Tag Archive for: weight

It’s Going to Be a While

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In the last Memo, When Will We Get Something Better?, we looked at research on a new drug to counter obesity. But don’t hold your breath.

The researchers developed a sophisticated algorithm and used AI to find the process and the potential obesity-protein hormone to help combat obesity. What’s next? Several years or longer of clinical trials to test its effectiveness and safety in human beings. If it works, it will be another pharmaceutical solution to obesity and a step better than the GLP-1 agonists currently available. Two of the researchers hold the patent for the process and the protein itself, but there are no shortcuts on the science.

In my opinion, the problem is this: that’s not really the solution. They’re looking for a pharmaceutical solution. This protein, called BRG for short, will still have to be regulated like a pharmaceutical, made like a pharmaceutical, and prescribed as such even though it’s a natural hormone made in the body.

Where the research should focus is on a natural way to stimulate the body to upregulate (turn on) the gene or genes with diet, exercise, or some other natural means. Turning specific genes on and off is where we want to be, not creating companies and chemicals that will create a single molecule. It’s just the wrong approach to me. It may very well work, but it’s not natural in any way. I’m not suggesting that people with massive obesity won’t benefit from it, but it’s treating the symptoms of the problem, not the problem itself.

The problem is that because we overeat the wrong foods while not moving enough, genes have become upregulated and stay that way. We need solutions that help us get to downregulating those genes so that weight loss can become permanent.  Eat less. Eat better. Move more. For life.

What are you prepared to do today?

        Dr. Chet

References:
1. https://med.stanford.edu/news/all-news/2025/03/ozempic-rival.html
2. Nature (2025). https://doi.org/10.1038/s41586-025-08683-y

When Will We Get Something Better?

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The quest for a pharmacological solution to obesity continues—the magic pill to make us thin. While Ozempic and Wegovy, discovered and developed to treat type 2 diabetes, have been successful in helping reduce HbA1c, it has also helped people lose weight; the problem is the side effects. As you might guess, there are receptors for GLP-1 agonists in numerous locations in addition to the brain, and other organs are impacted.

That’s why a press release from Stanford seemed promising: “Naturally occurring molecule rivals Ozempic in weight loss, sidesteps side effects.” This research used a unique approach: they designed a specific algorithm that used artificial intelligence to identify the hormone segments made by an enzyme prohormone convertase 1/3 (PC1/3); basically, it cuts prohormones into smaller segments. Some may have metabolic activity, most would not.

Based on the analysis of 2,600 protein segments, the researchers identified 373 potentials and tested the top 100 most likely to succeed. They identified a hormone segment with 12 amino acids that appears to impact hunger 10 times better than the GLP-1 agonists, which are cleaved from the same prohormone. When they tested it in mice and minipigs by injecting it into the muscles of the animals before eating, it reduced food intake by 50%.

The volume of work done by the specific algorithm using AI probably saved years compared to testing each prohormone by trial and error, but what’s next? When will it be available? I’ll cover that on Saturday.

What are you prepared to do today?

        Dr. Chet

References:
1. https://med.stanford.edu/news/all-news/2025/03/ozempic-rival.html
2. Nature (2025). https://doi.org/10.1038/s41586-025-08683-y

HIIT: Specific Fat Loss

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What were the results of HIIT training? The researchers found that there were reductions in overall weight as well as subcutaneous and visceral fat. What’s the difference? The fat just under the skin is subcutaneous fat; visceral fat is behind the abdominal muscles and around the internal organs and is more related to the development of cardiovascular disease and type 2 diabetes. There were no differences in the outcome variables with two exceptions:

  • Those who were in the running group lost a greater percentage of subcutaneous fat than the cycling group at 16.1% vs. 8.3%. The other difference was that positive changes in the microbiome were correlated with the loss of subcutaneous fat. Before you get too excited, the actual loss of subcutaneous fat was close to two pounds in the running group and about one pound in the cycling group. Still, ask your butcher for one pound of fat and see what it looks like. It’s a lot and probably worth the effort doing the HIIT program.
  • The other benefit was an improvement in some positive bacteria in the microbiome. It wasn’t associated with running or cycling; it was correlated with the loss of subcutaneous fat. It seems that visceral fat would show more benefit, but that wasn’t the case. Maybe someday we’ll find out why.

The obvious problem with doing a running HIIT program is that you have to be able to run—at least for 45 seconds. While my running is progressing slowly, I do intervals only while walking or riding the exercise bike. But running for 45 seconds? I can handle that.

Finally, while I was puzzled about the microbiome benefits, I also questioned why there was a difference between cycling and running when it came to the loss of subcutaneous fat. The researchers didn’t have a reason to explain it. I’ll give you my informed opinion: running integrates more of the core during the actual interval than cycling does. My hunch could be tested with sensors that detect the electrical activity of muscles, but that’s fine tuning that might not be necessary. As a scientist, I always want to know why, but that’s not important; it’s just important that it is.

We’ve seen that 30 minutes of moderate walking can prevent the loss of muscle and a HIIT running program can help lose subcutaneous fat in those who are overweight. How about getting fitter faster? Is that possible? Find out next week when we look at SIT training—and sitting does have something to do with it!

What are you prepared to do today?

        Dr. Chet

Reference: Med Sci Sports Exerc 2024 May 1;56(5):839-850.



HIIT and Fat Loss

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One of the “facts” exercise professionals will tell you is that there is no such thing as spot reduction; by that I mean you cannot target a specific area of your body, let’s say your abdominal area, and lose fat by doing a targeted exercise such as sit-ups or leg lifts. You can make the muscles underneath the skin stronger for sure, but there doesn’t seem to be any evidence that you can reduce the amount of fat in that area.

With 35 years of experience in the field, I would say that requires a qualified answer—it needs to be qualified with the word yet. There hasn’t been a study that proves that you can reduce fat in a specific area yet. Is it theoretically possible? Yes, I think it is. The problem is this: who would do the high quantity of exercise focused on one area long enough per workout session to do themselves any good? It may be that we’ve approached it all wrong by focusing on resistance exercise. Let’s take a look at another study that compared high-intensity interval training (HIIT) on a cycle ergometer versus a treadmill.

Researchers began with two questions. Is there any difference in the fat mass in specific areas of the body after training using a cycle ergometer (an exercise bike that measures the energy output of the cyclist) or a treadmill? In addition to that, is there any change in beneficial microbes in the microbiome after training?

Let’s take a look at what they did. Researchers recruited 16 men with a mean age of 54 and initial BMI of 29.9. After assessing initial fitness level, body fat, and body-fat distribution using the DEXA scan, and taking an initial stool sample for analysis of the microbiome, the subjects were randomly assigned to the bike or the treadmill. To make sure that there were no significant changes in diet, the subjects were required to maintain their typical diet and do seven-day diet records periodically during the study.

Think of this as intervals for the everyday exerciser. The HIIT bike program required them to do ten intervals for 45 seconds each at 80–85% of the maximal heart rate (MHR), and then a 90-second active recovery, or a HIIT running program which were nine intervals for 45 seconds at 80–85% of MHR and again with 90 seconds of recovery between intervals. They were to do this exercise under supervision three times per week for 12 weeks. The goal was to have all exercisers use the same number of calories during the workouts, whether cycling or running. The subjects were then retested to examine the differences if there were any. What did they find? I’ll tell you on Saturday.

What are you prepared to do today?

        Dr. Chet

Med Sci Sports Exerc 2024 May 1;56(5):839-850.

Spot Reduction? Maybe

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Researchers collected data from four prior studies that put a group of sedentary overweight and obese men and women on a walking program. To determine the distribution of muscle, fat, and bone, they took MRIs of their entire body. That gave the researchers not only the amount of muscle and fat mass, but exactly where that muscle and fat were located.

Once researchers assessed the fitness level of these subjects, they developed an exercise prescription for them that had them exercise at 60% to 75% of their maximal aerobic capacity for 30 minutes a session, five days a week, for six months. Their heart rates were monitored throughout the exercise session to make sure that they did not exercise above those levels; that also allowed subjects to increase the speed or grade of the treadmill as they got fitter. The subjects used a food log to track all the food they ate.

Results

Did the subjects lose some weight? Yes. Even though they were trying to maintain what they ate, they were using more calories in exercise than they had been, so they did lose some weight—in this case, just a little over two pounds in the exercising group. The controls actually gained about half a pound in the six-month study.

Now to the good stuff. The results of the MRI showed that there were definitely regional differences in skeletal mass and fat mass. As was expected, the exercising muscles, primarily the hips, thighs, and legs, saw maintenance of the skeletal muscle mass but a decrease in the fat mass. In the upper part of the body, there was a slight decrease in muscle mass in the arms and upper torso with a very slight decrease in fat mass compared to controls.

The Bottom Line

So what does this all mean? First, because the mean age was around 55, maintaining muscle mass is critical—this is the time of life when age-related muscle loss starts to occur.

Second, if this were confirmed in several clinical trials, it would mean that there should be a focus on weight training or aerobic training that utilizes the entire body. Elliptical trainers and recumbent cross trainers come to mind as something that would use both the arms and the legs, so that may be part of the solution. And from personal experience, I can say that dance classes can have a similar effect.

In order to preserve muscle mass, exercising all your muscles is important; 60 to 75% of maximal fitness would be classified as moderate exercise. That means you don’t have to kill yourself in order to obtain the benefits of regular exercise to your cardiovascular system. Add to that some weight training a few days a week, and you have your own prescription for sustaining muscle mass and maybe losing just a little bit of fat mass along the way. But what if I told you that you could increase the loss of fat mass, especially in your abdominal region, by changing up the intensity of your workouts for a few weeks? Next week’s Memos will look at that research.

What are you prepared to do today?

        Dr. Chet

Reference: MSSE. 2024. 56(5):776-782.

Is Spot Reduction Possible?

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One of the questions that I’ve thought about over the years is what happens to the skeletal muscle and fat mass in non-exercising parts of the body. If you’re a runner or a walker, what happens to your upper body? What happens to your lower body? Do you retain or even increase the muscles in your thighs and calves? Do you lose fat from your legs? How about your upper body? Do you maintain the muscle mass that you had, or do you lose some? What about the fat mass? Lose or gain?

When I was a graduate student, I ran the body composition laboratory. Over my years in the lab, I underwater weighed probably 5,000 people, from five-year-olds to 90-year-olds, from those who were underweight to morbidly obese, from tiny little gymnasts to a Big 10 hockey team. While underwater weighing was the gold standard at the time, it used some assumptions about the distribution of skeletal muscle, bones, and fat mass that weren’t as precise as they should be. These days, state-of-the-art is dual X-ray absorptiometry, which is called DEXA for short. But that doesn’t give us a precise analysis of body composition to answer those questions either.

We now have that technology in magnetic resonance imaging. Using MRI can begin to give us the answer to those questions about muscle and fat mass. Can you get rid of that stubborn belly fat? We finally may have some answers, and I’ll tell you about the latest research on Saturday.

Don’t forget to send me your list of vegetables and fruits you ate over the weekend—and remember the ketchup!

What are you prepared to do today?

        Dr. Chet

Today!

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I’ve said before that in my opinion, the single most important thing you can do to limit the problems of aging is to get to a normal body weight and maintain it. If you’ve been overweight most of your life, as I have been, that can be a real challenge. While the research on what’s called Blue Zones is somewhat controversial, all we have are the observations of different researchers over the years. What seemed obvious to me, as a professional observer, is that people who lived longer seemed to be a normal weight for their height. And to me, that is the absolute goal to work towards.

It’s not easy, and it’s not going to happen overnight. But whether you’re 20, 50, even 70, if it takes you five years to get there, you’re still relatively young. That means that when you do get to be 80, you’ll actually be 80 instead of having died when you were 77. When do you begin to eat less, eat better, and move more to get to that normal weight for height?

Today. No matter how long it’s going to take, you begin today.

Insider Conference Call

I’ve been asked about cyanocobalamin, a synthetic form of vitamin B12. That’s the topic of the evening along with answering personal and product questions. If you’re not an Insider, become an Insider by 8 p.m. Wednesday evening and you can join in the conversation.

What are you prepared to do today?

        Dr. Chet

I’m Alive: V2.55

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When I opened my eyes this morning, I knew I had another year to do what I was created to do: teach people how to be healthy and fit. For those of you who are new readers or those who need a refresher, here’s the story: when I wake on May 10th every year, my superstitious belief is that I have at least one more year to live. My dad died on May 10, 1969. In case you’re wondering, I’m version 2.0 (my father was the first Chester John Zelasko), and it’s been 55 years since my father died. It makes no sense in the real world, especially for a guy who’s a scientist, but every May 10 is a milestone for me.

Last weekend as I pulled into the parking lot where I work out, there was an SUV with a number of plastic bags on the roof arranged in no particular order. As I walked past it, I couldn’t help but notice the car was packed to the ceiling, including the passenger’s seat. In fact, it encroached on the driver’s seat. I don’t know how anyone drives without being able to see the rearview or sideview mirrors, but I guess that person somehow managed. I could speculate whether they were moving or living in their car, but here’s how I saw it.

We all carry the baggage with us—memories of every time we didn’t complete a goal we set, especially health goals. We know the foods we should eat and the ones to avoid. We know that exercise will make us fitter, stronger, and more flexible. We know we have supplements and/or medications we should take for our health or to deal with conditions we may have. In retrospect, we ask ourselves why? Why don’t we do that?

It may not be the only reason or reasons, but I think we carry the baggage of past failures with us. And we continue to lose fitness, strength, and on and on. You know the worst sentence I can think of? “What difference will it make now?” It will make a huge difference. Can you walk your daughter down the aisle, or will you need a walker? Will you need a wheelchair in five years, or can you postpone that? Will you still have the flexibility 15 years from now to take care of your own personal needs, or will you need someone else to bathe you and clip your toenails? In 20 years, will you still be chugging along, or will you be so heavy you can’t stand up without help? I can think of hundreds of examples, but insert your own. It matters.

The important point is that you can change your trajectory. Joining a workout group or taking charge of your diet can make a world of difference in your future, so stop putting it off till next month.

I have my own baggage to deal with, so this version is going to overcome as much of it as I can this year. I’m going to spend the year encouraging you to do the same. We have things to do, and we just have to find a way to drop the baggage and get out of our own way to be the next version of ourselves. All the people who need you will be glad you’re making the effort.

What are you prepared to do today?

        Dr. Chet

Eat Less, Eat Better, Move More—for Life

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In Tuesday’s Memo, Dr. Donal O’Shea suggested that there’s compelling evidence that eating less and moving more won’t result in permanent weight loss because the set point theory is just too strong and will defeat the effort of 90% of the people. However, he didn’t provide any evidence that’s true. I’ll give him the benefit of the doubt, because every study done on diets shows that people do gain back some or all of the weight they lost. He attributes that to the complexity of obesity.

The Complexity of Obesity

Take a good look at the graphic used in the heading. What you can’t read are the 198 determinants (all those gray lines) that contribute to obesity. He narrows them down to just seven categories, five of which are not under the control of people once they are fat. In case it’s difficult to read, here is the list.

  • Societal influences
  • Food production
  • Activity environment
  • Biology
  • Individual psychology
  • Food consumption
  • Individual activity

He also gives a compelling argument that the immune system, working in conjunction with fat cells, causes inflammation in a variety of ways which prevents people from losing weight.

The problem that I have is two-fold. First, it seems the last three are under the control of the individual: eating, moving, and deciding to do so. The exterior forces are what they are, but biology can change. Aging is the perfect example of that.

As for immunity, here’s the real question about the immune system: is it cause or effect? The increase in inflammation is remarkably similar to the increase in cortisol found in people who are obese. Is it the cause of obesity or is it the result of being obese? It makes a difference.

Why Medication Won’t Be the Permanent Solution

Before I get into this, I think that medications may play a role in the solution for some, maybe even most severely overweight people. But they will not be a permanent solution, and the reason may be found in the proteome. You may remember that those are the proteins coded for in our DNA; they range from hormones such as insulin to catalysts for other chemical reactions. There are about 5,000 proteins that are the most researched, but with about 20,000 genes, there may be at least 15,000 more genes that are not researched. That doesn’t count the post-translational modifications, modifications made to the protein as it’s being made; the total could get into the millions.

It’s unrealistic to think that a combination of three, five, or even ten receptor agonists will solve obesity and not cause issues elsewhere in the body by interfering with the production of other necessary proteins. I’m not suggesting that temporary use to get the bulk of weight off an individual won’t be a good way to start, but it’s not a permanent solution as I see it, even if you can afford to take it the rest of your life.

The Bottom Line

The issue with O’Shea’s approach is that it comes from a strictly medical perspective. A nutritional solution isn’t considered and somewhere along the line, just like with gastric bypass, people will exceed their desired caloric intake and regain weight. Why? Because they haven’t learned anything.

Remember, in those seven categories he cited, food consumption and activity levels are under the control of the individual. That means both the quantity and the type of food as well as the amount of activity are under the control of the individual. I’ll say it again: it was, it is, and it will always be about the calories—how much you take in versus how much you use. Take in more than you use, and you gain weight. It’s that simple.

Obesity is complex because our bodies are complicated, but this is still my recommendation: eat better, eat less, and move more. If I were to add two more words that I’ve implied but haven’t stated, they would be “for life” because the only way to hold on to your progress is to keep working on your lifestyle.

What are you prepared to do today?

        Dr. Chet

References:
1. SETU. Understanding Obesity: Rethinking Diagnosis & Treatment. 2024.
2. Nat Chem Biol. 2018 Feb 14; 14(3): 206–214.

Should You Forget “Eat Less, Move More”?

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Eat less. Eat better. Move more.

If you’ve been reading the Health Memo for any length of time, you know that’s my simplified solution, my mantra, to the problem of excess body fat we face in the U.S. and around the world. That’s why an article about an endocrinologist from Ireland who said “Eat less, move more is not the treatment for obesity—get over it” caught my attention. The quote was taken from a talk and interview given by Dr. Donal O’Shea that included a series of recommendations to primary care physicians on how they should approach the topic of excess body weight with patients. He went on to suggest that in a short time, medicine will have solutions for obesity that will essentially render obesity obsolete. Semaglutide is just the first jab at it—pun intended.

I went a little further and listened to a talk by Dr. O’Shea in which he went into detail about why 90% of weight gain is irreversible in 90% of the people. Then he used this example: if you donate a pint of blood, your body will replace it over the next six weeks to get your body back to its blood-volume set point. He says your body weight also has a set point and once it’s raised, it cannot be reversed; no matter what you do, your weight will return to its set point. Therefore, medications such as semaglutide and the ones being developed that will impact other receptors are the only solution.

Should we just buy stock in pharmaceutical companies and forget about nutrition and exercise? Dr. O’Shea is a good scientist and is certainly compassionate toward patients. But is he correct? No, and I’ll explain why on Saturday.

What are you prepared to do today?

        Dr. Chet

References:
1. Eilish O’Regan. Irish Independent. 04-28-24
2. SETU. Understanding Obesity: Rethinking Diagnosis & Treatment. 2024.