Resistant Starch - We Aren't Getting Enough
Do you know what a resistant starch is? Well, easy. It's a form of starch that resists digestion, making it past your stomach and small bowel to the large colon. There, magic happens in the right circumstances. So, not always. It depends on the type of resistant starch. Let's see. They use the initials RS for the "Resistant Starch" type.
RS-1 is the whole grain. Imagine a whole, raw kidney bean. It hasn't been cooked. Its carbohydrate molecules are tightly packed and then coated with an outer fiber barrier that keeps digestive enzymes out. It sure is resistant. In fact, so much so that some of those raw, whole beans get pooped out to grow new beans.
Under an electron microscope, there is an orderly, packed, dense matrix of long molecules. Imagine a milkweed pod filled with seeds, all highly packed. That's RS-1. No digestive enzyme could get into that tight, dense matrix.
RS-2 is what happens when you cook the RS-1 in water. Heat it and add water. The starch molecules fluff up, sort of like a milkweed escaping its pod and letting its fluffy fibers stretch out. With RS-2 carbs, that is essentially adding lots of water molecules which lets the molecule fluff up. That creates lots of entry points for digestive enzymes to chop up the long chains of glucose into single glucose molecules. Think of a dandelion seed that you blow on. It's all puffy with many points of attachment for enzymes to digest. They can do so, rapidly. Most of what we eat is RS-2. Eat a serving of rice or hot potatoes, and your glucose spikes rapidly. One serving of rice and my glucose will go from 95 to 160 in half an hour.
RS-3 is RS-2 cooled down after cooking. The long strings of glucose contract and curl up. They can't get back to their original source of manufactured density, but their twisting and curling make it hard for enzymes to get in to digest. RS-3 is like white rice, heated up and cooked (fluffy and rapidly digested), then put in the fridge and cooled down. Those long chains coil up. Enzymes can't get it. Glucose rises much less rapidly. Cooked rice, pasta, and cooked potatoes, cooled down, are resistant starches. Blood sugar rises much more slowly.
RS-4 is an artificial, man-made resistant starch that is chemically altered to make thickening agents for packaged food. You are likely getting quite a lot of this. They aren't made by nature. They may be useful too, just need research to prove their safety.
The magic of resistant starches is that they don't get digested in your small bowel, and therefore make it to your colon where your community of bacteria that define many features of your well-being reside. They love resistant starches and blossom. Research is now proving that. More resistant starches turn into more beneficial bacteria. They make loads of beta-hydroxybutyrate which plays a huge role in calming inflammation. The alteration of your biome is critical to many diseases. A fine study from China giving increased resistant starches to folks with fatty liver found about a 10% reduction in intra-hepatic triglycerides, the fats that infiltrate and damage the liver.
Americans get about 3.5 grams of resistant starches a day. It is thought that we are optimally served if we get 20-35 grams of fiber a day. There is pretty good evidence that folks eating over 30 grams of fiber a day simply never get diverticulitis, appendicitis, colon cancer, heart disease, GERD, or irritable bowel. Goodness, that's what afflicts all of us.
www.What will Work for me. Well, the best dietary sources of resistant starches are raw potatoes and green bananas. That doesn't work very well. But raw potato starch added to a smoothie works just fine. Beans are magnificent sources. All beans. Oatmeal is another great source. Make a Muesli breakfast of raw rolled oats with some raisins figs, and slivered almonds. Maybe better yet is to get in the habit of making extra rice and eating it the next day, cold. Ditto for potato salad. You get to have some carbs, in a good form. It's surprisingly good for you. I was just visiting our grandchildren in Switzerland. Our hotel breakfast every morning was Muesli. I loved it. No sugar needed.
References: Cell Metabolism , mSphere, Nurition Jr, Jr Amer Dietetic Association, HealthLine, GimmesomeOven, Br Jr of Nutrition, Global Prebiotic Association, , National Geographic,
Pop Quiz
1. What is resistant starch? Answer: Carbohydrates that resist digestion for several reasons: still in their raw, tightly packed form, cooked and cooled down, or naturally high in fiber (like beans).
2. What happens to the stored form of glucose in plant carbohydrates when it is heated up with lots of water? Answer: Imagine a dandelion or milkweed seed that is tightly packed until its envelope opens. They fluff up and spread all the arms of the "amylose" (that's the molecule of long chains of glucose that we call carbs) molecule out creating a massive increase in enzyme accessibility. Enzymes can then cut the bonds between the glucose molecules at a thousands-per-second rate.
3. Cooling of pasta, rice, and potatoes does what to the starch. molecule? Answer: it shrinks down the long chain of glucose molecules into a tangled web that is all coiled up again. Enzymes can't digest it as quickly. It's that simple.
4. Name some really good sources of resistant starches. Answer: raw oats, all beans, cooled rice/potatoes/pasta, green bananas, Jerusalem artichokes
5. Can I just take a pill? Answer. Well, yes. You can buy Inulin, which all by itself is a resistant starch. It is extracted mostly from Jerusalem artichokes, chicory, and onions. But far better to make your food be rich in resistant starches.
The Sardine Fast - You're Not Kidding?
Sometimes really outrageous ideas come across the news that just need a bit of digging to understand. Sardines? Let's dig in.
An Internist in South Dakota, Annette Bosworth, MD, who is a prolific Youtuber, and somehow lost her license for some of her other political activities, who goes by the name of Dr. Boz, came up with this idea in 2023. She is an advocate for the carnivore diet and supports herself selling bison liver/meat capsules for humans. Already, the source sounds a bit eccentric.
If it weren't for the over 600,000 people who have viewed her YouTube vlog on sardines, and the dozens of Hollywood personalities who have tried it, you could shake this off as too weird to take seriously. But hang in there. Consider, 10 days of sardines only. You can get mustard, curry, olive oil, black pepper, or just plain brine, but it remains just plain sardines. There aren't many people who like sardines all that much. You eat them only because you are hungry. Really hungry.
Sardines are ocean-caught fish, rich in omega-3 fats. DHA, the most common omega three fat is incredibly liquid and doesn't freeze in ice cold water. That allows many fish to thrive in freezing cold water. But grass-raised animals also are rich in omega-3 fats, until they eat artificial carbohydrates like corn and beans. Our hunter-gatherer forebears ate lots of meat, if they could get it and tended to settle in venues where they had access to meat, either animal or fish in source. The ratio of omega 3 (the healthy stuff from animals) to omega 6 (the omega fat from seeds and nuts) used to be one:one. Animals get their omega-3s from green plants or algae in water. Because our animals are feedlot raised, their content of omega-3s plummets and omega-6s rises to create a modern ratio of about 1:20. Folks who eat lots of fried food will be 1:50. The problem with omega-6 fats is that they are the precursor molecule to inflammatory cytokines, so we tilt the balance to making more inflammatory markers.
Sardines are similar to the eulachon fish of the Pacific Northwest. The First Peoples of the Northwest used to harvest it, dry it in the sun, and make cakes of it that they traded far and wide. Called the Oolichan, it actually had less omega-3s and more saturated fat. It was called the candlefish because it would burn when lit. The Innuit of Alaska sought out seals and walruses for their blubber, which was much higher in omega-three fats.
Sardines have about 2 grams of DHA for each 3 oz can. That's about as high a food source as any other fish. When you eat the "sardine diet, or sardine fast" you are getting the majority of your calories from omega three fats. You are eating an Innuit diet. Early descriptions of the Innuit didn't include obesity. Modern Innuit eat 20 times the omega-3 fats because they still catch ocean fish and an occasional seal. But they have added sugar and flour in their trade with "outsiders" and have developed obesity. Interestingly enough, with their high intake of fish oil, and omega-3 fats, they have not developed the level of diabetes of other First Peoples. There is something protective about that high omega-3 fat diet.
But back to our sardine diet. One 3.5-ounce can is only 191 calories. Two cans is 382 calories. And you feel stuffed. Get the drift? Fifty percent of your calories will be from fat, and that's omega-3 fats. Three meals a day of omega three fats and you are getting 6 grams a day of omega three fats, but only 1100 calories.
You are getting no carbs or glucose source so your body has to switch to fat burning. It takes a day or so to get there so the first day may feel a bit rough as your peroxisomes gear up to burn fat. But once you are burning fat, it doesn't matter where you get it from. Sardines? Your own fat stores?
That's the 10-day sardine challenge. Not everyone makes it. That may happen in part because your partner may want nothing to do with you for those 10 days. But you will be in ketosis, and you will lose weight. You can feel a kinship with the First Peoples of the Pacific Northwest or the Innuit of Alaska.
www.What will Work for me? I haven't done this experiment. Not sure I ever will. I wanted to read the details. I suspect there is a nugget of truth in it. Our bodies were tuned to getting more omega-3 fats in their food chain. That's just another element that disappeared in our industrial; food system. There are clues that we really need more omega-3 fats back. Preferably from natural, real-world sources. Pills just don't provide the same benefit. This idea may have legs (or is it fins?). Maybe we really do need more DHA.
References: Slate, BMC Research Notes, McGill U, Frontiers in Nutrition, Science Daily, Eat This Much,
Pop Quiz
1. What is an omega-3 fat? Answer. It is a polyunsaturated fat with the first double bond on the 3rd carbon in the long chain. EPA is 20 carbons long with 4 double bonds. DHA is 22 carbons long with 5 double bonds. DHA is is critical component of plasmalogens, giving them their fluidity and flexibility. DHA is also a precursor molecule for many anti-inflammatory compounds.
2. Where does DHA come from? Answer: Green plants only. Algae in the ocean, and grasses and green leaves on land. Fish eat algae, and then up the food chain.
3. Why are sardines good for you? Answer: They are power-packed with DHA, getting 2 grams per 3.5 ounce can.
4. So, just what is the sardine diet? Answer: Eating JUST SARDINES, three times a day. Or whenever you feel hungry. Which you won't.
5. What happens to your body? Answer: You end up only eating 1000 calories a day because you just don't feel hungry. You get into ketosis and you lose weight. Something spooky about all that DHA. We used to have it in our food chain when our animals were raised on grass and in just the last 100 years, it got deleted, inadvertently, when all our animals were moved to feed lots.
PQQ - In Mother's Breast Milk for a Reason
PQQ is an antioxidant found in mother's breast milk. It's also found in a wide variety of foods like spinach, soy, and legumes. It acts like a vitamin in that you can induce a deficiency state which recovers in a dose-dependent fashion.
Why isn't it listed as a vitamin? Well, because it just hasn't been studied that much. When compared to CoQ10, it appears to win. If nature put it in mother's breast milk, there must be a reason. What's this all about?
It all comes down to the electron transport chain and NAD. NAD was the first fuel the first cell that started life on Earth 4 billions years ago. It has to pass electrons to NADH+, and that energy source still powers sirtuin proteins, which groom and care for your chromosomes. David Sinclair has shown that the degradation of sirtuins can be reversed by taking metformin (go figure, but that's why you are on metformin) and then extra NAD to give them their power source. The rest of the cell runs on ATP, a far more efficient source of energy.
NAD also plays a critical role in capturing high-energy electrons and passing them off to various components in the chain which then feed the electrons into the ATP cycle. That's the nugget of the electron transport chain. CoQ10 is the other key electron harvester and conduit between electron transport chain segments.
We know a ton about CoQ10 and consider it central to making fuel for your body to run on. PQQ acts like CoQ10, and maybe even a little better.
If those electrons are impeded in the electron transport chain, they spill out of the mitochondria and cause oxidative stress like a tidal wave. That's what COVID does within 2 hours of infection. And profound fatigue follows. Ditto probably for CIRS and mold disease.
Ditto also for Chronic Lyme, long Epstein Barr, on and on. It's the mucking up of the electron transport chain that deprives us of fuel so we feel fatigued and tired, brain-fog galore, and frustration that no one knows how to fix us. We can take CoQ10 as a supplement and it's been proven to help with high-energy needing conditions like congestive heart failure. But what to do if it doesn't work or help? That's where PQQ might play a role. Methylene blue also likely is helping in that space.
You see if you improve the electron transport chain and keep those high-energy electrons in the mitochondria, they don't spill out and cause oxidative damage to membranes, thus depleting plasmalogens and further degrading cellular function. It's that delicate nexus of biomechanical energy production that is sitting in the mitochondria and giving us our fuel. PQQ might just be better at repairing it when it's broken. No harm in trying.
www.What will Work for me. I'm obsessed with this topic. Plasmalogen replacement therapy rebuilds broken membranes caused by oxidative stress. That we know and are witnessing every day. But tools to repair the electron transport chain from incoming artillery fire, like COVID and CIRS (mold and Lyme) damaging the mitochondrial electron transport chain are needed. We haven't parsed out all the details, but a mother's breast milk has plasmalogens and PQQ. There just must be a reason. I'm adding PQQ to my armamentarium for folks with extreme fatigue. It's something to try. I'm intrigued by the lack of human detailed studies. The good news is PQQ is safe to try. The hints that it has a vitamin quality to it suggest that we usually get enough but in our ultraprocessed food chain, perhaps we don't.
References: FASEB, Dietary Interven Liver Disease, Biomolecules, MSBiotechnology, Molecular Metabolism, Vetback, Frontiers in Physiology, Redox Biology, WEbMD,
Pop Quiz.
1. What is PQQ? Answer: A vital cofactor that captures and passes on electrons. That makes it a potent antioxidant because it becomes oxidized and saves other molecules that were oxidized and damaged by that oxidation.
2. Where is it naturally found? Answer: In soy, legumes, spinach, and mother's breast milk.
3. Do we become deficient in PQQ? Answer: We may be but its deficiency may be covered by CoQ10, which we also need. CoQ10 has been widely studied. PQQ has not. If deficiency can occur, it may be considered a vitamin.
4. Extra Credit. Why might PQQ play a role in extreme fatigue from COVID or CIRS? Answer. Electrons get backed up by toxin mediated blockage of the electron transport chain. They escape out of the mitochondria and make a firestorm of oxidative stress.
5. Is PQQ safe to take as a supplement? Answer. Yes. And there are lots of providers trying to hawk it to you.
Muscle Atrophy and Aging
Last week we explored how apples, Fuji for example, have ursolic acid and how eating those apples, including the peel where most of the ursolic acid resided, contributed to a lowering of triglycerides and a tendency to gain weight.
There is another side to ursolic acid that is part and parcel of its calorie redistribution. It helps muscles grow. The research was done in lab rats, where consumption of ursolic acid was shown to increase skeletal muscle mass, fast and slow muscle fiber size, grip strength, and exercise capacity.
As you can imagine, the body-building community is interested in this topic and research labs have jumped in to see if there are credible human results. Imagine a study in which 9 young men do a standardized exercise program, take leucine or ursolic acid, and then submit to a muscle biopsy to see if changes can be observed. That study showed marginal effects of ursolic acid but the amino acid leucine appeared to be beneficial in humans.
How does leucine fit? Leucine is one of our amino acids central to signaling to build muscle. Considering that you will lose some 40% of muscle mass when you have an episode of prolonged immobilization or underuse, rebuilding muscle after a prolonged illness is an important topic. Think over your own lifetime and consider when you spent a week or two down for the count and not able to exercise. Or how about 6 hours in front of the TV watching inane programs that mesmerize you with their content? Your only exercise is standing to go to the fridge for more food, or cheering when your team scores.
The combination of the two, ursolic acid and leucine might just be the ticket to building better muscles. Considering that aging by itself makes us lose about 1.5% per year of our muscle mass over age 55, some strategy to avoid that is key. With that idea in mind, a recent randomized trial from Brazil of 28 men doing an eight-week muscle-building program showed no benefit to the addition of ursolic acid, but good effects with leucine. Shucks. But that's where it stands.
www.What will Work for me. Leucine works. The best research says you need about 55 mg/kg/day or about 500 mg for a 200-pound man. The supplement HMB is a metabolite of leucine that also makes that stimulation. It is widely sold for its muscle-building capacity. Ursolic acid works in lab rats but here is a word of caution. Humans are different than lab rats, and the real problem is that we are living way past our biological/reproductive age. Nature starts to shut us down over age 50, and our challenge is to negotiate strategies that get us around that. I have a hunch that the extra protein older folks need is first in line. Then, peptides that stimulate growth hormone, mTor agonists and urolithin may be what we are left with. And the gym. Shoveling mulch once a year isn't enough. Sitting on a lawn mower doesn't qualify either. Pickleball might suffice. Leucine and extra protein for anyone over age 60 is likely in order, along with the gym.
References:J Physiology, Jr Nutrition, Foods, PLOS 1, Int Jr Molecular Medicine, Int Soc Sports Nutrition, Clinical Nutrition, Advances in Nutrition,Jr of Nutrition, Jr Cachexia and Sarcopenia,
Pop Quiz
1. As we age, what happens to our muscle mass? Answer: It shrinks by 1.5% per year.
2. What does extra protein do to reverse that? Answer: Helps, probably because you then get extra leucine.
3. What does leucine do for muscles? Answer: Stimulates growth.
4. If you are sick in bed for a month, how much muscle mass did you lose? Answer: Up to 40%.
5. If you spend 6 hours on the couch every day watching TV, what's happening to your muscles? Answer: Come on, you know the answer. It's not good.
Fuji Apples and Weight Gain
It's the ursolic acid. Apples have it, but it is mostly in their peel. The societal cost of obesity keeps rising and attempts to understand how to contain that increasing rise have been stymied because of lack of understanding. Eating "more fruits and vegetables" isn't specific enough for many. This week's paper on Fuji apples is in that line of research. Apples are versatile, long-lasting, and inexpensive. They are now in season and are at their peak of quality and ripeness.
Ursolic acid is found in all apples, to a varying degree. The problem arises with long-term storage. To avoid spoilage very cold (33 degrees) and low oxygen (2-4% vs normal 21%) and high CO2 atmospheres are used, with loss of apple mass reduced dramatically with those strategies. Interestingly enough, it is a robust topic of study as different varieties need different storage strategies. The content of different species of ursolic acid varies as well from 0.45 mg g−1 to 3.52 mg g−1. That's an almost 10-fold variability. The variety called Spartan is the highest, with Cortland the lowest. Ursolic acid makes up some 70% of the antioxidant compounds in apples. The peel has 41% of it, with only 10% of the apple mass.
What is it about ursolic acid that helps with obesity? That's the nugget we are interested in. How is it better than Ozempic (and all the knockoffs), other than the $ 750 per month price tag? That's what this particular research was about. This is one of the many articles beginning to appear investigating the specifics of food contents in their relation to health issues. This particular one was looking at obesity and ursolic acid in apples, Fuji in particular (the dominant apple in Korea where the study was done).
In Korea, the WHO (World Health Organization) recommends that folks eat 400 grams of fruits and vegetables a day. No one does. In America, the FDA is our authority and recommendations are likewise ignored. The average American eats 1/2 a serving of vegetables a day, but only if french fries are included as vegetables. That makes potatoes #1. Pizza with its tomatoes and hamburgers with ketchup make tomatoes the number two vegetable. Possibly not in the best nutritional form. The Chinese and Croatians are the champion vegetable eaters at around 1 kilo per day.
But back to ursolic acid. It appears to lower triglycerides by about 25%. That reduces triglyceride storage, which means less fat gain. Pretty basic first pass. There is no explanation of what metabolic pathway is interrupted or redirected. The conclusion that apples help reduce fat storage because of their ursolic acid content may be a little premature, but the pattern fits.
I suspect the effect of volume of food in a whole apple, the fiber in the peel and apple, and the time spent eating all also play a part. All fruits and vegetables also tip you to a slightly alkaline balance. Who cares. Apples are a great food and if we can talk you into eating more, that's good. If it replaces a hamburger on a white wheat bun, I suspect you are better off.
www.What will Work for me? I'm having fun buying any variety of organic apples I can find. There appear to be more kinds and I want to encourage those farmers willing to diversify and grow new varieties. They just have to be organic. And I wash them as soon as I get home.
References: Food, Molecule, World Pop Review,
Pop Quiz
1. What is it in apples that provides their extra metabolic kick? Answer: Ursolic acid is the 70% active form.
2. Are all apples the same for ursolic acid content? Answer: No, up to a 10-fold difference. If you can find Spartans, they are the best,
3. What does ursolic acid do that appears to be the key benefit? Answer: Inhibits triglyceride accumulation and uptake.
4. Do we know the mechanism of that inhibition? Answer: No, not yet
5. Where is the ursolic acid found in the apple? Answer: Mostly in the peel.
Sunlight Helps you Live Longer
Everyone knows that you need sunlight to get Vitamin D. And it's now widely accepted that skin color around the world is driven over time by humans need for Vitamin D, balanced by the need to protect from loss of folate with too much sunlight. Africans can protect their folate, Caucasians can live in Scotland and Sweden in the fog and still generate a tiny bit of D, sufficient to stay alive.
We've known that low levels of D lead to more heart disease, cancer, infections etc, etc, but we have been puzzled why giving D as a supplement hasn't had the homerun effects we were hoping for. There is clear benefit at preventing multiple sclerosis, but not quite so clear with cancer. Why the ambivalence? There must be something more. Anyone from Wisconsin who has arrived at Fort Lauderdale and completed a beach walk in February will tell you there is something more and they feel just great. Not just good, great. There must be something more.
Well, enter Richard Weller, the first dermatologist researcher to show that exposure to sunlight produces Nitric Oxide, and that may be more important for your health than the Vitamin D. Gareth Hazel in Nature Communications showed that skin exposed to actual sunlight produced NO across the whole spectrum of UV wavelengths, not just the isolated segment that makes Vitamin D, or sunburn. Even the longer wavelengths that are much less damaging to your skin helped make NO.
It's not a trivial issue. As we age we naturally make less nitric oxide (NO), by about 12% per decade. NO is critical for keeping our arteries flexible and our blood pressure low. It plays an outsized role in helping our immune system kill bacteria and viruses. It downshifts our response to inflammation. You want every molecule of NO you can get. The extrapolation of the beneficial effect of NO from sunlight accounts for some 300,000 excess deaths per year in the USA secondary to lack of sufficient sunlight exposure, and subsequent less NO. Europe is worse off as they are farther north and more congested. Tanning beds won't provide quite the same because they don't offer the full spectrum of UV radiation.
How much sunlight do you need? Not much. A Standard Erythemal Dose or SED is what it takes a caucasian with skin type II (can tan but will burn if enough exposure) about 20 minutes of low-intensity sunlight. But even some clouds will allow you some SED effect. You will still get some NO. You can look up your Fittzpatrick Skin Typeand see where you fit. You need to get your sunlight, as often as you can. No burning.
www.What will Work for me. I was a champion for Vitamin D at Aurora Health Care 15 years ago. There is modest benefit on many fronts but there is no money in a supplement that costs pennies...so little research. Had I stayed longer I would have done a study on Vitamin D and prenatal care (massive reduction in preemie births) and congestive cardiomyopathy in young African Americans. I'm certain I would have shown dramatic benefit. But the money all goes to whiz-bang antibodies and fancy procedures that generate big dollars. Not much for lowly Vitamin D. We all still need to be on Vitamin D. Keep taking your 5000 iu a day. But recognize that you need the sunlight too. Not too much. No more than 1 SED (what it takes to make your skin a little color change). And now we can buy NO supplements to make up for your aging. (www.n1o1.com. I take those too.
References: Nature - Scientific Reports, J. Investigative Biology, Int Jr Environmental and Public Health, TED Talk by Weller, Fitzpatrick Skin Types,
Pop Quiz
1. Sunlight provides what benefit besides VItamin D? Answer: Your skin make nitric oxide.
2. Why is it important to keep being exposed to sun? Answer; As we age, we naturally lose about 12% of our NO per decade of live. A 70 year old will be down 85%.
3. When does heart disease kill the most of us? Answer: In our 60s and 70s and 80s. Concurrent with 75%, 85% and 95% reduction in NO. (Forgive the rounding error)
4. Why is sunlight better than a tanning bed? Answer: You get the whole spectrum of UV radiation, which all contributes to NO production.
5. Got your winter plans made yet? Answer: I hear Sanibel Island is gradually recovering.
Short of Energy? Have you tried methylene blue?
"I'm so tired! Anything you can help me with?" is the # 2 reason for people to see a doctor. We have had all sorts of strategies over the years. The American College of Anti-aging Medicine strongly advocated "Adrenal Fatigue" for years. Then along came mold and its syndrome of fatigue. Even that didn't get to the root cause. The COVID pandemic unleashed a flood of research about mitochondrial damage. The curious collapse of cardiovascular function with COVID-19 pointed to something amiss in mitochondria. The heart is made of 33% mitochondria because it uses so much energy. Just take a peek at an electron microscope picture of the heart and see how many there are. Same for your brain. The brain and heart both have about 5000 mitochondria per cell. No wonder "brain fog" factors prominently in COVID along with extreme fatigue.
That's the clue. Malfunctioning mitochondria means less energy, means heart failure, and brain fog, means "I'm so tired". It's becoming apparent that the electron transport chain is a touchy metabolic process. The job of mitochondria is to take high-energy electrons in carbohydrates and proteins and extract the energy in the process of making water and carbon dioxide. Those electrons get transferred down 5-6 steps through several complex proteins that do their best to hang onto those slippery, energetic electrons. It's tricky to hang on to them because they are sometimes a particle, and sometimes a wave. Go figure. Physicists have been arguing about that forever.
But mitochondria have to be in perfect condition to do it just right. Even on a good day, they don't do it perfectly and about 2% of electrons escape. When they do that, "oxidate stress" is made and hydrogen peroxide is made as a byproduct of trying to recapture those escaping electrons. There is a frantic response to quench peroxide so it too doesn't cause damage with the uncontrolled "high energy" it still has. That's what you take antioxidants for, to neutralize those oxidants. And that's why your body has developed plasmalogens on the outside of the cell to neutralize peroxide before it causes damage, (and all the other lesser oxidants that are made by those errant electrons.). Methylene blue can reroute electrons in the mitochondrial electron transfer chain directly past the "short circuit" (from NADH to cytochrome c), increasing the activity of complex four and effectively increasing mitochondrial ATP production. With that rerouting, you also get a dramatic reduction in brain oxidative stress.
Back to that electron transport chain. COVID mucks it up. And probably many other things do too. That's where many mysterious toxins do their damage. Mold, for example. Lyme disease is likely another. But if you look under the hood at all those "mysterious" brain diseases, you will find hints that they are all doing the same thing. Google "mefloquine" toxicity, or black widow spider bites, or red tide, or ciguatera poisoning (all very deep rabbit holes). The electron transport chain is disrupted, and that unleashes neuroinflammation.
What would happen if you found a chemical that allowed those tricky electrons to just bypass the site where they escape and allow the electron to stay inside the mitochondria, and go on down to the end of the electron transport chain? What do you think might happen? Yup, yup, yup. A boost of energy.
Let me introduce methylene blue. That's what it does. When it keeps mitochondria functioning, there is a dramatic reduction in neuroinflammation and all of its downstream effects. Alzheimer's, Parkinson's, fibromyalgia, and chronic fatigue are all in the mix of subsequent problems. It's been around for over a 150 years (Wikipedia) and has been found to be quite safe. Anesthesiologists use it. Urologists use it(well, used to).
ER doctors have it in their armamentarium for rare poisoning, cyanide. Cyanide immediately poisons the mitochondria. Methylene blue salvages that. Well, you don't have to be as dramatic as cyanide. How about more subtle poisoning? How about a little bit of CIRS and mold poisoning from an older home with too much mold toxin? How about chronic Lyme with its horrible fatigue? How about? How about? There's a long list of candidates.
How about a 70-year-old guy/woman with a bit of a fatigue issue? How about all of us who feel worn out and can't get our engine running like we used to?
www.What will Work for me? It's a bit tricky to take and there are some caveats. Too much is another poison so there are some clear limitations on its use. And getting it is no small problem. It's only prepared by compounding pharmacists who have to make capsules of it. And there is one very interesting side effect. Your urine turns quite blue. In fact, it has to be in capsules or your mouth turns blue. When you try and make it at home, and you spill a few crystals that your alert puppy licks up, you get a blue-tongued puppy that you have to watch like a hawk so you don't get blue spots on your carpet. I've been obsessed with it as a tool for those who still feel fatigued. I've tried it for a month. The blue is off the dog's tongue and I feel my energy is up enough to notice. Want to try the experiment yourself? I'll show you how. (If you're an old guy/gal who dribbles a little, you might want some protection so that you don't show blue pant stains.)
References: Cells, Research Gate, Molecular Neurobiology, VA Public Health, Clinical Toxicology, Nutrients,
Pop Quiz
1. What is methylene blue? Answer: A potent blue dye invented 150 years ago.
2. Is there a real role for it in traditional medicine? Answer. Yes, it reverses cyanide poisoning in a jiffy when you give it IV. (Maybe 100 times a year in all the USA). There are other uncommon uses, but nothing mainstream quite yet. An ER board question about fava bean poisoning and "methemoglobinemia" would have methylene blue as an answer.
3. If you get too much, what happens? Answer: You paradoxically get methemoglobinemia. So there is trouble at the top end too.
4. Just what does methylene blue do in the mitochondria? Answer. It captures escaping electrons and keeps them safely in the mitochondria, to be turned into energy (as ATP) instead of damaging oxidants.
5. How can you be sure if you took your methylene blue dose each day? Answer: Your pee is blue. (Be careful to flush or your toilet bowl will gradually get a blue ring in it.)
Eating More Alkaline Foods is Proven to be Better for You
I have waited for this study to be done for years. This is hugely important. The study is simple. Take folks who are showing metabolic stress by having high blood pressure enough to be putting out albumin in their urine. That means they are on the path to kidney disease and eventually heart attacks. Split them into three groups: control, oral bicarbonate, or fruits and vegetables - 2-4 cups a day. The core idea is to see if reversing our acid diet of animal products is good or bad for us.
Results? The fruits and vegetable arm dropped 1 point on BMI (body mass index) weight scoring, from 28 to 27 (still not ideal - we like ,25). But their blood pressure dropped more (129 versus 135), their HDL's went up more, their Lp(a) dropped more than the controls. The bicarb group didn't improve as much. What does this mean and how did these results come about?
Mammals evolved for some 50 million years eating green plants and fruits. Hominids, (gorillas, chimps, orangutans, bonobos,) all eat pounds of leaves a day and all the fruit they can find in fruit season. Plants have a biological ash that is alkaline so when all is fed and done, the animals that eat plants have an alkaline diet and they show it by having alkaline urine. Animals have more sulfur-containing amino acids so their digestion and metabolic processing leave an acid residue. You can see that in yourself. If you eat nothing but salads, fruits, and green vegetables, your urine pH will be higher than 7.0. If you focus on dark green vegetables, you can even gut your pee up to pH 8.0.
We humans had to start eating animal to support or enlarging brain with its calorie demands. So our metabolism had to try and adjust to that. Could we? If you measure the urine of hunter-gatherers, their urine pH is alkaline most of the time because they eat plants that don't run away. When the occasionally catch an animal, they feast on that and their pH becomes acidic for a day or so.
The formula is simple. It takes 3 servings of plants to neutralize the acid in one serving of animal. It takes 6 servings of plant to neutralize one serving of cheese. Grain-derived products are about 1 serving of acid to 1 serving of plant. Hence, a Big Mac has 2 hamburger patties (2x3=6) and 2 cheese servings (2x6=12) and 2 bread servings: (2x1-2). You have to eat twenty servings of vegetables and fruits to make up for the acid in a Big Mac. Hmmm. Hence, you can understand my American's urine is usually pH 5.0, very acidic. That's the transition we made. Some humans eat only animal. But most eat a combination and generally, animals are not as common as plants so plants make up the majority. In the 19th and 20th century, we became much more wealthy and could afford much more animal. This is a new and abrubt transition, to a large degree. Has it been bad for us?
Yes, it's bad for us. For every serving of animal, you lose amount a milligram of calcium from your bones, because that's the reservoir of bicard to neutralize the acid that's going through the system. In this modest study, with just a whisper of fruits and vegetables, not even close to getting their urine alkaline, their serum bicarb actually went up a teeny tiny bit. from 25.05 to 25.40. Not a lot but a bit. Their dissolved CO2 went from 26.25 to 26.7. Those are small, but meaningful. You can change the bicarb in your blood, and the pressure on your bones to sacrifice some bicarb to neutralize the acid.
Maybe most importantly, their renal function as measured by the decline in GRF (glomerular filtration rate=the ccs of blood washed clean per minute) declined from 102 at baseline to 97 in the fruits and vegetables, and to 92 in the untreated controls. That was a halving of their loss of function.
And that's just what Khambatta shows in his diet with his book, "Mastering Diabetes". On a pure, vegan, 0% fat diet, insulin consumption drops 98% and coronary artery disease goes away. Esselstyn proved the same thing. On a pure vegetable, very low fat diet, Essylstyn proved reversal of heart disease. Ornish has proved the same. We can rid ourselves of the curse of heart disease with this alkalizing diet taken to its logical conclusion.
Did you get that? More fruits and vegetables helps at whatever level you can muster. You have to have some animal for the B12 found nowhere else. But the crushing metabolic load of animals and their fat is hard on our hearts, our arteries, our kidneys and our bones. This research proves it.
www.What will Work for me? My blood pressure this week was 102/65 at the doctor's office. My weight has been slowly drifting down as I eat mostly vegetables and fruit. I had two eggs for breakfast today and 2-3 times a week. But two apricots for lunch, or two apples for many days have been a staple during the wonder of summer. Most suppers are large salads and an Esselstyn recipe here and there. I'm on a chickpea curry binge recently making samosa chaats (Indian snack food) with lots of onion, tomato and chickpea curry on a samosa. Yummy supper. If you make this recipe, make sure you get the associated chutneys from tamarind and cilantro bases (add water to make a topping sauce). They make it pop with flavor. (Indian Grocery across from Mayfair has shelves of them. As do all Indian Groceries.)
References: Am J Medicine ,
Pop Quiz
1. When you eat animal products (meat, eggs, cheese, milk, fish,) what happens to the pH of your urine? Answer: It goes lower (Do your own science project. Get some pH paper at Walgreens or CVS. You can measure it for yourself.
2. Why? Answer: All animal products have more sulfur-containing amino acids that get turned into sulfuric acid. That makes for more acidic urine.
3. If you eat a pure vegan diet for a week, what pH will your urine be? Answer: Greater than 7. As much as 8 if you stick with it for a week.
4. What happens to your bones when you eat an all-meat diet? Answer: The acid content, flowing through your system is calling for "neutralizing" and balancing out the acid by sharing some of the bicarb locking in your bones with calcium. You lose the calcium too. Any wonder we are having an epidemic of osteoporosis along with our heart disease?
5. What happens to your blood pressure on a more alkaline diet? Answer: It falls. The more vegetables, the further it falls. Being alkaline is good for you. It's our basic biology.
Alpha-Gal Syndrome - Ever Heard of It?
Alpha-Gal is not a late-night comedian's joke about your wife? It's a real disease that comes about in an unusual way. It all starts with a tick bite. That tick injects a tiny bit of "alpha-gal" sugar into its victim, and that induces an allergy to a sugar called alpha-gal from any other source. Its chemical name is galactose-alpha-1,3-galactose, two galactose molecules hooked together. It is naturally present in all mammalian meats, except hominids.
When humans, injected with "alpha-gal" and now immunologically sensitized to that sugar, eat beef, pork, lamb, goat...they get an allergic reaction. It may take a couple of hours to get wound up, but it can be very severe, even fatal. And it's not just the meat. Any mammalian food products like milk, cheese, and gelatin can set it off.
What are the symptoms? They may include hives; swelling of the lips, tongue, throat, or eyelids; cough; difficulty breathing; wheezing; heartburn; nausea or vomiting; abdominal pain; diarrhea; or decreased blood pressure.
Well, who cares? It's such a bonkers diagnosis, it's way too rare for me to worry about. Is it? Whoa, Nellia, it has been reported in over 110,000 people in the last decade. That's not all so rare. So, explain, how was it discovered.
Remember that animal protein connection? Well, if you want to read a real medical detective story, this is it. The monoclonal antibody, cetuximab, was approved in 2006 for the treatment of head and neck cancers. Some of the patients given it developed allergic reactions. A Dr Tina Merritt, at Fayetteville, Arkansas, had two severe cases and the detectives were off and running. When they looked at other cases of allergy to cetuximab, they found those patients had pre-existing IgE-specific antibodies for cetuximab and that the target of those antibodies was the oligosaccharide, galactose-alpha-1,3-galactose .
The researchers were puzzled. They found the allergy to the cetuximab only in a limited region of the country. Tick country. When they asked patients with the allergic reaction if they had had tick bites, they lit up and related that they had been bitten by Lone Star ticks and had had reactions to them. How's that for good detective work? (Sounds like a 60 Minutes story in the making...expect to see it come up some day.)
www.What will Work for me. This sounds arcane and trivial, aside from the fact that I was bit by a Lone Star tick at a family reunion in New York. We foolishly went for a walk, waiting for our family to arrive. We thought it would be nice to explore the local state park for possible future walks. We came back and had some 40 ticks on us and were frantically brushing them off. I found one embedded in my leg the next morning and pulled it out. Except, it didn't all come out. I was sick off and on for the next month, with fevers up to 101 every day and extreme fatigue, until the tick wound scab fell off and within hours, my fatigue cleared and fever disappeared. I was on Doxycycline the whole time, to no effect. It wasn't Lyme disease. I eat very little animal meat except chicken and fish (not mammals). There is something about ticks we don't fully understand. They carry more than just Lyme disease. Did I have a mild form of alpha-gal? We are at the end of summer. Ticks are everywhere. Please, please, please, get some DEET and wear long pants when you go in the woods. Or stay home with your real Alpha-Gal. Ditch the woods with grassy edges until the first frost.
References: Yale Medicine, JAMA Open Network, Jr Aller Clin Imm.,
Pop Quiz
1. What is alpha-gal? Answer: A sugar composed of two galactose molecules present in all mammals except hominids.
2. What foods have galactose in them? Answer: Milk has lactose which is a sugar made by combining galactose and glucose. Celery has it. Cherries and avocados have it.
3. What is the syndrome? Answer: Allergic up to severe anaphylaxis
4. How is it caused? Answer: The Lone-Star Tick injects the alpha-galactose molecule on biting a person. That person then becomes allergic to animal products.
5. Is this worth-while talking about when it might be the rarest thing on earth? Answer: Time out. It's a new diagnosis but there have been 110,000 people diagnosed with it in the last 10 years. There are likely multiple of that who have had it. If you have weird, allergic type reactions to animal protein, including milk, gelatin (all those supplement capsules), you may have a mild form of it.
Hallmark of Aging 12 Dysbiosis
What's dysbiosis? It essentially means the disordered distribution of bacteria in one's colonic/gut biome. It's been quite a journey, exploring the functions of our gut biome. We first knew the gut was where food went in and digestion happened. Then we added protection against dangerous bugs and parasites, and production of essential metabolites including vitamins, amino acid derivatives, neurotransmitters, secondary bile acids, and short-chain fatty acids. The amount of unique DNA in our gut biome is on the order of 100 times our own DNA, so we are really carrying around quite a treasure trove of metabolic capacity in our gut of which we are just becoming more fully aware.
Observations made on elderly humans show changes in their gut microbiome with superagers tending to substantially reduce Proteobacteria and a significant increase in Verrucomicrobia. If you transplant those bacteria with a fecal transplant into mice genetically modified to die young, they live longer. Apparently fecal transplant works, as does oral supplementation with helpful bacteria, like Akkermansia. The heterogenicity of aging biomes is daunting and still not uniform.
What is more uniform is an interesting convergence in plasma concentrations of microbiota-produced amino acid derivatives. Breakdown products like indoles from tryptophan are correlated with healthy, longer life whereas and p-cresol sulfate from phenylalanine are highly correlated with frailty and increased mortality.
Lactobacillus reuteri has been found to reduce osteoporosis. Akkermansia keeps popping up in review articles about its role in establishing a healthy gut and gut barrier, leading to better aging, better cognitive function and longer life.
What didn't make the Cell review was lactulose. Lactulose has been used for decades in Internal Medicine to salvage end-stage liver failure patients for a few more months of hopeful waiting for a liver transplant. The use of lactulose results in a massive upregulation of the healthy bifidobacteria in their gut with resulting clinical improvement in the liver failure patient's well-being. The gut essentially takes over for the dying liver, at least for a few months. The same effect happens in normal humans too. In fact, lactulose is so safe, it has now become the standard of care for pediatric constipation. Regular folks on the Standard American Diet of no fiber, saturated fat, lots of sugar are often constipated and benefit massively from lactulose.
And fiber. Dear old fiber. The more fiber one eats, the more short-chain fatty acids are made and the more diversity develops in the colonic biome. Stools become softer and more regular. Cancer risk goes down. Heart disease risk goes down. that we should all eat more fiber. Longer life (29-54% reduction in mortality).
www.What will Work for me? Akkermansia sounds like a good idea. Lactulose sounds like a no-brainer. But the cheapest and most effective of all is fiber, fiber, fiber. More green beans, fewer cookies. This whole topic is waiting for AI to sort out the complexity. I suspect what they will find is that a single meal of saturated fat and sugar will change your biome to the worse, and then gradually it will claw back. I'm annoyed the review didn't mention the biome of the tongue where Nitric Oxide is made. That may be as important as any other. Please don't use mouthwash.
References: Cell, Nature Medicine, Nature Reviews, Aging Disease, Nature Communications, Archives Internal Medicine,
Pop Quiz
1. What is our gut microbiome? Answer: All the variety of the 5000+ species of bacteria living in our gut.
2. What is the proportion of DNA in our gut bacteria compared to our DNA? Answer: around 100 to 1 gut to human. We are lucky we are the managing partner of our condo association. (Or maybe we aren't, and just don't know it yet.)
3. What is lactulose? Answer: An indigestible sugar to humans but a super food for bifidobacter, beneficial colonic bacteria. Bidobacter is good stuff, present in the gut of superagers.
4. Can you name a bacteria in the gut that helps reduce osteoporosis? Answer: Yes, lactobacillus reuteri
5. What's the cheapest way to get lots of gut diversity? Answer: Fiber, fiber, fiber.