#83 - Bill Harris, Ph.D.: Omega-3 fatty acids
Dr. Bill Harris, a PhD in human nutrition and omega-3 expert, discusses fatty acid families, the history of omega-3 research, and the health benefits of EPA and DHA. He provides insights on increasing EPA/DHA intake and the importance of testing omega-3 levels.
Deep Dive Analysis
18 Topic Outline
Dr. Bill Harris's Journey into Omega-3 Research
Defining Fatty Acid Families: Saturated, Mono, Polyunsaturated
Significance of Fatty Acids in Cell Membranes
Historical Context of Fat Phobia and Cholesterol Lowering
Conversion Pathways of Omega-6 (LA to AA) and Omega-3 (ALA to EPA to DHA)
Early Salmon Oil Study: Triglyceride Lowering and LDL Elevation
Evolution of Omega-3 Understanding and Supplementation
Distinction Between Prescribed Fish Oil Drugs and OTC Supplements
Health Benefits and Mechanisms of EPA
REDUCE-IT Study: EPA-Only for Cardiovascular Risk Reduction
Potential Benefits of ALA and its Conversion Limitations
Health Benefits and Brain Role of DHA
Omega-3 Index: Measurement, Target, and Genetic Variability
Recommended Fish for EPA/DHA Intake and Mercury Concerns
Revisiting Omega-6 Fatty Acids: Arachidonic Acid Misconceptions
Critique of Omega-6 to Omega-3 Ratio
VITAL Study: Low-Dose Omega-3 in Primary Prevention
Importance of Measuring Omega-3 Status and Future Research
10 Key Concepts
Saturated Fatty Acid
A long carbon chain with only single bonds between carbon atoms. These fats are typically solid at room temperature, like lard or butter, and can raise cholesterol levels by affecting LDL receptor efficiency.
Monounsaturated Fatty Acid
A long carbon chain containing one double bond. Oils rich in monounsaturated fatty acids, such as olive oil, are liquid at room temperature but may solidify in the refrigerator.
Polyunsaturated Fatty Acid
A long carbon chain with two or more double bonds. These oils are liquid at room temperature and typically remain liquid in the refrigerator, found in vegetable and fish oils.
Omega-3 Fatty Acid
A family of polyunsaturated fatty acids where the first double bond is located at the third carbon position when counting from the 'omega' (final) carbon. Key examples include ALA, EPA, and DHA, primarily found in flaxseed oil and fish oils.
Omega-6 Fatty Acid
A family of polyunsaturated fatty acids where the first double bond is located at the sixth carbon position from the 'omega' (final) carbon. Linoleic acid (LA) is the principal dietary omega-6, found in vegetable oils like soybean and corn oil, and is converted to arachidonic acid (AA).
Arachidonic Acid (AA)
A 20-carbon, four-double-bond omega-6 fatty acid derived from linoleic acid. It is crucial for metabolism and serves as the precursor for many prostaglandins, which can be both pro- and anti-inflammatory.
EPA (Eicosapentaenoic Acid)
A 20-carbon, five-double-bond omega-3 fatty acid derived from alpha-linolenic acid (ALA). EPA is known for its cardiovascular benefits, including reducing platelet stickiness and producing anti-inflammatory resolvins.
DHA (Docosahexaenoic Acid)
A 22-carbon, six-double-bond omega-3 fatty acid derived from EPA. DHA is highly concentrated in the brain and retina, contributes to cell membrane fluidity, and produces anti-inflammatory protectins.
Omega-3 Index
A measure of the percentage of EPA plus DHA in red blood cell membranes. It serves as a stable, long-term marker of omega-3 status, with a target range of 8% to 12% considered healthy.
Residual Risk
The remaining risk of cardiovascular events in patients who are already on standard therapies like statins to control cholesterol levels. Addressing residual risk is a key focus of new cardiovascular treatments.
14 Questions Answered
Saturated fats have only single bonds between carbon atoms, monounsaturated fats have one double bond, and polyunsaturated fats have two or more double bonds in their carbon chain.
Fatty acids are fundamental components of every cell membrane in the body, influencing the membrane's physical characteristics, flexibility, and the function of embedded enzymes and receptors crucial for cellular metabolism.
Omega-6 and monounsaturated fats replace some saturated fatty acids in cell membranes, which changes the membrane's fluidity and makes LDL receptors in the liver more efficient at removing LDL particles from the blood, thereby lowering cholesterol.
Linoleic acid (an omega-6) is predominantly found in vegetable oils like soybean and corn oil, while alpha-linolenic acid (an omega-3) is rich in flaxseed oil, chia seed oil, and to some extent, soybean and canola oil.
No, the conversion of ALA to EPA and DHA in the body is very limited, with less than 1% of ingested ALA typically converting to the longer-chain omega-3s.
EPA contributes to heart health by reducing platelet stickiness (acting as a mild blood thinner), producing anti-inflammatory molecules called resolvins, and improving cell membrane flexibility to enhance cellular metabolism.
In studies like REDUCE-IT, pure EPA (Vascepa) at a dose of 4 grams per day showed virtually no change in LDL cholesterol or ApoB levels, unlike some high-dose combined EPA+DHA products in hypertriglyceridemic individuals.
DHA improves platelet function, makes platelets less sticky, produces anti-inflammatory protectins, and is particularly important for brain and retinal health due to its high concentration in these tissues.
While DHA is abundant in the brain, studies on depression have shown that products richer in EPA tend to be more effective in affecting depressive symptoms than those rich in DHA.
The recommended healthy range for the Omega-3 Index (red blood cell EPA plus DHA) is 8% to 12%.
Oily fish like salmon, sardines, herring, and mackerel are excellent sources of EPA and DHA. Albacore tuna is also a good source, but generally has more mercury than chunk light tuna, though the benefits of fish consumption typically outweigh mercury concerns.
Arachidonic acid is not inherently bad; it is an essential fatty acid that gives rise to both pro-inflammatory and anti-inflammatory molecules, playing a crucial role in normal metabolism.
The omega-6 to omega-3 ratio is problematic because it presumes omega-6s are bad (which is not supported by evidence showing higher LA levels are associated with lower disease risk), doesn't differentiate specific fatty acids within each family, and can be misleading as the same ratio can exist with vastly different absolute levels.
The VITAL study, using 850 mg/day of EPA+DHA in healthy individuals, did not show a statistically significant effect on its composite primary endpoint, but it did show a significant 20% reduction in heart attacks and fatal heart attacks, particularly in those with low fish intake.
25 Actionable Insights
1. Health Target: Aim for 8-12% Omega-3 Index
Strive to achieve an omega-3 index (red cell EPA + DHA) between 8% and 12%, as this range is considered healthy, compared to the average American’s 4-5%.
2. Health Monitoring: Measure Blood Omega-3 Levels
Assess omega-3 status (e.g., red cell EPA DHA) as regularly and importantly as cholesterol, as low omega-3 levels have significant health implications.
3. Dietary Protocol: Consume Both EPA and DHA
For overall health and any medical condition, aim to consume both EPA and DHA, as they naturally occur together in fish and are both beneficial.
4. Dietary Protocol: Prioritize Oily Fish
To maximize EPA and DHA intake through food while minimizing mercury concerns, prioritize oily fish such as salmon, sardines, herring, and mackerel.
5. Dietary Flexibility: Fish or Supplements for Omega-3s
While consuming fish is preferred, obtaining EPA and DHA through supplements (either EPA-only or EPA+DHA) is an effective alternative, considering personal preferences, cost, and ecological factors.
6. Supplement Protocol: Take Ethyl Ester Omega-3s with Food
To ensure optimal absorption of ethyl ester forms of omega-3 supplements (like Vascepa and Lovaza), always take them with food, as absorption is significantly reduced on an empty stomach.
7. Health Protocol: Re-test Omega-3 After Four Months
After making changes to omega-3 intake (diet or supplements), wait approximately four months before re-testing blood levels to allow for the red blood cell turnover and reach a new steady state.
8. Health Monitoring: Focus on Omega-3 Index
Concentrate on raising the absolute levels of EPA and DHA (Omega-3 Index) if they are low, rather than getting distracted by omega-6 to omega-3 or AA to EPA ratios, as increasing EPA/DHA addresses the core issue.
9. Health Protocol: Increase EPA/DHA to Lower AA
If the goal is to lower arachidonic acid (AA) levels, the most effective strategy is to increase EPA and DHA intake, typically through fish oil supplementation.
10. Dietary Focus: Focus on Increasing EPA/DHA
Instead of overly focusing on reducing omega-6 fatty acids, prioritize increasing EPA and DHA intake in the diet, as the primary problem is a lack of these beneficial omega-3s.
11. Dietary Principle: Fish Benefits Outweigh Mercury
The health benefits derived from consuming fish, including its omega-3 content, generally far outweigh the potential downsides of small amounts of mercury.
12. Dietary Strategy: Replace Saturated with Unsaturated Fats
If reducing saturated fat intake, replace it with monounsaturated and polyunsaturated fats rather than carbohydrates or other macronutrients to avoid potential health problems.
13. Decision-Making: Evaluate Interventions by Safety, Cost
When evaluating interventions with even a hint of benefit, especially those that are extremely safe, cheap, and have no drug interactions, consider adopting them.
14. Depression: Use EPA-Rich Omega-3s
For potential effects on depressive symptoms, choose omega-3 supplements that are richer in EPA than DHA.
15. Dietary: Avoid High-Mercury Fish (Pregnancy)
Pregnant and lactating women should avoid high-mercury fish like tilefish, swordfish, king mackerel, and shark due to potential adverse effects on neurodevelopment.
16. Supplement Choice: Reputable Omega-3 Supplements are Quality
High-quality omega-3 dietary supplements from reputable companies are generally comparable in quality to FDA-approved pharmaceutical-grade products.
17. Health Monitoring: Prefer Red Cell Omega-3 Test
Opt for a red blood cell omega-3 test over a plasma test for a more stable, long-term marker of omega-3 status.
18. Health Monitoring: Access Omega-3 Index Test Directly
Individuals can order a finger-stick omega-3 index test directly from OmegaQuant’s website for $50 to assess their red blood cell EPA and DHA levels at home.
19. Supplement Protocol: Take Omega-3s with Dinner
If practicing intermittent fasting or not eating breakfast, take omega-3 supplements at night, as close to dinner as possible, to ensure they are consumed with food for better absorption.
20. Mental Model: Body’s Buffering Capacity
Recognize that the body has a significant buffering capacity in cell membrane composition, meaning dietary changes may not drastically alter tissue levels of certain fats as much as one might expect.
21. Prioritize Trust in Information Sources
When evaluating health information, prioritize sources that are transparent about financial incentives, as direct payment for recommendations can compromise trustworthiness.
22. Deconstruct Complex Terms
Overcome intimidation by complex terminology by breaking down terms and understanding their underlying meaning or context to make learning easier.
23. Utilize Visual Aids for Complex Topics
For technically dense subjects like fatty acid chemistry, refer to diagrams and figures in show notes to better understand the material.
24. Reference Studies for Deep Understanding
When discussing scientific subject matter, consult the referenced studies to gain a deeper, evidence-based understanding.
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5 Key Quotes
The problem is the lack of EPA and DHA. If you get those up, your arachidonate levels will go down. That's the best way to lower, if you want to lower arachidonate is to take fish oil.
Bill Harris
I don't think the benefit, the cardiovascular benefit comes from lowering triglycerides.
Bill Harris
It's the liquidness that was important, not the source, not whether it's a plant or an animal. It's the physical property of the oil. That's the important thing.
Bill Harris
What's the point of the omega-6 to omega-3 ratio? It's good versus good. So why are we doing this?
Bill Harris
The benefits of eating fish, even if there's some mercury in it, far outweigh the downside of the mercury.
Bill Harris