The Bacteria in Your Gut Define Your Real Age

The Bacteria in Your Gut Indicate Your Real Age


No kidding. How old you are "biologically" can be understood by the changes that happen to the "biome" in your gut. Let's explain. For starters, we all have about 100 times the number of cells in our gut compared to our entire bodies. 100 times. Our gut doesn't just digest the food we eat, it has an immune function that is only now becoming more understood. And real understanding comes from recognizing that our brains, our immune system, and our guts are all on a team together. Your brain will never be happy if your gut isn't happy. How so?

For starters, a healthy gut needs to be mostly low oxygen-consuming "anaerobic" bacteria. That might be the crux. Your gut cells lining your intestinal lining are formed deep in the depths of your villi in your intestine: the "crypts of Lieberkühn". A healthy human gut lining uses a ton of oxygen with the paradoxical effect of making very little available inside the gut. That results in more "anaerobic" bacteria in your gut, which results in the making of more short-chain fatty acids, the major one being beta-hydroxybutyrate. In this desired, balanced world, we make all the signaling messages for us to produce a balanced set of T-reg cells (the T cells that boss around your immune system and balance it) and macrophages (the garbage trucks that clean up cellular gunk).


This is where it gets fun and very interesting. The Western diet that we now eat, characterized by high saturated animal fat, no fiber, and too much protein, changes the way energy is consumed in our gut lining, thereby changing the amount of oxygen getting into the gut (much more gets in) thereby changing the beneficial bacteria to not-so-good bacteria. These changes lead to different levels of T-reg cells, different levels of beta-hydroxybutyrate, different levels of macrophages, different levels of neurotransmitters in our brain. Throw in antibiotics that we take orally and which decimate huge populations of gut bacteria and add a good dollop of sugar and a whole raft of artificial poisons: no wonder we are a mess. I've carefully selected some reading in the references you can do a deep dive into. Click on some links and spend an afternoon in the dizzying depths of your suffering gut, your aging brain and your faltering immune system.

But let's just look at some of the clinical implications for you. A study from Cornell two years ago showed that midlife folks in America who eat a Mediterranean diet, (more vegetables, fish, fruits, legumes, olive oil, less red meat, animal protein, saturated fat, tiny bit of alcohol) can be shown to develop less amyloid in their brains and have better cognitive performance.

A study from Wake Forest with folks with mild cognitive impairment versus controls show in an immediate change in gut flora, beta-hydroxybutyrate and central nervous system markers of Alzheimer's as determined by spinal tap) when diet is changed to a "Modified Mediterranean ketogenic diet" (which meant it was high fat with olive oil and less carbs) versus the American Heart Association diet.


There is an explosion of interest in this idea. Lots of papers are being published. You can correlate the amount of beta-hydroxybutyrate in your gut and blood with your cholesterol forming amyloid plaques. The biome of your colonic bacteria is correlated with their oxygenation. Eating more olive oil makes for better synapses. If you read one extra paper, read the Frontiers in Endocrinology about gut bacteria and your brain.

All these advances are now being commercialized. You can measure your "biological age" by measuring your gut bacteria in relationship to the health of your white blood cells and your genetic markers of mitochondrial health. As you age, your ability to make a healthy "redox" environment in your mitochondria deteriorates. Your production of NAD+ drops and your SIRT proteins, tasked with keeping your DNA properly protected, disintegrates. A company by the name of VIOMEwill happily tell you your "biological age" compared to your calendar age based on whether your diet, your gut bacteria, and your blood markers are in healthy ranges. Got $ 300 looking for a brand new test?


WWW. What will work for me. I've been taking NAD-riboside and metformin to align with Sinclair's admonitions. That should be helping. And I make myself an Instapot of legume curry every week. I use that to eat less animal protein. We have a giant salad made with olive oil every night (mostly). I should be the picture of virtue. Well, my Viome test came back raunchy. I'm biologically "older" than my calendar age. Bummer. Faced with data, I do the obvious. I attack the validity of the test. And then I look at the brownies in the fridge and have an apple instead.


References: Science, Neurology, Lancet, Nature, Nature Reviews, Aging Cell,Frontiers Micro,


Pop Quiz

1. Your colon has more or fewer cells in it than the rest of your body? T or F.                    Answer:   True, 100 times more. Trillions and trillions more.

2. The beneficial cells in your gut depend on what sort of environment?                             Answer: low oxygen, high fiber, not too much protein, sugar, or animal fat and please, please, hold off on the antibiotics and artificial .....everything.

3. Can you name the immune cells that direct your immune system that depend on eating a Mediterranean diet? Answer: T-reg (aka bossy pants)

4. Can you identify the elements of a Mediterranean diet?                                      Answer: More vegetables, more whole grains, fish, fruits legumes, and LOTS of olive oil, with less animal fat, protein sugar)

5. What short-chain fatty acid comes out of your colon that is wonderful brain food?                        Answer: beta-hydroxybutyrate, made when you eat olive oil, made when you fast for more than 12 hours, made when you tip the balance of nutrients to more plant away from refined grains, sugars, and animal products)


Monolaurin: Better than you Thought

Monolaurin - Better than you Think


You've heard of some of the back and forth about coconut oil, but have you heard of monolaurin? It turns out to be quite an interesting compound. Coconut oil is about 50% lauric acid. It is the 12 carbon chain in coconut oil that has a melting point just at your skin temperature, so is ideal for being a foundational fat for many beauty products. The other two main ingredients are shorter fatty acids being 10 and 8 carbons long. They are liquid at room temperature so make up the ingredients of MCT oil. When you eat coconut oil or any coconut, you will make some monolaurin in your natural digestion of it. But the actual product monolaurin is the product of binding lauric acid with glycerin, the otherwise foundation of "triglycerides". It's easy to manufacture and has its own powerhouse of benefits.


Here are some of them. For example, the scourge of MRSA in hospitals with its terrible antibiotic resistance has been found to be markedly helped by taking monolaurin in addition to vancomycin (in lab rats). Mortality dropped from some 88% to about 40% when monolaurin was added. That's quite a benefit.


But let's talk autoimmune (AI) illnesses. Here is a Gordian knot that we have a terrible time controlling. What is the most common autoimmune illness? If you consider eczema to be an autoimmune illness, that's it! Some 25% of children and 10% of adults have it compared to Rheumatoid Arthritis, the "most common" mainline AI disease. You can treat eczema with a new antibody (dupilumab) targeting IL-4 and IL-13, two inflammatory cytokines meant to attack bacteria and viruses but get mistakenly turned on to attack your skin. When you give folks with eczema dupilumab, eczema gets better and the genes that are turned on in eczema get turned off. Magic. Works. Expensive.


Did you know you might get the same effect with monolaurin? There is precious little published research so I'm going on single-author and personal experience. I've had several clients spontaneously report to me that monolaurin helped their eczema. "When I take it, it goes away! When I stop, it comes back." The stuff is way too cheap. It will never be funded for research in our current medical world. What I suspect is going on is that the secondary skin infections that occur with eczema have staph and strep bacteria in them. Two forces at work. The monolaurin probably inhibits the bacterial infections enough to be helpful. And the emollient quality of the oil increases the skin moisture and decreases skin cracking and opening up to allow bacterial invasion. That's my hypothesis. And support for that might be from its activity against candida as well. In that study, IL-1, another inflammatory cytokine was shown to be markedly downregulated with monolaurin.


Dr. Jon Kabara has been the inventor and chief promulgator or monolaurin and sells it under the label Lauricidin. His list of testimonials on his web site is about as good as you can get to see folks detailing how it has helped their skin. Of note, this is the classical unresearched scenario with only high-pressure testimonials and no randomized controlled trial. But with a compound that is GRAS (generally recognized as safe) with exceedingly rare allergy or toxicity, trying it isn't so awful for you.


WWW. What will work for me. I was so startled by my client who had such an amazing response to it, I wanted to read more. I get the conundrum of no research, but for the obvious reason that it's way, way, way too cheap. There isn't enough money in it. And there is a reasonable biochemical hint in some research that there are plausible reasons for how it might work. I had a horrible skin infection on my knees with dozens of abscesses back in the 1950s in India. I suspect monolaurin would have helped that. That would possibly be called erysipelas today. I remember as a 6-year-old in boarding school in India treating it with daily Mercurachrome (iodine). Yuck. Glad that's over.


References: Healthline,J Food Med, Jr All Cl Immun, Peer Journal,


Pop Quiz


1. What is monolaurin?                            Answer: Simple combination of the 10 carbon chain called lauric acid that comprises 50% of coconut fat with glycerin.

2. Can you make it naturally?                  Answer: Well yes. It's in mother's breast milk, in tiny amounts.

3. Is there any research on it to explain how it might work?                  Answer: A few tiny studies that show some modest effect in rats.

4. And, anything else?                              Answer: Well, yes. Monolaurin appears to help prevent candida and has been shown to down-regulate a variety of inflammatory cytokines.

5. Where can I get it if I want to give it a whirl?                          Answer: Look up Lauricidin and buy it from the original developer of it. Or from any of 100 other sellers. I suspect you have to try the dose that works for you. And I would love to hear your story of how it helped you.


Melanotan II - Getting a Sexy Tan

Melanotan II -Get a Really SEXY Tan


Melanocyte stimulating hormone (MSH) is what makes you tan. Nifty, huh? Can you imagine tanning without the sunburn? It turns out MSH has a ton of other features, like all hormones, that are even more important than tanning. It plays a critical role in gut integrity, chronic pain, chronic fatigue syndrome, and CIRS (Chronic Inflammatory Response Syndrome). This shouldn't be surprising as all these molecules come from chopping up POMC (proopiomelanocortin) in the pituitary in one piece or another. There are some 17 pituitary hormones that come out of POMC, depending on what pieces it is cleaved into and where it is made. Altering POMC's pieces for variable effects has been a hot topic since the 1960s.  Tanning is just one.  


With that in mind, tanning would be a nice effect, if you could control it. Researchers at the University of Arizona, trying to accomplish that, embarked on trying to get the tanning component isolated. They basically abandoned the idea in 2002 as there were too many "adverse" side effects: nausea, moles instead of tan, yawning, and stretching. But in the meantime, rats given it in the lab demonstrated increased sexual activity. One of the researchers gave himself a dose (and made a dosing error, getting a double dose) and had a subsequent 8-hour erection. Really!


With that discovery, various companies fought over patent rights but a company called Palatin has emerged with a slightly altered fragment called bremelanotide. It has been FDA approved for female sexual arousal disorder under the brand name Vyleesi. It is now the first drug on the market aimed at women. It is the same thing as PT-141, used in men for erectile difficulty and available from many peptide houses that make it in various forms. Recent interest in intranasal administration makes it much easier to take than an injection. But all forms do have some dosing issues with nausea being an issue with some folks.  Injections can be altered in amount whereas a nasal spray is trickier to alter.

But what about the tanning? It doesn't take too much time on Google to find images of folks who have taken "too much melanotan II" to think perhaps that isn't a good idea. No commercial company will touch it, for all those reasons.

But various peptide houses still sell it as a sexual enhancer. And if you don't get nauseated too much, and you can stand the stretching and yawning feeling, it works. Men do get erections from it that nothing else appears to provide. Is it a nitch compound that can be used safely? I would advise against it. You are messing with your "gearbox" when you stimulate all those receptors the POMC system plugs into. The long term effects are just a little too unknown.

But isn't it nice to have a nice, flakey topic in the middle of a pandemic, election chaos, social angst, and general, all-around stress? It's a hard time. We need Arlo Guthrie to sing, "Hard Times Come Again No More." Listen to that as my take away. Music and art are good for your soul.


www.What will work for me. I see my dermatologist enough to not want any more moles or skin disorders. I don't need to tan. And it sounds like the PT-141 version is a safer product for men and women. The nasal administration form only comes in one dose and is more difficult to alter for those who get nausea as a side effect. We all need human touch and "skin-time" in these Hard Times. Let's get through them, with some kindness and tolerance for one another.


References: Wikipedia, Wikipedia - POMC, PLOS1, BBA, BMCNeurology,


Pop Quiz

1. What is Melanotan II?                     Answer: The original fragment of MSH that was initially researched, trying to find "tanning with a shot" instead of sunlight.

2. Did it work?                                Answer: yes, but variably with too many side effects.

3. What were the side effects?                          Answer: Irregular tanning with the emergence of extra moles, nausea, stretching and yawning.

4. Does it work on anything else?                         Answer: Well yes: it induces an increase in sexual desire in men and women.

5. Is there a safer alternative?                       Answer: Yes. Bremelanotide or PT-141 is on the market as Vyleesi and works on sexual desire in men and women. Vyleesi doesn't make you tan. It works centrally and allegedly doubles the likelihood of a satisfactory response.



Wearing Eyeglasses May Protect your from Covid-19

Eyeglasses Protect you from Getting COVID-19


If you haven't heard this on the news, you might enjoy the concept. A study of 300 Chinese admitted with COVID in Wuhan found that only 16 wore eyeglasses whereas some 31% of the population there have severe myopia (very common in China) and need eyeglasses. If every group of the population had equal risk, one would have expected roughly 100 folks in the cohort. That suggests an 80%, roughly, reduction of risk by wearing eyeglasses. That's huge.

But is it real and should I go out and buy eye-protection? The limits of the study are that it was observational, not prospective. (Bless the heart of the lowly ward technician whose responsibility it was to inventory patients' possessions and made the observation.). And, the researchers used data from population studies in the area to come up with their 31% having myopia. They didn't check the vision of all the patients admitted. Ok, point taken.

What does this speak to? Here is my take on the implications. I believe this is another piece of evidence that the primary mode of infection is airborne particles, whether they be droplets that fall to the ground in a minute or two (sneeze or cough) or aerosolized tiny particles (talking, singing) that float around a little longer. Either one will do it. Which is the worst has huge implications for the safety of health care workers as it takes a MUCH higher level of protection to guard against the aerosolized particles. There have been many nurse protests about lack of adequate PPE for that reason. And there have been many deaths of health workers to support that fight.

What isn't said in the article is that there is less and less evidence that COVID-19 is primarily spread by contact with surfaces. On a dry surface, the airborne particle, which is primarily water, dries out. When it is dry, the 10,000 virus particles desiccate and fall apart. They stop being infectious. It hasn't been extensively studied, but surface contamination is not the primary means of spread. Cardboard, paper, cloth, your paper mail are all forms of dry, water-absorbing surfaces.

Your eyes are moist and wet. They drain right into your nose through your tear ducts. Your nose has lots of receptors for the virus to bind to and get its lifestyle started.

WWW. What will work for me? I naturally wear glasses. The study considered that folks who wore glasses more than 8 hours a day were in the safer group compared to less use of glasses. If I didn't have glasses, with this evidence, I would try and ramp up my use of dark glasses when out in public. I am making a real effort to keep my hands off my face and my eyes, something difficult to do in ragweed season when my eyes itch. I'm better at taking an antihistamine just to control the itching for these few weeks. Would I advise you to wear glasses indoors when outside of your own home? I would. It's not that hard to do. I still take wipes with me into public restrooms and use hand sanitizer when I touch surfaces. I've stopped wiping my mail or making my packages sit outside for a day. I do wear a mask when I leave my home, but only when within 30 feet of people or in closed buildings.

References: AJMC, New York Times, JAMA Ophthalmology, UptoDate, J Virology


Pop Quiz

1. What did this study show? Answer: In Wuhan, China a group of 300 patients had an 80% underrepresentation of COVID in eyeglass wearers.

2. Was the study constructed in a fashion to consider good, reliable medical evidence? Answer: No. It was observational, not prospective, vision was measured to see who needed eyeglasses and the incidence of eyeglasses was projected from prior, earlier studies of the population. Still, not bad.

3. What are the "implications" of this study, not yet supported by hard science. Answer: Another piece of the puzzle that supports the primary spread is moist, water-laden particles floating in the air that hit your moist eye, or nose or mouth when you breath in air contaminated with the COVID-19 from someone else.

4. Can a person make tiny droplets when just speaking? Answer: Yup.

5. When do you spray out even more particles? Answer: Singing, shouting, speaking loudly. Amp it up with coughing and sneezing.

Have an idea for next week? Write us!


Reverse Coronary Artery Disease with Pycnogenol and Centella

Reverse Atherosclerosis? Really!

We have been chasing this Holy Grail for years. Is there a way to turn off the inflammatory process that causes plaque to form in your arteries? Now that we can measure calcium buildup in arteries with ultrasounds and CTs of the heart, we have begun to explore other avenues that start with prevention.

The very first evidence came out in the 1970s and 80s with Ornish and Pritikin encouraging folks to eat less animal protein. Their early work was encouraging but going without meat in America can be a challenge. Esselstyn is now the current standard-bearer of this concept, and he has a similar approach: vegan, no fat.

More recently, Dr. Gundry has focused on the damage caused by lectins in our food and how their avoidance can reduce the inflammation of arteries and reverse "endothelial dysfunction". He hasnow published, and we reviewed, his research showing that the combination of fish oil, pycnogenol and grape seed extract markedly reduced that first step of damage: endothelial dysfunction. He used 50 mg of Pycnogenol.


Now,this week's headline study ups the ante to 150 mg a day of Pycnogenol (Mediterranean Pine Bark Extract) along with a new partner, Centella Asiatica. Add in the Centella and real change happened. Everyone got dietary and lifestyle advice. (Not Ornish or Esselstyn level, but "advice" and counseling.) The control group had progression of vascular disease. So, lifestyle changes were inadequate. The Pycnogenol alone group had the halting of progression. But throw in Centella and there was a 10% regression. In another study on folks with stents in their arteries, lifestyle advice only show 60% progression of disease. Pycnogenol patients had an 18% progression. Pycnogenol and Centella patients had 9% progression. Regression is good. In fact, it's huge.


Just what makes Centella Asiatica so potent? Well, it has been used in India as an herb for wound healing for some 3,000 years, so it's not new. There is precious little bench research on it. Perhaps there should be more. Wikipedia details how it has been used in curries and salads throughout South Asia for millennia. It's just food.

Pycnogenol we know about. Thank you, Dr. Gundry, for making that well known. Now, just up that dose to 150 mg.


www.What will work for me. I'm hot on this topic. It is one of our intractable problems. I believe that animal protein with its abundance of branched-chain amino acids creates a credible risk for vascular disease, which is why "dietary advice" always recommends less animal protein, more vegetables. But I've had numerous failures as this diet isn't easily maintained, living in America. Chondroitin plays a role, yet to be fully understood. In mice, it's great. I get a cardiac calcium scan every 5 years. If I show any progression, I'm going Gotu Kola (Centella's Indian name) and Pycnogenol. In the meantime, less meat, less sugar, more veges, and good exercise.


References: Ornish, Pritikin, Esselstyn, American HeartMinerva Cardioangiol., Minerva Cardioangiol, Science Direct,


Pop Quiz

1. What is Centella Asiatica? Answer: a plant that grows all over South Asia that is edible and been used in wound healing for several thousand years. Not new.

2. What is Pycnogenol? Answer: like aspirin, an extract of tree bark. In this case, French Mediterranean Pine Bark.

3. This week's study showed what? A modest reversal of vascular plaque compared to progression in folks not taking pycnogenol and Centella.

4. Is there any toxicity from Centella? Answer: well, it's been in food in South Asia for thousands of years, so the answer is probably not. But concentrate the active terpenoid out of it, stay tuned. I hope more research gets done.

5. Where can I find this stuff? Answer: The supplement industry has been on it for a year or two now. Life Extension has a product called Arterial Protect. Get a cardiac calcium scan and then try it for a year. Remember to eat less meat and sugar. And don't think cheese and yogurt aren't also animal protein/fat.


Fasting to Fix COVID-19

Now, that's a wild claim if I ever heard one! But when a client came into my office and stated that she had been diagnosed with a COVID test, was feeling awful with multi-system symptoms, and fasted for a few days and her COVID cleared right up, I was intrigued. When my dog gets sick, she doesn't eat. What's going on?

There is more than just a bit of evidence to support this.

 

First of all, the average person with a BMI of 25 has between 80 and 100 days of reserve fat stores, so we aren't talking about depriving you of critical calories. We are talking about an immune reboot. So, let's look to see if there is any evidence.


There hasn't been a lot until recently. From Yale, in 2018, comes a very interesting examination of just what is going on. Opposing effects in viral versus bacterial infections! All based on glucose. In a mouse model, glucose was necessary for adaptation to and survival from the stress of viral infection but it prevented adaptation to the stress of bacterial inflammation by inhibiting ketogenesis, which was necessary for limiting reactive oxygen species (ROS) induced by anti-bacterial inflammation. Hmmm. That's a mouse model, not human, but there were such dramatic differences that glucose alone determined whether mice lived or died in viral versus bacterial infections.


How about humans? Well, if you have HIV and are a Muslim during Ramadan, it has been studied. Subjects in that study showed they could cut their dose of anti-virals in half and have no change in their CD-4 cell count. And humans naturally have the same "sickness behavior" when we get ill as do animals. We don't eat and we lay down and withdraw. So, does fasting help us?


A recent "MasterMind" conference of doctors treating COVID-19 with Peptides came to the conclusion that giving ketone-esters was worthy of making the cut as efficacious. Ketone esters are a salt of ketones that gets into your blood very effectively without the fasting. When you fast, you burn up your glucose in about 12 hours and starting switching to ketones. By 48 hours, the switch is pretty much complete and you are now running on chopped up fats from your fat stores. The most common ketone you make is beta-hydroxybutyrate and you can monitor its level with a ketone meter you can buy. (Keto-Mojo is one good brand.) If you want to do a deep dive into the topic, there is quite a list of benefits of ketones on your immune system. This is serious stuff. You modulate a vast array of immune responses to the better when you fast. COVID appears to take over your mitochondria in your cells and robs you of energy. The cell is meant to turn into a factory to make new viruses and then burst, releasing the viruses to infect other cells. A reasonable hypothesis of ketones is that you bypass the COVID-19 bypass, tricking it by keeping the cell alive until your immune system can come along and gobble up that cell.


That's the race we have in infections. Can you ramp up your immune response faster than the virus can ramp up its invasion? Everything that slows it down gives you some added time. Being obese means you have pre-existing inflammation and higher glucose: gives the virus a leg up. Being old means you have a slower immune response. Gives the virus a leg up. Fasting turns off glucose, boosts up your immune system......makes a credible response.

 

WWW. What will work for me. I'm an older person so I have risk with COVID. To modulate that, I can do a regular 5-day fast mimicking diet and boost stem cells. There is good evidence for that. So, that I do. My ketones regularly get up to about 3.5 or 4 on day 4-5 of the 800 calorie fast mimicking diet. I haven't seen any research on fasting with COVID itself. We can't advise doing it until that happens. But I have seen it work in one person and I'm fascinated. More to come. Stay tuned.


References: Cell, Yale News, Inter J Prev MedMed (N.Y.),


Pop Quiz:


1. When you fast, what happens to your internal fuel sources? Answer: You switch over a few days from running off glucose to chopping up fat molecules to make ketones. (Beta-hydroxybutyrate is 4 carbons long - a piece of the 18 carbon long fat molecule you have in your fat cell.)


2. What do ketones do? Answer: A whole raft of benefits on your immune system. It gives it a nudge upwards. And the COVID-19 appears to prefer people with high blood sugars: the overweight and the elderly. If COVID likes sugar, let's take it away.


3. Do we have credible evidence that some sort of fasting is useful in COVID? Answer: No. Our current culture is that you need to have a randomized, placebo-controlled trial. I haven't seen how we can pull off a placebo meal.

 

4. Is there another way to get ketones? Answer: Yes. You can eat them straight up. Ketone-esters are a nifty way of getting your blood level up quickly without waiting to burn off your fat. There are proponents for that strategy. (Search for KE4 brand that appears to be the best on the market. The dose is 1/6th bottle three times a day)


5. Should you fast if you get COVID? Answer: Do what feels right. We intuitively don't feel like eating. It may not be so bad for you. We just don't have proof to advise one way or another. But liquids you can't do without. If you get a fever, you lose a lot of fluids. Drink.


The Bradykinin Hypothesis for COVID

The Bradykinin Hypothesis for COVID

Bet you haven't heard of "bradykinin"! Most haven't. It is part of the balancing system of your blood pressure. When you take an ACE Inhibitor for your blood pressure, you are lowering the activity of ACE, but raising bradykinin. So the bradykinin system lowers your blood pressure and makes blood vessels ooze out fluid and get leaky. Then it intersects with your immune response, and everything else.


The data for this important study comes from analyzing the messenger RNA activated in 9 COVID patients in China. The patients were having the virus sampled so they could sequence its genes. The rest of the lung fluid was not used. This study took that lung fluid and analyzed the mRNA (messenger RNA) in the human cells to see just what genes were turned on in those humans. mRNA tells you that. It is produced only when genes are activated. You can see what the cell is thinking is happening and how it should respond. Nifty, huh?! Now, run all that data through the second fasting supercomputer in the world at Oak Ridge for a week and this hypothesis emerges. Compare these 9 sick folks with 40 normal controls and you get this study.

 

And the changes in gene activation weren't subtle. The ACE2 gene was up 199 fold, angiotensin - 34 fold, and the enzyme that activates it, REN, up380 fold. Other pertinent enzymes like the angiotensin receptor 1, (ACGR1), up 430 fold. This is a remarkable and very dramatic change to your balance of your angiotensin/bradykinin balancing act.


And it helps explain many of the weird symptoms of COVID. Low blood pressure, loss of smell and taste, puffy toes, Lungs fill up with jello-like fluid, explained by the bradykinin activation of hyaluronic acid. The shifting balance between angiotensin and bradykinin also explains the weird blood clotting and emboli that COVID has demonstrated. Lungs end up weighing over 4 times normal lungs.  


The net effect of all this activation of bradykinin is that the virus gets in the cells and takes over the house, sort of like a burglar that not only breaks in but opens all the doors and windows and lets in everyone else. Hence the storm.

By focusing on the genes that are activated, you can parse our the real cause of the ongoing damage in COVID. And if you chase that down, quite a few drugs emerge that have specific impact on the bradykinin system. This gives hope for future treatments and will require good, randomized trials to see if anything emerges.

But for now, one simple strategy you can do comes forward. Vitamin D. It has already been shown to have a dramatic effect in COVID patients, which would explain much of the tilt of severe COVID disease in folks with skin pigment, which inhibits Vitamin D production and elderly whose skin doesn't make much.


References: eLife Sciences, Wikipedia, MedRxIV, Elemental, Elemental - Vitamin D, Science Daily,


WWW: What will work for me. I'm taking Vitamin D every day. Daily use has been shown to be better than monthly by some increment. So, it's worth the extra effort. And I'm really trying not to be too lax about exposure. I forgot to take a mask on a bike ride and we got off in a park with other folks around. There was lots of wind, so the risk was low. But small micro errors will add up in time. We are only 6 months away from the credible chance for a vaccine. Hang in there.


Pop Quiz:

1. What is the bradykinin system? Answer: part of your blood pressure control system that is intertwined with your immune response system.

2. How did this study detect that notion? Answer: they analyzed the activated genes by measuring the messenger RNA in COVID lung fluid compared to controls.

3. What difference does all this make? Answer: It's September and the sun is no longer high enough to make much Vitamin D. If you are older, hence less able to make D (80% reduction by age 70), or have skin pigment (85% reduction if skin type 6 - Ivory Coast Black) please, please take 5000 iu a day. If you are just starting from scratch, take 20,000 a day for a month to get loaded up.

4. What else can I do to stay ahead of this pandemic? Answer: Same story. Avoid indoor large groups that have prolonged exposure.

5. Where else is the messenger RNA measurement being used to beneficial effect? Answer: You can measure activated DNA via mRNA molecules in the exosome fraction of your blood. It is being used clinically in patients with Chronic Inflammatory Response Syndrome by Ritchie Shoemaker. This might be the future all all medicine, the assessment of how your body turns on its genes and what that portends for clinical decisions.


COVID Strategy: Arginine and Nitric Oxide

COVID Strategy: Arginine and Nitric Oxide


This is an easy idea for you to implement and one that might be the most significant of all, surprisingly! Arginine is an amino acid you naturally make. It's there in you already. One of the uses your body makes of it, besides being one of the building blocks of protein, is to break off one of its Nitrogen side groups and use it to make Nitric Oxide. Nitric Oxide is a hugely important signaling messenger for many reasons. It makes blood vessels relax and calm down. It helps with men's erections. It helps in wound healing after surgery.  But for now, the topic at hand is it prevents Corona Viruses from duplicating by some 87%. That was research on the SARS COVID virus, but the whole family is affected by arginine.

There are other indications. Nitric oxide is known to alter the spike protein on the COVID virus making it unable to attach to your ACE receptor. Hmm. African Americans are known to have less nitric oxide. That is thought to add to the increased incidence of high blood pressure in African Americans. What about increased morbidity from COVID?

In a normal diet in America, you get about 5 grams of arginine a day, with about 54 mg per gram of protein being the rule. If you have an infection, you want more. This might be a huge topic as much of the long-term morbidity of COVID might be the damage, scarring and ill effects that enhanced healing of those "internal wounds" might reverse.


This is obviously a hot topic and research on the fly is tricky. But it is being done. A good RCT is ongoing right now that should produce credible results. It is in asthma and only using 1 gm a day extra. I find that odd as it is only a small extra dose, and only in asthma.

Oh well. It is a food, not a dangerous drug so you can find it for yourself. You can actually give yourself the building blocks for arginine and make it yourself more effectively by taking its chemical sister, citrulline. Your kidneys actually have the enzyme that puts out the arginine and you can make it more evenly and effectively by taking advantage of that. Ditto with Glutamine. It is the amino acid that is the building block for you to make arginine.

www.What Will Work for Me. This is really cool. It's simple, basic viral biology and makes sense. The Arginine-Citrulline-Glutamine pathway is one of the most complicated and confusing in all of medical school chemistry pathways. There are so many circles, everyone got confused. But not to worry. A recent meeting of Functional Medicine doctors added the formula of Citrulline, 5 grams a day with 5 grams of glutamine as the easiest way to get more arginine and nitric oxide. Gradually increase the glutamine to 10 grams a day and you are all set. Now, I would add fish oil to that because of such positive effects on wound healing. It is my belief that the lingering, long-term damage from COVID is happening because there is dysfunctional scar tissue forming in organs that have been damaged by the COVID virus. We want those organs to heal. Again, just a food that is quite deficient in our diet.


References: Journal of Virology, MedPage, Amer Jr Phys Heart Circ, Adv in Wound Care, Clinical Trials, Science Direct, American Journal Clinical Nutrition, Pathways Common,

Pop Quiz

1. What is Arginine? Answer: an amino acid you use in making protein that you naturally get about 5 grams a day in food.

2. What is so special about arginine? Answer: Your body uses it to make Nitric Oxide which plays a huge role in wound healing and now, in COVID therapy.

3. Can you name one specific thing Nitric Oxide does to COVID? Answer: It messes up the spike protein's ability to bind to the ACE receptor.

4. Are you meant to take some every day to keep yourself primed against COVID? Answer: Yup

5. Ok, how do I do that - just repeat it and give me the bottom line? Answer: Order from Citrulline (an easier way of getting arginine) 5 grams a day, and Glutamine, 5 grams a day. At least have them on hand to start taking the second you think you might be ill. And throw in a gram of fish oil. That appears to add in synergistically. In fact, keep taking the fish oil year-round.


Rapamycin - And Your Aging Plan
 

Rapamycin is a macrolide antibiotic found at the base of giant stone moai on Easter Island, otherwise known as Rapa Nui. Hence the name, "Rapa"-mycin. It was thought to be promising as an antibiotic against yeast and was in the process of being developed for such when it was found to be a bit too toxic for comfort, and almost abandoned. It wasn't toxicity, it was potency!  Some of the scientists working on it squirreled it away and were determined to develop its secrets, as they just had a hunch it could do much, much more. So right they were.

Rapamycin appeared to have anti-proliferative and immunosuppressive effects, meriting further study. Just what was it doing?

mTOR is the "molecular target of rapamycin". Rapamycin forms a "gain-of-function" complex with a binding protein called (FKBP12), and this complex binds and specifically acts as an inhibitor mTOR. And mTOR inhibition is magic. Why? mTOR is basically a nutrient response pathway. It functions as a master regulator of cellular growth and metabolism in response to nutrient and hormonal cues.  


The core problem humans have today is that our environment has changed from what we were designed to live in. We have a metabolism that is used to prolonged periods of calorie shortage and designed to survive that by avidly saving calories in the brief interludes of excess, and then using them up cautiously. In a world of excess calories and sedentary behavior, our own biochemical systems go into meltdown. We get chronic illnesses like diabetes, heart disease, dementia.

The TOR pathways have two complexes called TORc1 and TORc2. TOR-c1 recognizes extra amino acids and turns on growth. TOR-c2 appears to recognize extra insulin and insulin-like growth factors. Dietary restriction (fasting in one way or another) appears to inhibit TOR. And that makes you live longer. This process was first found in yeast, and if you watch the published literature, it is now climbing up the ladder of mammals to humans.

mTOR inhibition has already made it to humans by the use of rapamycin analogs on cardiac stents. When you put a stent into someone, you don't want the scar tissue around the healing process to go on too long, or you plug the stent up. Hence, stents have been coated with rapamycin for almost 20 years now. Nifty!

But what about taking on the whole concept? What would happen is we take rapamycin as an anti-aging strategy?


Well, that is the state of the art! Combine all the evidence-based literature you can find, and consider what it takes to treat aging as a disease. It's not "just natural". It's an illness of its own sort. Super agers, those folks who live looking and acting healthily into their late nineties and even 00's, look different than other humans. They aren't on any pills. They never got diabetes. Their mitochondria are still making peptides that communicate with your hypothalamus (next week - stay tuned). And rapamycin fits in that system by suppressing all the inflammation caused by too many calories. Combine the peptides that activate your mitochondrial based peptides, intermittent fasting, sufficient exercise, limit excess protein with rapamycin, and we are beginning to formulate a means by which we humans can add some 20 years to our "healthspan". Interested?


www: What will work for me? I'm interested. I do my monthly five-day calorie restriction. This is the last week of the month so I'm on it now. 800 calories for 5 days. And I'm planning a good bike ride this afternoon. But it's eyeing rapamycin that is on my radar now. I'm trying to learn just where it fits. It appears to me that taking one pill a week of rapamycin, in conjunction with Thymosin A, CJC/ipamorelin, and oral BPC peptides, with metformin, NAD+ might all be in the mix. Throw in some real attention to love and community, and survive this pandemic, and we might be ready for showtime.


References: Cell Metabolism, Nature, Biochem BioPhys Acta,


Pop Quiz

1. What is rapamycin? Answer: an antifungal antibiotic that targets the protein complexes that control your aging modulation system.

2. How does it do that? Answer: It gauges how much food you are getting and turns on proliferation in respsone to that.

3. What's wrong with nutrients? Answer: We get too many. And that's bad. You want to inhibit that.

4. Is rapamycin being used in humans already? Answer: Yes. It has been on stents for 20 years to inhibit proliferation on coronary arteries.

5. Where else might proliferation be a problem? Answer: Well, generally speaking, cancer is unregulated proliferation. Anti-aging is all about inhibiting many loci of proliferation: coronary arteries, cancers, fat tissues.. On and on.


COVID Strategy: Metformin

COVID-19 Strategy: Metformin

How would you like to reduce your risk of dying with COVID by 75%? Whatever risk group you are in. I’m in. Just explain why and how.

Here is an observational study from China just published a few weeks ago. 283 patients admitted to a hospital in Wuhan were selected. All were diabetic. Of that group, 104 were on metformin and 179 were not. All were reasonably well controlled in their diabetes. They were matched to be just about identical in every aspect including age, gender, and other risk factors. They stayed in the hospital for the same 20 some days. But survival wasn’t the same. Diabetes is one of the clearly identified risks of COVID-19 mortality. Of those on metformin, 3 died. Of those not on metformin, 22 of 179 died. That is 2.9 % compared to 12.3 %. A 75% reduction in mortality. Wow!

Why? Well, we aren’t certain we know exactly why but this sure brings up a lot of excitement. The authors reference some prior research that may give us a clue. Metformin appears to slow down Complex 1in the Electron Transport Chain in mitochondria. That is the first step of taking fuel (known as glucose or fat) and turning it into water and carbon dioxide and ATP, your energy molecule), and burning it. Slowing it down has the same effect as fasting or intense exercise. You make your cell feel like it’s not getting as much fuel as it needs, so it has to hunker down and go into survival mode.It turns on AMPK, the critical switch to turn on your “hunker down and wait it out” mechanism. That is of high interest for those working on lifespan and longevity. But here it appears to cross-reference to enhanced immune function. When you turn on AMPK, you then inhibit mTOR and its downstream immune effects: instead of turning monocytes into macrophages (Pitbulls) you slow all that down as your cell goes into “hunker down and wait it out mode”. You don’t get the cytokine storm you have been hearing so much about.

And that’s not all. Metformin also inhibits the whole NF-kappa B complex that is the basic pathway to starting inflammation. It’s the activation of that that curcumin inhibits. Putting a clamp on that activation is at the exact pivot point of systemic inflammation. NF-kappa-b is the nexus of the cytokine storm. It is where all the hundreds of cytokines that COVID-19 appears to initiate meet and fuel the fire of inflammation. Without it, inflammation goes nowhere.

Finally, metformin appears to augment autophagy, which is the programmed recycling of dead and dying cells. That is the organized garbage removal your body is meant to do when it has junk to dispose of. Disorganized, chaotic cell death happens when viruses kill the cell and they spew out by the millions. All the cell contents just blow up. That is unorganized and leads to a much greater inflammatory response. By boosting autophagy, you dampen uncontrolled, runaway inflammation. Metformin is being used in tuberculosis treatment to help conquer antibiotic-resistant TB by just this mechanism.

But there is something about ketones that metformin also induces. We know COVID, and all viruses, hijack your mitochondrial energy glucose pathway to make fats instead of energy. But there are hints that taking ketones bypasses that and feeds your starving cell just when it is being overwhelmed by the virus duplicating itself. (See last week’s newsletter). If you take purified ketone products like KE4 (10 ccs three times a day) you restore energy to cells and prevent cell death. When you prevent cell death, the virus is trapped inside and now spread. That allows your immune system time to race to the rescue and kill that cell (and its viruses).

Metformin induces mild ketosis. Is that how it works? It shifts you from glucose metabolism to ketone metabolism? We see it working in the lab, and now in 278 diabetic Chinese. 75% reduction in mortality!

WWW: What will work for me? I’m taking it for longevity reasons. I’ve been on 850 mg a day now for about 6 months, starting, paradoxically, just before COVID showed up. I’ve had no side effects. I’ve lost maybe one pound. My ketones have been getting up to 4.4 and 4.7 when I’m on my 5-day fast mimicking diet when I take metformin concurrently, which is the highest I’ve been able to ever get, so I’m tickling the idea that metformin really does induce ketones. Ketone, or beta-hydroxybutyrate, are just tiny fragments of fat. That’s otherwise known as weight loss. If I haven’t convinced you to take metformin for longevity, for goodness sake, take it for COVID protection.

Pop Quiz

1. Metformin is a drug used for what? Answer: The number one drug in the world to treat adult-onset diabetes. Available over the counter in most countries. Costs about $ 0.02 a pill in other countries.

2. Metformin is a pharmaceutical, foreign substance, not safe to take? T or F. Answer: this is actually a fascinating saga. It is an extract of the French Lilac plant discovered because folk medicine had used it for sweet urine for centuries. In Mid 1800s two Frenchmen isolated it and eventually, metformin was produced. It’s pretty safe. You could call it an herbal extract.

3. Its use in diabetes has been found to help COVID-19 patients reduce their mortality by how much? Answer: 75%

4. This type of study Is considered sufficient to proves its value. T or F. Answer: False. A retrospective, observational study could be in error and randomized, placebo-controlled trials are warranted. The fact that so much basic science supports the mechanism is tempting to call it a day. During science on the fly during pandemics is tricky.

5. Would you take it if you could get it? Answer. ?

References: Am Jr Tropical Medicine, Current Drug Therapies, Diabetes, Metab and Sig Transduction, Cell, PLoS One,


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