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Did you know that blood cholesterol levels are influenced by far more than the foods we eat?
Are you eager to know how to assess healthspan using your own body's data?
This episode of Longevity by Design is an Ask Me Anything between Dr. Gil Blander and Ashley Reaver. We gathered frequently asked questions from the Longevity by Design audience and discussed topics fundamental to longevity.
Ashley Reaver begins the conversation with a deep dive into cholesterol—including the relationship between dietary cholesterol and blood cholesterol, the two most impactful nutrients on our blood cholesterol levels, how to navigate a family history of high cholesterol, and much more.
Dr. Blander then answers questions about health metrics, explaining why VO2max is one of the best markers to assess heart health. He also discusses other markers of healthspan, the value of quality sleep, and the latest science on NAD+ precursors, including NMR and NM.
Episode highlights
Cholesterol is essential for the body and is produced by the liver. In the past, there was a belief that eating foods high in dietary cholesterol like eggs and certain shellfish had a major impact on raising blood cholesterol levels. However, research shows that dietary cholesterol intake has a relatively small effect on blood cholesterol for most people.
When foods containing cholesterol are eaten, the cholesterol is broken down and absorbed like other fats, but it does not directly enter the bloodstream. The body regulates its own cholesterol levels through internal processes. While eggs do have some nutritional impacts on cholesterol, the outdated recommendation to avoid them due to their cholesterol content is no longer advised.
Ultimately, the once believed strong relationship between consuming dietary cholesterol and having high cholesterol in the blood is not as significant as previously thought for the majority of people.
On average, about 80% of the cholesterol in our blood is made by the body itself, while around 20% comes from dietary intake. This is because as humans we need cholesterol for many essential functions like hormone production and digestive processes, so our bodies are equipped to produce it endogenously from energy sources. However, genetics are not the sole determinant of cholesterol levels. Even for those predisposed to high cholesterol, diet can influence up to 20% of blood cholesterol. While some individuals may see greater changes from diet than others due to genetic sensitivity, for most people the large majority of blood cholesterol is produced by the body regardless of dietary cholesterol intake. So while high cholesterol can run in families, lifestyle factors like diet can play an important role in managing cholesterol levels.
For the majority of people, lifestyle changes can significantly impact cholesterol levels in just 3 months. For those working to improve their markers of cholesterol, getting bloodwork done every 3 months is recommended. Frequent testing provides motivation and feedback to keep efforts on track, rather than only checking yearly.
Ashley Reaver also says which biomarkers are most useful to test:
While total cholesterol may be checked, it does not provide the full picture. A "normal" total cholesterol can hide an unfavorable ratio of LDL to HDL. Focusing on LDL, ApoB, triglycerides, and HDL will provide actionable data to make informed lifestyle and dietary choices to optimize cholesterol health.
Ashley Reaver shares a common misconception about cholesterol: that having a family history of high cholesterol means nothing can be done to improve your levels. While genetics do play a role, with about 80% of cholesterol production based on inherited factors, the remaining 20% can be significantly impacted by lifestyle.
Beyond just genetics, families often share similar diets and habits that influence cholesterol levels. Even if you eat differently than your family, most mainstream and fad diets are too high in saturated fat and too low in soluble fiber—both critical nutrients for cholesterol management. So while genetics set the baseline, a family history does not mean high cholesterol is inevitable or untreatable.
Focusing on lifestyle factors like diet quality, exercise, and stress management can meaningfully impact the 20% window where cholesterol levels can shift. Having relatives with high cholesterol is not a reason to think changes won't make a difference; it simply means being more vigilant about cholesterol-lowering behaviors.
To effectively lower ApoB and LDL cholesterol levels, Ashley Reaver explains there are two main dietary strategies to focus on: limiting saturated fat intake and increasing soluble fiber intake.
Saturated fats can downregulate LDL receptors in the liver, causing more LDL to remain circulating in the blood. Major sources of saturated fat in the American diet include red meat, full-fat dairy products, and tropical oils like coconut and palm oil. Monitoring overall saturated fat intake and limiting intake from these sources can help optimize LDL receptor function.
Soluble fiber is also a key nutrient in managing cholesterol, as it has a beneficial effect on lowering cholesterol levels. Soluble fiber binds to bile acids in the digestive tract, which utilizes cholesterol stores for bile production. This forces the body to pull from circulating cholesterol to replenish bile, effectively lowering blood cholesterol levels. Excellent sources of soluble fiber include oats, barley, beans, nuts, seeds, and some fruits and vegetables. Focusing on increasing daily soluble fiber intake can directly reduce LDL and ApoB levels.
Making dietary changes to limit saturated fat intake, especially from red meat and full-fat dairy, while increasing soluble fiber intake from whole plant foods can provide a nutritional strategy to optimize cholesterol levels. Coupled with other lifestyle factors, these diet modifications can allow the 20% window where cholesterol is modifiable to have a powerful impact on heart health, even with a family history of high cholesterol.
Insoluble fiber does not have a direct effect on lowering cholesterol levels. While insoluble fiber provides benefits like digestive regulation, it does not bind to bile acids or impact cholesterol recycling like soluble fiber does. However, many plants contain both fiber types, so consuming foods like beans still provides cholesterol-lowering effects.
Diets high in fruits and vegetables but low in grains, beans, nuts, and seeds may not provide enough soluble fiber for optimal cholesterol reduction. Though insoluble fibers are an important part of an overall healthy diet, soluble fibers are the most integral for direct LDL cholesterol lowering through the bile acid pathway. Obtaining sufficient soluble fiber from diverse whole plant foods is key for reducing cholesterol.
Fiber supplements like psyllium husk or Metamucil can be useful for increasing daily fiber intake, but should not be relied on as the sole source of fiber. Supplements typically provide about 5 grams of fiber per serving. However, daily fiber recommendations are 25-38 grams for most adults. Consuming enough supplements to meet the full fiber requirement would be impractical and likely uncomfortable.
The best approach is obtaining as much fiber as possible from whole food sources like grains, beans, nuts, seeds, and produce. Supplements can then make up any remaining difference in fiber needs. But focusing first on a high fiber diet will provide greater benefits than just taking isolated supplements.
To close Ashley's segment of the Ask Me Anything, she discusses the concerning prevalence of claims that cholesterol levels don't matter. Although cholesterol is just one risk factor for cardiovascular disease, elevated LDL and ApoB levels are associated with increased risk of events like heart attacks. With high rates of obesity, diabetes, hypertension, and other risk factors in the U.S. population, dismissing high cholesterol as unimportant can be dangerous.
While an individual's overall risk depends on multiple factors, the pervasive notion that cholesterol simply doesn't matter flies in the face of strong evidence linking elevated levels to heart disease. Ashley finds this nonchalant attitude towards cholesterol levels in the general population to be one of the more troubling and reckless perspectives regularly shared online.
Exercise—especially cardiovascular fitness—is very important for achieving optimal healthspan. Dr. Blander shares that the best physiomarker for assessing cardiovascular health is VO2max. VO2max is the maximum rate of oxygen consumption during intense exercise, measured in milliliters of oxygen per minute per kilogram of body weight. Higher VO2max indicates greater exercise capacity and is associated with lower risks of cardiovascular disease and mortality.
Directly measuring VO2max requires performing a treadmill test with specialized equipment in a lab. More accessible estimates can be obtained from devices like Apple Watch and Garmin, though these tend to underestimate true VO2max. Dr. Blander shares that while the absolute number may not be precise, tracking VO2max trends over time still provides a useful metric to monitor cardiovascular fitness. Striving to improve VO2max through exercise provides significant heart health benefits.
VO2max typically declines with age. This reduction in aerobic capacity makes daily activities more difficult. Preserving VO2max allows us to remain active and independent as we age.
On average, men have 10-15% higher VO2max than women in young adulthood. However, the rate of decline is similar between genders—about 10% per decade after age 30. Though some reduction is inevitable, staying physically active can substantially slow the decrease. Just as with LDL cholesterol, fighting the effects of aging on VO2max takes effort but allows us to function at a higher level later in life. Regular exercise creates a training effect that maintains cardiovascular fitness. Setting goals to stay in a higher fitness percentile for your age helps circumvent the natural drop in VO2max. While aging does lower aerobic capacity, prioritizing cardiovascular health through midlife and beyond can enable an active lifestyle as we age.
VO2max correlates strongly with several other health markers—both physiological markers and blood biomarkers.
Physiologically, higher VO2max is associated with lower resting heart rate, higher daily step count, higher levels of physical activity, more restful sleep, longer sleep duration, and more REM/deep sleep.
VO2max also correlates favorably with biomarkers like HDL cholesterol, testosterone, and iron. This means as VO2max increases, there is a greater likelihood that HDL cholesterol, testosterone, and iron will be within the optimal range.
Conversely, VO2max has an inverse relationship with LDL, triglycerides, blood glucose, and inflammation markers like CRP and white blood cell count.
Though correlation does not prove causation, the consistent associations between higher VO2max and healthier levels of numerous independent biomarkers is noteworthy. This indicates VO2max provides a single metric reflecting robust overall health across diverse bodily systems. Improving this measure of cardiovascular fitness appears linked to improved metabolic, inflammatory, and hormonal status along with better sleep, activity levels, and other physiological factors. The breadth of these beneficial correlations makes VO2max a remarkably informative health indicator.
Getting adequate high-quality sleep is critical for overall health and wellbeing. Dr. Blander discusses a study of 100,000 InsideTracker customers, which found that those sleeping 7-9 hours per night had the healthiest profile based on VO2max and blood biomarkers. VO2max was highest in the 7-9 hour group compared to those sleeping less than 5 hours, 5-7 hours, or more than 9 hours. Optimal levels of LDL, HDL, and other biomarkers also aligned with sleeping 7-9 hours nightly. Sleeping too little or too much was associated with poorer measures on these markers of health.
Sleep should be a priority, not an afterthought. To optimize sleep, factors like bedtime routine, room environment, temperature regulation, and sleep preparation during the day all play key roles. Focusing on getting 7-9 hours in the right conditions provides significant health advantages versus skimping on sleep. Along with diet and exercise, quality sleep is a pillar of overall wellness and longevity.
Grip strength has been shown to closely correlate with longevity. People with weaker grip strengths tend to have shorter lifespans, while those with stronger grips live longer. This is likely because grip strength serves as a marker of overall muscle health and tone. Stronger muscles metabolize more energy, protect against falls and fractures, and allow one to perform daily activities like carrying groceries. Weaker muscles lead to a higher risk of broken bones from falls, which can drastically reduce lifespan in the elderly.
One can use various data like genetic testing and physiological metrics to identify if they have a predisposition for weak grip strength. This knowledge allows for preventative action by focusing on strength training to build muscle mass. While genetics influence factors like grip strength, lifestyle choices can overcome and improve upon what nature provides. Focusing on the right types of exercise based on personalized data allows us to actively combat risks to maximize health and longevity.
There are several key tests beyond standard bloodwork that can give meaningful insight into one's health. A DEXA scan is highly useful—it takes just 2 minutes but provides data on bone density, body fat percentage, muscle mass, and visceral fat levels. Tracking visceral fat is particularly important since it is the most dangerous kind of fat. This scan allows you to monitor changes over time and make diet and exercise adjustments to lower concerning visceral fat levels.
Another important test is a VO2max test, which measures the maximum amount of oxygen utilized during exercise. This score indicates overall cardiovascular fitness. Getting a calcium score scan to look for plaque buildup in the arteries can also catch early signs of potential cardiovascular issues. Detecting problems early on allows for preventative care through medication or lifestyle changes instead of more invasive interventions after disease has progressed. Regularly undergoing these types of tests provides objective data to optimize diet, exercise, and supplementation to maximize health and functionality.
There is ongoing debate about whether NMN or NR is a better NAD+ precursor for anti-aging benefits. However, current research has yet to demonstrate significant benefits in humans from taking either supplement. Preliminary studies in model organisms suggest NAD+ analogs may provide some health and longevity advantages, but robust data proving these translate to humans is lacking.
Until more conclusive human studies emerge, it may be prudent to avoid taking either NMN or NR. While excitement surrounds NAD+ precursors, there are potential risks with taking these unproven supplements. More research is needed to weigh the costs versus benefits in humans.
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