Oxidized Phospholipids And Autoimmune Diseases
The Holy Grail of medicine is "just what starts it all". We have yet to find that unified hypothesis of disease that would explain how the human body gets in trouble. Inflammation is a pretty broad excuse and doesn't quite get down to the details that matter.
I have witnessed two remarkable events in the last month that might give insight. They both got my curiosity going. One was in a client with modestly abnormal oxidation of cholesterol and a high cardiac calcium score. On taking Plasmalogens, Nitric oxide, and a statin, showed the most dramatic improvement in oxidation levels I've ever witnessed. I've seen dozens of statins not changing much. The second was a person with interstitial cystitis who was desperate, having failed all conventional therapy. She started on Prodrome Glia, the plasmalogen designed to repair white matter in the brain and have potent anti-inflammatory effects. She took a 100 mg per kg dose and had 80-90% symptom relief in just 3 hours.
There have been reports in the literature for almost twenty years that oxidizing compounds are the actual cause of coronary artery disease. It was in 2006 that Tsimikas published in the J Am College of Cardiology the results of the Bruneck Study, a 10-year follow-up of 765 men for coronary artery disease with the finding that it was oxidized phospholipids (that's plasmalogens) that predicted future coronary artery disease better than any other marker. The sequence of disease in coronary artery disease is now widely acknowledged as being some sort of oxidizing stress that damages the endothelium, the lining of the arteries throughout the body. With damage to the endothelium, the cells that make up the lining pull apart, leaving gaps. Into those gaps come oxidized LDLs. Cholesterol accumulates. It was the oxidation of the plasmalogens in the endothelial cells that made the gaps. This leaves the "oxidizing stress" as the first initiator of coronary artery disease. The subsequent damage to plasmalogens makes for oxidized phospholipids, which are the acknowledged most accurate predictors of future stress. Lowering cholesterol with statins is a sideshow. Repairing oxidative stress is the main act.
We've also heard the recent report of 7 children from Seattle with COVID myocarditis and C-reactive proteins above 100 resolved in just 48 hours with Prodrome Glia. This suggests that the pathology of COVID myocarditis is plasmalogen loss in the sarcoplasmic reticulum (the membrane, made of plasmalogens, that surrounds all muscle cells and sequesters calcium releasing when needed it to allow contraction). COVID depletes that membrane plasmalogen content and heart symptoms follow. Replenishment repairs the damage in 48 hours.
These three disparate events can only be explained by depletion of membrane lipids (plasmalogens) by some oxidizing stressor. The body can only repair those membranes slowly in the environment of ongoing oxidative stress. Interstitial cystitis waxes and wanes with mysterious irregularity and can last a lifetime. Want to fix it in 3 hours? Want to repair your coronary artery disease? Your COVID? The Holy Grail of common pathways may be before us. Maybe all autoimmune diseases are caused by membrane damage, exposing naked tissue below that then develops antibodies. We've been chasing the antibodies. Perhaps we should be focusing on repairing the loss of phospholipid building blocks in the membranes.
www.What will Work for me? I'm letting these observations soak in. The more I look in the published literature, the more evidence I find to support the observations I'm seeing. The question is, "What is the source of oxidative stress and how can I fix it." Oxidate stress probably comes most reliably from processed carbohydrates and fructose. Table sugar and white flour converted into donuts, chocolate ice cream, fast food with no fiber, and just about every prepared food we eat puts us at some risk. Visceral fat is the manifestation in our abdomens that we have oxidative stress in abundance. My little poochy tummy is there. It's my job to lose it.
References: Subcell Biochem, Jr Am College of Cardiology, Biochem Cell Biol, Matrix Biology, Arterio Thromb Vasc., Natur Clin Pract Urology,
Pop Quiz
1. What is this evil Darth Vader called oxidative stress? Answer: Extra electrons that escape the mitochondria and cause the production of reactive oxygen species.
2. Why are the mitochondria so touchy? Answer: The mitochondrion is a miraculous organelle upon which all animal life depends. It is what it is. It functions best when it has food fed to it in a regulated fashion. A flood of calories from processed foods overwhelms it. Think putting gasoline into your gas can with a small funnel that overflows. That's oxidative stress. When you light the match. In human history, we have never had mounds of sugar on top of highly refined flour, on top of mounds of saturated fats that we call Thanksgiving or fast food, or a bag of chips during a football game. Our food has been so purified, it gets digested too fast with too many calories. That tips the balance.
3. Why do plasmalogens get depleted? Answer: A plasmalogen is a membrane lipid, making up some 20% of every cell membrane in your body, but 70% of your myelin in your brain and in the synapses in your brain. It is the only lipid with a precious, vinyl ether bond on the outer surface of the cell that is positioned to soak up peroxide, made by oxidative stress. They are the anti-oxidant of first resort. Vit C and E are intracellular. They come second. That saves the cell but depletes the plasmalogens. You get in trouble when you have ongoing oxidative stress that strips away your plasmalogens. As you deplete plasmalogens, you deplete cellular function. (This, in a nugget, is my explanation of the Holy Grail of Medicine). Let's see if this plays out.
4. Has this hypothesis been proven? Answer. No, not in large studies. But the clinical story is before us that can be explained in no other fashion, and the bench research supports it.
5. What's changed that this is just coming out now? Answer: Dayan Goodenowe has learned how to manufacture the plasmalogen supplements that survive digestion and show up in your blood as the missing, damaged plasmalogen building blocks to repair the oxidized membranes. We have never had the ability to repair damaged membranes before. We had to just wait. We are at the dawn of a revolution in medicine. Aren't we lucky?
Red Meat and Processed Meat and the Risk of Diabetes
It's been a hunch for years but has never been properly studied. Immigrant studies back in the seventies first gave a clue. Japanese immigrants to Hawaii had the rate of diabetes and heart disease as other Hawaiians in the 1950s, only to have rates increase to 160% of the Hawaiian caucasian population in the 1970s. The same trends were observed in PIMA Indians and Canadian Indigenous peoples, an increase in diabetes and heart disease.
In a similar fashion, the Seventh Day Adventist Study in 1985, showed a dramatic difference between the predominantly vegetarian Adventists and the rest of the American population.
There have many smaller studies but none has been as authoritative as the Women's Health Study released in 2004. In this very large study, 39,876 female health care professionals were randomized who were free of diabetes, cancer, stroke or heart disease. They had to complete a 131-question food frequency questionnaire. They were free of diabetes at the start and were then assessed to see if they developed it over the next 6 years. Samples of the total population were then contacted by phone and had confirming blood samples. The methods were rigorous and met statistical thresholds for validity.
Red meat intake was considered the sum of hamburger, beef, or lamb as a main dish, pork as a main dish, beef, pork, or lamb as a sandwich or mixed dish, and all processed meat. Total processed meat was calculated as the sum of hot dogs, bacon, and other processed meat (sausage, salami, and bologna). The semiquantitative food frequency questionnaire was validated against a subset of women who had a two-week detailed dietary analysis and then projected on the whole group.
Meat consumption was categorized by aggregating nine possible responses into four categories for red meat and total processed meat (<1/week, 1/week, 2–4/week, ≥5/week). The subtype of red meat and processed meat were categorized into three categories (<1/week, 1/week, ≥2/week). At the beginning of the study the variability of meat intake was almost 10 fold from least to most. During the 8.8 years of follow-up (326,876 person-years), the researchers documented 1,558 cases of type 2 diabetes. Across the spectrum of consumption, risk for diabetes with red meat consumption was 29% higher, processed meat 43% higher.
That's a lot of numbers but 43% is pretty awful. Processed meat stands out as particularly awful. What gives? How can one be safe on the Carnivore Diet if red meat does this to you? Recent evaluation of gut microbiome suggest that all that meat/saturated fat changes the microbiome of the gut producing substances like TMAO, found to be strongly linked to vascular disease. That premise has been rigorously argued and several well-done studies suggest it's not true. What to believe? I think there is more to be understood by the saturated fat in our red meat created by feeding our animals corn and beans. High, refined carbohydrates make inflammatory fat in our visceral fat and marbling in our muscles. So to in the animals we eat. That's what has changed since the 1950s, a massive shift of animals from pastures to feedlots. The food they eat gets reflected in us. It's their inflammatory meat we are eating and being harmed by. Processed meats are particularly concentrated with their saturate fat (think bacon).
www.What will Work for me? I accept the premise that processed meat, bacon included, just isn't good for us. I love liverwurst and braunschweiger. Shucks. What sparked this inquiry was a recent review in BMC Medicine demonstrating a metanalysis of all the data on red meat consumption and heart disease. The more fish and nuts, the better off we are. Start making that shift for yourself. Unless you are a deer hunter, goose, duck or moose hunter.
References: Diabetes Care, Diabetes Care, Am Jr of Public Health, BMC Medicine,
Pop Quiz
1. Eating processed meat like bologna, bacon, and bratwurst more than three times a week does what to your risk of diabetes? Answer: Some 43% higher risk.
2. How about just plain red meat like hamburger and steak? Answer: Well, a little better but still in the range of 25%.
3. What does red meat have to do with blood sugar? Answer: Just about every study notes that the more red meat eaten results in total more calories and resulting greater BMIs. The makes for more visceral fat. Bigger fat cells are all naturally insulin-resistant.
4. Is it the fat in red meat that causes the problem? Answer: lots of smoke but not proven.
5. How much fat do you see in grass-raised animals? Answer: it's deer hunting season right now. Virtually none. The fat in our red meat is because those animals have been force fed large amounts of grains that are not in their normal food supply. Grass is their preferred, natural food. They develop inflammatory fats in their muscles and viscera (just like we do on a diet of refined carbs), and we then eat the meat and ingest all those inflammatory cytokines.
An Influenza Shot Can Reduce Your Risk of Alzheimer's by 40%
No kidding. A well-done study from the U. of Texas (Houston) shows just that. The researchers took 2.6 million older adults to find 930 thousand matched pairs who did or didn't get flu shots. The risk reduction was 40%. This study has street cred because it was so large.
I would hope the reader would be able to identify the mechanism that gives this finding credibility, but let me repeat the probable mechanism so that it makes sense to you. Infections like influenza, COVID, and indeed, any other virus-like RSV, measles, etc, are oxidizing events. There is one common pathway in the brain for expressing oxidative stress. Mitochondria fail and start to spew out reactive oxygen species (ROS) which mostly get turned into peroxide as a first pass of neutralizing the ROSs. If the body's natural antioxidant defenses of glutathione are sufficient, there is no brain damage. As we get older, our defenses get less robust and we can't keep up. The peroxide makes it all the way to brain cells, be they axons or neurons, and damages the plasmalogens in the myelin or in the synapses which results in fewer synapses and impaired communication between neurons.
Alzheimer's is a disease of brain shrinkage caused by a lack of synapses. (Yale proved that last year by reporting cognitive function is a linear measure of synaptic density) We have some 200 billion neurons which are connected to roughly 4,000 other neurons by synapses, for a total of something on the order of 4 quadrillion synapses. That makes for a lot of resilience and redundancy which gives the brain leeway to take an infection or two. Alzheimer's, being a 25-year disease, presents with a very subtle loss of word finding, word replacement, or minor memory lapses that can go on for years.
Then a COVID virus takes whole and spews up a hurricane of peroxide and trillions of synapses get damaged and unhooked. Think brain fog. Many folks report brain fog for weeks after COVID or flu. Or anesthesia, or head injury postpartum, or with ADHD, CIRS, depression, anxiety....on and on.
As we age, our ability to remake replacement plasmalogens just fades away. We are short of B12, or folate, or choline or whatever, we just can't keep replacing those lost plasmalogens like we could when we were younger.
Part of what makes the plasmalogen molecule so intrinsically valuable is their vinyl ether bond that has the capacity to capture peroxide. That bond, the very possession of which by definition changes a phosphatidyl-choline molecule into a plasmalogen, sits on the surface of the membrane and is the antioxidant of first resort. It soaks up the peroxide and protects the cell beneath it. That chemical soaking up destroys the plasmalogen, but the cell is saved, as long as there aren't thousands or millions of peroxides more.
As we age, our ability to parry away oxidative stress declines. We are all losing brain volume. Do the math. The average human loses 5% of their brain volume over 10 years. If you have 200 billion neurons and lose 5% of them over 10 years, you are losing 634 neurons a second. We are all on the pathway to dementia if only we live long enough to have it afflict us. If you get repeated flu or COVID, you just get it sooner.
Once triggered, microglia in the brain get activated. The microglia are the garbage trucks of the brain. Their problem is that they are sloppy. They kill off the damaged cells they find by putting out glutamate to suffocate the cell. Unfortunately, that damages the otherwise healthy cell next to it. It's a Domino chain reaction that becomes very persistent. Hence, prolonged symptoms after head injury, COVID, etc.
That's why you need a flu shot or a COVID shot. It protects your brain. Your brain is your most precious asset. The vaccination is 1/10th the problem of the native infection.
www.What will Work for me? Well, I'm getting my COVID and influenza shots this week. You should too. I'm also taking my B Vitamins, creatine, and Egg Yolk Lecithin. I'm also of the belief that each of us should take a bottle of Prodrome Neuro and Glia after having COVID or influenza. I'm on a tear to prove that I can stop and reverse that brain shrinkage. So far, I think it's working.
References:J Alzheimer's Disease, Alzheimer's Dementia,
Pop Quiz
1. How much do I reduce my risk of Alzheimer's by getting a flu shot? Answer: 40%
2. Is this a credible claim? Answer: Yes. Huge study with rigorous methods.
3. Explain the plausible mechanism. Answer: Influenza, like COVID and many other severe viruses, creates a storm of inflammatory cytokines. They invoke the inflammatory cascade in your brain with results in peroxide being produced. That peroxide destroys plasmalogen molecules, designed to be the last line of defense before the cell gets damaged directly.
4. What happens to synapse density in the brain with plasmalogen destruction? Answer: You lose synapses (connections between nerve cells).
5. Is there a correlation between synaptic density and cognitive function? Answer: Yes. Directly measured at Yale by PET scanning. Indirectly measured by blood plasmalogen levels.
Visceral Fat Shrinks Your Brain
The gut-brain-immune triad is more complex and more important that any of us imagined. For starters, if you take 10,001 older Americans (average age 52) and do a whole body MRI scan with volumetric calculations of brain regions and body fat, notably visceral fat, you can show that quantity of visceral fat directly predicts loss of brain volume. Testing multiple areas of the brain the same findings were revealed with odds ratios of 5.1 and p values of < 0.001. The more visceral fat, the smaller the brain. Ouch!
Furthermore, if you take the bacteria in the gut of Alzheimer's patients and feed it to mice who are genetically programmed to get the same AD as humans, you can show that the human gut microbiome makes the mice develop an increase in their Alzheimer's behavior and pathology. This suggests that one avenue to prevent Alzheimer's would be to feed your own biome a healthy dose of probiotics and prebiotics to get your gut to blossom into a more brain-supporting biome.
What do visceral fat and an unhealthy gut biome have in common? We know pretty clearly that one serving of red meat will have a negative impact on memory and cognitive function. One serving. One meal! (Bummer!). Why would that happen? Cows being raised for beef are stuffed full of corn and beans, not their natural food, which is grass and green pasture plants. They get visceral fat and they are inflamed, just like we humans. We eat that meat and we are getting a dose of all their inflammatory cytokines, and their inflammatory fats. We also know that eating saturated fat can be shown to contribute to dysbiosis, increase intestinal barrier permeability, chronic low-grade inflammation, oxidative stress, and dysfunction of the blood-brain barrier, affecting the central nervous system.
There's your link. Saturated animal fats alter your biome and make for leaky gut. That leads to increased visceral fat that becomes a shower of inflammatory cytokines. Processed foods thrown into the mix compound the problem.
Those circulating cytokines will damage the lining of your blood vessels, the blood-brain barrier, and your plasmalogens (present in your endothelial cells and your brain). Remember, plasmalogens have a vinyl ether bond that is on the surface of the membrane on the outside of the cell. That's handy because it is the first to see peroxide, the universal marker of oxidative stress. If you use up plasmalogens, you have less synaptic density and less neurotransmission of signals. That's called lower memory function.
It sounds like the core nugget to take away is to increase your healthy gut biome because that is what leads to visceral fat. Considering that your gut biome is dramatically altered for the worse whenever you eat any sort of saturated animal fat made by corn-fed American animals (dairy, butter, yogurt, cheese, meat, steak, hamburger, sausage) we need to consider intentionally swapping out our meals of red meat for alternatives that have minimal processing, organic, with healthy omega fats. And processed foods, the engine that drives visceral fat has gotta go.
www.What will Work for me? Sounds like more avocadoes, more nuts, less hamburger, steak, and Braunschweiger. We are just learning how to measure the human gut biome. Lactulose is the best modulator for growing more Bifidobacter. Prebiotics like inulin work well too. Adding just plain fiber by eating whole foods adds a lot. Ground flax seed is particularly potent but commercial fiber products add an appreciable quantity. Better, just avoid processed foods that have all the fiber removed. That includes any grains. Replace your grains with whole vegetables. There are thousands of recipes and ideas.
Green Bean Salad: 2 pounds fresh green beans cut into 1-inch pieces. Boil for 3-4 minutes. Add 1/4 red onion diced. Add 1/2 cup goat feta. Add: 3/4 cup of vinaigrette made with 2/3s apple cider vinegar 1/3 olive oil and 1 T Dijon mustard. Add 1 packet of Stevia to the dressing.
References: Aging and Disease, Internal Review Neurobiology, Brain, Curr Dev Nutr, Jr Neuroimmunology,
Pop Quiz
1. What's the correlation between visceral fat and brain size? Answer: The more visceral fat, the worse your brain.
2. How does red meat contribute to cognitive function? Answer: One meal of American corn/bean-fed red meat will show reduced memory function.
3. What's the thread that ties all of these disparate ideas together? Answer: the inflammation caused by visceral fat and red meat depletes plasmalogens in the membranes of cells, notably the endothelium in your arteries and in your synapses and myelin in your brain.
4. The biome of bacteria in Alzheimer's patients does what to rat memory function? Answer: Decidedly worse.
5. Name some steps you can do to improve your own natural gut biome. Answer: fiber, fiber, fiber. Lots of organic whole vegetables and fruits. Cut processed foods and sugar. Cut red meat. Replace with nuts and fish. Add inulin and lactulose as supplements. (Jerusalem Artichokes are native American root vegetables in your organic grocery store now: rich source of inulin. They look like small potatoes and are often called "Sunchokes". )
6. Extra Credit Pop Quiz. If you have 200 billion neurons, and lose 0.5% a year after age 50 (so called "normal aging"), how many neurons are you losing each second? Answer: 317 . Can you afford to accelerate that?
Visceral Fat Causes Artery Disease
Visceral fat is the fat around your organs. It is internal fat and very different than subcutaneous fat. Subcutaneous fat is what you pinch on your side or arm or wherever. Subcutaneous fat is designed to store calories in order to make it through winter or any other calorie-deprivation period. It does not cause inflammation.
Visceral fat is a whole different affair. It spews out all sorts of inflammatory cytokines. Those cytokines cause damage and dysfunction in the endothelium of your arteries. The endothelium is essentially a thin layer on the inside of the artery that is nice and stretchy. A healthy endothelium is another term for normal blood pressure.
What happens if you gain weight? Well, take 43 young adults (18 women) and assign them to gain 4 kilograms (9 pounds) over 6 weeks. Then, with an MRI measure their total body subcutaneous fat, and their visceral fat. Add their flow-mediated dilation (FMD) to the mix and measure how it changes from baseline, to weight gain, and back to baseline after weight loss. The level of subcutaneous fat did not predict or correlate with changes in flow-mediated dilation. Visceral fat did. Flow-mediated dilation is the best measure we have of a healthy response to blood flow changes. The quantity of visceral fat in your tummy predicts the dysfunction and level of dysfunction in your arteries. There you have it. That's the link.
This is a big deal. In fact, it is the core of the heart disease story. Endothelial dysfunction is the first step in developing coronary artery disease. As endothelial cells get damaged, they pull apart from each other, opening gaps through which small, dense LDLs can get in. That's how cholesterol lipid pools get started. Repairing levels of cholesterol with statins doesn't fix the endothelial dysfunction, (ED). If you want to fix coronary artery risk, you have to stop the engine that's driving it. It is not cholesterol. It is the endothelial dysfunction, caused by visceral fat. Cholesterol is like the crowd at a football game. It gets all the attention, and affects the game a teeny, tiny bit, but is not the main game.
The real question is what is the initial damage to the endothelium that makes it so vulnerable to visceral fat inflammation? Answer: deficiency in plasmalogen lipids.
Speaking of ED, Endothelial Dysfunction highly correlates with Erectile Difficulty. In fact, in a study of 6,000 US Army soldiers, loss of visceral fat correlated strongly with increased muscle mass, increased pulse wave visibility, and increased erectile ability. (Podcast Communications)
Want to fix your artery disease? Lose your visceral fat. Repair your plasmalogen deficiency (Prodrome Glia and Neuro, 4 capsules of each a day). Take Nitric Oxide lozenges twice a day (Two companies now.). Get more Vitamin K2.
How can you fix visceral fat? It actually burns off faster than your subcutaneous fat when you have demand for stored calories. Intermittent fasting, fast-mimicking diet, Bright Line Eating, Whole Foods Diet....any diet that focuses on real, whole food with no artificial ingredients, sweeteners, sugars, or additive chemicals - they all work. That means no cured meats, no pizza, no fast food. No processed foods. Eat the apple, not the sauce. Eat the potato, not the chip. Then, make sure you get a good night's sleep, reduce stress, no alcohol, and exercise in bursts. No 5-mile runs. Certainly no 10+ mile runs either. Marathoners are all full of visceral fat, even though they look skinny. The extreme stress of marathon running makes for visceral fat, even when one appears trim. Do burst exercises instead: 100-yard sprints, 50-yard swims, 3 minutes on the exercise bike.
Your muscle mass will improve. Your face will slim down. Your belt line will get smaller. You will be able to see your pulses beating when you look at your wrist or your arm. Both men and women report better sexual function. Ah, there's a great motive! It's doable.
www.What will Work for me? I got confirmation from my MRI place that they are working on getting the MRI protocol set up so that your visceral fat can be measured. This should be interesting. I want to get mine done. I'm not sure I want to know the answer. I'm trying to buy more whole vegetables to make fresh vegetables. Frozen would be ok too, but fresh green beans are so delicious.
References:JAMA Network, J Am Coll Cardiology, Dhru Purohit Podcast 433, Nephrology Dial Trans,
Pop Quiz
1. What effect does visceral fat have on your arteries? Answer: You can measure endothelial dysfunction that takes as little as a 9-pound weight gain to cause.
2. What is endothelial dysfunction? Answer: The elegantly slender covering cells of your arteries pull back and stop covering the whole artery wall. There are gaps. A simple measure of that is whether you have high blood pressure. Not a perfect correlation, but cheap to measure. MRI of your abdomen is the gold standard.
3. What's wrong with gaps in the wall of your endothelium? Answer: That's where small, dense, oxidized LDLs get in. That's what it takes for heart disease to get started.
4. How does visceral fat damage the endothelium? Answer: Visceral fat spews out showers of inflammatory cytokines. Regular fat doesn't. Those inflammatory cytokines circulate in your blood. Your arteries have plasmalogen lipids as part of their membranes. Plasmalogens are the first line of defense for a cell against oxidizing stress. They have a vinyl-ether bond that is on the surface of the cell, waiting to deactivate peroxide, the universal messenger of oxidative stress. The plasmalogen content of the endothelial cell membrane gets depleted. The cell shrinks and pulls its membranes back in. Gaps open up. LDLs get in.
5. Is there published literature to support the plasmalogen hypothesis of coronary artery disease? Answer: You bet.
Visceral Fat is in Your Muscles Too!
Last week we learned that not all fat is the same. So-called "visceral fat" is inside your abdominal cavity and wrapped around your organs. It is intensely inflammatory" and associated with virtually all the disabling, degenerative diseases of aging. "Why are my knuckles so big?' or "Why is my knee arthritis so bad?" are both probably best answered by "The inflammation spewing out of visceral fat".
Accumulating visceral fat is probably a product of too many processed foods. The human body evolved to eat whole foods, minimally processed. Adding sugar, or multiple ingredients is a problem. Polishing and grinding grain provides for rapid digestion and higher glucose spikes than eating whole grains. All those changes overwhelm the natural storage of fat under your skin in so-called subcutaneous fat. Subcutaneous fat on your hips doesn't look aesthetically pleasing but is harmless in regard to creating inflammation.
What about muscles? Our muscles take a hit too. Because of the increasing ability of the CT and MRI scanners, we are able to examine muscles and ask the question, "What happens to them with aging?". Well, the answer is pretty simple. We lose muscle inexorably with aging. Sarcopenia. Old age is strongly associated with frailty and loss of muscle. Does it need to be? Well, maybe not.
What recent research is showing is that legs filled with intramuscular fat are unhealthy with much less lean muscle. Intramuscular fat is strongly associated with visceral fat. When you lose the visceral fat, the muscle rebounds and returns.
This just doesn't just happen to humans. Go your your local grocery store and look at the steaks. The marbled steaks are full of intramuscular fat. That makes them juicier and tastier. How did the cow or pig get that marbling? They were fed corn and beans. Lots of corn and beans. Keep the lights on late at night so the animals keep eating. (Just like humans. Perhaps the next step in animal husbandry is to give them inane TV shows to watch so they too can eat endlessly). And, as mentioned last week, outdated candy from Halloween. It's cheaper than corn and makes animals get fatter, faster. Ditto for humans.
That fat is also uniquely inflammatory, just like visceral fat. It damages the muscle around it and the inflammatory cytokines circulate around the body and damage the heart too. Intramuscular fat is strongly associated with heart failure.
Recent research done in the military (6,000 MRIs done on abdomens and legs), reported by conference presentations shows that the loss of visceral fat/intramuscular fat results in a dramatic return of muscle mass. This may be the clue to sarcopenia....we have visceral fat and intramuscular fat that leads us to have bodywide inflammation. We have now proven it causes damage to one muscle we can easily measure, your heart. It's not a big jump to assume it also damages all your muscles.
What's the fix? 1. Avoid processed foods. If it has more than 5 ingredients, it is ultra-processed. Avoid any form of sugar, or any form of flour, and focus on the whole food. Don't eat inflammatory meat. That means grass-raised and grass-finished. Same for dairy and eggs. 2. Exercise in bursts. No marathons. No five-mile runs. Do sprints. Running, swimming, biking....bursts. 3. Get a good night's sleep. Darken your lights after 7 p.m. and avoid those blue light screens late at night. 4. Reduce stress. Excess cortisol drives fat into your gut. 5. No alcohol. Alcohol tips your metabolism into visceral fat deposition.
www.What will Work for me? This is recent research that ties these lines of evidence together. Advances in the MRI scanner, making it faster, allow it to happen. You can prove it with the CT scanner but you can't justify the radiation. I'm stymied by my own visceral fat. That darned little poochy tummy that just won't go away. My own insulin resistance speaks to having more visceral fat than I thought I had. I'm fascinated that my back pain gets better every time I do my 5-day, fast-mimicking diet. I just found an MRI scanner site that is willing to get the software and do the scan.....it may take a month or two to get it set up. Does insurance pay for it? Considering that this might be the source of all metabolic trouble that causes long-term disability.....you would think they would. Maybe they will eventually.
References: International Journal Endo, ScienceDirect, J Cachexia Sarcopenia,JACC Heart Failure, Frontier Immunology, Nutrition Facts,
Pop Quiz
1. What is intramuscular fat? Answer: Fat from eating too much carbohydrate foods, usually ultraprocessed.
2. What does it look like on autopsy (otherwise known as the butcher shop)? Answer: Ummm, ummm, yummy marbling.
3. What happens to your leftover, outdated candy that you didn't buy at Halloween? Answer: it is fed to animals to get them fatter, faster.
4. Does the inflammation from inflamed animals get passed on to the humans who eat their products (meat, butter, eggs, dairy)? Answer: YES! Now we know why corn-bean-raised animals cause so much inflammation. Just one meal of heavy animal products is enough to cause inflammation. The more processed, the worse it gets. That bratwurst, liverwurst, salami just isn't good for you.
5. What is the first step to your losing your poochy tummy? Answer: Stop eating sugar, processed, and ultra-processed foods. Many for vegetables. (Then add burst exercises, good sleep, no alcohol, and stress reduction)
Visceral Fat, The Source of All Metabolic Evil
"Eeewwww,......gross!" said my anatomy partner in medical school as she lifted out the heart of our cadaver. His heart was almost completely covered with fat.
"Is that why he died of heart disease?" she asked.
"Oh, no....that's just part of the accumulated fat," our anatomy instructor said.
He was wrong. Visceral fat, the extra fat wrapped around your organs is a different kind of fat. It spews out inflammatory cytokines. For example, if you take 66 folks with GERD who are suffering from all the vagaries of acid reflux, and measure their visceral fat, you will find that they universally have more visceral fat than the norm. They can be shown to have high levels of the inflammatory cytokines IL-6, IL-1β, and IL-8. We have dozens of inflammatory cytokines that all rise in various ranges in response to the aggravating stimuli, but visceral fat appears to take the cake.
It's not just acid reflux that is caused by visceral fat, it is just about any chronic condition that afflicts us as we age. Just type in coronary artery disease and visceral fat to Google. The very first article you will find will be from the journal, Obesity, which confirms a direct correlation with the quantity of visceral fat to the extent of coronary artery disease.
Not happy with that? How about osteoarthritis? You know, those nasty swollen, nobby knuckles you get as you get older. One of the most common questions I get is "How do I get rid of these?" and folks show me their hands and their big, puffy knuckles. They can't get rings on and off anymore. You know the drill. Type into Google Osteoarthritis and Visceral Fat and the first article you read will be from the American College of Rheumatology meetings that show a direct correlation with pain in hands and joints from visceral fat.
Ok, are you with me? Want to get personal and serious? Type in Visceral Fat and Alzheimer's. That is our number 1 dread as we age. Again, from the journal, Metabolites, we see a study correlating visceral fat with the risk of developing cognitive decline. Bummer.
On and on. You can type in diabetes, high, blood pressure, and cancer, and in each, you will find recent research showing the link.
Now, do you want to get personal? Type in Face Shape and Visceral Fat. Oh dear. One more time, you will find studies showing that our face gets puffy and droopy in relationship to our visceral fat.
Subcutaneous fat, that which makes up our natural energy storage so that we can make it through the starvation season (winter, dry season, famine) while pregnant is not inflammatory. It is what you can pinch and which you cover up with layers of obscuring clothing. It's harmless. No inflammatory cytokines.
Estrogen protects women from getting visceral fat. During women's reproduction years, women tend not to get visceral fat. Men have no such protection. So, women going through menopause will accumulate visceral fat and change their fat storage compartments. They will observe that their tummies get a little bulge under their waistline that just wasn't there before. Their faces will look a little puffier and saggy. Double bummer.
Where does visceral fat come from? Our modern diet of processed foods, particularly sugars, refined carbohydrates, trans fats, and saturated animal fats is to blame. Throw in lack of exercise, stress, and alcohol and you have a perfect storm to accumulate visceral fat. Suddenly, we understand the Brazilian research showing that eating ultra-processed foods correlates with all sorts of metabolic diseases.
How can we measure visceral fat? Well, that's what's changed. The old method of standing on a fancy scale and measuring total body fat and guessing what percent is visceral fat is not quite up to snuff. But the MRI scanner now does it just fine. As costs come down and MRI speed and accuracy improve, we can now calculate the volume of visceral fat, just like we can calculate the volume of our brain, by adding serial slices of the MRI and then making a sum of it all. Does insurance pay for it? Not yet. But it might be the smartest thing they do. Seeing your image of your visceral fat, and looking in the mirror and your puffy eyes and saggy cheeks, you might just be motivated to do something about that.
www.What will Work for me? Well, from one saggy-cheeked guy to another, this is a total bummer. When I look at myself in the mirror sideways, just before I hop in the shower, I realize why I take my glasses off before I go into the bathroom. Yuck. Getting old is not for the faint of heart. I want to learn more about this visceral fat stuff and how to get rid of it. Next week, how to get rid of it.
References: Cleveland Clinic, Jr Neurogastrointestinal Motility, Obesity, Amer Coll Rheum, Metabolites, Nutrients, Jr Ster Biochem,
Pop Quiz
1. What is visceral fat? Answer: The deep, internal fat inside your organs that is wrapped into the membranes that surround your organs.
2. What is the principal cause of it? Answer: Our modern, ultra-processed food diet. Sugar, white flour, trans fats, multiple ingredients of unknown origin, and artificial sweeteners all add up.
3. Does it affect male pattern baldness too? Answer: Google any irritating condition you may have and there is research indicating trouble, some association.
4. How does visceral fat wreak its havoc? Answer: Uniquely, it puts out showers of inflammatory cytokines that put the whole body on edge.
5. Does visceral fat affect coronary arteries? Answer: There is anecdotal evidence, aside from the well-documented clinical evidence, of segments of coronary arteries that dip out of the visceral fat around the heart into the heart muscle. The artery segments inside the fat were severely atherosclerotic. The artery segment inside the heart muscle was clean.
How to Repair Post-COVID Heart Inflammation in Children
The COVID pandemic is not yet over. As of Oct 6, 2023, some 230 people are dying from COVID-19. Most of those were over age 65 of whom a majority were unvaccinated. Children hardly get COVID at all. That is likely attributable to the protective effect of Nitric Oxide in children, among other features. But some do, and with some severity. Much has been made about children getting cardiomyopathy from the COVID-19 vaccine leading to vaccine hesitancy.
We now know considerably more than we did before about COVID. It is a nasty virus. It attaches to the ACE receptor in the endothelium and can infiltrate cardiac muscles, causing direct damage. It can also set off cascades of inflammatory markers that cause indirect damage. A study from Turkey (Türkiye?) of over 200 children infected with COVID revealed elevated troponin levels, indicating damaged heart muscle.
Why are we all so susceptible to inflammation from COVID in our hearts? We are beginning to get insight. See if this makes sense to you. Heart muscle fibers are surrounded by a unique membrane called the sarcolemma. It helps conduct electrical impulses that fire off the muscle. Its membrane content is very high in plasmalogen lipids. The vinyl ether bond of plasmalogens is the antioxidant of first resort in the sarcolemma. COVID sets off a tidal wave of inflammation, stripping the heart sarcolemma membranes of protection. With heart muscle exposed to the whirling inflammatory markers, troponin shows up. This can end very badly.
Not published yet in the literature is a lecture given by a pediatrician from Seattle of 7 children with COVID and cardiac symptoms. This pediatrician measured CRP, by luck, and found it to be very high. Normal CRP is under 1. A level of 2 confers a doubled risk for cardiovascular disease. These reported cases had CRPs up to 120. Very, very high. Several of them had been to local ERs and sent home being told they would be all right in a couple of days without measurement of the CRP. The pediatrician reported administering Prodrome Glia, the plasmalogen supplement that elevates blood levels of native serum plasmalogen lipids. The children all repaired their symptoms within 3 days. Their CRPs were back below 1 in that time frame as well. This is a stunning development. The speed of repair suggests the discovery of the key to healing.
So, just what happened? The hurricane of inflammation that COVID set off is short-lived as the immune system will ramp up to protect you. That ramping up happens in 1-2 days if you have been vaccinated or had the infection on your own. The virus has about a 24-hour generation life and is in a race with the immune system to multiply and spread faster than the immune system can respond. Children ramp up very fast. The infection is resolved but once the inflammation gets going, it takes much longer to repair the damaged membranes. Prodrome Glia is the key missing membrane building block to fix the defect. A dose of 100 mg per kg overpowers the inflammation and calms the hurricane down.
www.What will Work for me? The pediatrician concludes that everyone should have Prodrome Glia for at least a week after a COVID-19 infection. I sense that she was right. We should also all be taking Nitric Oxide or at least have it handy so that we can gobble it down every couple of hours if we get infected. And no one has ever died if they have been on Vitamin C and E as counters to the cytokine storm of severe COVID. Having those handy may also be a prescient strategy. I also take peroxide from (CVS/Walgreens) dilute it two to 1 and spray it in my nostrils and back of my throat when I am out in high exposure circumstances. Plane trips, theatres, and crowded restaurants all qualify.
References: Am Jr Cardiovasc Disease, Pediatric Cardiology, Mass General Clin Trials, Frontiers Nutrition, Biologyonline, Frontiers Cell Bio,
Pop Quiz
1. What does COVID infection do to the heart? Answer: It attaches to the ACE receptor on the sarcolemma and invades the cells, emitting lots of inflammatory markers.
2. Why is the heart so susceptible? Answer. We are not sure but it seems likely to me that where ever the infection is in the body, it has blood picking up the virus and taking it back to the heart and lungs first.
3. Is it safe to be vaccinated? Answer. Well, to some degree, no. There is a real risk to being vaccinated because we are given a nasty protein from a nasty virus. There is no perfect vaccine with no side effects, ever. There is some incidence of various side effects. Good research from Oxford shows that the risk of the vaccine is about 1/10th the risk of the native virus. It's an odds game. I'll accept those odds and get my booster.
4, When is this cursed virus going to leave us alone? Answer: Never. It is around for the rest of our lives.
5. How expensive is peroxide, Vitamins C and E? Answer: Pennies a day.
Your Brain Shrinks as You Age
Is this real? Is this normal? What is happening here?
Take 653 cognitively normal adults, 447 men and 206 women, mean age 55 at the beginning and follow them annually with volumetric MRI scans. A total of 7915 scans, roughly 12 each were obtained over that time period. A volumetric MRI scan is able to precisely count the pixels in each brain region and calculate to a very high degree of accuracy the area that particular brain region occupies. When you add the layers together from successive slices of the brain, you get the volume of that nucleus or region of the brain. What happens with aging?
This is the first study of its kind taking cognitively normal adults and observing just what happens to various parts of their brains as they age, one year at a time. Overall, they observed a -0.4% decrease in size, per year in the size of the brain. It was roughly -0.3% in folks in their forties and -0.5% in their 80s. The same pattern was found when looking at white matter. There is annual shrinkage in white matter too. White matter is composed of the axons connecting the neurons to other neurons, or other structures. Those computer cables are coated with plasmalogen lipids with an olive oil (oleic acid) fat on the molecule. That coating is called the myelin. Grey matter typically has plasmalogens with DHA (fish oil) as the side chain.
That average brain was reduced in size by 6.7% over 15 years.
If the volume of the brain is shrinking, then the water regions of the brain must be expanding. That was documented and is indeed, the case. Rates of +1-1.5% a year increase in brain water were observed. There was as much as a 10-fold variability in different subjects, suggesting that those losing more volume may be of interest for future intervention to prevent cognitive loss.
Is this normal? Well, if you read the reports of radiologists who are examining CT scans in ERs, you see the phrase, "normal aging shrinkage" all the time. It's not normal. It's decline and is a problem.
Here is the key takeaway. Goodenowe, in his own personal experiment taking 100 mg/kg per day of plasmalogen supplements increased his brain by 7.9% in just 16 months. He reversed 17 years of aging with his personal experiment.
We may all have normal cognition, at the moment. One of the other takeaways from the study was no person ever had their brain expand. Period. Brain enlargement just doesn't happen without intervention.
The question remains, can you slow it down? Can you address the oxidative stress that is getting the whole thing started? Or are we just preprogrammed to disintegrate with time and get out of the way for the next generation?
www.What will Work for me? I'm trying to wrap my "brain" around this. We all laugh off our senior moments and take it as inevitable. Well, aren't we fortunate to be living in this time? We have an emerging technology to keep our brains healthier. I'm going to start offering volumetric MRI scans to my clients who want to know what is happening to their brains and see what we find over time. It might be a valuable tool, particularly when you consider that your grandchildren are still only 3 years old and you want to be around to see them graduate from more than kindergarten.
References: Jama Network ,
Pop Quiz
1. Your brain is shrinking at what rate? Answer: depends on how you want to slice this cheese. Different areas, different rates but overall, about 0.4% a year.
2. How many neurons (the computer chips) cells do you have? Neurons: Probably about 200 billion.
3. How many neurons are you losing each day? Answer: These are big numbers, but I get 21 million neurons a day.
4. Why are we losing neurons? Answer: Various forms of oxidative stress that use up the plasmalogen lipids in the membranes of your neurons.
5. Why are you losing plasmalogens? Answer: They are miracle molecules that allow our brains to function at quantum speeds. But they have a vinyl ether bond that is both an amazing neutralizer of peroxide, preventing reactive oxygen species from damaging the neuron, but sacrificing the plasmalogen molecule as a result. We have to consider, what is setting off that oxidative stress.
How to Stop Heart Disease in Its Tracks
Considering that half of us will die from heart disease, that's a bold statement. If you were to ask 100 cardiologists, they would likely say, "Take a statin." as their primary tool against heart disease. I am going to show you that they are probably behind the curve. They haven't fully embraced the pathophysiology of how heart disease develops. Statins inhibit the production of cholesterol. That's not the root problem. Inhibiting statins is like giving your infected finger warm soaks. Yes, it helps but some good antibiotic treats the core problem. Let me explain and see if I can convince you. (This article is a return to an important topic, just with new information.)
We have known since 1993 that the inner lining of arteries, the so-called endothelium is the barrier that controls the transport of cells, solutes, and fluids between the artery as a transport system and the extravascular space as a destination. Inflammatory mediators can make the cells of the endothelium contract, opening up intercellular gaps through which various processes lead to increased entry of larger molecules and entities like oxidized LDLs into the cell wall. Please note: the first step in developing arterial heart disease is shrinkage of cells in the lining, leaving gaps in the normal defense.
We have also known that CRP predicts cardiac mortality with far better predictive capacity than cholesterol. What's more, we have known that phosphatidylcholine infusion to experimental volunteers completely neutralizes the effects of CRP protein. Hmm. Now we are on to something! Is this suggesting that if we gave phosphatidylcholine by IV to everyone that heart disease would be ended? It's a little unwieldy, but is that an alternative cure?
From experiments done in the 1990s, we know that dysfunction in the hypoxanthine/homocysteine uric acid ecosystem generates hydrogen peroxide and that peroxide, on a linear basis increases endothelial permeability. That's step one in creating heart disease.
You see, peroxide antagonizes the relaxation qualities of nitric oxide. Once you release peroxide, you start damaging the surface membranes and create lipid peroxides and malondialdehyde. That observation was documented in 1989 by Stringer in the British Medical Journal! He noted that lipid peroxides were better predictors of heart disease than cholesterol. Triglycerides being high was also correlated. Elevated malondialdehyde is a clear indication that peroxide is damaging lipid membranes. You can measure elevated lipid peroxides and malondialdehyde in the systemic arterial system, but not in the pulmonary artery system. Why? It's as though the venous system is cleaning up the damage that starts in the heart.
Well, if it's oxidative stress that's going on, then glutathione should be low and malodialdehyde should be high. What is observed in coronary artery disease? Just that.
Guess what happens when you administer DHA-plasmalogen precursors (the next step after the previously mentioned phosphatidylcholine) to blood malondialdehyde levels in folks with very high levels (high oxidate stress). Yup, yup, yup. Goes straight down.
Oxidative stress making high lipid peroxides, high CRP, high malondialdehyde, and low gluathione is setting the table for endothelial cells to shrink and that starts the cascade of small, dense, LDLs slipping into the walls of the damaged artery. If you want to stop heart disease, that's what you should address. We don't have an easy ability to measure malondialdehyde yet but we can measure CRP and glutathione.
The problem with the statin explanation is that it sucks up all the oxygen in the room. No one ever talks about anything else. There is just too much money in statins. Imagine if we explored the oxidized endothelium a bit more, and started dismantling all the cath labs and Coronary Care Units. One person's life-saving venture is another's economic loss.
Let's repeat and summarize. Oxidative stress that makes peroxide is the first step. That likely starts with dysfunction in the ATP breakdown system that makes hypoxanthine and then uric acid. Peroxide damages lipid membranes, causing them to contract and shrink. Once you have shrinkage, LDLs can get in. They get oxidized too, making for small, dangerous LDLs.
What has changed is that we now have the oral form of plasmalogen precursors that take phosphatidylcholine into its final, useful form, plasmalogens that will populate and repair the damaged membranes that got it all started. That will be the cure.
Taking a statin is showing up for the party at 11 pm. A little late and on the wrong topic. May help a little, but let's get on with a real cure.
www.What will Work for me? I have measured my CRP for years and I'm distressed that it has been 1.7-2.8 indicating that I have a double to triple risk for heart disease. My father had a heart attack. I've been an ER doc for 25+ years and believe me, I'm a bit spooked by having heart disease. I've been to the ER for chest pain and had a stress test, that I passed. Small comfort. I've been on Prodrome Glia and Neuro (the two dominant forms of plasmalogen precursors, made from phosphatidylcholine) for over a year now. My CRP is now 0.3, below the 1.0 threshold. I have repaired my endothelium. I'm taking NO to boot. You can too. There is no toxicity to Prodrome Neuro or Prodrome Glia.
References: Br J Pharm, Asian Pac J Cancer Prevention, Jr Thrombosis and Hemostasis, Oxid Med, BMJ, Biomedical Reports, Jr of Clin Diag Research, Frontiers Dev Cell Biol,
Pop Quiz
1. What do statins do? Answer: Inhibit the manufacturing of cholesterol by your cells.
2. Why is cholesterol harmful? Answer: Small, dense, oxidized LDLs can migrate into the artery wall and accumulate in plaques that expand and plug up arteries. That process is killing half of us.
3. What is the first step in developing cardiovascular disease? Answer: Damage to the lining of your arteries caused by peroxide that causes the lining cells to shrink. (Imagine holding a candle to Saran wrap.....it shrinks)
4. What happens to CRP, the best indicator of heart disease risk, when you give plasmalogen precursor supplements? Answer: It normalizes
5. What happens to the wall of your arteries when you take Plasmalogen supplements and Nitric Oxide? Answer: You repair the root cause of artery disease.