Weight Loss, Mental Health, and Sleep

It’s been an interesting month in my Dasein and there are a couple of new developments that I’d like to share! Aside from those, I must remark on a new health tech tool that I finally invested in that has been absolutely worth the cost. Let’s dive in.

1.     The Next Blockbuster in Metabolism - Retatrutide

It has been an amazing few years in the realm of metabolic therapy, with semaglutide [Ozempic/Wegovy] providing the first significant swing (not to denigrate its earlier brethren, liraglutide [Saxenda] and dulaglutide [Trulicity]), followed shortly afterward by tirzepatide [Mounjaro], people that had been struggling to lose weight despite trying everything finally caught a break. The nutrient and energy sensing circuitry are vital to survival, and when such a system gets hijacked by unconscious sociocultural norms, there's no wonder we have an obesity epidemic. I also understand that there is a brooding outrage among those that have already done the difficult work to achieve their desirable body composition via means of discipline and willpower. It's a sad state of affairs when we can't rejoice when others are offered a chance to suffer less, but those internal battles of pride, anger, and resentment are to be dealt with from within. This latest development by the pharmaceutical company, Eli Lily - Mounjaro's mother - is sure to become one of the most influential drugs in history. Retatrutide (brand name will be unknown until after phase III trials are complete) brings one additional receptor stimulation profile to the already best-in-class Mounjaro: glucagon. It is beyond the scope of this newsletter to dive into metabolic mechanisms of glucagon and the interplay with GLP1 and GIP agonism but suffice to say obesity will no longer be an issue - so long as accessibility is adequate. In phase II trials, 100% of participants lost at least 5% of their body weight at the middle dose of 8 mg (studied doses were 1, 4, 8, & 12mg). That is essentially a guarantee that if you take this peptide, and you carry weight that is beyond what your frame should have, you will lose at least 5% of your total body weight. But that is just the tip of the iceberg. At the 8 and 12mg doses it was common to see 20-30% reductions in total body weight. It is simply incredible, and a testament to the neuroendocrine control of metabolism. The cherry on top of this sundae is that every single cardiometabolic risk factor also improved - systolic blood pressure, diastolic blood pressure, hemoglobin A1c, fasting glucose, fasting insulin, triglycerides, and LDL cholesterol. Whether those are secondary to the medication itself or the behavioral changes it instigates, I don't think they can be teased apart. I do know that it will be incredibly important to counsel and ensure that healthy lifestyle behaviors are the foundation upon which the new baseline will be maintained - this should not be a license to consume whatever brings pleasure or comfort.

2.     Hypnosis

I'm afraid I've been behind the curve with my recommendations for mental health and psychotherapeutic tools. With the psychedelic renaissance at the forefront and ketamine-assisted psychotherapy so powerful, I failed to give hypnosis its due credit. That said, with humility the opportunity to grow arose and I scoured the relevant literature to see where the meat of the therapy was, and I was not disappointed. Approaching the subject skeptically, I walked away with great curiosity and appreciation for those who bore the responsibility to show the medical community that it is a modality with significant power. Using PET scans to evaluate the activation of brain regions under hypnosis, it was shown that the suggestions led to activation of regions responsible for such sensations, regardless of what objective reality was in the environment. For example, when subjects were given the suggestion to see color, the color perception areas of their cerebral hemispheres were activated whether they were looking at color or black-and-white patterns. When subjects were given the suggestion to see black and white, the color perception areas of the brain showed decreased activity regardless of what the subjects were viewing. This implies that hypnosis is not a process of simply following instructions but actually involves a change in the brain’s perception and generative modeling. Research has been done in most areas of medicine, from urological conditions like impotence to neurological conditions like migraines and chronic pain, all of which show significant positive effects. While the outcomes generally depend on the individual's susceptibility to hypnotic induction, about two-thirds of the population fall into this category. For the other third, there is still a positive impact, but it seems to take much longer with more volitional buy-in. The neurophysiology behind hypnosis is also well-established thanks to the help of functional magnetic resonance imaging (fMRI), and there is also a profound overlap with neural signatures evoked by ketamine therapy. There was even a study that showed induction into a state that mimicked MDMA in individuals that had previously undergone MDMA-assisted psychotherapy. Overall, to me it seems the power of suggestion in a state of ego-dissociation combined with heightened somatic and emotional awareness lies in the ability to change long-standing beliefs about one’s self. A cool resource I came across, if anyone is interested, is called Reveri. Reveri is an app co-developed by David Spiegel, MD (arguably one of the most prominent researchers and clinicians in the hypnosis field), that offers a validated hypnosis-susceptibility test and guided hypnosis sessions that can be done at home (no affiliation, just a cool resource).

3.     Eight Sleep - https://www.eightsleep.com/ (no financial affiliation)

Having had the Ooler from ChiliSleep (now SleepMe) for a couple of years, I knew the difference that sleeping with a temperature-controlled mattress was a non-negotiable for my sleep quality. As a warm-bodied individual, cranking up the A/C was the only option I had prior to using the Ooler, which was largely ineffective and made for a very expensive electric bill (especially in Texas Summers). However, my appreciation for the Ooler waned as it seemed to lose power, get noisier, not get as cold, and its internal water-cleaning system did not do a great job (not to mention the cumbersome nature of cleaning out the unit). After looking into more options, I came across Eight Sleep and, while the investment was steep, I can’t imagine my life without it! Not only will Eight Sleep keep your mattress at your desired temperature, but it will also actually provide suggestions based on learning your particular changes throughout the night and automatically adjust the temperature to match what is optimal for sleep staging and waking up refreshed. Additionally, the app provides insights into heart-rate variability, heart rate over the night, body temperature (helpful for the ladies tracking basal-body temperature for fertility/natural family planning methods), sound production, and sleep stage estimates of REM, deep, and light sleep based on aforementioned biometrics. The staging actually matches up relatively well with both my Oura ring and Withings sleep mat. If you want to level-up your sleep game, Eight Sleep is a must.

That’s all for this month! Hope this was informative and helpful, I appreciate you taking the time to read!