The Wild Health Take: Week 8

Each week Dr. Carl Seger listens to your favorite podcasts to summarize the data and give you our precision medicine take.

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Here's this week's take:

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‍Who: The DRIVE with Peter Attia

What:  #215 The gut-brain connection | Michael Gershon, MD

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1. The gastrointestinal tract (GI tract, aka digestive tract) is technically outside of the body; The system starts at your mouth and ends at the anus. It even has its own nervous system (Intestinal Nervous System, or INS) that communicates with the Central Nervous System (CNS). The GI tract has to be able to maintain communication with the CNS, while remaining separate because the gut hosts space for a community of organisms (mainly types of bacteria) that are dangerous to the rest of the body. All vertebrates have this separation between the INS and the CNS (intrinsic & enteric nervous systems). Endocrine cells in the gut are responsible for 90% of the body’s serotonin; The brain is responsible for only 2-3%. Serotonin is important for triggering nausea and inflammation as well as sensing pain. SSRIs prevent the reuptake of serotonin in the brain, but they also have a long-term impact on gut function. SSRIs make the gut move faster (speeding up digestion) at first, but actually downregulate digestion and slow down gut function long term, causing chronic constipation. These effects can be passed onto the fetus in pregnant women and to breastfeeding children.
2. The prevalence of cancer cells varies within the different organs in the digestive tract. This is likely because of the rate of epithelial (cell) turnover. In the small intestine, for example, epithelial cells turnover at a faster rate than the large intestine or the colon, making these two areas more susceptible to the formation of cancer. Another factor that plays into the formation of cancer cells is how long food (and toxins) sit in the lumen. In the small intestine, they move through relatively quickly, where they tend to sit in the large intestine for longer. The limited time exposed to transient toxins is theoretically why we see less cancer in the small intestine. Dr. Gershon feels that tests looking at microbiome have limited utility at this point.
3. The gut is wired to feel pain from pressure (like distention), which is different from the rest of the body. If there are cuts within the gut lining, those will not cause pain the same way pressure does (like bloating). The Vagus nerve sends signals to the brain to maintain homeostasis within the body. This means that the CNS communicates sympathetic and parasympathetic tone to the gut (hence the gut-brain connection). This is a major factor in appetite regulation, along with hormones that send a signal to the brain through the blood-brain barrier. Intestinal distention can cause satiety and decrease interest in eating. Endocrine cells in the gut produce hormones like ghrelin that are downregulated with increased nutrient absorption. That means that ghrelin is always working and needs to be downregulated which happens with adequate intake and absorption of a nutrient-dense diet. Liquids and solids impact appetite as well. The rate of stomach emptying varies depending on what you put into it. Liquids empty out of the stomach faster, while solids empty at a slower rate. Proteins and fats will also help slow stomach emptying, keeping satiety higher and appetite lower. This is why people who have gastric bypass can reverse the benefits of the surgery if they drink high calorie beverages after surgery.
4. Leaky gut refers to the normally tight junctions between cells in the wall of the digestive tract coming apart which allows material to pass into the bloodstream. Materials that pass through the lining of the digestive system and move into the bloodstream can be harmful and can potentially cause disease. Allergies, food sensitivities, stress and toxins can all cause these tight junctions to loosen up. There are some labs we can test to identify leaky gut, however it would need to be pretty severe for these labs to identify the condition. GI diagnostic tests, like microbiome tests, are not typically relied upon with researchers because they cannot show the full picture of bacterial makeup within the microbiome. These microbiome tests typically give the classes and populations of organisms. Before we know what to do with this information, it is important to know exactly what species are there. The most reliable GI diagnostic tests are currently designed to look for cancer, as 90% of cancer cells can be identified.
5. There are some things we can do in order to maintain optimal gut flora. Eating a balanced diet, first and foremost, ensures we have adequate nutrients and fiber intake (fiber feeds the beneficial gut bacteria). Avoiding trendy diets like cleanses (liver, colon, etc.) can also help, as these increase the risk of dehydration and decrease the amount of nutrients and fiber our bodies need to produce a healthy gut microbiome. Incorporating prebiotics and probiotics into our diet can also help support optimal gut flora. Probiotics are organisms that have beneficial effects on the gut. Prebiotics are the material that feed these beneficial bacteria. Probiotic foods are things that are fermented or have added live cultures.

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How: This information can be helpful in understanding the underlying reasons some people have a challenging time maintaining their appetite (whether they cannot control feeling hungry or are never hungry). It can also help us understand what impact medications and other lifestyle factors can have on the gut. We can use the information from this podcast to help guide some of our patients to healthier (and more sustainable) habits to improve their digestion and overall health as a result.

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Who: Tara Brach

What:  Homecoming to Your True Nature

The nature of trance: living in a constricted reality or with the belief that we must play a specific role. Our identity includes what is expected of us, what we can and can’t do with our lives and/or the feeling that something is missing in our lives. Question to ask ourselves: “Who am I really?” and “How do I wake up from that trance, that limiting identity, and live from my true nature?”

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1. The possibility to live with more freedom and more love is our ultimate goal. The places where we are most stuck in trance are our portals in transformation.

1. Consider the mythological story: The deer goes in search of a specific scent all over the world. Through forests, deserts, and so forth. At the end of his life, he lies down and is pierced with his own horn. At this point, he realizes the scent which he was searching for all his life was within his horn, within him. This story shows us that we have to be present with our true self and less concerned with chasing what we think we need.

1. In daily trance, the attention is focused on waves. We are chasing certain personas that we forget our larger belonging. The waves of our being (thoughts and sensations) are all filled with “oceaness”, which is something mysterious, infinite and pure. It fills everything. When we identify with the small self, we identify our “oceaness.”
2. One of the most freeing forms of meditation is the backward step. Consider shifting from focusing on the object (self) to sensing the awareness of itself (the ocean).
3. How do we awaken to realize who we are beyond the story of self?

1. Pathway 1: Bringing mindfulness, compassion and love to the waves that are arising. Ask, “how can we bring a wise attention to the waves to allow us to pool into our oceanness?”

1. We start with the waves, or our self portal. These are the times we feel trapped, ashamed or fearful. The practice is the pause to meet the tangle of those emotions with mindfulness and compassion. In a moment of mindfulness, the identity of self has opened up to witnessing the emotion or feeling being held with compassion. It allows you to widen the feeling of trance. If you can’t hold yourself in that space, reach out to others for aid.

1. Pathway 2: Bring direct inquiry and attention to the ocean itself.

1. We get a lot of mirror imaging from our caregivers, which tends to stick with us and impacts us. We get trapped in believing what the world tells us we are. We can get stuck in the dream for decades. Awakening from that limiting story, we become more relaxed and accessible to our creativity and intelligence.

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How: Today’s lesson is a reminder to realize your potential. Your true nature is always within you, but you must acknowledge, identify and encourage that self with compassion. Ask yourself, “who am I really?” Bring direct attention to those feelings and allow them to be awakened and grow.

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Who: Andrew Huberman Ph.D., Professor of Neurobiology and Ophthalmology at Stanford School of Medicine

What:  The Science & Treatment of Bipolar Disorder

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1. Bipolar Disorder, or Bipolar Depression, is a condition where people undergo massive shifts in their energy, perception, and mood. All of the symptoms are maladaptive and can be damaging to those diagnosed with this disorder and those in their lives. This condition is severe and associated with 20-30x greater incidence of suicide. It affects about 1% of people, and the typical age of onset is usually 20-25 years old. There are 2 subtypes of Bipolar Disorder: Bipolar I and Bipolar II.  Bipolar I is characterized by an extended period of mania, lasting for 7 days or more. Mania is defined as having at least 3 of the following symptoms: distractibility, impulsivity, grandiosity, flight of ideas, agitation/paranoia, no sleep, and rapid pressured speech. Bipolar I may only have manic episodes, then return to baseline and not experience a depressed state. Bipolar II is characterized by both manic episodes (4 days or less) as well as depressive episodes. Some may also have a state called hypomania which is a somewhat suppressed or shortened level of mania. This can take a lot of different forms from person to person, making it hard to diagnose. Mania is the defining characteristic of this disorder. The heritability of bipolar disorder is 85% - a gene or set of genes leading to increased susceptibility for Bipolar Disorder presenting itself.

2. In Bipolar Disorder, as well as many other psychiatric disorders, certain neural pathways are activated or excited for too long and can lead to atrophy, or death, of neurons. People with Bipolar Disorder, over time, exhibit signs of atrophy in the neural circuits that allow people to assess their own internal states, called interoception. Additionally, there appear to be deficits in connectivity between the parietal lobe and the limbic system. The limbic system is responsible for shifting our state from relaxation to action and is like a volume control for our alertness. In Bipolar Disorder, studies have shown the parietal lobe is not able to suppress certain elements of the limbic system, leaving it revving too high for too long. Disruptions in this circuitry combined with a lack of interoception lead to the classic symptoms of Bipolar.

3. Lithium is a naturally occurring element and first-line treatment for Bipolar Disorder.  It requires close monitoring and routine blood levels.  Lithium increases BDNF, which is permissive to neuroplasticity and is a potent anti-inflammatory. Using this therapy early on in the diagnosis has proven neuroprotective to help prevent neuronal death and the loss of interoception. A homeostatic plasticity is a particular form of neuroplasticity where neuro receptors are added or reduced in response to overactive or underactive neural circuits.  This mechanism leads to homeostatic regulation of all circuits to keep them functioning normally. Lithium and ketamine both have effects on homeostatic plasticity. When neurons are exposed to lithium for a period of time, receptors are reduced and become less excitable thus helping to aid in the control of mania. Conversely, ketamine increases the number of receptors on postsynaptic neurons leading to greater excitability. It is an effective treatment for major depression and major depressive episodes associated with Bipolar disorder.

4. Another treatment showing great promise and outcomes is electroconvulsive therapy (ECT). This induces a global seizure in a patient's brain for a very effective treatment for treatment-resistant major depression by causing an indiscriminate release of serotonin, dopamine and other neuromodulators. However, it doesn’t address the manic component. Transcranial magnetic stimulation (rTMS) is similar but non-invasive. A coil is placed on the outside of the skull which can increase neuroplasticity and reduce the amplitude and episodes of mania for those with bipolar disorder. This is still an early technique. Psilocybin is being explored as a clinical therapy for the treatment of OCD, major depression, and eating disorders. It is showing promise for the treatment of depressive symptoms of bipolar. Cannabis does not seem to be effective at treating mania or depression of bipolar disorder, but it may help with sleep in insomnia related to mania. Myoinositol and Omega 3’s are shown to change cell membrane fluidity to allow more passage of neurotransmitters and electrolytes in and out of the cell.  Both are being explored for the ability to reduce symptoms of depression and mania associated with bipolar. Studies have found that a high dose of 9.6g of fish oil per day for 4 months greatly reduced the symptoms of depression in bipolar.

5. It is important to stress that, due to the severity of symptoms of Bipolar Disorder and its high correlation with suicide, it should not be managed by natural therapies or remedies alone. As the disorder is a chemical and neural circuit disorder, the best treatment approach for patients with bipolar disorder includes a combination of pharmacological interventions, talk therapy, and lifestyle interventions to help support the patient and reduce the suffering associated with bipolar.

How: Bipolar disorder can have severe symptoms of mania and depression, causing significant impairment and disability for patients with an increased risk of suicide. Diagnosis is difficult but important to start early treatment. Lithium is a mainstay of treatment and may be used in conjunction with talk therapy, but is best treated under the care of a psychiatrist. Myoinositol and omega 3 are supplements that may help with depressive symptoms, but shouldn’t be used alone.