A "top" nutrition researcher exits, followed by two damning articles challenging his studies and claiming that a flagship $170 million NIH initiative is "designed to fail."
As always, I appreciate the deeper understanding of the science — in this case, the limitations with Hall’s UPF study.
I’m not sure yet how (or whether) that discussion relates to Hall’s complaints about censorship. Alice Callahan’s NYT article addresses the removal of the term “health equity” as one example of censorship. This has nothing to do with the MAHA agenda (the obliteration of DEI language is a MAGA agenda item). If that act of censorship was representative of a general culture shift at NIH, I would certainly understand Hall not wishing to stick around.
I understand that the greater point of this article is to address why journalists chose to spotlight the censorship story over the “doomed to fail” story, and I look forward to continued reading as your series unfolds.
Thank you, Gary, for giving these issues the time and detail they deserve with your usual clarity. I'm convinced one could drive a truck through the holes in Dr. Hall's conclusions. Looking forward to your other part(s)! -- Fritz
I would love an explanation sometime why both theories cannot be true at the same time. Why cannot both the amount of calories eaten and the type of calories eaten both influence weight? So the missing piece for me is understanding why these two theories are "either/or" instead of "both/and".
There are many ways to think about the either/or-both/and problem, but here's an easy one: imagine if 2500 calories/day of a diet of protein and fat (i.e., keto) made you thinner and 2500 calories/day of a diet of protein, fat and carbs made you fatter. Same calories. Opposite effects on fat storage. What good would it do to discuss the calories? That may or may not be possible, but it can be tested, and if it is, then only one theory is useful. The carbohydrate-insulin model can explain what happens in that kind of scenario; energy balance (we eat too much!) models can not. And the value of a theory in science is how useful it is at explaining what we observe.
I also get into that in my post back in January. If you have time to read that and still need more clarity let me know. (And there's always my book Why We Get Fat, which spends the first half discussing most all of the problems with the calorie/overeating thinking.)
I read Why We Get Fat a long time ago and was convinced the carb-insulin model was real (the photos you had in it were pretty convincing by themselves) - I'll go back to it. But your answer doesn't quite get at what I am curious about as it describes a case where the carb-insulin model effect overwhelms a possible energy balance effect. Suppose I eat 2500 calories a day of protein and fat compared to 3500 calories a day of protein and fat. Presumably the latter could make me gain weight compared to the former. It is certainly possible (and I think likely - I lost 36 pounds on a carnivore diet in 3 months) that I won't want to eat 3500 calories, since fat and protein are very filling (hence the success of the carnivore diet). But if I did (say, at a delicious Brazilian all-you-can-eat steakhouse, as I have done) a huge amount of meat, it seems likely I'd gain some weight. That's what I was thinking of when I asked if both could be true.
Yes, under that scenario both could be true. You can think of calories, though, as just a measure of quantity and you can force the system to do something it might not want to otherwise do. All kinds of consequences could result from the forced over-feeding you're describing and this gets very complicated. For instance, if you were still 20 or 25 you might just burn off those excess protein and fat calories or store some (protein) as muscle, because other hormones (testosterone and GH) would be working both to minimize fat storage and maximize the use of protein. As you get older and secrete less of those hormones, how you use the protein and fat will change. But I would argue (and do) that you can't understand what's happening under these different scenarios without paying attention to the neuroendocrine regulation of fat storage and metabolism, which is something the CIM does, and the energy balance models do not.
The other issue, as I note in a footnote, is that if you assume the UPFs make people fat because they make them eat too much, you have to now ask what's the difference between people who get fatter in a UPF-rich environment and those who stay lean? The world is still full of lean people who eat these foods to what I would think of as excess (like my 16-year-old son). If the answer is, those who do, eat too much, doesn't that imply they simply lack the willpower to eat less and that's considered an unacceptable answer these days (as it should be)?
I don't pretend to understand all the details concerning epic controversy between the carbohydrate insulin model and the energy balance model. I do, however agree that human nutrition science is complex and difficult--not to mention expensive. However, what if they were both correct? On the one hand, too much carbohydrate too fast triggers an increase in insulin, which basically tells the body to store fat. Seems simple. On the other hand too much carbohydrate too fast is, in the modern diet, is accompanied by excessive fructose, which triggers the autonomic nervous system into the fight or flight mode, instructing the liver to dump glucose into the bloodstream. So, my first question: "Is obesity both a brain (nervous system) thing and an insulin (hormonal) thing?"
Additionally, "...fructose is thought to be associated with insufficient secretion of insulin and leptin and suppression of ghrelin(1)." "...which can lead to overeating and weight gain.(2)"
(1) Brandi Jones, "Want to Lower Appetite? Get to Know Ghrelin and Leptin," Very Well Health, 2023.
(2) Kathleen J Melanson, et al "High-fructose corn syrup, energy intake, and appetite regulation," The American Journal of Clinical Nutrition, 2008.
See my reply to Andy in Tx above. I would agree that obesity is both a brain (CNS) and hormonal thing, but then the question becomes what is the brain doing. This gets to the GLP1-RA issue. The "experts" tend to assume that if something effects body weight regulation and it works in the brain then it's doing it by directly influencing eating behavior. It's quite likely (more likely I think, FWIW) that the effect on the brain/CNS is then effecting intermediate metabolism--glucose and fatty acid metabolism and storage--and that in turn is feeding back on appetitive behavior. That's the hypothesis that came out of the world of physiological psychology, as I discussed in my first book, GCBC, and was ignored by the obesity researchers for some fascinating sociological reasons. So, yes, both can be true but it still does not mean that obesity is an energy balance disorder and, as soon as you assume it is, you'll be led down a whole world of blind alleys (if I'm right, of course).
Regarding, "What is the brain doing?" I don't know either in this case. However, I have had experiences with "What the brain is doing" concerning exercise. As a foolish 82-year-old, I have decided to train for the 2025 Minnesota Senior Games this coming August. I haven't sprinted or run in track since I was 18 year old. Training is going surprisingly well, however, but my first attempt at running 400 meters went like this. My first attempt ended rather quickly as I thought I was going to die. After about 15 minutes rest, my second attempt made it about half way. Then after another rest, I made the whole distance. Researching the phenomenon, exercise physiology tells me that my brain was protecting my body. Then, somehow, a delayed chemical feedback comes back to the brain letting it know that there is still more capacity.
Now, that I am better trained and my sprinting style and speed has improved, I have the same problem with the 200 meter sprint. But it is my leg muscles that tell me to back off (at the 150 meter mark). We just now need to imagine the conversation regarding food and diet.
My guess is that, like in running, the physical feedback for fulness is slower than the brain feedback, and the brain feedback can be blocked by fructose. Which is interesting.
What I understand is that normally serum fructose is kept quite low, such that it is difficult to measure. But in starving mode, to protect the body the brain, I suppose, signals the production of fructose. Fructose then gets into the cells and shuts down some of the mitochondria, and perhaps also blocks the satiety signal so we don't stop eating when food is available, so that we store fat for future needs. However, when dietary fructose causes this signaling and food is always available we simply get fat. Hope this helps.
Gary E
P.S.: What was most interesting is that what should have been the most challenging training, hill sprints, turned out to be the first for achieving my goals. Looking back, during COVID (2010/2021) when I could no longer play pickleball with my friends, I started, what I call, stair trudging. We have three flights of stairs and I started walking and then faster, and then with a weighted vest, in a high intensity intermittent training (HIIT) fashion. Four years later, my brain already knew I could do it.
P.S.S: Another situation where it seems there is an inner control and an outer (the brain?) control. That is the bladder. In a fight-or-flight situation, the inner control is shut off from an external control--you don't want to have to stop to take a pee while running from the lion. The mind controlling the bladder to protect the body?
I agree with the "good carb/bad carb" thing, and part of the "bad carb" thing is fructose. In a traditional human diet the only fructose is part of fruit and vegetables, which is relatively little fructose compared to the industrial diet. Normally that fructose is converted to glucose in the small intestine so blood serum fructose is kept low. However, when the body anticipated danger, fructose is released and triggers the fight or flight response. In the modern dietary context ongoing high level fructose keeps the body in flight or flight chronically, keeping insulin low, glucose high, in a situation where high level energy production is expected but not happening. This would be an energy balance situation. So a guy sitting watching TV, drinking a Coke and eating Doritos puts his body into fight or flight. Intake of calories goes up, but energy expenditure does not. To me, this, while a special case is when energy imbalance takes place. A special case but all too common. Excessive fructose also shuts down mitochondria function, lowering the ability to produce cellular energy, making one feel tired, in seeking more energy, more fructose is consumed. A second special case of energy imbalance, that is all too common. (if I'm right, of course). The more I learn about fructose the more I think it is central to the chronic illness epidemic.
A 'Marian Nestle adipose tissue arachidonic acid' web search brings up an article that says, "In this follow-up study, we found that a high content of linoleic acid in adipose tissue was associated with a lower all-cause mortality, whereas a high content of arachidonic acid, DGLA, and DTA in adipose tissue was associated with a higher all-cause mortality. The content of linoleic acid in adipose tissue was not correlated with the content of arachidonic acid in adipose tissue." https://pubmed.ncbi.nlm.nih.gov/39914497/
And that is because dietary arachidonic acid and dietary linoleic acid interact with each other. High linoleic acid intake improves insulin sensitivity by displacing arachidonic acid from cell membranes. Excerpt from a 2010 article by Norwegian animal science researchers: "Because arachidonic acid (AA) competes with EPA and DHA as well as with LA, ALA and oleic acid for incorporation in membrane lipids at the same positions, all these fatty acids are important for controlling the AA concentration in membrane lipids, which in turn determines how much AA can be liberated and become available for prostaglandin biosynthesis following phospholipase activation. Thus, the best strategy for dampening prostanoid overproduction in disease situations would be to reduce the intake of AA, or reduce the intake of AA at the same time as the total intake of competing fatty acids (including oleic acid) is enhanced, rather than enhancing intakes of EPA and DHA only. Enhancement of membrane concentrations of EPA and DHA will not be as efficient as a similar decrease in the AA concentration for avoiding prostanoid overproduction. https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-9-37
If you are among the scientifically curious, try these web searches:
Fabulous article Gary. I love the way you unpack research. I'm looking forward to the next one.
As always, I appreciate the deeper understanding of the science — in this case, the limitations with Hall’s UPF study.
I’m not sure yet how (or whether) that discussion relates to Hall’s complaints about censorship. Alice Callahan’s NYT article addresses the removal of the term “health equity” as one example of censorship. This has nothing to do with the MAHA agenda (the obliteration of DEI language is a MAGA agenda item). If that act of censorship was representative of a general culture shift at NIH, I would certainly understand Hall not wishing to stick around.
I understand that the greater point of this article is to address why journalists chose to spotlight the censorship story over the “doomed to fail” story, and I look forward to continued reading as your series unfolds.
Thank you, Gary, for giving these issues the time and detail they deserve with your usual clarity. I'm convinced one could drive a truck through the holes in Dr. Hall's conclusions. Looking forward to your other part(s)! -- Fritz
I would love an explanation sometime why both theories cannot be true at the same time. Why cannot both the amount of calories eaten and the type of calories eaten both influence weight? So the missing piece for me is understanding why these two theories are "either/or" instead of "both/and".
Hi Andy,
There are many ways to think about the either/or-both/and problem, but here's an easy one: imagine if 2500 calories/day of a diet of protein and fat (i.e., keto) made you thinner and 2500 calories/day of a diet of protein, fat and carbs made you fatter. Same calories. Opposite effects on fat storage. What good would it do to discuss the calories? That may or may not be possible, but it can be tested, and if it is, then only one theory is useful. The carbohydrate-insulin model can explain what happens in that kind of scenario; energy balance (we eat too much!) models can not. And the value of a theory in science is how useful it is at explaining what we observe.
I also get into that in my post back in January. If you have time to read that and still need more clarity let me know. (And there's always my book Why We Get Fat, which spends the first half discussing most all of the problems with the calorie/overeating thinking.)
Best,
gt
I read Why We Get Fat a long time ago and was convinced the carb-insulin model was real (the photos you had in it were pretty convincing by themselves) - I'll go back to it. But your answer doesn't quite get at what I am curious about as it describes a case where the carb-insulin model effect overwhelms a possible energy balance effect. Suppose I eat 2500 calories a day of protein and fat compared to 3500 calories a day of protein and fat. Presumably the latter could make me gain weight compared to the former. It is certainly possible (and I think likely - I lost 36 pounds on a carnivore diet in 3 months) that I won't want to eat 3500 calories, since fat and protein are very filling (hence the success of the carnivore diet). But if I did (say, at a delicious Brazilian all-you-can-eat steakhouse, as I have done) a huge amount of meat, it seems likely I'd gain some weight. That's what I was thinking of when I asked if both could be true.
Yes, under that scenario both could be true. You can think of calories, though, as just a measure of quantity and you can force the system to do something it might not want to otherwise do. All kinds of consequences could result from the forced over-feeding you're describing and this gets very complicated. For instance, if you were still 20 or 25 you might just burn off those excess protein and fat calories or store some (protein) as muscle, because other hormones (testosterone and GH) would be working both to minimize fat storage and maximize the use of protein. As you get older and secrete less of those hormones, how you use the protein and fat will change. But I would argue (and do) that you can't understand what's happening under these different scenarios without paying attention to the neuroendocrine regulation of fat storage and metabolism, which is something the CIM does, and the energy balance models do not.
The other issue, as I note in a footnote, is that if you assume the UPFs make people fat because they make them eat too much, you have to now ask what's the difference between people who get fatter in a UPF-rich environment and those who stay lean? The world is still full of lean people who eat these foods to what I would think of as excess (like my 16-year-old son). If the answer is, those who do, eat too much, doesn't that imply they simply lack the willpower to eat less and that's considered an unacceptable answer these days (as it should be)?
I don't pretend to understand all the details concerning epic controversy between the carbohydrate insulin model and the energy balance model. I do, however agree that human nutrition science is complex and difficult--not to mention expensive. However, what if they were both correct? On the one hand, too much carbohydrate too fast triggers an increase in insulin, which basically tells the body to store fat. Seems simple. On the other hand too much carbohydrate too fast is, in the modern diet, is accompanied by excessive fructose, which triggers the autonomic nervous system into the fight or flight mode, instructing the liver to dump glucose into the bloodstream. So, my first question: "Is obesity both a brain (nervous system) thing and an insulin (hormonal) thing?"
Additionally, "...fructose is thought to be associated with insufficient secretion of insulin and leptin and suppression of ghrelin(1)." "...which can lead to overeating and weight gain.(2)"
(1) Brandi Jones, "Want to Lower Appetite? Get to Know Ghrelin and Leptin," Very Well Health, 2023.
(2) Kathleen J Melanson, et al "High-fructose corn syrup, energy intake, and appetite regulation," The American Journal of Clinical Nutrition, 2008.
Hi Gary,
See my reply to Andy in Tx above. I would agree that obesity is both a brain (CNS) and hormonal thing, but then the question becomes what is the brain doing. This gets to the GLP1-RA issue. The "experts" tend to assume that if something effects body weight regulation and it works in the brain then it's doing it by directly influencing eating behavior. It's quite likely (more likely I think, FWIW) that the effect on the brain/CNS is then effecting intermediate metabolism--glucose and fatty acid metabolism and storage--and that in turn is feeding back on appetitive behavior. That's the hypothesis that came out of the world of physiological psychology, as I discussed in my first book, GCBC, and was ignored by the obesity researchers for some fascinating sociological reasons. So, yes, both can be true but it still does not mean that obesity is an energy balance disorder and, as soon as you assume it is, you'll be led down a whole world of blind alleys (if I'm right, of course).
gt
Regarding, "What is the brain doing?" I don't know either in this case. However, I have had experiences with "What the brain is doing" concerning exercise. As a foolish 82-year-old, I have decided to train for the 2025 Minnesota Senior Games this coming August. I haven't sprinted or run in track since I was 18 year old. Training is going surprisingly well, however, but my first attempt at running 400 meters went like this. My first attempt ended rather quickly as I thought I was going to die. After about 15 minutes rest, my second attempt made it about half way. Then after another rest, I made the whole distance. Researching the phenomenon, exercise physiology tells me that my brain was protecting my body. Then, somehow, a delayed chemical feedback comes back to the brain letting it know that there is still more capacity.
Now, that I am better trained and my sprinting style and speed has improved, I have the same problem with the 200 meter sprint. But it is my leg muscles that tell me to back off (at the 150 meter mark). We just now need to imagine the conversation regarding food and diet.
My guess is that, like in running, the physical feedback for fulness is slower than the brain feedback, and the brain feedback can be blocked by fructose. Which is interesting.
What I understand is that normally serum fructose is kept quite low, such that it is difficult to measure. But in starving mode, to protect the body the brain, I suppose, signals the production of fructose. Fructose then gets into the cells and shuts down some of the mitochondria, and perhaps also blocks the satiety signal so we don't stop eating when food is available, so that we store fat for future needs. However, when dietary fructose causes this signaling and food is always available we simply get fat. Hope this helps.
Gary E
P.S.: What was most interesting is that what should have been the most challenging training, hill sprints, turned out to be the first for achieving my goals. Looking back, during COVID (2010/2021) when I could no longer play pickleball with my friends, I started, what I call, stair trudging. We have three flights of stairs and I started walking and then faster, and then with a weighted vest, in a high intensity intermittent training (HIIT) fashion. Four years later, my brain already knew I could do it.
P.S.S: Another situation where it seems there is an inner control and an outer (the brain?) control. That is the bladder. In a fight-or-flight situation, the inner control is shut off from an external control--you don't want to have to stop to take a pee while running from the lion. The mind controlling the bladder to protect the body?
I agree with the "good carb/bad carb" thing, and part of the "bad carb" thing is fructose. In a traditional human diet the only fructose is part of fruit and vegetables, which is relatively little fructose compared to the industrial diet. Normally that fructose is converted to glucose in the small intestine so blood serum fructose is kept low. However, when the body anticipated danger, fructose is released and triggers the fight or flight response. In the modern dietary context ongoing high level fructose keeps the body in flight or flight chronically, keeping insulin low, glucose high, in a situation where high level energy production is expected but not happening. This would be an energy balance situation. So a guy sitting watching TV, drinking a Coke and eating Doritos puts his body into fight or flight. Intake of calories goes up, but energy expenditure does not. To me, this, while a special case is when energy imbalance takes place. A special case but all too common. Excessive fructose also shuts down mitochondria function, lowering the ability to produce cellular energy, making one feel tired, in seeking more energy, more fructose is consumed. A second special case of energy imbalance, that is all too common. (if I'm right, of course). The more I learn about fructose the more I think it is central to the chronic illness epidemic.
ge
A 'Marian Nestle adipose tissue arachidonic acid' web search brings up an article that says, "In this follow-up study, we found that a high content of linoleic acid in adipose tissue was associated with a lower all-cause mortality, whereas a high content of arachidonic acid, DGLA, and DTA in adipose tissue was associated with a higher all-cause mortality. The content of linoleic acid in adipose tissue was not correlated with the content of arachidonic acid in adipose tissue." https://pubmed.ncbi.nlm.nih.gov/39914497/
And that is because dietary arachidonic acid and dietary linoleic acid interact with each other. High linoleic acid intake improves insulin sensitivity by displacing arachidonic acid from cell membranes. Excerpt from a 2010 article by Norwegian animal science researchers: "Because arachidonic acid (AA) competes with EPA and DHA as well as with LA, ALA and oleic acid for incorporation in membrane lipids at the same positions, all these fatty acids are important for controlling the AA concentration in membrane lipids, which in turn determines how much AA can be liberated and become available for prostaglandin biosynthesis following phospholipase activation. Thus, the best strategy for dampening prostanoid overproduction in disease situations would be to reduce the intake of AA, or reduce the intake of AA at the same time as the total intake of competing fatty acids (including oleic acid) is enhanced, rather than enhancing intakes of EPA and DHA only. Enhancement of membrane concentrations of EPA and DHA will not be as efficient as a similar decrease in the AA concentration for avoiding prostanoid overproduction. https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-9-37
If you are among the scientifically curious, try these web searches:
prostanoid overproduction metabolic syndrome
Kevin Hall adipose tissue arachidonic acid
Kevin Hall endocannabinoid system
NIH Omega-3/6 ratio endocannabinoid system