymphocyte functions. Lipids. 1996;31:737–745[CrossRef][Web of Science][Medline]
  27. Nair J, Barbib A, Velic I, Bartsch H. Etheno DNA-base adducts from endogenous reactive species. Mutation Res. 1999;424:59–69
  28. Fang JL, Vaca CE, Valsta LM, Mutanen M. Determination of DNA adducts of malonaldehyde in humans: effects of dietary fatty acid composition. Carcinogenesis. 1996;17:1035–1040[Abstract/Free Full Text]
  29. Chen L, Bowen PE, Berzy D, Aryee F, Stacewicz-Sapuntzakis M, Riley RE. Diet modification affects DNA oxidative damage in healthy humans. Free Radic Biol Med. 1999;26:695–703[CrossRef][Web of Science][Medline]
  30. Vanderveen EF, Grekin BC, Swanson NA. Arachidonic acid and metabolites in cutaneous carcinomas: evidence suggesting that elevated levels of prostaglandins in basal cell carcinomas are associated with an aggressive growth pattern. Arch Dermatol. 1986;122:407–412[Abstract/Free Full Text]
  31. Narisawa T, Sato M, Takahashi T. Inhibition of development of methyl-nitrosurea induced rat colonic tumors by peroral administration of indomethacin. Gann. 1982;173:377–381
  32. Neichi T, Koshihara Y, Murota SI. Inhibitory effect of esculetin on 5-lipoxygenase and leukotriene biosynthesis. Biochim Biophys Acta. 1983;753:130–132[Medline]
  33. Fulton AM, Heppner GH. Relationship of prostaglandin E and natural killer sensitivity to metastatic potential in murine mammary adenocarcinomas. Cancer Res. 1985;45:4779–4784[Abstract/Free Full Text]
  34. Howe GR, Hirohata T, Hislop TG, et al. Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies. J Natl Cancer Inst. 1990;82:561–569[Abstract/Free Full Text]
  35. Hunter DJ, Spiegelman D, Adami HO, et al. Cohort studies of fat intake and the risk of breast cancer — a pooled analysis. N Engl J Med. 1996;334:356–361[Abstract/Free Full Text]
  36. The Women's Health Initiative Study Group. Design of the Women's Health Initiative clinical trial and observational study. Controlled Clinical Trials. 1998;19:61–109[CrossRef][Web of Science][Medline]
  37. Pariza MW. Dietary fat, calorie restriction, ad libitum feeding and cancer risk. Nutr Rev. 1987;45:1–7[Web of Science][Medline]
  38. Eid A, Berry EM. The relationship between dietary fat, adipose tissue composition and neoplasms of the breast. Nutrition and Cancer. 1988;11:173–177[Web of Science][Medline]
  39. Berry EM, Zimmerman J, Peser M, Ligumsky M. Dietary fat, adipose tissue composition and the development of carcinoma of the colon. J Natl Cancer Inst. 1986;77:93–97
  40. Yam D, Ben Hur H, Fink A, et al. Insulin and glucose status, tissue and plasma lipids in patients with tumors of the ovary or endometrium; possible dietary implications. Br J Cancer. 1994;70:1186–1187[Web of Science][Medline]
  41. Brenner RR. Endocrine control of fatty acid desaturation. Biochem Soc Trans. 1990;18:773–775[Web of Science][Medline]
  42. Berry EM, Hirsch J, Most J, McNamara DJ, Cunningham-Rundles S. Dietary fat, plasma lipoproteins and immune function in middle aged American men. Nutrition and Cancer. 1987;9:129–142[Medline]
  43. Lardinois CK, Starich GH, Mazzaferri EL, De Lett A. Polyunsaturated fatty acids augment insulin secretion. J Am Coll Nutr. 1987;6:507–515[Abstract]
  44. Storlien LH, James DE, Burleigh KM, Chisholm DJ, Kraegen EW. Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure and obesity in rats. Am J Physiol. 1986;251:E576–E583
  45. Stout RW. Insulin as a mitogenic factor: role in the pathogenesis of cardiovascular disease. Am J Med. 1991;90(Suppl 2A):62–65
  46. Dietze GJ. Modulation of the action of insulin in relation to the energy state in skeletal muscle tissue: Possible involvement of kinins and prostaglandins. Mol Cell Endocrinol. 1982;25:127–149[CrossRef][Web of Science][Medline]
  47. Babbs CF. Free radicals and the etiology of colon cancer. Free Radic Biol Med. 1990;8:191–200[CrossRef][Web of Science][Medline]
  48. Lands WEM. Eicosanoids and health. Ann NY Acad Sci. 1993;676:46–59[Web of Science][Medline]
  49. Jones DB, Carter RD, Haitas B, Mann JI. Low phospholipid arachidonic acid values in diabetic platelets. Br Med J. 1983;286:173–175
  50. Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campbell LV. The relation between insulin sensitivity and the fatty acid composition of skeletal muscle phospholipids. N Engl J Med. 1993;328:238–244[Abstract/Free Full Text]
  51. Storlien LH, Kraegen EW, Chisholm DJ, Ford GL, Bruce DG, Pascoe WE. Fish oil prevents insulin resistance induced by high fat feeding in rats. Science. 1987;237:885–888[Abstract/Free Full Text]
  52. Cunnane SC, McAdoo KR, Horrobin DF. n-3 Essential fatty acids decrease weight gain in genetically obese mice. Br J Nutr. 1986;56:87–95[CrossRef][Web of Science][Medline]
  53. Berry EM, Hirsch J. Does dietary linolenic acid influence blood pressure? Am J Clin Nutr. 1986;44:336–340[Abstract/Free Full Text]
  54. Berry EM. Dietary fatty acids in the management of diabetes mellitus. Am J Clin Nutr. 1997;66:991S–997S (Suppl)[Abstract/Free Full Text]
  55. Raheja BS, Sadikot SM, Phatak RB, Rao MB. Significance of the ratio for insulin action in diabetes. Ann NY Acad Sci. 1993;683:258–271[CrossRef][Web of Science][Medline]
  56. Budowski P, Crawford MA. Alpha linolenic acid as a regulator of the metabolism of arachidonic acid: dietary implications of the ratio, n-6:n-3 fatty acids. Proc Nutr Soc. 3rd edn. 1985. p. 221–229
  57. Special Committee. Expert's recommendations on fats and oils in human nutrition. Food Nutr Agric. 1994;11:2–6
  58. Berry EM, Kohen R. Is the biological antioxidant system integrated and regulated? Medical Hypotheses. 1999;53:397–401[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Berry, E.M.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Berry, E.M.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?