Metabolic Problems of Processed Foods 5 Membrane Integrity

Metabolic Problem of Processed Food Number 5 Membrane Integrity

When I read Lustig's new book, Metabolical, and he listed his eight problems of processed foods, I was stunned by his listing "Membrane Integrity" as #5 on his list. He is the first major author that I have seen to list this. Hurray! It should be on the list, maybe even higher up. Now, he doesn't go into the detail of it all but he gives a decent start. Most importantly, it's on the list. This is the fundamental, main reason, processed food is killing you and me. Let's give the details.

It starts with "membrane science". This is the field of medicine that Goodenowe is introducing in his discovery that plasmalogen deficiency is the prodrome for most of our modern illnesses. How do these two approaches converge?

Every cell in your body is encased in a membrane of lipid fats that keep the outside world out and the inside world in. That's what giant soap bubbles are, a huge container composed of a lipid bilayer - two layers of fatty acids. In your cells, you have many embedded proteins recessed in that bilayer that are the passageways or gatekeepers for different nutrients going in or out. The sodium-potassium pump is the most prominent one. It uses up some 10% of your energy just keeping sodium outside the cell higher than potassium and potassium inside the cell higher than sodium. That simple gradient drives most other "pumps" that keep different nutrients coming and going. You don't just have membranes around the cell, you have them inside the cells as well. There is a special membrane separating the nucleus with its DNA from the rest of the cell. You have the endoplasmic reticulum, where proteins are manufactured, folded, sorted, packaged, and shipped out. You have the mitochondria, making your body's weight in ATP daily. You have the peroxisomes, chopping up fat, making plasmalogens, neutralizing peroxide. On and on.

Membranes need a certain level of fluidity. Here comes the rub. All of your membrane lipids are attached to various long-chain fatty acids which give them different qualities. Adding double bonds form a 30-degree bend in an otherwise straight molecule. Olive oil has one double bond. Fish oil, DHA, has 5 double bonds. Each additional double bond makes for more fluidity. DHA is incredibly fluid. It plays a fundamental role in plasmalogens. Those jutting out internal lipids like DHA play a huge role in providing a scaffolding for your embedded proteins to hang on to. Gaining or losing a double bond is no trivial matter. Throwing in transfats becomes a problem, if not a catastrophe. But those double bonds have another more serious vulnerability. Double bonds are very vulnerable to oxidation. That 30-degree bend can be "flipped" into a trans configuration making the molecule straight, more rigid, less flexible.

Here's the nugget of it all. The oxidizing propensity of processed foods trashes our membranes, making them less flexible.  The trans fats common in processed foods compounds the trouble. We overwhelm our ability to neutralize the excess peroxide that is created by too many calories all at once. Plasmalogens get used up trying to neutralize the excess oxidizing capacity. Our membranes get more rigid.

Many problems stem from that shift to rigidity. In our mitochondria, we start exporting more substrate for cancer cells to make their energy supply. In our arteries, we start accumulating plaque. In our brains, we stop being able to ship neurotransmitters and start stealing choline from our depleted plasmalogens.

Clarity into these details is gradually emerging in the bench science world. Lustig is the first to bring to the lay-person marketplace of ideas the danger caused by our processed foods. It's all about the function of our lipid membranes. Processed foods alter the proper mix and throw in wild cards. It's a mess.

The problem is that processed food has emerged because it is what we like. Our food manufacturers make what they make because we buy more of it. Sweet tastes good. Fast food is easy, on the way home. We don't have to cook. It comes in a convenient package. Our burdened membranes are crying for relief.

www.What will Work for me. I'm on vacation in Door County. Every second establishment is selling ice cream. It's cherry season and the trees are loaded with cherries. There are no kids from eastern Europe to provide service jobs in the restaurants and as best we can tell, very few farm workers to harvest the cherries. Our favorite "cherry" place has 900 forms of cherries with sugar and flour added. We were biking on Washington Island and stopped at the Jackson Harbour restaurant. The cherry pie was delicious. Oh well.

References: Lustig's new book Metabolical, Biochem Biophys Acta, Biomed Research, Chem, Medical News Today,

Pop Quiz

1. Every one of your 30 trillion cells in your body is delineated in its boundary with what?         Answer: A lipid membrane. Just like a soap bubble.

2. What makes a healthy membrane?                     Answer. It has to be fluid, meaning it allows proteins embedded in it to move around easily and quickly. (It also has to be strong. That's where cholesterol comes in. Cholesterol makes it more rigid and more sturdy. That's good too, in the right circumstances.). And it has to be made with the right lipids. Fish oil, DHA, is a key ingredient.

3. What makes more fluidity in membranes?                       Answer: the quantity of plasmalogens with their DHA (fish oil) molecule attached to them.

4. What is the core problem with processed food and membranes.                   Answer: Aha! The nugget. Processed food makes for too much oxidation. Too much peroxide. Damaged fatty acids making for diminished plasmalogens and more rigid membranes. But hang on to that thought. This is an emerging science and more information is likely to come out to refine the dangers of "the wrong fats" in our membranes.

5. What is the number one method to cut down on oxidation?                            Answer. Less sugar and less rapidly digested white carbohydrates. Think whole foods you have to actually chew to digest.

The Metabolic Problems of Processed Food 4 Insulin Resistance

Metabolic Problems of Processed Food #4: Insulin Resistance

Adult-onset diabetes is high blood glucose AND HIGH insulin. That's right. High insulin because the core defect in the cell on the path to diabetes is resistance to insulin. That means it takes a higher level of insulin to push glucose into the cell. Insulin is there, it's just that the cellular receptors are acting like it isn't.

Cardinal to this resistance is fatty liver, bigger tummy fat, usually high CRP and other markers of inflammation, higher levels of endotoxin. We can measure those things and see them. If your doctor will measure it for you, you want a level of insulin below 5. That's the level someone is at when they are optimally sensitive and their cells are open to its effects. Now, the "normal" range of insulin in many labs is listed as 2.5 to 25. That is because the lab collects 1,000 samples, discards the top 5% and bottom 5%, and calls everything in between "normal". It's not normal. It's what the population of Wisconsin has. Calling it normal suggests the population is normal. We know it's not. We do know that fully 50% of Americans have fatty liver and metabolic syndrome. They aren't normal. They have insulin resistance. "Healthy" insulin is below 5, when your glucose level is below 85, and your A1c is below 5.5. That is what you want to be.

What's going on that makes you insulin resistant? It's actually so complex and so multifactorial that there is intense debate as to the full cause. Fructose, added to 68% of American foods, might be the central lead actor. When you eat any fructose, you have no inhibitory controlling enzymes that limit how fast it floods into your liver. That might be the key tipping point. But not the only one! We do know that there are multiple inhibitory proteins that make you more insulin resistant. PC-1 is a prime candidate. We also know that fatty liver is clearly a player. Just look at what a fatty liver looks like under an electron microscope. If your liver cell is chock full of fatty globules, the fatty globules basically fill up the cell with "dead space" around which the cell has to signal to itself and manufacture the proteins it is tasked with making and digest the food it is tasked with digesting. That's a hard one to prove, but that's where multiple authors appear to be heading in their attempts at proof.

And the same hypothesis would work with your fat cell. As you put on weight, you don't make more fat cells. The ones you have just get bigger. Again, their central space is filled with one, huge, obstructing globule of fat.

There are dozens of inflammatory modulators, molecular signals, chemokines and hormones all of which have impacts, but the action can be best understood with the following explanation. Your fat cells are responsive to insulin when they are small and have only a tiny amount of intracellular fat. As you get fatter, your fat cells become larger and less responsive. You need more insulin. Bigger cells, higher insulin. Again, bigger fat cells, even higher insulin until finally, you can't get your fat cells to respond, even with the insulin level of 45...55....65?. And 45 isn't sustainable. Your pancreas acts as though it only has a fixed amount of insulin to produce and secrete in a lifetime. If you burn up your supply, you eventually are calling for your pancreas to make 50 units, and it can only make 45. Your blood glucose rises to 140. But your pancreas is pooping out. It can only then make 40. Your blood glucose rises to 170. You can then only make 30. Your glucose is 200. ...and on and on. Your doctor can always prescribe insulin shots, and give you a zillion units of insulin. We can finally whip those poor, beleaguered fat cells into submission. But what we can't fix is the damage caused by that high insulin, which is inevitable kidney damage and frontal lobe brain damage.

How does processed food make all that happen? Easy. It's front and center. Refined grains and sugars, the epitome of processing, deliver calories to your liver so fast, it just plain can't keep up. Fructose is the arch-enemy in that regard, as it rushes into your liver with no controls at all. You begin to get fatty liver with one good sugared soda. Processed food is the delivery method of choice to create insulin resistance because it comes with lots of little microtoxins that add to the mix: trans fats, pesticide residues, artificial sweeteners, and just too many calories, too fast.  Too many calories, too fast.  No fiber to modulate your immune response in your gut.  That whole field of medicine is just awakening but Lustig puts it front and center with his motto: "Protect the liver, feed the gut."

How do you fix it? Opposite of processed foods. Whole foods, plain and simple. Fasting for 18 hours a day and compressing your calories draws down on all the stored fats in your liver. Losing weight by fasting, whole foods, avoiding white carbs and sugar, sugar, sugar is the only real cure. Read labels. If added sugar is on the label, you can't have it. You can prove it to yourself by getting a ketone meter and measuring your blood glucose and ketones while you do a 5 days fast mimicking diet (800 calories of vegetables only, 50% fat, very low protein). Your glucose will drop to the 70-80 range. Just 5 days will do it. Keep up the 800 calories and your weight will come off you.

www.What Will Work for me. I do a 5-day fast-mimicking diet every month. I've been doing it for 3 years now and it doesn't feel so hard anymore. I measure my glucose and ketones each time. My insulin, which normally runs 7-10 (not quite what I want it to be, but below the average for men of 14) will drop to 2 on day 5. Last month my glucose hit 59 and my ketones got to 5.1 on day 5. A personal record. I have the genes within me to be insulin resistant and diabetic if I would succumb to ice cream, cookies, and bagels. It's harder to eat whole foods. But that's the journey I'm on. Join me. It's the only means of beating insulin resistance.

References: Metabolical by Lustig, Nature, Diabetes, WebMD, Nutrients, NYT,

Pop Quiz

1. Adult-onset diabetes has very low insulin levels. T or F. Answer: Trick question. In the beginning, very high. Anything over 15 is the sine qua non for Type II diabetes. But as your pancreas burns out, it starts to fall. Eventually, it burns out completely in some folks and they become essentially insulin-dependent.

2. What food group has no effect on insulin? Answer; Fats. Again, a trick question because we didn't go over it in the column above. But that means you can eat fats and not bump your insulin.

3. The only food that stimulates insulin is sugar. T or F. Answer: False. Any form of white carbohydrate, processed so that it is digested rapidly, will boost blood glucose and thereby insulin. But more unknown is that large amounts of animal protein also are potent stimulants to insulin release. The simplest form of "processing" that causes trouble is grinding up grains to first remove their fiber coat that slows down digestion, but then to pulverize them into talcum powder dust that allows them to be digested and converted to pure glucose very quickly. Think whole grains of oats turned into little small circles, stars or animals and coated with sugar.

4. Where do green vegetables come in in regard to insulin? Answer: Aha! Another trick question. The bacteria in your gut digest their cell walls and make beta-hydroxybutyrate, a short-chain fatty acid from green vegetables. BHB is all the craze right now. It's the ketone you measure in your blood. You don't touch insulin when you have BHB on board as a supplement. So green vegetables don't turn on insulin and allow BHB to stay around - meaning your fat cells and all the calories in them are available for use.

5. What is the single worst food you can eat that makes you develop insulin resistance the fastest? Answer: fructose in liquid form.

The Problem with Processed Foods 3 - Mitochondrial Dysfunction

Metabolic Problem of Processed Foods #3 Mitochondrial Dysfunction

Mitochondrial dysfunction sounds like it's a big mouthful, but it is at the heart of all diseases. Big claim.

You need mitochondria to make energy. Without them, you lose about 90% of your energy-making capacity. So, you want to make them happy. Now, they are designed to survive at just a tiny trickle of energy coming through, and then leap up to a 10,000 fold increase in just seconds. That's pretty impressive. Faster acceleration than a Tesla. Mitochondria make energy by separating electrons and protons in separate spaces, and keeping them in separate spaces until you need ATP. They do that by taking advantage of the inherent stored energy in glucose or fat. Those energetic electrons get jammed onto NADH and don't really want to sit still. If NADH can't pass them on the whole mitochondria shuts down.

If your mitochondria are working properly, you match the energy output to the energy input. Your cells are happy. Your electrons in the mitochondria have someplace to go because the energy they represent is matched to the energy you are burning.

What happens if your mitochondria are slightly old and beat up, a little low in their key building blocks? It's harder to keep those electrons sequestered. More escape leading to more oxidation. That was last week's email. You get oxidation, damage to your cell by labels on the cell that it is getting old and your immune system should do something to terminate it.

But a bigger problem is lurking from processed food. You get calories too fast, from too many directions. The funnel of fuel coming into the electron transport chain gets overloaded. When you eat finely refined grains and free sugars, you flood the mitochondria with too many sources at the key nexus of energy production, Coenzyme A (made from Vitamin B5, pantothenic acid). It's the shuttle that puts carbon fragments into the citric acid cycle to stoke the electron transport chain, or when it gets overwhelmed, to push it off to fat production. Guess what happens when you eat refined sugar and white flour: aka, a donut? You aren't burning ATP so you don't need any more energy. But there's all this fuel. Your Coenzyme A pushes it into making lipids. You get fatty liver or fatty pancreas. And if you get lots of fructose, you do it twice as fast. Some 50% of American's have fatty liver.

If you have a bigger tummy, feel fatigued a lot of the time, and feel achy and washed out, you likely have mitochondrial dysfunction.

www.What will Work for me. You can change this. It's not that hard to do once you see the big picture. You can't afford to eat refined foods. Sugar in particular is extra wicked because it has more fructose in it. Cut the sugar. Ban any sugared drinks. Then cut the refined flours products. Eat whole foods that take time to digest, resulting in your liver getting energy much more slowly. Make sure you have fiber in the mix. Then, burn some of those calories with exercise. Finally, free up your mitochondria by fasting. That cleans out the fuel lines in your mitochondria. You can test your own fatty liver by getting an SGPT or ALT. If it's over 25, you probably have fatty liver. If your AST or SGOT is up, you need a GGT test and if it's up, you really need to get an evaluation of your fatty liver. And you need to get off sugar, asap. Do all those. You can send me an email in about, let's say, 3 months, telling me your fatty liver is better. Get your AST down to 20.

References: Metabolical, Wikipedia, Frontiers in Endocrinology, Annual Reviews of Pharm, Gastroenterology, Am Jr Roent,

Pop Quiz

1. Mitochondrial dysfunction is more simply defined as?                                       Answer: freezing up the mitochondria with too much fuel arriving too fast, forcing your mitochondria to make fats so fast, you can't get them out of your liver. You don't even have time to export them out of your liver. You get fatty liver.

2. What's the simplest way to diagnose fatty liver?                                          Answer: Get an AST on a chem panel. If it's over 25, you got game. Time to stop your favorite forms of fructose.

3. Which makes mitochondiral dysfunction faster, glucose or fructose.                             Answer: Fructose is at least twice as fast.

4. How come fruit doesn't lead to fatty liver as much?                                                       Answer: Fructose is nature's candy and is not a good way to lose weight, in general. But it does have fiber built in to it. Fiber is magic. Eat a diet of 40 grams of fiber a day and your fatty liver will go away. Slowly, but away.

5. What's wrong with flour products?                                                                             Answer: when you grind grains up you lose the protective effect of fiber that slows down the delivery of fuel to your liver. The burst of calories that rush into your system is just plain too hard on your metabolism. You can tell. You just have to take a nap....

The Problem with Processed Foods 2 - Oxidative Stress

Metabolic Problem of Processed Foods #2 Oxidative Stress

What is oxidative stress? You hear that word all the time. Do you know what it means? Lustig thinks it is so important, he calls it problem #2, hence this column. Short of reading his book, Metabolical, here is the quickie synopsis. It's oxygen molecule picking up an extra electron, making oxygen carry a negative charge. That's a hot potato you have to cool off. It is terribly damaging. That's oxidative stress.

Oxygen radicals are a standard outcome of three normal reactions in the body: glycation; energy metabolism in our mitochondria; and iron metabolism (sort of like rusting, which happens anytime you have iron in cells). Or from anything that causes inflammation, which, when properly harnessed kills invading cells instead of you. Oxygen is everywhere, dissolved in your blood and cellular water, so any of those processes find oxygen around if you tip over the edge and make that free electron available.

Alright, you are a pretty careful person who exercises regularly and are very careful about what you eat, but once in a while you indulge in a pizza or have a drive-through moment and get a hamburger: fast food. There is no fiber in fast food. The bun is digested instantly because it's pure white flour and the huge order of french fries are piping hot and delicious with your favorite ketchup. The 600 calories in the fructose-laden soda don't help. Without realizing it, you have taken in 1800 calories with no slowing down the digestion by fiber. Your blood glucose rises rapidly and you jam those calories into your mitochondria. Your mitochondria depend on electrons moving "downhill", meaning there is an absence of electrons down the electron transport chain and CoQ10 is just waiting to pass those electrons on to Cytochrome C. What happens if you are sitting on the couch, not burning any energy, yet having just eaten that burger, soda and fries? (Did I forget to mention the small chocolate shake?). Your electron transport chain is chock full of electrons. You are fully loaded with ATP. Your electron transport chain is full.

An analogy, if I may. It's like a flooded gasoline engine. Your gasoline tank if full and you pull up to the gas station and start the pump. Your tank overflows. Your engine chokes. Your NAD+/NADPH saturates and backs up. NAPDH should be much less than NAD+ but their ratio starts changing. You gotta get rid of that extra electron on NADPH. Your body, like your gasoline engine, runs best when you burn the fuel cleanly and don't flood the engine. Your electrons want a down hill gradient to flow into.

You do get rid of those hot electrons. That's where NOX enzymes sweep in, grab the excess NADPH and its extra electron and pop it onto the closest available oxygen outside the cells. Whew, just in time. That saves the electron transport chain so it's not completely plugged up and jammed. But it also makes the next hot potato, peroxide. The enzyme superoxide dismutase is meant to grab that oxygen with an extra electron in it and turn it into peroxide. That hot potato will damage everything in sight. Peroxide is like a stalker, hunting for a place to park its extra electron. At least you got rid of it outside the cell of origin, but now it's hunting for another place to dump those extra electrons. If it oxidizes a lipid molecule on the surface of your cell (the next cell down the road), that is a potent marker of cellular decline and your immune system will see that lipid damage as a signal that the cell is unhealthy and can't maintain itself properly. Time to kill it off and process that cell into the recycling bin. (Just google immune activate by lipid peroxidation.). Can't let that happen. You can only afford to oxidize so many cells. Too many oxidized cells is otherwise known as "The Biochemistry of Death." That's it. The Grim Reaper gets you.

Your cells have ways of protecting themselves too. Each cell has peroxisomes in them that make plasmalogens and catalase. And you have glutathione. Ah, our old friend, plasmalogens. Plasmalogens are incredibly valuable. They are the ONLY lipid in your cellular membranes with a precious vinal ether bond in the cis-configuration that is right on the surface of the cell, outside the cell. Guess what it soaks up and stops cold! You got it. The peroxide. Presto. The hot potato is stopped cold. But you have to make a whole new plasmalogen molecule to replace the burned-out one. But at least you stopped the hot potato, the oxidative stress. Catalase also enzymatically processes peroxide. The two together are your line of defense. And we could write paragraphs on glutathione too.

Did you get all that? Oxidative stress starts with processed food that delivers nutrients at too high a rate to your mitochondria, overwhelming them. You didn't need those calories that fast. You tip the balance so far, so fast that you force your mitochondria to make too much NADPH that has no place to go, no place to hide. And before you know it, you have to kick an electron out of the mitochondria, and then out of the cell, hoping someone else can deal with it. Someone else can, if they have sufficient plasmalogens in their membranes and catalase in their peroxisomes to gobble up the peroxide. But what happens if you keep eating fast food every day? Bit by bit you wear your plasmalogen pool down. The oxidative stress adds up. That is aging in a nutshell. Forcing oxidation to happen more, forces you to age faster.

And just what happened to the only known experiment of daily fast food? (The Movie: Super Size Me about eating at McDonald's every meal for a month.). He was developing liver failure in just one month. No joking. Just one month. If you get liver failure in one short month by regular fast food, why are you subjecting yourself to that risk once a month? You are using up your metabolic reserves. I know, I know. They brought such a huge pile of fries, you can't stand throwing them out so you finished them off. Oxidative stress. Right there. Bummer.

Now, open your eyes at the grocery store. How many items do you see made from ground-up grains, with multiple added sugars, refined oils and just too many calories all at once?

www.What will Work for me. Don't get me wrong, I love french fries. I've done a couple of experiments with them. In one, I had ketones of 4.1 in my blood on day 6 of my monthly 5 day fast mimicking diet. I had been on 800 calories for 5 days. I was proud of myself. I was out doing errands on Saturday and my car swerved into the drive-through of the local merchant-of-death hamburger joint. I was obliged to order something. In a brief lapse into sanity, I only order a small fries, and only eat four of them. I race home and 20 minutes later, my ketones were 0.0. Twenty minutes. Four fries. That is the definition of processed fast food. The nutritious Peruvian Potato that comes in some 4,000 varies, filled with fiber and antioxidants, has been converted into a massive, Idaho potato with 10 times the carbohydrate and none of the phytonutrients. Chop that up and deliver that to customers and we can eat calories at a rate far faster than we can burn. That's oxidation for you. Brought about by the whole system that uses genetic engineering to grow zombie foods containing no fiber and unbalanced quantities of carbohydrates. The factory that peels and cuts the fries, the restaurant that fries them and gives them to me piping hot with luscious salt on them. Who could resist?

References: Metabolical by Lustig, Gut, Oxidative Medicine and Cellular Longevity, PNAS, Investigative Ophthalmology, Int Jr of Molecular Sci, Supersize Me,

Pop Quiz

1.What is oxidation? Answer: in the general world, it's called rusting with iron. In your cells, it is the production of free oxygen radicals with an extra electron on them. That is a very bioactive compound that breaks chemical bonds, most dangerously on your membrane lipids that signals your immune system to attack.

2. Your cells can protect Answer: Internally with enough glutathione and superoxide dismutase, and then with catalase and plasmalogens in their membranes.

3. What do plasmalogens do to hydrogen peroxide? Answer: Boom shak-a-laka. They stop it cold. Done. Fixed. But you use up the plasmalogen molecule and you have to make a whole new one.

4. What happens to my ability to fight oxidation over time? Answer: As we age, we appear to gradually degrade our plasmalogen supply. If only we slowed down our eating of high-calorie foods. "No french fries over age 65". Just try!

5. Can we repair this deficit? Answer: Yes, we are just learning how and our application may be imperfect and open to refinement, but the ability to replace and rebuild plasmalogen supply, glutathione supply, NAD supply......choline, homocysteine. We are learning how valuable selenium is in its relationship to glutathione. On and on. We are lucky to be alive in an era of so much innovation. But don't get starry eyed about miracles. First focus on the basics. Make a downhill flow of electrons possible. Empty out your tank by burning your ATP. That's called exercise. And empty out your glycogen store. That's called intermittent fasting. See, it all comes together.

The Eight Demons of Eating Fast Food: Number 1 is Glycation

The Eight Metabolic Problems of Processed Foods: #1 Glycation

Robert Lustig's new book, Metabolical, is a tour de force. Read it, if you can take the time. Re-read some of its chapters. He clarifies the core metabolic problems that are literally killing us sooner than we should, all because of food being too processed. Here is the first item on his list of the "Eight Metabolic Processes" made worse by modern food.

1. Glycation. That is the glucose molecule sticking to stuff. If it sticks to a protein, it is called the Maillard reaction and is the fundamental driving engine of wrinkles, cataracts, and aging in general. This is sort of like basting your arteries with sweet barbeque sauce. Your arteries get stiffer, your joints weaken, you get old. Your immune system thinks you have an invader and goes nuts. Glycation is what makes diabetes kill you sooner. If the glucose happens to stick to a protein, it's called the Maillard reaction. It's basically metabolic rusting out.

The higher your blood glucose, the more glycation happens. High glucose is a problem but fructose drives the Maillard reaction 7 times faster than glucose. And fructose generates 100 times more free oxygen radicals. Now, a specific breakdown product of fructose called methylglyoxal drives the Maillard reaction 250 times faster than glucose. Where do we get extra glucose/fructose from? A little here and a little there, but 80% of American foods have extra sugar added to them. Modern food has a lot extra sugar added to it because you eat more when you taste real sugar. Table sugar is half glucose and half fructose. Sugared sodas have an even high proportion of fructose (typically 55% fructose) in the form of high fructose corn syrup.


Can you measure the Maillard reaction? Not really easily. You can measure the amount of glucose in your blood, averaged over the last 100 days. That is the Hemoglobin A1c. That number reflects the percentage of hemoglobin molecules with a glucose stuck on them. The definition of diabetes is now an A1c of 6.4 and above. A better definition of optimal health by the Institute of Medicine calls for an A1c below 5.7. Bredesen, our hero for cognitive decline prevention, advocates for 5.5 and below.

If the natural cleaning up processes of your body aren't working effectively, your tagged proteins with fructose or glucose on them start to accumulate and we called the Advanced Glycation End Products or AGEs. The more AGEs you have, the higher the rate of vascular disease and death.

How do you slow glycation down? Easy-peasy. It all relates to the amount of time your body is exposed to higher levels of glucose. (and or fructose). And that is fundamentally related not just to sugars but "processing in general. Let's give one simple example: oats. Completely unprocessed, whole oat grains are coated with an impervious fiber coating that your digestive enzymes can't penetrate. It takes an hour to cook and then some chewing before you swallow because of their natural fiber which keeping your digestive enzymes away from the carbohydrate inside. That slows digestion down, making the glycemic index around 19, meaning a whole grain oat cereal will raise your blood glucose at only 19% of the rate of pure glucose. You can't even find "whole grain" oats unless you go to the feed store. Now, if you crack that whole grain in half and expose an open face of stored carbohydrate to be available to digestive enzymes, the glycemic index becomes 53. It cooks faster too. 

What happens if you roll it and smash it out? That's more "processing". You expose more surface area for digestion. Glycemic index 59. It's rising with more processing. What happens if you smash it to smithereens under high-pressure steel rollers?  Put it in a small aluminum envelope with 4 fake blueberries.  Your glycemic index hits 83.  Almost as good as pure sugar. What we are doing by processing is making the food called oats easier to cook, easier to prepare, easier to eat and...and...and subsequently bad for you. Your blood glucose rises faster. You glycate more.  To add insult to injury, you then advertise that oats are good for you as part of a whole diet.  Nonsense.  Utter, nonsense.  

The devil is in the details. You want WHOLE oats meaning you have to see the grain in its full form. Not "make FROM oats" but "made OF" whole oats. Every food processor wants to trick you into thinking you are getting all the goodness of the whole grain by getting all the ingredients with the fiber and germ all ground up for you. And there is some teeny benefit to getting those vitamins and fiber. But that benefit turns out to be vastly overpowered and negated by the increased glycemic index. (We can go down the rabbit whole of same issue with glycemic load. It's the same argument.)

Now, the final insult is that your digestive system and enzymes and hormones were designed for whole grains. Your blood sugar is meant to rise slowly for a long time to match the length of time insulin lasts. Insulin lasts some 6-8 hours. What happens if you eat refined, powered grains in the form of white bread or bagels? Yup. Your insulin shoots up to respond to the rapid rise in blood sugar you get because white bread is so easily digested. And then what happens? Insulin lasts 8 hours but your glucose gets cleared out in 4. You crash with hypoglycemia and get starving hungry. Hypoglycemia is the net effect of the insulin/refined grains mismatch. You get on that treadmill and you can't get off.

Glycation is wicked. It's enemy number one on Lustig's list. More to follow.

www.What will Work for me. The answer is very simple. Eating for your health comes down to avoiding any grain that has been ground into talcum powder before being baked, cooked, fried, boiled. Our bodies were designed to eat whole foods, chewed slowly, minimally cooked. In that context, your blood glucose rises very slowly and your A1c stays low. You don't glycate. My a1c hovers around 5.7-8 all the time unless I'm very disciplined. I'm a borderline diabetic with awful genes. I'm trying not to eat any bread or flour product at all. If I'm in a place where that is awkward, I find Trader Joe's has wonderful Norwegian "Crispbreads" using no wheat with lots of flax seeds, sunflower seeds and oat flakes and big chunks of a few other seeds.

References: Metabolical by Lustig, Aging Clin Exp Res, Harvard Health, Medical News Today, JCEM

Pop Quiz

1. What is glycation? Answer:                                     Glucose sticking to substances all over your body.

2. More glycation happens under what circumstances?                                   Answer: High blood glucose resulting from the rapid digestion of grains turned into flour as fine as talcum powder that is too easily digested. (Or too much glucose or fructose from sugared drinks....or ice cream...or cookies.....)

3. What is the Maillard reaction?                                      Answer: That glucose or fructose sticking to a protein molecule. Your immune system gets nuts over that.

4. How long does the rise of glucose from eating white bread last compared to insulin?                Answer: Eating a slice of white bread will raise your glucose for 2-3 hours. Insulin, once stimulated lasts for 6-8 hours. Bad mismatch.

5. So what happens 4 hours after a meal to someone who has just eaten a lot of white bread?             Answer: They become hypoglycemic and get low blood sugar. Yikes!

A Hot Bath (Sauna) is as Good as Exercise

A Hot Bath is as Good as Exercise

The Romans did it. They built the hot baths at "Bath" 2000 years ago, trying to civilize those feisty Celts. Queen Victoria took a dip. The Japanese do it. The Fins won't let you build a house or an apartment without a sauna. American's have hot tubs galore. Is there anything to this idea of a "hot bath" other than hedonic adaptation? Well yes. You feel better when you get out of it, and intuitively, you want to do it again. Are there real health benefits?

Well, yes! And the evidence is accumulating as to the exact mechanisms and physiology. We have reported on the epidemiology of saunas on heart disease. In a study published in JAMA Internal Medicine in 2015 from Finland, 2300 men were followed for 20 years and their sauna use was recorded. Over those 20 years, once-a-week sauna resulted in a 49% death rate, compared with 38% of those going two to three times a week and just 31% of those who went four to seven times a week. Frequent visits to a sauna were also associated with lower death rates from cardiovascular disease and stroke. Now, compare that to the 5 days of life extension you get with taking statins. Hmmm....And that was for only 14 minutes.

The Review article on the physiology of "hot baths" is pretty good. The take-home message is that all the markers of metabolic stress that come out in the "metabolic syndrome" get better with sauna. As they do with exercise. Your blood pressure actually goes up in a hot bath. Your heart rate increases. Your arteries have to stretch and dilate to deliver more blood flow to dump the heat. All those mechanisms are the same as what's going on with exercise, without the exercise. There are even reports diving down to endothelial dysfunction, the core root problem of vascular disease. After the sauna, your blood pressure is down 7/5 mm of Hg. That's as good as a blood pressure pill, without the pill. And the same salutary effect is seen with stroke.

The key takeaway is around the idea of "hormesis" which is essentially the rebound benefit from the temporary stress. Exercise is a stress. You deplete your energy supply and force your mitochondria to use up their ATP and start burning fat. If you push to the point of failure, you are just one molecule of ATP short of collapse. You turn on repair and resilience genes. Acute heat exposure is the same temporary "stressor". The mechanisms all go down to the inner workings of the cell. We now know that endothelial dysfunction in the arteries is the first step of developing vascular disease, our 21st century nemesis. Vascular disease can't get started without plasmalogen deficit. It appears that "hot baths" reverse that.

www.What will Work for me. Isn't this interesting? The Fins are onto something here. They have proven the epidemiology of benefit from saunas and are now leading the way in exploring the physiology so that we get more insight into what's going on and how we can improve on it. The question arises, can we get the same effect with sun-bathing? Again, heat exposure for a brief period of time. Now, we are all distracted by the sunburn and melanomas, but is there a similar "hormesis" effect? With this summer's record-breaking heat, I feel we are all getting our saunas. It's only 14 minutes you need. More is likely a bit better.

References: The Conversation, Int Jr Envir Res Pub HealthJama Internal Medicine, J Hum Hypertension, Neurology,

Pop Quiz

1. How long a sauna do I need to get some measurable benefit? Answer: 14 minutes

2. And just how often do I have to do that? Answer: just like exercise, 4 or more times a week is best, but 1-2 a week is better than none.

3. Compared to statins, how much benefit do I have on vascular disease? Answer: well, statins add 5 days to your life. You reduce heart attack deaths by over a third with saunas. It's apples to oranges comparisons, but it feels like some 10 fold better results.

4. If I sauna and exercise, what happens then? Answer: you will have to arrange for some other way to die than heart disease, at some later date.

5. How do I get a sauna? Answer: You can buy one for your home for about $ 1800 or so and get a kit to make an infrared sauna.

Could Ivermectin Help End the COVID-19 Pandemic?

Could Ivermectin Help End the COVID Pandemic?

This ivermectin story has actually got legs to it. If you want to take the full dive, listen to Dr. Pierre Kory's full podcast, done June 1. He is one of America's premier pulmonary/critical care doctors on account of having published more studies than anyone else, but also because he was at St. Luke's, Milwaukee, right here in our hometown.

But here is the story. You see if it has credibility.

The story might begin in Peru. COVID was winning! Hospitals were being flooded with COVID patients. Vaccines were not available. Peru started using Ivermectin and fatalities dropped dramatically. They reported this in April this year. In brief summary, their mortality dropped 74% in a month when ivermectin was used, starting about 10 days after they started using ivermectin broadly in multiple provinces. That took bold initiative on the part of public health workers and elected officials.

Or we could look at Africa. Ivermectin has been used widely in Africa to treat river blindness (onchocerciasis), to great success. There are wide swaths of Africa where folks are taking ivermectin weekly to prevent onchocerciasis. Guess what the statisticians tell us about why COVID has not affected Africa like it has the rest of the world? Bingo: the data shows a protective effect despite the huge challenges of measuring COVID in poverty-ravaged areas. Taking ivermectin appears to be protective against getting COVID.

Take the story of Mexico. In crisis over COVID with its ICU's full, it started using Ivermectin. Test positive and you and everyone in your family get ivermectin, even before you get sick. Mexico's current COVID situation is with ICU beds at 80% empty and the country back on its feet having an election.

There are some 30+ studies. For example, a small study in Egypt at Zagazig University. Of 204 subjects in the treatment, (all had one family member test positive for COVID) only 7.4% developed the disease. The untreated control group had 58% develop the disease. It's a small study, done outside the USA. It was not published in a major US journal. It wasn't randomized, but it did have a control group. Is it valid?

How about India, where it is now being used in some states despite WHO saying not to? But the government of India has now cautiously endorsed its use. COVID in India is exploding because of crowding, poverty, lack of vaccine...they seem to recognize the crisis and the need for decisive new approaches.

You get the idea. We have a world at war with a virus. We have a drug that is cheap, widely available, tiny toxicity profile, long history of safe use and with many studies showing efficacy of one degree or another, and few clinical trials. We know ivermectin has an effect on viruses. There is actually quite a robust literature on it. It works in viruses by "inhibiting recognition of the nuclear localizing... integrase protein by the host heterodimeric importin (IMP) α/β1 complex, and has since been shown to bind directly to IMPα to induce conformational changes that prevent its normal function in mediating nuclear import of key viral and host proteins". Did you get that? But do we have a "large, statistically powered study" to prove it? No, and we never will. It is too cheap. There is no profit incentive and in America, our health care system runs on a corporate profit model, not a public health model.

What is the reason for the silence around using it? What is the "hidden force" behind the scenes preventing our using it? Why don't we have a proper, randomized, placebo-controlled trial being conducted in America, if it shows such promise in multiple places all over the world? Hmmm. You might find Merck's comment instructive. Even WHO is being cautious. The FDA does not appear to be enthusiastic either, specifically stating it is NOT approved for use in humans with COVID.

www.What will Work for me. If I were "in charge", I would make the proper study of ivermectin the highest priority. In a war you need many tools to attack the enemy. And you don't put false arguments out there about "not being studied". In World War II, we never had a randomized, placebo-controlled trial of parachutes prior to D-Day. We just used them after the first demonstration that one worked. They didn't work perfectly, but those early parachutes helped win D-Day and Omaha Beach. My editorial comment is the following. Our health system is sadly broken and focused on profit and shackled by economic interests. This drug is a tool with promise that might serve us well, as part of our armamentarium. I'm writing to my elected officials asking them to please advocate for a study of the drug. You won't get immunity from taking it. That comes only with having the disease, or getting vaccinated. The track record of the vaccine has now been long enough that we can be pretty confident there won't be mystery side effects "sometime in the future". Some side effects would have happened already, and have not been observed. Our elected officials would generate more trust and credibility if they found a way to study this drug instead of stubbornly resisting it.

References: Youtube with Dr Pierre Kory, International Jr Inf Diseases, Inter Jr Good Conscience, SSRN, MedRxIV,

Pop Quiz

1. What is the way to move the needle towards action in America? Answer: all of us writing to our elected officials. Make a politcal noise, peacefully. Please write today.

2. Can you explain how ivermectin works? Answer. Well, its complicated but you can simplify it to say the virus hijacks some proteins. Ivermectin blocks the hijacking.

3. Are you immune to COVID if you take ivermectin? Answer: No. We don't know that yet.

4. If you take ivermectin once a week to prevent river blindness, what are your chances of getting COVID? Answer. Very, very, very low.

5. What is ivermectin used for that is in your home already? Answer: look at the heartworm package for your dog. It might be ivermectin, right in your dog medicine cabinet.

The Mitchondrial Threshold

The Mitochondrial Threshold: The Explanation for All Diseases

How do you explain the root causes of diseases? What is the underlying cause? Let's take a stab at it. See if I can explain to you, in plain enough English the key ideas and have it make sense to you.

It helps to go backwards, so let's make one example: heart disease. A heart attack is actually the final end-product of 30 years of arteries accumulating lipids and small, dense LDLs stuffed full of triglycerides. But what got that started? We call it endothelial dysfunction, of which the very first step is the lining cells of arteries being stressed by too much peroxide. They can't neutralize it faster than it's being made. Peroxide comes from Reactive Oyxgen Species (ROS). (Very elegant research backin the 70s proves it.). So they stop being connected to each other and the artery lining gets leaky. In comes the LDLs. Let's go back another step. What makes the peroxide?

In short, oxidative stress. Now we are back to the mitochondria, our energy factories. Our mitochondria like a regular supply of fuel which they get fed via fatty acid breakdown in the peroxisomes or pyruvate via the glucose pathway. Those are like two separate hoppers, or supply trains, feeding raw energy into the engine. They work best when there is a gradient going downhill all the way through. The very first complex in the electron transport chain is Complex 1 which will push 4 protons into the "reservoir". Now, an active athlete is using up all their ATP in their cells, so the electron transport chain has something to do, a destination for its protons. Ditto for a person who is fasting. Very few protons linger in the "reservoir". The electron transport chain always has an empty slot for the next electron and proton. So, they all get used properly and no reactive oxygen species get pushed out. But what happens to a well-fed, middle class office worker who just had a big breakfast of sugar coated cereal and a luscious coffee purchased on the way to work with 600 more calories of high fructose corn syrup. With little calorie expenditure pulling ATP out of the mitochondria, and both sources of fuel wound up, the electron transport chain backs up. It has more fuel arriving than it can handle and it can't turn anything off. Its only way to cool off is literally to cool off, turn on uncoupling so it makes more heat. But that isn't enough. 

The backing up makes for more reactive oxygen species, (loose electrons that escape complex I and III in the electron transport chain). And that makes for more peroxide. Remember peroxide going out there and damaging your lipids and your endothelium, starting artery disease? It took 40 years for it to turn into a heart attack, but it started sitting in the booster seat in the back of the minivan stuffing your face with french fries and ketchup. They overwhelmed your mitochondria, flooding you with "oxidative stress". The fructose in the ketchup flooded your liver forcing you to make fat. Or in the sugared fruit drink that came in a pouch, or in a donut covered with sugar.

And that is the "Mitochondrial Threshold". Our modern food supply of too much nutrition, of too many kinds of foods, delivered all at once, without any fiber in it to nourish our gut and slow down the delivery of calories. Hence, the cause of all diseases is our modern food supply, delivered with too many purified calories, devoid of any fiber to slow their absorption. We have met the enemy, and it is us.

You can walk through this same scenario with cancer. Dysfunctional mitochondria, with altered internal dynamics pushing nutrients into alternative pathways. In the case of cancer, its citrate being exported into polyamines and feeding cancer.

But underlying all of them is the damage to the mitochondria that overwhelms the mitochondrial ability to repair its own membranes. What is in the mitochondrial membranes that is sucking up and absorbing the reactive oxygen species that gets overwhelmed?


What would happen if you maintained your plasmalogens? Plasmalogens are in place to catch the occasional reactive oxygen species with their precious vinyl ether bond on the outside of the membrane, the only membrane lipid to have such a feature. We deplete them with our modern, highly processed diet. Then, inexorable flooding of our mitochondria leads to mitochondrial dysfunction. Once upon a time we made sufficient plasmalogens to absorb the occasional reactive oxygen. Now, the ensuing flood of ROS leads to chronic disease. That's where diabetes,heart disease, neurodegenerative disease all start. How to repair? 

First! Don't produce so many reactive oxygen species by eating so much highly processed food that floods your mitochondria with too many nutrients all at once, and depleting your plasmalogens. Two, make sure you get the proper nutrients to make sufficient plasmalogens. Understanding how we deplete them and how plasmalogens create a means of measuring our biochemical reserve creates a whole new methodology of gauging susceptibility to chronic disease.

This hypothesis is the nexus of Robert Lustig's brilliant new book Metabolical. Read it. He has a chapter detailing the three great controlling enzymes that get overwhelmed by our eating processed foods. It's sobering and it fits the missing understanding of complexity. And he has a chapter about how to measure where you are. Get the lab.

My addition to this is my understanding Goodenow's contribution that I call the metabolic "shock absorbers" to dysfunction, plasmalogens. His book isn't published yet but this is some of the advanced ideas detailed in it. We can overwhelm our mitochondria in daily living, and our plasmalogens soak up the errors and neutralize the reactive oxygen species. Eventually we wear that reserve down. That's when trouble starts.

www.What will Work for me. Ah, I now understand why intermittent fasting works. You empty out your electron transport chain and allow your mitochondria to get back to running on lean. They like that. I also get how Goodenowe's discovery of plasmalogen absence predicts coming metabolic catastrophe. Their adequate presence means you still have metabolic resilience. They might just be considered your metabolic shock absorbers. The metabolism of fructose fits curiously into the picture as an accelerant, like pouring gasoline on a campfire. Then metformin speeds up your mitochondria to help them clean out. Exercise also gets you to running on lean. What gets you the sickest, fastest? Fast food. Lustig brilliantly simplifies his advice. " Feed the gut, protect the liver". That comes down to more fiber (known as whole food, vegetables and fruit) and less fructose. That comes down to less processed food. Hereafter I'm ordering the GGT enzyme in addition to the AST and ALT so I understand Lustig's lab. I've measured my plasmalogens. I was low. I'm now taking them as a rebuilding plan. My mitochondrial threshold lies in the balance. My brain, my pancreas, my liver, my heart all lay in waiting.

References: Br J Pharm, Nephrology Dial Trans, Atherosclerosis, Metabolical,

Pop Quiz

1. Step one in getting in trouble is? Answer: Per Lustig, what we put in our mouth in the form of highly processed food that gets too many nutrients into our cells too fast.

2. What is Lustig's simple admonition about eating: Answer: Feed the gut, protect the liver. (Aka, more fiber, less sugar)

3. What correlates the best pending vascular disease? Answer: Low plasmalogens.

4. And just what role do plasmalogens play in this whole dance? Answer: They are your metabolic shock absorbers, soaking up excess free oxygen radicals.

5. Can you overcome them? Answer: Have you watched the movie "Supersize Me."? Yes, we all are routinely engaged in that practice with our low fiber, highly refined, western diet choking us with too much sugar.

Statins Add 5 Days to Your Life

Statins Add 5 Days to Your Life

There are cracks in the "statin empire". The $ 18 billion industry has reached out as far as it can possibly go, even to the extent of advocating that virtually all adults should be on statins. But does it make sense and are we really treating a disease or a symptom?

The first crack appeared about 9 years ago around the simplistic rule of 200. Cholesterol above 200, you need statins. Below 200, "You're fine". Well, the Norwegians tested that in 2012 with the HUNT Study and followed some 50,000 folks for 10 years. They found that women with cholesterol over 200 lived longer than under 200. Oops! Is there a problem here? Of course, there is. The real problem is that you get into trouble in your arteries from small, dense LDL particles that have been oxidized. They occupy less volume. You can have a "low" cholesterol and not really be protected. Taking a statin, ironically, reduces the number of large, fluffy, harmless LDLs and not the dangerous small LDLs. That "magic" number of 200 doesn't make sense. It is simply a super easy tool that advertisers and patients can glom onto and believe that sounds like it makes sense. (Statins do have some helpful effect, probably as an anti-inflammatory nature.

Ask the question. Are you interested in how long you live, or how low your cholesterol is? I would contend you want to live longer. If I showed you a study of 12.6 million people, followed for some 10 years and having 694,000 deaths, you would say, "Sounds like a pretty good study to me - it's got big numbers." Well, they found that the ideal cholesterol was between 210 to 249. Sounds like the crack is getting bigger.

Ok, so just what benefit do I get from statins? Let's look at that. A study published in the British Medical Journal looking at 6 primary prevention and 5 secondary prevention studies (all they could find that included mortality and had sufficient scientific rigor) showed a surprising finding. The median survival advantage is just 4-5 days. Not much, considering cost, side-effects, and inconvenience. In fact, perhaps just plain nuts except for in very focused situations, like smokers who have had a heart attack. But folks with negative calcium CTs of their heart being advised to take a statin? That's just plain nuts. (Just look at that study. Folks with score of zero had zero mortality.)

Don't get me wrong. Cardiac disease remains the number one killer in America. It's worthy of being addressed. Just find for me the right tools. I would contend that you want to turn off oxidation and the production of small, dense LDLs. Well, now that's a worthy challenge. Once you understand what's happening, you can shape your own strategy to change it for yourself. We have to dive down into your mitochondria and the membranes of your cells. I can't fit it into this column so it's coming next week. In the meantime, consider cutting out sugar and white flour for the whole week. (Hint: if you measured the volume of your LDLs before and after the week, your LDL volume would have gone up. Your oxidized LDLs would have slipped into "safe" territory and your oxidation count would have gone down.). So next week, we will put the icing on the cake (sorry, wrong image), the olive oil on the avocado, and walk you through how oxidation gets started and how that leads to leaky endothelium in your arteries....and that's what we need to be treating. Stay tuned.

www.What will Work for me. I started my monthly 5-day fast mimicking diet this week. My first-morning fasting glucose after a 13 hour fasting period was 103. Ugh. I have such lousy genes. The Whitehall Study shows that every point over 85 on your fasting glucose results in a 6% increase risk of diabetes. Indeed, my father died of diabetes. The fast-mimicking diet will drop my glucose to the 70s by day 5, which gets me briefly into the safe zone. But insulin resistance and diabetes is all wrapped up in leaky artery endothelium, which is all wrapped up in oxidized, small dense LDLs. I'm intensely interested in this topic. And my physiology represents just about 50% of folks who think they are pretty ok and don't have much trouble, until they do. That's why this is such an important topic. But I'm not convinced a statin will help me. I am going to avoid fructose, sugar, and white flour.

References: BMJ Open, Stat News, Sci Reports, JACC Cardiovascular Imaging, Lancet,

Pop Quiz

1. Statins are an important part of cardiac care and prevention? Answer: Oh, such a loaded question. Yes, for a small number. No, for probably most people, particularly for those with a negative cardiac calcium scoring test.

2. And even if I have risk, how much extra life do I get by taking statins? Answer: 4-5 days. If that comforts you. Make sure you use those 4 days well.

3. My muscle aches and brain fog that I get with statins are worth it, aren't they? Answer: You have to decide

4. What is the level of cholesterol correlated with the longest life-span? Answer: between 210-250. Now, oxidized, small dense LDLs, that’s another story.

5. Did you know that the vast majority of primary care physicians have review of their medical decision-making around statins with economic consequences in their salary for not treating people with cholesterol over 200? Answer: Sad, isn't it? Guess who designed those "quality guidelines"? Yes, statin compensated doctors. The problem: you get caught in the cross-hairs.

The Trouble With Diabetes Isn't the Glucose, It's the Insulin

The Problem with Diabetes Isn't the Sugar, It's the Insulin

We have had an increase of diabetes in America and around the world of unprecedented magnitude. We are increasing at about 10% a year, and our health care system has been helpless to decrease it. Some 60% of people in America are on the path to getting it. What gives?

The clue comes in a unique experiment done almost twenty years ago by Ron Kahn's lab at the Joslin Clinic. The core idea from his experiments was that blood glucose is actually a red herring. It's not the problem. The problem is INSULIN resistance. Blood glucose is just a symptom. Your blood insulin is only partially related to your glucose level. The experiment was to genetically knock out insulin receptors in different tissues in lab mice, and then watch what subsequently happened. Every tissue has insulin receptors. Brain, fat cells, brown fat, muscle, pancreas beta-cells, blood vessels, and kidneys were the tissues they chose. All the mice got sick in one way or another, but only the liver and brain knock-outs got high blood sugar. Only the brain knock-out became obese and developed metabolic syndrome. And to put the final irony, the kidney knockout didn't get high blood glucose but got the kidney disease of diabetes anyways.

WHOA! This has huge implications. The logic is a bit complex but nevertheless compelling. It's not the glucose. It's the insulin that causes the illness.

If you think it through, we see the same effect in humans. Insulin deficient type I diabetics take 20 plus years to get kidney disease. But type II adult-onset diabetics already have the kidney disease before they get the high blood sugar. Why? Because they have had surreptitious insulin resistance for years that was not diagnosed. Their insulin level was over 5 and no one blew the whistle.

Why this dichotomy? Insulin is a two-edged sword. It helps control blood glucose, that's one edge. But it also serves as a proliferative agent. It increases the growth of cells. In the heart and kidney, those cells are the smooth muscle cells in the walls of the arteries, and you get heart attacks and kidney failure as a result. (This has been proven in every intensive insulin program ever done: you reduce blood glucose but raise risk of chronic disease. Bummer.)

What causes insulin resistance? We've known this for 20 years, but it somehow doesn't quite bubble up to the top. Finally, a recent review acknowledges that fructose, half of table sugar, (sucrose is glucose and fructose stuck together) is the real enemy. It drives metabolic syndrome starting with insulin resistance in the liver. Soon thereafter, hypertension shows up too.

Fructose is the enemy. But fructose is in every liquid calorie you drink that is manufactured using high fructose corn syrup. Fructose is in almost every prepared food you eat, every mouthful of ice cream you eat, and on and on. Fruit is some 6% fructose, so even that contributes a little but our body appears to be able to handle the quantity that comes with fruit. But more than two servings of fruit a day and LDLs will go up.  But fructose was never in any food prior to this century.  Real food does not have fructose in it.  Period.

What is so awful about fructose? You can't slow it down. It floods into your liver and demands attention. You have no controls or gates that limit how quickly it gets into your liver. It has to be labeled with a phosphate group from ATP, which exhausts your ATP supply. You get an oversupply of acetyl-CoA in the liver and the liver cell panics and switches to making fatty liver. The fat globules accumulate. And that's the beginning of insulin resistance. Guess how badly Big Food wants you to understand this. Guess how much lobbying money goes into not regulating it?

How do you reverse diabetes? It's not weight loss per see, though that may be extremely helpful. You reverse diabetes by focusing on the insulin resistance and your insulin level. This is where the power of intermittent fasting works. By compressing calories into an 8 hour window, your body has burned up it's glycogen stores in 10-12 hours and you then have at least 4 hours of running on ketones, which means the pressure on your insulin evaporates. The first ketones to go are from your fatty liver. As you reduce fatty liver, your metabolic syndrome fades. Or, once a month fast mimicking. Same thing. But you start by stopping the sugar, high fructose corn syrup in particular.

www.What will Work for me. I've measured my insulin on day 5 of my fast mimicking behavior when I eat 800 calories a day for 5 days: 50% fat and 50% green vegetables. It's been as low as 2. Otherwise, my insulin runs 7-8. I'm tip toeing along the edge of metabolic syndrome. So, I'm close to trouble. For the last month I've started skipping breakfast and eating my first meal at least 10 am. I want to see if I can get my A1c down below 5.6, where it appears to have been permanently parked. And no sugar, no sugar, no sugar.

References: Ann Rev Physiology, Critical Rev Clin Lab Sci, Nutrition and Metab, Penn Med News,

Pop Quiz

1. Through most of human history, when did we get sugar? Answer: Only in the fall when fruit ripened which we could get for a couple of weeks. Or, if we found a beehive. Sugar has shown up in our food supply only in the last 100 years in quantity.

2. And just what does sugar (fructose in particular) do to make metabolic syndrome? Answer: Insulin resistance.

3. Which comes first for adult-onset diabetics, the high blood glucose or high insulin? Answer: Insulin is way first. If you had observed the range of "normal insulin" in our labs in Southeast Wisconsin over the last 30 years, you would have noted that the "range of normal" has been creeping up every couple of years. The supposed normal range is now typically 3-29, depending which lab you use. It used to be 1.9-19 about 15 years ago. What happened in the interim? We have eaten more HFCS, ice cream, sugared sodas, ketchup....etc.

4. What is the cardinal first step in lowering your insulin? Answer: It starts in your fatty liver begging you to stop the fructose. Then, give your liver a break and let it burn up all the energy you stuffed into it with fructose by lengthening the time you don't eat each day. Get to 16 hours, your fatty liver will go away.

5. What is a healthy insulin level? Answer: Less than 5. Measure it. Pay heed if it's higher.

6. Can you take enough meds for diabetes to reverse the harm of fructose? Answer: No. Meds are just a bandaid to cover the symptom of high blood sugar. High blood glucose is the symptom. High insulin is the disease.