Source
Full Notes
Dr. Bill Harris on Omega‑3 Fatty Acids
- Dr. Bill Harris: founder of Omega Quant, Fatty Acid Research Institute
- 40 years researching fatty acids, particularly omega‑3
- Over 300 publications on fatty acids
Omega‑3 Fatty Acids: Early Research
- Dr. Harris began studying omega‑3 fatty acids in the late 1970s
- Initial interest: how dietary fat affects cholesterol
- First study: high fish oil diet and its effects on cholesterol levels
- Participants consumed 25 grams of omega‑3 from salmon oil and salmon steaks daily for a month
- Found that omega‑3 lowered triglycerides, but not cholesterol
- Later studies with hyperlipidemic individuals showed even greater reductions in triglycerides
Omega‑3 and Inflammation
- Inflammation was not a topic of interest during early omega‑3 research
- Platelet aggregation was studied, as it was believed to be a mechanism of cardioprotection in Eskimos
- Omega‑3 reduced platelet aggregation and bleeding time, similar to the effects of aspirin
Safety of Omega‑3 Fatty Acids
- Most concerns about omega‑3 safety involve potential “blood thinning” effects
- Early research showed some reduction in platelet aggregation and extended bleeding time, but not to dangerous levels
- Later studies found no increased risk for bleeding with omega‑3 supplementation, even at high doses
Omega‑3 and Cardiovascular Health
- Omega‑3 fatty acids have been linked to reduced atherosclerosis and improved heart health
- Research has shown mixed results, with some trials showing positive effects and others showing no effect
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More recent studies, such as the REDUCE-IT trial, have shown promising results for omega‑3 supplementation in cardiovascular health
Omega‑3 Fatty Acids and Cardiovascular Disease
- Omega‑3 fatty acids have cardioprotective benefits
- EPA and DHA from marine sources are more potent than ALA from plant sources
- ALA can be converted into EPA and DHA in the body
- Conversion rates vary among individuals
- Omega‑3 index: a measure of omega‑3 levels in the blood
- Higher omega‑3 levels associated with lower risk of sudden cardiac death
- Can be modified through diet or supplementation
Vegetarian and Vegan Omega‑3 Sources
- Algal oil: derived from microalgae, the original source of EPA and DHA in fish
- Future possibility: genetically engineered plants that produce EPA and DHA
- More sustainable and environmentally friendly than relying on fish sources
Omega‑3 Index as a Risk Factor for Cardiovascular Disease
- Omega‑3 index measures blood omega‑3 levels
- Higher levels associated with lower risk of sudden cardiac death
- Can be modified through diet or supplementation
- Omega‑3 index can be used as a risk factor, like cholesterol
- Allows doctors to monitor and manage patients’ omega‑3 levels
Omega‑3 Index
- Allows doctors to monitor and manage patients’ omega‑3 levels
- Developed by Dr. William Harris and Dr. Clemens von Schacky in 2004
- Measures EPA and DHA levels in red blood cells
- Long-term marker of omega‑3 status, reflecting levels in other tissues
- Not yet recognized as an official risk factor by American Heart Association or NIH
Measuring Omega‑3 Levels
- Plasma omega‑3 levels are more variable and affected by daily fluctuations
- Red blood cell omega‑3 levels are more stable and long-term
- Omega‑3 index may be a better indicator of brain levels than plasma levels
Variability in Omega‑3 Index
- Some people have higher or lower omega‑3 index despite similar dietary intake
- Genetic factors may play a role, but specific genes have not been identified
- Variability in response to omega‑3 supplementation is also observed
Clinical Trial Design
- Ideal trial design would measure omega‑3 index at baseline and after treatment
- Analyzing data based on achieved omega‑3 index can provide clearer results
- Titration of omega‑3 supplementation is important for individual patients
Collaboration with Clinical Trial Researchers
- Encourage researchers to use Omega Quant for measuring omega‑3 index in trials
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Address heterogeneity in research by incorporating omega‑3 index measurements
Heterogeneity in Omega‑3 Cardiovascular Trials - Reasons for inconsistent results in omega‑3 trials:
- Low dose
- Higher background omega‑3 levels in the population
- Short-term treatment
- Decreased incidence of heart disease due to improved medications and lifestyle changes
- Successful omega‑3 trial: Reduce It
- 4 grams of EPA
- Strongest predictor of benefit was the omega‑3 level achieved
Omega‑3 Index
- Average American omega‑3 index: 5%
- Japan’s average omega‑3 index: 9–10%
- Vegans and US military personnel: 3.5%
- Ideal omega‑3 index: above 8%
- Maximum observed omega‑3 index: 15–16%
- Dolphins at SeaWorld: 18–19%
DHA vs. EPA
- DHA is typically present in higher amounts than EPA in cell membranes
- Both EPA and DHA are important for biological functions
Target Omega‑3 Index and All-Cause Mortality
- Study involving 17 cohorts and around 45,000 people
- Omega‑3 levels measured at the beginning of the study
- Participants followed between ages 65 and 75
- Higher omega‑3 levels correlated with a 15% lower risk of death during the study period
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Dose-dependent relationship between omega‑3 levels and risk of death
Omega‑3 and Mortality -
Omega-3s have a protective effect on health, not just heart disease
- 15% decrease in all-cause mortality observed in a study
- Omega‑3 index: lowest group under 4%, highest group around 7%
- Average omega‑3 intake in the US: 100–150 mg/day, median intake is zero
- In Japan, average intake is 900 mg/day, and average lifespan is 5 years longer than the US
Omega‑3 and Inflammation
- Higher omega‑3 levels correlate with lower levels of inflammatory biomarkers
- Omega-3s are not just anti-inflammatory, but also pro-resolving of inflammation
- Specialized pro-resolving mediators (SPMs) are molecules made from EPA and DHA that suppress inflammation
- SPMs help prevent inflammation from getting out of control
- Chronic inflammation is at the root of many diseases, including cardiovascular disease, dementia, and cancer
Omega‑3 and Cardiovascular Health
- Reduced trial with high EPA showed a dramatic lowering of triglycerides
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Omega-3s may help suppress chronic inflammation related to cardiovascular disease
Omega‑3 and Cardiovascular Health - Triglyceride lowering is often associated with cardiovascular health and omega‑3
- FDA indication for drugs that lower triglycerides
- Lovasa lowers triglycerides by 20%, approved for people with triglycerides over 500
- Vascepa is the only one indicated for reducing risk for cardiovascular events
- Omega-3s may be cardioprotective through other mechanisms
- Anti-inflammatory
- Anti-platelet (thinner blood, less likely to clot)
Omega‑3 and Red Blood Cell Distribution Width (RDW)
- RDW measures the variation in red blood cell sizes
- High RDW is a predictor of adverse outcomes
- Ideal red blood cell sizes should be uniform
- Omega-3s may affect red cell biology
- Make cell membranes more flexible
- Improve oxygen delivery to tissues
Omega‑3 and Small Dense LDL Particles
- Small dense LDL particles are more atherogenic
- Inflammation can cause larger LDL particles to form small dense LDL particles
- Omega‑3 index may have an inverse correlation with small dense LDL particle size
Omega‑3 and COVID-19 Mortality
- Pilot study with 100 people admitted to the hospital with COVID-19
- Higher omega‑3 levels correlated with lower mortality risk
- Not statistically significant, but a strong trend
- Another study from Chile showed similar results
- Higher average fish intake correlated with lower risk of death from COVID-19
Omega‑3 and COVID-19 Spike Protein
- In silico experiments showed that DHA can hold the spike protein in a closed conformation
- Prevents interaction with the ACE2 receptor
- Could potentially suppress infection and negative outcomes through the renin-angiotensin system
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Linoleic acid (omega‑6 fatty acid) also showed similar effects in silico
Omega‑3 and Omega‑6 Ratio -
Omega‑3 to Omega‑6 ratio is often discussed in relation to health
- Major dietary sources of Omega‑6 are vegetable oils and refined oils
- People have become scared of consuming Omega‑6 through whole foods like nuts and flaxseed
Thoughts on Omega‑3 and Omega‑6 Ratio
- The ratio concept is imprecise and not very helpful
- It’s unclear which specific fatty acids are being referred to when discussing the ratio
- The best way to fix a bad ratio is to increase Omega‑3 intake (EPA, DHA)
- Higher Omega‑6 intake (linoleic acid) is associated with lower cardiovascular and diabetic risk
2013 Bratsky Paper on Omega‑3 and Prostate Cancer
- Study found a correlation between plasma phospholipid Omega‑3 and prostate cancer
- Criticisms of the study:
- Very small difference in Omega‑3 levels between those who did and didn’t get cancer
- Discussion in the paper went beyond the data, turning an association into cause and effect
- Study has not been confirmed and has been refuted by other studies
Strength Study on Omega‑3 and Cardiovascular Disease
- Used EpiNova, an EPA + DHA supplement with free fatty acids
- Study found no effect and was stopped early for futility
- Possible reasons for the lack of effect:
- Chronic inflammatory response from taking free fatty acids daily
- Insensitive measurement of inflammation (CRP)
Personal Omega‑3 Intake
- 2–3 grams a day from supplements
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Salmon once a week
Omega‑3 Research and Clinical Trials - Cochrane report from a couple of years ago
- Looked at 70 trials in pregnant women given omega‑3
- Found that giving omega‑3 reduces risk for premature birth, especially early premature birth before 34 weeks
- No more research needed on this topic, question is settled
- ORP trial from Australia
- Largest study in the field, but compliance with DHA supplementation was not very good
- Change in omega‑3 index was not much, so no benefit seen
- Could be because women weren’t taking it
- Omega Quant’s Mother’s DHA test
- Measures red cell DHA levels in pregnant women
- Over 5% is where you want to be to prevent preterm birth
- Obstetricians could easily measure this and counsel pregnant women
- Brain development
- Mixed evidence on the benefits of higher omega‑3 levels in mom for child’s brain development
- Some studies show kids doing better, others show no difference
- Never doing worse, either no different or better
- Recent study on DHA supplementation in pregnant women
- Found a benefit in preterm birth and reduced risk for adverse outcomes in delivery
- Haven’t looked at mental outcomes in the baby yet
Omega‑3 Importance Across the Lifespan
- Important for development, aging, and overall health
- Low hanging fruit for people willing to make the change
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Consistent supplementation can provide benefits, even if other lifestyle factors are not ideal
Omega‑3 Supplements and Heart Health -
Some people prefer taking supplements over changing their diet
- Lavaza and EpiNova: capped at 4 grams
- Studies showed good triglyceride reduction at 4 grams, better at 8 grams
- Practical limitations: affordability and consumption
- Higher doses of omega‑3 supplements may be more effective, but more research is needed
Safety Concerns: Atrial Fibrillation (AFib)
- Small but statistically significant increase in AFib in clinical trials for people with preexisting heart conditions
- Cause of AFib increase not yet understood
- No increased risk for stroke, but AFib itself can be problematic
- Ongoing research on the relationship between omega‑3 levels and AFib development
Dr. William Harris: OmegaQuant and Fatty Acid Research Institute
- OmegaQuant: offers omega‑3 testing and information on Dr. Harris’ research
- Fatty Acid Research Institute: conducts research on fatty acids and their health effects
- Omega Matters Podcast: interviews with omega‑3 experts
Find more information on Dr. Harris’ work at omegaquant.com and the Fatty Acid Research Institute website.
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