Fish oil supplementation does not lower C‐reactive protein or interleukin‐6 levels in healthy adults

Abstract

Background The n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may prevent a range of chronic conditions through anti-inflammatory actions. However, since clinical trials using these fatty acids for primary prevention are yet unavailable their putative role in disease prevention rests, in part, on evidence of anti-inflammatory actions in healthy individuals. Objective To investigate in a double-blind, placebo-controlled clinical trial whether supplementation with a moderate dose of EPA+DHA reduces common biomarkers of chronic, systemic inflammation in healthy individuals. Methods A total of 261 healthy individuals aged 30–54 years who were free of inflammatory conditions and consumed ≤300 mg/day EPA+DHA were included in the study. Participants were randomly assigned to 18 weeks of either fish oil supplementation providing 1400 mg/day EPA+DHA or matching placebo. Outcome measures were serum levels of C-reactive protein (CRP) and interleukin (IL)-6. In a substudy, ex vivo cytokine production was measured. Missing data for CRP and IL-6 were estimated using regression imputation. Data analyses conformed to intention-to-treat principles. Results Participant blinding was verified. Is the meaning of this sentence still correct? EPA+DHA levels increased by 64% in the active treatment group, but serum levels of CRP and IL-6 were not affected by supplementation (P ≥ 0.20). Findings were consistent with and without imputed values and across subgroups. Similarly, EPA+DHA supplementation did not alter ex vivo production of four pro-inflammatory cytokines (P ≥ 0.20). Conclusions Supplementation with 1400 mg EPA+DHA did not reduce common markers of systemic inflammation in healthy adults. Whether this or a higher dose affects other measures of inflammation, oxidative stress, or immune function warrants examination.

Foamy Monocytes Are Enriched in cis -7-Hexadecenoic Fatty Acid (16:1n-9), a Possible Biomarker for Early Detection of Cardiovascular Disease

“…Unexpectedly, IL-6 protein levels in serum from 22:6n-3 treated cells were no different from those in serum from control untreated animals. The inability of 22:6n-3 to lower serum IL-6 levels has recently been reported in a study with human subjects (Muldoon et al, 2016), and may suggest that, unlike 16:1n-9-treated cells, the peritoneal cavity is not a major source for circulating IL-6 in 22:6n-3-treated cells; multiple sources for circulating IL-6 may exist in the 22:6n-3-enriched cells that compensate for the inhibition of Il6 gene expression in the peritoneal cavity. …”

Systemic inflammation and resting state connectivity of the default mode network

“…To be eligible for AHAB-II, individuals had to be between the ages of 30–54 years, working at least 25 hours per week outside of the home (a sub-study involving this cohort was focused on the association between occupational stress and coronary heart disease risk (Joseph et al, 2016)), and speak English as their first language. Individuals were excluded if they (a) had a history of cardiovascular disease, schizophrenia or bipolar disorder, chronic hepatitis, renal failure, major neurological disorder, chronic lung disease, or stage 2 hypertension (SBP/DBP ≥ 160/100); (b) consumed ≥ 5 alcoholic drinks 3–4 times (> approximately 201 grams of alcohol) per week; (c) took fish-oil supplements (because of the requirements for another sub-study (Muldoon et al, 2016)); (d) were prescribed insulin or glucocorticoid, anti-arrhythmic, antihypertensive, lipid-lowering, psychotropic, or prescription weight-loss medications; (e) were pregnant; (f) had less than 8th grade reading skills; or (g) were shift workers. Finally, all participants were screened for prior and current DSM-IV Axis-I disorders using the Mini International Neuropsychiatric Interview (MINI) (Sheehan et al, 1998).…”

Omega-3 Supplementation and the Neural Correlates of Negative Affect and Impulsivity: A Double-Blind, Randomized, Placebo-Controlled Trial in Midlife Adults

“…Of the 255 participants who completed the full trial there were missing data on the following outcome measures: BDI (n = 1), CMH (n = 6), BIS (n = 3), BPAQ (n = 6), all EMA measures (n = 10). An earlier paper from this trial demonstrated no group differences in adherence 48 between the two groups.…”

“…Compared to those on placebo participants receiving fish oil reported somewhat more “fishy belch or aftertaste” and “loose stool, bloating or gas pains,” but less “minty belch or aftertaste.” No serious adverse events were reported by any participants enrolled in the trial (completed or not). Additional detail on these analyses have been reported previously 48 .…”

“…The trial was designed to test several putative primary prevention mechanisms, each linked to low dietary intake in published research: a) chronic systemic inflammation, b) low cardiac autonomic control, c) subtle cognitive functioning, and d) behavioral measures of reward-related impulsivity and negative affect. The trial’s first published report presented findings related to chronic inflammation, along with details of the protocol and study design, adverse events and study blinding 48 . The current report describes affect outcomes and substudy functional MRI results.…”