Greetings everyone.

As you might imagine, I got a lot of feedback from the last Arrow. Most of the replies were thankfulness that I had survived – so far – and wishing me well. The outpouring of support was overwhelming and truly appreciated. I can’t thank those who relayed such sentiments enough. 2025 was a brutal year for the family as a consequence of my health issues. Thankfully, we’re now back on an even keel.

Many people replied that they were amazed that I could continue to churn out posts week after week while going through all I was going through. I intended to address this in the last Arrow, but I ran out of space. Probably a thousand or more words ended up on the newsletter equivalent of the cutting room floor. Since I won’t run out of space now, I’ll tell you what happened.

MD ended up writing three or four of The Arrows when I was at my lowest. As you could see from the photo I posted in the last issue, I appeared to be at death’s door around Christmas. In fact, I probably wasn’t really at death’s door, but I sure did look like it. And felt like it. There was no way I could rally to write a lengthy Arrow. Unbeknownst to me, MD, with a bird’s eye view of the situation, took it all in hand and wrote the Christmas 2025 one on her own.

I was still in no shape to do it for the next few weeks, so she stepped in and wrote those as well. I was in no condition to write those, but I did offer some advice as to subject matter. I was so unspeakably happy that I had a wife to step in when I faltered. I was also unspeakably chagrined to find that her Arrows got better ratings than mine. But she is a great writer, so I shouldn’t have been as bothered as I was.

Another issue a number of people asked about is why? Folks want to know what I thought about why I was afflicted with cancer when I was otherwise in such good health.

The short answer is that I have no idea. I am male, which is a strong risk factor. Males get bladder cancer 27 times more often than women do, so that is one risk factor. The other main risk factor is a history of heavy smoking. I’ve never smoked a cigarette in my life, though I did grow up in a household of heavy smokers. But so did a lot of (maybe most) people in my generation.

And I drew a great ticket in the parental lottery. Both my mother and father lived to be one month from 94 years old. Both smoked heavily. My father, a sailor, drank fairly heavily until he was older. My mother didn’t drink much until she was older, then took to white wine with a vengeance. Given my parental history and the fact that I never smoked and didn’t really drink all that much, I figured I would live forever.

But cancer gave me a wake up call. And I still don’t know why I got it.

A possible risk factor is COVID. If you recall, my urologist asked me if I had been vaccinated. I hadn’t. I did get the Omicron variant of COVID, but the mildest case imaginable.

MD came down with it first, and when she did, I began taking ivermectin (as did she). She got sick on Tuesday, and I got it Wednesday night. I went to bed and woke up with fever and a drenching sweat. I felt pretty fatigued all day Thursday, went to bed Thursday night, and woke up on Friday morning, having had another drenching sweat that night. But with no fever and no fatigue. I felt completely normal.

But I did get exposed to the spike protein. As did all those who got vaccinated. I got exposed to the virus’s nucleocapsid also, which those who were vaccinated did not.

The statistics are all over the place on whether the cancer incidence has gone up or stayed the same since COVID. It all depends on who’s trying to cover whose rear end, I suppose. I’ve seen stats that say the incidence of cancer has decreased or remained about the same since COVID, while others report a significant increase.

A recent paper by the oncology departments of Tufts medical school and Brown medical school indicate that cancer has been significantly on the rise. I saw another statistic showing bladder cancer specifically was up by 62 percent.

But given the variation in the statistics, who knows?

Too bad we don’t have a public health institution we can rely on. But unfortunately we don’t.

One reader asked a question I, myself, have thought about since all this went down. He asked if I thought there would have been a different outcome had I taken the immunotherapy course first.

I don’t know.

But I do have one reported experience to go by.

Dr. Paul Marik, who was probably among the most prominent critical care specialists in the world until he ran afoul of the COVID vaccine complex and got canceled, reported a case history of someone who took exactly the opposite course from what I did.

The patient ended up with all kinds of issues with the immunotherapy.

Obviously, I don’t know how I would have fared had I done the immunotherapy first. The patient described above had a bad go of it, but I have no idea how long he was on the protocol. I wasn’t on it for very long, and I suspect the reason is that I had already knocked most of my tumor out with the repurposed drugs I took.

What I do wish I had done was to have taken the Natera test when I was first diagnosed. Given how the cancer was all over my bladder, I’m sure the tumor burden would have been sky high. But I didn’t take the test until after I had been on the repurposed drugs for months. At that point, the test showed only a minimal tumor burden, which tells me the drugs were working. That idea was amplified by the fact that as soon as I quit taking the drugs, the tumor burden increased steadily and dramatically.

Did the drugs slap it down so much that it didn’t take many infusions before the cancer was gone? Who knows? But that would be my bet.

The patient Dr. Marik describes did not have much luck with the immunotherapy and was at “the point where hope begins to quietly fade.” You can see from the graphic below that he had nodes like I did. He ended up on the repurposed drugs, and is now cancer free.

I may have vastly improved continuing on the repurposed drugs also. But after seeing my tumor burden climb, and my sense of well-being turn to absolute crap, I didn’t want to try. I was willing to give immunotherapy a chance.

Another common question I got in emails and comments was about how I look today. The cadaverous photo I posted in the last Arrow showed me at my worst during all this. When I started my second infusion on February 17 of this year, I weighed in at 152.2 pounds. When I went in for my last visit on March 31, I weighed 182.2 pounds, exactly 30 pounds more. On the same scale at about the same time of day wearing exactly the same clothes and shoes.

I gained 30 pounds in 42 days. I’ve probably put on another 5 or 10 pounds since, but I’ve been watching what I eat. When my appetite came roaring back about the same time my tumor burden score was 0.00, I was ravenously hungry. But I still probably didn’t eat as much as I ate pre-cancer, yet my muscle mass came back pretty quickly. I was surprised about that.

I’ve written countless times that as people get older, they have a much more difficult time gaining muscle mass than they did when younger. That’s what studies show. Now I know that that depends.

I don’t think I’ve ever gained 30 pounds over six weeks at any point in my life. And most of it was muscle. I’m still wearing old pants I wore years ago. I want to keep it that way.

It’s made me even more of a firm believer in the notion of nutrient partitioning. In other words, the idea that the body determines where energy goes. Some people send it to fat. In my case – at least during this one period – most of it went to muscle.

Below are a couple of photos.

A subscriber had written me an email wondering if I would post a current photo. She was creeped out by the one in the last Arrow. I read it to MD, who grabbed her phone and took the photo above.

Every morning when I get up, I grab a cup of coffee and my phone, do a couple of the NY Times puzzles, then scan a few websites while I sit in my favorite chair. Which is where I’m sitting in the photo above.

You may note that my hair is very short, at least as compared to what it used to be. I lost a ton of my hair right around the first of the year. I don’t think it happened due to the immunotherapy, because I had just undergone my first infusion. I’m pretty sure it was telogen effluvium as a consequence of my not eating much of anything several weeks before. (You can read about telogen effluvium in this article MD wrote a few months ago.)

Not all of it fell out, but a lot did. And when the new hair started coming in, the old hair kind of stood straight up. MD badgered me to get it all cut the same length, because, as she constantly remarked, I was beginning to look like a possum.

I relented and got it cut. Short. As the new hair came in, it was much thicker and had a tiny bit of curl, which I have never had. I discovered I loved having it short. It is really no muss, no fuss. No bedhead when I get up in the morning. I think I’m going to keep it this way, at least for a while. I’m way too old and way too married to worry about my appearance. So…

To forestall a million questions, let me tell you about the big blue ball I’m resting my feet on.

When I was first starting to work out, my back – which was severely lacking in strength – was sore all the time. I went to physical therapy, and the therapist told me I needed to get a big ball to help roll out my back. I was to sit in a chair, throw my arms over the ball, and roll it away from me in a manner that stretched my back. I had no idea where to get one of these balls, but as it turned out, my son had one he had used for his back years before.

I borrowed it.

MD squawked because it is an eyesore, and, knowing me, she figured it would be in the middle of the floor all the time. So I agreed to put it in the garage when I wasn’t using it. But then it was out of sight, out of mind, so I never used it. And more or less forgot about it.

My back got worse as my workouts got more intense. My physical therapist asked if I was using the ball. I sheepishly told her I hadn’t and promised to get it out and give it a go. Which I did.

Both MD and I knew that if I had to put it in the garage and go get it every time I needed to use it, I seldom would. She relented. I brought it in and used it as directed, and it seemed to work a bit, but not like I figured it would. Since we’re in kind of a cramped space, I moved the small ottoman I usually use to put my legs on and replaced it with the big blue ball.

Every morning (and whenever I read, other than in bed), I sit on the chair and rest my legs on the ball, as shown in the photo above. Amazingly, just doing that alone has gotten rid of my back pain.

When I stretch my legs out using the ottoman, they don’t move. And when I get up, say, to get more coffee, I’m stiff in the back and can barely move. My back hurts like the devil. But if I put my feet and ankles on the ball, I have no pain or stiffness whatsoever. I can leap up, grab coffee, or whatever without a bit of pain.

I’m sure it’s because I’m constantly slightly moving the ball around to keep my legs balanced, which I did not have to do with the ottoman. I’m sure it’s that constant perpetual small movement that prevents my back from being sore, even if I sit there for two hours. It’s wonderful.

I looked the thing up on Amazon, and they practically give them away. It costs about 15 bucks plus tax. Here is the link if you’re interested. I’ve never used it on anyone but myself, so I can’t vouch for its efficacy in any case but my own. And I have no idea if it’s the best one available. It’s just the one I borrowed.

Below is another photo MD snapped of my son and me at a golf tournament last week. It was a two-day event, and we tied for second. Here I am making a critical putt.

As you can see, I at least don’t look like a stickman in this one.

Okay, most questions answered. Let’s get on with our regularly scheduled programming.

The Arrow is a reader-supported publication. To receive new posts and support my work, please consider becoming a paid subscriber.

Metabolic Flexibility

Metabolic flexibility is a simple term to understand, while hiding a vast amount of biochemistry and physiology. It is defined as the capacity to switch between fat and carbohydrate oxidation in response to fasting, feeding, and changes in energy demand (e.g., exercise). In other words, it is the body’s ability to use the fuels available to underwrite the cost of activity.

Seems simple enough, but it really isn’t.

Most people are born with great metabolic flexibility. Breast milk contains carbohydrates, fats, and proteins. The growing baby is able to use all of them appropriately.

But as people age, they tend to lose this ability, or at least lose it to some extent. And disease follows.

We humans have basically four calorie-containing fuels we use to animate our lives: protein, fat, carbohydrate, and ketone bodies. Oh, and alcohol, so I guess there are actually five. We metabolize them all differently. Alcohol is metabolized first. It is a calorie-rich poison. One that I, myself, enjoy a lot. But not too much. Alcohol contains ~ 7 kcal/g, so it is intermediate between carbohydrates (~4 kcal/g) and fat (~9 kcal/g). There are plenty of calories in that before-dinner cocktail. And those calories are used by the body first before any food is metabolized.

Protein comes second in terms of how quickly it is used. But protein isn’t used as an energy source as are fat, carbohydrate, and alcohol. The digestive system breaks protein down into its constituent amino acids and absorbs them. Then it uses those various amino acids for repair and building of protein structures (think muscle and organ infrastructure) and for the raw materials of the countless enzymes the body continuously produces. We use protein as an energy source only when we’re in starvation mode.

That leaves fat and carbohydrate, which are the primary external sources of our energy.

Metabolic flexibility is basically defined as how the body ends up using these two macronutrients.

It so often has been stated that carbohydrates provide immediate energy that it has become axiomatic. There is some truth to this statement, but it isn’t necessarily the best way to look at the situation.

I tend to look at it differently.

In my view, carbs are a sort of poison much like alcohol, and the body wants to get rid of them as quickly as possible.

There is a body of evidence for what is called glucose toxicity. In other words, glucose in large doses is harmful to many body structures, including the lining of the arteries. This idea has been studied by scientists for years. In fact, PubMed shows there have been 27,434 studies on glucose toxicity going all the way back to the early 1900s. Here is a graphic of the list.

In 1994, when the anti-fat and anti-cholesterol hysteria was at its zenith (and cholesterol-lowering drugs were flooding the market), the first paper appeared on lipotoxicity. Since then there have been 5,369 papers published on that topic, or about one fifth the number on glucose toxicity.

If you look at both of these graphics, you can see that the idea of lipo (or fat) toxicity is kind of petering out, whereas the studies on glucose toxicity are on the rise. Perhaps I’m simply imagining that because of my own bias, but it seems pretty obvious to me.

There is an actual disease of too much glucose in the blood. It’s called diabetes. There really isn’t a disease caused by too much fat unless you include hyperlipidemia, which isn’t really a disease like diabetes is, but instead is a lab number used to justify cholesterol-lowering medications. ^₁

If untreated, diabetes will kill you, or, at the very least, cause significant problems including shortening of life. Elevated cholesterol won’t. It’s still in the lipid-hypothesis stage. And many studies show those who have the highest cholesterol when elderly have the longest life expectancy. Hardly what you would think a deadly disease would do.

So the body gets rid of carbohydrates not just for quick energy, but to rid itself of a poison. But you may be thinking: the body needs carbs, so why would they ever be toxic? Well, the body needs oxygen to survive, but too much of it is toxic as well. Even too much water can be toxic.

The dose makes the poison.

Before we go on, I need to briefly discuss ketone bodies, which I’ll refer to as ketones from hereon. We don’t really consume ketones via the diet. I know there are now what are called exogenous ketones that we can consume. But these are a recent addition to our diet. For millennia, the only ketones we ever used were those we, ourselves, made from fats. Metabolically, ketones are used as a substitute for carbohydrates. Carbohydrates are water soluble; fats are not. Ketones are water soluble, so when we need a nutrient to be water soluble, ketones fit the task. Thus no carbs are really needed at all. There are no carbohydrate-deficiency diseases, but there are fat- and protein-deficiency diseases.

Our bodies operate much like an assembly line in a factory. We have all kinds of little assembly lines throughout the body manufacturing various substances. All of these assembly lines are operated by enzymes. The enzymes are the worker bees. One specific enzyme catalyzes one reaction in the assembly line. Just like an assembly line, each worker (enzyme) adds (or in some cases subtracts) one part of the process. One enzyme hands the product to the next, which then adds the next step and passes it on.

We don’t have all these enzymes circulating around all the time. There are simply way too many of them. Our DNA contains the codes for them, but we don’t go through the energy-consuming process to actually produce them unless we really need them. And when we do need them, they can’t be produced in a nano-second. Depending upon the circumstances, it can take some time to build the enzymes, most of which are extremely complex protein structures.

Let’s look at a for instance.

Those who don’t drink alcohol, or who drink it sparingly (yours truly comes to mind), get inebriated and have hangovers more often than those who drink alcohol regularly. Those who drink a lot already have onboard all the enzymes necessary to metabolize the alcohol they consume fairly rapidly. Those who don’t drink, or don’t drink much, have to make the enzymes before they can do their work. It takes time, so they do suffer the ill effects that those who already have plenty of enzymes ready and waiting do not.

Unfortunately, the production of these enzymes (not just the ones involving alcohol, but all of them) slow down with aging. Like everything else, as we get older, the process doesn’t work as well. But, as with the enzymes catalyzing the metabolism of alcohol, the more often enzymes are put to the test, the more of them there are hanging about and the faster they work.

Some metabolic processes use many enzymes in numerous steps. Others not so much.

Glucose, for example, can be metabolized pretty quickly. It doesn’t have to go through a long, arduous process with many inhibitory points along the way to end up converted to ATP, the energy currency of life.

Fat, on the other hand, does have to go through quite the gauntlet before it can be converted to ATP. Fat has to first get into the mitochondria, the organelles within the cell that produce the vast majority of the body’s energy. Through a complex process, if there is a lot of glucose floating around because of carb consumption (or diabetes), the fat can’t even get into the mitochondria. The doorway is closed if there is too much glucose.

Instead fat is converted to the storage bin, i.e., fat cells or adipose cells.

If the fat does make it into the mitochondria, it still has to go through a fairly laborious process called beta-oxidation, which requires four steps and multiple enzymes, to be chopped into two-carbon molecules, which are then fed into the Krebs cycle. Once the fat has two of its carbons chopped off goes back and repeats the same process again to have two more carbons chopped off. This continues until the entire fat molecule has been broken down into two-carbon chunks. And that’s just the fats with an even number of carbons. Those with an odd number go through a different process. (See what I mean. It’s kind of complex.)

When the fats are broken down into two-carbon chunks and combined with coenzyme A, they are called acetyl Co-A and are then shunted to the Krebs cycle, where they go through yet another energy-extracting process.

Carbs don’t have nearly that much of a hurdle. They start throwing off energy before they ever get to the mitochondria. Once there, they go directly to the Krebs cycle without having to go through anything like the beta-oxidation process fats go through.

These processes are driven primarily by the insulin to glucagon ratio.

If insulin is elevated and glucagon is low, the converting-carbs-to-energy process is favored. And fat is sent to storage. If carbs are low, then glucagon elevates and drives the process in the opposite direction.

But glucagon is not going to be high if a lot of glucose is present. Consequently, a high-carb diet keeps insulin high, glucagon low, and favors the burning of carbohydrate and the storage of fat.

If you are trying to lose excess fat, or to prevent excess fat accumulation, you don’t want insulin to be high. You want to lower insulin levels while increasing glucagon levels.

Eating cupcakes will not help you do this.

Metabolic flexibility worsens with age.

Below is a terrific graphic from a study I read recently. The study is a mouse study, most of which I take with a grain of salt, but the graphic perfectly depicts what happens to metabolic flexibility with age.

I’ve had the same conversation over the years with countless patients.

It goes like this.

Patient: “My 14-year-old daughter (or son) can eat everything and not get fat. All I have to do is look at food, and I gain weight.”

Me: “Were you able to eat everything in sight when you were 14 years old?”

Patient: Looks quizzical. Thinks about it for a few seconds. Then says, “Yes, as a matter of fact, I was.”

Most of these conversations occurred years ago before the widespread use of high-fructose corn syrup and seed oils. Kids are now fatter than ever, so all bets might be off if I were to ask the question now. But I think it still holds true since metabolic flexibility declines with age.

Kids are still better able than adults to deal with incoming food to convert it to energy instead of storing it as fat. Plus, they use some of the energy they consume to fuel growth, whereas adults only have the option of storing it. They don’t grow any taller. (But they can and do grow wider.)

Here is the situation as I see it.

The body pretty much keeps the skids greased for carbohydrate metabolism, because it wants to get rid of them, get them out of the blood. There is a small storage area for glucose in the body. The liver stores ~ 90 g of glycogen, and the muscles store ~ 500 g, which is used only for the muscles in emergency need. The liver uses its glycogen to maintain the body’s blood sugar. The conversion from glycogen to glucose is about 1.1:1. So, essentially, the amounts are the same. For convenience you can think of it as roughly 1:1.

So, that 600 g of glycogen stored in the muscle and liver represents about 660 g of glucose, which converts to 2,640 kcal, which is about a day’s worth of energy. That is all the body stores. It burns the rest.

Fat, on the other hand, has a virtually unlimited storage space. The average 70 kg person, who is not overweight, carries enough stored fat to fuel him (or her) for a walk from St. Louis to Miami. I may be off by a few miles, but you get the picture. It’s a lot of stored energy.

These guys could probably walk halfway around the world.

The path glucose follows to convert to energy is fairly streamlined.

Glucose -> pyruvate -> Krebs cycle -> electron transport chain (ETC) -> ATP

The fat pathway to energy, not so much.

Fat -> gets into the mitochondria (the process is blocked by excess glucose) -> go through beta-oxidation, a four-step process by which the fat is chopped into 2-carbon molecules, -> Krebs cycle -> ETC -> ATP.

The way I’ve described it may not seem like a big difference, but it requires many more steps and more enzymes than glucose goes through.

If we go face down in the carbs, the glucose pathway is totally greased. Glucose flies through it and converts to energy. And it prevents the fats from even getting into the mitochondria, which is where their metabolism begins.

If we eat a high-carb diet, we have at the ready plenty of enzymes to convert the glucose to energy. At the same time, we don’t have as many to catalyze the fat burning process. In fact, we end up storing the fat instead.

Eating a lot of carbs, especially as we age, can make us insulin resistant. What this means is that we have fewer insulin receptors on the surfaces of our muscle cells, the cells that take up most of the excess glucose. Glucose can still enter the muscle cells by diffusion, but the process is greatly enhanced if insulin can recruit GLUT-4 transporters to come to the cell surface and drag glucose molecules in.

What makes us insulin resistant?

Usually too much insulin.

We have insulin receptors on the surface of our cells. But when we have too much insulin in circulation, a few things happen. We reduce the number of insulin receptors; the receptors are blunted; and even the processes downstream from the receptors can malfunction. All of which means it takes a lot more insulin to have the same glucose-uptake effect than if the receptor situation were normal.

We’ve all experienced this ourselves with different receptors.

Let’s say we walk into a room where the smell is awful. At first, we almost can’t stand it, but with time, it gets better. We have smell receptors in our noses, and over time they become resistant to the horrible smell.

We walk out of the room, and we don’t notice anything, because there is no wretched smell.

We stay out in the fresh air for a while, then walk back in the room. The smell about knocks us down. Then we more or less adapt to it.

What happened is that our smell receptors became resistant. Then when we left the room, our smell receptors lost their resistance. When we went back in, the receptors worked great. We almost gagged at the smell, then the receptors became resistant again.

This is kind of what happens with insulin.

If we are in a constant mode of carb consumption, we become insulin resistant. It requires more and more insulin to do the job it needs to do. One of insulin’s primary jobs is to keep our blood sugar within a normal range. If we are insulin resistant, it takes a lot more insulin to do this. But keeping blood sugar in the normal range is only one of insulin’s jobs. One of its other jobs is to store fat.

So while our blood sugar is normal, the excess insulin is storing fat like crazy. And creating all kinds of other metabolic havoc.

Plus, and this is where metabolic flexibility comes in, since the fat we eat is redirected from going into the mitochondria to be burned, it is going into fat storage instead. And since we’re mainly in fat storage mode, the number of enzymes involved in fat burning lessens. It’s not energetically economical for our bodies to have all these enzymes lying around just in case. We can make them if we need them, but it takes time.

Burning fat is a lot more efficient than burning carbs, but it’s not going to happen if we’re insulin resistant.

How do we get rid of insulin resistance? Cut the carbs. Then the body has to convert to fat burning to generate the energy needed for life. And, unfortunately, it takes a bit of time. We have to become fat adapted, which can take anywhere from a few days to a few weeks. During which time we don’t feel our best. It’s sometimes called the keto flu.

But once we’re adapted, we feel fine. And usually have even more energy than before because we’re no longer insulin resistant.

If we load up on carbs, we burn carbs and not fat. And we even reduce the levels of all the enzymes we need to effectively burn fat.

By the same token, we do the same with carbs. If we are on a high-fat, low-carb diet, we will diminish the levels of enzymes necessary to burn carbs. But these return much more quickly than do all the many enzymes required to burn fat. Because, remember, the body wants to get rid of the glucose.

To use a simplistic analogy, shifting to fat metabolism is like opening a closed-down factory. It takes a while. If you need to switch to carb metabolism, it is more like flipping a switch.

If you’ve been on a low-carb diet for a while and, for whatever reason, your doc wants to see a glucose tolerance test, you will be told to eat a bunch of carbs the day before. The reason is that if you’re fully fat adapted, you may not be able to quickly metabolize the carbs given to you in the glucose tolerance test. And your test will come out looking as if you are diabetic, which may be far from the case.

Young people who haven’t been overwhelmed with high-fructose corn syrup and seed oils tend to be metabolically flexible. They can eat pretty much whatever they want and burn it effectively. Unfortunately, that fades with age.

When you’re old and eat a lot of carbs, you store fat. The only way you can reverse this is to reduce the carb intake, restore insulin sensitivity, and burn fat.

Below is a graphic from a recent in-depth article on metabolic flexibility. Take a look to see all the processes that take place when glucose is high. The only one I disagree with is the one I’ve circled in red. If you don’t have insulin resistance, eating carbs will decrease your hunger. But the brain cells can become insulin resistant, too. If that’s the case, it will take a lot more carbs to curb your hunger than if you weren’t insulin resistant.

In looking at the graphic above, you can see that almost everything that happens leads to fat storage. Or to glucose burning. If you look at the heart, you will notice that glucose ends up fueling the heart. The heart burns fat and ketones preferentially, so burning glucose in the heart ain’t all that great.

As discussed above, the best way to reverse metabolic inflexibility is to cut carbs and follow a lower-carb, ketogenic diet. It will enhance your ability to burn fat despite minimally decreasing your ability to burn carbs as effectively. Which shouldn’t really matter because you won’t be consuming a lot of carbs that need to get burned on such a diet.

How do you know the status of your metabolic flexibility? If you are overfat, as measured by your waist-to-hip ratio or by your mirror, you’re metabolically inflexible. If you’ve got type 2 diabetes, you’re metabolically inflexible. Probably the same if you’ve got high blood pressure, kidney issues, or heart problems.

You can always get a fasting insulin and fasting blood sugar to see if you are insulin resistant. But if you’ve got any of the issues described above, you probably are.

I haven’t mentioned it yet, but another way you can improve metabolic flexibility is to exercise, exercise, exercise. Exercise improves insulin sensitivity and fat burning.

If you both exercise and consume a low-carb diet, you’ll have the best of all worlds.

And you may even become smarter.

As I was doing the research on this topic to see if what I thought I knew about metabolic flexibility was still accurate (it was), I came across a nice paper showing that exercise and low-carb dieting improves brain-derived neurotrophic factor (BDNF). (Disclosure, one of the authors of this paper is Tim Noakes, who is a friend of mine. But I didn’t realize this until after I read the paper and took a look at the authors. Make of it what you will.)

You may not be aware of BDNF or what it does. The below is from the introduction of the study that I have edited for brevity and clarity.

As you can see, BDNF is good stuff. It’s not only involved in metabolism, it increases brain plasticity and function.

Let’s take a look at what the study showed.

Twelve subjects with metabolic syndrome completed a randomized, two-phase crossover dietary and exercise trial. They used themselves as controls. For four weeks they consumed a low-carb Paleo type diet along with remaining sedentary. There was a four-week washout period, then the subjects underwent a four week program of the same low-carb Paleo type diet along with high intensity interval training.

The end result showed that the LC Paleo diet alone increased improved variables for cognitive function, including increased peripheral serum BDNF levels 20 percent, psychomotor speed and cognitive flexibility -14 percent (lower is better – they were able to think and perform faster), and self-perceived cognitive symptoms and functioning +8 percent.

When the high-intensity interval training was added to the LC Paleo diet for four weeks, the outcome improved even more. The increase in BDNF was almost doubled to 38 percent. The psychomotor speed and cognitive flexibility were still -14 percent (the only outcome that didn’t change, but stayed the same). Their self-perceived cognitive symptoms and functioning doubled to 16 percent vs 8 percent via diet alone.

The subjects’ BDNF inversely correlated with their percent body fat, fasting glucose , triglycerides, and insulin sensitivity. In other words, all those parameters got better as BDNF increased.

I guess the take-home message here is that the low-carb, Paleo diet alone brought about significant BDNF changes even while the subjects did nothing but sit on their duffs for four weeks. But adding pretty intensive exercise made it even better. By double, in fact, for two of three parameters studied.

It wasn’t studied in this paper, but in other papers I have read, BDNF also increases with intermittent fasting.

Ultimately, metabolic flexibility comes down to reclaiming your ability to move seamlessly between burning glucose and fat, instead of living in a permanently carb-locked, insulin‑resistant state. When insulin is kept in check through lower carbohydrate intake and regular movement, fat can once again reach the mitochondria, be oxidized efficiently, and support everything from body composition to cardiac and brain function.

What this means in practice is pretty straightforward, even if the underlying machinery is not. If you are obese, hypertensive, or on the spectrum of metabolic syndrome, assume your metabolic flexibility is impaired and treat it like a modifiable risk factor, not a character flaw.

Shift your default diet toward a lower‑carbohydrate, higher‑protein, higher‑fat pattern, add exercise that challenges both your muscles and your mitochondria, and give yourself enough fasting time between meals for insulin to fall and fat oxidation to rise. The upside is not just better glycemic control and easier access to stored fat, but also improvements in BDNF, cognitive performance, and overall brain health – benefits that become increasingly valuable with age. In short, restoring metabolic flexibility is less about chasing a number on the scale and more about rebuilding robust enzymatic and hormonal capacity, allowing yourself to fuel your life from whatever substrate is available at the moment.

With greater metabolic flexibility, you’ll be able to eat a lot more of what you want most anytime. You just can’t eat everything you want all the time. But that’s a small price to pay for vastly better health, cognition, and longevity.

1. When I ran this Arrow through AI to check for typos and other mistakes, it came back telling me there was a disorder of too much fat: fatty liver disease. It’s really not a disease of fat itself, but of fat misplaced. Typically, cutting the carbs reduces fatty liver disease, so I would consider it a disorder of too many carbs.

Odds and Ends

• Your great-grandmother's slang (in MD's and my case our grandmother's as well.)

• Paul Revere's midnight document chase was maybe just as significant as his ride.

• I love weird words, thus this list of unusual ways of expressing emotions called my name. 

• New gigantic dinosaur species found, heavier than four African elephants, called the last titan of Thailand. Catchy. Sounds like the headline on a carnival sideshow poster, but I'm not sure how they know it's the last.

• What could be 'about as welcome as a root canal'? Surely almost anything, but the idea that those occurred 59,000 years ago frankly amazes me. 

• Well-preserved Medieval Latin notebook found in excavation of a German latrine. Maybe there's still hope for that one AirPod I dropped down the flushing toilet about a week after getting them.

• Rubik's Cube Art? A creative urge can take you so many directions.

• 6 subjects no longer (or rarely) taught in schools these days. And the kids are the worse for it IMHO. Latin, for instance. MD took four years of Latin in high school in the late 60s and early 70s. Now it's a rarity. Happy to say all three of our boys and most of our grandsons have at least had a year or two of it. One is but 4, so he won't have his chance for a while yet.

• English words can mean something very different abroad. So speaker beware -- some of these I knew; some I didn't.

• Don't shoot till you see the whites of their eyes, so said General William Prescott before the Battle of Bunker Hill. Humans are the only primates to have white always visible around their irises. Ever wonder why?

• The Roman vomitorium wasn't what you might think. 

• Are some given names in danger of going extinct? The oldest first name still in use in the US is apparently Myrtle with an average age of 84 for people bearing it. That was my dear granny's name, and to be fair, she loathed it. MD's mother was Edith (Edith Mary to be precise) which had been HER grandmother's name, and it's also one in the 'endangered' zone. Is yours endangered?

• What would a tavern menu from 1776 have looked like? I found this completely fascinating.

• It's been said that one of my favorite literary icons, Dorothy Parker, answered her telephone with, 'What fresh hell is this?' which I find hilarious and too often appropriate. But we now most all say 'hello' and here's why. 

• 600 year old Chinese surgical instruments coated in an anesthetic compound derived from poisonous plants. As Paracelsus remarked: the dose makes the poison.

• You've likely heard of some of these unusual bird names, like the Blue Footed Booby or the Laughing Kookaburra but many on this list of 100 best bird names will give you a smile. And smiling is always good.

• MD and I visited Gaudi’s architectural masterpiece Sagrada Familia on two different trips to Barcelona. It's taken 144 years to complete, and it is amazing. Build it yourself in less time with the newly released 12,600 piece Lego set.

• Incredible underwater find from the time of the American Revolution-- I'd love to go see these when they're finally displayed. 

• Let the herd be thinned.

Newsletter Recommendations

Video of the Week

The VOTW is a great example of how some people are just put together differently. In most cases, it is a matter of genetics. You can take two guys with the same height, same weight, and roughly the same body composition, and one can throw a fastball at 100+ miles per hour, while the other probably couldn’t throw it at 60 miles per hour.

What’s the difference?

They are hooked up in a different way. Where the one guy’s ligaments are attached just a little differently, but that difference is what makes his fastball hum. The other guy could work the rest of his life and never come close to throwing a fastball at 100 miles per hour.

The guy in the following video is a man who is just hooked up right. Despite his relatively small frame, he can lift enormous amounts of weight. More so than heavily muscled gym rats.

What I especially love about these videos (there are a number of them) are the looks on the meat heads' faces when he seemingly effortlessly outlifts them. I could watch his videos all day long.

Here is another. Hilarious.

Time for the poll, so you can grade my performance this week.

That’s about it for this week. Keep in good cheer, and I’ll be back soon..

Please help me out by clicking the Like button, assuming, of course, that you like it.

This newsletter is for informational and educational purposes only. It is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice.

Thanks for reading all the way to the end. Really, thanks. If you got something out of it, please consider becoming a paid subscriber if you aren’t yet. I would really appreciate it.

Finally, don’t forget to take a look at what our kind sponsors have to offer: HLTH Code, Precision Health Reports, and Jaquish Biomedical.

And don’t forget my newest affiliate sponsor Lumen. Highly recommended to determine whether you’re burning fat or burning carbs.