August 22 , 2020

 Latest numbers show that we are all over the map with cases and deaths nationally. All of the former hotspots minus California are on the decline, while the formerly untouched midwest is on the rise. This is becoming a pattern. High burn infection rate turns into colder spot while the virus jumps to a new unaffected area. New York and the northeast continue to have little to no disease now after massive winter/spring disease. Florida, Georgia, Arizona and Texas are seeing major declines in cases and deaths after peaking last month. There have been similar daily deaths over the past few months despite the significantly higher number of cases. North Carolina peaked on July 23rd.

More than 80% of deaths are skewed toward the over 55 age group and 94% of all deaths occurred in a person with a comorbid chronic health disease. As with the first newsletter on this topic, keep solace with the fact that there is a 99+% chance of survival for all of us.
NC death cases

This is a long newsletter. Lots of information has come to light lately.


 After running with a few friends on a sidewalk, a gentleman coming in the other direction walked quite far away with the intent of decreasing his risk of exposure to SARS2 which I found reasonable on the face of it. It brought to mind an analogy to understand risk. It is clear from the data that COVID risk is heavily defined by prolonged exposure to the virus via aerosol droplets, i.e. being in a closed room for 20 plus minutes without a mask with an infected person = bad idea. This is how viral load comes to be a major player.

 Star Wars analogy: Imagine that a Jedi is the equivalent to the human that is less than 60 years old and maximizing lifestyle choices for health. In the Star Wars movies, a Jedi is the pinnacle of balance in mental and physical abilities like a well tuned immune system in a human. The clone troopers represent a SARS2 virus particle. Thus, if we imagine a bunch of clone troopers coming to kill the well trained Jedi knight, the outcome is total destruction for the clones. However, if the Jedi is injured through poor choices like not sleeping, eating poorly for a while, drinking too much alcohol or smoking and being stressed out, then the number of troopers needed to win the battle decreases and the outcome can change. As we age, we develop more risks for dysfunctional Jedi abilities leading to less clones needed to beat us.

 This is simplistically what is happening with COVID19. The volume of viral particles needed to get into your system and kill you is directly related to your inherent Jedi powers and time spent in the war zone. The more time you spend in the war zone the more clones you will have to kill off. The more time you spend abusing your body, the less viral particles needed to hurt or kill you.

The new news:

 1) Peter Attia has produced another outstanding podcast, #123, on metabolism, metformin, mTor, rapamycin and COVID19. It is deep, so go only if you are highly motivated to learn deep science. I will try and parse it down to consumable information here. He goes into the undiscussed reality that most individuals succumbing to COVID19 are metabolically unhealthy. His guests, Drs. Joan Mannick and Nir Barzalai are the preeminent experts on metabolism regarding the mammalian target of rapamycin pathway and metformin pharmacological effects on autophagy and aging respectively.

 Where the discussion gets really interesting is when they discuss the effects of metformin and rapamycin on COVID19 death rates. In a study by Dr. Luo and colleagues, we see a data set showing that death risk reduction for patients admitted to the hospital with COVID19 was dramatic for the group on metformin at admission for metabolic disease. The metformin group had a 3% death risk while the non metformin group had a 12% risk. That is a 4X risk reduction which is massive. (Luo et. al. 2020) They further go on to discuss that around 60% of Chinese diabetic patients are on metformin, yet the majority of hospital admissions were for diabetics not on metformin. Further showing the benefits of prevention of COVID19 acquisition or illness severity or both in the treated group.

 The takeaways from this analysis and discussion for me are simple: this is yet another example of the reality that metabolic health is critical for survival. Metformin is a drug that affects many metabolic pathways including mitochondrial function, reactive oxygen species production, blood glucose control and much more (Kulkarni et. al. 2020)(see below for more detail*). It is essentially simulating a healthy lifestyle pattern for a diabetic or anyone for that matter. However, if one reduces the antecedent dietary triggers of disease, than your co-morbid disease risk is reduced as well as your death rate without any drugs. This is and will continue to be a screaming point for me.

 Dr. Attia further goes on to discuss the fact that the production and distribution of a safe and effective vaccine is a very tall order and that we are likely to be here with SARS2/COVID19 for a long long time, if not forever. I completely agree.

 Which means that we better get busy as a society reframing the story around immune health enhancement and metabolic repair through lifestyle choices over the tiresome current reality of politically appointed lockdowns and ineffective messaging that leads to ebbing and flowing of disease and angst. We are neither that stupid nor gullible to believe that this narrative makes sense.

 2) We need to be very clear about something. The death risk from COVID19, unless the healthcare system in the United States gets overwhelmed, is a reflection of the poor metabolic health of Americans on balance. According to the CDC, 94% of COVID19 deaths are related to at least one co-morbid disease regardless of age. That is to say that SARS2/COVID19 is picking on people that have made choices in life, actively or passively, that have set them up for a bad outcome. This is just a fact without emotion. We must individually perform better over time to reverse these trends in the immediate future. Another way of saying this is as follows, if you under 50 years old and taking care of yourself through quality lifestyle choices and are devoid of metabolic disease, then your risk of death is "almost" zero. You are still at a dramatically reduced risk in the other age direction based on the same principles.

 3) Carolina Lucas et. al. wrote a fantastic paper in Nature looking at the misfiring of the immune system in severe COVID19 disease. What they found is that individuals that develop severe disease have an immune makeup that shows that they are poorly adapted to surveil, respond to and kill SARS2. This is shown by the low volume of circulating T cells that are critical to early identification and then killing of viral particles. This leads to increased viral loads and massive pro inflammatory cytokine release secondarily which in turn leads to massive inflammation throughout the lungs and other organs compromising function and leading to death. (Lucas et. al. 2020) Since 94% of deaths occur in individuals with metabolic chronic disease, we can likely infer that the underlying chronic disease is an antecedent trigger for immune dysregulation which is well known in diabetic circles. (Barron et. al. 2020)

 4) McKinsey Corporation has produced a quality analysis of economic growth, lockdowns and what the future holds. It is reasonably long but a good read.

 5) SARS2 is airborne! Yes, the masks of high quality will help reduce transmission. N95 masks really work. Surgical masks definitely help, but are not as effective at promoting a tight seal like an N95. Being in a closed space for greater than 20 to 30 minutes with a sick individual unmasked is a sure way to contract the infection especially when you up the ante with a large indoor crowd.

6) Sweden continues to look good without locking down.

7) Why are COVID19 patients losing their sense of smell? A group of scientists have figured this issue out. Read here.

8) An excellent 18 minute podcast by Docsmo on the SARS2 vaccines is available here.

For now, using a mask of the surgical type appears to be a great idea to prevent spread. The best idea for survival is still rooted in caring for yourself through healthy eating, adequate rest, exercise and stress reduction.

Knowledge is power,

Dr. M

Peter Attia Podcast #123
Luo American J Tropical Med Hygiene
Kulkarni Cell Metabolism
Lucas Nature
Barron Lancet Diabetes and Endocrinology
McKinsey Economic Analysis
Wei-Haas National Geographic
Dean American College of Cardiology
Le Bert Nature
Sekine BioRxIV
McConnell Atlantic
Macartney Lancet
Jing Lancet Infectious Disease
Li Clinical Infectious Diseases
CDC Death Statistics
Jiang Harvard Medical School

*Metform mechanism of action from Dr. Attia's show notes:
Mechanisms of metformin action in attenuating hallmarks of biological aging-The cellular uptake of metformin is via the organic cationic transporter 1 (OCT1), after which it exerts three arms of action- 1) metabolic; 2) oxidative and 3) inflammatory. 1) Metformin inhibits mitochondrial complex I and thereby oxidative phosphorylation leading to an increased AMP:ATP ratio, causing a direct activation of AMPK. AMPK-dependent mechanisms (blue) contribute to the downstream inhibition of mTORC1 (improved nutrient-sensing and autophagy), activation of PGC-1α (improved mitochondrial biogenesis), transcriptional regulation via DNA/histone modifications and miRNAs. Extracellularly, metformin downregulated Insulin/IGF1 signaling, also leading to mTORC1 inhibition. 2) The inhibition of mitochondrial ETC also leads to AMPK-independent effects (red) including reduced reactive oxygen species (ROS), reduced advanced glycation end-products (AGEs) and thereby reduced macromolecular damage. 3) The AMPK-independent (red) anti-inflammatory and senotherapeutic effects of metformin are evident via the downregulation of pro-inflammatory cytokines, NF-κB signaling, and activation of Nrf2-Gpx7 and ATM-signaling, respectively. These three arms work to mitigate the aging-induced dysregulation in cells, thereby attenuating hallmarks of aging. (Attia #123)