Dr. Bill Harris on the Omega‑3 Index: Increasing Omega‑3 to Promote Longevity & Transform Health

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

• 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
• 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

• 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

• 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

• 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

• 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

• 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

• 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.