Dietary intake of polyunsaturated fatty acids (PUFA), particularly omega 6 (ω-6), is associated with improved cognitive function in older adults, new research suggests.
The study provides important “pieces of the puzzle” of the diet and cognition connection, but the results aren’t “ready for prime time,” study investigator Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, told Medscape Medical News.
“I don’t think we’re there yet when it comes to recommending supplementation to the general public,” said McIntyre, adding a larger “more compelling study” is needed.
The study was published online January 14 in The American Journal of Geriatric Psychiatry.
Clinically Meaningful?
Research shows that 25% to 50% of community-dwelling adults aged 65 to 85 years have some cognitive impairment. Other evidence indicates cognition is affected by dietary fat intake.
Many lines of research show that alterations in lipid homeostasis can cause brain dysfunction, said McIntyre. “This shouldn’t surprise us because our brain is made up of protein, water, and fat.”
This new analysis used combined data from the 2011–2012 and 2013–2014 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of ongoing cross-sectional surveys conducted by the Centers for Disease Control and Prevention (CDC). The data are collected in two phases ― an in-home face-to-face interview, and a physical examination.
Researchers obtained dietary intake information through two 24-hour dietary recall interviews. Dietary information included total energy (kcal/d), intakes in grams per day (g/d) of total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), PUFA, total ω-3 and total ω-6 fatty acids, and milligrams per day (mg/d) of cholesterol.
For cognitive function, the researchers used total and delayed recall scores of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the animal fluency test, and the digit symbol substitution test (DSST).
The study included 2253 adults aged 60 years and older (mean age, 69.4 years) and 51% non-Hispanic White persons.
After adjusting for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, income, and total energy, dietary intake of PUFA and ω-6 fatty acid was positively associated with DSST.
The DSST score increased about 0.06 standard deviation (SD) (about 1 score) with each SD increase in these fatty acids (8.8 g/d for PUFA and 7.9 g/d for ω-6) (P values were 0.02 for PUFA and 0.01 for ω-6).
However, it’s unclear what an improvement of 1 DSST score means clinically, said McIntyre. “The P value is significant, but how does that translate? Does this mean a person can now think more clearly or function better?”
“Million Dollar Question” Remains Unanswered
The fact that ω-6, considered neuroinflammatory, was associated with improved DSST score illustrates the complexity of this field, said McIntyre.
“We’re learning that when it comes to inflammation, many of the molecules in our brain that are implicated as anti-inflammatory can also be pro-inflammatory, so bad guys can be good guys and good guys can be bad guys.”
It speaks to the notion of homeostasis, he added. “Just like a seesaw; when you push this part down, that part goes up.”
The analysis showed the animal fluency score increased about 0.05 SD (around 0.3 score) with each SD (1.1 g/d) increase in dietary intake of ω-3.
There were no significant associations between other dietary fat intake and cognitive performance.
Researchers investigated the role of oxidative stress and antioxidant biomarkers (gamma glutamyl transpeptidase [GGT], bilirubin, uric acid, and vitamin D).
Cells produce oxidative radicals that are normally “mopped up” by our “innate antioxidant capability,” said McIntyre. “But in states of cognitive impairment, these oxidative stress markers accumulate and they exceed what the normal innate response is able to manage.”
The study showed GGT levels decreased with increased PUFA and ω-6 fatty acid intakes; levels of bilirubin decreased with increase in most dietary fat intakes; uric acid levels decreased with MUFA intake and ω-6/ω-3 ratio; and vitamin D levels increased with ω-3 fatty acid intake but decreased with SFAT intake.
Causal mediation analysis showed the association between dietary intake of fatty acids and DSST performance was partially mediated by GGT levels. However, McIntyre emphasized that this does not prove causality.
“The million dollar question is, is this the sole explanation for the association? In other words, is it the oxidative stress that caused the cognitive impairment and therefore correcting it improved it, or is it the case that oxidative stress is a proxy of other activities that are also taking place?”
A “Plausible” Link
In an accompanying editorial, Candida Rebello, PhD, Integrated Physiology and Molecular Medicine Pennington Biomedical Research Center, Baton Rouge, Louisiana, said the finding that ω-3 and ω-6 fatty acids are positively associated with cognition in older adults makes some sense.
She noted that aging is associated with an overt inflammatory phenotype, and evidence shows these fatty acids are precursors for bioactive molecules that play a role in self-limiting the acute inflammatory response.
Rebello said the positive association of ω-6 fatty with cognition shown in this study contrasts with the “common belief” that increasing dietary intake of these fatty acids enhances inflammation, but agreed the association is “plausible.”
She said it’s “essential” to determine “the underlying mechanisms that regulate the diverse features of inflammation and sort out the processes that protect from neuronal damage and those that contribute towards it.”
She noted the ratio of ω-6 to ω-3 is about 15:1 in the present day Western diet, as opposed to a 1:1 ratio in diets of the past. Omega-3 fatty acids are found in fish oil supplements and fatty fish like mackerel and salmon, while cereal, grains, and vegetable oil are sources of ω-6.
Attaining a measure of balance of fatty acids in the diet may be a “prudent approach,” said Rebello. “Substituting some meat entrées with fatty fish and polyunsaturated vegetable oils with monounsaturated fats such as olive oil are small changes that are likely to garner adherence.”
Rebello noted that the study used NHANES food intake data, which rely on participant self-report and so may not be accurate.
The study received funding from the MOE (Ministry of Education in China) Project of Humanities and Social Sciences and the Research Startup Fund of Southwest University. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. He is a CEO of Braxia Scientific Corp.
Am J Ger Psych. Published online January 14, 2022. Abstract, Editorial
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