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,


Corona Virus CURE might be in the Offing: Peptide Therapies Mature

If you heard a story of a physician contacting COVID, his oxygen saturation plunging into the 80 within hours, and then his recovery in 3-4 hours, you might be skeptical.  That would be prudent.  And then you might explore.

Ok, here it is.


First point.  Viruses are invading pathogens that have to take over the cellular factory to make copies of themselves.  All they want is more of their own DNA/RNA, and coating proteins so that they can make their own packages.  The factory they take over is the mitochondria.  Your mitochondria are your energy factories, making up 10% of you.  Muscle cells have several hundred mitochondria, but your heart has 5,000 as does your brain.  That is as much as 30% of the weight of your heart is mitochondria.  COVID-19 is particularly good at that hijacking.  When you hijack your mitochondria, you feel extreme fatigue.  Of course  you do, your energy is turned off.


Now, your defenses against COVID require you to activate your Sirtuin Proteins, the family of proteins that nurture, groom, and defend your DNA.  The virus wants in, to take over your cellular command, and you want to hold it off.  The Sirtuin family does that.  Sirt-1 is the champion protector.  It's ONLY food is NAD+.  You turn on protection by having NAD+ around.  The problem with aging is that we don't make it anymore.  That makes an avenue by which you can fight back. You can take NAD+ as a supplement.  Easy, peasy.  You just need to hold the virus at bay long enough for your immune system to kick in and do it on your own.  The problem is that the virus is voracious. There is a frantic rush to who gets there first.  Does the virus invade and replicate faster than your immune system can ramp up? That's the key nexus.  Can you accelerate the ramping up and holding off?


This is where the race is decided.  Can you give your cells a lifeline of energy so that they can survive long enough for your own immune system to ramp up?   If we give you antibodies from folks who had the COVID-19 virus, we slow it down.  So, convalescent serum helps.  If we give heparin, we slow down the spiral of lethal clotting that gets activated in some folks, long enough for your immune system to balance things back again.  Ok, but that's pretty dramatic and is treatment after the cow is out of the barn.  How about just feeding your cells that have been attacked so they can hang in long enough to keep themselves together and not just explode with a shower of new viruses?  That's the thread to follow.


What do mitochondria use to make energy?  Two choices.  Carbs (glucose) or fat.  That's it.  Just two choices.  What happens with carbs?  Well, that's what the COVID-19 hijacks.  They take over the mitochondria and the whole mechanism of glucose production to divert making ATP and instead make fat to make viral membranes.  Can COVID-19 use fat?  NO!   And if they can't use it, well, you can.  What happens with adult-onset diabetics?  They are addicted to running on glucose and have a high baseline of insulin.  They are insulin resistant.  And any trace of insulin makes ketones (little tiny fat pieces) disappear.   Most COVID injured folks have insulin resistance or hypertension, both of which have key defects in the mitochondria.  


Read that three times and you will understand the key strategy here.  Ketones are present only, only, only when there is no insulin around.  Any intensivist in a hospital will tell you that they can cure diabetic ketoacidosis with 2 U of insulin infused per hour.  But in adult onset diabetes, it isn't the lack of insulin that's the problem, it's insulin resistance with super high, insulin levels.  That means there is high glucose circulating.  COVID-19 loves that.  They take over the mitochondria and they make lots and lots of fat molecules to make coating proteins.  So folks with diabetes are very vulnerable to COVID.  


We can make you ketogenic if you burn off the glucose stores in your body, including in your liver.  It takes 2-3 days to get there.  Or, we can get you ketogenic by giving you ketones.  Just cheat a little.  Buy ketones.  What we call "ketones" are actually a very simple molecule called beta-hydroxybutyrate.  It's a 4 carbon piece of fat that your chop off a longer fat molecule as you digest it.  You can buy them.  


And when you take ketones, your mitochondria love it. They can lap them up and the COVID-19 can't.  You bypass the roadblock the virus lays down and give a lifeline of energy to your cell. " Just give me a day or two of energy until my own immune system can mount an effective response".  That's all your cells are asking for.

Do you see the strategy that's emerging?   You want to be ready for COVID? Get yourself on the real ketogenic diet based on vegetables and fat and cut the carbs. Get rid of bread, rice, potatoes and any form of free carbohydrates.


And if you get COVID-19?  Ramp up your immune system with Thymosin-A1 and take Ketone-Esters.  Ketone Esters are the fastest way to get ketones into you.  They give your cells the vital energy you need and that your mitochondria can convert into ATP that the COVID-19 doesn't have access to.  


And that's it.  There is a buzz going around in the Functional Medicine world of giving COVID-19 patients in the ICU ketone esters orally.  And then ramping up their immune response with Thymosin A-1.  And folks with COVID are up and walking around in a day or two.  


WWW.What will work for me?  If I were to get ill with COVID, I would take Thymosin A-1 three times a day and Ketone Esters 4 times a day.  It's my plan.  I have a steroid inhaler to use to keep the virus tamped down on my lung receptors.  I have Vasoactive Intestinal Peptide to turn off the cytokine storm.  I'm taking NAD+,  and selenium, zinc, and Vitamin D every day.  And Melatonin every night.  I think we have a strategy to keep this virus at bay until we get a vaccine.  But start by ordering yourself some Ketone-esters.  Yes, they cost a little.  You are worth it.  We can order each of these for you is you want to get yourself prepared.  Better yet, wear a mask and wash your hands and get the vaccine.  But just in case.......


Pop Quiz


1.  The COVID-19 virus appropriates what process in your cell that saps your energy?     Answer: The glucose metabolism pathway.  It turns it around to make viral membrane fats.


2.  Anything else?   Answer: Well yes, if you said NAD+ you would have been right too.  It robs your NAD+, stealing your ability to nourish your Sirtuin proteins that protect your DNA


3.  What do you feel when that happens?   Answer:  Extreme fatigue


4.  What nutrient supplement can you take to bypass that and feed your starving cells?    Answer:  Ketone esters, called beta-hydroxybutyrate.  The virus can't use that so you trick it


5.  And just what does Thymosin A do?   Answer: It is the peptide you make to turn on your virus response in your white cells.  You have lots of it as a child but stopped making it a couple of decades ago.  Sorry, true.  It's been proven by good research to help you cure chronic hepatitis B, and now being extended to COVID-19.


References:  Trends in Microbiology, Science Direct, Am Jr Physiology, Medium, OHSU, Cell Symposia, Med

Corona Virus is FAR WORSE that we thought - It's Horrible for your Heart

It's not "just the flu".  It's not "just a virus".  It's a secret organ killer, and we don't understand yet just where it chooses to strike and how awful it is when it does.  This week's finding is on heart disease.  COVID attacks the heart.

We first had a report in early July from the Cleveland Clinic that cardiomyopathy incidence increased dramatically amongst COVID patients.  Cardiomyopathy is basically the muscle failing.    Their study showed that stress cardiomyopathy increased from 1.8% to 7.8% during the pandemic as they reviewed all their cardiomyopathy patients.  Now, that is terribly alarming because it was simply looking at what showed up.  They had enough patients to look for ordinary cardiomyopathy, that we often toss off as "usually caused by some sort of virus", which was only seen in 1.8% of folks before.  Now, with this COVID pandemic, that incidence quadrupled, and the population did not all have COVID. If everyone had had COVID, what would we see?

That's what this week's German Study reports on.  From 100 patients who had recently recovered from proven COVID, 33% had been hospitalized and 67 were able to recover at home.  They had MRI scans done of their hearts.  What they found was quite remarkable.  Ongoing inflammation showed up in 60% of the patients, who were studied on average 71 days after diagnosis.  Their troponin levels were still elevated above 3 in 71 of the 100 and above 13 in five.  That's enough to diagnose a heart attack!  The MRI scanner can see fibrosis of the heart muscle with so-called T1 and T2 measurements.   60% of the patients showed ongoing inflammation, regardless of pre-existing conditions or severity of illness.  The study leaders actually biopsied the hearts of those with the worst inflammation and found their heart muscle all filled up with lymphocytes.   This is a very important finding as it gets right to the "heart" of it.  COVID-19 damages your heart and results in scar tissue and reduced capability.   All this research is being done on the fly as a pandemic is in progress, so we have no long-term data to look to.  That will come in time.  

We've known COVID attacks the lungs and blood vessels.  We now know is has widespread involvement and damage to hearts.  But that's not all.  Did you know that half of COVID patients show damage to their liver with elevated liver function tests?  Kidneys?  Same thing

This is one nasty virus.  It certainly precipitates severe disease.  Is there a common thread?  I would propose one.  The COVID-19 has a predilection for taking over your NAD fuel system in mitochondria.  Your organs have 2-3000 mitochondria in each cell.  They burn a lot of energy. Your heart has 5000 mitochondria per cell : 30% of the mass of every heart cell is mitochondria.  It has to beat constantly.  Damage the mitochondria and you rip out the energy production that makes the cell work.  As we age, our mitochondria weaken and our ability to maintain our NAD supply weakens.  NAD comes from Vitamin B3 but it is essentially lacking as we get older.  COVID loves NAD.  What little there is, it gobbles up and uses for its own duplication.

Whoa!  That suggests a clue to help yourself.  If you are low on NAD, would it help to take more as a supplement?   Who knows.  Hasn't been studied.  If you had no other options, would you give it a whirl?

WWW: What will work for me.  David Sinclair has shown us that NAD supplementation is a critical anti-aging strategy.  If you are over 50, you should be on NAD-Riboside and NMN, for the rest of your life.  But now, with COVID, should you be on more?  I think it goes right to the biology of how COVID causes its damage.  So, I'm taking it every day.  And hearing this story helps me double down and increase my vigilance against getting it.  I'm getting much more patient with myself and doing much better wearing my mask.


References:  USA Today, JAMA Network Open, JAMA Cardiology, UEG Journal, Preprints, Nadovim


Pop Quiz

1.  If you are a person who gets COVID, what is the likelihood that your heart will show heart damage by MRI scan?   Answer: 60% if you measure those who had symptoms and documented disease.  We don't know about those who didn't realize they got the disease.  I suspect 10 years from now we will have studies on those who never realized they were sick but got a blood test that showed that they had had it.   I bet the number won't be zero.


2.  What is the likelihood that someone who didn't show any symptoms has heart damage?    Answer:  We don't know but it may not be zero.


3.  Is heart the only organ that is damaged?   Answer:   No.  Virtually every specialty is detailing how its organ is being damaged. There is certainly live and kidney damage.


4.  What is the unifying hypothesis that weaves these all together?   Answer: Damaged mitochondria with the known hijacking of NAD that viruses do, and COVID does exceptionally well.


5.  What happens if I take NAD as a supplement?    Answer.   To give an honest answer is going to take a randomized trial, which we don't have right now.   It is a known nutrient that declines with aging and its use as an antiaging supplement is well established.  Its use with COVID is conjectural, but taking it has no known harm, and certainly has benefit for antiaging purposes.  

COVID Strategy: Interferon

Have you ever heard of interferon?  Perhaps with cancer?  That's what this column is for.  I want to explain it in layman's terms so that you understand it.  And perhaps, understand how to benefit and turn your own interferon on.


Interferons are the proteins you make to fight back early against viruses and cancers.  You make three kinds of them.  Insufficient or inappropriately timed interferon production may explain why some folks get sick with COVID, and some folks don't.   This is all research on the fly as this particular COVID virus hasn't been studied intensively yet in mild cases.  But the carona viruses that make the common cold has been studied and comparisons can be made and some conclusions can be conjectured.  It's good to know this.


Type I interferons go by names like  IFN-α, β, ε, κ, and ω.  There are two other types, all produced by immune cells at different times of infections.  It's all in the timing and the amount of response that determines your body's ability to fight back against viruses and clear out the infected cells.   They can be released either by an infected cell, or by a cell that detects interferons being released by its neighbor and so joins in. That makes for a "feed-forward" system that accelerates the response.  The infected cell may be doomed but other responding cells may get their defenses up in time to limit the spread of the invader.  In particular, immune cells also get turned on and come to join the fray.  They can gobble up the virus, or inactivate it with antibodies.  All of this activity happens in a mad dash to contain the invasion.


Type I and II interferons are doing most of that immune response.  Type III stops viral replication inside the infected cells and shores up the integrity of membranes where the virus is coming in.  So, Type IIIs make your lungs better suited to getting infected.    It's I and IIs that are turning on the inflammatory cytokine storm that may overwhelm the host if it is badly timed.  


Now, viruses can fight back.  They usually carry their own genetic code for duplication, but also coating proteins and then, most importantly some proteins that neutralize host defenses. Carona viruses have about 10 different genes that either block interferon receptors or block their activation or even basic transcription.   Clever little devils.  But that's exactly what you would expect.  Evolutionary pressure on viruses forces that. They won't succeed and duplicate until they evolve and develop the genes to get around that.   So, we have to fight back.  Guess whether humans make a strong or weak response of interferons to the common cold carona virus!    Strong!    Guess what humans make to super dangerous carona viruses like SARS and MERS!  You got it.  Weak. 


There have been very tiny studies of patients in ICUs with COVID looking at the activated genes of sick folks.  Sure enough, a weak interferon response but an inappropriately abundant inflammatory response.  If you call in too many immune cells, you make "neutrophil extracellular traps" where you end up with tiny pus pockets, if you will, and cause complete dysregulation and blood clotting.  If you bring the hammer down of corticosteroid use, dexamethasone and heparin, you can stop that runaway "trapping" and clotting.  It's blunt instrument, but it appears to be working.  COVID survival is better with dexamethasone and heparin. 


So, who gets sick with COVID.  Old people.  And they don't make a sensible interferon response.  Nor do folks with cancer or diabetes.   Diabetes is an inflammatory disease in most cases where inflammation is already ramped up.  (See last week's blog)


There are some studies giving interferon as a drug.  In China, 3000 health care workers were given interferon nasal spray and not one got COVID. 


Can you get interferon?  Well, yes.  It is on the market but not widely used and few doctors are familiar with it.  And it's confusing as which do you use, when.  Type I? II?  III?   Might cost some $ 4000 dollars just for the drug, which insurance will not cover.  But a peptide called Thymosin A-1 might be similar in effect.  Cheaper and fewer side effects with the same outcome in one study comparing Thysomin 1 to Interferon in Chronic Hepatitis B infection.  Another peptide, VIP, also works to turn on interferon responses.  No one on VIP has developed COVID yet either.   Hmm.  There are options out there.   So does Vitamin D.  Selenium.  Melatonin


www. What will work for me.   Well, I'm taking Thymosin 1 myself.  Every day.  Will it work. Haven't a clue.  And the research on VIP is so intruiging, I suspect it may be another breaththrough drug when the RCT being conducted on COVID and VIP is completed.   But don't neglect the melatonin, Vitamin D, selenium.  They all work through the augmentation of interferons through your own equipment.  Equipment that has gotten rusty and beat up with aging.   Repair it a little. Go eat some Brazil nuts.


References:   Cell, MedRXiv, Medium, Antiviral Research, MedRxiv, Science Direct,  Jr Cell Physiology, Immunity and Ageing


Pop Quiz


1. What are interferons?     Answer: The proteins you make in response to invasion of "pathogens".


2.   Interferon response uses a "feed forward" system.  What does that mean?    Answer:  Infected cells turn on other cells and they all cycle upwards to contain the spread of viruses.  


3.   Why do some folks get severe COVID and some not?    Answer:  A robust early interferon response is characteristic of the common cold.  A weak response is seen in folks in ICUs with COVID.


4.   Who else has a weakened interferon response?    Answer:   Diabetics, cancer patients, overweight folks.  Anyone with inflammation already turned on.


5.   Can you raise your own interferon?    Answer.  Yup, yup, yup.  all it takes is some supplements, some Thymosin A1 or VIP.   Might be useful to consider.

How A High Fat Diet Makes you Diabetic

 Lose weight, eat fat! Go Keto! All the admonitions to eat fat so that you can lose weight. Is it real? What is the underlying premise and how does that all work? And is there a dark under-belly of problems? Well yes. Let's explain so that you understand the nuance.


First of all, losing weight is incredibly important for general health. In fact, in the short term, if you can muscle your way through any diet that gives you discipline, losing weight trumps every concern in this newsletter if you can keep it off. It is one of the main pillars of longevity: getting your BMI below 25. Ok, that said....


First, why is fat important in a weight loss diet? Fat doesn't turn on insulin. Fat is insulin neutral. Hence, when you eat fat, you feel sated and full. When you eat high glycemic carbs like bread, flour, sugar, rice, corn, or TOO MUCH protein, you turn on insulin which makes you store calories aka, weight gain. Everyone knows that foods that generate free carbohydrates quickly make you gain weight. Fats don't do that. So the first takeaway is that high glycemic foods will make you gain weight. The second is that too much-concentrated protein also turns on insulin as any extra protein gets turned into glucose, and then turns on insulin.....and you gain weight. (Get it? Insulin is the enemy).


The second key principle is that the nature of the fat you eat matters. Saturated animal fat (bacon fat, steak fat, animal fat) is the fat animals make when they eat too many carbs. Just like you. Force feed animals corn and beans instead of grass and they put on weight, just like you. They weigh more so the farmer gets paid more. You like that fat because it makes your steak taste juicy. And animal protein drives up TMAO, the chemical most closely associated with developing coronary artery disease.


A third critical principle is the magic nature of green vegetables. Above-ground vegetables like broccoli, spinach, Swiss chard, cauliflower..... is that they are secret fats in disguise. They get turned into BHB by the bacteria in your colon. When you eat a salad with olive oil, you are eating the fatty molecules in olive oil and your gut is changing the cell wells of the lettuce or other green vegetables into BHB in your gut. Neither affects insulin. That little magic trick might be the best takeaway from this blog for you. No effect on insulin by non-root vegetables (note: this does not include peas and beans).


Unsaturated fats break down easily to beta-hydroxybutyrate (BHB), the short tiny fatty acid that is the same fatty acid you make when you lose weight. The sequence is as follows. When your insulin level gets low enough, your fat cells open up and share their saved fats which get chopped up into BHB. That's called weight loss. Your mitochondria love BHB. In fact, it is one of the most conserved metabolic pathways in nature. You want to teach your body to run on BHB. It's good for your brain, your heart, your muscles your longevity. Olive oil and nut oils are champion precursors to BHB. Coconut oil is a combination of shorter saturated fats that can only be made into BHB. To lose weight, you must generate BHB and that happens ONLY when you have very low insulin.

But what's the real problem with saturated fat? That's the title of this blog. Get to the point! Ah, here is the most important takeaway today. Saturated fat has its own hidden secret. It is inflammatory. Here is the deep dive. Protein Kinase C-epsilon (PKC-e), is an enzyme that inhibits insulin action when it is activated. It puts a tag on the insulin receptor and makes it inactive. You need higher insulin. You become diabetic. That, by the way, is the definition of insulin resistance. For the last several years, it was thought that PKC-e was located in your liver. Not! It's in your fat tissue all over your body, most particularly, your gut. When PKC-e is turned on, your fat cells get big, engorged, and spew out inflammatory cytokines. They make your whole body inflamed. But what we really now see is there is a straight path from eating saturated fat to inflammation, insulin resistance, and diabetes. That pathway goes right through your fat cells and PKC-e. Once you are insulin resistant, you continue to have high insulin all the time and that makes you stay fat. Voila. A perfect trap you can only wiggle out of with careful attention to detail.

And if you simplify that and "reverse engineer it", that is the perfect way out of diabetes. Follow this. Stop eating high saturated fat food (animals fed on grains, eggs from chickens fed grains, milk, and cheese from cows fed grains) and high glycemic foods (potatoes, rice, bread, wheat, oats, corn, beans). Cut down on too much protein. Consider 6 oz a day as sufficient protein. Eat lots and lots of above-ground vegetables, olive oil, macadamia oil, avocado oil and coconut oils (A wee bit controversial but I think I'm right. The Kitavan study shows folks who eat no grains, smoke like chimneys and get 50-70% of their calories from coconut oil, and have no heart disease). Doesn't that sound like the Mediterranean diet? Yup!

WWW: What will work for me. I'm so eager for the farmer's markets to start working in these COVID times. I know, we have to keep our distance and wear masks, but I really want some farm-raised, organic vegetables. Some of our farmers will take orders you can pick up at the Farmer's market and spend less time being in the crowd. And we are cutting down our meat consumption and spreading out our cooking it. Tonight, pizza on the deck with friends, made with veges on cauliflower crusts, untouched by anyone in personal pizzas, and all of us 8 feet apart.

Pop Quiz

1. What foods turn on insulin? Answer: any carbohydrate product that has been processed by grinding such as wheat flour, or rices with their hulls removed, oats that are crushed, and any portion of animal protein that exceeds your metabolic need for protein. We eat about 3 times too much as a general rule.

2. What foods fail to turn on insulin? Answer: Fat. Two kinds of fat. The first kind looks like a fat, smells like fat, tastes like fat, must be fat. The second kind is the secret kind. Green vegetables that are digested in your gut to make beta-hydroxybutyrate, a short-chain fatty acid that is counted as a fat. (See Gorilla Diet: all green leaves but ends up being 60% beta-hydroxybutyrate - magic trick in your colon turning cell walls into fatty acids.)


3.  What fats are safe for you?   Answer: the ones that don't turn on PCEe, unsaturated fats.


4.  And just what does PCEe do?    Answer: Ah! Here is the rub.  It makes fat cells sickly, too big, inflamed and they proceed to spew out inflammatory cytokines that mess every part of your body up.  It's the slippery slope of diabetes.  


5.  What on earth can I eat?   Answer: eat like a gorilla.  Lots and lots of green, leafy vegetables that includes all the broccoli, cauliflower, avocado, spinach, Swiss chard....if it grows above ground, it's probably ok if you aren't sensitive to lectins, and it's not a legume or a grain.  Those who can tolerate lectins or who cook their legumes enough can tolerate and eat them.  And all the olive oil you want, all the safe nuts you want.  (Put cashews and peanuts last and choose almonds, walnuts, pistachios, macadamias first.)




References:  Diabetes, Medical News Today, Harvard Health Letter, Harvard Health Letter-Good Fats, NIH-Research Matter, Am Jr Physiology, Frontier Nutrition,  Cell Metabolism, Jr Nutrition


 

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