The Arrow #150

Hello everyone.

Greetings from Little Rock

MD and I are on a whirlwind trip for the next week or so. Got into Little Rock late last night. MD is visiting her writing sisters today to work on her latest Caddo Bend book, which she is desperate to get out by the end of the year. I’m holed up in a hotel working on this issue of The Arrow. Tomorrow morning we leave for Fayetteville, where the entire family is assembling to celebrate MD’s birthday, which was a few days ago. We’ll be staying there for a few days, then heading back to Little Rock for Thanksgiving with our youngest.

Our anniversary was November 1, which we celebrated by going to the Getty Villa museum. One of our favorite places. We’ve celebrated multiple anniversaries there. Beautiful setting, nice lunch, and terrific exhibits.

One inspired me greatly. Got my creative juices flowing. Next time I buy some real estate, I’m going to have a few of these boundary markers made to delineate the property. No little stakes with flags on them for me after seeing this. What style; what pizzazz. People were so creative and so appreciated beauty two plus millennia ago. It’s shameful how sterile things are today.

I’m certain I’ll be the envy of all our neighbors. Let’s see them top this one.

Don’t Remain Ignorant Due to the Fox News Fallacy

I read about the Fox News fallacy for the first time in an article a couple of weeks ago. I’ve been confronted with it numerous times, but had never had it codified for me until I read about it in a Substack I subscribe to.

The Fox News fallacy is basically defined as blowing off anything presented on Fox News as unreliable. Since the article I read about this was written by a progressive writer, he names the fallacy after Fox News, because the people he is warning are other progressives. He’s saying to Democrats that just because Fox News says prices are up, incomes are down, and many people are suffering isn’t a lie just because that’s how it’s reported on Fox News. And he’s saying that to ignore the situation just because it was reported on Fox News is insane.

If a conservative writer had written the same article, he/she would probably have called it the MSNBC fallacy or the CNN fallacy. It depends on what side of the political spectrum you’re on as to what is a fallacy and what is the truth.

By ignoring or, worse yet, taking the opposite view without any reflection, you end up seeing just one side of an issue.

Most cable news channels slant their news not by outright lying, but by choosing what to cover. If something happens that makes conservatives look good and liberals bad, Fox News will be all over it. And CNN and MSNBC will ignore it. Just the opposite happens if the event is pro-liberal.

If you blow off something just because it was on Fox News, then you are falling for the Fox News fallacy (or the CNN fallacy, as the case may be) and may be denying yourself information you could find valuable.

The reason I’m even bringing this up is because of an email an economist friend sent me a while back. It was about a video I posted in The Arrow of a talk William Briggs gave a few months ago. The talk was totally apolitical. It was about scientific fallacies and how to spot them. Briggs gave the talk at Hillsdale College, which is a conservative liberal arts college in Michigan.

My economist friend, who loved the info in the video, had sent it to a friend of his, whom he thought would also enjoy it. He explained what the video was about and how he thought his friend would find it illuminating. The friend quickly emailed him back just two words. “Hillsdale College.”

The friend was obviously a victim of the Hillsdale College fallacy. And, as a consequence, denied himself a wonderful video. Here it is in case you are not suffering from the Hillsdale College fallacy. It is terrific. And important. And funny.

Modifiable Risk Factors and Risk of Death

A while back a paper appeared in the New England Journal of Medicine (NEJM) titled Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality that is enlightening.

Before I get into the specifics, I’ve got to tell you that the data involved is not from randomized clinical trials, but from observational studies. And, as we all know (or should know), observational studies don’t prove causality. But you can draw certain conclusions from them under particular circumstances.

We’ve all heard the axiom that correlation doesn’t equal causation. And that is true. It doesn’t mean correlation might not actually mean causation; it just means it needs to be tested with a randomized, controlled trial (RCT). But how about the opposite? Does lack of correlation mean there is no causation? That’s a tricky question. And a lot of people argue about it.

In my view, the lack of correlation is stronger in terms of lack of causation than correlation is in terms of causation. If there is no association, then, in my opinion, at least, odds are there isn’t causation.

With that said, let’s look at this NEJM study.

Here is the data chart.

If you look at the middle column, the one titled non-HDL cholesterol, which is another way of saying LDL-cholesterol, you’ll see that the odds of dying are essentially the same irrespective of increases in LDL over all ages in both males and females. There is a downward trend in developing heart disease with increases in LDL as people get older.

All in all, there is not a big risk involved with increasing LDL levels. Yet every cardiologist out there wants to put people on statins who have any kind of elevation above what is considered optimal.

Take a look at the column on the far right. Having diabetes is an enormous risk factor for both developing heart disease and for dying in general.

Now riddle me this. If there is essentially no risk of dying from an elevated LDL level, especially as compared to dying from diabetes, why would any cardiologist contemplate putting someone on a statin when a) LDL levels don’t matter, and b) a significant number of people who go on statins develop diabetes?

It certainly doesn’t make sense to me. Yet I hear from readers all the time about how their cardiologists are threatening to fire them over not taking a statin.

Take a look at the second column from the right, the one on smoking.

Smoking is a huge risk factor for both heart disease and early death. The fact that both heart disease and deaths trail off with age does not mean that you are less likely to die or develop heart disease as you age. It’s an artifact of the survivor bias. All the people who are really sensitive to the effects of smoking have already died. Those who are left alive are a bit harder to kill, but will still die earlier than if they hadn’t smoked.

Seeing this chart got me wondering about statins and heart disease. We know a few facts. We know that cardiologists and even primary care doctors have put everyone and their brother on statins over the past 30 years or so. We know that smoking causes heart disease and early death. And we know that smoking rates have declined precipitously over the past 25 years or so.

Given these knowns, we might assume that the rates of cardiovascular disease would have plummeted over this same time period.

So, I decided to take a look.

In taking a look, I discovered that it is almost impossible to determine the change in incidence of coronary artery disease (CAD) over time. I tried every possible combination of terms I could think of and always ended up with charts and graphs of a decrease in deaths from heart disease. There has definitely been a decrease in deaths (more about which later), but how about in heart disease in general?

I became so frustrated that I actually went to the CDC site. Big mistake. The frustration I experienced with Google was multiplied many times over while dealing with the CDC site. It infuriates me that we—the US taxpayer—fork over billions of dollars to the CDC (and a thousand other government agencies) and yet they can’t make a site that is easily searchable. Unlike MD, who cuts and runs at the first sign of a technical issue online, I can forge ahead and fiddle with it till I get it figured out. But not with the CDC. If I spend more than a few minutes on the CDC site, I become crazed. So, needless to say, I came away empty handed. Which really pisses me off, because I know the data is there.

The closest I came to any kind of graphic showing the incidence of CAD was the one below in an article in BMC Public Health. The graphic showed the change in the incidence of CAD worldwide, not just in the US.

I’m assuming the US would be included in the “High income” category (the dotted green line). As you can see, CAD is falling a bit, but not nearly as much as one would expect given the reduction in smoking, shown below.

The stats I found showed that smoking peaked in the US in 1965, when 42 percent of adults smoked. By 2012, only 18 percent of adults smoked. I suspect it’s closer to 10 percent by now.

If we look at deaths from heart disease, we can see from another graphic in the BMC Public Health article that they have dropped considerably in “high income” countries.

There have been many lifesaving methods developed over the last 30 or so years to jerk people who are having heart attacks from the jaws of death. There are clot busters, stents, medications, emergency bypasses, to name a few. So one would expect a decrease in deaths.

But what about incidence?

Smoking, one of the main risk factors has dropped precipitously. But at the same time, the incidence of diabetes has skyrocketed. And diabetes is a major risk factor for heart disease. Has the increase in diabetes offset what should have been a large reduction in CAD occasioned by the decrease in smoking? If statins are such a wonder drug for the prevention of heart disease, why hasn’t the widespread use of these drugs along with the drop off in smoking significantly reduced the incidence?

I don’t know the answer. But it is interesting to ponder.

Speaking of diabetes…

Diabetes Costs Skyrocket

A new paper in Diabetes Care details the cost of treating diabetes in 2022 was an unbelievable 412.9 billion dollars. That’s billions with a B. $412.9B! Here is what the article says.

The total estimated cost of diagnosed diabetes in the U.S. in 2022 is $412.9 billion, including $306.6 billion in direct medical costs and $106.3 billion in indirect costs attributable to diabetes. For cost categories analyzed, care for people diagnosed with diabetes accounts for 1 in 4 health care dollars in the U.S., 61% of which are attributable to diabetes. On average people with diabetes incur annual medical expenditures of $19,736, of which approximately $12,022 is attributable to diabetes. People diagnosed with diabetes, on average, have medical expenditures 2.6 times higher than what would be expected without diabetes. Glucose-lowering medications and diabetes supplies account for ∼17% of the total direct medical costs attributable to diabetes. Major contributors to indirect costs are reduced employment due to disability ($28.3 billion), presenteeism ($35.8 billion), and lost productivity due to 338,526 premature deaths ($32.4 billion).

Just to put this in perspective, the total United States defense budget in 2022 was $877B, which was more than the next ten countries’ defense spending combined.

So, the cost of dealing with diabetes in the United States was almost half the defense budget, which dwarfs the defense budgets of the next ten countries in the world. In fact, spending on diabetes in the US is more than the defense budgets of China, Russia, and India combined. With some left over for the Saudi defense budget.

This boggles the mind. At least it boggles mine. Especially since diabetes is so easy to correct. (I’m talking type 2 diabetes here, not type 1. The prevalence of type 2 diabetes is over 90 percent of all cases.)

I couldn’t find a graphic showing the increase in prevalence of type 2 diabetes in the US over the past, say, 50 years. Here is the closest I came.

Type 2 diabetes has really gone up since the 1980s when the new dietary guidelines came out. And type 2 has trended with the increase in obesity. Both are probably driven by the increase in insulin resistance and the metabolic syndrome, which is probably provoked by the increase in carbohydrate intake. Which is itself probably driven by the increase in ultra-processed foods.

More about which in a moment. But first, my piteous plea for subscribers.

To become a paid subscriber to The Arrow costs a measly 20 cents per day (19.78022 cents, to be exact, and that’s if you sign up monthly). If you sign up for an annual subscription, it’s only 16.438356 cents per day. A bargain to be sure. And The Arrow won’t raise your insulin or give you metabolic syndrome.

Ultra-Processed Foods

The new nutritional bête noire these days is ultra-processed foods (UPF). Everyone is getting into the act. Even the venerable Wall Street Journal jumped into the fray a few days ago with an entire article on the dangers of UPF.

In my view, UPF are unquestionably problematic. Mainly for what they do to the incretin GIP and insulin levels via GIP. (For those new readers, here are a couple of recent segments on incretins.)

As discussed in these previous segments, the combination of fat and carbohydrate causes the incretin GIP (glucose-dependent insulinotropic polypeptide) to be released from the K cells in the upper small intestine. GIP then signals the pancreas to release insulin. A lot of insulin in the case of the fat-carb combo.

In the first of the segments linked above, I showed a graphic from a study showing how a similar amount of carbohydrate from beans would vastly increase the insulin response depending upon whether the beans were whole or broken up, i.e., processed. The more processing any particular carb undergoes, the greater the insulin response it triggers. Even if the glycemic index of the carb is the same whether processed or not.

For example, in one interesting study, subjects were instructed to eat a pound of apples, after which their glucose and insulin were measured. After a few days, these same subjects ate the amount of applesauce that would be created by the same pound of apples. Again, glucose and insulin were measured. Finally, the subjects consumed the same amount of apple juice that could be extracted from these apples. Glucose and insulin were checked again. When the subjects consumed both the applesauce and the apple juice, they did it two ways. First, they just ate the applesauce or drank the apple juice. As you might imagine, you could eat the equivalent amount of applesauce or apple juice obtained from a pound of apples faster than you could eat the pound of apples. So, the researchers had the subjects also eat the applesauce and drink the apple juice over the same time period as it took them to eat the pound of apples.

Here is the graphic showing the results in terms of glucose and insulin. Bear in mind as you look at this, that both apples and apple juice have essentially the same glycemic index.

Looking at the upper graphic, you can see from the blue smudge that all the glucose levels within the first hour are about the same irrespective of how the apple was prepared: raw, sauced, or juiced.

But you can see from the bottom figure the difference processing makes in the insulin response. The more processed—the juice—runs the insulin way higher than the intact apple. And the sauce (or puree as they call it in the chart) is intermediate.

What I find interesting about this is that the act of chewing the intact apple would reduce it sort of to a sauce, or puree, in the mouth. Same with the beans mentioned above. So you would think the apple and the puree or the intact vs processed beans would give the same insulin response, but such is not the case. Does it have something to do with the saliva signaling to GIP? I have no idea. But something is going on.

The more processing, the greater the GIP, and the greater the insulin response. When you throw fat into the mix, the response is even greater.

As the WSJ points out, most of the UPF are a combination of fat, carbs, and salt. I don’t know how salt figures into the incretin situation, but just the fat and the carbs are enough to send insulin through the roof. If your insulin stays high for a lot of the time, you’ll probably develop insulin resistance and hyperinsulinemia.

According to the WSJ, people are eating a lot more UPF than I would have expected. And I figured it was a lot.

Ultra-processed foods now make up a majority of Americans’ diets. About 58% of the calories that U.S. adults and children ages 1 and older consume in a day come from ultra-processed foods, according to an analysis of federal data collected from 2001 to 2018. Among children, the number is higher—and is growing. In 2018, children ages 2 to 19 received 67% of their daily calories from such foods, up from 61.4% in 1999, according to another analysis of federal data. [Links in the original]

So, if almost 60 percent of calories come from UPF, how can anyone eating such a diet not become insulin resistant?

Since obesity typically follows insulin resistance and hyperinsulinemia, it’s easy to see why so many people are overweight.

In a recent paper, Jeffry Flier laid out the rationale as to how chronically elevated insulin levels drive obesity. Here is his diagram. Let’s walk through it.

Forget the high dietary glycemic load. He’s just talking about carbohydrates in his paper. Let’s look at it in terms of the incretin and insulin response.

Starting with UPF (high carbs and fat) on the left, we see that insulin goes up. If insulin goes up, it drives fat and carbs into the fat cells and glycogen (the storage form of carbs into the glycogen stores in muscle and liver; carbs, however, also go into the fat cells). When fat and carbs leave the blood and go into storage, the amount of fuel (carbs and fat) in the blood decreases. The nutrient sensing system in the hypothalamus (located in the brain) senses that fuel is low, so it increases food intake and decreases energy expenditure. It does this by making us hungry and making us more lethargic. All in an attempt to get fuel back in the fuel lines, i.e., the blood.

When we’re hungry and lethargic, we eat more. Over time this process leads to obesity. It’s a pull phenomenon. The sequestration of fat in the fat cells as a result of chronically elevated insulin levels ends up “pulling” more food into the system by the increase in hunger.

It’s pretty easy to see that if you’re getting almost 60 percent of your food in a form that massively increases the insulin response you might develop a weight problem. Which has happened to countless people since the huge increase in UPF we find all around us.

Of course not everyone believes this. Or at least pretends not to believe it.

“Attempting to classify processed foods as unhealthy simply because they are processed misleads consumers,” says David Chavern, chief executive of Consumer Brands Association, a trade group representing the consumer products industry, including food manufacturers.

What else would David Chavern say if he wanted to keep his job?

Everyone wants to point at addiction and the reward centers in the brain. In my view, the knowledge of how incretins, particularly GIP, work and an understanding of how the pathways in the graphic above operate can explain it all without the need to bring addiction into the picture. Or who knows? Maybe that is the definition of addiction.

In nature, most foods are either high in fat, like meat, or high in carbohydrates (which turn into sugar in the body), like fruit. Ultra-processed foods are often high in both fat and carbs, which causes them to act more potently on the reward systems in our brains and can make them addictive, said Ashley Gearhardt, a professor of psychology at the University of Michigan who studies food addiction. [My bold. We’ve discussed this multiple times.]

One of the things that keeps popping up in this WSJ article and in just about everything ever written about wholesome foods is “whole grains.” No one eats whole grains. They are processed to some extent before they ever get to a human. And once they are processed, even a bit, they end up stimulating the heck out of GIP.

I tried a whole grain once. I was an adolescent and was riding in the back of my grandfather’s pickup as he drove around his farm gathering eggs from the hen houses, slopping the hogs, and doing all the other chores. In the back of his pickup was some freshly harvested wheat. I knew bread was made from wheat, so I decided to peel off some of the grains of wheat and eat them. I figured it would have a bread-y kind of taste.

Nothing of the sort.

I chewed and chewed and chewed and chewed. All I got was a mouthful of a white, slippery, kind of gummy tasteless blob that I couldn’t break down. I kept chewing thinking it would ultimately break up, so I could swallow it. It never did. I ended up spitting the whole thing out.

I now know it was the gluten that held it all together. And I now know the wheat has to be dried and ground before it can be used for much of anything. So, the old “whole grain” thing has never held any fascination for me. The grains have to be processed before they can be eaten. I suppose if you swallowed a handful of unprocessed grains of wheat, you wouldn’t stimulate much of an insulin response. But they wouldn’t be very tasty.

Then the minute you start breaking them apart with any kind of grinding, you’re going to start ratcheting the insulin response. Then add a little fat to them, and your insulin takes off.

This is why UPF are so problematic. Even if they are so-called “healthy” processed foods. Ain’t nothing healthy about them.

According to a new article in The Federalist, the FDA is trying to crack down on all the UPF, but they’re getting pushback from Big Food. And if the boys and girls who work at the FDA aren’t careful, they won’t get their six-figure jobs when they hop from their government jobs into industry.

Earlier this year, General Mills and Kellogg threatened the Food and Drug Administration (FDA) over new rules that could strip the “healthy” labels from the producers’ boxes of chemically processed grains drenched in sugary syrups marketed as cereal. The food companies behind Fruit Loops and Lucky Charms claim the FDA’s latest guidance discriminates against corporate free speech.

“We know cereal is a nutritious, affordable, accessible breakfast choice for many families across cultures, lifestyles, age and socio-economic demographics,” the companies wrote in a joint filing with Post Consumer Brands, the producer of Fruity Pebbles. “Yet, the restrictive criteria put forth in FDA’s proposed rule for ‘healthy’ would disqualify many grain foods, including the overwhelming majority of the ready-to-eat cereals on the market from using the term ‘healthy.'”

Do tell. Can you imagine yourself “threatening” the IRS if it didn’t give you a ruling you liked?

Read the entire article. It’s great.

I just realized the Flier paper above is behind a paywall. Here is a link to the full text from my Dropbox.

Okay, I’ve got a couple of deals for you.

Keto-Mojo

I just got an email from Keto Mojo telling me that all Keto—Mojo meters and strips are eligible for Flexible Spending Accounts (FSA) and Health Savings Accounts (HSA). Since these accounts are going to run out at year’s end, you can use them to stock up on these kits and strips and be ready to test for ketones in your blood. It’s like getting them free. Check it out here. Scroll to the bottom of the website and look for HSA + FSA Eligible.

Gabrielle Lyons Forever Strong Summit

Dr. Gabrielle Lyons has put together a Forever Strong Summit that will take place in Austin, TX on Jan 14, 2024. She will be joined by Bedros Keuilian, Jason Redman, Evy Pompourous, Kirsten Holmes, Don Saladino and Molly Galbraith. Should be a great event. I wish I could go, but I’ve got a speaking gig myself across the country on that date.

She has a couple of packages available if you are interested. A Platinum VIP Package and a Gold Package. She’s giving readers of The Arrow 10 percent off. If you’ve read her book or listened to her podcasts, here’s a chance to meet her.

Wegovy Cuts Heart Disease Risk by 20%

You’ve probably read about this study released last week in the New England Journal of Medicine (NEJM) showing that those who take a weekly injection of 2.4 mg of semaglutide reduce their risk of developing heart disease by 20 percent. Is this really true? Let’s take a look.

First, the manufacturer of Wegovy is desperate to get an indication for treatment other than obesity or diabetes. Why? Because if the drug is approved for the prevention of heart disease, insurance companies will have to pay for it. Right now it is approved only for obesity, which is considered a lifestyle disorder by the insurance industry. They don’t pick up the tab for lifestyle disorders. Its little brother Ozempic is approved for diabetes, so if a patient has elevated blood sugar, he/she can get insurance to pay for Ozempic, even if all they want it for is to lose weight. Getting approval for preventing heart disease could put major bucks in the till for Novo Nordisk, the Danish company that makes Wegovy.

What you have to realize is that all those bucks flowing into Novo Nordisk coffers will result in an increase in insurance premiums for us all. If an overweight patient comes into a doctor’s office and is found to have an elevated LDL (almost all obese people have elevated LDL levels), then, Bingo!, insurance pays. Which means we all pay.

That’s the Novo Nordisk game plan.

Here are the details on the study, which included exactly 17,604 people from 41 different countries. All the subjects were 45 and older, had BMIs of 27 or greater, and had been diagnosed with heart disease. But not diabetes. Ozempic has already been shown to reduce the risk of heart attack in those who are diabetic and are on heart medications. This study is designed to see if people who are overweight and on heart meds (over 90% were on a statin), but who are not diabetic, will have reduced risk.

The 17,604 subjects were randomized into two groups, one of 8803 who got the Wegovy injections weekly. The other group of 8801 subjects were injected with a placebo.

After about three years, 569 (about 6.5 percent) of those getting the Wegovy experienced a heart attack or stroke or died from a heart-related cause. Of those getting the placebo injections, 701 (about 8 percent) had a heart attack, stroke, or died from heart disease.

If you look at the relative risk, which you get by comparing the results from the drug to the results from the placebo, you come up with about 18.8 percent increased risk for those who didn’t take the drug.

But if you look at the absolute risk, you find it differs by only 1.5 percent (8-6.5).

And here’s the kicker.

Those on the drug lost 9 percent of their body weight over the course of treatment, while those on placebo lost less than 1 percent, which figures.

What I find interesting is that the studies on Wegovy for weight loss showed pretty stout numbers after 68 weeks, which was the term of the study. During that time, subjects lost almost 18 percent of their body weight. In this study, subjects were on the drug for an average of 33.3±14.4 weeks. So, if these subjects on semaglutide lost only 9 percent of their body weight, that must mean they regained some of their weight even while on the drug.

Another interesting note is that about 300 more patients went off the semaglutide than went off the placebo, which is a bigger difference than the numbers who developed heart problems.

So, as always, the drug companies promote the relative risk differential, but the reality is that the study shows only about 1.5 percent of the subjects were helped in terms of heart attack, stroke, and heart death prevention.

Not a good outcome in my book. I’m not sure I would sign up for weekly injections that are not without side effects to give me a 1.5 percent chance to not have a problem.

Especially since studies like this can’t differentiate the benefit of the drug directly as to whether the benefit came from the drug itself or from the weight loss. I would predict that if you could get subjects with all the same underlying issues to lose 9 percent of their body weight on a ketogenic diet, you would find a much larger differential than 1.5 percent.

But no one will fund such a study. Imagine how much Novo Nordisk paid to fund this study of 17,604 subjects. Based on the one study MD and I did in our clinic on about 90 subjects, I would say they forked over at least $200M in today’s dollars. They must see a real upside.

AI and Video. Getting Better and Better

You almost can’t believe anything you see now. AI is getting so good with video. Take a look at this one.

Scary, eh?

Okay, it’s time for

Video of the Week

Below is a pretty funny video of unintended consequences.

These are all, of course, governmental fiascos of one kind or another. They would be a lot funnier if we didn’t have to pay for them. If we screw up and, say, fill out a tax return incorrectly, we’re hammered with penalties and interest. If we don’t pay, they seize our bank account. If they screw up, well, we pay for it, too.

Okay, time for a poll on this slightly shorter than normal newsletter.

If nothing else, just click the Like button. It’ll make me feel better.

That’s it for this week. Keep in good cheer, and I’ll be back next Thursday, which will be Thanksgiving for those of us here in the USA. We’ll be drinking a lot of Dry Farm Wines. You should be, too.

Thanks for reading all the way to the end. Really, thanks. If you got something out of it, please consider becoming a paid subscriber. I would really appreciate it.

Finally, don’t forget to take a look at what our kind sponsors have to offer. Dry Farm Wines, HLTH Code, Precision Health Reports, The Hustle (free), and now The Morning Brew (also free).