Search

This is a qualitative review of the evidence linking dietary fat composition to the risk of developing dementia. The review considers laboratory and animal studies that identify underlying mechanisms as well as prospective epidemiologic studies linking biochemical or dietary fatty acids to cognitive decline or incident dementia. Several lines of evidence provide support for the hypothesis that high saturated or trans fatty acids increase the risk of dementia and high polyunsaturated or monounsaturated fatty acids decrease risk. Dietary fat composition is an important factor in blood-brain barrier function and the blood cholesterol profile. Cholesterol and blood-brain barrier function are involved in the neuropathology of Alzheimer's disease, and the primary genetic risk factor for Alzheimer's disease, apolipoprotein E-ϵ4, is involved in cholesterol transport. The epidemiologic literature is seemingly inconsistent on this topic, but many studies are difficult to interpret because of analytical techniques that ignored negative confounding by other fatty acids, which likely resulted in null findings. The studies that appropriately adjust for confounding by other fats support the dietary fat composition hypothesis. [ABSTRACT FROM AUTHOR]

Background Paraoxonase 1 (PON1) is a cardioprotective, HDL-associated glycoprotein enzyme with broad substrate specificity. Our previous work found associations between dietary cholesterol and vitamin C with PON1 activity. The goal of this study was to determine the effect of specific dietary fatty acid (DFA) intake on PON1 activity. Methods 1,548 participants with paraoxonase activity measures completed the Harvard Standardized Food Frequency Questionnaire to determine their daily nutrient intake over the past year. Eight saturated, 3 monounsaturated, and 6 polyunsaturated DFAs were measured by the questionnaire. To reduce the number of observations tested, only specific fatty acids that were not highly correlated (r < 0.8) with other DFAs or that were representative of other DFAs through high correlation within each respective group (saturated, monounsaturated, or polyunsaturated) were retained for analysis. Six specific DFA intakes - myristic acid (14 carbon atoms, no double bonds - 14:0), oleic acid (18:1), gadoleic acid (20:1), α-linolenic acid (18:3), arachidonic acid (20:4), and eicosapentaenoic acid (20:5) - were carried forward to stepwise linear regression, which evaluated the effect of each specific DFA on covariateadjusted PON1 enzyme activity. Results Four of the 6 tested DFA intakes - myristic acid (p = 0.038), gadoleic acid (p = 6.68 × 10-7), arachidonic acid (p = 0.0007), and eicosapentaenoic acid (p = 0.013) - were independently associated with covariate-adjusted PON1 enzyme activity. Myristic acid, a saturated fat, and gadoleic acid, a monounsaturated fat, were both positively associated with PON1 activity. Both of the tested polyunsaturated fats, arachidonic acid and eicosapentaenoic acid, were negatively associated with PON1 activity. Conclusions This study presents the largest cohort-based analysis of the relationship between dietary lipids and PON1 enzyme activity. Further research is necessary to elucidate and understand the specific biological mechanisms, whether direct or regulatory, through which DFAs affect PON1 activity. [ABSTRACT FROM AUTHOR]

The fatty acid composition of cultured human skin fibroblasts was modified by adding either oleic or linoleic acid to the growth medium. After the cultures became confluent, they were washed and transferred to different maintenance media in order to determine the stability of the various fatty acyl modifications. Some changes in fatty acid composition occurred under all conditions. When the maintenance medium was supplemented with fatty acid, the cellular neutral lipid and phospholipid fatty acyl composition were altered markedly within 16 to 24 hr. If no supplemental fatty acid was available during the maintenance period, however, the modified fatty acyl compositions were sufficiently retained so that appreciable differences between the cells enriched with oleate and linoleate persisted for at least 48 to 72 hr. This considerable degree of stability occurred when either 10% delipidized fetal bovine serum or 10% fetal bovine serum containing its inherent lipids were present in the maintenance medium. Although the triglyceride content of the fatty acid-modified cells was quite labile, neither the cholesterol nor phospholipid content changed appreciably during culture in any of the maintenance media. Since the fatty acid compositional differences persisted during several days of maintenance under certain conditions, these modified cultures appear to be a useful experimental system for assessing the effect of lipid structure on fairly long-term cellular functions. [ABSTRACT FROM AUTHOR]