While research on n-3 PUFA has produced exciting results, it is not without inconsistencies and there are several factors that currently limit the utility of some study outcomes. For example, food frequency questionnaires, often used in nutritional epidemiology as a method of assessing dietary intake, may produce inaccurate results. Questionnaires are subject to recall bias and the food composition databases they are based upon may lack precision in quantifying actual nutrient intake. Alternatively, erythrocytes have been used as biomarkers for dietary intake of fatty acids, however, they too lack complete accuracy. Some sources indicate erythrocyte membrane fatty acid composition is reflective of typical diet at approximately 4 months [296
], whereas other research suggests RBC membrane levels of fatty acids reflect dietary intake after only 3 weeks [96
]. Further, fatty acid levels in the blood do not necessarily accurately predict levels in all tissues, possibly due to inter-individual differences in fatty acid metabolism [298
]. Identification of tissue-specific biomarkers for fatty acid intake would be of high utility.
The relationship between ALA and chronic disease is unclear. In terms of research on insulin resistance, cell culture work is lacking, however animal studies tend to support a beneficial role of ALA on insulin sensitivity. On the other hand, human outcomes demonstrate a greater degree of variability. This could be explained, in part, by the fact that supplementation study results can be confounded by background intake of fish, walnuts, flaxseed, or other n-3 PUFA-rich foods in humans [177
Similarly, research on ALA and prostate cancer in rodents fails to demonstrate any significant association, while human dietary questionnaire-based studies suggest a trend towards a tumour-promoting role of ALA. Interestingly, blood and tissue analyses in this area produce a wide range of results, from positive associations between tissue ALA and prostate cancer to negligible or negative associations between ALA levels in the blood and prostate cancer risk. In contrast, the literature surrounding breast cancer and ALA is more consistent and suggests an anti-tumourigenic effect of this fatty acid in rodents and humans. Several factors could be contributing to such variability in study results, including tissue-dependent differences in tumorigenesis, diverse modes of ALA supplementation and measurement, and variability in study length, subject characteristics and outcome measures. Further, ALA-rich flaxseed, which is often used in human supplementation studies, has varying degrees of bioavailability depending on whether it is administered in its whole, ground, or oil form [299
The robust cardioprotective effects of n-3 PUFA from marine sources are well documented, however a general consensus on the beneficial relationship between ALA and CVD is still lacking. Part of the problem stems from the fact that chronic diseases like CVD take many years to develop and are often defined by the co-existence of multiple risk factors. Further, each risk factor could be differentially impacted by ALA and other dietary fatty acids making it difficult to determine the precise mechanisms and complex interrelationships involved. This could help account for some of the discrepancy in the literature surrounding ALA and CVD. The results of several recent human studies, however, are intriguing and warrant further investigation.