Your Gut May be Dangerous for Your Brain
This is a major public health discovery. Researchers at LSU have just published the finding that the bacteria family Bacteroides fragilis make a lipopolysaccharide called BF-LPS, the most potent neurotoxin found to date. That's it. The bacteria that is present in your gut at all times, make a poison that gets out of your gut, into your blood, and proceeds to enter your brain and damage it.
"LPSs, in general, are probably the most potent microbial-derived pro-inflammatory neurotoxic glycolipids known," says Dr. Lukiw. "Many laboratories, including our own, have detected different forms of LPS within neurons of the Alzheimer's disease-affected human brain." as quoted to ScienceDaily.
The pathway of effect is fairly straightforward. The BF-LPS leaks out of the GI tract enters the bloodstream and is able to penetrate the blood-brain barrier after which it enters brain cells. Inside the brain, it increases inflammation and inhibits a very specific cell-integrity protein called neuron-specific neurofilament light (NF-L,). Deficiency of this protein leads to progressive nerve cell atrophy, and then cell death, as is observed in Alzheimer's-affected neurons. In fact, you can measure elevated spinal fluid NF-L proteins up to 22 years before developing Alzheimer's. Spooky!
What's the solution? Go to the source. Change your gut by changing your diet. This is where saturated fat becomes a recognizable problem. Eating more bacon and corn-fed steak is dramatically increasing your saturated fat. That leads to higher levels of colonic Bacteroides. That leads to higher LPs in your blood. That leads to lower levels of NF-L. Increasing your Bifidobacter families of colonic bacteria do the opposite. And you get that by eating more fiber. Hence, more fruit and vegetables, more flax seed, and whole grains. How does this square with lectins? With Plasmalogens? Time will tell.
The LSU team also reported that adequate dietary fiber intake can head off the process. We Americans average somewhere in the 10-15 grams a day of fiber. If you can get your fiber up to 25 or better, 30 grams a day, you get a huge increase in Bifidobacter and a dramatic downregulation of Bacteroides. And if you take lactulose as a supplement, you get the same effect. Can you eat all the bacon you want and just take lactulose to make up for your sins? Not sure. Not studied. But better, get yourself sufficient fiber with lots of vegetables and flax seed, or even Metamucil and other forms of bulk fiber, and then take 5 grams of Lactulose a day. Lactulose comes with the added benefit of increased calcium and magnesium absorption.
www.What will Work for me. Well, now I understand why we need to be cautious with the so-called "Keto" diet that is based on meat. Corn and bean-fed animals get fat, just like we do when they eat too many concentrated carbohydrates. The fat they store is saturated fat that causes inflammation in us when we eat it. And now we know at least one dramatically damaging pathway by which that inflammation wreaks its havoc. I'm pretty good at keeping my keto diet intact by not eating till lunchtime, five days a week. That puts me into ketosis for at least 6 hours those 5 days. And if I stay away from sugar and white flour, I can keep my glucose below 100, most of the time. When I eat spinach and broccoli, asparagus, and salad, my glucose stays put. But fruit....not so good. So, I'm aiming to get my fiber from vegetables. Piles of them. And lactulose it is.
1. When you eat saturated fat (bacon, steak, butter, cheese - all from corn and bean-fed animals ) you encourage what group of bacteria in your colon? Answer: Bacteroides
2. What membrane lipid do those little Bacteroides make that gets into your blood? Answer: LPS's - lipopolysaccharide. Steven Gundry calls them "Little Pieces of S..."
3. What's so bad about BF-LPS, the lipopolysaccharide from Bacteroides? Answer: It is an intensely neurotoxic compound. Kills nerve cells.
4. What's so bad about nerve toxin in your gut? Answer: It has no problem getting into your blood and then soaking right into your brain. There it causes awful damage.
5. You can alter this process by doing what? Answer: Cut down on saturated fat, switch to grass-raised animals, and increase your fiber in your diet by lots more vegetables. Then you increase the Bifidobacteria in your gut. Ask for triple broccoli at the restaurant. Not double, triple. Skip the potatoes. Consider taking lactulose as a supplement to increase that even further.
Turkey Tail Mushrooms and Breast Cancer
You know turkey tail mushrooms. If you ever walk in the woods, you will see them as one of the more common mushrooms growing off tree trunks, like a circular shelf. If you look at the bottom of them, they look like a turkey tail, fanned out. They are found all over the world, In China and Japan, they have been used for years as immune boosting agents and in the treatment of a variety of cancers, most commonly breast cancer.
We don't have large, randomized, placebo-controlled trials in the US. That is our scientific standard of care. But I heard an anecdote of a midwestern woman with advanced breast cancer who started taking turkey tail mushroom and proceeded to get a full remission. A search of Pubmed finds that she is not alone.
Perhaps you would like to know about turkey tail. It's been around in Chinese medicine for millennia. What does it do?
To know how it works, you need to learn about the CR3 receptor in cancer. That's what turkey tail seems to modulate. In a clinical trial conducted in Washington, turkey tail appeared to show a faster rebound of immune function after radiation. Up to 9 grams a day was found to be safe and well tolerated.
The real question is whether the "home run" anecdote of a patient with advanced cancer who gets better is able to be duplicated in others. The problem arises in that medicinal plants have dozens, if not hundreds, of compounds, each of which has its own effect. In turkey-tail, only the compound PSK has been studied in isolation. In a randomized trial from Europe comparing PSK with tamoxifen versus tamoxifen and mitomycin over 5 years, survival in the PSK group was 89% while the mitomycin group came in at 94%. (P value 0.06, not quite significant). That's not a cure or an improvement. But it's only one compound out of the many hundreds, if not thousands in turkey tail.
That's the conundrum. The state of science as we now know it revolves around one, solitary compound, extracted and studied in isolation. There is no food of any kind that is one pure compound. All of our vitamins, proteins, and minerals come in mixes, and mixes are what we are designed to eat and react to. The development of complex, artificial intelligence may be able to parse out those complex interactions, but for now we are left with a shrug and a question mark.
www.What will Work for me. Traditional medicine has used foods for millennia and found them to be effective, in some circumstances. I think mushrooms have enough of a proven immuno-supportive role that they deserve further consideration. The Brits have published literature from their national nutritional survey showing improved cognitive function in those who eat more mushrooms. Good enough for me. I am a regular the "Mr Mushroom" at our farmers market.
1. What is turkey tail mushroom? Answer: One of the most common mushrooms found in the woods growing on decaying tree trunks.
2. Is it safe for me to pick it and eat it in the woods? Answer: If you are not an experienced mushroom hunter, no! Please let someone make the stuff for you. There are many vendors.
3. What dose is safe? Answer: 9 grams a day has been studied and is safe
4. How does it work? Answer: We really don't know but we think it has something to do with boosting the immune surveillance of your body against the ability of cancers to hide from your immune system.
5. Should we all be taking some mushrooms? Answer. Yes. Good for your brain, your immune system, and probably more if we got around to studying them. That is not likely to happen if you can't patent them. And when they grow freely in the woods, that won't happen.
Vitamin D Improves Clinical Function in Heart Failure
In 2004, a report of two cases from Great Britain of infants presenting in severe congestive heart failure was published. Literally, 6-week-old infants, were admitted to ICUs with huge, dilated hearts and all indications of severe congestive heart failure. There were found to be recent immigrants of African descent who had had no prenatal care. Their vitamin D levels were unmeasurably low. On being given Vitamin D, their congestive heart failure was completely cured. Cured.
In 2011, Great Britain with its national database reported more cases. Again, immigrant women of color (requiring much more sunlight to get sufficient Vitamin D,) with litte prenatal care had infants presenting with severe congestive heart failure. Again, unmeasurable Vitamin D. Again, cured completely with Vitamin D.
This author had just moved to the Aurora Sinai ER in Milwaukee and was struck by the number of young, African American men presenting to the ER in congestive heart failure. I measured Vitamin D in all of them and to a patient they were below 10. I gave all of them 100,000 IU three days in a row and made appointments with cardiologists, after printing out the above two papers to present to their cardiologists, trusting that the system would pick up on their deficiency.
This author went to the Department of Cardiology at St Luke's Medical Center with the above information in hand and suggested that Vitamin D should be added to the protocol for congestive heart failure, even if not on American Heart Association guidelines yet. I showed the 25 assembled cardiologists the publication from the Journal of the American College of Cardiology by Victor Soukoulis about Vitamin D, CoQ10, carnitine being inadequate. But we didn't have a randomized, placebo-controlled trial to prove its benefit. Nothing happened. I was informed that the cardiologists did procedures to reverse disease and were not in the business of nutritional supplements. I was discouraged. No, I was furious.
Now we have proof. With that background, this week's paper is huge. First of all, it was randomized, placebo-controlled, and multi-hospital in design. Seventy-three patients whose Vitamin D level was below 30 were given 4000 iu of Vitamin D for 6 months/or a placebo. The authors wanted to prove an improvement of "endothelial dysfunction" which is awful in congestive heart failure. That did not improve in 6 months. But the clients were able to walk further, had better blood pressure and fewer symptoms. Their Vitamin D levels rose from below 30 to about 50.
What is endothelial dysfunction? It is essentially the inability of the vessel walls to relax due to lack of nitric oxide. Simplified, it is high blood pressure that can't relax. It is the first step to developing coronary artery lesions because the high blood pressure proceeds to damage the walls of the artery. Ok, so one micronutrient, by itself didn't solve the whole picture. But Vitamin D improved all the other halo effects around the margins. All in just 6 months.
And was 4,000 enough for 6 months? No! If they had gotten weekly blood levels of D, they would have seen the levels climbing and very likely just got to 50 in the final week. They should have given a loading dose of 100,000 Iu to raise their blood level 14 ng. From 30, they would have been at 44 in one day and then, 6 months of 44 -50 would have showed even more benefit. And how about throwing in some CoQ10, carnitine, magnesium and ribose too! The study wasn't near long enough. Vitamin D turns on DNA and makes cells grow. That doesn't happen overnight. It takes weeks to get started. To get full effect, you likely need 1-2 years.
But don't complain. Instead, find any old person you know or are living with and make sure everyone you love and care for knows their Vitamin D, or at taking at least, at least, 4,000 IU a day. 5,000 is easier, One pill.
Folks over 70 make 20% of the Vitamin D of 20 year olds, given the same amount of sun. That's what our wrinkles are: the loss of cholesterol in our skin from which Vitamin D is made when UV radiation hits our skin. And our dermatologists yell at us for being out in the sun too much so we don't get sunlight anyway. And have you seen any folks over 70 in swimming suits lately....not many?
The paper's "Conclusion: A daily vitamin D dose of 4000 IU for chronic HF appears to be safe. This dosage did not improve endothelial function but did improve the 6-min walk distance, symptoms, and left atrial diameter at 6 months." This is enough. We have our randomized, placebo-controlled trial. I was not heeded 11 years ago. But I was right. And for that, I feel considerable satisfaction.
www.What will Work for me. I'm taking 30,000 IU of D every day and have a blood level of 140. I sleep better. My calcium is normal. I've written columns about that. For those of you with anyone in your circle with a "weak heart", please make sure they are on Vitamin D. It's proven. And I biked 20 miles yesterday.
1. What does Vitamin D for elderly with congestive heart failure? Answer: Helps them function better, walking further, and feeling less short of breath.
2. How does Vitamin D do that? Answer: unfair question. We didn't cover that. But Vitamin D controls 10% of the human genome and fundamentally is the hormone that turns on stem cells and has them develop into mature cells. A heart has to replace its muscle cells every 30 days. You need enough D to do that.
3. When you take 4000 IU of D a day, you are likely to get an overdose of the D. T or F. Answer: This is not a joke. There has been so much brouhaha over raising the daily minimum from 400 to 600, both laughably inadequate, that the thought that someone had the audacity to give 4000 Iu a day, sufficient to get a blood level of 50 after 6 months is simply wonderful. They proved it's safe. So, let's get everyone on 4,000 IU a day.
4. When you start a new course of Vitamin D and want to get your blood level up quickly, you should do what? Answer: You need a loading dose. 100,000 IU is safe. Those babies in England were given 600,000 IU. And they simply got better. No toxicity.
5. Pregnant women should have how much Vitamin D to have infants born with healthy levels of 50? Answer: 6400 IU a day. And studies from Finland show that babies who get 2,000 IU a day end up with 80% less insulin-dependent diabetes.
Glutathione, The Most Accurate Predictor of Cognitive Decline
Do you know what glutathione is? Wikipedia reports that it is your body's most important natural antioxidant and is "capable of preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals. That makes it hugely important. You want higher glutathione levels.
How do we get to cognitive decline and glutathione? Easy. It turns out glutathione is just about the most important antioxidant to protect your mitochondria. Your brain, particularly your frontal cortex that mediates "executive function", and which makes us human, has about 5,000 mitochondria per neuron. That is about the highest in the whole human body. Your brain uses a ton of energy, and needs a boatload of mitochondria to make it......... which means it needs a lot of glutathione to protect those mitochondria. It's your frontal cortex that takes it on the chin with Alzheimer's. That's the part of your brain that shrinks the most with Alzheimer's.
So, take 511 adults, employees of Emory University with an average of 18 years of education, average age of 49, 64% women and measure their glutathione, and a whole raft of cognitive functions. Follow them for four years and repeat all the testing yearly. What you find is that declining glutathione predicts loss of executive function more accurately than other testing...and proceeds loss of memory. It becomes a remarkable biomarker of future cognitive decline.
Well, well. That has been enough for authors to call for Glutathione to be given to folks with mild cognitive impairment (which is a lot of us who forget just why we opened the fridge and where, or where are my car keys.). The problem is that because it is just three amino acids hooked together, when you take it orally it gets lost in your gut and digested into the component amino acids.
But you can get it IV. It is relatively inexpensive to manufacture. And giving it IV only takes about 5 minutes. No side effects, no toxicity, no harm, no danger. I suspect with all the interest in it, there will be more means of giving it. Inhalational with a ventilator? Transdermal? Intranasal? I'm sure the ideas will come out.
www.What will Work for me. This study from Emory was an observational study, not a randomized, placebo-controlled trial. But I'm totally fixated on it. I've been taking IV glutathione myself to lower my own body-burden of environmental toxins. I have no side effects. I have a raft of clients who swear by it and come and get their IV fix once a week to once a month. We don't have proof that administration of it fixes things at all....yet. The accumulated evidence appears to be fascinatingly coherent. The biology and chemistry all fit, and make sense. I'm going to start measuring it in folks who are curious. We need to learn this stuff.
Meantime, did you know that when you take NAC (N-acetyl cysteine) you boost your own glutathione? How about at least a gram a day of NAD? Alpha lipoic acid boosts you too. As does turmeric. Take em all! Doses? Who knows. At least some.
References: Perlmutter, Jr Neuroinflammation, Neurochem International, Antioxidants, Wikipedia, AntiOxidant Redox Signal., Am Jr Alzheimer's Dis and Other Dementia, Jr Alzheimer's Dis, Jr Gerontology,
1. What is glutathione? Answer: Your first and foremost antioxidant in your blood. It complements your plasmalogens, which provide protection in your cell membranes.
2. . What happens with glutathione with aging? Answer: Super complex answer. Drops like a rock in folks who have serious disease (chicken? egg ?) but there are many studies that show healthy older folks have plenty.
3. This quoted study of 511 university folks showed what? Answer: Glutathione reduction predicted loss of executive function more accurately than memory.
4. You can easily replace it with oral supplementation? T or F? Answer: False. Liposomal forms help a little but orally is generally miserably ineffective.
5. There is good proof that IV glutathione fixes Alzheimer's. T or F. Answer: Whoa Nellie, not proven yet at all. Calls for study exist and there is a lot of interest in it. The barrier is the cost of IV administration for the long term. So, take NAC instead, and alpha lipoic acid and turmeric.
Lactulose to Supercharge your GI Tract
You have never heard about lactulose before. That's amazing because you probably should be on it for the rest of your life! This is interesting.
What is lactulose? It is an undigestable sugar made of galactose and fructose linked together. We have no enzymes to digest it. It passes right through our gut where our colonic biome loves it. Just plain love it. They have a party and the desirable lactobacilli and bifidobacter families, the really good ones, proliferate like crazy. And when that happens, your stool gets softer, you absorb more calcium and magnesium, and your immune system gets happy.
We have used lactulose for some 60 years for folks with end-stage liver disease who were getting mental confusion from too much nitrogen buildup. Give them lactulose and their brain fog gets better. And constipated kids have much better bowel movements. It works super well to help with severe constipation. But other than that, it has had little medical use, despite its proven safety. The discovery of our colonic biome as a really valuable organ has opened up the door to more investigation and lactulose has now emerged as a very powerful prebiotic. Good food for your colonic biome.
Here is what happens. It passes through your gut to your colon. In your colon, you chop it up into short-chain fatty acids, acetate, propionate, and beta-hydroxybutyrate. Said otherwise, that is a two-carbon, a three-carbon, and a four-carbon fatty acid. Your colon mass increases. Those short-chain fatty acids are the principal food for the cells of your colon, so first of all, your colonic wall gets fed. With increased biome mass, you pass on a lot of beta-hydroxybutyrate to your body. That is the principal ketone you make when you are fasting. It turns on all the good things we have been talking about in the prior several weeks. You increase brown fat. You uncouple mitochondria to burn off heat and help with weight loss. You activate your immune system. You renew your mitochondria. This is all good. (We know that gorillas, eating a pure vegan diet and munching for 7 hours a day convert the green leaves they are eating into beta-hydroxybutyrate with the net effect of getting some 55-70% of their calories from beta-hydroxybutyrate. That implies that a high vegetable diet is a short-chain fatty acid with tons of healthy BHB in it.)
But it's not just ketones (BHB) that you get with lactulose. You get increased calcium and magnesium absorption. That study took 24 young men and gave them a diet with 0 grams of lactulose, 2 grams or 4 grams a day. In a dose-dependent fashion, their absorption of both calcium and magnesium increased. In aging mice, lactulose reverses the bone loss of menopause by this effect. You want to build better bones? Start with building a better colonic biome with lactulose! (Hasn't been proven in humans, and may never be. Not enough money behind it. It's generic and too cheap.)
What is the dose and how can you get it? Oddly, it is prescription only because of its use in liver failure, where it is dispensed in 15-gram packets. That's not how much most of us otherwise healthy folks need. Two grams a day, split into two doses may be enough for some petit, slender women. Four grams a day, six grams a day....we don't know your dose until you try it.
www.What will Work for me. We have here the introduction of a prebiotic that encourages the growth of the most desirable colonic species, lactobacilli, and bifidobacteria. You make it easier to have soft, easy-to-pass bowel movements. Your immune system has a cross-talking conversation. Your body gets more ketones. Your bones get more calcium. This stuff should be on your dining room table and sprinkled on all your food.
1. What is lactulose? Answer: An indigestible sugar that works as a powerful prebiotic to nourish your colonic biome. That helps the probiotic bacteria you are taking to take hold and multiply. (Other good prebiotics are Jerusalem artichoke and chicory root - two hard-to-find substances.)
2. What fatty acids are made as a result of taking lactulose? Answer: Just count. 2-carbon, 3-carbon, and four-carbon fatty acids, clumped into the acronym SCFAs (short chain fatty acids.)
3. What role do those SCFAs have? Answer: they are the principal food for your colonic cell walls, and represent the form of energy flow from your colon into your body.
4. What happens to bone metabolism with lactulose? Answer: Well, proven in mice to help. Not yet studied in humans.
5. If I'm constipated, do I have a healthy colon? Answer: NO! America has a runaway problem with diverticulosis because we are way too constipated, leading to higher pressures in our colons, leading to "hernias" in our gut wall called diverticula. That's just one sign. Constipation means your colonic biome is really damaged, and that has emerging huge implications for general immune health.
Ketones Turn on Uncoupling
Your body has two fuel sources. Carbohydrates and fat. You could add protein but generally speaking, protein is used for muscle building and extra is broken down into glucose. If you have any carbohydrates (glucose) around, your body will naturally default to running on that first. Here is the catch. You only can store 1500 calories of carbohydrates. Every pound of fat is 3500 calories and given that the average woman is 30 percent fat, she has 40-50 pounds of fat or 140,000 calories of fat. That is the reserve she needs to make it through winter, pregnant.
Back to carbs. When we eat a meal, we fill up our carb tank first. That gives us about a 12-hour fuel source during which our body burns glucose exclusively. You can prove that for yourself by measuring your own ketones. Ketone meters are widely available (Keto-Mojo is on Amazon). They measure beta-hydroxybutyrate (BHB). Six hours after a meal, your BHB level is zero. Twelve hours, it is 0.1. Sixteen hours, 0.4. Almost like clockwork. If you do "intermittent fasting" and skip breakfast, thereby going 16 hours with no food, your BHB will start to climb as your body begins to switch over from glucose/carbs to fat. If you do a 5-day, fast mimicking diet of 800 vegan calories, <8% protein, and 50% fat, your ketones will keep rising until by day 5 you are at 4.0. If you eat three meals a day, 5-6 hours apart, you will never have any ketones in your blood. Never.
That's what civilization has done for us. By giving us "food security", and manufacturing delicious, prepared carbs in easy packages, we eat meals three times a day with sufficient carbs in them to always have a topped-off tank of carbohydrates, and never ever burn off our glycogen/carb stores. So we never access our fat stores.
Inside our cells, our peroxisomes never get challenged to chop up fat and make ketones. Because of that, they wither. Literally. Without any demand to make ketones, the peroxisome doesn't petition the nucleus of your cell for the enzymes it needs to make ketones. The effect of that is easy to measure. You go on a "diet" and cut down on calories. But you are unable to burn fat. Your glucose declines and you become hypoglycemic. Without any fuel around, your brain goes into panic mode and you feel awful. You have to eat. Your diet fails.
You want ketones. Their presence means you are burning fat. But ketones are much, much more than that. They turn on uncoupling of your mitochondria. That means they induce your mitochondria to burn some calories as heat. Suddenly, you aren't just burning fat, and losing some weight. But the fat you are burning is being used as heat, so you are getting an extra 20-30% boost in fat usage. So much for the adage, "A calorie is a calorie is a calorie". And ketones act as very powerful hormones on many tissues in your body. They turn on the messages for your mitochondria to multiply. That means you can make more energy and burn more calories. That heat production is mediated through "uncoupling proteins" that basically let extra high energy proteins escape the mitochondria by giving up their energy as heat instead of making ATP fuel.
Why would they do that? Think back to 10,000 years ago, before agriculture. You are huddling in a cave in November in Europe (Or China, or India, or Peru), the beginning of winter. There has been a frost and all the plants you used to munch on are dead. You only have animals for food. (It could be Africa, at the beginning of the dry season. Again, no plants for the next 4-5 months.) You need to make heat to keep you warm. You are eating the fat from the animals you catch. Your body senses the lack of plant foods, carbs. You start pulling on your stored fat stores and putting out ketones. That turns on uncoupling protein and that makes you warmer. The teleological explanation makes perfect sense for a hunter-gatherer. Our planet Earth was much, much colder for some 100,000 years during the ice ages. We needed to stay warm to survive.
But you want to lose weight and you are trapped by feeling too awful when you cut your calories. Now you know why you feel awful. You need to induce your cells to learn how to burn fat into ketones. Not only that, you want to supercharge your mitochondria and burn some extra calories as heat. You can't do it all at once. It takes a week or so to turn on the cellular messaging from your peroxisomes, your ketone manufacturing organelles, to your nucleus and get the mRNA back to manufacture your necessary enzymes. And as you do that, you make brown fat. Brown fat is fat cells full of mitochondria, uncoupled, and making heat. A calorie is now being burned for heat.....sort of like in your home. You can use energy to make electricity or heat. Carbs make electricity, but you also need heat, and uncoupled mitochondria, brown fat, make heat. You lose weight.
www.What will Work for me. I'm trying to explain this concept from several angles so that I get the concept in my head. I learn better when I have a lot of various angles to get a better handle on the idea. My current fascination is with ketones from ketone esters. Eating ketone esters routinely blunts your appetite while turning on uncoupling. The price of ketone esters has just dropped 75% so they are now almost affordable. Juvenescence is much cheaper than KetoneAid (the first on the market). This may mean you don't have to starve to get your uncoupling, you just have to have ketones around. Instead of not eating to get BHB, you can just swig some ketone esters. I'm going to try that for a couple of weeks, 4 times a day: one capful. See what happens.
1. Your body makes ketones every day, naturally. T or F. Answer: Trick question. It would if you went more than 12 hours without food but in America today, we never go 12 hours. We eat every 8 hours. So, False. True if you intentionally skip breakfast.
2. How many calories of glucose can you store? Answer: 1500.
3. If you skip breakfast and don't eat for 14 hours, how certain are you that ketones will be in your blood? Answer: 100%
4. Ketones in your blood means what? Answer: You are beginning to switch over to burning fat. Aka, losing weight.
5. Ketones do what to fat tissue? Answer: they act as a hormone and turn on the multiplication of mitochondria, changing white fat to brown fat, chock full of mitochondria and burning fuel to make heat. That gives you a 20-30% boost in your calorie consumption. Helping you lose weight faster.
Uncoupling Proteins - Or A Calorie is Not Just a Calorie
"A calorie is a calorie is a calorie". You have heard this bored into your head a thousand times. You don't believe it. And you are right. You can't lose weight and you are certain "Something is amiss." It is. Sometimes a calorie is much, much less. I'm serious. If it gets "uncoupled", you turn calories into HEAT instead of ATP energy molecules. And that makes some calories about 70% of a calorie. Put another way, you can make yourself burn 30% of your calories by how you conduct your life. Want to learn more? But if you can't uncouple, you are stuck with a metabolism that won't give anything away.
Now, remember, you make your body weight in ATP molecules every day, Your mitochondria, (10% of your body weight) turn the low energy molecule ADP (diphosphate) into ATP, (triphosphate) and that is the universal energy molecule for all your cells. Your mitochondria can make 38 ATP from a single glucose molecule. And out comes CO2 and water in exchange. And each ATP molecule gets regenerated some 10,000 times a day.
There are some challenges your body must face that no one ever really put together. What happens if you are a newborn with a huge body surface area to volume? How do you keep that little tyke warm? What happens when you have a lion charge you and you have to go from sitting to sprinting a 10-second 100-meter dash? What do you do if you just stuffed yourself with a feast and are just bloated with turkey and dressing, sweet potato pie, and cheesecake, and ice cream.....? Each of those circumstances requires massive, rapid changes in your metabolic pathways. Each of them involves uncoupling. We'll explain.
Your mitochondria are what you have to respond to that challenge. They must take a resting muscle to a sprinting runner in 1 second, increasing their output by some 40,000 fold. They can do that. But they also need a release valve, almost like a steam engine that lets steam out of the system. That's called uncoupling. You make heat instead of ATP. Your body needs to learn how to do that.
For all that to happen flawlessly and rapidly, we need to have some metabolic pathways in place, working fluidly. One of the most important pathways that needs flexibility is the ability to flex-fuel from glucose (carbs) to fat (many kinds). Your body defaults to running on glucose anytime glucose is around. That's because glucose used to be rare, showing up only once a year during fruit season, or the rare finding of honey. Repeat that. Glucose, for most of human history, was not the default fuel, eaten three times a day. It was rare. The rest of the time, our food was green leaves (think spinach and dandelions, broccoli and kale) or animal products. Green plants get fermented by your colonic biome to make short-chain fatty acids, most notably beta-hydroxybutyrate (a ketone). Fat gets used up, but only after all glucose stores are depleted. If glucose is around, you put out insulin and store any excess calories as fat. That makes insulin your storage hormone that prepares you for winter by storing excess glucose as fat.
Now, with the discovery of agriculture and growing grains just 7,000 years ago, we have carbs year around. With modern farming, we have carbs and sugar at our fingertips 24/7. Hence our metabolism is always running on glucose. Without any demand to burn fat, the enzymes that chop up and prepare fat for our mitochondria are not needed. If not needed, we don't ask our DNA for them to be made. Our peroxisomes, those little organelles next to our mitochondria that chop up fat to present to the mitochondrial furnace, are diminished. They don't have enough to do. Our mitochondria keep getting glucose because we keep eating every day, every 8 hours, and snacking in between. If you go on a diet, and you are glucose addicted, your peroxisomes will not chop up fat and make beta-hydroxybutyrate for you. You become hypoglycemic and feel awful. Your diet fails.
This is a journey that will take you a few weeks to master. I want you to understand how to uncouple your mitochondria and turn on uncoupling proteins. But to do that, you have to start with the basic mechanics of how your energy flow works.
That we feel hypoglycemic when we don't get our regular carbs is another clue. But when you heat a huge meal like Thanksgiving and find yourself hot and sweaty at two in the morning, you are demonstrating uncoupling. That heat is coming because your mitochondria are getting way too many calories thrown at them all at once. They can't manage the overload and to let the steam out of the system, they pull out UCP3, uncoupling protein 3, and say "Let er Rip" and just waste a ton of calories in heat instead of metabolizing it in a proper, orderly fashion. You do gain weight from that dinner, but the heat you felt at 2 am was the even more weight you would have gained had not your mitochondria been uncoupled. The reason for doing that is complex. We'll explain.
Isn't this interesting? Don't you want to know more? We'll get to it next week. This is enough for this week.
www.What will Work for me. This is the fourth of July. You don't want to eat so much that you feel like a furnace and get all hot at 2 am. If you do feel that way, recognized the warning sign. Your mitochondria are begging you to please, not overload the system too fast with so many calories. I'm fascinated with this uncoupling idea. The best way to get yourself able to uncouple is to first get your mitochondria responsive to fat and glucose. The way to start doing that is to let yourself burn off all your carbs every day. To do that, you have to go at least 12 hours without eating. That's when ketones will start to show up in your blood. (You can prove it to yourself by buying a ketone meter from Keto-Mojo and measuring your ketones. After 12 hours of no food, you will have 0.1 mg beta-hydroxybutyrate in your blood. Your peroxisomes are beginning to burn some fat. Now, extend that to 13 hours, then 14, then 15....by the time you get to 18 hours, you will have accomplished step one in getting yourself to uncoupling. Your peroxisomes have "petitioned" your DNA to provide the programming to make fat chopping enzymes. You are making ketones, and they are the key. We will explain that next week.
1. What is the best sign that you are carb addicted and unable to make ketones? Answer: You get hypoglycemic and feel woozy when you go more than 4 hours without food. The woozy feeling of hypoglycemia is your brain complaining because it is metabolically unable to make and run on ketones. It needs to be trained to do so. And that is possible.
2. What happens when you flood your mitochondria with too many calories all at once (like a milkshake, hamburger and large fries)? Answer: Pay attention. You feel sleepy and you feel hot. That hot feeling is uncoupling. Adrenaline will also turn on uncoupling. So when you are embarrassed and your face flushes and you get all hot.......there you have it.
3. What is uncoupling of mitochondria? Answer: The letting off of excess calories into heat instead of ATP to escape the calorie overload.
4. How much of my metabolism can I affect by uncoupling? Answer: About a 30% swing if you believe the animal research.
5. You mean that a calorie is sometimes only 70% of a calorie? Answer: Yup.
If You Love Your Milwaukee Custard Ice Cream, Don't Read This Column
Sepsis is what kills the most people in hospitals. It is when uncontrolled infections take over in a runaway spiral of inflammation. Most of that inflammation is driven by the lipids off of the surface of gram-negative bacteria from the bowel like Pseudomonas, Proteus, or Klebsiella species called lipo-polysaccharides (LPSs). Now, did you know that if you have a slightly big tummy, a bit of high blood pressure and slightly high CRP you likely have "metabolic syndrome", and the connection between lowgrade metabolic syndrome and the release of LPS is pretty high? LPSs are wicked little devils that wreak a lot of havoc. They basically come off the wall of bacteria from your colon, coming through "leaky gut" into your blood. No wonder Steven Gundry calls LPSs, "little pieces of s..t". They are. And they cause you harm.
Now, if you want to study animal models of inflammation, you take mice and inject their foot pads with LPSs. Makes for a dandy experimental model. But it's not so easily controlled. It would be oh so convenient if we could find a standardized method of inducing inflammation that could be precisely controlled by dose. Now, we have known since the 1980s that you can get precisely calibrated inflammation of mice footpads with carrageenan injections into their footpads. You don't have to deal with all that messy stool bacterial gunk.
Wait! Did I just say carrageenan? Didn't I see that on a list somewhere of ingredients in Culver's Icecream? What is carrageenan? Well, Wikipedia will tell you that it is used as a food additive to make ice cream creamy and smooth. It has been observed as having NOAEL (no-observed-adverse-effects-level) in rats at levels that would be about 1/2 pound a day of it for humans. Ok? But is it really safe?
Here is the conundrum. We extra carrageenan with alkali from seaweed. So far so good. But when we expose it to acid, it turns quickly into poligeenan, a substance known to cause cancer. Guess what carrageenan is going to find in your stomach! Acid! Oh, dear. And there have been a slew of animal studies showing that carrageenan exposures results in changes to bowel wall similar to that seen in inflammatory bowel disease. For example, 30 days of carrageenan given to guinea pigs makes 100% of them get gut ulcerations.
It should be distressing that we know it causes trouble in animals in many models but we say it is safe in humans because we haven't studied it enough. But that is where we are today. No clear evidence that it is safe. Lots of smoke. No obvious fire because we haven't looked at it enough. And goodness gracious, do we love our Milwaukee custard, 100% of which has carrageenan in it? Did you know that inflammatory bowel disease is the #1 reason for admission to Children's Hospital of Wisconsin? Lots of smoke.
www.What will Work for me. Ice cream is something I can't have in the house. I like it. A lot. Sugar and fat sure work for me. But I also have a stubborn CRP that I can't find the cause of. Carrageenan sounds like a possible culprit. But it's not just in ice cream. Did you know that carrageenan is found in coffee creamers, soy milk, sliced turkey, canned soups, microwave dinners......ouch. Now you know what that ingredient you didn't know about stands for...maybe it's time to reconsider eating it.
1. Carrageenan is extracted from....? Answer: Red seaweed by an alkaline extraction process.
2. What happens to carrageenan if it is exposed to acid? Answer: It makes a different compound called poligeenan. And it is not safe by everyone's consensus.
3. What environment does food meet when you eat and swallow it? Answer: Acid
4. In animal models, like guinea pigs, what happens to the GI tract when given carrageenan for 30 days? Answer: 100% of the guinea pigs got gut ulcers.
5. Carrageenan has been proven to be safe? T or F. Answer: There has been no study in humans to prove it and no one has dropped dead from eating it, in the short term. But there are no meaningful studies in humans that are long-term or look specifically at gut health. You might wonder why. Huge industry pressure to leave your hands off.
Melatonin, Your Night Time Mitochondrial Repair Tool
You thought melatonin was your "sleep hormone" that you made every night. Well, that was how it was discovered. And that is still true. But did you know that it is much, much more? Both plants and animals make it in mitochondria and chloroplasts where melatonin plays a primary role in protecting the electron transport chain from OH molecules, which are incredibly toxic. In fact, melatonin plays a more important role in anti-oxidant function than vitamin C or E, and as opposed to those two vitamins, it doesn't deplete glutathione.
You can actually call melatonin your mitochondrial repair hormone. You can call it your uncoupling hormone. Or you can call it your heat production hormone. All three of those monikers are true when you understand the role of mitochondria in your body. At night, when you fall asleep, your mitochondria have a chance to slow down and repair themselves, getting themselves back into tip-top shape. They can clean up the damage from all the extra calories they had to burn during the day and petition the nucleus to send them out some extra repair proteins.
Now, that has huge implications for cancer. Cancer is essentially a "broken mitochondria disease", if you subscribe to Seyfried's description. Seyfried made CT scans of mitochondria in cancer and showed that the inner membranes of mitochondria are all disrupted and broken. Those mitochondria can't make ATP, so the cancer cell has to invade other cells to get food. Melatonin repairs that initial damage that starts cancer cells down that journey. Folks with decreased melatonin from shift work have more cancer. And, with over 3,000 published studies on melatonin and cancer, there is increasing evidence that the scale is tipped in the direction of benefit of taking melatonin if you have any cancer. Life Extension just published a nice review of melatonin's benefits that lists some of those benefits.
It is in the repair of your mitochondria that melatonin probably plays its most important role. That repair process happens during the night when you are asleep. So sleep and melatonin are associated together, but they aren't the whole show. It is the process of uncoupling the production of energy, making heat instead of ATP, that allows mitochondria to take a deep breath and regenerate themselves.
We will explore this topic in the weeks to come. Repairing your mitochondria, uncoupling, ketosis, weight loss, cancer therapy, and brain health are all tied up in this topic. Rather than overwhelming, let's just bite off one little chew at a time.
And that is melatonin, a miracle-working hormone that you likely need more of. It is your sleep hormone, but so much more. You probably need to gradually raise your dose if you aren't on any. And consider eating those foods that come power-packed with melatonin naturally built-in: pistachios and mushrooms for starters.
www.What will Work for me. I love pistachios. Mushrooms are showing up in farmer's markets all over the place now. I'm trying to get into the habit of eating them in my eggs, my salads, or in just about every stew or casserole I make. I've been advocating for 10 mg of melatonin at bedtime for years. I'm going to raise that for anyone with cancer. William Falloon now advocates up to 50 mg a day with pretty good evidence for its safety. Your blood level of melatonin when you were a tiny tot was 200 pg/ml and drops by an order of magnitude over your lifetime.
1. What is melatonin? Answer: Trick question. It was discovered as your sleep hormone, with which it is related, but probably should be known as your mitochondrial repair hormone.
2. How does melatonin keep your mitochondria safe? Answer: Complex answer. It is your best antioxidant, protecting your glutathione levels. And it activates decoupling proteins, letting the steam out of your metabolic kettle.
3. Name a disease for which broken, disordered mitochondria is central to the pathophysiology? Answer: Cancer
4. Can melatonin help prevent cancer? Answer: Yes
5. What happens to my melatonin as I age? Answer: You have less than 10% of what you used to have as an infant.
You Want to Be in Ketosis
Yup. Every day. You want to be in ketosis! What is ketosis? What is a ketone? Let's explain. A ketone is a carbon-oxygen double bond that is naturally made whenever your body shifts into "fat-burning". But it is so much more. It turns out to be a critical signaling compound that turns on anti-aging in many ways. The question is how to make them and how to lead a lifestyle that encourages their production. Note, we are not talking about the terrible ketoacidosis of uncontrolled diabetes that occurs in the vacuum of no insulin. The "house of medicine" has been misled, thinking that all ketosis is a prodrome to that condition, when in fact we are talking about a natural, in fact, beneficial state of physiology.
So, let's start with that. First of all, you have two major fuel sources to burn. Your fat stores, of which you are likely at least 20% fat and possibly as much as 50%. And carbs, which we eat every day. Now, consider that you can only store 1,500 calories of carbs. Anything more gets pushed into fat for longer-term storage. Fifteen hundred calories will only last you about 12 hours or so. Eat supper, and top off your carb tank. That's 7 pm. Now, 12 hours later, it's 7 am and you do a finger stick for ketones. Your level will be 0.1. You are beginning to turn on ketones/fat burning. Primarily a ketone body called beta-hydroxybutyrate (BHB). It's a 4 carbons long molecule. But you eat breakfast and have a carb source: cereal, toast, orange juice. You have a rise in glucose in your blood, and an insulin response. Ketones disappear upon the presence of insulin. But if you skip breakfast, have only black coffee, by lunchtime, your BHB will be 0.4.
If you then continue to never fill up your carb tank and only eat 800 calories a day of which 50% is fat (this is the foundation of the Fast Mimicking Diet) for 5 days, your BHB will rise daily until on day 5 you will be at 4.5. You do that because your body needs 2,000 calories a day, and you are only getting 800 so you have to draw on your fat stores to make up the deficit. You are in full fat-burning mode and losing weight. More importantly, your ketones have dramatically turned on your anti-aging mechanisms, and folks who do that 4 times a year will add 16 years to their health span. 16 years. Probably the singularly most powerful antiaging tool we have. (Read Longo's book: The Longevity Diet).
Prior to civilization and growing grains as crops, we were hunter-gatherers. We didn't have carbs year around. The natural cycle of nature was that we had 8-10 months of adequate food sources, but every year 1-4 months of food scarcity during which we had to switch to our fat stores. We only had carbs for the few weeks than any particular fruit was ripening. We had a much better chance of survival if our metabolism could switch back and forth from fat to carbs.
But that is a hard diet to do for most folks because they have been on carbs for so long, they have not stimulated the enzymes to make ketones in their peroxisomes. It's even more difficult if we are insulin resistant and thereby have elevated insulin all the time. (Insulin instantly turns off ketone production.) Folks who are insulin resistant (88% of us) try it, can't make ketones, become hypoglycemic and feel too awful. They quit and fail. Once your are ketone competent, your glucose can be 45 and you have no symptoms of hypoglycemia.
Is there a way around that to teach your body how to get back to "flex-fueling"? Yes. The key is breakfast and the timing thereof. At 7 am, everyone, always, is in nascent ketosis. 0.1. You have made the first timid step. So, we now know unequivocally that you can make some. We just want to wake up your DNA, and make more enzymes to manufacture more ketones. It takes a week or two for your DNA to get that done. Start a process of stretching out breakfast to 8 am. Then 9. Then 10 until you make it to noon. You will be in ketosis for 6 hours. Your enzymes will develop and you will feel the effects of that for yourself. You will find it to be easier, and finally easy.
How well does that work for weight loss and longevity? Groundbreaking work on monkeys and mice in Madison and the University of Texas on diet and fasting was completed just a few years back that showed that calorie restriction worked in prolonging life, but calorie compression worked just as well, regardless of the calories. Mice fed in a 3-hour window, versus 24/7, were remarkably healthier. They lived longer. They weighed less. The exact same calories over 24 hours led to weight gain. Same process has been proven in every animal species ever studied. Can you compress your calories into 12 hours, then 11, then.........6? What was more amazing is that it didn't matter what type of calories the compressed timing mice ate. (Unending chocolate ice cream?)
What you have done is to activate your "metabolic gym". You have turned on all the genes that make the enzymes for you to make ketones. Your metabolism can switch back and forth between carb and fat burning. Your brain learns to run on ketones, as do your muscles, your gut, and your kidneys...... And your body starts bathing in the wonderful, metabolic effects of ketone magic. (Read next week)
Now, there is a lovely little trick you can do to keep nudging yourself into ketosis. You can have coffee with a tablespoon of MCT oil in it. What is MCT oil? Mid Chain Triglycerides. It is a byproduct of coconut oil with carbon fat chains that are only 8 and 10 carbons long. Those are liquid. They go directly into your fat cells and can only be broken down into ketones. Add a tablespoon of MCT oil to your coffee (they have no flavor) and your blood ketones pop right up. You will feel the energy boost and very likely also feel your thinking to be a bit clearer.
www.What will Work for me. I've learned to do this and am now finally, at the point of feeling confident that it is not too hard. The bottle of MCT oil is finally empty, after using 1 T a day. Most importantly for me is that my average blood glucose has dropped some 20 points and my waist size has dropped two notches on my belt. I have been using Ketone Esters, another nifty trick to make ketones, regularly when I feel a little woozy and thing I'm short of fuel. They are amazing for giving you your energy back in 5 minutes. Two molecules of ketones, bonded together in an ester bond, gets into my blood faster than any other food source, and raises your ketone level very rapidly without turning on insulin. Try it.
1. What is a ketone? Answer: The "Fourth Fuel". It is the fragment of a fat molecule that is the common pathway of fat burning, or weight loss. Carbs, fat and protein are the first three.
2. What does ketosis mean? Answer: That you have turned on making ketones.
3. How do you do that? Answer: By not eating for 12 hours and burning out your carb tank of glycogen.
4. Can you do it faster than 12 hours? Answer: Of course. That's why exercise is so good for you. It uses up your carb tank and switches you over to ketones.
5. Can you raise your ketones faster than sitting around waiting for hunger? Answer: Yup. Just a tablespoon of coconut oil will do it. Put it in your coffee and call if Bullet Proof Coffee.