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Coronary heart disease (CHD) mortality rates associated with tissue HUFA proportions. Results from the United States, Japan, and Greenland were discussed earlier (10,11,12) as were quintile results from the Multiple Risk Factor Intervention Trial (MRFIT) study [■ (13)] and those from Quebec Inuit (14), Quebec Cree (15), and Quebec overall (16). For abbreviation see Figure 1. 

Coronary heart disease (CHD) mortality rates associated with tissue HUFA proportions. Results from the United States, Japan, and Greenland were discussed earlier (10,11,12) as were quintile results from the Multiple Risk Factor Intervention Trial (MRFIT) study [■ (13)] and those from Quebec Inuit (14), Quebec Cree (15), and Quebec overall (16). For abbreviation see Figure 1. 

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The 2002 ISSFAL Meeting arranged a special evening discussion with professional dietitians about diet-tissue-disease relationships involving essential fatty acids and eicosanoids. The balance of eicosanoid precursors in human tissues differs widely, reflecting voluntary dietary choices among different groups worldwide. An empirical quantitative die...

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... Type D personality has been identified as an independent risk factor for the incidence and prognosis of CHD. The pathophysiological process of CHD involves activity of omega-6 fatty acids in chronic inflammatory processes in the vascular wall, which promotes the development and growth of atherosclerotic plaques, and coronary events [56]. Omega-3 fatty acids compete for substrates with omega-6 fatty acids and therefore exert anti-inflammatory effects. ...
... alpha-linoleic acid and linoleic acid, respectively) are essential fatty acids that cannot be synthesized in human bodies. The only route to obtain these essential precursors is through dietary intake, and thus food choices have an important effect on tissue levels of both fatty acids and their responses [56]. Fish is a primary food source of omega-3 fatty acids, and fish oil supplements are also commonly used to promote omega-3 fatty acids intake. ...
... Furthermore, the notion that n-6 PUFA are pro-inflammatory and that n-3 PUFA are anti-inflammatory (129,130) contrasts with the new understanding that such broad categorisation of n-6 and n-3 PUFA is far too simplistic (131) and has little to no direct support from studies in humans (37,132,133) . In fact, evidence shows that higher LA levels are associated with reduced inflammatory status (134)(135)(136) . ...
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... HUFA have a lower prevalence of cardiovascular disease than populations having more than half [3]. Such evidence led to the hypothesis that eating foods with nutrients that maintain less than 50% n-6 in HUFA is an effective form of primary prevention of cardiovascular disease [4]. ...
... Removing these items leaves the remaining 90 items with an average score of -4, corresponding to a HUFA balance near 60% n-6 in HUFA [24]. That balance links to a lower risk for CVD than one near 80% n-6 in HUFA [3]. ...
... That impairment may be less for people with less than 50% n-6 in HUFA [3]. ...
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A hyperbolic, saturable, competitive dynamic of ligand binding to metabolic enzymes and lipid mediator receptors gives non-linear dose-response interactions that need careful management when planning or interpreting nutrient-based interventions. Relatively indiscriminate metabolism during accumulation of HUFA from n-3 and n-6 nutrients allows the amounts of n-3 and n-6 nutrients to determine the HUFA balance accumulated in tissue phospholipids. However, when HUFA-based eicosanoid actions are more intense with n-6 than n-3 mediators, they cause healthy physiology to shift toward pathophysiology. The proportion of n-6 in tissue HUFA directly relates to the severity of conditions caused by excessive n-6 actions. In the absence of n-3 nutrients, dietary linoleate (18:2n-6) has a very narrow therapeutic window below 1 percent of food energy, and it is widened by n-3 nutrients. The predictable quantitative dynamics of competing n-3 and n-6 nutrients allows design of successful preventive nutrition protocols that confirm and extend the epidemiologically observed benefits of n-3 nutrients.
... The %n-6 in HUFA biomarker was first seen to relate linearly to CHD deaths in 1992 [2]. This was confirmed with more data in 2003 [26], discussed in 2009 [25] and discussed as a valid health risk assessment biomarker in 2015 [14]. ...
... With a growing recognition of the need by clinical researchers to develop successful large-scale preventive nutrition interventions [26], approaches to designing low-cost high-throughput assays were discussed at the 2004 ISSFAL workshop. Discussants regarded the finger-tip blood spot on filter paper to be less labor-intensive than centrifuging to obtain red blood cell (RBC) membranes [14,27] and there was considerable debate about the use of the "Omega-3 Index" [28] versus a HUFA-based approach [2,3]. ...
... Explicit information from finger-tip blood-spot assays plus explicit information on foods that either raise or lower the blood biomarker empowers participants of wellness programs to choose voluntarily a HUFA balance that fits their own personal priorities. Observational data from the longitudinal MRFIT study [60] show the quintile with an estimated HUFA balance near 63% n-6 in HUFA had nearly half the cardiovascular deaths compared to those with an estimated HUFA balance near 80% n-6 in HUFA [12,26]. ...
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Careful handling of data on fatty acid composition is needed when interpreting evidence for the influence of dietary n-3 and n-6 essential fatty acids on brain function and health conditions. The relative dietary supplies of competing n-3 and n-6 nutrients determine the balance of 20- and 22-carbon n-3 and n-6 highly unsaturated fatty acids (HUFA) which accumulate competitively at the 2-position of tissue phospholipids. In turn, the HUFA balance expressed as the %n-6 in HUFA affects the likely intensity of n-6 eicosanoid actions in diverse health conditions. As a result, measures of HUFA balance are important, valid biomarkers for designing and monitoring successful preventive nutrition interventions. Successful interventions must also consider the ability of fatty acid ligands to saturate binding sites of enzymes and receptors and give paradoxical dose-response results.