Maillard Reaction - The Devil in Your Food
Of course, it was described first in France! The Maillard reaction is all about flavor and "browning". It's the "roux" of fine French dining. The chemical reaction is simple. Sugars (carbs) and amino acids (meat) combine with all sorts of odd reactions that add flavor and pleasing aromas to food. Most chemical reactions are facilitated and controlled by enzymes. The Maillard reaction is "non-enzymatic", facilitated by heat. There are hundreds, if not thousands of them. Making gravy is basically mixing some butter or fat with some flour and then gradually stirring it while heating it. Voila! Gravy! Maillard.
America was founded on the "gravy" culture whereby every ounce of fat off the animal was combined with ground-up corn or wheat to make stews or gravies. We have now perfected the Maillard reaction with the barbecue grill. Take some meat, slather it with a sugar coating called barbecue sauce, then flame it with the grill on high heat.
You see, nature never did this. Wild animals don't cook. Nor did humans have access to sugar in great quantities until the 20th century. It was expensive and rare. Fuel has always been precious and carefully used. Many indigenous peoples used hot rocks to cook food very slowly, at lower temperatures. Then, we discovered oil and nuclear power, and electricity and gas became common. Factories could manufacture food in quantity with high pressure, high heat cooking. This is all a formula for mass Maillard. The problem is, it is so complex that it's hard to get a handle on it.
That picture is becoming more clear. It's been right before our eyes. Cancer. Dogs and cats, living in our homes, are dying of cancer at many times the rate compared to decades ago. What are they eating? Canned dog food. Maillard reaction soup. Both dogs and cats are descendants of carnivores, who age raw food. When they captured game, what did they eat first? The liver and internal organs. That's where the real nutrition lies. And they ate it raw.
The process is actually quite well-known. Maillard formation can be divided into three major stages depending on colored products. At the first stage, sugars and amino acids condense, and following condensation, "Amadori rearrangement and 1-amino-1deoxy-2 ketose" form. (I warned you: it's complex) In the second stage, dehydration and fragmentation occur to the sugars. Amino acids are also degraded in this stage. Hydroxymethylfurfural (HMF) fission products such as pyruvaldehyde and diacetyl are formed in this intermediate stage. This stage can be slightly yellow or colorless. In the final stage, aldol condensation occurs and finally, the heterocyclic nitrogenous compounds form, melanoidins, which are highly colored. Brown gravy. Grilled meat. Processed sausage.
If you just focus on one, acrylamide, you will find a highly carcinogenic compound. It is formed with just 60 seconds of microwaving. It is pervasive. And it's not just meat. Soybeans, a major foundation of many food products, has oil, protein and carbohydrates all in one little bean. What happens with high-pressure heating and "extrusion" of the oils and proteins? You got it. All sorts of Maillard products with names like furosine.
How about dairy products, produced with high-temperature pasteurization? How about pasta making? Traditional pasta processes were low temperature and took 3-4 days to complete. Modern machinery accelerates that to minutes with high temperature and guess the result. We can go on.
www.What will Work for me? I've had four dogs, two died of cancer at age 8. I've seen, it with my own eyes. I've seen dogs improve from mangy, malnourished animals to sleek, shiny, buff creatures on a raw food diet. I have walked through the pet store and seen the proliferation of freeze-dried raw meat products for dogs which our new puppy scarfs down like she has seen heaven on earth. If this is what the veterinary industry is turning to for our animals, what on earth are we humans tolerating all this Maillard reaction stuff for? I've measured my own acrylamide and was stunned to see how high it was. We so cheerfully eat those French fries, cooked at 400 degrees in soybean oil. No more! We eagerly look forward to our summer grilling and dig out that delicious barbeque sauce. Am I willing to go raw? Or at least lower-temperature cooking? I don't know. Change has to start with knowledge. But my achy heart for the death of our last loved dog from bladder cancer is being assuaged by the delight of a new cocker puppy, even if it involves waking at 2 am for a potty trip outdoors. And I'm buying her raw food. Simple.
References: Food Chemistry, Int Jr of Food Sci, The Grio,
Pop Quiz
1. What is the Maillard reaction? Answer: the abnormal chemical bonding of sugars to amino acids facilitated by high temperature.
2. Can you name some foods that have Maillard reaction products in high concentration? Answer: French fries. Anything grilled. Processed meats. But don't forget the pasteurized dairy, the high-temperature pasta, and the ultra-processed foods that sound so good for you.
3. What's the answer to reducing Maillard products in our food supply? Answer: raw food can be interpreted as more salads, and more vegetables. Cooking can be changed to lower-temperature stews and casseroles. This may explain some of the damage caused by "ultra-processed" foods, all of which are made with high-pressure, high-temperature foods.
4. Why haven't we heard more about this before this? Answer: There are 20+ amino acids and dozens of different sugars making for thousands of different combinations. The complexity is daunting. That inhibits the research. We humans are restless and don't eat the same food often. We like variety. Studying just what we eat is a very tasking process. That makes for long-term population studies, that are expensive and slow.
5. Name one chemical that can now be measured that is a product of high-temperature heating of potatoes and soybean products. Answer: acrylamide.
A2 Milk is a Better Milk
It all started with an alert pediatrician in New Zealand who wondered why children from Samoa never had insulin-dependent diabetes until they immigrated to New Zealand. One of his partners conjectured, "Well, they've got brown cows and we've got black cows." A quick little study in their practice revealed that observation to be accurate.
It took a couple of years of investigation to find that black cows, Holsteins, have a casein protein sequence with a single amino acid change at position 67 on the protein leading to an indigestible, 7 amino acid fragment that is different from brown cows. It was called A-1 casein. In fact, A-1 protein is present only in black cows. All other cows in Africa, India, and brown cows in Europe have the A-2 gene. Actually, all mammals including humans have the A-2 or other casein subtypes, but not the A-1 gene.
That 7 amino acid fragment is not benign. It has the ability to bind to the morphine receptor in the gut and brain. The morphine receptor is not there for the purpose of making the cow mellow, it is part of the immune system. When you block it, you are activating the immune system. Rat studies show that newborn rats, susceptible to developing diabetes with A-1 milk, will not get diabetes if given naloxone (morphine blocker) prior to A-1 milk, thus blocking the morphine receptor. Rats aren't humans but there is some biological principle here.
It's not just diabetes. There is equal concern around mental health, schizophrenia in particular. It's been noted for decades that folks with schizophrenia do better when on a diary-free diet. There are trials underway trying to parse the issue out, but there is not big money behind it so studies are slow and small. The FDA does not permit A-2 milk to advertise that it might be better for mental health, diabetes, or schizophrenia. The only claim that can be made is for "better digestion". Well, that too is now pretty well proven.
New Zealand has taken that data with serious focus. They have bred the A-1 gene out of their cow herd completely. Australia has followed suit. Keith Wolford, the professor of dairy science and author of the book "The Devil in Milk" details all the nefarious politics around trying to hide the damaging risk of A-1 milk and the desire to maintain New Zealand's "brand" of standing for pure, clean agricultural products. The US has paid virtually no attention to the topic and the American dairy herd, predominantly Holsteins, is heavily A-1. (Not every cow is. It takes genetic testing and then some 10 years to clean a given herd of the gene)
A-2 milk has shown up on the grocery store shelf in Wisconsin in the last five years. But what about yogurt, cheese, butter, cream cheese, ice cream, and any other product with A-1 protein it it. How about milk collection systems? A milk truck picks up milk from several farms and mixes them all together. That's no good. Any given milk truck doesn't know where it is ending up at the end of the day. What cheese maker is calling for product? Hmmm,...Illinois? Collecting A-2 milk has to be clean and separate from A-1. It requires its own collection system and separate cheese-making, yogurt, and ice cream-making. That's tricky.
And that's what has changed in Wisconsin. One brave dairy farmer has stepped out and is now making A-2 cheese and has a herd of A-2 cows. Milkhaus Dairy will ship you A-2 cheese and is thinking about Ice Cream. Woo Hoo!
Where there is smoke, there is usually fire. Enough, serious scientists are on board with this for me to believe there is enough to take seriously. The huge differences in incidence of diabetes in different societies speaks to some sort of environmental influence. Holstein cows are incredible milk machines and have been adopted all over the world. As that has occurred, insulin-dependent diabetes shows up.
www.What will Work for me. I pleaded with my children to raise my grandchildren with A2 milk. That's not hard in Switzerland, where the cows are mostly "Swiss". California is an early adopting state and there are several "Brown Cow" dairys. If I had an autoimmune disease, I would avoid A1 milk. Goat milk, sheep milk, buffalo milk, donkey milk, and camel milk are all fine. It's just those pesky, efficient black cows. I did order some cheese from Milkhaus Dairy. There is no doubt that human infants benefit by good, healthy, protein. Older adults do too. Just don't mess with my immune system.
References: Frontiers Nutrition, The Devil in Milk, Nutrition Diabetes, Indian Jr Endo, Nutrients, Trials, Milkhaus Dairy, Nutrients,
Pop Quiz
1. What is A-1 milk? Answer: A genetic variation of the beta-casein protein at position 67 where there is a proline for histidine (two amino acids that are in all proteins and share two of the three codons. A single mutation allows the switch. The result is a 7 amino acid fragment that is indigestible and which proceeds to activate the morphine receptor. The fragment is called BCM-7 for Black Cow Milk-7. You don't want A-1 milk.
2. What kind of cows have A-1 milk? Answer: All black cows come from a common ancestor. The mutation is thought to have arisen some 10,000 years ago. The resultant cows may have been more mellow and easier to handle. The penetration is only 80-90%. Not all black cows have it.
3. How much A-1 milk is there in India or Africa? Answer: None. They have brown cows (A-2), buffalo (A-2) and goat milk (A-2). Recently they have been importing Holsteins, and getting diabetes to show for it.
4. Is all this science conjecture or is it proven with hard fact? Answer: It's a bit of fact, and a bit of pattern recognition. Hard, irrefutable facts take a lot of money and there is precious little to support this type of research.
5. If you measure the urine of autistic children, do you find more or less BCM-7 in their urine? Answer. No fair. Not covered. But google it. Guess what you find? Yup, more BCM-7 than in normal kids.
Plant Nitrates from Vegetables, As Essential As Vitamins
Life probably couldn't have started without lightning. You see, lightning creates the energy to break the nitrogen bonds of atmospheric nitrogen and make nitric oxide. That step introduces nitrogen into the food chain and starts the production of amino acids and DNA. Now, we have the ingredients for life. That nitrogen is precious. One of the key ingredients from lightning was NO, nitric oxide that is very reactive and can go in multiple directions.
That same role is now played by dietary nitrates from vegetables. It takes a circuitous route to get back to NO. Nitrates from vegetables are concentrated in your saliva, and then a particular, unique biome of bacteria in the crypts of your tongue convert the nitrates to nitrites. Upon swallowing, those nitrites are converted to NO in the stomach, which affects the whole body.
There are two, critical choke points in that process. Salivary conversion of nitrates to nitrites is erased with mouthwash of any kind. That's number one. Drugs that neutralize stomach acid block the final conversion to NO. That's number 2. Both stop the production of NO, almost completely.
NO, once made, turns on an enzyme called soluble guanylate cyclase or just chemically alters many proteins to generate all sorts of endocrine effectors. Those effects are life-giving. Oxygen can penetrate tissues. White cells can kill viruses. Blood can flood smoothly through responsive blood vessels. NO is the real deal. And it drops by 12% per decade. Add that up and if you are over 60, you are deficient.
Under conditions of exacerbated physiological stress such as chronic inflammation, the enzyme responsible for endogenous NO production in endothelial cells, endothelial nitric oxide synthase (eNOS), may generate reactive oxygen species thus decreasing NO production. This change in enzymology is termed eNOS uncoupling. That explains the missing link between chronic inflammation and how it plays out in making us worse off. Sick!
Just about every known disease is associated with low NO. For example, studies have reported a decrease in whole-body NO synthesis rate of 31% with high blood pressure, 61% in renal failure, 73% in heart failure, and 40% with hypertension. The list goes on. That's the science that's being filled in now. Studying NO is so complex because it is so fleeting and nuanced in its effect, that no one fully grasped the scope of its importance. Well, important it is.
We get nitrates from our food. Only. We can make some NO from animal products but that process is pretty unwieldy and the best evidence we have is that most NO comes from the plants we eat. Clearly, prepared meats have measurable, harmful effects on human health, but the nitrates themselves may be beneficial. All that fuming about the nitrates in ham is misplaced. However, you can't put in the nitrates without making other secondary products. They are the problem.
The conundrum comes with too much nitrate intake, as shown in cardiovascular disease. A U-shaped curve of benefit shows up that demonstrates "tolerance" or adaptation to high doses that erases the benefit. Something is amiss. Like the three bears, you want your porridge "just right". Same for NO. Not too little. Not too much. And vegetables provide that. The convoluted, complex pathway through our saliva and gut is fragile.
There is clear evidence that the natural nitrates in vegetables have a demonstrable beneficial effect on cardiovascular health. It's the nitrates that do it, at the level vegetables provide when eaten. And irony upon irony, organic vegetables have dramatically fewer nitrates in them. That's what fertilizer is. Our depleted soils are so lacking in nitrogen, we are now dependent on the addition of artificial nitrogen. Lightning just isn't keeping up.
And that's how we get to the call for nitrates in vegetables to be considered a conditional, "essential" nutrient, almost a vitamin.
www.What will Work for me? My take-away. If you are over 60, you likely need to be on some sort of program of nitrate enhancement, in addition to 5 servings of vegetables a day. The path to healing cardiovascular disease, our number one killer in men and women, is founded on sufficient NO in our arteries. No questions asked. Nobel Prize for that one. My cardiac calcium score is not zero. I'm taking NO lozenges every day. It's my only "candy". Nice, lemony flavor. I just baked 3 packages of Brussels sprouts with lots of black pepper and a tract of paprika and olive oil. I've ditched the mouthwash and I'm flossing with grim determination. The average American eats 1/2 serving per day of vegetables, only if you count french fries as a vegetable. Buck that trend.
References: Science Direct, Cell, J Animal Sci Tech,
Pop Quiz
1. What is the original source of nitrates? Answer: Lightning.
2. Where do we get most of our modern nitrates from? Answer: Artificially making nitrogen-based fertilizers. Then through plants.
3. How much does NO production decrease per decade? Answer: 12%
4. What are the odds I die of heart disease? Answer: 50%.
5. Hmmm. Las Vegas odds for NO versus heart disease? Answer: Don't be a sucker. You need the NO. I know it's expensive. Death is worse. And more certain.
Ultra-processed Food is a Real Problem
This has been a slippery question. What are ultra-processed foods and do they really make a problem? This column first reported the Brazilian studies that kicked off the discussion and identified ultra-processed food as an item of concern. There have been some studies refuting its risks.
This week's report is on the first meta-analysis (statistical distillation of all studies) of studies looking at the topic. Of over 4,500 articles, only 25 were found to have sufficient scientific rigor to be included. "A consistently positive association between high UPF intake and increased risk of developing diabetes (37%), hypertension (32%), hypertriglyceridemia (47%), low HDL cholesterol concentration (43%), and obesity (32%) was observed, even if the quality of evidence was not satisfying." It appears the tilt is developing, confirming the Brazilian's identification of risk.
What is the definition they used for ultra-processed food? Ultra-processed foods are: ready-to-eat or ready-to-heat industrial preparations made largely or entirely with substances extracted from food, often chemically modified, with additives, and with a small proportion of whole food. Therefore, the term "ultra-processed" includes soft drinks, packaged snacks, sugared breakfast cereals, cookies, processed meats, and packaged frozen or shelf-stable meals, but also flavored yogurts, low-calorie or low-fat products, breakfast cereals, and products "fortified" with beneficial nutrients. Oh dear. Sounds like the whole grocery store.
More simple definitions include: more than 3-4 ingredients, more than 2 steps away from the native food, wrapped in paper/plastic, added sugar, and processed fats. For example, fresh yogurt is minimally processed but cheeses have become ultra-processed because of the added salt, colorings etc. Whole grains are ok. You are allowed to remove the inedible husk of wheat, oats, rice. But once you grind it into flour, bread becomes ultra-processed. (I'm particularly annoyed at salted nuts being "ultra-processed) NOVA (not an acronym but the name given by the Brazilians for the food classification system) classification is pretty clear.
What might be the physiological problem that this is trying to capture? There is now little debate about the risks. It's the rush of too many nutrients overwhelming our metabolic capability to properly process the calories. We get too much, too fast. It forces us to manufacture visceral fat, develop fatty liver, fatty pancreas, fatty heart. Visceral fat has been shown to be the driver of uncontrolled inflammation, yielding us with heart disease, cancer, arthritis, dementia and most of our degenerative diseases of aging. Bummer. Eating our modern, ultra-processed foods is the first domino of what has been an elusive search for causation. It's not the single item, it's the whole ecosystem. Our mitochondria are wonders of nature for their ability to convert food into metabolic fuel. But they are touchy little engines and get overwhelmed when we provide too much fuel, too fast, because we made it so concentrated, pure, varied. Too bad it tastes so good. Ice cream is on the list.
www.What will Work for me? How on earth am I meant to go on a road trip and not pick up McNuggets and a milkshake on my drive? I can't take a sandwich? I can't pick up a sub on the way? What this explains to me is why my grandparents, who kept gardens into their later years, eating most of their food from their own little plot, lived so well, so long. My father was planting his beans into his late 80s. If I look in my fridge, I have 3 containers of yogurts (at least two of them are simple, fresh, no additives) but I'm shamed by all the cheeses, ketchup, whipped cream in a can, soda....my fridge is a battlefield. Nature made me to eat foods in a fashion that we just aren't doing anymore. I'm in a sulk.
References: Advances in Nutrition, Public Health Nutrition, Curr Devel Nutr., World Nutrition, Am Jr Preventative Medicine,
Pop Quiz
1. Define in your own words what is an ultra-processed food? Answer: More than one step away from the plant, with any additives, particularly sugar or salt.
2. Is bread ultra-processed? Answer: Count the steps: Grind the flour (1), mix with yeast, sugar, preservatives, and bromine. (2). Put butter on it. (3). Yup. It's Ultra-Processed.
3. My yogurt with fruit is bad too? Answer: Count the ingredients. What's in my fridge has 13 ingredients. I don't know what two of them are.
4. What is happening in my body when I eat this stuff? Answer: It is so refined and so purified, it rushes into me, overwhelming my ability to digest it in the fashion nature designed. My metabolism wants those calories delivered more slowly. Fiber helps. That "overwhelming" results in oxidative stress, and fat accumulation in problematic places. That visceral fat is the secret inflammation engine that drives degenerative aging.
5. How do I get rid of visceral fat: aka, that poochy tummy of mine? Answer: No processed food. Just about all successful dietary plans start that.
LDLs Play Little to NO ROLE in Heart Disease
Half of us are dying of heart disease so this is no trivial matter. Our obsession with cholesterol started with President Eisenhower who had multiple heart attacks while in the White House, with a stroke thrown in for good measure. He finally died of congestive heart failure in 1969 at age 78. He went on a low cholesterol diet and his blood cholesterol went up. He was miserable. Lesions in the heart that plug up the heart are filled with cholesterol so it was just assumed you had to eat less cholesterol. It was there, it must be the cause. That started the obsession with cholesterol. It's been misplaced.
To fix a disease, you have to understand what is causing it. We have had multiple studies in the last few years that reflect an alternative reality. Bathum's study in Scand Jr Pri Health Care is one of the best, among many. In that study, over 118,000 adults, over age 50 were followed for LDLs, Triglycerides, HDLs, statin use, and mortality. With over a million human years of data, their data showed what many other studies have shown: LDL cholesterol has no impact on mortality. In fact, low cholesterol (< 190) has higher mortality than a total cholesterol of 270. For example, for ages 60-70, total cholesterol of 193-232 has 0.68 of the mortality of cholesterol below 193. And 0.67 of the mortality if their cholesterol was between 230 and 270. That's a 32% reduction in mortality, having a cholesterol way above what we consider normal in America, being < 200. We are advising people to lower their cholesterol into a range that is associated with a higher mortality.
Now, confounding all that is that folks on statins had lower mortality as well, somewhat in the same range, some 30%. That confirms the irrefutable benefit statins provide to heart disease once one has had a heart attack. Hmmm. But is the cholesterol lowering effect what actually makes the benefit. That hasn't been proven. And the people who were started on statins were all those with higher cholesterol and therefore lower mortality to start with. So, maybe, just maybe, there is NO BENEFIT.
The authors concluded that only high triglycerides were associated with higher mortality, at least in women. HDLs are protective, yes. But LDLs appear not to be the main problem if any problem at all.
Are we barking up the wrong tree? It is unequivocal that cholesterol accumulates in artery walls. That is proven and clearly apparent. But what is making the cholesterol accumulate?
Ah! There is research to show just that. If you do metabolomic studies of the lipids that predict future heart attacks and strokes, it's not cholesterol that comes out on top, it's plasmalogens, at low levels. Remember, metabolomic studies measure everything, without bias, and then observe what statistically holds up to benefit. That study called the SCORE Study, followed 1852 adults for 16 years and obtained blood levels on 1,228 metabolites every year. They then did the number crunching for statistical validity of what predicted future trouble.
Yes, cholesterol was in the mix but it was low plasmalogens that emerged as most predictive of future unstable angina and heart attack. Whoa! Once again, high cholesterol didn't predict future trouble. Low plasmalogens did.
Here is the probable sequence. Oxidative stress releases a flood of peroxide and the -OH ion. Plasmalogen lipids, present in the endothelial cells of arteries, are the only lipids to contain a vinyl-ether bond that soaks up those peroxide and -OH ions, neutralizing them. That depletes the plasmalogen molecules which are critical for playing a key role in membrane function. Without plasmalogens, membranes get stiffer and have a hard time secreting cholesterol, so HDL levels fall. Endothelial cells shrink their footprint, exposing the basement membrane for LDL particles to stick to. Without that loss of plasmalogens, the endothelial cells would maintain their coating of the artery, protecting them. So LDLs are at the party. They play a huge role in making trouble with accumulations of cholesterol, but they aren't the core root cause. It's fixing the root cause that will prevent the disease.
It's the oxidative stress, probably most prominently driven by the sugar and white flour we eat, and the visceral fat we then develop. That depletes plasmalogens and cells start to separate with membranes that get stiffer and less functional. THEN, and only then, do LDLs start to accumulate.
Got it? It's not the cholesterol that is the root cause. It's that tummy fat, that sugar, that ice cream that starts the ball rolling. We lose plasmalogens. We can measure that. And their loss is the single best predictor of future heart disease. If you want to see into the future for your #1 risk, measure your plasmalogens.
Then, there is the inexorable loss of Nitric Oxide with aging. That is the other prominent wild card in the mix. Eat all the vegetables you can.
www.What will Work for me? Now, here there is some hope. We can now measure and replace missing plasmalogens. I have personally been tormented for years with lousy HDLs and I have done everything but stand on my head to get my HDLs up. I have never been successful, until this last year when I started taking plasmalogen replacements. From an HDL of 28, I am now up to 58. I'm thrilled. Combine plasmalogen replacement with Nitric Oxide replacement as the means of regrowing your glycocalyx and giving your arteries their natural coating, and we can really get to the heart of your heart. How interested is BIG Pharma and BIG Health Care in cutting your risk of heart disease, the #1 health-spend in America? You are interested. But you may not get help. Should you be on a statin? They do reduce mortality, but not for the reason you think. The cholesterol effect is irrelevant. They likely are playing a role as antiinflammatory, reducing the oxidative stress, and reducing the loss of plasmalogens. That research is waiting to be done.
References: Scan Jr Pri Health Care - Bathum, Heart Attack and Stroke, JCI Insight, MedRXIV,
Pop Quiz
1. If I measure everything in my blood, every year, for over a decade, what compound will jump out as being the best predictor of future heart attacks? Answer: Plasmalogens
2. What role do plasmalogens play in the wall of the artery? Answer: No fair. Diidn't fully discuss this. But here it is. They are the most fluid of membrane lipids because they are where DHA, fish oil, ends up. That fluidity and the ability to shape shift allows some unique properties. The membrane can stretch and bend. That's very useful for an artery with a pulse going through it. It's also important to allow the endothelial cell of the artery membrayes to be very thin and connect to all their partner cells. Finally, the proteins embedded in the wall of the endothelial cell can shape shift because of that fluidity. All that is degraded as plasmogens are lost. Their achilles heel is the vinyl-ether bond they possess that is the anti-oxidant of FIRST resort, That protection is nice, for a short term event. It becomes a liability with persistent oxidative stress.
3. Who has a lower life expectancy, someone with a cholesterol of 150 or someone with 250? Answer: I'll take the 250 any day of the week.
4. What is the best marker of my artery cells being healthy? Answer: Lower triglycerides and higher HDL. They indicate properly function cholesterol transport.
5. How can I naturally raise my own plasmalogens? Answer: First, stop the burning. This is why you need to cut down on sugar and white flour. Lose the tummy fat. Intermittent fasting and compressing calories into 8 hours turn on peroxisomes to make more plasmalogens. Exercise also deplete glucose stores and switches you to fat burning, stimulating the peroxisome to make more plasmalogens. So, the simplistic phrase "Eat right and exercise more!" holds water. Do it.
Carbon 60 Buckyballs, Are They Good for You?
When you see the following statement, "Carbon 60 is the most powerful antioxidant currently known – over 270 times stronger than vitamin C!", you might think this is something to explore. Is there any validity to the breathless claims that rats treated with it lived twice as long as untreated rats? Or, if treated with radiation showed virtually no toxicity. Where is all this coming from? Is it worth taking a look?
Carbon 60 is a fullerene, the discovery of which garnered a Nobel Prize in 1996 for Harry Kroto. Imagine a soccer ball of carbon atoms (60 to be exact) in which they are constructed to make 20 hexagons and 12 pentagons. The hexagons all have 3 double bonds in them, separated from each other by the pentagons. This is a very elegant structure.
Those double bonds cover the whole surface of the "soccer ball" or fullerene molecule. What do they do? Well, double bonds have a curious affinity to suck up peroxide and the hydroxyl ion. Those two "Reactive Oxygen Species" are the end products of the oxidative stress cascade that happens everywhere in your body when you are exposed to "oxidative stress". By that I mean anything that overwhelms and taxes the mitochondria, leading it to lose its grip on electrons. When you overeat sugar and saturated fat (aka, ice cream, hamburger with bacon and cheese, giant steak, etc etc) your mitochondria are overwhelmed and the normal leakage of 1-2% of electrons turns into a flood. COVID with its unique toxins creates oxidative stress too. As does smoking, air pollution, microplastics, environmental toxins...the whole gamut of bad things. An escaped electron will damage cells without discrimination. To dampen that damage, we have several enzymes to capture that electron and get it out of the cell into the blood in the form of peroxide. Superoxide dismutase (SOD) and catalase are the two loose electron police. Catalase gets induced and you can measure higher catalase levels in folks with Long COVID, Autism, or other brain diseases.
Glutathione is your next line of defense. It gets diminished, battling the flood of electrons. If peroxide overwhelms glutathione, it then converts into the Darth Vader of Reactive Oxygen species and makes the -OH ion, the hydroxyl ion. Both peroxide and -OH will attack membranes and damage them. This is where plasmalogens come in. They have a double bond on the surface of the cell that captures peroxide or -OH and neutralizes it. But you lose the plasmalogen molecule.
With the depletion of plasmalogens, you set off all sorts of other problems. That depletion is actually the engine driving Alzheimer's, coronary artery disease, cancer, and just about all diseases of aging. This column has covered those connections in great detail.
So, this is no ideal question. Could an exogenous form of plasmalogens be a helpful supplement? That's what C-60 is. It is the only molecule that provides a potent source of double bonds that will suck up reactive oxygen species. Double bonds are so fragile, and actually so rare that we have only a tiny supply of them. We can only make a minuscule quantity of them in our peroxisomes. Could we really take them as a supplement and augment our meager supply? Wow? This would become a backup plan for supporting membranes and soaking up reactive oxygen species.
The problem is, they aren't a natural molecule and they don't fit back into the matrix of our cells. We need plasmalogens for many other reasons. Their fluidity and ability to shape-shift give cellular membranes the basis for their function as they allow proteins to also shape-shift, facilitating activation and deactivation.
There is a company, C360 Health, now hawking C-60 as an antioxidant, claiming the sun, moon, and stars in benefits. They have some impressive graphs showing a reduction in inflammatory cytokines. All those cytokines are set off by the cascades of reactive oxygen species made when peroxide and -OH damage those double bonds.
www.What will Work for me. I love ideas from right field that come out of "nowhere" when you weren't expecting it. There appears to be little toxicity to this C60 fullerene, to date. I'm not ready to endorse it quite yet, but I understand the chemistry and it fits into the concept of Membrane Biology as defined by plasmalogen lipids that drive functionality of mammalian membranes. That functionality will reshape medicine and require a rewrite of all of our textbooks. Medicine is going to be radically reshaped as the plasmalogen revolution rolls over our understanding of modern diseases of aging. This cute, little, Nobel Prize Winning Soccer Ball may have a role in there somewhere. It is the only double bond that survives gut digestion. If it is safe, that may be important. To date, we don't have much human safety data. For now, that's a safety warning. Stay tuned. This is interesting.
References: Neurobiology Aging, Wikipedia Kroto, Biomaterials, ResearchGate, C360Health,
Pop Quiz
1. What is C-60? Answer: It is a fullerene, a ball-shaped molecule, like a soccer ball of carbon rings filled with double bonds. Nobel prize in 1996 for its discovery.
2. What happens when you give it to rats? Answer: They live much longer. (This is a mistake. We need something to get rats to live shorter)
3. How does it have its biological effect? Answer: Dramatic reduction in inflammatory cytokines.
4. How does that reduction in inflammatory cytokines come about? Answer: Those double bonds snarf up the reactive oxygen species that set off all the inflammatory cascades.
5. Is it safe to take? Answer: Time will tell for sure.
Very High Levels of HDL Lipids are a High Risk for Dementia
You have always been told that HDL is your "good" cholesterol, the more the better. Well, the shine has come off the apple. HDL over 80 isn't so good. There appears to be a U-shaped curve with increasing benefit up to 80, and then a sharp increase over HDL of 80. Published in the LANCET this January is a great study using 16,703 participants over age 70 (from Australia) and 2411 participants over age 65 from Kaiser Health in California. It was part of a randomized, placebo-controlled trial of baby aspirin. 830 cases of dementia developed over the 6 years of the study. Comparing HDL levels to dementia risk in that population showed a 27% increased risk when HDL rose over 80. That's alarming. No matter how they analyzed the data, that association continued.
This study confirms the findings now of multiple other studies over the last decade that appear to show much the same finding. One of the largest was from Great Britain, looking at some 415,00 adults that found an increase in all-cause mortality of some 11% for HDL over 80. In their data, that held true only for men.
What is a bit confounding is that we don't know how to lower that high HDL. All we find are pablum recommendations of "eat right" and "exercise more". Ok, ok, nice try. Let's first understand what HDL is and what role it plays. Here is a brief physiology lesson.
HDL is part of cholesterol transport. Cholesterol is made in the liver. It is a critical membrane lipid that is rigid and strong. It's water-insoluble and needs a transport protein that can carry it through the blood. Some 40% of cellular membranes are made of cholesterol, wherein it provides the strength and firmness to make a strong membrane. Like the joists or framing of a house that give a house rigid structure and form, you need structural strength to make a cell wall and the requisite shape of a cell. That's the role of cholesterol. But a house has to have windows and doors to see out and get in and out. Ditto for a cell. Part of every cell are membrane regions with much less cholesterol and more plasmalogens which can shape shift and move. Embedded proteins that allow cross-membrane communication need that ability to shapeshift to communicate.
Cholesterol is absolutely indigestible. The only way to get rid of it is to excrete it in your bile. To get from your cell, where there is too much cholesterol, back to your liver, you need a transport protein. Voila, therein lies the role for HDL particles. They are the taxi ride to the airport.
There you have it. Cholesterol is always coming (LDL particles) and going (HDL particles). If you eat a lot of animal protein, you ingest more cholesterol. Plants have virtually none (except for some "sterols" in some nuts and seeds).
The issue with coronary artery disease isn't the coming and going of cholesterol. It is the inflammation and endothelial dysfunction that make the artery wall naked and amenable to absorbing the cholesterol that's the problem with coronary artery disease. Taking a statin lowers the production of cholesterol but doesn't do much for endothelial dysfunction driven mostly by the inflammation caused by visceral fat, and inflammatory foods (sugar etc).
How to lower your HDLs? We are still dancing around that. My suspicion is that we will eventually see the role for Nitric Oxide. The inexorable march of NO decline with age can now be reversed with NO lozenge therapy. What is most interesting is that we are finding that HDLs are much more than just passive taxis. They have all sorts of antiinflammatory properties and even can be shown to protect mitochondria. Stay tuned. This is interesting.
www.What will Work for me. I'm such a sugar addict, I don't know how I'm going to even get my HDL up above 40. I've hovered in the 28-30 range for decades. I finally got above 40 when I started taking plasmalogens. Now, I'm a year into NO which will start generating research studies now that we can easily obtain it. My bet is that NO/plasmalogen therapy will have a much, much greater effect on reducing vascular disease than statins. It's going to take 10 years to show that. I don't have 10 years to wait. My expiration date is probably sooner than that.
References: The Lancet, American Jr Cardiology, Adv Exp Med Bio., ATVB, Biomedicine and Pharmacotherapy,
Pop Quiz
1. What role does the HDL particle play in our lives? Answer: It's the shuttle bus for cholesterol from the cell back to the liver to be excreted in bile.
2. What does a "healthy" level of HDLs mean? Answer: Your cells are happy. They have enough cholesterol for their needs and are shipping the extra back to be excreted. Everything appears to be copesthetic. Calmness prevails.
3. Except when your HDL is above 80. What happens then? Answer: There appears to be a biphasic curve with increasing mortality and dementia, maybe only for men. This occurs only in 5-6% of the population and may not be relevant for women.
4. What role does cholesterol play in the body? Answer: Critical component of all membranes, giving them structural firmness and integrity. And the skeleton to make many hormones (Cortisol, estrogen, testosterone, progesterone, DHEA...) all of which have to be excreted in the bile.
5. What role does NO play with HDLs? Answer: There is strong evidence that HDLs stimulate more NO production. That may be why there is a protective effect from HDLs. But it may be the other way around, that NO induces better HDLs. This needs to be parsed out. Time will tell.
Long COVID and the Cause of Extended Fatigue
Did you see the headlines this week? "Long COVID Destroys Your Exercise Capacity". It's a pretty good study looking at the exercise capacity of long COVID patients and how their residual fatigue can go on for months. There is clearly damage to mitochondria with resultant downregulated energy production. What to do with a curious increase in amyloid in muscles? This fatigue is no small problem as it is estimated that there are some 65 million people around the world with this syndrome.
There may be a research clue that pulls this persistent nightmare together. In Brain Research Bulletin another lovely study puts forward a hypothesis that fits with the plasmalogen explanation.
Here is that explanation in a nutshell. Plasmalogens are the lipids that allow multicellular organisms to exist because they can shape-shift rapidly. This allows embedded proteins to move and change shape very rapidly. That's how a cell talks to the cells around it, by exporting hormones and peptides to communicate with its neighbors, near and far.
A characteristic of plasmalogens is that they also have a vinyl-ether double bond on the surface of the cell. That double bond is the anti-oxidant of first resort. Get that? First. Vitamin C and E are second in line, inside the cells. Blueberries and goji berries are also down the road. The vinyl ether bond is on the outer surface of a cell's membrane and it is particularly focused on capturing peroxide and destroying it. Peroxide is the universal pathway of oxidative stress from failing mitochondria, so its presence means there is trouble. COVID is a particularly problematic virus in making a firehose of oxidative stress. That makes a lot of peroxide. That damages a lot of plasmalogens. That plasmalogen loss saves the cell from destruction by the peroxide but loses the plasmalogen molecule. With the loss of the plasmalogen molecule, the membrane gets stiffer and less functional. The cell can't communicate as well. At the macro level, the affected human's individual cells leave a global sense of fatigue, brain fog, and malaise.
There is proof that folks with long COVID had much higher levels of malondialdehyde than healthy controls. Double, in fact. Malondialdehyde is the fragment left over when the chemical reaction of peroxide meets a vinyl ether bond. Poof and you have this extra malondialdehyde molecule and are missing one plasmalogen molecule.
All the research pieces are there. All in different places. No one has pulled them all together until Goodenowe produced his plasmalogen supplements for the treatment of cognitive trouble from Alzheimer's, autism, RDCP, and Parkinson's.
That's what we are seeing in the clinical world. As we reported several months ago, 7 children with COVID myocarditis, expecting to get better over 2-3 months were healed in 24 hours with plasmalogen supplementation. A severe post-COVID headache, expecting to be ill for 1-2 months repaired in 4 hours with plasmalogen replacement therapy. And dozens of other similar case reports.
My hypothesis, not proven, but the parts are all working is: that COVID produces a firehose of oxidative stress, damaging mitochondria. Peroxide is released from the damaged mitochondria. Peroxide depletes membranes all over the body of plasmalogens, exceeding the capacity of the body to repair itself. There is a curious bottleneck like a circle of falling dominoes. The body can't repair itself fast enough to catch up until it gets some external help. Long COVID is a membrane disease of depleted plasmalogens, which we can now repair.
Summary: Long-COVID is the result of plasmalogen depletion in cellular membranes leading to dysfunctional, inadequate function. That is expressed at the individual's level as fatigue, brain fog, vertigo, anosmia....on and on.
www.What will Work for me? I'm personally using Prodrome Glia, the branded name of plasmalogen replacement, on every patient I see, and it's working. Prodrome Glia is essentially the phospholipid that is in mothers' breast milk. It's really hard to allergic to "Mom". The implications of this are massive if it is true. This may be the cure for the current diseases we call Fibromyalgia, Chronic Fatigue Syndrome not to mention autism, ADHD, Alzheimer's, Parkinson's. I suspect we need to flesh out the protocols and reinforce the science. But the textbooks of medicine all need rewriting. Hang on to your seat belts. You heard it here first. Long COVID is the laboratory that allowed us to study and experiment.
References: Apple News, Nature Communications, Brain Research Bulletin, Nature Reviews, Int Jr Mol Sci,
Pop Quiz
1. What is the key problem that COVID causes that turns it into long COVID? Answer: A fire hose of oxidative stress (which means way, way way too much peroxide which overwhelms our capacity to safely neutralize it.)
2. What is the normal first line of defense for a cell against wayward peroxide? Answer: the vinyl-ether double bond on the surface of the cells and intrinsic to the plasmalogen molecule grabs and dissolves the peroxide.
3. How can you prove that plasmalogen depletion is occurring with long COVID? Answer: Study from Italy showing a doubling of malondialdehyde with Long COVID. Malondialdehyde is the compound made when peroxide meets a vinyl-ether bond.
4. Why are plasmalogens so crucial to membranes? Answer: They are the most fluid of membrane lipids which allows embedded proteins to shape shift. With conformational change in shape, a protein can send its message to the cell next to it. Or, a packet of neurotransmitters can fuse with a basement membrane up to 1,000 times a second. That allows us to sense the world around us in real-time. That is a second "super-power" of plasmalogens.
5. What did Goodenowe find about plasmalogens that makes them so extremely important? Answer: No fair. Not covered in this letter. Months ago, we detailed how the Religious Orders Study from Rush Presbyterian showed Goodenowe's discovery by his metabolomics method that plasmalogen content of blood is the most accurately predictive blood test for life span and cognitive function.
Have We Had Diabetes Backwards all These Years?
This is huge. This is why you are fat and can't get "unfat". Let's explore.
Our current standard teaching of diabetes is that you are diabetic because you are insulin-resistant. You are insulin-resistant because you are too fat. Avoid carbs like the plague and eat nothing but fat and protein and don't touch sugar, fruit, pasta, rice, or bread or you will spike your sugar. That's the standard line everyone is familiar with. The problem is, no one gets better. The logic has an inherent flaw. You can't blame the disease on a symptom. It's like saying you got pneumonia because you have a fever. In the standard model, insulin is the uber enemy.
Maybe that model is backward. Let me start with the Randle Cycle as explained by Philip Randle back in 1963 in the Journal Lancet laid out his hypothesis. It goes as follows. When you eat a fatty meal with lots of carbs: (meatloaf, mashed potatoes, and gravy) you absorb the fat first in your duodenum. The fat globules go straight into your lymph system and show up in your circulation hours before glucose shows up. In that time, cells all over your body see the fat and take it on as the fuel of the day. They turn off insulin receptors. When glucose shows up, cells are already resistant to it. The more saturated fat you eat, the more insulin-resistant you become. Your cells can't turn fat absorption off and as you fill up all the standard places to store fat, you start packing in fat in all the unusual places, like your liver. Even your beta cells in your pancreas get stuffed with fat, and start to die.
The enemy and cause of all this trouble is the saturated fat. Consider the following experiment. This is just what Cyrus Khambetta did with his insulin-dependent diabetes. Start eating a very low-fat diet, with less than 15 grams of fat a day. All the fruit you want. Bananas, papayas, mangoes, grapes. You name it, you get it. Just no fat. Over the course of a month or two, your insulin resistance will disappear. Khambatta had his insulin-to-carbohydrate ratio change from 1:3 to roughly 1:33. That means his insulin resistance disappeared and now is in a normal range with normal function. His A1c is now in the low 5s and he eats his heart out on fruit. Just no fat. Included in that no fat means no meat, no dairy, no eggs, no cheese, and very limited nuts.
There have been dozens of authors who have published supportive studies that show the same thing, again and again. Esselstyn proved that you could reverse coronary artery disease with this approach. His book Prevent and Reverse Heart Disease proved the same hypothesis.
As the years have gone by, more and more research supports this cause of diabetes and fills in much more detail about the cause. I found one good review article to do a nice deep dive if you have a long, lazy afternoon and are in the mood.
www.What will Work for me. I'm frustrated by how rigid my own glucose metabolism is. I have been eating "keto" by and large, avoiding carbs and sugar like an angel. But lots of butter, fat, meat.....and vegetables with olive oil. Switching to a no fat diet is no small challenge. I think I found a clue in my Goodenowe Prodrome Scan. It has "Ceramides" on its list and mine are quite high. I want to explore that. There is a link with ceramides, high fat and diabetes. That may be a further unpacking of the real, root cause of insulin resistance and then visceral fat, inflammation and obesity all as secondary, downstream effects. The problem is not small. How do you have friends and go to a restaurant that cooks with NO FAT and NO ANIMAL? You can do it if you have no friends.
References: Frontiers Endocrine, Mastering Diabetes by Cyrus Khambatta, Am Jr Phys Endo Metab., Lancet,
Pop Quiz
1. What is the Randle Cycle? Answer: You absorb fat faster than carbs and cells, presented with fat, turn off their insulin receptors, making the later arriving carbs stuck in the blood.
2. Insulin resistance is where in the Randle cycle? Answer: Insulin rises as a secondary effect. Not a primary effect.
3. How does the Randle Cycle differ from today's traditional diabetes teaching? Answer: The method of response is diametrically opposite. Remove the fat and your insulin resistance goes away. You can eat huge amounts of carbs, to satiety, and not get fat and not have high glucose.
4. What is the principal drawback of this method? Answer: You have to get to below 15-30 grams (1/2 to 1 oz) of fat. That includes the fat in the banana, the apple, the mango etc - all of which do have some fat.
5. What role does linoleic acid have in this approach? Answer: Its reduction might be the most important or not. Research will tell. We do know that with modern agriculture's ability to grow soy, corn, canola etc, our linoleic acid consumption increased from 1% of our diet to 9-10 %, and in some cases, even greater. It gets oxidized with high heat cooking and becomes a poison.
Galectin 3 Perpetuates and Amplifies Inflammation
Ever heard of Galectin? It's a protein that turns on inflammation and is being found to play an outsized role in diabetes. It may be the key link to the level of inflammation that you feel in your joints. It was first discovered with respect to its ability to accentuate prostate cancer, if not all cancers some 20 years ago. It is an approved test for congestive heart failure.
With more research the means by which it accentuates and perpetuates inflammation is becoming more clear. It's not just in cancer or heart cells, galactin activity appears to show up in virtually all inflammatory processes. In that context, it appears to be an accelerant. As stated in the Cell reference, "Gal-3 contributes to the initiation and amplification of the acute inflammatory response by recruiting macrophages to injury sites and perpetuates a state of chronic inflammation through the activation of proinflammatory pathways."
This is where the story gets interesting. A young boy growing up in Israel on a kibbutz had his grandmother hand him one of the oranges she grew and told him, "This will heal all diseases." The prophecy turned out to be prescient! Sure enough, when Dr. Eliaz studied citrus pectin (the white stuff on the inside of the orange peel) he found if he chopped it up into small pieces so it would be absorbed into your blood, it became a remarkable inhibitor of prostate cancer.
It would have been enough if prostate cancer was inhibited. But on a monthly basis now we are seeing papers and studies in which modified citrus pectin helps diabetes, Alzheimer's, heart disease, chronic pain. I have personally seen a patient with prostate cancer live years past his expected demise taking only modified citrus pectin.
Inflammation is elusive. We don't quite understand just why it gets started. Everything from the gut biome to visceral fat is implicated, including the kitchen sink and your father's irritating uncle. This is a non-toxic, as natural a process as we can devise, inexpensive experiment we might all benefit from.
www.What will Work for me. Modified Citrus Pectin will lower your blood sugar. How, we aren't sure. But the lower your sugar, the longer you live. If you are one of the 60% of us who have modestly elevated fasting blood glucose, you might try the experiment. If you have any form of cancer, you might consider adding this to your regimen. Heart failure? Slam dunk. Heavy metal question? It's an impressive chelating agent. But what you might really try is 5 grams, three times a day for a month to see if your chronic pain gets better. Back pain? Hip pain? Give it a whirl. No toxicity. No prescription. You can buy it online. The only proviso is that the actually chopping-up process is some delicate chemistry and not everyone does it right. The raw, unprocessed orange peel sitting in the orange juice factory recycling pile doesn't do it. The good process is owned by the company Eco-Nugenics. It's on Amazon. Orange bottle.
References: Review Endo Meta Disorders, Jr Inflamm Research, LifeExtension, Cell,, Rev Cardiovasc Med., Journal Clin Oncology,
Pop Quiz
1. What is modified citrus pectin? Answer: The pectin molecule is cleaved into smaller molecules that penetrate the gut wall and successfully get into your blood. The whole molecule remains in your gut and has modest benefit as fiber.
2. What is galectin? Answer: It is a lectin that has pro-inflammatory qualities that help cancer cells metastasize, hearts stay inflamed, and diabetes remain out of control.
3. What does MCP do to galectin? Answer: It binds to it, inactivating it and consequently reducing the perpetuation of inflammation.
4. Does it lower blood glucose? Answer: This was the gimme question. (Yes!)
5. Any toxicity to MCP? Answer: Some GI issues but very rare serious toxicity.