Three human-evidenced publications on omega-6 and omega-3 polyunsaturated fatty acids, with the first a 2021 blog post that cited 72 references:
“In the area of heart health, which is why most consumers swallow fish oil, the data is hopelessly conflicted:
- One meta-analyses found that protective effects were dose-related, which is always persuasive;
- In marked contrast, three recent powerful clinical trials found fish oil to have no effects on cardiovascular pathology in either primary or secondary prevention; and
- Yet another meta-analysis found null results, except for a slight degree of protection in subjects who had gallantly taken fish oil supplements for over ten years.
Can these all be right? I think they can, based on secondary bioavailability.
Levels of omega 3s in the bloodstream are irrelevant, except in terms of their calorie content. That is not where they do their anti-inflammatory thing. They become precursors for resolvins, maresins, protectins, and anti-inflammatory eicosanoids only after they have been incorporated into the host’s cell membranes.
Getting them into cell membranes is secondary bioavailability (or bio-efficacy), and this is a much more complicated procedure. Seafood does it, but fish oil doesn’t.
Specifically, there is something in oily fish which enables secondary bioavailability, but which is missing in commercial fish oils. That something is a lipophillic polyphenol called phlorotannin.”
https://drpaulclayton.eu/blog/fish-oil-upgrade-to-snake-oil/ “Fish Oil? Upgrade to Snake Oil!”
A second paper was a 2021 review that focused on ratios of ω-6 to ω-3 PUFAs:
“Chronic diseases including obesity, type 2 diabetes, cardiovascular disease, cancer, and Alzheimer’s disease are rising exponentially in the modern world. Though these diseases are multifactorial in nature, their prevalence is mostly associated with an unbalanced increase in dietary n-6 PUFAs and decrease in n-3 PUFAs.
Mostly, these diseases escalate on the fact that inflammation in conjunction with obesity is the basis of every chronic disease.
Considering antagonistic effects of n-3 and n-6 PUFAs, both n-3 and n-6 SC-PUFAs and LC-PUFAs in their proportional ratio with each other, which is close to 4:1, play a significant role in regulating body homeostasis of inflammation and anti-inflammation, vasodilation and vasoconstriction, bronchoconstriction and bronchodilation, and platelet aggregation and antiaggregation.”
https://www.hindawi.com/journals/jl/2021/8848161/ “Overconsumption of Omega-6 Polyunsaturated Fatty Acids (PUFAs) versus Deficiency of Omega-3 PUFAs in Modern-Day Diets: The Disturbing Factor for Their ‘Balanced Antagonistic Metabolic Functions’ in the Human Body”
A third paper was a 2020 human adolescent study:
“Obese youth 9–19 y of age with nonalcoholic fatty liver disease were treated to see whether 12 wk of a low n–6:n–3 PUFA ratio (4:1) normocaloric diet mitigated fatty liver.
Independent of weight loss, a low n–6:n–3 PUFA diet ameliorated the metabolic phenotype of adolescents with fatty liver disease. This trial was registered at clinicaltrials.gov as NCT01556113.”
https://academic.oup.com/jn/article/150/9/2314/5870325 “A Low ω-6 to ω-3 PUFA Ratio (n–6:n–3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth”
My ω-6 to ω-3 PUFA 4 : 1 (1400 / 350) intake at breakfast and dinner via Balance Oil:
At lunch I eat an ounce of walnuts with a ω-6 to ω-3 PUFA 4.4 : 1 ratio: