The effect of n-3 polyunsaturated fatty acid supplementation on cognitive function outcomes in the elderly depends on the baseline omega-3 index.

Both epidemiological and preclinical studies have shown the benefits of n-3 polyunsaturated fatty acid (n-3 PUFA) on dementia and cognitive impairment, yet the results of clinical randomized controlled trials (RCTs) performed to date are conflicting. The difference in the baseline omega-3 index (O3i) of subjects is a potential cause for this disparity, yet this is usually ignored. The present meta-analysis aimed to evaluate the effect of n-3 polyunsaturated fatty acid (n-3 PUFA) on cognitive function in the elderly and the role of baseline O3i. A systematic literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science up to June 27th, 2023. The mean changes in the mini-mental state examination (MMSE) score were calculated as weighted mean differences by using a fixed-effects model. Fifteen random controlled trials were included in the meta-analysis. Pooled analysis showed that n-3 PUFA supplementation did not significantly improve the MMSE score (WMD = 0.04, [-0.08, 0.16]; Z = 0.62, P = 0.53; I2 = 0.00%, P(I2) = 0.49). Out of the 15 studies included in the meta-analysis, only 7 reported O3i at baseline and outcome, so only these 7 articles were used for subgroup analysis. Subgroup analysis showed that the MMSE score was significantly improved in the higher baseline O3i subgroup (WMD = 0.553, [0.01, 1.095]; I2 = 0.00%, P(I2) = 0.556) and higher O3i increment subgroup (WMD = 0.525, [0.023, 1.026]; I2 = 0.00%, P(I2) = 0.545). The overall effect demonstrated that n-3 PUFA supplementation exerted no improvement on global cognitive function. However, a higher baseline O3i and higher O3i increment were associated with an improvement in cognitive function in the elderly.

N-3 polyunsaturated fatty acids prevent the D-galactose-induced cognitive impairment by up-regulating the levels of 5-hydroxymethylcytosine in the mouse brain.

Decreased 5-hydroxymethylcytosine (5hmC) levels caused by mitochondrial dysfunction in the brain are closely associated with the development of neurodegenerative disease. It has been reported that n-3 polyunsaturated fatty acids (PUFAs) prevent cognitive dysfunction by improving mitochondrial function in the brain. However, whether n-3 PUFA prevents cognitive dysfunction by increasing the levels of 5hmC in the brain is undisclosed. Mice were randomly divided into six groups (n = 10), injected with D-galactose (200 mg kg-1 day-1) for the model group and given different oils [0.1 mL per 10 g body weight per day, fish oil (FO), peony seed oil (PSO), corn oil (CO) and olive oil (OO)] for the prevention groups, and injected with the same dose of saline for the normal control group (NC) for 10 weeks, respectively. Peony seed oil and fish oil have shown preventive effects on D-galactose-induced cognitive dysfunction in behavioral tests. The content of docosahexaenoic acid (C22:6n-3, DHA content) in the brain was significantly higher in FO and PSO groups than in the other groups. Brain oxidative stress and neuronal apoptosis were significantly lower in PSO and FO groups than in the other groups. RNA-seq results showed that the different genes between PSO and FO compared with the model group were involved in the DNA demethylation process and the 5-methylcytosine metabolic process. The brain levels of 5hmC and the ten-eleven translocation family of dioxygenases (TETs) were significantly higher in FO and PSO groups compared with the model group, as analyzed by dot-blot and western blot. In conclusion, peony seed oil and fish oil increased the C22:6n-3 content, which activated the TET activity, led to up-regulation of the 5hmc level, resulted in inhibition of neuronal apoptosis, and then improved the cognitive function in D-gal-induced mice.

Effects of brown seaweed polyphenols, a class of phlorotannins, on metabolic disorders via regulation of fat function.

It is well known that fat dysfunction is the main driver of development of metabolic disorders. Changes in diet and lifestyle are particularly important to reverse the current global rise in obesity-related metabolic disorders. Seaweed has been consumed for thousands of years, and it is rich in bioactive compounds, especially unique polyphenols. The aim of the present review is to summarize the effects of different seaweed polyphenols on fat function in metabolic disorders and the related mechanisms. Seaweed polyphenols activate white adipose tissue to "brown" or "beige" adipose tissue to enhance energy consumption. In addition, the amelioration of fat factor imbalance and inflammatory response is also considered as an important reason for the regulation of lipid function with seaweed polyphenols. The present review provides an important basis for using seaweed polyphenols as potential dietary supplements to prevent metabolic disorders.