FoundMyFitness
#085 Dr. Peter Attia on Mastering Longevity – Insights on Cancer Prevention, Heart Disease, and Aging
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Quick takeaways
- Dietary choices that address insulin sensitivity and lower triglyceride levels can help reduce APOB.
- Genetic factors play a role in APOB levels, with some individuals having genetically low APOB.
- Pharmacological interventions can effectively lower APOB levels, with PCSK9 inhibitors and base editing trials showing promise.
- Statins are highly effective at lowering LDL cholesterol levels and can have reversible side effects such as muscle aches and insulin resistance.
- Limited evidence suggests that statins have minimal impact on mitochondrial function, but more research is needed.
- Maintaining optimal blood glucose levels through exercise, sleep, and hormonal regulation is crucial for long-term health.
Deep dives
Dietary Factors and Insulin Resistance
Dietary choices that address insulin sensitivity and lower triglyceride levels can help reduce APOB. Carbohydrate restriction is effective in reducing triglyceride levels, and saturated fat consumption can impact cholesterol synthesis and LDL receptor production.
Genetic Variation and APOB
Genetic factors play a role in APOB levels, with some individuals having genetically low APOB. People with extremely low LDL cholesterol and APOB levels due to a hypofunctioning PCSK9 gene have no increased incidence of cardiovascular disease or other major illnesses.
Pharmacological Interventions
Pharmacological interventions can effectively lower APOB levels. PCSK9 inhibitors, which target a protein that degrades LDL receptors, are one option. Additionally, base editing trials show promise in editing genes like PCSK9 to achieve lower APOB levels.
The importance of statins in treating ASCVD
Statins are a class of drugs that are highly effective at lowering LDL cholesterol levels, which is important in treating atherosclerotic cardiovascular disease (ASCVD). They work by inhibiting cholesterol synthesis, primarily in the liver, leading to increased LDL receptor production and greater clearance of LDL cholesterol from the bloodstream. Although statins are effective, they can have side effects such as muscle aches and insulin resistance. However, these side effects are generally reversible when the medication is discontinued.
Mitochondrial function and statin use
There is limited evidence on how statins affect mitochondrial function, but available data suggest that any impact on mitochondria is minimal. Studies using lactate production as the gold standard for measuring mitochondrial function do not show a significant reduction in performance or impairments with statin use. While statins may indirectly affect coenzyme Q10 (CoQ10) levels in the body, there is mixed evidence on whether CoQ10 supplementation offsets any potential negative effects. More research is needed to fully understand the relationship between statins and mitochondrial function.
The importance of glucose regulation and metabolic flexibility
Glucose regulation is a crucial aspect of overall health, and maintaining metabolic flexibility is key. Metabolic flexibility refers to the body's ability to efficiently shift between using glucose and fatty acids as fuel sources. Exercise plays a significant role in enhancing insulin sensitivity and promoting metabolic flexibility. Other factors, such as sleep, energy balance, and hormonal changes, also influence glucose regulation. Maintaining optimal blood glucose levels is important for long-term health, with lower average blood glucose levels associated with better outcomes. Continuous glucose monitoring (CGM) can provide insights into postprandial glucose spikes and variability, contributing to a better understanding of individual glucose disposal and insulin sensitivity.
Symptoms and Consequences of Menopause
Menopause is accompanied by the cessation of three key hormones: estrogen, progesterone, and testosterone. This hormonal change leads to a range of symptoms such as hot flashes, night sweats, brain fog, sleep disturbances, vaginal atrophy, reduced libido, and bone loss. These symptoms can have a significant impact on a woman's quality of life and overall health.
Misinterpretation of the Women's Health Initiative
The Women's Health Initiative study, which linked hormone replacement therapy (HRT) to an increased risk of breast cancer, has been widely misinterpreted. The study actually used a synthetic progesterone called MPA, and it was the MPA component that showed a slight increase in breast cancer incidence. On the other hand, the group receiving estrogen alone had a lower incidence of breast cancer. Overall, the study did not demonstrate an increased risk of breast cancer mortality for women using HRT.
Hormone Replacement Therapy Options
Hormone replacement therapy (HRT) options include bioidentical estrogen, usually administered through a patch, as well as various options for progesterone, such as bioidentical oral progesterone or a progesterone-coded IUD. Topical estrogen creams or suppositories can be used to alleviate vaginal symptoms. It is important to work with a healthcare provider to determine the most appropriate HRT regimen based on individual needs and preferences.
Importance of Early Hormone Replacement Therapy for Women
Initiating hormone replacement therapy (HRT) early after menopause is associated with reduced risk of heart disease, dementia, and bone mineral density (BMD) decline. Late initiation of HRT may not provide the same benefits and could potentially increase the risk of Alzheimer's disease (AD). The timing of initiation is especially important for women with the E4 variant of the APOE gene. However, further research is needed to understand the long-term effects of HRT after 10 years.
The Impact of Testosterone Replacement Therapy in Women
The role of testosterone replacement therapy (TRT) in postmenopausal women is still being studied, particularly in relation to sexual function. Testosterone plays a significant role in libido, orgasmic function, and arousal for women. TRT, when used in women with low testosterone levels, can have profound impacts on sexual health. However, further research is needed to determine the optimal dosage and the potential risks associated with TRT in women. Each patient should be assessed on an individual basis.
The Importance of Sleep, Nutrition, Exercise, and Mental Health
Optimizing sleep is essential for overall health and wellbeing. Consistency in bedtime and wake-up times, avoiding stimulating activities close to bedtime, and using sleep-promoting supplements such as glycine and magnesium can improve sleep quality. In terms of nutrition, maintaining a balanced diet and avoiding junk food is important. Prioritizing protein intake throughout the day, stopping eating before bed, and consuming alcohol in moderation are beneficial practices for nutrition and sleep. Regular exercise, including cardiovascular and strength training, is crucial for physical and mental health. Additionally, prioritizing mental health by seeking therapy, practicing dialectical behavioral therapy, and engaging in stress management techniques can enhance overall wellbeing.
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Show notes are available by clicking here
Peter Attia, MD is a highly respected expert in preventive medicine, focused on the crucial subject of longevity and cardiovascular health. He's also the author of the NY Times best selling book Outlive - which I highly recommend if you have not read it already. Peter's philosophy transcends the conventional goal of merely extending lifespan; it's about enriching the quality of every year, ensuring that each stage of life is lived with optimal health and vitality.
In this episode, we discuss:
- (00:00) Introduction
- (07:36) Defining cardiovascular disease
- (09:43) Coronary plaque and fatality risk
- (13:34) How ApoB predicts heart disease
- (21:34) Factors elevating ApoB
- (27:23) Does high ApoB cause cardiovascular disease
- (37:01) ApoB thresholds for ASCVD prevention
- (40:27) Dietary factors raising ApoB
- (49:33) Genetics of ApoB and LDL
- (53:24) Does low LDL increase cancer?
- (56:19) Cholesterol-lowering drugs
- (59:59) Statins, uses, and side effects
- (1:03:12) Are statins toxic to mitochondria?
- (1:09:56) Ubiquinol for statin-induced muscle soreness
- (1:11:09) How to train in zone 2
- (1:17:09) Statins and neurodegenerative disease risk
- (1:21:54) Cholesterol synthesis in the brain (desmosterol role)
- (1:25:58) Statin alternatives
- (1:36:49) Berberine for CVD Risk Reduction?
- (1:39:36) Muscle as a glucose sink
- (1:51:38) Hemoglobin A1C Levels and Mortality Data
- (1:55:35) 80/20 Zone 2/VO2 Max Training Protocol
- (2:02:12) Insights from VO2 max testing data
- (2:12:17) How obesity increases cancer risk
- (2:15:03) Cancer screening
- (2:40:32) Menopause – hormonal shifts and health effects
- (2:45:13) Hormone replacement therapy (HRT)
- (2:58:57) Perimenopause diagnosis with hormone levels
- (3:02:04) HRT's impact on dementia, cancer, and heart disease risk
- (3:07:42) Vitamin D
- (3:16:24) Testosterone replacement for women's sexual function
- (3:18:47) HRT safety 10 years post-menopause
- (3:23:05) Testosterone & TRT
- (3:32:33) Blood pressure
- (3:45:30) Peter's longevity optimization routines
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