AMA #3: supplements, women's health, patient care, and more (EP.26) | The Peter Attia Drive

Attia notes that the HbA1c was designed to diagnose type-2 diabetes, not to optimize metabolic health. It cannot detect glucose variability — two patients can have the same average glucose with standard deviations of 10 vs. 30, yielding vastly different insulin exposure profiles that the A1c conflates. His own beta-thalassemia trait makes his A1c read 5.6-6.0 (pre-diabetic range) while his CGM-imputed A1c equivalent is 4.5-5.0, illustrating the unreliability dramatically.

Attia describes the CGM as the single tool that stopped him eating a cookie on an airplane because he knew he would face the data afterward. The behavioral mechanism is internal competitiveness: he is more driven by not wanting to see a spike than by long-term disease prevention. He also uses CGM data to empirically calibrate personal rules: one drink is tolerable, two is a brick over the head; eating close to bedtime tanks both resting heart rate and HRV as measured by Oura ring.

During the year-long 600 mg/day experiment, the first person to notice a change was Attia's wife — she remarked about four months in that something was different. Her observation: decreased emotional volatility. Attia later concluded the change may be largely explained by meditation and self-awareness added afterward, given confounders. The OTC dose is meant to replicate naturally occurring groundwater lithium concentrations, not produce a pharmacological effect.

Attia frames it as empirical trial: rather than testing for PCSK9 over-expression directly, he simply trials berberine for 6-8 weeks and watches for response. Patients with the PCSK9-driven phenotype occasionally show dramatic LDL-P reductions. Regarding the AMPK benefit: 'I prefer to just use metformin if we're going to go down that path — pharmacologically with potent drugs that we understand, that are consistent from batch to batch.'

Attia's practical pattern: post-partum women with TSH around 2.0, free T3 slightly below 3.0, reverse T3 just above 12, presenting with fatigue dismissed as post-partum adjustment. Brief thyroid support normalizes the panel and the symptoms in weeks. He does NOT advocate thyroid supplementation in patients with a genuinely normal full panel.

Attia originally used a First Beat chest-strap EKG device with proprietary HRV algorithm before consumer rings existed. He had patients wear the device 72 hours continuously. The compliance problem with chest straps — skin irritation, mail-in data delays — made the Oura ring a practical upgrade. He cross-references CGM data with Oura overnight HRV to derive personal behavioral rules about alcohol, meal timing, and room temperature.

The tracer study tracked all intermediaries of NAD and its precursors in vivo. Attia emailed Rabinowitz the day before this recording and received confirmation of his reading: cells form NAD entirely in the cytoplasm and import it as intact NAD into mitochondria — and the transporter for NR/NMN at the cell membrane is simply absent in non-hepatic tissues. The popular pterostilbene-NR combination product (Basis) would not change this, as pterostilbene modulates sirtuin activity, not the NR uptake problem. NAD infusion clinics are 'quackery' on the same logic: extracellular NAD is not taken up by cells.

The pituitary is one of only two tissues in the body with portal circulation (the liver being the other), giving it direct chemical access to the hypothalamus. In a fasted or ketotic state, circulating FGF21 rises and reaches pituitary receptors through this portal route, then signals down to suppress gonadotropins specifically in the female. Attia is careful to clarify this is about optimization, not absolute impossibility: 'Obviously it's possible, I mean I'm not suggesting it's not — but we're talking about optimization.' He extends the caveat to pregnancy: he is agnostic about whether ketosis during pregnancy is optimal, noting ancestral exposure does not by itself confer optimality.

The philosophical core of this answer is that reference ranges reflect where a population actually is, not where it should be. Attia uses the rower height analogy: the reference range for male height is correct statistically, but a competitive heavyweight rower should be 6'2"-6'4" regardless of the population average. Applied to cardiovascular risk: 'heart disease and atherosclerosis are the most ubiquitous causes of death, so to be average on the disease that is the most common strikes me as just backwards mathematics.' He also notes that most labs use two-standard-deviation distributions based on a population that includes two-thirds overweight or obese adults, so 'normal' already encodes excess disease.

The three main drivers of IGF-1 are amino acid intake (especially methionine), insulin levels (indirectly via binding proteins), and exogenous GH use. Attia notes that because IGF-1 is stable relative to GH (which changes within minutes of a sauna), it provides a meaningful signal of cumulative growth-factor environment. His updated target: a 'snapshot' read between the 60th and 80th percentile in re-fed state, with deliberate periodic drops via fasting.

Aspirin Works is a urine-based test measuring metabolites of platelet activation; a high result predicts responsiveness to aspirin's platelet-inhibiting effect. Attia's personal stack at time of recording: enteric-coated 81 mg aspirin daily, justified by positive Aspirin Works test plus strong family history of heart disease (even with normal LP(a) and normal LP-PLA2). The anti-platelet mechanism is primary; anti-inflammatory effect is secondary and smaller. Separately: aspirin on long flights was common clinical advice, but Attia's research team found the data did not support it — low-molecular-weight heparin (injectable) is the only option with meaningful evidence.

Attia notes these patients are 'kind of the easiest saves' — if you look beyond TSH to free T3 and reverse T3, the picture becomes clear and targeted thyroid support resolves their fatigue rapidly. He distinguishes this from primary hypothyroidism. The mechanism he suspects involves repeated cortisol surges during labor and the postpartum period perturbing the HPT axis. He uses the Oura ring metaphor of a slowly warming pot of water to describe how women experiencing gradual decline in thyroid function post-pregnancy often do not notice how impaired they have become.