The Arrow #166

Hello friends.

Greetings from Montecito.

Over this past week, I’ve been immersed in trying to figure out how the new platform works. It is vastly more complex than Substack, so I have a lot more to learn. But, strangely, it is also a bit less sophisticated than Substack in other respects.

An aggravating aspect is that every single thing I’ve tried to find out by entering a question in the help window has come back with a response not providing an answer to my question. But, the same thing happened with Substack. I had to fill out a help request there because I could never find what I was looking for with their help search.

In both cases, when I fill out a help request, I get a bounce back email telling me someone will get back to me within 48 hours. It’s strange in both cases that most of what I’m looking to find out is not available in the vast array of videos and other help resources.

Substack has a much better comment set up than the new platform. There is no character limit on Substack whereas there is one here. The max is 1,000 characters. I haven’t made a help request yet, because I haven’t finished going through all the provided help sources. Once I do, if I can’t find the answer, I will send an inquiry.

The reason I don't do this right off the bat is based on my many experiences doing book signings in bookstores all over the country. If I’m looking for a book, I go into a book store and look for it. Having been in hundreds of them, I pretty much know how bookstores are laid out. So I wander through until I find the section the book I’m seeking should be in. Then I search for it alphabetically by title or author (depending upon the preference of the store). I’ve done this in bookstores the world over and have usually found the book I’m seeking. When I don’t find it in any of the places it should be, I may ask one of the staff people for help. Usually, I’m told they don’t have the book.

When I was doing book signings all the time, the bookstore staff usually set the thing up close to the front door. I can’t tell you how many people burst through the door, accosted the first staff person available, and said “do you have [insert title] book?” People don’t walk through the door at Macy’s and ask the first person they see if the store has Hermès ties. Why would they do that in a bookstore?

I feel the same way if a company has gone to the trouble to develop a huge collection of help videos and articles. I like to wander through them looking for what I’m seeking, and, like in bookstores, often getting surprised and delighted by what I do find serendipitously. Only if I can’t find it roaming through do I ask for help.

Having said that, I really do want to find out if the comments section can be modified.

There is one comment issue I can deal with. This one just came in as I was writing the above. I had a few people who commented and wanted to know if their comments ever got replied to. It’s pretty obvious in Substack, but not so much so here. If you look beneath the comment (yours or another’s), you’ll see a little dialog bubble. If it has a number in it, that means there is a reply to the comment. The number tells how many replies there are. In the one shown below, there are three replies to the comment above. Of course, all you have to do to reply to a comment is to click on Reply (shown below), and a dialogue box will open for your comment.

One thing I did discover that I found delightful was that people could comment on the poll I put up at the end. And, I assume, on any poll I put up wherever. These comments show up in a little window alongside the poll data.

I’ll list some of these in a bit and comment on them.

You may notice a change in how The Arrow looks as we go along. I’ve been learning how that works, so have fiddled with it a bit. This version will look a bit different than last week’s. And I suspect next week’s will look different than this one.

Okay, on to some of the comments.

First, I’ve gotten comments on the poll and comments in emails from people saying they couldn’t open the YouTube of the Blues Brothers. I suspect this is due to a browser update issue. Sometimes old browsers or new browsers that haven’t been updated have difficulty with videos and other links. I got many comments from people who loved the video, so I know a lot of you were able to open it. If you’re having trouble like this, try updating your browser.

Here was another:

Just witness[ed] first hand (me) 2 ingrown toenails and Doc totally ignored them short of antibiotic ointment recommendation!

This is a public service announcement. If you have an ingrown toenail similar to (or worse than) the one I showed the photo of last week, antibiotic ointment won’t do squat. It has to be fixed. If your doc tries to give you antibiotic ointment or an oral antibiotic, he/she doesn’t know how to fix an ingrown toenail, so head for the nearest podiatrist. More on the toenail post in a bit.

Here is another:

“I wonder how many of your readers know who Joe Friday was.”

I guess I’m showing my age here. One of the early shows on television was Dragnet featuring LAPD detectives Joe Friday (played by Jack Webb) and his partner Bill Gannon (played by Harry Morgan). One of Joe’s oft repeated lines when dealing with a witness was, “Just the facts, Ma’am (or Sir)” Look up Dragnet on YouTube if you want to see some scenes from a 1950s/1960s detective drama.

There were also multiple comments saying there was no Like button.

There is, but it took me a bit to find it, too. It’s on the left side of the online version of the post. It’s in an array that looks like this blown up version:

If you click the arrow pointing left, you get taken back to the top of the post (this little display stays on the left all the way down the post). The heart is the Like button. (I guess you don’t just get to like it; you have to love it.) The little conversation bubbles are the comments. The other thing with the two lines and the three circles (I have no idea what it is called. Someone enlighten me, please) expands when clicked to what is shown. If you click any of those icons, it will allow you to insert the entire post into whichever social media you click. The upper left one inserts it into an email, so you can forward it to someone.

Finally, in last week’s Arrow I looked at the wildly incorrect statistics on babies born to mothers who had conceived during rape. I could not find statistics on the odds of a woman getting pregnant after one random act of intercourse. Based on the stats I could find on odds of getting pregnant at particular times, I estimated the rate to be ~5 percent on a one off case at a random time.

Thanks to a reader who sent me a link to a paper on the very subject I had been seeking, it turns out the percentage of pregnancy in a woman of childbearing age is ~3 percent. So the stats I stated last week based on my guess of 5 percent are even lower.

Now let’s get back briefly to the ingrown toenail and the use of a local anesthetic to deaden the toe.

How To Deaden a Toe or Finger or the Tip of a Nose

What follows is kind of an inside baseball like discussion of local anesthetics used in fingers, toes, nose tips, and, believe it or not, penises. If you have no interest, skip on down.

When I wrote in the last Arrow that the doc was unenlightened about the use of the combination of lidocaine ( a local anesthetic) combined with epinephrine (a vasoconstrictor that prevents bleeding and keeps the lidocaine in place prolonging anesthesia), I didn’t realize there was a controversy. I was taught in medical school in no uncertain terms that you should never use this combo on fingers, toes, penises, and noses out of a worry than you could cause gangrene due to a lack of circulation.

Right off the bat, I received this email in part saying:

I'm a family doc in northern California and have a comment on your recent outrage over toenail removal. I absolutely side with you in support of removing ingrown toenails in primary care and find it professionally satisfying AND beneficial for my patients. Shame on this doc for watering down our noble profession and punting to the specialists! However, you are uninformed on current evidence regarding use of vasoconstrictors for digital blocks on extremities. Current recommendations support the safety of lido with epi for most patients and vasoconstriction is beneficial for pain relief and hemostasis during the procedure. Exceptions would include patients with peripheral vascular disease. Here is a sample article reviewing this topic. This medical lore continues to be passed down and I do my best to educate colleagues on the safety of lido with epi for toenail removal, so I was a little disappointed that someone as well read as you hadn't come across this yet. I'm happy to give you a pass this time as I imagine it's been quite a while since you dove into the latest stimulating literature on toenail removal. 😉 [Link in original]

I responded that I learned it the way I described it in medical school. MD graduated a couple of years after I did, and she learned it the same way. But that was a long time ago for both of us. I appreciated the updated info, and said that I was willing to change to keep up with the times.

Then I received this missive from Medscape, the same online medical subscription journal that inspired my rant, titled Bigfoot, Bermuda Triangle, 'No Lido With Epi'?

As it turns out, this is a controversial topic. And not at all settled. Docs on both sides of the debate chimed in.

Combining epinephrine with lidocaine helps make the numbing last longer, stop bleeding, and reduce the use of lidocaine required, all of which improve the chances of an effective and comfortable intervention for the patient, Lin [the doc I criticized in the last Arrow] said. The approach also reduces the use of tourniquets, which come with their own risks including nerve injury. [I have never had to use a tourniquets.]

However, in areas with limited circulation, this vasoconstrictive effect may be more pronounced, potentially leading to complications for patients with complicating factors.

Clinicians who regularly use the combination of epinephrine and lidocaine for surgery do concede that it can pose certain hazards and considerations in areas without robust blood flow.

But the literature largely points to its safety.

But then the article goes on to lay out the arguments for each side. The folks opining on the use of lido with epi all said the studies, such as one linked in the email I posted above, showed the complications were rare.

But then this:

Marie Hanna, MD, MEHP, chief of regional anesthesia and acute pain management at Johns Hopkins University, in Baltimore, Maryland, counts herself among the cautious. Citing Principles of Office Anesthesia: Part I. Infiltrative Anesthesia, Hanna said epinephrine should never be used in digital and penile blocks or in skin flaps with marginal viability.

"It is perfectly fine in certain areas, like the wrist or the arm," Hanna said. "But specifically for use in end organs like nose, fingers, ears, toes — all of these with tenuous blood supply — it is not good practice." [Link in the original]

The Medscape article kind of summarizes the debate by calling the worry about use of the combo a “medical myth.” Then goes on to say that if a procedure goes awry and you end up being sued over it, you don’t want the opposing lawyer to know about the medical myth.

I’ve never worried about getting sued; had I worried about getting sued, I would never have treated patients with elevated LDL with low-carb diets. I worry more about the outcome for the patient. If the downside is the loss of a fingertip or anything else that is avoidable, I’ll eliminate that possibility. I can fix an ingrown toenail so quickly that I don’t need any kind of long-term anesthesia and bleeding is usually minimal.

Okay, here is my weekly plea for paid subscribers. It costs pennies a day and is hugely enlightening. Where else can you learn about the proper injectable anesthetic mix for an ingrown toenail repair. That alone is worth the price. Imagine yourself on the savannah with the sudden onset of an ingrown toenail. You’ll be glad you forked over. Just click the upgrade to paid button below, and you’re in business.

A number of commenters both via email and the comments section brought up what must be a recent article by Dr. Mercola on why he abandoned his long-term low carb diet. Let’s take a look.

Burning Glucose vs Fat and the Randle Cycle

I think I may have written about this a year or two ago, but it’s probably well worth going over again, especially in view of the recent Mercola article. I had a few phone conversations with Dr. Mercola several years ago—about what I can’t even remember now—and he is a very nice man. But he and I have a major disagreement over the section on the Randle cycle he wrote in one of his recent newsletters.

One of my correspondents sent me a link to his recent commentary, and when I tried to open it, I got the message below in flashing lights.

I was then taken to his most recent article, which had nothing to do with the Randle cycle. My correspondent then sent me a pdf file of the article in question. I’ll reproduce what I need to in an effort to explain our differences of opinion.

It’s a long article broken up into many sections, much like The Arrow. In the section titled “Why I Changed My Mind About Low-Carb Diets, he starts out by saying

One of the foundational concepts of health that I’ve had to radically revise my thinking on, based on the work of the late Ray Peat and his student Georgi Dinkov, is the idea that eating a low-carb diet long-term is the best way to optimize your metabolic and mitochondrial health.

As we will see, based on what he writes later on, both Ray Peat or Georgi Dinkov are (were, in the case of the former) apparently behind in the scientific literature.

The next thing he writes is pretty stunning.

I now realize that this was misguided, and the reason for that has to do with the fact that your body requires glucose and if you aren’t eating it you will go into a hypoglycemic coma and die. [My bold]

I’m sure a lot of you who are reading this have gone for at least a day or two without carbs—I know I have many times—and none of us have gone into a hypoglycemic coma and died.

Dr. Mercola follows that with a sentence that says, “Obviously, your body has safeguards to prevent that and the major one is the hormone cortisol.”

Cortisol is a stress hormone. It is part of of the fight or flight response. If you are confronted by a dangerous situation—say you suddenly come upon a lion—you will have an immediate surge of cortisol. I absolutely, one hundred percent, guarantee it. Coming upon a lion, or, say, getting mugged, is an acute stress, and cortisol will flood your bloodstream.

If we are chronically stressed about finances, divorces, job loss, the frigging Covid lockdowns we secrete cortisol, but not as much as if a snake were to fall on us. But the chronic cortisol does take its toll over time.

Cortisol does stimulate a release of glucose from the liver. We need it because we either need to run from the lion or fight it. In either case, we need a lot of glucose quickly. Not so much with the chronic stress, but we still put out more glucose than we need. Often with consequences over time.

But if we go on a carb-free diet, we aren’t going to get a jolt of cortisol. Nor are we going to go into a hypoglycemic coma and die. Nature has endowed us with a set of compounds called ketones that take the place of glucose in most tissues should we be lacking.

Dr. Mercola goes on in a section titled “How Does Cortisol Work?” to discuss how cortisol works.

But just how does cortisol increase your blood sugar? It does it by breaking down your muscles, bones and brain. It sacrifices your lean muscle mass to release amino acids that your liver converts to glucose in a process called gluconeogenesis.

So, ultimately, cortisol also is going to cause inflammation and impair your immune function. And it increases food cravings. So, you do not want your cortisol to be elevated. For a long time, I was a proponent of a low-carb diet, but now I realize that chronic low-carb is not a good idea.

As a fuel, glucose is vastly superior to fat, and this was something I simply got wrong. [My bold]

You would have to go a long way down the starvation trail before you would lose bone and brain. Your muscle mass, along with your fat mass (more about which later), are the reservoirs for blood sugar, but your production of the ketones that take the place of glucose minimize muscle loss.

As to the sentence about cortisol causing inflammation… Cortisol is an anti-inflammatory agent. Which is why you get cortisone (a synthetic cortisol) injected into your joints if they are inflamed. And why you buy tubes of cortisone at the drugstore to put on red, itching mosquito bites to knock the inflammation down.

He writes

As a fuel, glucose is vastly superior to fat, and this was something I simply got wrong. The same thing goes for fasting. Both low-carb and fasting are great interventions in the short-term for those who are overweight and metabolically inflexible.

However, once you’ve regained your metabolic flexibility, it is important to revise your strategy and add healthy carbs back in, or else these strategies will backfire and lead to decreased metabolic health, compromised mitochondrial function and impaired metabolism. [My bold]

Okay, let’s parse this. He’s correct about both fasting and low-carb being great for dealing with overweight and metabolic inflexibility. But, in my view, at least, he is incorrect in saying “once you’ve regained your metabolic flexibility,” you need to revise your strategy.

This is like saying I’m going to lose 50 pounds, then I’ll be normal and can eat anything I want without gaining weight. Just like I did as a kid.

All too many of us have discovered the falsity of that statement. Some of us multiple times.

It is my view, after a long career taking care of a lot of overweight patients, that once your metabolism is broken, it pretty much stays broken. You can keep it operating as if it isn’t broken as long as you follow your low-carb diet. In the case of most people, they can never go back to eating whatever they want whenever they want all the time. Sure, you can blow it out from time to time, but if you go back to your old diet all the time, you’ll go back to your old weight. Probably a little higher in weight, in fact.

Metabolic flexibility is the ability to metabolize whatever you have coming in without consequence. Most of us could do it as kids. I, for one, ate everything that wasn’t red hot or nailed down. And I never gained an ounce. I wanted to gain weight because I played high school and college football. In that sport, everyone wants to be bigger. I was no exception.

I remained that way—unable to pack on the pounds—until I hit my mid-thirties, then it all came on with a vengeance. I had lost my metabolic flexibility. At least in part on account of the anything-and-everything-without-gaining-a-pound diet I indulged in when I was younger.

Since I started low-carb dieting, I’ve been able to keep my weight pretty much in check. But I work at it. As I’ve learned from bitter experience, if I don’t, here comes the excess weight. So I have lost my metabolic flexibility. I can’t eat everything I want, every time I want to without paying the price. Sucks, but that’s life once you’ve blown your metabolic flexibility. Better to never lose it in the first place, but when people have it, they don’t think they’ll ever lose it. So they seldom do what they need to do to preserve it.

So, going back to the Dr. Mercola quote from above, you can’t just get down to your goal weight, proclaim that you’ve regained your metabolic flexibility, and start throwing back the carbs willy-nilly. If you try to add the carbs back in, you will be setting yourself up for trouble. Trouble with a T that rhymes with P and stands for FAT, to paraphrase The Music Man.

If you decide not to go face down in the carbs after you’ve worked so hard to lose all your weight, or reverse your type 2 diabetes, or whatever, I guarantee you your mitochondria will be just fine. Their function won’t be compromised one bit.

If you decide to eat what Dr. Mercola says he eats, then all bets are off.

And now I eat 3 to 4 pounds of watermelon virtually every morning at 5:30 as my first meal, followed by three eggs and 8 ounces of white rice and 2 ounces of maple syrup one to two hours later.

That sounds like a lot of carbs, and it is. I have additional fruits later in the day and now my carb intake is about 475 grams a day.

Well, a pound of watermelon is 34 grams of carb, so 3.5 pounds would be ~120g then the rice would 46 and the two ounces of maple syrup adds another 36g, which totals to 202g of carb, which breaks down in the GI track to a bit over a cup of sugar. To start the day. Then another 275g of carb over the rest of the day.

Dr. Mercola goes on to describe how on this diet he dropped his weight from 192 pounds to 182 pounds while maintaining the same muscle mass. God bless him! I’m not saying it didn’t happen. I wasn’t there to observe. But I can say I’ve never seen it happen like that to anyone else.

How does all this magic happen?

Through the agency of the Randle cycle, so he says.

What’s the Randle cycle?

It’s an hypothetical construct published in a paper in 1963 written by a British scientist named Philip Randle, after whom the cycle was named.

The hypothesis seemed to make sense, and it was adopted by most everyone over the succeeding three or so decades. Researchers nibbled around the edges of it, but no one really proved (or disproved) it existed as a body-wide phenomenon. Until Robert Wolfe took a look at it.

In the mid 1990s, Wolfe's group did kind of a deep dive on the Randle cycle and determined that for the most part it did work. But in the opposite way Philip Randle thought it did. In other words, the Randle cycle ran in reverse.

In hypothesizing his eponymous cycle, Randle thought that increased oxidation (burning) of fat prevented the oxidation of glucose. In other words, if you ate and consequently burned a lot of fat, your body couldn’t burn as much glucose, and your blood sugar would go up. If, on the other hand, you consumed a lot of carbs, your body would burn those carbs, and not as much fat. Had Randle been correct, then the recommendation to those with type 2 diabetics to eat a lot of carbohydrates and keep fat low would have been on the money.

Same for obesity.

And that is basically the advice we were all given, yet over the intervening years both type 2 diabetes and obesity have gone through the roof.

In the mid 1990s, Robert Wolfe, through some clever experimentation, showed that it’s almost the opposite.

Wolfe et al showed that fat oxidation doesn’t have much effect on what glucose does. You can have a lot of lipolysis (basically fat moving from inside the fat cells into the circulation) and it has little effect on what happens to glucose levels in the blood. Running blood sugar up by eating a bunch of carbs, however, stimulates the release of insulin, which pretty much slams to door on lipolysis.

So, using the same reasoning people do when they believe lipolysis and fatty acid oxidation control blood sugar levels, knowing the system runs in reverse should make them believe the opposite. In other words, don’t worry about fat, just control carb intake.

But obviously Dr. Mercola’s go-to people haven’t gotten the message yet that the Randle cycle runs in reverse.

Dr. Mercola starts off his section on the Randle cycle with the title “The Vital Metabolic Switch You Need To Understand.” Then he writes

This is one of the most important principles in food science that I never learned or understood until recently. My strong guess is that this is also true for most natural medicine clinicians. That is why I created the figure below to help you visualize so you can better understand this vital concept.

Unfortunately, I don’t think he understands it yet. He created the graphic below to help his readers better understand the workings of the Randle cycle (as he understands it).

Take a look at it long and hard and tell me if this graphic makes any sense to you at all. There are no arrows showing what does what. It’s just sort of a bunch of boxes, diamonds, and ovals with words in them.

It reminds me of a marketing group I once hired to help us sell a weight-loss product we had developed. The mechanism of action was complex, and required a lot of explaining at a pretty technical level. I told the marketing folks that one of our big problems was that we didn’t have a quick and easy answer when someone asked us how the product worked. They told me, Ah, don’t worry about that. We’ll just put up some diagrams. Then the customers will know there is science involved. I said, Uh, the diagrams would have to be incredibly complex, and laymen wouldn’t understand them. They replied, No, no, no, you don’t want technical diagrams. That will just confuse people. We’ll come up with some that looks science-y. That’s all they need to know.

Needless to say, we didn’t take that route. But that’s what the above diagram seems like to me. Just something that implies science is involved. And the Randle cycle, of course. And everyone will know it’s science.

Dr. Mercola goes on to write

Low-carb diets have helped at least tens of millions of people improve their health for a very good reason and that is there is a stealth switch that controls what fuel your mitochondria can burn as they can only burn one fuel at a time: either fat or glucose.

The switch has been given the name the Randle Cycle, but it is more helpful to visualize it as a railroad switch that changes the tracks of the train, and the train can only travel down one track, not both. This is because only one type of fuel can be burned at a time.

The above is simply not true. All fuels—fat, carbohydrate, and even protein—are converted to acetyl CoA. Acetyl CoA is the big energy/materials clearing house. Everything pretty much feeds into it and can be converted to almost anything else. If energy is needed, all the fat, protein, and carbs ultimately convert to acetyl CoA, which then feeds into the Krebs cycle. As the Krebs cycle turns, NADH and FADH are thrown off, which carry high-energy electrons to the electron transport chain where they are use to maintain the electrochemical gradient that ends up making ATP. About 85-90 percent of the ATP you make every day is made via this process. When the electrons get to the electron transport chain, it doesn’t know where they came from and it doesn’t care.

So, the idea that the mitochondria can burn only one fuel at a time is simply not accurate. Now there are some things that inhibit this a bit or accelerate that a bit, but overall all fuels end up throwing off the high-energy electrons that provide the energy to churn out the ATP.

I spent about 30 minutes looking for a graphic online to showing how everything feeds into or out of acetyl CoA, which ultimately merges into the Krebs cycle, which dumps high-energy electrons into the electron transport chain. Everything I found was either too complicated or too simple. Below was the best I could come up with without creating my own.

More from Dr. Mercola. He discusses how incredibly energy efficient burning glucose is. As we’ve shown, it isn’t any more efficient than burning fat. In fact, it is less so. Each glucose molecule has to go through glycolysis before it can be cleaved into two molecules of pyruvate, which then feed into the Krebs cycle. Fat also goes through a process called beta-oxidation in which it is broken off bit by bit before entering the Krebs cycle. The process of beta-oxidation fires off high-energy electrons that go directly to the electron transport chain.

There is some net production of ATP in the process of glycolysis, but not as much as there is in beta-oxidation of fats. So, overall, fats generate vastly more ATP per molecule than does glucose.

Here is what Dr. Mercola writes (he is discussing how much energy glucose produces when it is burned in the mitochondria):

…it is also incredibly efficient at energy production by creating 36 to 38 adenosine triphosphate (ATP) for every molecule of glucose that is metabolized. It will also generate metabolic water and carbon dioxide, which are also important for your health.

For this to occur, as indicated in the figure above, you will need to consume less than 30% of your calories as fat. When you consume significantly more than that amount the switch changes to burn fat in your mitochondria and you will not be able to burn glucose until your fat decreases to less than 30% of calories.

Since glucose is unable to be shuttled into the mitochondria to burn, it winds up backing up into your blood stream, raising your blood sugar. This is a major contributor to diabetes. What little glucose is burned for fuel is done by using glycolysis which is a primitive pathway that bacteria and cancer cells use.

I mean what can I say. This is absolute nonsense, especially the part about how you will be able to burn only a little glucose through glycolysis. All of your glucose goes through glycolysis and converts to pyruvate, which, as we’ve shown above, feeds into the Krebs cycle, which strips it of high-energy electrons and sends them to the electron transport chain.

The above can be done only if oxygen is present. If there is no oxygen, then the only way to produce energy is via glycolysis, which only throws off a couple of ATP. We end up using glycolysis for energy when we are operating under anaerobic conditions, i.e., not enough oxygen. That happens when we do some sort of high-intensity exercise. Which is why we can’t do such exercise for any length of time. Dr. Mercola is correct in that a molecule of glucose can produce 36-38 ATPs. But only if burned in the presence of oxygen. What he doesn’t say is that a molecule of fat will produce significantly more ATP.

As long as there is oxygen, you burn both fat and glucose. You probably spend 99+ percent of your time operating aerobically, so you are almost never dependent upon glucose alone.

After having written this long description of why Dr. Mercola’s take on the Randle cycle is the reverse of what it should be, mainly because Dr. Wolfe’s experiments demonstrated the Randle cycle to run in reverse to the way Dr. Randle presented it. (I’ve got to say Dr. Wolfe isn’t the only one to say this. At a meeting in Dallas in 1996, MD and I discussed it with Dr. Denis McGarry (RIP), one of the giants in the field and a prince of a guy. He told us he thought the Randle cycle ran in reverse, but wasn’t ready to go public with his thoughts because of what it would imply about the current dietary dogma. Dr. Wolfe spoke at the meeting about his experiments. We had our conversation with Dr. McGarry after Dr. Wolfe’s talk.)

At the end of Dr. Wolfe’s paper—which was the one he presented at the Dallas meeting in 1996—he writes the following (which I have edited minimally for clarity. You can read the entire article here.

Although it is clear that the traditional glucose−fatty acid cycle is flawed, it clearly would not have endured so long if it had absolutely no merit. Indeed, in many circumstances, some fatty acid effect on glucose can be shown, even if glucose availability predominates in importance. The modest increase in fatty acid oxidation during exercise when fatty acid concentrations were elevated... Thus, whereas glucose availability predominates in determining the mix of substrate oxidation, there is a reciprocal relation between glucose and fatty acids in which fatty acid availability also plays a role, albeit a minor one. This is to be expected, considering that the mechanism whereby glucose inhibits fatty acid oxidation is by limiting their entry into mitochondria by inhibiting carnitine acyltransferase. For any given enzyme activity, within some range of substrate concentration, a greater concentration of fatty acids will cause more fatty-acyl-CoA to be transferred to the mitochondria… whereas our explanation of the normal relations between glucose and fatty acids places great weight on glucose availability as the controlling factor, the mechanism whereby glucose controls metabolism can be overridden to a modest extent when there are large changes in fatty acid concentrations. Furthermore, a direct effect of fatty acids on glucose clearance may also exert some control over substrate oxidation in certain circumstances, provided that the actual rate of glucose uptake is impaired.

In essence, there are a few situations in which fatty acid oxidation has some minimal control over glucose oxidation. But not many, and when those situations exist, fatty acids play a minor role.

Soybean Oil: Bad In Yet Another Way

I came across a paper this week I found both interesting and disturbing.

Before I get into it, I need to issue the caveat that it is a mouse study. But studies like these often don’t get approved with human subjects. If you find that something bad happens with mice or rats, then it’s sometimes more difficult to get approval to test the same thing on humans.

Plus, the mice can be sacrificed to look at their brains. It would be extremely difficult to get approval for such a study in humans.

The study looks at what happens to mice brains when they consume soybean oil.

Just for context, before we get into the guts of the study, I want to remind everyone about just how much soybean oil we consume.

The graphic below shows how vegetable oil consumption has increased over the past decades.

I apologize for this chart being so difficult to read, but that’s how it came. The lines all bunched on the bottom are lard, butter, beef tallow, and margarine. The blueish line screaming upward is vegetable oil.

The chart below shows just how much of this vegetable oil comes from soybeans.

As you can see, soybean oil makes up the vast majority of the vegetable/seed oils we consume.

You might be asking yourself, how do we consume so much? You might be saying, I never use soybean oil, so where does all this consumption come from?

Well, it comes from both dining out and eating ultra-processed packaged foods (if we really want to call them food).

Below is a chart I’ve used in a couple of talks I’ve given showing the increase in dining out since the 1960s.

Back when I lived at home in the 1960s, we never, ever went out to eat. My mother prepared all of our meals, and we ate a home. According to this chart, so did most everyone else. But that has changed. This chart ends at 2013. I’m sure that a more up-to-date chart would show an even greater increase in meals away from home.

Back about 15 years ago (maybe more) I went undercover at a restaurant just to check things out. Here I am pretending to be a chef in an upscale dining place:

MD and I paid to go behind the scenes at a nice restaurant to help prepare a meal for everyone who also paid to do the same. We were all assigned our particular part of the meal to prepare and cook. It was so long ago that I can’t even remember what my assignment was, but it obviously involved chopping spring onions.

While I was in the back, I took the opportunity to sneak around and look to see what kinds of oil they used.

Here’s what I found. A whole lot of this stuff:

And this stuff:

I didn’t take those photos. I remembered the names and looked them up online.

But that’s what they used. Those specific brands. And they used them for everything. And this was an upscale restaurant.

So, these brands of oils and others like them are what your stuff is cooked with and your salad dressings are made with when you dine out. Which is why intake has skyrocketed. Everyone is eating out more often, and the restaurants all use cheaper, crappy oils.

Now, on to the paper.

This same group of authors published a paper in 2015 showing that the linoleic acid (an 18-carbon polyunsaturated fat (PUFA) found mainly in vegetable and seed oils) caused diabetes, insulin resistance, fatty livers, and obesity in mice much more so than did coconut oil and fructose.

In 2017 they published another paper showing the soybean oil genetically modified to contain less linoleic acid did not cause as much diabetes, insulin resistance and all the rest in mice, which was pretty strong evidence that linoleic acid is bad ju ju, at least for mice.

Then comes this current paper looking at what happens to mice brains when they consume a lot of soybean oil.

The study showed a number of brain issues in male mice consuming soybean oil versus coconut oil. The interesting part of this study is that the researchers also tested soybean oil with reduced linoleic acid levels and found no difference. Whereas the linoleic acid had caused the diabetes, obesity, insulin resistance and fatty livers in the mice in the previous studies, in this study both the mice getting the full-linoleic acid soybean oil and those getting the reduced-linoleic acid soybean oil had the same brain findings. Those getting the coconut oil did not have the same changes.

Which indicates, of course, that the brain issues found were not driven by linoleic acid, but by some other component of soybean oil. They tested stigmasterol (a substance I had never heard of), which they speculated might be the culprit, but it turned out not to be.

So there is some component of soybean oil that adversely affects the brain. At least mice brains. And just the brains of male mice, at that.

Among the findings in this study, the one I found most interesting is that the soybean oil caused a dysregulation of the gene expressed in the paraventricular nucleus of the hypothalamus coding for oxytocin. Oxytocin is produced in the hypothalamus, then travels to the pituitary, where it is stored and released. Oxytocin targets the breasts and uteruses of postpartum women and affects other portions of the brain than the hypothalamus. It is called the love hormone and the socializing hormone because of its calming and loving (for lack of a better word) effects.

The researchers found the gene regulating its production to be defective, yet there were elevated levels in the circulation, which tells me the oxytocin made from the defective genes was not functional. They found elevated levels in the circulation of the mice that received both the high- and low-linoleic acid soybean oil, but normal amounts in those that consumed coconut oil.

Usually this means the product of the defective gene—in this case oxytocin—doesn’t work properly and so doesn’t bind to the receptors. Since there is no feedback to say, Hey, we’ve got plenty of oxytocin, the gene keeps signaling to make more. And the levels in circulation go up.

Oxytocin has a calming effect which helps mothers bond with their babies and helps just regular folks be more sociable and friendly with others. This study was in mice, so we can’t directly translate it to humans, but it does make me wonder about all the soybean oil most of us are consuming.

Is that why there is so much partisan rancor and intolerance of opinions of others today? The massive increase in the amount of soybean oil we are all chugging down? Everyone has defective oxytocin, so instead of loving our enemies, we hate them.

Don’t laugh. It’s a possibility.

The authors of the study leave a somber warning about the combined results of their studies.

All told, our results demonstrate that different dietary oils can have differential effects on hypothalamic gene expression and raise the possibility that the SO-rich American diet may be not only contributing to increased rates of metabolic disease but also affecting neurological function.

Okay, this issue of The Arrow is reaching Tolstoyian length. I have another study to go over, but I’ll leave it till next week.

Odds and Ends

Video of the Week

Unfortunately, I don’t have anything as good this week as the Blues Brothers, consequently whatever I put up will be a disappointment. So, I’ll go with one I’ve got.

I’ve been fascinated by the new libertarian leader of Argentina Javier Milei. It will be interesting if he can pull his country out of its financially disastrous position with his policies that go so much against the grain of the previous rulers. We’ll see if the old saw about how a country can easily vote itself into socialism, but it will have to shoot its way out holds in his case.

If he does what he says he will do in this video, there will be an impact. Whether it will be positive or negative will ultimately be known.

I’ll have to say, he has a flair for the dramatic.

I’m sure you would be able to figure this out from context, but just in case, the Spanish word afuera means “out” or “gone.”

Time for the poll. While working on The Arrow today, something went wrong, and I thought I had lost about 2,500 words. I put in an emergency call to my tech guy, who finally got back to me before I totally went into a blind panic. Then, while he was directing me how to check first this, then that, the frigging internet goes out. I’m madly trying to get it hooked up to my phone, which then starts ringing with another call coming in. It all got fixed, but not without a lot of time spent and a lot of angst.

All this is to tell you I don’t have time today to be clever with the poll, so it’s the same old, dreary star rating. Let me know what you think.

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Okay, that’s about it for this week. Keep in good cheer, and I’ll be back next Thursday.

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