Coronavirus Covid-19: Some Questions and Answers

Many people have been asking questions about the Coronavirus outbreak. First, if you’re scared, you should be. This pandemic is not a hoax as expressed by people like Trump and Hannity, and the USA is woefully unprepared to diagnose, prevent, contain, mitigate, and treat this exponentially spreading and deadly disease. Understand, even if you don’t die from the disease, if you are severely infected with the disease you may suffer permanent scaring in you pulmonary system, potentially resulting in lifelong  respiratory problems. Be concerned, take action, and don’t panic. Follow good public health practices such as social distancing, cleansing your hands, and not touching your eyes, mouth, or nose unless you have cleansed your hands. To best set your immune system to fight the infection and quell the inflammation induced by your immune system response to the SARS-CoV-2 virus that causes Covid-19, eat right, exercise, don’t smoke, limit or stop alcohol consumption, and sleep well. In my book, “Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts,” I detail much of what you can do to become healthier and improve your innate and adaptive immune systems. Eat vegetables, with soluble and insoluble fiber, limit salt and sugar intake, no processed oils, including olive oil, especially coconut oil and even MCTs. I’ll now answer some of the questions I’ve been asked about Covid-19.

Why is it called the novel “coronavirus”?

Novel because we’ve never seen this virus in the human population previously. This virus probably originated in bats and then spread to other animals with whom humans interact, including those animals in our food supply. The virus is called a coronavirus because of the 3 dimensional shape of the virus; named for the crown-like spikes on the virus’ surface.

What does this mean and what is known about how the virus compares to
others in the same family?

Human coronaviruses were first identified in the mid-1960s. There are seven coronaviruses that can infect people. These types of viruses are typically responsible for common colds more than serious diseases. However, coronaviruses are also behind some more severe outbreaks, including Covid-19, SARS, and MERS. These viruses mutate in time and new strains emerge. When the virus mutates, chemical and structural changes can result that may change the viruses’ spread and infection patterns. The dangerous new strain called SARS-CoV-2 started circulating, causing the disease COVID-19 in 2018, but seriously emerged in 2019. Scientists discovered and had warned that this disease would spread in 2018, but the Trump administration had dismantled the “Predict” program begun by President GW Bush and expanded by President Obama. Trump ignored warning after warning that an outbreak was imminent. We were caught totally unprepared for this pandemic because of Trump and his lack of scientists (Ph.D.) in key positions. Scientists, such as Prof. Dr. Wayne Getz, Ph.D. at UC Berkeley have published very recently the specific needs in order to understand, predict, and contain future outbreaks, especially due to zoonotic disease, borne from animal transmission.

I’ve heard that the novel coronavirus may be spread by droplets. Can you explain what this means and what is known thus far about the spread of the virus / how long these droplets may spread the virus between humans/on surfaces?

Yes, SARS-CoV-2 virus spreads most readily in droplets originating from our upper respiratory system and transmitted to others when we cough, sneeze, and even during talking. If you’ve ever smelled onion or garlic on someone’s breath, then you’re inhaling some form of droplets from that person, including any viruses contained in their breath. While the CDC recommends distancing yourself 3-6 ft from someone who is coughing or sneezing, a study from scientists at MIT found evidence that these droplets can travel much farther. Scientists have also found that these droplets that have landed on surfaces can remain active, potentially for hours. If you touch a surface with viral droplets, and then put your hand in your eyes, nose, or mouth, transmission may occur. This is known as fomite transmission. Viruses are not alive, but we refer to them as active or inactive. If you wash your hands with soapy water or 60-90% alcohol, you’ll inactivate the virus. The virus has a lipoprotein (Fat-protein) structure that covers the genetic material to protect the fragile RNA. Also expressed on the outer surface are proteins with specific amino acid sequences that impart a number of functions to the virus, including whether it can bind to proteins in lungs or cardiovascular systems. Washing your hands or applying alcohol can disrupt the lipoprotein coat and inactivate the RNA rendering the coronavirus harmless. This is similar to what is done to inactivated viruses for the development of an inactive vaccine.

Is our healthcare system prepared for this outbreak?

No. We still have few people being tested and have no idea of the spread, rate of infection, and morbidity and death rates from this disease. People who were originally diagnosed with influenza and died have now been found to have died of Covid-19. Our hospitals and clinics are likely to be overwhelmed with severe cases of Covid-19 within a few weeks. In Germany, for many reasons, including the country is run by a scientist (Dr. Merkel is a PhD level physical chemist), has medical care for all, and their physicians who earn an M.D. degree in addition to medical training have scientific training unlike here in the USA, has responded much better to the pandemic than has the USA. Science and evidence based decision making, with scientists who are trained and experienced at solving problems, leads to better outcomes. Unfortunately in the USA our response team is run by physicians, not scientists. Fauci and the rest have done a poor job at protecting the people of the USA. Our healthcare system is a mess in general, and this becomes becomes especially transparent during these times of crisis.

If a package is handled by an infected delivery person and they coughor sneeze on the package, could you theoretically become infected by touching it?

Yes, this would be an example of fomite transmission. A number of variables would contribute to whether you become infected in this way, including the level of infection of the person sneezing, how long the droplets sat on the surface, the volume of the droplet material on the surface of the package, and how much of the droplet you transmitted to your eyes, mouth, or nose. The fomite transmission won’t occur through the skin. A number of studies found evidence that fomite transmisssion is less probable than transmission by breathing-in aerosoled droplets from a cough or sneeze that contain the virus. Be careful, because the SARS-CoV-2 virus remains stable in the air and remain active for hours, perhaps even days, on some surfaces.

How does Covid-19 kill people?

Basically they die of suffocation, even when on a respirator. This virus, SARS-CoV-2 attaches itself to a number of sites in the body using the ACE2 receptor, including in our alveoli in the lungs. This virus also seems to bind to integrins that are expressed throughout the body. This possible pathway of entry is just beginning to be studied. The virus attaches to epithelial cells in the lungs, including in alveoli, where gas exchange occurs (Oxygen comes in, CO2 goes out) and sets up of a dramatic immune response to kill the virus. Along with cells dying from the virus, in the process of our killing the infection, collateral damage occurs where our own cells are damaged or killed. The damaged cells build up in the alveoli. Also liquid begins to seep into the alveoli because the matrix that normally prevents liquid flow has been damaged. Gas exchange stops occurring in the alveoli because of debris and liquid. No matter how much oxygen you pump-in, not enough enters the blood to sustain cellular respiration. If the patient is saved using a respirator, the damaged alveoli will likely suffer from scarring, called fibrosis, with possible ensuing respiratory problems. Scientist and physicians in China report that the those affected by Covid-19 respond well to steroids. Prophylactic and therapeutic low dose steroid oral tablets/inhalers at the earlier stage of COVID-19 and high dose steroid treatment according to the severity of the disease can play important roles in decreasing the fatality and pulmonary fibrosis.

I’ll answer more in an upcoming post.

 

 

Coronavirus Covid-19: What is it, and what can be done to mitigate the spread and effects of this virus?

The Trump adminstration is ill-prepared to respond to the current Covid-19 pandemic and is spreading disinformation about the virus (Thielking, 2020). As of Feb. 23, the CDC had tested just 479 people, not including those who were evacuated from other countries. Testing kits sent out by the CDC nationwide turned out to be faulty, meaning that just 12 labs across the country can currently run tests outside of the CDC. And the CDC didn’t allow the State of California and UC Berkeley to begin testing for Covid-19, even though UC Berkeley trained the scientists who developed the technology (PCR – Dr. Kary Mullis, Ph.D.) underlying the diagnostic tests, for over a week after having set-up a testing center. And the Trump administration allowed untrained, non-garbed federal workers to be directly exposed to known Covid-19 carriers in the Davis, California area. As a result, one patient was likely exposed to one of these workers and wasn’t tested as requested by physicians at UC Davis Medical Center, and now the patient is on a ventilator fighting for her life. Trump appointed morons, such as Chad Wolf, acting secretary of the Department of Homeland Security, said, in a wildly innaccurate statement, the fatality rate is ‘similar to seasonal flu.’ Therefore it is up to you to take good care of yourself during this pandemic, because Trump doesn’t care and Pence is incapable.

Unlike their common-cold-causing viral cousins, the emergent coronavirus Covid-19 can induce a viral-induced inflammatory, immune response throughout many of the patient’s organs. COVID-19 binds angiotensin-converting enzyme 2(ACE2). ACE2 is a receptor, an entranceway for Covid-19 to the airways and alveoli, where O2 – CO2 gas exchange occurs, and blood vessel linings. Death due to massive alveolar damage and progressive respiratory failure can occur.  This is why the Covid-19 epidemic has killed nearly 3,000 people, surpassing the SARS death toll in just weeks. While the death rate for Covid-19 (about 2%) appears to be a fifth of SARS, the novel coronavirus has spread faster (spread factor may be 3-5), although the data for Covid-19 are not yet clear.

For most patients, COVID-19 primarily stays in their lungs, because like the flu, coronaviruses are primarily respiratory diseases – most of the receptors they attach to in our bodies are located in the respiratory system. The virus spreads typically when an infected person coughs or sneezes, spraying droplets that can transmit the virus to anyone in close contact. Best to avoid being near people expressing such symptoms. Coronaviruses typically cause flu-like symptoms, where patients start out with a fever and cough that can progresses to pneumonia or even respiratory failure. Based on early data from China, 80% of the Covid-19 cases are mild and don’t require hospitalization (Zhang et al, 2020).

Initial infection of the Covid-19 coronavirus rapidly invades the two major classes of human lung cells; cells that make mucus and cells with hair-like protrusions called cilia. Mucus, part of the immune system, helps protect lung tissue from pathogens and make sure your breathing organ doesn’t dry out. The cilia cells move the mucus, clearing out foreign agents like pollen or viruses. The physical movement of the cilia may also induce mechanical autophagy (Kim et al, 2017), another means to clear pathogens from our cells. Activated by the presence of a viral invader, our bodies step up to fight the disease by recruiting immune cells to the lungs, including adult stem cells that also have immune cell properties (Maguire, 2020), to clear away the damage and repair the lung tissue. Holes are created in the lung tissue by the immune system’s hyperactive response that also creates scaring that both protect and stiffen the lungs. At this point patients often require ventilators to assist their breathing. The robust inflammatory response also makes the membranes between the aveoli and blood vessels more permeable, that can fill the lungs with fluid, reducing gas exchange and affecting the aveoli’s ability to oxygenate blood. Because the receptor recognition of Covid-19 virus is similar to that of SARS, which affects receptors in the gut, and because a number of patients have reported stomach problems during Covid-19 infection, Covid-19 is likely to present in the small intestine as does SARS when it infects humans (Wan et al, 2020).

So what can be done to avoid and mitigate the effects of coronavirus Covid-19? First, make sure to follow the advice of public health officials, not Donald Trump or his political appointees. These people are numbskulls (Levin, 2019). Second, avoid people with respiratory symptoms such as sneezing, coughing, and labored breathing. Wash your hands frequently, and avoid touching your eyes, nose, or mouth without having washed your hands. Don’t be led to believe that a surgical mask protects you from the virus- it doesn’t. Only a N-95 mask works well (about 95% filtration of virus particle) if properly fitted to the face. Respiratory viruses transmit mostly through droplet spread — which is coughing or sneezing on somebody — or in some cases by fomite transmission, which means you contaminate a surface which another person then immediately touches, and then touches their mouth, nose, or eyes. Viruses can maintain themselves in active state for hours, even days on surfaces, but Covid-19 is reportedly easily inactivated by alcohol.

To mitigate the effects of a virus infection, including Coronavirus Covid-19, you should be eating a mostly plant-based diet that includes significant amounts of insoluble and soluble fiber. I explain this in my book, Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts, but briefly, without you having to read my book which is a tome, here’s why. Soluble fiber is fermented and regulates the innate and adaptive immune systems to better fight viral infection and to better resolve the inflammation induced by the activation of the immune system (e.g. Trompette et al, 2018). And insoluble fiber will upregulate the immune system in a number of ways, including to induce mechanical autophagy that helps to clear infectious agents (Kim et al, 2017). Also, eating a plant based diet rich in many types of antioxidants sets-up an antioxidant cascade (Villanueva and Kross, 2012) that also helps to fight viral infection (e.g. Beck, 2001; Crump et al, 2013). My video update on Covid-19 is here. Let’s all do our part to mitigate the spread and ill-effects of this dangerous virus so that all may be healthy.

 

References

Beck MA (2001) Antioxidants and viral infections: host immune response and viral pathogenicity. J Am Coll Nutr. 20(5 Suppl):384S-388S.

Crump KE et al (2013) Antioxidant Treatment Regulates the Humoral Immune Response during Acute Viral Infection. J. Virology, DOI: 10.1128/JVI.02714-12.

Kim SW et al (2017) Shear stress induces noncanonical autophagy in intestinal epithelial monolayers. Mol Biol Cell. 28(22): 3043–3056.

Levin B (2019) JANET YELLEN: TRUMP IS AN EVEN BIGGER IDIOT THAN HE LOOKS. Vanity Fair, Feb 25, 2019.

Maguire G (2020) Stem Cells, Part of the Innate and Adaptive Immune Systems, as an Antimicrobial for Coronavirus Covid-19. Stem cells, health, technology, Feb 23, 2020.

Thielking M (2020) Trump’s no stranger to misinformation. But with the coronavirus, experts say that’s dangerous. STAT, Feb 26, 2020.

Trompette A et al (2018) Dietary Fiber Confers Protection against Flu by Shaping Ly6c Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism. Immunity. 2018 May 15;48(5):992-1005.e8

Villanueva C and Kross RD (2012) Antioxidant-Induced Stress. Int J Mol Sci. 2012; 13(2): 2091–2109.

Wan Y et al (2020) Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J. Virology, DOI: 10.1128/JVI.00127-20

Zhang et al (2020) Vital Surveillances: The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) — China, 2020. China CDC. http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51

 

 

Stem Cells, Part of the Innate and Adaptive Immune Systems, as an Antimicrobial for Coronavirus Covid-19.

China is in a state of emergency, with 76,936 infections and 2,442 deaths from Covid-19. China’s leader, Mr. Xi has said, coronavirus Covid-19 is the “the fastest spread, the widest scope of infections and the greatest degree of difficulty in controlling infections” of any public health emergency since the founding of the People’s Republic of China in 1949. With 600 cases in S. Korea, parts of Northern Italia now on lockdown because of an outbreak there with 132 new cases, 7 deaths in Iran with Pakistan and Turkey having closed their borders with Iran – people are scarred (NY Times, Coronavirus update, 2020-02-23).

So how do we best fight this spreading, deadly disease? Public health measures are our first line of and most important means of defense in this newly emerging epidemic. The development of new antimicrobials is another means of potentially fighting this infectious agent. And stem cells, and the molecules that stem cells release may be an important new means of developing such antimicrobial therapeutics. Although premature, stem cell treatments in clinical trials for Covid-19 infections are currently underway in China. Why would anyone think that stem cells can fight a viral infection such as Coronavirus Covid-19? Let’s have a quick look why. But first, a quick why  not. Stem cell transplants cause the tissue in the host to age; specifically, the very cells needed to fight the infection, the T-cells, have been found to express markers for advanced aging following bone marrow stem cell transplants (Wood et al, 2016). Therefore the immune system that is needed to fight the Coronavirus infection may be compromised by the stem cell transplant. This doesn’t happen when the molecules from the stem cells are used instead of the stem cells themselves (Maguire, 2019).

Now for the rationale. First, as part of the innate immune system, stem cells release peptides, known as antimicrobial peptides (AMPS) (Esfandiyari et al, 2019) that have been found to fight viral infections (Hsieh and Hartshorn, 2016). Stem cells are activated by viral infections to release these AMPs, and, interestingly, the stem cells themselves are protected from the viral infection and remain normally active cells even when infection affects the tissue compartment in which the stem cell resides (Wu et al, 2018).

Now, here’s some new and very powerful research suggesting that stem cells are part of the adaptive immune system. Drs. Shruti Naik, Ph.D. at NYU and Elaine Fuchs, Ph.D. at Rockefeller University found that if patches of skin in mice were wounded, causing inflammation, then allowed to heal, subsequent wounds in the same patch of skin would heal about 2.5 times more quickly than adjacent, previously unwounded skin. The effect in previously wounded skin could last up to six months given the conditions of the experiment. This functional adaptation was attributed to epithelial stem cells (EpSCs) and did not require a canonical immune response because skin-resident macrophages and T cells were not involved. What the study found was that EpSCs maintain chromosomal accessibility, where the DNA is less tightly packed and open to signals from the damaged tissue, at key stress response genes, activated by the inflammatory stimulus. This epigenetic change in the chromatin allowed, during a secondary inflammatory challenge to the same skin patch, genes in that patch of skin to be transcribed rapidly. While the secretome of skin stem cells has previously been shown to be altered by wounding, the exact nature of changes in the secretome was not reported in this study. However, underlying the memory of the stem cells in this study is Aim2, a portion of DNA that encodes an activator of the inflammasome, a conglomerate of proteins that contributes to the skin’s defense against bacteria and viruses. An emerging area of research is quickly expanding as scientists continue to explore stem cell memory, and the field of immune-stem cell interactions, and stem cells as a part of the immune system. The stem cell functions described here also means that your health is not just genetic. What you do, including wounding yourself or having an infection may have long term consequences to your health. And optimizing your health, including through diet, will minimize the negative consequences of these wounding events or infectious events, including viral infections (Maguire, 2020).

Wu and colleagues discovered that stem cells are hardwired to express antiviral interferon-stimulated genes (ISGs), which help them fight viral infections. Further, β-glucan, a bacterial and fungal cell wall component induced IL-1β release, which was capable of training both hematopoietic stem cell (HSCs) and myeloid progenitors. These conditioned HSCs and myeloid progenitors were able to more efficiently ward off inflammatory challenges when compared to naïve HSCs. Further, IL-1β-trained HSCs exhibited dramatic changes in their energy metabolism, displaying augmented glycolysis and cholesterol biosynthesis, adjustments that turned out to be critical for conferring downstream functional changes in β-glucan-dependent HSC training (Mitroulis et al., 2018). Combine this stem cell training with conditioning of the canonical adaptive immune cells, T-cells, through a high fiber diet that induces a allostatic state (Sterling, 2020) and is pro-resolving for viral infections (Trompette et al, 2018). What I’m describing here is a “systems therapeutic” for “physiological renormalization” (Maguire, 2019) so that the body can better fight the viral infection and more quickly and efficiently resolve the ensuing inflammation that induces much of the damage to the body.

So what can you do now why scientists are working on new antimicrobial therapeutics to fight Coronavirus Covid-19? First, follow public health measures as instructed by your local health authorities. Second, eat well, including a predominantly whole food plant based diet that includes soluble and insoluble fiber that will set the immune system in a state to better fight the infection and resolve the inflammation (Trompette et al, 2018; Maguire, 2020) and may induce mechanical autophagy in the gut to help clear infection (King, 2012). Like stem cells that release a rich variety of antioxidant types (Hong et al, 2019), eating predominantly plants will also provide a rich variety of antioxidants to setup the antioxidant cascade (Villanueva and Kross, 2012) to help quell the viral infection (Beck, 2001; Crump et al, 2013). More on this subject can be found in my book, Thinking and Eating for Two (Maguire, 2020).

References

Beck MA (2001) Antioxidants and viral infections: host immune response and viral pathogenicity. J Am Coll Nutr. 20(5 Suppl):384S-388S.

Crump KE et al (2013) Antioxidant Treatment Regulates the Humoral Immune Response during Acute Viral Infection. J. Virology, DOI: 10.1128/JVI.02714-12.

Esfandiyari R et al (2019) Performance evaluation of antimicrobial peptide ll-37 and hepcidin and β-defensin-2 secreted by mesenchymal stem cells. Heliyon. 2019 Oct; 5(10): e02652.

Hong HE et al (2019) Antioxidant action of hypoxic conditioned media from adipose-derived stem cells in the hepatic injury of expressing higher reactive oxygen species. Annals of Surgical Treatment and Research 97(4):159.

Hsieh IN and Kevan L. Hartshorn KL (2016) The Role of Antimicrobial Peptides in Influenza Virus Infection and Their Potential as Antiviral and Immunomodulatory Therapy. Pharmaceuticals (Basel). 2016 Sep; 9(3): 53.

King JS (2012) Mechanical stress meets autophagy: potential implications for physiology and pathology. Trends in Molecular Medicine, DOI:https://doi.org/10.1016/j.molmed.2012.08.002

Maguire G (2020) Physiological renormalization using systems therapeutics. Future Sci OA. 2020 Jan; 6(1): FSO428

Maguire G (2019) Transplanted stem cells survive a long time: do they make you sick? J Roy Soc Medicine, https://doi.org/10.1177/0141076819851657.

Maguire G (2020) Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts. Berkeley Free Speech Press, Berkeley, CA.

Mitroulis I et al. (2018). Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity. Cell 172, 147–161.e12.

Naik S et al (2017). Inflammatory memory sensitizes skin epithelial stem cells to tissue damage. Nature 550, 475–480.

Sterling P (2020) What Is Health?: Allostasis and the Evolution of Human Design. MIT Press, Cambridge, MA.

Trompette A,  Gollwitzer ES, Pattaroni C et al. (2018) Dietary fiber confers protection against flu by shaping Ly6c − patrolling monocyte hematopoiesis and CD8+ T cell metabolism. Immunity 48(5), 992–1005.

Villanueva C and Kross RD (2012) Antioxidant-Induced Stress. Int J Mol Sci. 2012; 13(2): 2091–2109.

Wood WA et al (2016) Chemotherapy and Stem Cell Transplantation Increase p16INK4a Expression, a Biomarker of T-cell Aging. EBioMedicine. 2016 Sep; 11: 227–238.

Wu X, Dao Thi VL, Huang Y, Billerbeck E, Saha D, Hoffmann H-H, Wang Y, Silva LAV, Sarbanes S, Sun T, et al. (2018). Intrinsic Immunity Shapes Viral Resistance of Stem Cells. Cell 172, 423–438.e425.

More Evidence That A Low-Fat, Plant Based Diet Extends Healthspan and Lifespan: Low Concentration MUFAs Activate SIRT1

Studies that have looked at whether consuming a diet rich in monounsaturated fatty acids (MUFAs) leads to reduced risk of heart disease have shown mixed results. The confusion arose because it makes a difference whether the MUFAs come from plant or animal products. In the first study to separately examine types of MUFA sources in relation to heart disease, researchers found that while MUFAs from plant-based foods such as olive oil and nuts do indeed lower risk, MUFAs from animal products such as red meats and dairy do not provide benefits. The studies were of calorie matched consumption of the different fat types and did not compare low fat versus high fat consumption (Zong et al, 2018). Much evidence has accumulated that low-fat, plant based diets have numerous positive effects in the human body, including shifting the innate and adaptive immune systems to a less inflammatory state, and one that resolves the inflammation more efficiently (Maguire, 2020). In other words, the low-fat, plant based diet allows one to regain allostais through physiological renormalization, where the body is healthy and in a state of optimal responsiveness (Sterling, 2020).

SIRT1, acting through PPAR-α/PGC-1α to upregulate mitochondrial biogenesis, has a wide-range of biological functions including chromatin structure maintenance, cell cycle control, metabolism, and the regulation of healthspan. Regulation of these pathways is partially dependent upon fatty acids, specifically monounsaturated fatty acids (MUFA) .

One study has found that MUFAs do not modulate SIRT1 activity (Feldman et al., 2013). However, this study employed a fixed concentration of 18:1 (100 μM) and used the H3 peptide as a substrate. As Najt et al (2020) have found, MUFAs do not activate SIRT1 at concentrations above 1 μM and do not enhance SIRT1 activity toward the H3 peptide pathway. Thus low-fat, i.e. low concentrations of MUFAs activate the SIRT1 pathway toward the H3 peptide and provide significant metabolic enahncement. These new mechanistic data translate into a recommended regimen of eating plants that are naturally high in MUFAs, and low in other fats, such as saturated fats. Given that low concentrations of MUFAs activate SIRT1, but high concentrations do not, eating refined oils, even if high in MUFAs, should be avoided.

References

Feldman JL et al  (2012) Sirtuin catalysis and regulation. J. Biol. Chem.2012; 287: 42419-42427

Maguire G (2020) Thinking and Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts. Berkeley Free Speech Press, Berkeley, CA.

Najt et al (2020) Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1, Molecular Cell (2019). DOI: 10.1016/j.molcel.2019.12.003

Sterling P (2020) What Is Health?: Allostasis and the Evolution of Human Design. MIT Press, Cambridge, MA.

Zong G et al (2018) Monounsaturated fats from plant and animal sources in relation to risk of coronary heart disease among US men and women. The American Journal of Clinical Nutrition, Volume 107, Issue 3, March 2018, Pages 445–453

True Food Kitchen – An Inflammatory Nightmare

The ever expanding True Food Kitchen (TFK) purports to be “a restaurant inspired by the philosophy that food should make you feel better, not worse.” The TFK corporation is located in Phoenix, Arizona and has about 30 locations across America, all of which are owned by the corporation and are not franchised. According to Forbes, this a rapidly growing chain and its revenue grew 46% in 2017 from the previous year (Stern, 2019). The menu at TFK offers dishes such as kale guacamole, edamame dumplings, Mediterranean quinoa, turkey burgers, and grass-fed burgers. Entrées include a poke bowl, grilled salmon and grilled fish tacos, and charred cauliflower and creamy tomato soup. To some who bobble their heads to the corporate marketing scheme, this all sounds healthy. But let’s have a look beyond the marketing hype, and delve into the nutritional value of some of the TFK menu items.

Say you start your meal with a bowl of Cream Tomato Soup. That bowl of soup will contain 18 grams of fat, 9 of which are saturated fats, and you’ll ingest 1500 mg of sodium. The recommended daily allowance for sodium is 2,300 mg. That one bowl is 65% of your daily allowance of sodium. Now if you order the chicken sausage pizza to go along with that soup, you’ll ingest 32 grams of fat, 12 of which are saturated, and 1610 mg of sodium. That just brought the amount of sodium in your meal to a total of 3,110 mg, well beyond the recommended allowance. You’ve also just ingested 50 grams of fat, of which 21 grams are saturated. The American Heart Association recommends no more than 13 grams of saturated fat per day.  Eating all this fat, including too much saturated fat, will clog your arteries and induce vascular inflammation. The nutritional chart lists coconut as one of the ingredients in the soup, such that some unknown quantity of medium chain triglycerides  (MCTs) will also be present in the soup. All of these fats, including MCTs (Haghikia et al, 2015) can have both acute as well as chronic effects on host inflammatory responses in both the innate and adaptive immune systems (Maguire 2020).  Likewise, the intake of sodium increases inflammation in the innate and adapative immune systems, and induces dysbiosis in the gut (Maguire, 2020).

Maybe you can have the vegetable crudites instead of the soup. If so, you’ve just ingested 63 grams of fat, 7 of which are saturated, and 1500 mg of sodium. This is no better than the soup, and maybe worse given the 63 grams of fat, about twice as much as in the soup. If you’ve eaten the soup and the pizza, 95 grams of fat was consumed in one meal. Eating that one meal has just exceeded the amount of fat one should eat in the entire day.

Well, you say, this meal is better than going to Burger King for a Whooper and fries. Let’s see: a Whopper has 40 grams of fat, 12 of which are saturated, and 980 mg of sodium. The fries have 10 grams of fat, 1.5 of which are saturated, and 330 mg of sodium. So the Burger King meal of a Whopper and Fries has 50 grams of fat, 13.5 of which are saturated, and 1,330 mg of sodium. The TFK meal of vegetable crudites and pizza has 95 grams of fat, 19 of which are saturated, and 3,110 mg of sodium. Thus, the TFK meal has 45 more grams of fat, 5.5 more grams of saturated fat, and 1,780 mg more of sodium than does the Burger King meal.

The point here is that neither of these meals is healthy, and the meal from Burger King is, in some ways, healthier than the meal from True Food Kitchen, a purported “health-driven seasonal restaurant.” TFK is the penultimate marketing scheme brought to you by a corporation that delivers empty words and poor nutrition, with a measure of inflammation, dysbiosis, and clogged arteries full of foamy macrophages .

References

Haghikia A et al (2015) Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. Immunity 43: 817-829.

Maguire G (2020) Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts. Berkeley Free Speech Press, Berkeley, CA.

Stern G (2019) True Food Kitchen: A Growing Restaurant Chain On A Mission. Forbes, Jan. 25, 2019.

 

Immune Therapy for Cancer: Enabling and Engineering T-Cells

T cell therapies are revolutionizing cancer treatment by achieving long-lasting remission in cancers, such as melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, and leukemia and lymphoma. An important function of the immune system is its ability to discern between normal cells in the body and those it sees as “foreign.” This lets the immune system attack the foreign cells, including cancer cells, while leaving the normal cells alone. To do this, it uses “checkpoints.” Immune checkpoints are molecules on certain immune cells that need to be activated (or inactivated) to start an immune response. Cancer cells sometimes develop the means to use these checkpoints to avoid being attacked by the immune system. But drugs that target these checkpoints have much promise as cancer treatments. These drugs are called checkpoint inhibitors, and first originated from the work of Prof. Dr. James Allison, Ph.D. at UC Berkeley. Dr. Allison would later be awarded the Nobel Prize in Physiology or Medicine for this work.

Importantly, checkpoint inhibition is a new paradigm in treating cancer, allowing the immune system to operate normally where T-cells can once again attack the cancer cells because of the drug therapy. Unlike previous methods, checkpoint inhibitors don’t work directly on the tumor or over boost the immune system. The checkpoint inhibitors simply institute “physiological renormalization” (Maguire, 2019), restoring normal T-cell physiology. The checkpoint inhibitor works by using a monoclonal antibody, a protein, that blocks the cancer cell signaling to the T-cell’s checkpoint mechanism. Normally the cancer cell is sending a signal to the T-cell that “fools the T-cell into thinking” that the cancer cell is a normal cell and one that should not be attacked by the T-cell. Important to the T-cells acting to kill the cancer cells, even when the patient is taking checkpoint inhibitors, is a plant based diet rich in fiber. The T-cell activity on the cancer cells is facilitated by fiber consumption, allowing the checkpoint inhibitor to work better to destroy the cancer cells (Worcester, 2019). I write about this in my new book, “Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts.”

While Dr. Allison’s work on T-cells began in 1985 at Berkeley, the same year I came to Berkeley and joined the same department, Molecular and Cell Biology, Prof. Dr. Jennifer Doudna, Ph.D. at UC Berkeley would begin work in about 2010 on a technology as revolutionary as that of Dr. Allison. As co-inventor of CRISPR-cas9 technology, along with Prof. Dr. Emmanuelle Charpentier, Ph.D of the Max Planck Institute in Germany, Dr. Doudna invented a technology that would allow cells to be engineered by editing their DNA. Using this methodology, T-cells can now be made to inherently avoid the cancer cell’s evasion mechanisms using their ability to activate the checkpoint in T-cells to stop the T-cell from attacking the cancer. Using the CRISPR-cas9 methodology, the T cell receptor (TCR) complex located on the surface of T cells, which is central for initiating successful anti-tumor responses by recognizing foreign antigens/peptides bound to MHC-molecules, the patient’s own T cells are genetically engineered to express a synthetic (transgenic) TCR that can specifically detect and kill tumor cells. CRISPR-cas9 engineered T cell therapies are just beginning to revolutionize cancer treatment by achieving long-lasting remission in blood-related cancers, such as leukemia and lymphoma. These therapies involve removal of patient T cells, “reprogramming” them to attack cancer cells, and then transferring them back into the patient. Targeted gene inactivation (knockout) using CRISPR-Cas9 can enhance T cell activity and has the potential to expand cell therapy applications (Hamilton and Doudna, 2020).

Until the study of Stadtmauer et al (2020), whether CRISPR-Cas9–edited T cells would be tolerated and thrive once reinfused into a human was unknown. Stadtmauer et al (2020) present data from a phase 1 clinical trial (designed to test safety and feasibility, but not efficacy) on the first three cancer patients treated with CRISPR-Cas9–modified T cells. Given one infusion of the engineered T-cells, the three patients did not experience the feared “cytokine storm” that patients have previously experienced in clinical trials using genetically altered cells. The authors found a high-level engraftment and long-term persistence of the infused CRISPR-Cas9 engineered T cells in one of the patients who was carefully analyzed 4 months after infusion. The procedure uses lymphodepleting chemotherapy, and therefore the negative side-effects associated with this procedure were observed.  Although only three patients were treated, these findings represent an important advance in the therapeutic application of gene editing and highlight the potential to accelerate development of cell-based therapies, however experience with more patients given infusions of CRISPR-engineered T cells with higher editing efficiencies, and longer observation after infusion, will be required to fully assess the safety of this approach.

References

Hamilton and Doudna (2020) Knocking out barriers to engineered cell activity. Science, DOI: 10.1126/science.aba9844.

Maguire G (2019) Physiological renormalization using systems therapeutics. Future Sci OA. 2020 Jan; 6(1): FSO428.

Sanders R (2018) UC Berkeley research led to Nobel Prize-winning immunotherapy. Berkeley News, Oct.1, 2018.

Staudtmauer EA et al (2020) CRISPR-engineered T cells in patients with refractory cancer. Science, DOI: 10.1126/science.aba7365

Worcester (2019) Diet appears to play an important role in response to anti-PD-1 cancer immunotherapy. MD Edge, March 1, 2019.

Why Are So Many People Leaving Texas – And Why Are Most of Them Coming to California

Texas ranked third in the United States for the number of residents moving out of state (467,338) in 2017. The most popular out-of-state relocation destination for Texans was California (40,999). Let’s put this exodus from Texas into perspective vis-a-vis California.

Texas had a population in 2017 of 28.32 million. On a per capita basis then, the percent of people leaving Texas was 0.016. California lost just over 661,000 people to domestic migration in the 12 months ended in July 2017. Given California’s population in 2017 of 39.4 million, the per capita basis of people leaving California was 0.016, approximately the same rate as in Texas.

The reasons people leave California have received considerable national attention, and the cost of living coupled with our progressive environment are two key reasons why low income, conservative people without college degrees are moving to Texas. On the other hand, high income, educated Texans move to California where they will enjoy the opportunity to prosper in the fastest growing economy in the USA, where most innovation in the US occurs, and where culture and beauty abound.

Simple cost of living averages do not address the quality of life, and the quality of the goods or services available, and Texas does not offer anything close to what California offers. Consider, the average lifespan in TX- 78.5; average income in TX – $59,206; 18.5 percent of Texas residents, aged over 25 years, held a Bachelor’s degree; and the suicide rate was 13.0 per 100,000 in Texas. Whereas in California, average lifespan in CA – 80.9; average income in CA – $71,805; 21.3 percent of Californian residents, aged over 25 years, held a Bachelor’s degree; and the suicide rate was 11.1 per 100,000 in California. Moreover, California is the world’s fifth largest economy, surpassing many countries with much larger populations. Texas has the 10th largest economy in the world. Whereas California leads innovation in the world, economically and socially, Texas is known for oil and finance, stultifying old industries, and is socially regressive led by Republican politicians like Rafael Cruz. California per-capita GDP was $58,619 in 2016, whereas per capita income for Texas was $29,525 in 2017. But those are numbers, and we must also consider quality from a cognitive point of view.

Drive through Houston, TX, the state’s largest city, and you’ll be aghast by the foul smells in the air, tacky neighborhoods where strip clubs stand next to churches, the lack of city planning, an overabundance of superfund clean-up sites, and the general ugliness of the area. Many other cities are worse, and once beautiful Austin now suffers from a lack of strong zoning rules that means tall, ugly skyscrapers now tower over the University of Texas campus. Drive through the state, and most of what you see is dull and banal, and often ugly.

Now drive through California. That drive can include sights of the world’s tallest trees, Redwoods, the largest alpine lake in all of North America, Lake Tahoe, and the world’s most innovative university, UC Berkeley, that is surrounded by mountains and trees, and not skyscrapers, except of course the university’s beautiful Campanile. The drive can continue across the Golden Gate Bridge, into the most beautiful large city in the US, San Francisco, and then onto the largest trees in world, the giant Sequoias in the beautiful Sierra Nevada Mountains close to the highest mountain in the continental USA, Mt. Whitney. Head down south along the dramatic Big Sur coastline to Santa Barbara and enjoy California wine in America’s Riviera, and then continue south to Los Angeles, where the world’s best symphony performs in the world’s best concert hall. A drive into the mountains surrounding Los Angeles brings us upon Mt Wilson where anyone can peer though the giant 100 inch telescope where Nobel Laureate, Dr. James Hubble, Ph.D., discovered the expanding universe. Finish the trip in San Diego for relaxation, surfing, and fish tacos in a beautiful city nestled on the Pacific with the best weather in the USA and a history that dates back to 1769.

These are just a few of the reasons why Texans are fleeing their state and moving to California. All are welcome in California.

NAD Supplements : More Reductionist Quackery for Profit

NAD (nicotinamide adenine dinucleotide) is a molecule that supports basic cellular function and metabolism in a number of important ways, including protecting our DNA (Sambeat et al, 2019), converting food into usable energy and regulating our sleep-wake cycles. NAD decreases as we age, and low levels of NAD are associated with increased risk of heart disease, Type 2 diabetes, Alzheimer’s disease, and accelerated aging. Decreased NAD levels in our bodies can result from 1. the body making less NAD as we age, 2. more NAD being used in the body as we age because of aged related stress and damage, including oxidative damage, and 3. poor diet, including increased alcohol consumption as we age. Some excellent work has found that SIRT, a molecule dependent on NAD to be synthesized in our bodies, is involved in preventing stem cell aging that even prevents a pro-inflammatory state of the macrophages in our innate immune system (Luo et al, 2019), and also prevents aging-associated inflammation and insulin resistance (He et al, 2020).

There are two forms of vitamin B3, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), receiving attention for their ability to increase NAD levels. In mice studies, NR and NMN increase NAD levels, while some newer, small studies suggest the same is found in humans. Sounds great, right? NAD is important to a number of normal cellular functions and keeps some of our cell types young, so taking “NAD supplements” must be healthy and will slow the aging process. Where can I buy this stuff?

If you’ve read my book, “Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts,” you’ll know to ask a few important questions before running off to the store to buy this supplement. And, after having asked those few questions, you’ll know the NAD supplement offered at your local store or online is a waste of money and potentially dangerous.

First, assuming that what you buy is actually the NAD supplement, and that is a big “if” given the supplement industry is rife with fraud, the increase in the concentration of NAD in blood cells shows that NR works to raise the concentration of NAD, but it is not evidence that having more NAD will increase life span or health span in humans, or even improve cellular function of any particular group of cells. We also don’t know how much NAD was getting into and affecting muscles or other organs, and that is difficult to measure. One study, sponsored by one of the NAD supplement companies,  found no correlation between the age of subjects and the level of NAD in their muscle and brain tissue (Elhassan et al, 2019). Therefore blood may not be an indicator for NAD throughout the body; not serving as a biomarker for the therapeutic effects in other tissues. The same study by Elhassen et al found that the supplement didn’t help improve the subject’s grip strength, muscle blood flow and metabolism, but concerningly increased a protein thought to be increased in type 2 diabetes and insulin resistance.

We also need to understand what levels of NAD are healthy. Is too much NDA dangerous? Some studies found that it is.  Deterioration of metabolic health, and dysfunction in fat cells along with an induction of glucose intolerance were found in those mice fed a large quantity of NAD supplements (Shi et al, 2019). Other studies in mice report similar results (Kourtzidis et al, 2018). Pools of increased NAD may also be a risk factor for cancer (Hong et al, 2019). And all NAD supplements are not the same in their actions, and supplements don’t act the same way as do the natural, endogenous precursors to NAD (Sambeat et al, 2019).

Again, if you’ve read my book, you know to ask the question, “compared to what?” If you go to Clinicaltrials.gov to see the basic study design of the trials testing NAD supplements, you’ll discover a level of stupidity in trial design that boggles the imagination. What is the NAD supplement being compared to? In none of the studies is diet being controlled for. And we know diet is very important for the levels of NAD in the body. For example, vegetables such as broccoli and cabbage contain 0.25–1.12 and 0.0–0.90 mg NMN/100 gm, fruits like avocado, tomato contain 0.36–1.60 and 0.26–0.30 mg NMN/100 gm, whereas raw beef has 0.06–0.42 mg NMN/100 gm. So if people are eating a poor diet, like most Americans, their natural supplementation of NMN will be low and easily raised by a NAD supplement. Further, without controlling diet in the NAD supplement group versus placebo group, especially in trials with small numbers of subjects, diet can easily confound the data. Moreover, in at least some of the studies, the placebo group was taking a sugar pill. Sugar has numerous deleterious effects within our different organs and microbiome, all of which can impact the clinical trials. The important clinical trial would be to compare the NAD supplement group with a group eating a whole food plant based diet. But given you can’t patent a whole food plant based diet, the monetary incentives are not in place to perform such a study. The mentality of all such gimmicks is to find that one “magic pill” to make me healthy and young, a reductionist strategy appealing to the lazy consumer, and to companies and providers who make a lot of money selling quackery. I have more to say about NAD and other supplements in my book. Hope springs eternal, but so do stupidity and greed.

References

Elhassan YS et al (2019) Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial. BioRxiv, doi: https://doi.org/10.1101/680462

He M et al (2020) An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance. Cell Metabolism, DOI:https://doi.org/10.1016/j.cmet.2020.01.009.

Hong SM et al (2019) Increased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level. Cancer Sci. 2019 Feb; 110(2): 629–638

Kourtzidis I.A., Dolopikou C.F., Tsiftsis A.N., Margaritelis N.V., Theodorou A.A., Zervos I.A., Tsantarliotou M.P., Veskoukis A.S., Vrabas I.S., Paschalis V., et al.  (2018) Nicotinamide riboside supplementation dysregulates redox and energy metabolism in rats: Implications for exercise performance. Exp. Physiol. 103:1357–1366. doi: 10.1113/EP086964.

Luo H et al (2019) Mitochondrial Stress-Initiated Aberrant Activation of the NLRP3 Inflammasome Regulates the Functional Deterioration of Hematopoietic Stem Cell Aging. Cell Rep. 26(4):945-954.e4.

Sambeat A et al (2019) Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage. Nature Communications volume 10, Article number: 4291

Shi W et al (2019) High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet.  Nutrients. 11(10).

The Origins of the Biotechnology Industry – Cetus Corp. in Berkeley, California

Contrary to a belief by many because of a false narrative often propagated by venture capitalists, the first biotech company was Cetus Corporation of Berkeley, CA, not Genentech of South San Francisco, CA. Cetus was co-founded by UC Berkeley faculty member, Dr. Donald Glaser, Ph.D., a Nobel Prize awardee. Amongst other accomplishments, Cetus developed Betaseron and Proleukin, and the PCR methodology that it out-licensed. Cetus was formed in 1971, five years before the inception of Genetech in 1976. Venture capitalists had no significant involvement in Cetus. Kary Mullis, who attained his Ph.D. at Berkeley, developed PCR while at Cetus, and is the only biotech employee to have been awarded the Nobel Prize. Imagine the world without PCR. Without PCR we wouldn’t have : DNA cloning for sequencing, gene cloning and manipulation, gene mutagenesis; construction of DNA-based phylogenies, or functional analysis of genes; diagnosis and monitoring of hereditary diseases; amplification of ancient DNA;analysis of genetic fingerprints for DNA profiling (for example, in forensic science and parentage testing); and detection of pathogens in nucleic acid tests for the diagnosis of infectious diseases (Kaunitz, 2015).

Although PCR has transformed the world, the technology does have inherent errors that constrain the interpretation of any analysis using the methodology. And with healthcare driven by profit motive, the use of PCR by commercial interests in the healthcare space is rife with fraud and incompetence, often making the use of this technology a detriment to health. I detail many of the problems with PCR based diagnostics in my new book, Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts(Maguire, 2020).

References

Bains W (2020) Genentech was not the first biotech company. Nature, doi: 10.1038/d41586-020-00187-1

Kaunitz JD (2015) The Discovery of PCR: ProCuRement of Divine Power. Dig Dis Sci. 2015 Aug; 60(8): 2230–2231.

Maguire G (2020) Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts. Smashwords, Los Gatos, CA.

The USA – No Democracy Means Poor Health and Poor “Healthcare”

You can think of the USA as having five principle institutions to govern us: 1. The Presidency, 2. The House, 3. The Senate, 4. The Judiciary, and 5. The Free Press. Unfortunately, none of these are democratic institutions. The least democratic of the five is the Judiciary. Judges are nominated by the President, who is voted-in by the undemocratic Electoral College, and approved by the Senate, an institution that represents land and not the people. For example, California has nearly 40 million people and two senators, whereas Montana has about 577,000 people and two senators. That’s one senator per 288,000 people in Montana, and one senator per 20,000,000 people in California. The House is more representative of the people than is the Senate. California has 53 representatives in the House, one representative for every 754,000 Californians, whereas Montana has one representative in the House, one representative for every 577,000 Montanans. Considering the Press, much of it is owned by the rich, particularly billionaires (Vinton, 2016). Even PBS is often a shill for the wealthy given it is a private corporation funded by billionaires (Hiltzik, 2014). If people are billionaires, what do you think they’re most interested in? Answer – money, of course. Plutocrats living in a society of trickle down economics is destructive and was brought to us in its current form by Ronald Reagan and his revolution for the rich (Hiltzik, 2019). The continued deregulation of the rich means that they own and control almost everything, including some public universities such as Florida State University (Strauss, 2011).

The privatization and deregulation of our food supplies, drug companies, physicians, and hospitals is literally killing us. And the press, being largely controlled by the wealthy, doesn’t care, or can’t say much about it, as long as their billionaire owners are making money. Even the so-called non-profit “patient advocacy” groups are paid for and controlled by the billionaires, working for the rich so that you’ll take more drugs that don’t work (Kopp et al, 2018). This is all detailed in my new book, “Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts,” where I include well over 2,000 references that give the details of the lack of health and “healthcare” in American society. If you want to learn why about 90% of American are sicker than they should be, why most of us will die young, and what you can do about it, read my new book.

References

Hilzik M (2014) How PBS sold its soul to a billionaire donor. LA Times, Feb. 17, 2014.

Hiltzik M (2019) Column: America is falling out of love with billionaires, and it’s about time. LA Times, Feb. 1, 2019.

Kopp et al (2018) KHN launches “Pre$cription for Power,” a groundbreaking database to expose Big Pharma’s ties to patient groups. Kaiser Health News, April 6, 2018.

Maguire G (2020) Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts. Smashwords, Los Gatos, CA.

Strauss V (2011) Did FSU let billionaire buy professorships? May 16, 2011.

Vinton (2016) These 15 Billionaires Own America’s News Media Companies. Forbes, June 1, 2016.