Creatine, Super Supplement
Creatine seems to be all the rage among podcasters and bloggers. They are all excited about brain support. There is some good reason for that. Let's explore.
Creatine was discovered as a chemical commonly found in muscle in 1832 that appeared to assist muscle metabolism. Bodybuilders have been using it to assist in increasing their strength training for decades. It is widely used in that context. There is recognition that the recycling of ATP, the energy molecule in our cells, is assisted by creatine. That explains its popularity with athletes.
But there is much more nuance to the creatine story. It all comes down to the methylation system and competition for methyl groups. There are two compounds the body must have that have high demand for methyl groups: creatine for muscles and choline for nerve conduction and plasmalogen production. Each of those takes 3 methyl groups to manufacture from scratch. A methyl group is a single carbon with three hydrogens waiting to be attached to a waiting compound. Creatine and choline together are 80% of the body's methylation demand.
It's the simplest of organic molecules, but foundational in its simplicity. Vitamins B12 and folate are both methyl donors. That's why you need those two vitamins. They supply those necessary methyl groups. However, the human body demands methyl groups to manufacture choline and creatine (3 for each). It's all about balancing supply and demand: the competition between choline and creatine.
That's the plasmalogen link. Plasmalogens are the membrane lipids that give the functionality of your cells. They are also critical for life. The plasmalogen molecule has choline on the end of it in its "head group" attached to phosphate. (Ethanoloamine, the main alternative to choline in plasmalogens is the same molecule with 3 fewer methyl groups on the end carbon.) They are interchangeable, sort of.
The same plasmalogen with choline will be found in muscle, with ethanolamine in the brain. The choline molecule in the head group of a plasmalogen can be scavenged in nerve cells if they are running low on the main neurotransmitter for muscle cells (and memory) called acetylcholine. If you don't have enough acetylcholine, you can't run your nervous system. It's a non-negotiable nutrient. If you run low on acetylcholine, you are dead. Gotta have it. No compromises. That's the "choline-steal" dilemma. That's why your body engages in stealing precious choline from precious plasmalogens. Evolution probably put the choline molecule on the head group of plasmalogens to supply that buffer for nerve cells to obtain choline when the nerve cell ran a little short.
Synapses in the brain will scavenge choline from the plasmalogen molecules of their synapse to recoup any choline deficit. That's called borrowing from Peter to pay Paul. You keep borrowing plasmalogen choline from your synapse membrane and your synapse runs out of plasmalogen lipids and collapses. Synapses collapse and the brain shrinks. Each memory is composed of thousands of synapses in intricate webs. You can lose one synapse and still remember that name, sort of. But you can't lose too many. That's called Alzheimer's. It likely starts with the "choline-steal" syndrome.
(Geek Alert. If you really want to dive in, here are the heady details. When you excrete acetylcholine in a nerve cell, you chop it in half and then retake up the choline component to be remanufactured as acetylcholine. Your nerve cell does that 100 times a second. The ability to reuptake choice is entirely dependent on the plasmalogen content of the synaptic membrane. Low plasmalogens, less re-uptake. Less re-uptake, more choline steal. More choline steal fewer plasmalogens. Peter and Paul are having a field day. Downward spiral.).
You can measure the competition for methyl groups in your homocysteine. Homocysteine is like an electricity meter of methyl groups. The higher it is, the more methylation demand is going on. Almost every brain disease has high homocysteine, meaning there is an unmet need for more methyl groups.
Now you can put the story together. If you take creatine as a supplement, you are reducing your absolute need for making your own creatine from scratch, which takes three methyl groups to make. That frees up demand for methyl groups to allow the demand for choline to be met more easily. Provide lots of choline as well and you have all the supplies you need to make more acetylene choline. Have enough acetylene choline and you can stop the Peter to pay Paul choline-steal syndrome. Did you intuit why creatine helps the brain? It's a long, round-about explanation but it's very real.
What will work for me? If your eyes are glazed over with confusion, simplify it. Measure your homocysteine. If it is higher than 8 or 9, you need more methyl groups. You can take B12 and folate and increase your supply of methyl groups. Or you can take creatine and choline and reduce your demand. Oral creatine boosts your muscle creatine demand, and takes away the competition for a precious resource for your brain (through the methyl group connection), choline for your neurotransmitters. I measured my homocysteine and I was 12, the average American level. I wanted 7. I took B12 and folate. Got down to 10, but no lower. When I added creatine and choline (in egg yolk lecithin), I was at 7 within a month.
If you start out at 7, congrats, you lucky devil. Just try asking your regular doctor for a homocysteine blood test. They aren't allowed to order it. Not paid for. Might be one of the most important tests you do. Take creatine. Got it? Now you understand why podcasters just don't go into all that detail. (Their eyes are glazed over too.)
References: Nature, [Frontiers in Nutrition], Wikipedia,
Pop Quiz
1. What is creatine? Answer: A critical component of all cells that help remake ATP for energy.
2. Why is creatine so important to take as a supplement? Answer: You can make it on your own, but it's expensive to do so. It requires 3 methyl groups to make, pulling away precious methylation capacity from making choline, which also needs 3 methyl groups to manufacture.
3. Can you explain the choline steal syndrome? Answer. No. (Kidding. If you don't reuptake enough choline in an acetylcholine nerve cell, you pick up the deficit by nabbing some choline off of the plasmalogen molecules in the synaptic membrane. Robbing Peter to pay Paul)
4. What's the easiest way to measure your creatine need? Answer: Blood test called homocysteine.
5. What level of homocysteine is ideal? Answer: Less than 9 or 10. Maybe even 7.
Are Carbohydrates Toxic?
There is increasing interest and research into the effects of excessive varieties of nutrients. Clues as to what is optimal arise from the fact that macronutrients (fats, carbs, proteins) are not fully interconvertible at the metabolic level. For example, any kind of macronutrient can yield fatty acids and cholesterol (that are made from the main metabolic intermediate acetyl-CoA), contrasting with the fact that fatty acids cannot be converted into glucose or other sugars. It's a one-way street. The human body can make most amino acids, except for the essential ones. We are left with the recognition that some macronutrients can cause short-term effects on metabolism and long-term effects on body composition.
We have known for quite some time that too many fats can cause "lipotoxicity". It's curious that the concept of "carbotoxicity" hasn't been developed despite clear evidence of problems with simple sugars like fructose.
What is ideal? What transitions have we had in human nutrition? Our first transition was 5 million years ago when humans began to develop a big brain and started eating animals. Five million years isn't enough time to convert our entire metabolism from vegan to the increased animal content of modern humans. But the next transition was when carbs began to appear with the transition from hunter-gatherer to farmer. Cavities showed up in skeletons. For most humans between latitudes 40 degrees north or south, 40% of calories arose from the carbohydrate sources: wheat, rice, and potatoes in their respective ecosystems. For societies further north or south, carbohydrate intake was in the 15% range. Both were consuming carbohydrates under the current recommendation of 60% for carbs as nutritionally appropriate.
The next transition was all about sugar. With the introduction of sugar cane from New Guinea via China, then India, and then the Caribbean the intake of sugar sky-rocketed in the 19th and 20th centuries from a rare treat to 18% of calories. Just sugar. And some 80% of prepared foods have some sugar added with some 56names to hide the total quantity of sugars in the unsuspecting consumer.
The invention of high fructose corn syrup (HFCS) in 1975 catapulted the consumption of fructose. In fruit, fructose is at about 6% of content which is digested in the small intestine to glucose with no fructose arriving in the liver. With HFCS, fructose floods into the liver and sets of the production of cholesterol and uric acid, both correlated with metabolic syndrome and coronary artery disease. The depletion of ATP and consequent AMPK activation results in a block in protein synthesis, induction of oxidative stress, and mitochondrial dysfunction in hepatocytes. Fructose is clearly toxic.
Even high intake of simple glucose containing carbs leads to an increase in postprandial glucose levels which trigger the release of insulin, driving glucose into numerous cell types. When this reflex is stimulated by rapidly absorbable glucose (ultra-processed plus sugar and HFCS), it may ‘‘overshoot,’’ causing a dip in blood glucose that stimulates appetite. Lots of animal research suggests that leads to overeating, paying a way to understand the problems with ultra-processed foods where raw carbohydrates, typically bound with fiber, refined, ground up into talcum powder flours that are exquisitely vulnerable to rapid absorption. That high insulin becomes chronic, and then depleting. It is likely the source of visceral fat and its attendant inflammation and toxicity.
www.What will Work for me. There you have it. The new recognition and discussion of the problem with carbohydrates. The human organism has the biology to digest carbohydrates, just not in the form of a flood. Timing is everything. Fructose in fruit is not a problem. Glucose bound in grains is digested very slowly when it's a whole grain. When it has been hulled, polished, pulverized into powder grains become "too nutritious". Is that another word for "toxic". If you take away all the fat and just eat fruit and vegetables, throw in all sorts of delightful spices (Curry anyone? the human body can process higher carb intake. It should be noted that whole vegetables and grains with higher fiber result in high ketone production.)
References: Cell, British Dental Journal, Healthline,J. Hepatology,
Pop Quiz
1. What percent of carbohydrates were in most hunter-gatherer diets? Answer: If within the 40 degrees of latitude range, about 40%. Well below our current 60% recommendation.
2. Whole vegetables and fruits are not just carbohydrates. What else is made out of them when eater? Answer: Gut bacteria break down the fiber into beta-hydroxybutyrate. (Gorillas, eating 17-18 pounds of green leaves a day get 60% of their calories from beta-hydroxybutyrate). Consider eating the gorilla diet. All the spinach you want.
3. What is the most common additive to breads to preserve shelf life and suppress mold? Answer: Aww, come on! It wasn't covered. Proprionic acid is the most common bread preservative. It is a natural product and was thought to be safe. It is now being intensively studied as a root cause of ADHD and autism. If it's bad for kids, it's bad for all of us. That alone makes bread a grocery shelf poison.
4. What is the glycemic index of white flour compared to whole grain wheat? Anwer: Jeezzz. You didn't cover that either. Whole grain wheat is likely around a glycemic index of 19 meaning glucose gets into you at a rate of 19% compared to pure, powdered glucose. So called Irish cracked oats, a whole grain cracked in half but still covered with its fiber is estimated to be around a glycemic index of 38%. How about quick oats, the whole grain smashed flat. Cooks in 3 minutes instead of 30 for Irish oats. Glycemic index 75 or so. And modern oatmeal, matched to smithereens in super thin flakes, cooks with hot water in 30 seconds? Glycemic index 85-90. Exact same food, ultra-processed. We chomped the whole grain when we were hunter gathereres. Now, we open the aluminum packet and tip it into our bowl with hot water. Add lots of brown sugar because that is more "natural". Ha ha. Flour has a glycemic index in the 90s. What a change!
5. What is the primary toxicity of carbohydrates? Answer: Their ultra processing making them into instantly absorbed glucose. It's all about the speed of exposure. They become "toxic".
Mitochondria and Peroxisomes, a Dating Pair of Organelles
You know what a mitochondria is, right? It is the little energy factory in your body. It takes the highly energized electrons stored in fats and carbs and extracts that energy to make the ATP molecule inside your cell. Each ATP molecule then goes out into the cell and energizes some sort of activity that needs energy. And it does it 10,000 times a day. Every day your body is making your weight in ATP, just keeping you alive. You are 10% by body weight mitochondria. Your heart and brain are both about 30% mitochondria as they both use so much energy.
How does that relate to the peroxisome? That's what's new and being discovered. They are clearly intimately linked.
Both mitochondria and peroxisomes are thought to have been tiny bacteria that invaded a larger cell, back a couple of billion years ago. Each had such unique and potent capabilities that the larger cell let them take up residence and the partnership has continued. Over time, most of the genes of these two organelles got transferred to the "big house", the nucleus of the larger cell. There are the only organelles in the cell that can duplicate themselves is such a fashion, giving rise to the hypothesis that they were separate entities at one point in time.
In mammals, peroxisomes play an indispensable role in many pathways, including manufacturing plasmalogens, chopping up fatty acids, making bile acids and DHA (fish oil), dismantling branched-chain amino acids, and the metabolism of reactive oxygen and nitrogen species (catalase is made in the peroxisome). Catalase is the most important enzyme for neutralizing peroxide making catalase the front-line defense against oxidative stress.
Mitochondria can duplicate themselves. Peroxisomes can't, but they use mitochondrial-based enzymes to fuse with membranes calved off of the endoplasmic reticulum to initiate new peroxisomes. Curiously, the ability to chop up fats is linked to peroxisomes multiplying by the PPAR family of signaling messengers. Mitochondria and peroxisomes share a sensitivity to another common signal, PGC-1α. It's complex and intertwined but they both have this intimate dance together.
For example, they both can multiply by splitting in two, or fission. You can spend a whole afternoon down the rabbit hole of mitochondrial fission protein (FIS), and mitochondrial fission factor (MFF) which work to make both organelles multiply. If you want a PhD in Molecular Biology, throw in ganglioside-induced differentiation-associated protein (GDAP) 1, and dynamin 1-like protein (DNM1L).
What's important for us to know is that they are linked, intimately. These organelles aren't just in the cell together. They often touch each other and have now been shown to share little packets of membrane with each other. We die when our mitochondria fizzle out. The internal membranes of mitochondria have a very high level of plasmalogens, manufactured in the peroxisomes. That's what you are nourishing when we take Prodrome Glia and Prodrome Neuro. Maybe it's the pair of organelles that really determine our longevity.
www.What will Work for me? We think the most accurate indicator of peroxisome's function is our level of triglycerides. High triglycerides are lethal, for many reasons. It indicates insulin resistance, fatty liver, coronary artery disease, and a whole raft of other problems. Triglycerides below 100, or even 75 is a notable target. How to get there? This is where the miracle of exercise comes to bear—and eating less ultra-processed food. Vegetables and fruit in whole food forms help reduce your triglycerides. Free sugars help accelerate the rise of triglycerides. We love the flavor sweet, but it is dangerous. Your peroxisomes tank.
References: Int Jr Mol Sci, Exp Mol Medicine, Science Direc, Frontiers Cell Biology,
Pop Quiz
1. What is a peroxisome? Answer: In intracellular organelle, intimately linked and acting in concert with the mitochondria.
2. How are they linked? Answer: For one, they are almost always proximate to each other, often kissing (touching each other) and exchanging packets of membranes. (Oh, this is getting so sexy, I'm not sure I can continue.). Let's call it dating.
3. What are the key functions of the peroxisome? Answer: Quite a few. They are the sole source of plasmalogens. That would be enough. But they make catalase, one of the primary antioxidant enzymes to neutralize peroxide and other reactive oxygen species. They chop up fats and branched chain amino acids.
4. What is the best measure of peroxisomal function? Answer: Low triglycerides.
5. How can I stimulate my peroxisome function? Answer. This is where all the standard adages of healthy living come into stark relief. Exercise and vegetables do it. Carbs don't.
Cancer Cells Have Way Too Much Cholesterol, Why?
Warburg noticed that cancer cells can grow without oxygen. For that, he got the Nobel Prize in Medicine in 1931. Interest in cancer skyrocketed. Despite his Jewish heritage, Hitler (obsessed with his own risk of cancer, protected him during the Third Reich. Understanding what's going on is all about cholesterol control and mitochondrial disruption. I thought you might like to understand that too. Let's give it a try.
The Frontiers in Cellular Biology link is an interesting example. The authors explore in exquisite detail how cancer cells export citrate in abundance instead of using it for energy. And they confirm the absolute recognition that cancer cells get overloaded with too much citrate, and how that comes on early in the cancer process. All well and good. But they leave the question of why unanswered. The literature in medicine is so vast, they didn't find Mandell or Natalie Munn. I find it so interesting that a very recent review article didn't get that connection.
It was Mandel in 1998 who reported (Biochem Biophys Res Commun 1998) the first clue that pointed the way to plasmalogens. She noted that HDL export out of plasmalogen-deficient cells was markedly decreased and markedly improved with the restoration of normal membrane plasmalogens. They concluded that plasmalogens play a critical role in HDL cholesterol efflux (export). As simple as that sounds, this is the nexus of cancer.
Natalie Munn at Tufts in 2003 (Journal of Lipid Research) with mutant hamster ovary cells that were missing the ability to make plasmalogens. Their deficient HDL export was completely restored to normal by genetically adding ethanolamine plasmalogens back to the environment. That work confirmed the recognition of the central role plasmalogens played in cholesterol efflux (export). Cells simply need sufficient plasmalogen content in their membranes to get rid of excess cholesterol. If they can’t get rid of it, it accumulates. That accumulation may be the cancer tipping point, because mitochondrial membranes then get rigid, and the mitochondria start exporting citrate. There you have it. You can see the steps laid out. Cancer starts with an environment of deficient plasmalogens. That is the prodrome state of a hostile biochemical environment. Cancer naturally happens because it is being goaded into a cancerous state.
It's actually quite simple. The HDL system is the means by which cells get rid of excess cholesterol. For that system to work, it needs sufficient plasmalogens in the membrane around the exporting system. Plasmalogens can shapeshift. They provide cells with functionality of their membrane lipids. If cholesterol accumulates, mitochondrial membranes get rigid and stiff and switch to exporting citrate instead of burning it for fuel. Cancer cells need that citrate to grow. Did you get that? It starts with low plasmalogens in the membranes.
And Goodenowe, in his metabolomics studies has shown that every cancer occurs in folks with low plasmalogens. That's the prodrome state. The reason cancer cells have so much cholesterol is that they lost their protective plasmalogens to oxidative stress, altering their internal mechanisms of cholesterol export. That’s the answer.
Cancer is an inevitable response to an environment that depletes plasmalogens.
www.What will Work for me? Anything that makes an oxidative state depletes plasmalogens. Too much sugar will do it. Ultra-processed foods get digested too fast and overwhelm your mitochondria. Sitting at a desk isn't so good either. Smoking? Pesticides? Lack of sleep. The list is long. Each contributes a few percent. Has it been proven yet? Nope. The supplements have only been on the market for 2 years, during which the last 6 months there was inadequate supply to keep up with growing demand. We don't have long-term studies. We do have good science. I'm taking them myself, in part just for that, to prevent my getting cancer.
References: Frontiers in Cellular and Develop. Biology, Cancer Metabolism, Biochem. Biophys Research Comm, Jr. Lipid Research,
Pop Quiz
1. What is the first step in "getting" cancer? Answer: Depleted plasmalogens from oxidative stress.
2. Why does oxidative stress deplete plasmalogens? Answer: Oxidative stress basically means mitochondria are losing control of electrons because of some damage to the mitochondria. Those electrons get turned into peroxide which attacks the plasmalogen molecule. That neutralizes the peroxide but you lose the plasmalogen. The whole molecule. Keep that up and you don't have enough for your HDL system to turn on properly.
3. To get rid of extra cholesterol, the body uses what mechanism? Answer: That's what HDL lipoproteins do, take excess cholesterol back to the liver to export in the bile.
4. HLD export is absolutely dependent on what? Answer: Sufficient plasmalogens in the membrane.
5. With excess cholesterol in the cell, what happens to mitochondria? Answer: They start exporting citrate. Making Warburg proud.
Prevent Influenza and COVID-19 with 99% Reliability
No, I'm not kidding. This is real science. As published in the Journal "Advanced Materials" the Harvard based authors used known viral suppressants to make a PCANS, Pathogen Capture, and Neutralizing Spray, that uses already known, approved and GRAS (generally recognized as safe) compounds to make a multimodal liquid that can be given intranasally as a spray.
Current nasal sprays available at your local pharmacy use single compound formulations, and subsequently only offer limited protection against respiratory viruses because they have only one mechanism of protection. They either neutralize the virus or block its entry into the cells lining the nose. That's where most viruses typically spend the first day or two duplicating and preparing to spread by sneezing or coughing to others, or diving down deeper into the lungs and causing more severe disease.
The spray is already on the market being sold as "PROFI" for $ 25 even though it has not been tested in humans. The authors tested it in lab rats and in that context measured a 99% reduction and protection from infection.
The authors cite three complementary mechanisms of inhibition. First, the spray makes a gel-like coating of the nasal passages that captures the virus and prevents it from entering the cells lining the nose. The "spike protein" equivalents that many viruses use to attach to cells appear to get all gummed up with the gel-like biofilm. The spray was shown in rats to capture twice as many particles as the normal mucus lining the nasal cavities. One of the principal authors claimed that the gel was about a 100 times stronger as a barrier than regular mucus.
This is a nifty idea. Considering the recent interest in Nitric Oxide for fighting viral infections, one would ask if the two could be combined. Remember, your nitric oxide declines by 12% per decade so if you are over 60, you are down 75%, and 85% if you are over 70. You just can't kill viruses on your own anymore.
Finally, there is hydrogen peroxide as a nasal spray. We know the virus spends at least the first two days in the nose before the person becomes infectious or the virus spreads to the lower respiratory tract. That is a time window in which peroxide could sanitize the nose.
Finally, there are some authors that suggest iodine drops in the eyes might also block another portal of entry as iodine is known to kill the virus.
www.What will Work for me. COVID will be with us now forever. It is getting milder but it is still a nasty disease for those who are traveling, are older, immunosuppressed or whatever. You may want to try some of these preventative strategies when you are going to be exposed to large crowds, traveling, celebrating, or just wanting to be careful. I just traveled for 11 days to Switzerland to help our son move into a new home. Planes, lines, customs, passport control, museums, and restaurants were all on our menu. We sprayed our noses with 1.5% peroxide twice a day and came back without any viral illness. We also took NO twice a day. Considering my desire not to get COVID again, I'm buying the Profi and giving it a whirl.
References: Profi , Advanced Materials, Harvard Medical School News, Applied Materials Today, Infection Control Hospital Epidemic,
Pop Quiz
1. What does PCANS stand for? Answer: Google will tell you it's for pecans. In this context, it stands for Pathogen Capture and Neutralizing Spray.
2. How did they make it? Answer: Using off-the-shelf ingredients, they formulated a blend of multiple ingredients that makes a gel inside the nose that lasts up to 8 hours.
3. How effective was it in preventing COVID in lab rats? Answer: 99%
4. Has it been tested in humans? Answer. No
5. Do you have a problem with that? Answer: Well yes. We humans aren't lab rats. Well, most of us aren't.
Cipro and Levaquin Can Cause Severe Long-Term Mental Health Issues
Quinolones are a class of antibiotics that include Cipro and Levaquin. Don't forget Norfloxin or Ofloxacin. Mefloquine is a quinolone derivative used for the prophylaxis against malaria. All of them are being recognized for causing a mystery illness that can include severe anxiety, depression, paranoia, and all the rest of the quinolone syndrome nightmare that many have experienced after taking Mefloquine for malaria while traveling. Then get a UTI and treat that and you get a double whammy.
Just ask the Canadian soldiers required to take Mefloquine while in Afghanistan and now are disabled for life. Just ask our VA in the USA about Mefloquine syndrome and you get "psychiatric symptoms such as anxiety, paranoia, depression, mood changes, hallucinations, agitation, and unusual behavior".
Are you going on a trip to warmer places this winter? Planning on taking malaria prophylaxis? Picking up some Cipro just in case you get a UTI? Hmmm. Maybe you should reconsider.
Just what is going on? The science is now coalescing, and it starts to make sense.
First of all, we have learned that quinolones directly damage mitochondria. When you upset the mitochondria, the site of careful energy extraction from electrons, the dammed-up electrons spill out and cause oxidative stress. That means there will be way too much measurable oxidizing compounds in the blood, most notably hydrogen peroxide and the hydroxyl ion (-OH). And there is.
Your first line of defense against oxidative stress in your blood is glutathione and folks suffering from that burst of oxidate stress have low glutathione. Do you see that in the quinolone syndrome cohort of patients? Yup, yup, yup. Down some 76 % in regular folks being given Cipro for 5 days.
If glutathione is down that far, the oxidizing compounds will make it to individual cell surfaces all over your body. There we now know that plasmalogens are the first line of defense on the outside surface of the cell. When they see hydrogen peroxide or the hydroxyl ion, they expertly neutralize it and in so doing make a malondialdehyde molecule as a byproduct. Malondialdehyde is the most potent signal to active microglia. Do we see high malondialdehyde in fluoroquinolone syndrome? Again, yes indeed.
Activated microglia are a problem. They are messy in their clean-up attempts. They are the white cells of the central nervous system, and they come scurrying on over to kill what they think is an invading bug. They flood the zone with glutamate trying to suffocate the invader and deprive it of methylation capacity. The problem with that is the brain is floating in water. You can't isolate where your glutamate goes to in a water environment and the cell next door also takes a hit. It too becomes damaged. It too needs to be cleaned up. And then the next cell and the next and the next in perpetuity. That is the basis for the chronic disease that never gets better. Or can it?
Well, this is the genius of Dayan Goodenowe. He located and identified exactly this pathway as the cause of autism, ADHD, multiple sclerosis, and many other central nervous system diseases. Depleted plasmalogens create the loss of cellular function. Plasmalogens are the key to maintaining proper cellular function and their sacrifice to salvage oxidative stress reduces cellular function dramatically. (For example, myelin is the insulation of the axons in white matter. It is some 20-40% plasmalogen in content. With less myelin, nerve signals don't travel effectively, if at all). What makes those suffering from all those maladies is the random nature of what part of the brain takes the hit.
What's the cure? Reverse flood the zone with all the building blocks to overwhelm the microglia and effectively silence them, turn them off, and put those attacking Rottweilers back in their cage. Calm the ongoing destruction. Add plasmalogens replenishment to help repair the damage that's happened. That's what works. That's the cure.
www.What will Work for me? Does this really work? There hasn't been any study published yet, but I'm certain it does. Other brain illnesses with this treatment pathway get better. But what I can tell you is that I will now consider the quinolones to be highly suspect and used only in desperate last-option situations. If you are a victim, please start taking B12 and folate the begin repairing your homocysteine and NAC in order to repair your mitochondria and raise your low glutathione. I'll help you. If you know anyone who has been "floxed", send them this article.
References: Report to Canadian House of Commons, VA Public Health. Mini Rev Med Chem., Jr Young Pharm, Jr Young Pharm, Oxidative Med Cellular Longevity,
Pop Quiz
1. What do the quinolone antibiotics do to mitochondria? Answer: Damage them almost immediately.
2. What is the observed consequence of a mitochondria that is damaged? Answer. Electrons escape outside the mitochondria and are very dangerous to every protein. They must be neutralized. Two enzymes, Super superoxide dismutase and catalase both play a role in capturing those errant electrons and turning them into hydrogen peroxide.
3. Peroxide is still an oxidizing problem. What is the body's main defense against it? Answer: Glutathione. And glutathione can be shown to be down 76% in just 5 days with someone taking Cipro.
4. If hydrogen peroxide gets past the glutathione defense wall, what happens next? Answer: The peroxide makes it to the outer surface of cell membranes and is neutralized by the plasmalogen molecules that make up some 20% of every cell wall in your body.
5. What happens when you damage a cell wall plasmalogens with a peroxide molecule? Answer: You make the chemical malondialdehyde, which in turn activates microglia, the attack dogs of the central nervous system. They have a messy clean-up process and start damaging cells in perpetuity, unless "reverse flooded" with abundant building repair repair tools to overcome the damage they've made. Malondialdehyde has been measured as high in folks who have the quinolone antibiotic syndrome.
6. Can this be fixed? Answer: No proof yet but I'm pulling together two parallel tracks of scientific discovery and it makes perfect sense, and is a completely non-toxic cure. To date, there has been no other. And the whole package of the oxidative stress and long term symptoms match up with Long COVID, Chronic Lyme, CIRS. And they get fixed with this package.
Low Grade Acidosis is the Driver on Most Chronic Diseases
Woo hoo! This is a major research article and it points directly to most of us. Let me explain.
When you eat an acid diet, you have to excrete that acid. The acid flows through your blood to be excreted in your urine. There's not enough acid to be evident on simple measurement of blood pH as we have many buffering systems that hide the obvious acid content of our diet. Animal products all have animal-based proteins that have abundant sulfur-containing amino acids. That sulfur turns into sulfuric acid in the biological ash left over after all that "meat, cheese, eggs, milk" are digested. As we have gotten wealthier and can afford more animal products, we eat more because we like meat and cheese.
Vegetable or plant-based foods have many fewer sulfur atoms and the biological ash of plants leads you to have an alkaline urine. Not much, but pH of 7.5-8 is alkaline. That makes a dramatic change in our physiology.
This speaks to mammals that preceded us for 65 millions years as vegans had their metabolism rotate around that acid/alkaline balance. Even primitive tribes who are hunter-gatherers to this day still eat predominantly plant products with an occasional successful hunt of animals. Their urine reflects that with an alkaline urine, most of the time. We have only had 5 million years for humans to diverge from other hominids as we needed more calories to grow our big brains. Eating animal products supplied that. It should be noted that hunter-gatherers typically go for the fat first. Fat is acid-neutral. But 5 million years has not been enough time to change our physiology around the excretion of acid. And the implications require us to live beyond 40-50 to develop those diseases.
This article details those metabolic processes. It's written in plain English and very understandable so if you want to give it a try, it's a worthy read.
This review is the first time I've seen this topic identified as a point of interest. The authors, James J DiNicolantonio and James O'Keefe give some nice summaries. For lab tests, they suggest some better guidelines than the "normal range". The normal range of the sick population will give you what is seen in the population and not what is ideal. For example, normal Bicarb is considered to be 23-30 meq, as that is what is observed. The authors argue that the optimal should be above 27 and as high as 35! Whoa, that's quite a shift.
www.What will Work for me? The diseases listed by James J DiNicolantonio and James O'Keefe in their article include insulin resistance, osteoporosis, renal failure, hypertension, kidney stones, sarcopenia and what have you. To excrete acid, you force your body to break down muscle to get the ammonium ion that can then bind to acid. That's basically listing what some 90% of us have. Then we wonder why sarcopenia in on the list. This research is getting to the bottom of why diets having lots of plant products are so good for you. See the article for their nice list of acid or base in foods. Raisins are king with a very high alkaline content. You can calculate your acid-base balance with a simple formula. Cheeses get -6 points per serving of acid. Meats get -3 points per serving (3 oz) of protein. Breads and grains get -1 point. Plants are easier. Generally, they rate +1 per serving. You want a balance at the worst. Americans are far worse off. Our urinary pH is around 5.5 on average. We are all low-grade acidic. Big problem.
References: BMJ-Open Heart,
Pop Quiz
1. What is the acid-base effect of meat? Answer: 3 negative points per serving
2. And plants have what formula? Answer: +1 per serving.
3. What's the highest acidic food? Cheeses. get -6 points
4. Can you calculate the acid load of a Big Mac with 2 servings of cheese, 2 meat servings, 3 bread servings? Answer: -12, -6 and -3 = - 21. To neutralize it, you would need 21 servings of salad, green beans, cauliflower...., And we didn't even get to the damage of those fries.
5. This is the fifth or sixth time I'm written about our acid base balance. Do you ever think much about it? It's not been in the mainstream. Now it is. Is that good? Answer: It's getting to the root cause of mordibity and how to live longer with less disease. That's good
Remission of Diabetes is Best Achieved with a Plant-Based Diet
Understanding what causes adult-onset diabetes is becoming more certain. Fundamentally, it is insulin resistance. A healthy insulin level is under 5. The average American is at 12. That means they are spending extra effort to secrete more insulin than is healthy to push their blood glucose down.
This harkens back to the Randle Cycle. We've known about the Randle Cycle since the 1960s. It is the competition between fat and glucose to get to the cell first. Cells will choose one fuel or the other, but not both. Fat gets absorbed high in the duodenum and gets directly into the lymph system and then blood within minutes of eating. Fat wins the race with carbs to get to the cell first. In the cells, it down-regulates glucose uptake. When glucose from carbs shows up, it has no place to go as the cells have their receptors turned off. It can only mill around in your blood. That's a higher blood glucose....by a tiny bit. The response to that is a boost in insulin levels. Insulin forces it into fat cells for storage. You get fat, but don't have the energy to burn. (Read Khambatta's brilliant book, "Mastering Diabetes". which explains in detail the Randle cycle and relates his experiences of switching to a <2% fat diet and watching his insulin need go from over 100+ IU a day to 2 IU a day.)
The way to cure diabetes is to honor the Randle Cycle. It's as simple as that. The less fat you eat, which includes eating animal protein (that always comes with fat as part of it), the closer you get. When you cut out the milk in your coffee, you are getting close. What is enticing is that you can eat ALL THE FRUIT YOU WANT. Fruit has no fat, and is high in fiber. It is also high in sugars, but they come in their natural form with fiber attached. It takes about a week to get engaged and your glucose receptors sensitized. Glucose then has somewhere to go (into the cells) and insulin sensitivity returns. You only need 2-5 units of insulin a day. Low insulin means you stop the proliferation of renal tubule cells. You stop adding to your visceral fat. You stop making the inflammatory cytokines of visceral fat. Coronary artery disease goes away. Cancer risk drops.
You see, diabetes isn't a disease. It's simply the natural state when we force the adverse effects of the Randle cycle. A normal A1c is probably 5.2. We define diabetes as an A1c above 6.4 but that was an arbitrary committee decision. It's not the blood glucose you really should be interested in. It's your insulin that matters. You want an insulin level below 5. Three is better. The "normal" range of 2.5-29 is nonsense. That is what is seen in the population, but it is not in the normal physiological range.
What's changed is that this Low Fat, vegan diet has become such a topic of discussion. Mainline medicine is jumping on board. The AMA-sponsored American College of Lifestyle Medicine published a study this July showing that a plant-based low-fat diet induced remission in a study of some 80 folks with high A1cs. There are more and more of these types of studies.
If you think about it, this shouldn't be all that surprising. It was only 1870 or so that we developed the tools to press oil out of seeds and our fat intake skyrocketed. With high fat being part of our diet, the scales were then tipped for the Randle competition to take hold. And we all got fatter and more insulin resistant. Keto diets work to a measured degree. Saturated fats, unfortunately, are deadly so feedlot-raised animals induce heart disease.
www.What will Work for me? All the fruit I want? Really? I've been toying with inducing the Randle cycle in myself. It works. It really takes a week to take effect. I can cut the salad dressing and use balsamic vinegar instead. And I can keep lots of fruit in the fruit bowl. If I'm hungry, I can have a piece. I'm surprised by how often I think I need a snack, but I'm not really hungry enough to peel that tangerine. And I've had multiple patients in my practice report success back to me. Ozempic be warned!
References: Wikipedia, Mastering Diabetes, AMA Ed Hub,
Pop Quiz
1. What is the Randle Cycle? Answer: The race of nutrients to get to the cell first and block the other nutrient family from absorption. Fat versus carbs.
2. What happens when fat gets to the cell first? Answer: it blocks the uptake of carbs so they mill around in the blood, making for a higher blood sugar that then requires a higher insulin.
3. How can I tell I'm losing the Randle cycle race? Answer: Your insulin level is higher than 5.
4. How can I fix my dysfunctional Randle cycle? Answer: Less than 2% fat, with a preponderance of vegetables and fruits.
5. Can you name an author who has advocated this tool? Answer: Pritikin, Ornish, Khambatta, Esselstyn. All said the same thing, and all have been generally ignored, to our collective peril.
Propionic Acid - a Poison Under Our Noses
Ever heard of propionic acid? It fits right before beta=hydroxybutyrate, a 4-carbon organic acid that is the principal ketone made with digesting fat and fermenting green vegetables in our colons. The biome of our colons thrive on beta-hydroxybutyrate, and indeed, it is the main food for the cells lining our colon.
Propionate is one carbon shorter. It is a three-carbon organic acid, also made in the colon at a much lower content. Acetate, another organic acid in the colon is a two-carbon fragment. There you have it. The family of 2,3 and 4-carbon acids, all made in the colon from fermenting complex carbohydrates by the biome of our gut.
Propionate has not been researched as much as the others as it is a "lesser" player. However, it has been shown to lower fatty acids in the liver, increase immune function, decrease appetite, and improve insulin sensitivity. These are all good, yes? There are review articles in the literature that suggest propionic acid plays a key role as a major mediator between nutrition, gut microbiota, and physiology. It sounds like nature has used a natural, 3-carbon acid in a sensible, balanced way. So far, so good.
What happens if we get too much? Propionic acid is a pretty good food preservative, so adding a bit of it to bread products gives you a longer shelf life. It is also naturally present in "Swiss Cheese" as the propionibacteria that help make the carbon dioxide bubbles in Swiss Cheese also make a lot of propionic acid. It is Generally Recognized as Safe (GRAS) in food products. But is it? It is naturally there, after all.
The problem is too much. When added to food products, the amount of propionic acid appears to exceed a threshold in human brains, particularly young ones. Autism has been rising precipitously and many, many mothers will tell you their affected children do much better when taken off bread products.
When human neural stem cells are exposed to propionic acid at levels found in bread and dairy products, the normal differentiation of the stem cells is drastically changed from making neurons to making glial cells. The neurons also didn't migrate, like they were meant to. This leads to altered brain structure. Oh dear, this is a big problem. Plus, the gut biome was altered. Which comes first? Is it the changing gut biome altering the immune system or the brain that then talks back to the gut?
The Europeans require a ceiling of 3000 mg per kg of propionate. Swiss cheese routinely measures between 3-5000 mg. Bread products also come close to pushing that ceiling. In America, the GRAS certification, (Generally recognized as safe) means bread and wheat product makers can use all the propionate they need to get long shelf lives of their pretzels, hot dog buns, bread, donuts, and pie crusts.
Our modern food supply is heavily dosed with preservatives like propionic acid. Of course, we don't want moldy, spoiled bread. Maybe we should be doing what the Europeans do, go down to the bread store every day and get fresh bread.
Many of those preservatives, notably propionic acid are labelled as GRAS. They might "appear" to be GRAS is perfectly healthy, adults who have reserve metabolic resources, but they dangerously tip the scale. If they are dangerous for small children, they aren't much better for older folks. We just haven't yet learned how to quantify the danger. It's not a poison per se, but it is a stark example of the dysfunction that occurs when subtle metabolic ratios and balances are altered.
www.What will Work for me? ADHD is autism "light". Both are on a skyrocketing trajectory. The teeny bit of estrogen in girls over boys is enough to tilt the odds of autism to 3:1 over girls, so this is by and large a boys' problem. This creates another reason to avoid wheat products. We haven't had the research yet on adults who can't lose weight, but it is not surprising to me anymore when I see a weight loss book that includes staying away from wheat. If you have any children or grandchildren who demonstrate the least bit of ADHD, get them off wheat. Maybe if you make it yourself from pure, organic wheat flour, you may be ok. And if it's bad for kids, it can't be oh-so-good for you.
References: Progress in NeuroPsychoPharmacology, Foods, Biochem Biophys Acta, Nature Briefing, Foods Sci Biotech,
Pop Quiz
1. What is propionic acid? Answer. A three-carbon acid naturally found in gut digestion as part of the digestion of various food products.
2. Why is it a problem, or a poison? Answer: It's all in the balance and total amount. When added to commonly consumed food products, it increases the total amount, raising the concentration.
3. What do we see in autism in regard to propionate? Answer: We find much higher levels in the stool of autistic kids and many improve when taken off of it.
4. Lab research on neuronal stem cells and propionate shows what? Answer: dramatic alterations of what cells develop into neurons (like an 80% decrease in quantity) and altered migration, leaving a brain that has structural damage.
5. Besides wheat, what other foods have propionate in them? Answer: Cheeses, particularly Swiss or Emmental cheeses.
Resistant Starch - We Aren't Getting Enough
Do you know what a resistant starch is? Well, easy. It's a form of starch that resists digestion, making it past your stomach and small bowel to the large colon. There, magic happens in the right circumstances. So, not always. It depends on the type of resistant starch. Let's see. They use the initials RS for the "Resistant Starch" type.
RS-1 is the whole grain. Imagine a whole, raw kidney bean. It hasn't been cooked. Its carbohydrate molecules are tightly packed and then coated with an outer fiber barrier that keeps digestive enzymes out. It sure is resistant. In fact, so much so that some of those raw, whole beans get pooped out to grow new beans.
Under an electron microscope, there is an orderly, packed, dense matrix of long molecules. Imagine a milkweed pod filled with seeds, all highly packed. That's RS-1. No digestive enzyme could get into that tight, dense matrix.
RS-2 is what happens when you cook the RS-1 in water. Heat it and add water. The starch molecules fluff up, sort of like a milkweed escaping its pod and letting its fluffy fibers stretch out. With RS-2 carbs, that is essentially adding lots of water molecules which lets the molecule fluff up. That creates lots of entry points for digestive enzymes to chop up the long chains of glucose into single glucose molecules. Think of a dandelion seed that you blow on. It's all puffy with many points of attachment for enzymes to digest. They can do so, rapidly. Most of what we eat is RS-2. Eat a serving of rice or hot potatoes, and your glucose spikes rapidly. One serving of rice and my glucose will go from 95 to 160 in half an hour.
RS-3 is RS-2 cooled down after cooking. The long strings of glucose contract and curl up. They can't get back to their original source of manufactured density, but their twisting and curling make it hard for enzymes to get in to digest. RS-3 is like white rice, heated up and cooked (fluffy and rapidly digested), then put in the fridge and cooled down. Those long chains coil up. Enzymes can't get it. Glucose rises much less rapidly. Cooked rice, pasta, and cooked potatoes, cooled down, are resistant starches. Blood sugar rises much more slowly.
RS-4 is an artificial, man-made resistant starch that is chemically altered to make thickening agents for packaged food. You are likely getting quite a lot of this. They aren't made by nature. They may be useful too, just need research to prove their safety.
The magic of resistant starches is that they don't get digested in your small bowel, and therefore make it to your colon where your community of bacteria that define many features of your well-being reside. They love resistant starches and blossom. Research is now proving that. More resistant starches turn into more beneficial bacteria. They make loads of beta-hydroxybutyrate which plays a huge role in calming inflammation. The alteration of your biome is critical to many diseases. A fine study from China giving increased resistant starches to folks with fatty liver found about a 10% reduction in intra-hepatic triglycerides, the fats that infiltrate and damage the liver.
Americans get about 3.5 grams of resistant starches a day. It is thought that we are optimally served if we get 20-35 grams of fiber a day. There is pretty good evidence that folks eating over 30 grams of fiber a day simply never get diverticulitis, appendicitis, colon cancer, heart disease, GERD, or irritable bowel. Goodness, that's what afflicts all of us.
www.What will Work for me. Well, the best dietary sources of resistant starches are raw potatoes and green bananas. That doesn't work very well. But raw potato starch added to a smoothie works just fine. Beans are magnificent sources. All beans. Oatmeal is another great source. Make a Muesli breakfast of raw rolled oats with some raisins figs, and slivered almonds. Maybe better yet is to get in the habit of making extra rice and eating it the next day, cold. Ditto for potato salad. You get to have some carbs, in a good form. It's surprisingly good for you. I was just visiting our grandchildren in Switzerland. Our hotel breakfast every morning was Muesli. I loved it. No sugar needed.
References: Cell Metabolism , mSphere, Nurition Jr, Jr Amer Dietetic Association, HealthLine, GimmesomeOven, Br Jr of Nutrition, Global Prebiotic Association, , National Geographic,
Pop Quiz
1. What is resistant starch? Answer: Carbohydrates that resist digestion for several reasons: still in their raw, tightly packed form, cooked and cooled down, or naturally high in fiber (like beans).
2. What happens to the stored form of glucose in plant carbohydrates when it is heated up with lots of water? Answer: Imagine a dandelion or milkweed seed that is tightly packed until its envelope opens. They fluff up and spread all the arms of the "amylose" (that's the molecule of long chains of glucose that we call carbs) molecule out creating a massive increase in enzyme accessibility. Enzymes can then cut the bonds between the glucose molecules at a thousands-per-second rate.
3. Cooling of pasta, rice, and potatoes does what to the starch. molecule? Answer: it shrinks down the long chain of glucose molecules into a tangled web that is all coiled up again. Enzymes can't digest it as quickly. It's that simple.
4. Name some really good sources of resistant starches. Answer: raw oats, all beans, cooled rice/potatoes/pasta, green bananas, Jerusalem artichokes
5. Can I just take a pill? Answer. Well, yes. You can buy Inulin, which all by itself is a resistant starch. It is extracted mostly from Jerusalem artichokes, chicory, and onions. But far better to make your food be rich in resistant starches.