Each week Dr. Carl Seger listens to your favorite podcasts to summarize the data and give you our precision medicine take.
Here's this week's take:
Who: The DRIVE with Peter Attia
What: Liquid Biopsies and Cancer Detection
Liquid biopsies look at blood samples and other non-solid biological tissue to determine cancer prevalence or existence. This can be helpful because CT scans need over 1 billion cancer cells bunched together (in a tumor) in order to recognize cancer. There could be hundreds of micrometastatic cells spread out throughout the body that go undetected by a CT scan. Liquid biopsies would be able to detect smaller quantities of cancerous cells, which could detect them faster. Liquid biopsies could initially look at protein biomarkers to help identify cancer prevalence, however there were some issues with this tool due to its detection of low levels of specific proteins without cancer prevalence with no way to differentiate. Low-dose CT scans have lower radiation risk to help offset the exposure in the case of screening.
Sensitivity vs. specificity. Sensitivity refers to how many subjects’ cancer diagnoses were correctly detected (if 100/100 women had cancer, but the test diagnosed 85 of them, it would have an 85% sensitivity and be 15% inaccurate). Specificity refers to the inverse of sensitivity. Ie., if a patient does not have cancer and the test is negative, this would refer to specificity. A test with low sensitivity can be thought of as being too cautious in finding a positive result, meaning it will err on the side of failing to identify a disease in a person with cancer. A test with low specificity can be thought of as being too eager to find a positive result, even when it is not present, and may give a high number of false positives. This could result in a test saying that a healthy person has a disease, even when it is not actually present.There are no perfect tests when trying to push the limit on how small of a tumor is being detected. Ideally we could develop a test with a very high sensitivity and therefore not miss patients with early cancer. Often, with very high sensitivities, you sacrifice specificity and end up with higher rates of false positives. Liquid biopsies often have a high specificity but low sensitivity.
Lung cancer is the #1 cause of cancer death in the US. The vast majority of cases cannot be cured. Incidents of lung cancer are decreasing due to decreases in smoking and treatments having improved (including screening). However, smoking is not the only cause of lung cancer. Environmental exposure to toxins (radon, pm2.5, smog) is another leading cause of lung cancer. Women (+ asian women) are at a higher risk of developing lung cancer. There are holes in our ability to measure total exposure to smoking, second-hand smoke exposure and environmental exposure, which affect how we screen for lung cancer.
Liquid biopsy testing can be used to identify recurrence of cancer slightly earlier than other testing modalities and may soon be able to be used to identify recurrence in other types of cancer. We can use this technology in several ways, including using it as a screening tool to look at patients. However, this could result in lower specificity. It can also be used in patients with known cancer, who can then have surgery to remove the cancer. Before and after this point liquid biopsy can be used to assess if the entire tumor has been removed and decide if the patient then needs radiation and/or chemotherapy. Hopefully this can help negate the need to biopsy a tumor and can tell what chemotherapy agents can be used to treat the cancer by looking at DNA as well as cell free RNA.
How: This episode is extremely complicated but provides insight into the future of medical research and how it may improve the diagnosis of cancer and cancer recurrence. While much of this podcast is not actionable at this time, it is important to follow as it contains important information on work that is advancing the treatment of cancer.
Who: Andrew Huberman Ph.D., Professor of Neurobiology and Ophthalmology at Stanford School of Medicine
Your nervous system includes your brain, spinal cord, and nerves. It controls all of your organs. The nervous system is made up of nerve cells called neurons. Neurons create chemicals that make other neurons more or less electrically active. Neural circuits are chains of neurons that lead to specific behaviors or emotional states. The neuromodulators, or chemicals, that activate neural circuits are dopamine, epinephrine, serotonin and acetylcholine. We can leverage these chemicals to produce desired outcomes in our feelings and behaviors to optimize our health and performance. Knowing which behaviors each of these neuromodulators produce and knowing where their baseline exists is key to understanding what tools can enhance certain states. Typically, the best order when considering interventions is behavior modification, nutrition, supplementation, then pharmacotherapy.
1. Dopamine, when elevated above baseline, increases states of motivation, drive and focus. To enhance dopamine levels above baseline, maximize sun exposure to your eyes and skin in the early part of the day, within 1 hour of waking. This sets in motion a biological cascade that releases dopamine and increases the expression of genes related to thyroid hormone and increased dopamine receptors. In addition, avoid bright light the last 7-8 hours of the day (17-24 hours from waking) to maintain baseline. Regular ingestion of 100-400mg caffeine daily will increase the number of D2 and D3 dopamine receptors, so the more dopamine in your system, the more potent its effect. Tyrosine rich foods also help maintain baseline levels of dopamine. Supplements that can help increase dopamine are Mucuna Pruriens, L-tyrosine and phenylethylamine, although these are powerful and can cause an emotional crash afterwards. Deliberate cold exposure also produces a significant release and circulation of dopamine. Ideal cold water immersion is done at a temperature that is safe to stay in for 1 to 10 minutes. The dopamine level increases are similar to what you would see with prescription pharmacology.
2. Epinephrine and norepinephrine are mainly responsible for generating our energy, fuel and baseline of forward center of mass. When epinephrine levels are high we are alert and can’t shut down our thinking; whereas, when it’s low, we have low energy and feel incapable of action. Any physical activity is scientifically proven to increase levels of epinephrine. Although it does take caloric energy, exercise gives neural energy by stimulating epinephrine release from the locus coeruleus in the brain. Caffeine does increase epinephrine, but pushing it out for 60 to 90 minutes from waking up will help to avoid the afternoon “crash”. Another tool is cyclic hyperventilation (Wim Hof, Kundalini breathing) involving repeating deep inhales and exhales for 25 repetitions, leaving you more alert.
3. Serotonin creates a state of contentedness, happiness, relaxation, satiety, soothing and a relief or lack of pain. When levels are too high, we may be unmotivated which leads to decreased energy and libido. Physical touch can increase serotonin transmission. Gratitude has been proven powerful to evoke serotonin. Both receiving, giving and observing gratitude are all effective. The amino acid tryptophan can lead to net increases in serotonin. White meat turkey, whole milk, canned tuna, oats, cheese, nuts and seeds, chocolate and some fruits are all high in tryptophan. Cissus quadrangularis at a dose of 300-600mg increases tryptophan and can provide a 39% increase in serotonin. This supplement may need to be cycled, but there is debate about how often. Myo-inositol, 900mg every 3 days, can increase serotonin levels. 5-HTP supplementation can increase serotonin levels, but varied effects are reported.
4. Acetylcholine is distinct in that it often works independently and is associated with states of focus as it relates to learning and coding new information. It has a particularly potent ability to allow neuroplasticity for neural circuits to change and grow in our brains. To optimize acetylcholine, regularly ingest foods that have the right precursors to produce acetylcholine including liver, eggs, soybeans, chicken, fish, mushrooms and kidney beans. Nicotine has been proven to increase acetylcholine. Smoking by vaping or cigarettes is addictive and has negative health effects so some will chew nicotine gum or use nicotine dipped toothpicks to achieve enhanced focus. Other supplements like alpha GPC 300 mg, 3-4 times a week before workouts, can stimulate choline pathways. However, there are a few studies linking risk of stroke with chronic aGPC use, so this should be used cautiously. Focus can increase acetylcholine. Narrowing the visual field then moving into a focused bout of work can further improve focus.
Muscle mass is inversely proportional to life expectancy. We need muscle mass (strength) to perform rudimentary movements as we get older or we will need someone who is able to do these for us, especially over the age of 65.
Protein needs to be used once ingested, it cannot be stored for later use. Protein that is not used is lost in urine. The recommended/minimal dietary intake is 0.8g of protein per kilogram of body weight per day. People can benefit from going all the way up to 1.6g per Kilogram of body weight. Optimal intake range would be around1.2g per kilogram of body weight. Protein intake is needed to support muscle mass, including lean muscle mass. It’s important to maintain protein intake levels as people age to maintain muscle mass.
Anabolic resistance declines as people age. Primarily comes from lack of movement as aging happens. As people age, this becomes less responsive, not necessarily due to sugar. It is important to maintain physical activity levels with activities like aerobic exercise and resistance exercising. Health benefits are seen at greater than 6,000 steps taken per day. However, for general aerobic exercise, 2 days per week is the minimum goal, with 3-4 days a week or 150 minutes per week being most ideal. Include resistance training twice a week for 30-45 min per session. This does not have to be in a gym. It can include air squats, sit ups, push ups, etc. at home. Something is better than nothing!
Benefits of exercise do not stop as we age. 13 of the 26 most common types of cancer are lower in those who have higher levels of physical activity as part of their leisure time. This includes gardening, walking, etc. Moving around in a leisurely way is better than a sedentary lifestyle. Improvements in mood, depressive symptoms and anxiety are noted here.
Sauna helps activate stress proteins called heat shock proteins. Heat shock proteins bind to other proteins to prevent them from misfolding. Protein misfolding can happen under stress and is thought to be associated with muscle atrophy and a multitude of disease processes. We think activation of heat shock proteins helps decrease muscle atrophy. So what we see is that sauna can provide results similar to exercise.
How can we apply this information:
Muscle mass and exercise are extremely important for longevity and aging. By eating the proper amount of protein each day and including regular exercise (both aerobic and resistance training), we are able to become less dependent on others as we age. Keeping an active lifestyle promotes longevity.
If we aren’t aware of our “dragons”, the emotions attached to them control us. Our identity gets hitched to them since we are not in full presence. Emotional reactivity is not personal, it's universal. We are mentally set up to react.
Mara is the God of greed and hatred and delusion. She represents the shadow side and the different forms that the dragons take in our inner life. Buddha had a mythological encounter with Mara and was faced with his dragons. He met those attacks and was able to move forward the next day. Mara continued to arise throughout Buddha’s life. Buddha would confront Mara directly and invite her to tea, displaying the invitation to confront your dragons head on, with kindness and an open heart. This is something each of us can do with our own dragons.
Consider “Having tea with the dragons.”
Step 1: The sacred pause: rather than reacting, sit and say “yes” in order to acknowledge the dragon.
Step 2: Start investigating how this feels throughout the body. Go deeper to identify what’s beneath this energy.
Step 3: Inevitably, we find something vulnerable that needs love. Address it with compassion and presence.
Prayer is the bridge between longing and belonging. “Having tea with the dragons” is the key to waking up to and moving to presence and compassion.
How do you invite the dragons when you are wounded and stuck? Include others in the process of healing. There’s nothing weak about involving others.
We begin with the life that is here. We learn to bring compassion to our current state. This allows movement through larger circles. It helps us to dissolve the differences we once saw in others. It helps us shift our presence into recognizing that we all belong to the life that is here and approach it with kindness.
How: Responding to vulnerabilities (“dragons”) with love is the ultimate goal. The more we address our own “dragons”, the better we express compassion to others. This is the first step in impacting the world in a peaceful manner. As you move through life, consider the metaphor, “Having tea with your dragons.” Sit down with vulnerable emotions and investigate how they feel throughout your body. Address it with compassion and kindness.