ω3 and ω6 Essential Fatty Acid Status in Human Health and Disease

  • Ralph T. Holman


In 1943 when I began research with Professor George O. Burr on the chemistry of essential fatty acids (EFA), there were no methods to measure individual fatty acids (FA) in tissue lipids. Using the new Beckman (Fullerton, CA) DU spectrophotometer, instrument #6, we explored the use of ultraviolet spectra in the study of auto-oxidation of individual FA, and found that the auto-oxidation of the polyunsaturated fatty acids (PUFA) induced drastic elevations of absorption in the ultraviolet range (Holman et al., 1945). Holman and Burr (1948) then exploited the alkaline conjugation reaction, at high temperature, to induce conjugation of the double bonds of the common essential FA. The fully conjugated polyenoic acids had distinctive absorption bands, which made it possible to distinguish and measure the content of the originally nonconjugated, methylene interrupted diene-, triene-, tetraene-, pentaene-, and hexaene-acids present in biological lipids. Using this new analytical method, we learned next that the lack of PUFA in the diet lowered the amount of arachidonic acid in liver lipids, and that a triene acid, not present in animals fed EFA, appeared in those lipids. Supplementation with corn oil elevated the arachidonic acid, but supplementation with cod liver oil elevated the pentaenoic and hexaenoic acids in all tissues analyzed by Rieckehoff et al. (1949). The dietary fat influenced the lipid composition of the animal!


Anorexia Nervosa Essential Fatty Acid Retinitis Pigmentosa Essential Fatty Acid Deficiency Linoleie Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams, R B., Sinclair, A. J., Lawson, S., and Sanigorski, A. (1996) High ratio of arachidonic acid to eicosaphentaenoic acid in blood correlates with severity of depression Lipids, 31.Google Scholar
  2. Alden, R. B., Svingen, B. A., Johnson, S. B., Konstantinides, F. N., Holman, R. T., and Cerra, F. B. (1986) Partial correction by exogenous lipid of abnormal patterns of polyunsaturated fatty acids in plasma phospholipids of stressed and septic surgical patients. Surgery, 100, 671–678.PubMedGoogle Scholar
  3. Brenner, R. R. and Peluffo, R. O. (1966) Effect of saturated and unsaturated fatty acids on the desaturation in vitro of palmitic, stearic, oleic, linoleic and linolenic acids. J. Biol. Chem. 241, 5213–5219.PubMedGoogle Scholar
  4. Brown, W. R., Hansen, A. E., Burr, G. O., and McQuarrie, I. (1937) Effect of prolonged use of extremely low fat diet on an adult human subject. J. Nutrition 16, 511–524.Google Scholar
  5. Burr, G. O. and Burr, M. M. (1929) A new deficiency disease produced by the rigid exclusion of fat from the diet. J. Biol. Chem. 82, 345–367.Google Scholar
  6. Casai, J. J. and Holman, R. T. (1965) The effect of kind of dietary carbohydrate upon the composition of liver fatty acids of the rat. J. Am. Oil Chem. Soc. 42, 1134–1137.Google Scholar
  7. Garcia, R T. and Holman, R. T. (1965) Competitive inhibitions in the metabolism of polyunsaturated fatty acids studied via the composition of phospholipids, triglycerides and cholesteryl esters of rat tissues. J. Am. Oil Chem. Soc. 42, 1137–1141.PubMedCrossRefGoogle Scholar
  8. Hansen, A. E. (1933) Serum lipid changes and the therapeutic effects of oils in infant eczema. Proc. Soc. Exp. Bio. Med. 31, 160–161.Google Scholar
  9. Hill, E. G., Johnson, S. B., Lawson, L. D., Mahfouz, M. M., and Holman, R. T. (1982) Perturbation of the metabolism of essential fatty acids by dietary partially hydrogenated vegetable oil. Proc. Natl. Acad. Sci. USA 79, 953–957.PubMedCrossRefGoogle Scholar
  10. Holman, R. T. (1960) The ratio of trienoic: tetraenoic acids in tissue lipids as a measure of essential fatty acid requirement. J. Nutr. 70, 405–410.PubMedGoogle Scholar
  11. Holman, R. T. (1964) Nutritional and metabolic interrelationships between fatty acids. Fed. Proc. 23, 1062–1067.PubMedGoogle Scholar
  12. Holman, R. T. (1981) Polyunsaturated fatty acid profiles in human disease, in New Trends in Nutrition, Lipid Research, and Cardiovascular Diseases, Lill, New York, pp. 25–42.Google Scholar
  13. Holman, R. T. (1993) A long scaly tale-the study of essential fatty acid deficiency at the University of Minnesota, in Essential Fatty Acids and Eicosanoids ( Sinclair, A. and Gibson R., eds.), American Oil Chemists Society, Champaign, IL, pp. 3–17.Google Scholar
  14. Holman, R. T. (1994) Omega 3 defiencies in humans, in Proceedings of The 55th Flax Institute of the United States ( Carter, J. F., ed), North Dakota State University, Fargo, ND, pp. 4–11.Google Scholar
  15. Holman, R. T., Adams, C. E., Nelson, R. A., Grater, S. J. E., Jaskiewicz, J. A., Johnson, S. B., and Erdman, J. W. (1995) Patients with anorexia nervosa demonstrate deficiencies of selected essential fatty acids, compensatory changes in non-essential fatty acids and decreased fluidity of plasma lipids. J. Nutr. 125, 901–907.PubMedGoogle Scholar
  16. Holman, R. T., Bibus, D. M., Jeffrey, G. H., Smethurst, P., and Crofts, J. W. (1994) Abnormal plasma lipids of patients with retinitis pigmentosa. Lipids 29, 61–65.Google Scholar
  17. Holman, R. T. and Burr, G. O. (1948) Alkali conjugation of the unsaturated fatty acids. Arch. Biochem. 19, 474–482.Google Scholar
  18. Holman, R. T., Johnson, S. B., Bibus, D., Spencer, D. C., and Donadio, J. V., Jr. (1944) Essential fatty acid deficiency profiles in idiopathic IgA nephropathy. Am. J. Kidney Dis. 23, 648–654.Google Scholar
  19. Holman, R. T., Johnson, S. B., and Hatch, T. F. (1982) A Case of human linolenic acid deficiency involving neurological abnormalities. Am. J. Clin. Nutr. 35, 617–623.PubMedGoogle Scholar
  20. Holman, R. T., Johnson, S. B., and Kokmen, E. (1989) Deficiencies of polyunsaturated fatty acids and replacement by non-essential fatty acids in plasma lipids in multiple sclerosis. Proc. Natl. Acad. Sci. USA 86, 4720–4724.PubMedCrossRefGoogle Scholar
  21. Holman, R. T., Johnson, S. B., Mercuri, O., Itarte, H. J., Rodrigo, M. A., and De Tomas, M. E. (1981) Essential fatty acid deficiency in malnourished children. Am. J. Clin. Nutr. 34, 1534–1539.PubMedGoogle Scholar
  22. Holman, R. T., Johnson, S. B., and Ogburn, P. L. (1991) Deficiency of essential fatty acids and membrane fluidity during pregnancy and lactation. Proc. Natl. Acad. Sci. USA 88, 4835–4839.PubMedCrossRefGoogle Scholar
  23. Holman, R. T., Lundberg, W. O., and Burr, G. O. (1945) Spectrophotometric studies of the oxidation of fats. III. Ultraviolet absorption spectra of oxidized octadecatrienoic acids. J. Am. Chem. Soc. 67, 1390–1394.Google Scholar
  24. Holman, R. T. and Mohrhauer, H. (1963) A hypothesis involving competetive inhibitions in the metabolism of polyunsaturated fatty acids. Acta Chem. Scand. 17, S84 - S90.CrossRefGoogle Scholar
  25. Holman, R. T., Smythe, L., and Johnson, S. B. (1979) Effect of sex and age on fatty acid composition of human serum lipids. Am. J. Clin. Nutr. 32, 2390–2399.PubMedGoogle Scholar
  26. Klenk, E. and Mohrhauer, H. (1960) Metabolism of polyene fatty acids in the rat. Z. Physiol. Chem. 320, 218–232.CrossRefGoogle Scholar
  27. Lloyd-Still, J. D., Johnson, S. B., and Holman, R. T. (1991) Essential fatty acid status and fluidity of plasma phospholipids in cystic fibrosis infants. Am. J. Clin. Nutr. 54, 1029–1035.PubMedGoogle Scholar
  28. Johnson, S. B., Gordon, E., McClain, C., Low, G., and Holman, R. T. (1985) Abnormal polyunsaturated fatty acid patterns of serum lipids in alcoholism and cirrhosis: arachidonic acid deficiency in cirrhosis. Proc. Natl. Acad. Sci. USA 82, 1815–1818.PubMedCrossRefGoogle Scholar
  29. Marcel, Y., Christiansen, K., and Holman, R. T. (1968) The preferred metabolic pathway from linoleic acid to arachidonic acid in vitro. Biochim. Biophys. Acta 164, 25–34.PubMedCrossRefGoogle Scholar
  30. Mohrhauer, H., Christiansen, K., Gan, M. V., Deubig, M., and Holman, R. T. (1967) Chain elongation of linoleic acid and its inhibition by other fatty acids in vitro J. Biol. Chem. 242, 4507–4514.PubMedGoogle Scholar
  31. Mohrhauer, H. and Holman, R. T. (1963a) Alteration of the fatty acid composition of brain lipids by varying levels of dietary essential fatty acids. J. Neurochem. 10, 523–530.PubMedCrossRefGoogle Scholar
  32. Mohrhauer, H. and Holman, R. T. (1963b) Effects of dietary essential fatty acids upon polyunsaturated fatty acids in rat heart tissue, in Biochemical Problems of Lipids Biochimica Biophysica Acta Library Vol. 1, Elsevier, Amsterdam, pp. 446–452.Google Scholar
  33. Mohrhauer, H. and Holman, R. T. (1963c) The effect of dose level of essential fatty acids upon fatty acid composition of the rat liver. J. Lipid Res. 4, 151–159.PubMedGoogle Scholar
  34. Mohrhauer, H. and Holman, R. T. (1963d) Effect of linolenic acid upon the metabolism of linoleic acid. J. Nutr. 81, 67–74.PubMedGoogle Scholar
  35. Ogburn, R. L., Jr., Sharp, H., Lloyd-Still, J. D., Johnson, S. B., and Holman, R. T. (1982) Abnormal polyunsaturated fatty acid patterns of serum lipids in Reye’s Syndrome. Proc. Natl. Acad. Sci. USA 79, 908–911.PubMedCrossRefGoogle Scholar
  36. Paulsrud, J. R., Pensler, L., Whitten, C. E, Stewart, S., and Holman, R. T. (1972) Essential fatty acid deficiency in infants induced by fat-free intravenous feeding. Am. J. Clin. Nutr. 25, 897–904.PubMedGoogle Scholar
  37. Phinney, S. D., Odin, R. S., Johnson, S. B., and Holman, R. T. (1990) Reduced arachidonate in serum phospholipids and cholesteryl esters associated with vegetarian diets in humans. Am. J. Clin. Nutr. 51, 385–392.PubMedGoogle Scholar
  38. Rahm, J. J. and Holman, R. T. (1964) Effect of linoleic acid upon the metabolism of linolenic acid. J. Nutr. 84, 149–154.PubMedGoogle Scholar
  39. Rieckhfoff, I. G., Holman, R. T., and Burr, G. O. (1949) Polyethenoid fatty acid metabolism. Effect of dietary fat on polyethenoid fatty acids of rat tissues. Arch. Biochem. 20, 331–340.Google Scholar
  40. Sharp, H. L., Lindahl, J. A., Freese, D. K., Burke, B., Johnson, D., Johnson, S. B., and Holman, R. T. (1988) A new hepato-pancreato-renal disorder resembling tyrosinemia involving neuropathy and abnormal metabolism of polyunsaturated acids. J. Pediatr. Gastroenterol. Nutr. 7, 167–176.PubMedCrossRefGoogle Scholar
  41. Siegenthaler, I. E. (1994) The use of flaxseed in Ethiopia, in Proceedings of the 55th Flax Institute of the United States in ( Carter, J. E, ed.), North Dakota State University, Fargo ND, pp. 143–149.Google Scholar
  42. Sinclair, A. J., Johnson, L., O’Dea, K., and Holman, R. T. (1994) Diets rich in lean beef increase arachidonic acid and long-chain omega-3 polyunsaturated fatty acid levels in plasma phospholipids. Lipids 29, 337–343.PubMedCrossRefGoogle Scholar
  43. Widmer, C., Jr. and Holman, R. T. (1950) Polyethenoid fatty acid metabolism II. Deposition of polyunsaturated fatty acids in fat-deficient rats upon single fatty acid supplementation. Arch. Biochem. 25, 1–12.PubMedGoogle Scholar
  44. Yao, J. K., Cannon, K. P., Holman, R. T., and Dyck, R. K. (1983) Effects of polyunsaturated fatty acid diets on plasma lipids of patients with adreno-multineuronal degeneration, hepatosplenomegaly and fatty acid derangement. J. Neurol. Sci. 62, 67–76.PubMedCrossRefGoogle Scholar
  45. Yehuda, S. and Carasso, R. L. (1993) Modulation of learning, pain thresholds and thermoregulation in the rat by preparations of free purified alpha-linolenic and Linoleic acids. Determination of the optimal w3/6)6 ratio Proc. Natl. Acad. Sci. USA 90, 10, 345–10, 349.Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Ralph T. Holman

There are no affiliations available

Personalised recommendations