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CHAPTERS
- 0:04 – 6:51
Why the podcast runs on subscriptions, and meet Bill Harris
Peter Attia explains why the show takes no ads and relies on a member model instead. He then introduces Bill Harris, an omega-3 researcher, and previews an episode that explains the fat families from the ground up.
- •Attia says trust and enthusiasm are why he avoids ads
- •Members get exclusive show notes, AMA access and deals on products he already likes
- •Harris is a professor and CEO of OmegaQuant, which Attia flags as a conflict of interest
- •Attia describes Harris as an honest broker of the science and a generous mentor
- 6:51 – 11:04
Harris's first salmon oil study and the start of his career
Harris describes how he got into omega-3 research through a postdoc assigned to test salmon oil's effect on cholesterol. The feeding study used about 25 grams a day of EPA and DHA and found a triglyceride-lowering effect nobody had known about.
- •Harris earned his Ph.D. in nutrition in 1978 and did his postdoc with Bill Connor
- •The metabolic ward diet included salmon steaks twice a day plus about 100 mL of salmon oil daily
- •Salmon oil lowered cholesterol like vegetable oil did, but uniquely lowered triglycerides
- •The work coincided with the Greenland Eskimo findings of Dyerberg and Bang
- 11:04 – 20:03
Saturated, monounsaturated and polyunsaturated fats; omega-3 vs omega-6
Harris explains the chemistry of fatty acids: single versus double bonds, how each class behaves at room temperature, and what omega-3 and omega-6 mean. He also explains the numbering shorthand such as 16:0 and 18:1.
- •Saturated fats have only single bonds and are solid at room temperature
- •Monounsaturates have one double bond; olive and canola oil are examples
- •Polyunsaturates have two or more double bonds and are liquid even in the fridge
- •Omega-3 and omega-6 name the position of the first double bond counting from the final carbon
- •Number notation gives the carbon count, then the number of double bonds
- 20:03 – 23:55
Membranes, tissue-specific fatty acid patterns, and diet vs. membrane composition
The conversation turns to why these fats matter: they make up every cell membrane. Harris and Attia discuss how the body selects fatty acids for each tissue, so membrane composition varies much less than diet does.
- •Every tissue has its own unique fatty acid pattern
- •Membrane physical properties, such as being loose or stiff, depend on fatty acid composition
- •Dietary fat intake varies much more than blood or membrane levels
- •Large differences in saturated fat intake produce only modest differences in membranes
- 23:55 – 28:08
The 1970s–80s low-fat era and how fats affect LDL
Attia sets the historical scene of the saturated-fat guidelines and the interest in polyunsaturated oils. Harris explains how replacing saturated fat changes membranes so the LDL receptor clears LDL better, and notes the mistake of cutting all fat.
- •People in the 1970s took tablespoons of vegetable oil to lower cholesterol
- •Less saturated fat in liver membranes makes the LDL receptor more efficient
- •The effect is mostly on LDL rather than HDL
- •Harris says the message went wrong when all fat was cut instead of just saturated fat, with sugar replacing it
- 28:08 – 40:20
The omega-6 and omega-3 pathways: LA to AA, ALA to EPA to DHA
Harris walks through the two metabolic pathways, naming the dietary sources of linoleic acid and ALA and the end products arachidonic acid, EPA and DHA. They also note that DHA is not converted back to EPA, and that Americans get only about 150 mg of EPA plus DHA a day.
- •Linoleic acid is essential and comes mostly from vegetable oils such as soybean
- •Elongation and desaturation turn LA into arachidonic acid, the precursor of prostaglandins
- •ALA from flax, chia and soybean oil is converted to EPA and then DHA
- •A recent paper suggests DHA is not retroconverted to EPA
- •Average American intake of EPA plus DHA is roughly 100 to 150 mg a day, versus 6 to 7 g for Eskimos
- 40:20 – 52:12
Findings of the early studies: platelets, Eskimos, and the LDL rise
Harris recounts the early results, including mild lipid changes, prolonged bleeding time and the Eskimo paradox of a high-saturated-fat diet with few heart attacks. He then describes the 1985 New England Journal papers and how capsule trials found that high-dose omega-3 raised LDL in people with high triglycerides.
- •Triglycerides fell from about 100 to 75 and cholesterol modestly in the salmon oil study
- •Bleeding time was prolonged no more than with aspirin, supporting an antiplatelet effect
- •Most of the 25 g dose came from oil rather than salmon
- •Capsule studies at 6 g/day raised LDL and ApoB in hypertriglyceridemic people, so the FDA stopped cholesterol-lowering claims
- •Harris says recent work points to DHA slowing LDL receptor clearance
- 52:12 – 1:01:57
Prescription omega-3s versus supplements and EPA's heart benefits
Harris explains the FDA-approved 4 gram dose for triglycerides over 500 and how Lovaza compares to over-the-counter capsules. They discuss supplement quality and the ways EPA is thought to protect the heart.
- •Lovaza is approved for triglycerides over 500 at 4 g a day
- •A 1,000 mg Lovaza capsule is about 85% EPA plus DHA
- •Reading labels matters because capsule size does not equal EPA/DHA content
- •Harris says supplement testing generally found products accurate and clean
- •EPA acts through antiplatelet metabolites, resolvins and changes in membrane fluidity
- 1:01:57 – 1:11:22
REDUCE-IT: pure EPA and cardiovascular events
Harris describes the REDUCE-IT trial of 4 grams a day of icosapent ethyl in statin-treated patients with elevated triglycerides. It cut events by about 25% with little change in LDL and only a modest triglyceride drop. They discuss possible mechanisms and why the study used EPA only.
- •About 8,000 statin-treated patients with triglycerides of roughly 150 to 500 were studied
- •Cardiovascular events fell about 25% over four to five years with virtually no side effects
- •Triglycerides dropped only about 15% and LDL did not change
- •Harris suggests resolution of inflammation and improved heart rate variability as contributors
- •The EPA-only design traces to Japanese drug history and the JELIS trial
- •Attia compares the effect to the PCSK9 trials
- 1:11:22 – 1:17:26
Red blood cell testing and the limits of ALA conversion
The discussion covers EPA's fate in the body and whether red blood cells reflect other tissues. Harris says EPA's benefits do not come through DHA conversion and that even large ALA doses barely raise EPA levels.
- •Giving pure EPA does not raise red cell DHA
- •Red cell omega-3 correlates with heart, muscle, liver and intestine, but least with the brain
- •Even 12 g of ALA might raise red cell EPA only from 1% to 2%
- •Harris says ALA may have benefits of its own but is no substitute for EPA and DHA
- 1:17:26 – 1:23:37
DHA, the omega-3 index and individual variability
Harris explains what DHA is thought to do compared with EPA, including a possible LDL-raising effect at high doses. They discuss target red cell levels and why people respond so differently to the same intake.
- •DHA makes protectins and improves platelet function in a way parallel to EPA
- •DHA may lower triglycerides and raise HDL more than EPA, but can raise LDL at high doses
- •Harris's target omega-3 index (EPA plus DHA in red cells) is 8 to 12%, versus about 4 to 5% for the average American
- •Some people reach very high levels on little intake, which Harris attributes to genetics
- •Harris's data show a 50/50 chance of an 8% index at about three oily fish meals a week plus a supplement
- 1:23:37 – 1:30:26
DHA and the brain, choosing fish, and mercury
Harris explains why DHA is abundant in the brain yet EPA-rich products fare better in depression studies. He and Attia then discuss which fish to eat and how to weigh mercury risk against benefit.
- •The brain and retina are rich in DHA, but giving DHA hasn't clearly helped depression
- •EPA-rich products look better in depression meta-analyses even though the brain holds almost no EPA
- •Harris favors getting both EPA and DHA, as fish naturally provide
- •Sardines, herring, mackerel and salmon are oily choices; tilefish, swordfish, king mackerel and shark are high in mercury
- •Attia notes individual variability in mercury clearance and suggests measuring levels if eating lots of tuna
- 1:30:26 – 1:44:55
Arachidonic acid, omega-6 ratios, and seed oils
Harris explains why arachidonic acid got a bad reputation and why he dislikes omega-6 to omega-3 and AA/EPA ratios. He cites large studies showing higher linoleic acid levels linked to lower disease risk, and he and Attia discuss seed oils.
- •Harris says arachidonic acid makes both pro- and anti-inflammatory molecules, so it is not simply bad
- •Meta-analyses found higher blood linoleic acid tied to lower risk of heart disease and diabetes, while AA was neutral
- •Less than 1% of dietary LA becomes AA, and AA levels are tightly controlled
- •Ratios can be changed by altering the denominator and distract from the lack of EPA and DHA
- •Harris prefers the omega-3 index and says the real problem is too little EPA and DHA
- 1:44:55 – 1:53:16
Fish versus supplements and the VITAL trial
Attia and Harris ask whether fish itself matters beyond its omega-3 content. Harris then argues the VITAL trial, which used one Lovaza capsule in healthy people, was misreported as negative because the dose was low and the composite endpoint masked a reduction in heart attacks.
- •Harris says supplements can deliver the benefit, though fish is preferred where practical
- •VITAL enrolled 20,000 to 25,000 relatively healthy Americans at 850 mg a day
- •The composite endpoint was not statistically significant, but heart attacks fell about 20%, according to Harris
- •Low fish eaters saw a benefit on the primary endpoint
- •Harris says pharma-grade and reputable supplements are essentially the same chemistry, and a pure EPA supplement isn't sold
- 1:53:16 – 1:57:25
Measuring omega-3 status, OmegaQuant, and test options
Harris urges doctors to measure omega-3 status as routinely as cholesterol. He and Attia discuss OmegaQuant's finger-stick test, other labs' assays, and why red cell levels take about four months to reach a new steady state.
- •Harris wants omega-3 status measured as often as cholesterol
- •OmegaQuant's cash-pay finger-stick test costs $50
- •Plasma tests give lower numbers than red cell tests, which are a more stable marker
- •Retesting makes sense about every four months after a change in intake
- 1:57:25 – 2:02:25
Upcoming STRENGTH trial, free fatty acids, and absorption
Harris previews the STRENGTH trial of an EPA plus DHA free-fatty-acid product and explains why absorption differs by form. Attia notes the implications for people who fast, and the episode closes.
- •STRENGTH is a roughly 13,000-patient trial with inclusion criteria similar to REDUCE-IT
- •The Epanova product is about 85% EPA plus DHA as free fatty acids
- •Ethyl esters are poorly absorbed on an empty stomach and need food
- •Attia describes taking fish oil with dinner when he skips breakfast
- •Results are expected after the study finishes in October of the following year
