#67 - AMA #8: DNA tests, longevity genes, metformin, fasting markers, salt, inflammation, and more
In this AMA, Peter Attia and Bob Kaplan discuss the utility of DNA kits for various diseases, longevity genes, inflammatory markers, advanced cardiac measurements, metformin for longevity, salt's role in health, and surprising markers from quarterly fasts.
Deep Dive Analysis
7 Topic Outline
Utility of DNA Kits for Health Information
Distinguishing Somatic and Germline Mutations
Genetic Testing for Cancer Susceptibility
Genetic Testing for Cardiovascular Disease Risk
Genetic Testing for Diabetes Risk
APOE Status and Alzheimer's Disease Risk
Genetic Guidance for Nutrition and Exercise
4 Key Concepts
Germline Mutations
These are genes inherited from one's parents, present in the base cell DNA. Some germline mutations, like BRCA or Lynch syndrome, can dramatically increase the risk of certain cancers, but they are relatively rare and often identifiable through family history.
Somatic Mutations
These are mutations acquired after an individual has received all their genetic material, meaning they are not inherited. Over 95% of cancers are driven by somatic mutations, which are not detectable by standard germline genetic tests like 23andMe.
Liquid Biopsies
This is an emerging technology that involves blood tests designed to find rare cancer cells or DNA fragments with acquired mutations. It aims to detect somatic mutations that are like a 'needle in a haystack' in the bloodstream.
Phenotype vs. Genotype in Health Assessment
Genotype refers to an individual's genetic makeup, while phenotype refers to observable characteristics or measurable traits. For many conditions like cardiovascular disease and diabetes, Peter Atiyah emphasizes that deep phenotypic assessment (e.g., measuring LP(a) levels, insulin response, or using a CGM) provides more actionable and insightful information than genetic predispositions alone.
6 Questions Answered
For most common diseases like cancer, cardiovascular disease, and diabetes, current DNA kits (e.g., 23andMe) offer very little actionable information because most relevant mutations are acquired (somatic) or phenotypic markers are more insightful.
Germline mutations are inherited genes that increase disease risk, while somatic mutations are acquired after birth and are responsible for the majority of cancers, not typically found in standard genetic tests.
For the vast majority (over 95%) of cancers, which are driven by somatic mutations, current genetic tests are not useful. Highly penetrant germline mutations (like BRCA, Lynch syndrome) are rare and often known through family history.
Not significantly. For CVD, important markers like LP(a) can be measured directly. For diabetes, phenotypic markers like hyperinsulinemia and continuous glucose monitoring (CGM) data are far more actionable and insightful than genetic predispositions.
Yes, knowing APOE status can be empowering and provide extra motivation for prevention. It might also influence decisions regarding contact sports for children due to a potential increase in susceptibility to head trauma.
Currently, Peter Atiyah is not convinced that existing genetic tests provide much actionable value for tailoring diet or exercise, as empirical determination of what works for an individual is often more effective and necessary.
14 Actionable Insights
1. Prioritize Phenotypic Health Data
Focus on deep phenotypic measurements (e.g., hyperinsulinemia, glucose disposal, CGM data) rather than genetic predispositions for conditions like diabetes and heart disease, as these provide more actionable and trackable insights for reversal.
2. Use Continuous Glucose Monitor
Wear a Continuous Glucose Monitor (CGM) for months to understand your glycemic response, as this offers orders of magnitude more insightful and actionable information than genetic tests for diabetes risk.
3. All-Hands-On-Deck for Dementia
Regardless of your APOE status (even with lower risk genes), adopt an ‘all-hands-on-deck’ approach to prevent dementia, as everyone with a brain is at risk of Alzheimer’s disease.
4. Measure LP(a) Directly
Instead of relying on genetic tests for LP(a) risk, directly measure your LP(a) levels, as it’s easier and provides the same important information for cardiovascular disease assessment.
5. Empirically Test Diet & Exercise
Empirically test different diets and exercise routines to determine what works best for you, rather than relying solely on genetic predispositions, as the empirical step is always necessary.
6. Monitor Insulin Resistance Markers
Monitor subtle markers of insulin resistance, such as ferritin elevation and patterns of glucose disposal, as these provide more valuable insights than genetic predispositions for diabetes.
7. APOE4 & Kids’ Contact Sports
If your child has the APOE4 gene, consider guiding them towards non-contact sports like tennis instead of contact sports like soccer, due to a potentially increased susceptibility to head trauma.
8. Use APOE4 for Motivation
If you have the APOE4 gene, use this knowledge as extra motivation to work harder on dementia prevention strategies.
9. Genetic Testing for Adopted
If you are adopted and lack family medical history, genetic testing for highly penetrant germline mutations (e.g., BRCA, Lynch syndrome) might be more beneficial to uncover unknown risks.
10. Calibrate Genetic Test Expectations
Calibrate your expectations for the overall yield and usefulness of current genetic tests, especially for cancer, cardiovascular disease, and tailoring nutrition/exercise, as their value is often low.
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3 Key Quotes
If you have a brain, you're at risk of Alzheimer's disease.
Richard Isaacson (quoted by Peter Atiyah)
I'm not sure how you could trust me if I'm telling you about something when you know I'm being paid by the company that makes it to tell you about it.
Peter Atiyah
I'm just not over the moon excited about using sort of the current crop of genetic tests.
Peter Atiyah