Every claim, every source.

This review compares the cardiovascular benefits of eating whole sardines against taking isolated fish-oil supplements. The authors argue that whole sardines provide a "matrix" of nutrients that fish-oil capsules lack: not just EPA and DHA, but calcium, vitamin D, B12, selenium, high-quality protein, and minor compounds (taurine, coenzyme Q10) absent from purified oils. Per 100 grams of cooked sardines, the USDA database reports 24.6 g of protein, 11.5 g of total fat, 473 mg of EPA, 509 mg of DHA, 382 mg of calcium, 4.8 µg of vitamin D, 8.9 µg of B12, and 52.7 µg of selenium. The review surveys randomized trials of sardine consumption versus control diets and concludes that whole-sardine intake produces favourable changes in lipid profile, inflammation markers, and insulin sensitivity, with the additional minerals and protein doing work that omega-3 supplements alone cannot. The framing throughout is that sardines outperform fish-oil supplementation as a delivery vehicle for cardiovascular benefit.

This NEJM review summarizes evidence that intermittent fasting regimens — alternate-day fasting, time-restricted eating, and periodic multi-day fasts — engage a "metabolic switch" from glucose-derived energy to fat- and ketone-derived energy after hepatic glycogen is depleted, typically within 12–36 hours of fasting depending on the individual and the protocol. The authors argue that repeated exposure to this switch produces adaptive responses across organ systems, including improved insulin sensitivity, reduced inflammation, increased mitochondrial biogenesis, enhanced autophagy, and improved stress resistance in cells. The review compiles findings from animal models alongside the available human trials at the time of publication. The review notes that, despite preclinical signals being strong and consistent, the human evidence base is more heterogeneous: the largest gains in metabolic markers (fasting insulin, HOMA-IR, lipid profile, inflammatory markers) appear in adults with obesity or metabolic syndrome, while effects in lean, metabolically healthy individuals are smaller. The authors flag practical issues — adherence over months, the early-fast hunger and irritability phase, and the lack of long-term outcome data — as the main barriers to clinical adoption rather than safety in healthy adults.

This 2019 meta-analysis pooled 26 double-blind randomized placebo-controlled trials of omega-3 PUFA supplementation for depression to ask a specific question: does the EPA-to-DHA ratio matter? The authors found that it does, decisively. Formulations that were either pure EPA or majority EPA (60 percent or more EPA) showed clinical benefit for depressive symptoms at relatively low doses (1 gram per day or less), while pure DHA and DHA-majority formulations did not. The therapeutic effect was specific to EPA-dominant supplementation. The mechanism inference is that EPA's anti-inflammatory effects (via resolvins and reduction of pro-inflammatory eicosanoids) drive the antidepressant signal, while DHA's role in neuronal membrane structure does not similarly translate to mood benefit at supplementation doses. The paper is the most-cited recent meta-analysis on omega-3 and depression and has shaped subsequent dosing recommendations: when omega-3 is used adjunctively for depressive disorders, EPA-dominant formulations at sub-gram doses are the evidence-supported choice. The paper does not claim omega-3 replaces antidepressant medication; it supports adjunctive use.

Philip Calder is the leading authority on omega-3 fatty acids and inflammation, and this 2013 BJCP review is his most cited synthesis. The paper traces the multiple mechanisms by which EPA and DHA modulate inflammatory responses: incorporation into cell-membrane phospholipids alters which substrates are available for eicosanoid synthesis (prostaglandins, leukotrienes); direct inhibition of leukocyte chemotaxis, adhesion-molecule expression, and T-cell reactivity; reduced inflammatory cytokine production (TNF, IL-1β, IL-6); disruption of lipid rafts that anchor TLR4 signaling; and generation of pro-resolution lipid mediators (resolvins, protectins) that actively terminate inflammation rather than just dampen it. The paper distinguishes "nutrition-dose" effects (typical 1–2 g/day EPA+DHA from regular fish intake, modest anti-inflammatory shifts) from "pharmacology-dose" effects (3–4 g/day or higher, with measurable effects on rheumatoid arthritis and other clinical inflammatory conditions). The clinical evidence base is strongest for rheumatoid arthritis; weaker and inconsistent for inflammatory bowel disease and asthma.

This meta-analysis pooled 11 randomized controlled trials with 618 total participants to ask whether omega-3 fish oil supplements improve insulin sensitivity in adults. Across all studies and measurement methods, the answer was essentially no. The overall standardized effect size was 0.08 (95% confidence interval -0.11 to 0.28) — statistically indistinguishable from zero. One subgroup analysis was the exception. When researchers used HOMA-IR — a calculation from fasting glucose and insulin — omega-3 supplementation showed a small but statistically significant improvement (effect size 0.30, CI 0.03 to 0.58). On more direct measures of insulin sensitivity, including the euglycemic clamp, the effect was absent. The honest read: at the doses and durations studied, typically 1 to 4 grams of EPA plus DHA per day for weeks to months, omega-3 supplements do not reliably improve insulin sensitivity in adults — though a small HOMA-IR signal exists.