Abstract

Excessive action of omega-6 eicosanoids formed from the body's omega-6 essential fats occurs in many health disorders, and it can be diminished with dietary omega-3 fats. The current abundance of omega-6 (n-6) eicosanoid-mediated disorders (e.g. thrombosic heart attack and stroke, cardiac arrhythmia, atherogenesis, arthritis, asthma, osteoporosis, tumour metastases, etc.) accompanies n-6 acid intakes that are more than ten times than the adequate level of 0·5% of energy. The n-3 and n-6 highly unsaturated fatty acids (HUFAs) are maintained in tissue phospholipids in a competitive, hyperbolic relationship to the dietary abundance of their 18-carbon polyunsaturated fatty acid (PUFA) precursors. In contrast, 18:2n-6 and 18:3n-3 acids are maintained in tissue triacylglycerols in a linear proportion to their dietary abundance expressed as percentage of daily caloric energy. The near absence of 20:3n-9 acid in plasma phospholipids in the U.S.A. population reflects very high intakes of polyunsaturated fats that compete with oleate for conversion to tissue HUFAs. The ethnic food combinations for Greenland, Japanese, Mediterranean, and American populations give proportions of omega-6 isomers in the body long-chain acids near 30%, 50% 60% and 80%, respectively. It is of interest that these values mimic clinical outcomes associated with cardiovascular mortalities ranging from 20 to 50 to 90 to 200 per 100 000, respectively.

Therapeutic treatment to cut excessive omega-6 eicosanoid signalling has involved billions of dollars being spent to develop and market new pharmaceutical agents while a preventive nutrition approach to cut excessive omega-6 eicosanoid signalling has yet to be applied systematically in dietetics, clinical nutrition and public health. Voluntary choices of food combinations can produce proportions of omega-6 HUFAs and of omega-3 plus omega-6 HUFAs in the total body ranging from 30% to 90%, respectively. Adverse effects of excessive omega-6 eicosanoid signalling can be lowered by two interdependent dietary changes: first, reduce the daily intake of foods overly rich in the precursors of 20:4n-6 acid; and second, simultaneously increase the omega-3 PUFAs in the diet to competitively inhibit the conversion of LA into tissue omega-6 HUFAs. An inter active computer software application has been developed to combine the complex biomedical information on competitive interactions among essential fats and eicosanoids, and to interpret and display the finding in terms of multiple daily food choices understandable by the general public.

References

[1]
Samuelsson
B
. From studies of biochemical mechanism to novel biological mediators: prostaglandin endoperoxides, thromboxanes, and leukotrienes. Nobel Lecture.
Biosci Rep
 .
1983
;
3
:
791
–813
[2]
Lands
WEM
. Biochemical approaches to solve the problem of atherosclerosis.
Hart Bull
 .
1979
;
10
:
152
–153
Lands
WEM
. Biochemical approaches to solve the problem of atherosclerosis.
Hart Bull
 .
1979
;
10
:
168
–169
[3]
Lands
WEM
, LeTellier PR, Rome LH, Vanderhoek JY. Inhibition of prostaglandin biosynthesis.
Adv Biosci
 .
1973
;
9
:
15
–27
[4]
Lands
WEM
, Libelt B, Morris AJ, et al. Maintenance of lower proportions of n-6 eicosanoid precursors in phospholipids of human plasma in response to added dietary n-3 fatty acids.
Biochim Biophys Acta
 .
1992
;
1180
:
147
–162
[5]
Lands
WEM
, Samuelsson B. Phospholipid precursors of prostaglandin biosynthesis.
Biochim Biophys Acta
 .
1968
;
164
:
426
–429
[6]
Samuelsson
B
, Hamberg M, Malmsten C, Svensson J. The role of prostaglandin endoperoxides and thromboxanes in platelet aggregation. Samuelsson B, Paoletti R. Advances in Prostaglandin and Thromboxane Research. New York: Raven Press; 1976. p. 737–746
[7]
Needleman
P
, Raz A, Minkes MS, Ferendelli JA, Sprecher H. Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties. Proc Natl Acad Sci USA. 3rd edn. 1979. p. 944–948
[8]
Black
KL
, Culp BR, Randall OS, Lands WEM. The protective effects of dietary fish oil and focal cerebral infarction.
Prostaglandins Med
 .
1979
;
3
:
257
–268
[9]
Culp
BR
, Lands WEM, Lucchesi BR, Pitt B, Romson J. The effect of dietary supplementation of fish oil on experimental myocardial infarction.
Prostaglandins
 .
1980
;
20
:
1021
–1031
[10]
Lands
WEM
. The biosynthesis and metabolism of prostaglandins.
Ann Rev Physiol
 .
1979
;
41
:
633
–652
[11]
Lands
WEM
, Pitt B, Culp BR. Recent concepts on platelet function and dietary lipids in coronary thrombosis, vasospasm and angina.
Herz
 .
1980
;
5
:
34
–41
[12]
Ridker
PM
, Manson JE, Buring JE, Goldhaber SZ, Hennekens CH. The effect of chronic platelet inhibition with low-dose aspirin on atherosclerotic progression and acute thrombosis: clinical evidence from the Physicians' Health Study.
Am Heart J
 .
1991
;
122
:
1588
–1592
[13]
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
[14]
Lands
WEM
, Culp BR, Hirai A, Gorman R. Relationship of thromboxane generation to the aggregation of platelets from humans: effects of eicosapentaenoic acid.
Prostaglandins
 .
1985
;
30
:
819
–825
[15]
Nair
SSD
, Leitch JW, Falconer J, Garg ML. Prevention of cardiac arrhythmia by dietary (n-3) polyunsaturated fatty acids and their mechanism of action.
J Nutr
 .
1997
;
127
:
383
–393
[16]
Hock
CE
, Holahan MA, Reibel DK. Effect of dietary fish oil on myocardial phospholipids and myocardial ischemic damage.
Am J Physiol
 .
1987
;
252
:
H554
–H560
[17]
Reibel
DK
, Holahan MA, Hock CE. Effects of dietary fish oil on cardiac responsiveness to adrenoceptor stimulation.
Am J Physiol
 .
1987
;
254
:
H494
–H499
[18]
Kang
JX
, Leaf A. Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocyte. Proc Natl Acad Sci USA. 3rd edn. 1994. p. 9886–9890
[19]
Xiao
Y-F
, Gomez AM, Morgan JP, Lederer WJ, Leaf A. Suppression of voltage-gated L-type Ca 21 currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes. Proc Natl Acad Sci USA. 3rd edn. 1997. p. 4182–4187
[20]
Lands
WEM
. Long-term fat intake and biomarkers.
Am J Clin Nutr
 .
1995
;
61
:
7215
–7255 (Suppl)
[21]
Lands
WEM
. Biosynthesis of prostaglandins.
Ann Rev Nutr
 .
1991
;
11
:
41
–60
[22]
Mohrhauer
H
, Holman RT. The effect of dose level of essential fatty acids upon fatty acid composition of the rat liver.
J Lipid Res
 .
1963
;
4
:
151
–159
[23]
Mohrhauer
H
, Holman RT. Effect of linolenic acid upon the metabolism of linoleic acid.
J Nutr
 .
1963
;
81
:
67
–74
[24]
Lands
WEM
, Hamazaki T, Yamazaki K, et al. Changing dietary patterns.
Am J Clin Nutr
 .
1990
;
51
:
991
–993
[25]
Lands
WEM
, Morris AJ, Libel B. The influence of dietary polyunsaturated fats on the composition of fatty acids in rat tissues.
Lipids
 .
1990
;
25
:
505
–516
[26]
Lands
WEM
, Pitt B, Culp BR. Recent concepts on platelet function and dietary lipids in coronary thrombosis, vasospasm and angina.
Herz
 .
1990
;
5
:
34
–41
[27]
Collins
FD
, Sinclair AJ, Royle JP, Coats DA, Maynard AT, Leonard RE. Plasma lipids in human linoleic acid deficiency.
Nutr Metabol
 .
1971
;
13
:
150
–167
[28]
Simopoulos
AP
, Leaf A, Salem N. Workshop on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids.
J Am Coll Nutr
 .
1999
;:
487
–489
[29]
de Deckere
EAM
, Korver O, Verschuren PM, Katan MB. Health aspects of fish and n-3 polyunsaturated fatty acids from plant and marine origin.
Eur J Clinical Nutr
 .
1998
;
52
:
749
–753