omega-3 fatty acids (omega-3 FAs) found in dietary fish or fish oils are anti-inflammatory agents that may influence Alzheimer's disease (AD).To study the effects of dietary omega-3 FA supplementation on inflammatory markers in cerebrospinal fluid (CSF) and plasma from patients with mild to moderate AD.Thirty-five patients (70.3 +/- 8.2 years) were randomized to a daily intake of 2.3 g omega-3 FAs or placebo for 6 months. The inflammatory markers interleukin (IL)-6, tumour necrosis factor-alpha and soluble interleukin-1 receptor type II (sIL-1RII) were analysed in CSF and plasma at baseline and at 6 months. The AD markers tau-protein, hyperphosphorylated tau-protein and beta-amyloid (Abeta(1-42)) were assessed in CSF. High-sensitivity C-reactive protein was assessed in plasma. A possible relation to the APOE genotype was investigated.There was no significant treatment effect of omega-3 FAs on inflammatory and AD biomarkers in CSF or on inflammatory markers in plasma, nor was there any relation with APOE. A significant correlation was observed at baseline between sIL-1RII and Abeta(1-42) levels in CSF.Treatment of AD patients with omega-3 FAs for 6 months did not influence inflammatory or biomarkers in CSF or plasma. The correlation between sIL-1RII and Abeta(1-42) may reflect the reciprocal interactions between IL-1 and Abeta peptides.
Low tissue levels of the major marine ω3 fatty acids (FAs) DHA and EPA are found in Alzheimer's disease (AD). We investigated if healthy proxies to AD patients have higher levels of these ω3 FAs. We observed lower levels of EPA and DHA in subcutaneous adipose tissue biopsies from 64 AD patients com pared with 16 cognitively healthy proxies. No significant difference was observed when pairwise comparisons were made between a subset of 16 AD patients and their co-habiting proxies. Larger studies are needed to replicate these findings and to determine if they could depend on FA intake or differences in metabolism.
Weight loss is common in individuals with dementia, especially in Alzheimer's disease (AD) and occurs early during the disease. The etiology of this weight loss is still unclear and is probably multifactorial. Potential contributing factors are: inability to prepare and eat foods, loss of appetite, increased energy expenditure and inflammatory components. According to some epidemiological studies high fish consumption seems to protect against AD. Omega–3 fatty acids, i.e. eicosapentaoenic acid (EPA) and dokosahexaoenic acid (DHA), in fat fish reduce inflammation, and act on cell membrane and gene expression. The effects of a daily supplement of ω3–acids on weight in patients with AD were studied. 204 outpatients with AD were randomized to receive either DHA/EPA (80/20%), 4 gram/day during 6 months (EPAX, Pronova AS, Norge) or to placebo (i.e. omega–6 fatty acids). After 6 months all patients received DHA/EPA in a further 6 months. Nutritional status was assessed by anthropometry and by biochemical analyses. Results from weight changes at 6 and 12 months follow up are presented. 174 patients completed the study; 89 in the EPAX–group (75 years, 57% women) and 85 in the control group (75 years, 46% women). The weight at baseline was 69.6 ± 12 kg (Body Mass Index (BMI) 24 ± 0.3 kg/m2) in the EPAX–group and 70.7 ± 12 kg (BMI 24 ± 0.5 kg/m2) in the control group respectively. At 6 months follow up the weight had increased by 0,7 kg (p=0.015) in the EPAX group and was unchanged in the control group (p<0.05 between groups). After another period of 6 months when both groups received treatment the weight had increased in both groups, with 0.7 kg more in the EPAX–group (p=0.008), and with 1 kg (p=0.011) in the control group (ns between the groups). Patients with Alzheimer's disease treated with a daily supplement of fish oils (omega 3 fatty acids) DHA/EPA (80/20%) gained weight significantly. This might be favorable as underweight is common among these patients and is associated with poorer prognosis. The effects on appetite and on inflammatory markers will also be studied.
OBJECTIVES: To study the effects of omega (Ω)‐3 fatty acid (FA) supplements on weight and appetite in patients with mild to moderate Alzheimer's disease (AD) in relation to inflammatory biomarkers and apolipoprotein E ɛ4 ( APOE ɛ4). DESIGN: Randomized, double‐blind, placebo‐controlled trial. SETTING: Specialist memory clinics in the Stockholm catchment area. PARTICIPANTS: Two hundred four patients (aged 73±9, 52% women) with mild to moderate AD. INTERVENTION: Patients with AD received 1.7 g of docosahexaenoic acid (DHA) and 0.6 g of eicosapentaenoic acid (EPA) (Ω‐3/Ω‐3 group; n=89, aged 73±9, 57% women) or placebo 0.6 g of linoleic acid per day (placebo/Ω‐3 group; n=85, aged 73±9, 46% women) for 6 months. After 6 months, all patients received DHA and EPA for another 6 months. MEASUREMENTS: Anthropometry, biochemical nutritional and inflammatory markers, and appetite assessed by caregiver. RESULTS: Mean weight and body mass index (kg/m 2 ) at baseline were 70.0±11.8 kg and 24.3±3.0 kg/m 2 , respectively. At 6‐ and 12‐month follow‐up, weight had increased 0.7±2.5 kg ( P =.02) and 1.4±2.9 kg ( P <.001) in the Ω‐3/Ω‐3 group. In the placebo group, weight was unchanged at 6 months but had increased ( P =.01) at 12 months follow‐up after Ω‐3 supplementation was initiated. Appetite improved in the Ω‐3/Ω‐3 group over the treatment period ( P =.01). In logistic regression analyses, not carrying the APOE ɛ4 allele and high plasma DHA concentrations were independently related to weight gain in the combined group of patients at 6 months follow‐up. CONCLUSION: A DHA‐enriched Ω‐3 FA supplement may positively affect weight and appetite in patients with mild to moderate AD. Not carrying the APOE ɛ4 allele and high DHA were independently associated with weight gain.
Background Little is known about the transfer of essential fatty acids (FA) across the human blood‐brain barrier (BBB) in adulthood. Objective Will oral supplementation for 6 mo with omega‐3 fatty acids (n‐3 FA), high in DHA, change the FA profile in cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD)? Methods FA in CSF were analyzed by gas chromatography and mass spectrometry in 33 patients; 18 received n‐3 FA and 15 placebo. Participants were part of the OmegAD Study, where 204 patients with mild AD received 2.3 g n‐3 FA daily or placebo for 6 mo in a randomized fashion. Correlation analyses were made with plasma FA, CSF markers of AD and of inflammation. Results At 6 mo a significant increase in CSF (and plasma) EPA, DHA and total n‐3 levels were noted in the n‐3 FA group, whereas no changes were observed in the placebo group. Changes of CSF DHA levels correlated significantly to changes of total and phosphorylated Tau and soluble IL‐1RII in CSF, i.e. the more the FA increased, the more the AD biomarkers decreased. Summary N‐3 FA supplementation conferred discrete changes of n‐3 FA in CSF, suggesting transfer over the adult BBB. Significant correlations between CSF n‐3 FA and CSF AD markers suggest possible relationships.
