Potential Role of Iron in a Mediterranean-style Diet—Reply

Gu, Yian; Luchsinger, J.; Stern, Yaakov; Scarmeas, Nikolaos

In their letter, Solfrizzi and colleagues1 interpret our recent findings as evidence supporting “a possible protective role against cognitive decline of both ω-3 and ω-6 polyunsaturated fatty acids (PUFA) intake and the detrimental role of saturated fatty acid (SFA).” While a dietary pattern representing high intake of both ω-3 and ω-6 PUFA, vitamin E, and folate, and lower intake of SFA and vitamin B12 seems to be associated with lower risk of AD,1 the isolated role of individual nutrients remains to be understood. We ran additional models in which we individually considered nutrients as possible predictors of AD. After adjustment for recruitment cohort, age, sex, education, and ethnicity, a Cox model including all 7 nutrients used in our reduced rank regression analyses simultaneously showed that none of them had statistically significant individual associations with AD risk; the hazard ratios (HR) and 95% confidence intervals (CI) comparing the highest tertile to the lowest tertile were 1.31 for SFA (95% CI, 0.85-2.03; P for trend = .18); 0.72 for ω-3 PUFA (95% CI, 0.49-1.07; P for trend = .07); 0.89 for ω-6 PUFA (95% CI, 0.59-1.35; P for trend = .52); 1.08 for MUFA (95% CI, 0.66-1.78; P for trend = .74); 1.16 for vitamin E (95% CI, 0.79-1.71; P for trend = .62); 1.23 for vitamin B12 (95% CI, 0.90-1.69; P for trend = .23); and 1.02 for folate (95% CI, 0.71-1.49; P for trend = .76). Therefore, the positive association between ω-3 and ω-6 PUFA and the negative association between SFA and this lower–AD risk dietary pattern may be best considered in aggregation with other nutrients. Overall, from a reductionistic, biological point of view it remains important to understand the individual roles of ω-3 PUFA, ω-6 PUFA, and SFA or the optimal ratio of ω-6 to ω-3 PUFA with regard to cognitive decline or AD development. Progress toward such understanding may shed light on the role of fatty acids in neurodegeneration. Nevertheless, the intercorrelation between various types of fatty acids and nutrients in general and the detection of significant associations only when they are considered in a holistic approach illustrates once more the importance of studying dietary patterns.



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Archives of Neurology

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February 11, 2022