Andrew Huberman interviews nutritional medicine professor Dr Marie Pierre St Onge on the bidirectional relationship between sleep and diet
Andrew Huberman, neuroscientist and host of the Huberman Lab podcast, interviews Dr Marie Pierre St Onge, professor of nutritional medicine at the Institute of Human Nutrition at Columbia University School of Medicine.
Summary
Dr. St-Onge runs one of the few laboratories in the world studying the bidirectional relationship between sleep and food intake. Her controlled inpatient research demonstrates that even severe short-term sleep restriction (around four hours per night for five nights) causes men to produce more ghrelin — the hunger-triggering hormone — while women experience a reduction in GLP-1, the satiety hormone, leading both sexes to consume approximately 300 calories more per day. A follow-up study found that milder but sustained sleep restriction of one and a half hours per night over six weeks in free-living conditions produced measurable increases in insulin resistance and blood pressure, particularly in post-menopausal women. On the dietary side, her research shows that higher fiber intake is associated with more deep slow-wave sleep, higher saturated fat intake with less deep sleep, and more refined carbohydrates and simple sugars with greater nighttime arousals. She also presents findings that shifting caloric intake earlier in the day reduces fat oxidation when meals are delayed, and that medium-chain triglycerides (MCTs) modestly increase the thermic effect of food and may support weight loss when substituted for other fats.
Key Takeaways
FULL TRANSCRIPT
The bidirectional relationship between sleep and food intake
Andrew Huberman: Sleep impacts how and what we eat, and how and what we eat impacts sleep. That's a different perspective than I think most people take. I think most people are familiar, however, with not getting the best night's sleep, maybe feeling like their impulsivity to eat quote-unquote bad foods is a little higher, and then also hopefully familiar with having a great night's sleep and feeling like they're just in control in a different way. Maybe you could share for us what's really going on beneath that experience, and when subtle or not-so-subtle chronic sleep loss — not an all-nighter necessarily, but 45 minutes less here, 90 minutes less there — how that plays out in terms of our nutrition. And then we'll go from the nutrition side to sleep.
Dr Marie Pierre St Onge: Sure. There are a couple of questions in there about the extent of sleep loss and how that influences food intake — what we see in the general population versus what we do in a lab to address causality. Let me start with the population-based studies. When I started being interested in sleep, it was coming from an obesity angle. My PhD is in nutrition. I trained as a postdoc in body composition and obesity research, and we were getting a lot of information from population-based studies that people who sleep too little have a higher body mass index than people who get an adequate amount of sleep. Then it became clear there is a higher prevalence of people with obesity in the short sleep group. Then studies evaluating changes over time showed that people who don't sleep enough tend to gain more weight. There was a famous nurses' health study that I really like to cite when I give talks, published in 2006, where they tracked nurses over 14 years, and those nurses who reported sleeping five or six hours had a much higher rate of weight gain over that 14 to 15-year period than the nurses who reported sleeping seven or eight hours per night.
Those are observations from large-scale population studies and cohorts, but what those studies tell us is that things are happening at a point in time or may influence something happening over time — but not necessarily that one causes the other. So I started my work in this field trying to uncover whether sleeping too little actually causes weight gain. Because I was coming from a lab where I trained in the measurement of energy balance — how much energy you eat versus how much energy you burn — I thought, well, if sleep leads to obesity and weight gain, it has to impact this energy balance regulation. So it's either that we eat more than we should, or that we exercise less and burn less, or maybe it's a combination of the two. Let's try this out and see.
My first study, my first NIH grant — the big R01s — was to look at exactly this. We had people who had adequate sleep, and we brought them into the lab and asked them, in a crossover design, to either sleep adequately — a 9-hour time-in-bed opportunity — or to sleep too little, with a 4-hour time-in-bed opportunity. We did this for five nights. We took all sorts of measurements in a controlled feeding condition. For the first three days, we had participants eat the exact same thing regardless of how much time in bed they got at night. We measured appetite-regulating hormones, did neuroimaging to isolate the impact of sleep duration on appetite-regulating hormones and neuronal responses to foods. Then on the last day we let them self-select their food intake and measured that in the lab.
From that study, we showed that in men specifically, we saw an increase in ghrelin in response to short sleep — the hormone that triggers food intake. In women, we saw a reduction in GLP-1, glucagon-like peptide-1, the satiety hormone, as a result of short sleep. And when we measured their food intake in the lab, they ate 300 calories more in the short sleep condition than when they got their regular adequate sleep of at least seven and a half hours per night. We also looked at neuronal responses to food stimuli and found upregulation in reward centers of the brain in the context of sleep restriction compared to adequate sleep. So altogether, we were really building a case that when you don't sleep enough at night, you have both physiological signals to eat more — for men, or not stop eating in women — that lead to greater food intake, which could also be impacted by pleasurable centers that are activated to a greater extent as a result of insufficient sleep.
Andrew Huberman: Amazing. This sex-specific split in the data — if I have it correctly — is that when men are sleep-deprived, getting four hours per night, the signals that drive appetitive desire to eat are higher. In women, it's more that the brake on eating, on satiety, is reduced.
Dr. St-Onge: Exactly.
As far as I know, the GLP pathways are not divergent by sex, but of course I'm not deeply versed in that literature. Is there any evidence that GLPs are functioning differently in men and women — circadian-wise or anything like that — or was this just an incidental outcome?
Dr. St-Onge: This was an incidental outcome. We really didn't know what to expect. We didn't know at all that we'd see sex differences. There had been prior studies that had shown that ghrelin was increased as a result of sleep restriction, and that leptin was reduced. When we got our data and analyzed it with all participants together, there was no effect.
Andrew Huberman: And that was surprising.
Dr. St-Onge: And people would say, "Don't you know sleep restriction increases ghrelin?" Well, I guess I don't know, because in our study it doesn't. But then we saw these sex-specific differences, and then it made sense — in the full sample, when we had an equal number of men and women, we saw no effect on ghrelin because there was no effect in women but there was an effect in men, which was reproducing what others had found, because all the prior studies had been done in men only.
Sleep deprivation, cortisol, and metabolic effects
Andrew Huberman: Whenever I'm sleep-deprived — four or five hours, which I consider sleep-deprived — I feel like my whole body is in a low level of pain. It's like a central ache. And I wonder to what extent people eat to overcome, to quell, the pain of sleep deprivation. Maybe people react differently. But what do you think is happening in that short amount of sleep that's missing? What is getting reset? Is it neural? Is it endocrine? What is the switch that allows people to enter a day in a much more healthy fashion, or essentially in a slightly sick fashion?
Dr. St-Onge: In our study, it was actually a 50% reduction in sleep. When they had a 9-hour sleep opportunity, they slept around seven and a half hours. These were all people we had screened to sleep at least seven hours, measured by actigraphy. In the sleep-restricted condition, they got on average about three hours and fifty minutes.
Andrew Huberman: So it's like staying up late working on a deadline and then trying to catch an early flight.
Dr. St-Onge: It's pretty brutal. And that was maintained for five nights.
Andrew Huberman: Were they coming unglued mentally too? I think I would feel terrible after that kind of stretch.
Dr. St-Onge: By the end, they were done. There was no way anyone would want to keep coming back for that. But they were in the lab, under supervision the whole time. We didn't let them go out on their own. No naps either.
What happens is I think there's some subconscious need to eat more when you're sleep-deprived. There's also a thermic effect of food — it gives you a jolt of energy to eat something. People know that eating wakes you up in a way. There's neuronal signaling that enhances pleasurable and reward centers of the brain. And when fatigue sets in, do you really want to have this conversation with yourself about what to choose at the buffet table? Others have also shown that sleepiness tends to correlate with triggers for more pleasurable food consumption with sleep restriction, and it's been reproduced. A meta-analysis showed 250 to 400 calories of overeating, which might not sound like much, but when you layer that day after day — roughly 3,500 excess calories per pound of body weight — and people accumulate that over time in a night-shift condition, or as new parents, or tending to a sick relative, or during final exams, it's a real thing.
Naveen Coven in 2022 published a paper where they had sleep restriction of about five hours per night versus seven and a half hours per night for two weeks, and participants gained half a kilogram in a two-week period. You do nothing — you just sleep less — and you gain almost a pound in two weeks.
Andrew Huberman: It strikes me that for a long time in stress research, the idea was that when people are stressed, they reach for comfort foods — carbohydrate, typically starch-fat or sugar combinations. The just-so story was always that cortisol's main role is to deploy glucose, and so people are doing this as a way to bring excess energy. What is the relationship between the forms of sleep deprivation you work on and stress? Is what you're studying essentially stress?
Dr. St-Onge: If you're thinking about physiological stress measured by cortisol levels, in that study cortisol wasn't changed in the short sleep condition.
Andrew Huberman: For five days of sleep restriction at basically four hours a night — cortisol is still peaking in the morning, still dropping in the evening?
Dr. St-Onge: Yes.
Andrew Huberman: Wow. That's very surprising to me.
Dr. St-Onge: I don't know. I think it may be the context of being in a lab where everything is safe and taken care of. There is nothing outside to aggravate. So maybe when you're in the context of sleep restriction but also dealing with your daily life — needing to take care of your kids, needing to get to work, needing to do all the activities of daily living — maybe then that becomes the added stressor.
Andrew Huberman: So the message is: if you suffer less than adequate sleep, get someone to take care of everything else. You'd better be in a spa.
Dr. St-Onge: Exactly. And in that study also, we didn't see any effect on glucose or insulin. Nothing. The curves were superimposable — while they were eating the exact same food at the exact same time, in the exact same quantity. The only thing we changed was the amount of sleep opportunity they got at night. To me, this means it's a combination of different things that causes the metabolic abnormalities we notice in free-living populations. People aren't isolated. They're not in a box where they're not sleeping enough and simultaneously choosing to eat higher fat, higher sugar, higher salt — a poor diet that then triggers a worsening, possibly compounded by the lack of sleep, of those cardiometabolic outcomes.
Because we did a follow-up study to this severe sleep restriction study, for exactly this reason — because we did not find any adverse impact on glucose, insulin, or lipid profile. We asked: why is it that in population-based studies we find that people who sleep too little have higher risk of cardiovascular disease, higher risk of hypertension, higher blood pressure, higher risk of type 2 diabetes? Because we had seen that food choices were different — that they ate a diet higher in calories, higher in fat and saturated fat — we thought maybe if you're in a free-living situation, that's when you start to see those cardiometabolic outcomes, compounded by more sedentary behavior and alterations in food choices.
So the follow-up study recruited good sleepers — people who sleep at least seven hours per night, verified by actigraphy, who report good sleep quality on questionnaires. We then said: you're either going to continue your excellent sleep, or you're going to go to bed an hour and a half later, getting an hour and a half reduction in sleep. Because when we screen people who sleep at least seven hours, they sleep about seven and a half on average. Reducing by an hour and a half gets to six hours, which is the short sleep threshold — what people who don't get enough sleep typically report. They can sustain that for prolonged periods, which is what people report in population-based studies.
When we did that, we saw that insulin resistance was increased after six weeks of sleep restriction compared to adequate sleep. Insulin sensitivity was reduced — worse actually in post-menopausal women compared to pre-menopausal women. Blood pressure was increased. Those cardiometabolic outcomes were adversely impacted by free-living mild sustained sleep restriction for six weeks.
Energy expenditure and spontaneous movement
Andrew Huberman: What's kind of the action end of things that causes weight gain if they're basically on an isocaloric diet? I have an idea what it might be, but I'm curious what the answer is.
Dr. St-Onge: I think they're more sedentary during the day. Less spontaneous activity. We also did a study to look at energy expenditure — which is really difficult to measure, in my opinion. There are multiple components to energy expenditure. We did a study — a small study, enrolling only women — using a metabolic chamber at Columbia. It's a small room in which we keep people and measure minute-by-minute oxygen consumption and carbon dioxide production. We were able to show that energy expenditure is actually increased in the context of sleep restriction in the metabolic chamber, because it is more costly energetically to remain awake than to fall asleep. So energy expenditure when participants were awake was identical in both conditions regardless of how much sleep they got the night before.
Andrew Huberman: So it's fidgeting, movement — the non-exercise-induced thermogenesis. It's a big number. People who fidget a lot, bounce their knee — sometimes these people are burning 1,500 calories more per day. It's a real thing. You sometimes observe people who are very lean and they tend to have a lot of spontaneous movement, stand up quickly, walk quickly.
Dr. St-Onge: For us it was about a 5% increase in energy expenditure, ending up being about 90 calories — nowhere close to the 300 calories more of intake they got over a day in the prior study. So it's still an imbalance towards a positive energy balance when we do the math, but there is an increase in energy expenditure — again, in the confines of a metabolic chamber, which for most people is equivalent to the size of their bathroom. You have a bed, a table, a sink, a toilet. That's it.
Inflammation and the practical value of knowing your hormonal state
Andrew Huberman: A little while ago I saw a study that said if you are one night sleep-deprived — getting one or two hours less sleep than you normally need to feel rested — it's actually advantageous to exercise because it offsets some of the increase in inflammation. But if you're going multiple nights that way and exercising regularly while sleep-deprived, it sets up a susceptibility to illness and injury. How much of what you observe under conditions of sleep deprivation do you think is downstream or upstream of inflammation? Is this just a body-wide response where a bunch of systems are dysregulated? Or can we pinpoint what's happening?
I think about this because if women knew their GLP-1 levels were down when they're down on sleep — so they should expect to feel less satiety — and if men knew their ghrelin levels were elevated when they're down on sleep — so they're going to feel hungrier — we have pretty big prefrontal cortexes, most people anyway, and we can intervene simply on the basis of knowledge. I think about this sometimes when I'm thinking about my own diet. Do I really want to eat this, or is it because I really didn't sleep last night?
Dr. St-Onge: So if you step back and think that maybe part of it is because you didn't sleep well the night before, then you can make appropriate choices. You can say, "Okay, I probably don't need the extra calories right now." Or maybe you say, "I had a really bad night last night and those extra calories, I don't really care — they're going to make me feel good and I need a pick-me-up." But those are all choices to make, because mood comes into play as well.
How diet affects sleep quality
Andrew Huberman: That brings us to the other direction of the equation — how what we eat impacts our sleep. Most people have heard "try not to eat too close to bedtime." This is an active debate in many households. Some people seem fine eating close to bedtime and even if they track their sleep. Other people it really disrupts their sleep. I'm interested in both the timing of food intake relative to sleep and the content of the food and how it impacts sleep.
Dr. St-Onge: When we started this conversation, I was telling you about population-based studies — cross-sectional data where two things happen at the same time and you don't really know causality. Early on in this field, we started thinking about sleep as the promoter of food intake, or as causing changes in diet and exercise, but didn't really think that maybe it's the other way around, or that the other way around is just as plausible. So I started thinking about that and said, what if we took the other approach? What if we looked at diet and examined how diet influenced future sleep?
My first paper in this field used data from the Multi-Ethnic Study of Atherosclerosis. It's actually kind of hard to find good cohorts that have good nutrition data, good sleep data, and data over years. MESA — the Multi-Ethnic Study of Atherosclerosis — is one of those great cohorts in the US that has all of the above. I paired up with a colleague, Susan Redline in Boston, who is a principal investigator on their sleep ancillary study, and we asked the question of diet quality and its impact on sleep duration and insomnia symptoms. We found that having a diet that more closely aligns with the Mediterranean diet was associated with a better probability of having adequate sleep and reduced insomnia symptoms in this cohort.
That launched a whole field of study. We've looked at this in different studies and different cohorts. Earlier this year we published data from the Women's Health Initiative — another large cohort with good diet data and sleep information. We took a really nice approach in this longitudinal analysis. Usually when we do longitudinal studies, we exclude people who have the condition at baseline. But insomnia is one of those conditions that's not necessarily static — it resolves. You can have insomnia and then a few years later not have it, or you can not have it now and develop it. So we broke our participants into two groups: people who had no insomnia at baseline and at three-year follow-up, and participants who had insomnia at baseline but not at three years — the healthful, improving-sleep group. The other group was women who had insomnia at baseline and at three years, and those with no insomnia at baseline but insomnia at three years — the persistent or progressing-toward-poor-sleep group.
We found that women who had a diet more closely aligned to the Mediterranean diet — and we also looked at the DASH diet, the Dietary Approaches to Stop Hypertension — were less likely to have insomnia at three years.
Andrew Huberman: And the DASH diet is what?
Dr. St-Onge: Dietary Approaches to Stop Hypertension was developed to reduce and prevent hypertension by increasing intakes of fruits and vegetables, nuts and seeds, consuming low-fat dairy, and a more plant-based type of diet. It has been tested in both low-salt and regular-salt profiles.
Andrew Huberman: How did those work out? Do you recall if the low-salt versus high-salt condition made a difference?
Dr. St-Onge: There is salt sensitivity, so there are some people who are very sensitive to salt and having a reduced-salt diet will really improve their blood pressure. Others not so much. But the DASH diet regardless of its salt content did better than the equivalent non-DASH diet — your average American diet, higher in saturated fat and sugars.
Andrew Huberman: Which seems to be changing now because of the GLPs. I feel like the typical American diet may not be changing so much in content, but in volume it seems like people are eating less. Certainly the snack food companies, from what I understand, are struggling. It just seems like people's appetites are down.
Dr. St-Onge: GLP-1s will do that.
Andrew Huberman: How many Americans have tried a GLP? The estimates are anywhere from one in seven — some people say it's more.
Dr. St-Onge: Which is pretty incredible.
Andrew Huberman: But this is interesting. How people eat impacts their sleep. I'm sure the listeners and I are also thinking: people who are eating a Mediterranean diet — olive oils, fish, fruits, vegetables — are probably more apt to walk more, exercise more, socialize more. How do you separate out the variables in a study like that?
Dr. St-Onge: In population-based studies, we adjust for a bunch of covariants. We have questionnaires asking about race, occupation, socioeconomic status, and then we adjust for different illnesses they may have, depression, physical activity level. We try to take all of this into consideration. Obviously there are always unmeasured factors — social interactions, for example, are usually not captured very well. But one thing we did in my lab, going back to that original inpatient study, was to look at how diet influenced sleep at night in the participants in the 9-hour time-in-bed opportunity phase only. In the 4-hour phase, participants were very efficient — there wasn't much variability in sleep duration. But in the 9-hour phase, there was variability. Some people got more or less. So we wanted to see if food intake was related to their sleep at night.
That study had polysomnography assessments of sleep every single night. We had a controlled diet initially and then let them self-select their food intakes. We took a very systematic approach. First: was the diet they chose different from the diet we gave them? It was. They ate almost 450 calories more. They ate 33% more saturated fat, a little less protein, a little more carbohydrates. So there was a difference between the diets.
Then: was their sleep at night different when they were eating the diet we fed them compared to what they self-selected? It was different — not in terms of duration, but in the time it took them to fall asleep, which was over 70% longer when they self-selected their diet. And their slow-wave sleep — deep sleep — was about 20 to 23% shorter when they self-selected their diet compared to what we had given them.
Andrew Huberman: Was timing of food intake a factor? Because when I think of what reduces slow-wave deep sleep, it's eating too close to bedtime.
Dr. St-Onge: We did not take that into consideration in that study. We didn't specifically look at when their last eating period was. It could have been different than in the controlled feeding condition, because in the controlled feeding condition they had set meals at specific times. But they all went to bed at 10 p.m.
Then the other question was: what was it that they ate that day that impacted how they slept that night? And we found that higher intakes of fiber were associated with more deep sleep, higher intakes of saturated fat with less deep sleep, and more refined carbohydrates and simple sugars with more arousals. When we talk about arousals in the context of polysomnography, it doesn't necessarily mean full-on waking up — it really means going from a deeper to a lighter stage of sleep. You may still be asleep throughout the night, but you're not getting deep slow-wave sleep or REM sleep as much as you would otherwise.
Andrew Huberman: Do you create a buffer between your last bite of food and the time you go to sleep? You personally?
Dr. St-Onge: Me personally, yes. I personally like to eat my last meal at least three hours before going to bed. I know there's variability — different people have different tolerance. What we know is that eating earlier is better overall for cardiometabolic health. Me personally, I feel better by eating earlier. If I eat too close to bedtime, I get hot.
Andrew Huberman: Right. It's the thermic effect of food. We want to be cooling off when we go to sleep.
Dr. St-Onge: Exactly.
Sleep asymmetry, chronotypes, and napping
Andrew Huberman: There seems to be something asymmetric about sleep requirements in my experience. If I go to bed at 10 p.m., fall asleep at 10, I need about six and a half, maybe seven hours to feel completely rested. If I go to bed at midnight, I could sleep till 9 and still not feel completely rested. The old adage is every hour before midnight is worth two after. Is there any real data to support that?
Dr. St-Onge: I'm not sure there's data to support that. I haven't seen anything. But what I can say is that if you usually go to bed at 9:30 or 10 and then all of a sudden you go to bed at midnight, you're kind of out of line with your personal circadian system. It's always harder to get a good night's sleep if you're not going with your internal clock or your internal circadian preference. This is what happens with shift workers — they're not sleeping at night, they're trying to sleep during the day when their melatonin should be low. They're fighting their circadian system. They should be getting seven hours, but they're not getting seven hours because their body is not designed to be sleeping during the daytime hours. Plus, you have everything else — the light, the noise, the kids, whatever life happens during the daytime when everybody else is awake and you're trying to sleep.
Andrew Huberman: Has your work explored napping at all? I'm a believer in naps and non-sleep deep rest, yoga nidra-type things, meditation. Do naps factor into this diet, nutrition, hunger equation?
Dr. St-Onge: We haven't done research on napping per se. For me, there's a lot going on with napping. I don't think we have very good data to be able to say what's appropriate about napping. What we do know is that you don't want to nap too close to bedtime, because you want to build sleep pressure throughout the day. If you're dissipating the sleep pressure too close to bedtime, you're not going to be able to fall asleep when time comes to go to bed at your usual hour, and then you get into a vicious cycle.
But there are some studies that say: what should you do if you can't sleep enough at night and you're feeling tired? Recommendations are that you should make it a short nap — 30 minutes, no more than an hour — early enough in the day if possible, so that you can have sufficient time to rebuild that sleep pressure. But then there's also the question of what the nap is for. If you had sufficient sleep opportunity at night and you're waking up not feeling refreshed, not able to maintain alertness throughout the day and needing a nap, I think you should check to see what's going on at night. Why are you not getting good enough sleep?
Andrew Huberman: I'm chuckling because my postdoc advisor sparked a huge debate about this. It was a big lab and we had a couple of people who liked to nap at their desks in the afternoon. He'd walk in, they'd be napping, then wake up and keep working. He had this theory that if you're napping, it's because you're sleep-deprived — that napping is unhealthy. It sparked a big debate and people brought data in. I think what you just described summarizes the takeaway. I'm a believer in the short nap, but I'm one of these people who can sleep anywhere, anytime, which may be reflective of sleep deprivation.
Dr. St-Onge: Maybe.
Meal timing and fat oxidation
Andrew Huberman: Someone had a really great question for me at the Obesity Society meeting a couple of years ago. I was showing data we had just obtained in the lab showing that if you eat foods later in the day, your fat oxidation is reduced. We had participants on a controlled diet who started eating one hour after waking up with a 10-hour eating window, or started eating five hours after waking up — a four-hour delay relative to the other condition. Same foods, same quantity, same timing between meals, done in a metabolic chamber. The meals consumed later in the day led to less fat oxidation. And someone in the audience stood up and said, "Would you then recommend that people eat medium-chain triglycerides in their evening meal as opposed to a different type of fat?" And my eyes just went wide, because my time studying medium-chain triglycerides was 15 to 20 years ago. I thought that was fascinating — timing of intake of different foods and how it influences metabolism is something that's fascinating to me.
Andrew Huberman: I confess I'm a first-bite-of-food-around-11-a.m. person. I'm trying to eat breakfast these days and shift things earlier. All it's really done is added a meal, because I take my last bite of food usually around 8 p.m. I can't seem to get much earlier. But many people have wondered whether it's best to eat more towards early day or whether it's just overall caloric load. You're saying it does indeed make a difference.
Dr. St-Onge: It makes a difference. You want to shift most of your caloric intake to the first two-thirds of your waking day roughly, as opposed to the last third. In that study, one hour after waking up — let's say 8 a.m. to 6 p.m. is the eating window. It's a 10-hour eating window. It could be 8 a.m. to 7 p.m. Versus noon to 10 p.m.
Andrew Huberman: The New York schedule.
Dr. St-Onge: Yes. And in Europe they eat very late often. I was on a Fulbright program last year in Spain, and I would joke with my colleagues there because they eat very late — even the children eat very late. They could have dinner at 10 or 11 p.m. and the children at 8 or 9 p.m.
Andrew Huberman: My dad's from Argentina. If you go to a restaurant in Buenos Aires at 9 p.m., you're not going to see many people. At 11 p.m. you'll see people in their 70s and 80s who are up early the next day. They nap in the afternoon.
Dr. St-Onge: There have been studies in Spain that have looked at timing of eating and its impact on weight management. I'm thinking of work by Marta Garaulet, where she showed that in her weight loss program, participants who have their bigger meal — lunch — earlier in the day have better weight loss than those who have their lunch later in the day. So even in those cultures where they tend to eat late, they still find that eating earlier tends to be better for you.
Andrew Huberman: I was very relieved when Alan Aragon — who I consider one of the best public educators on the topic of protein and nutrition — reassured me that, except in rare circumstances where people are really trying to optimize every bit of muscle protein synthesis, 95% of the effect of getting enough protein can be accomplished by having two meals, maybe a little snack. It can be evenly or unevenly distributed. The whole notion that you could only assimilate about 30 grams per meal is totally false — it turns out you can assimilate up to 100 grams, with conditions like exercise setting that up. I find that very liberating. You could have breakfast and an early dinner with a snack in the middle. What I'm hearing from you is that you really want to avoid the big late dinner — you just don't want to eat too close to bedtime.
Dr. St-Onge: Correct.
Medium-chain triglycerides and the thermic effect of food
Andrew Huberman: What about medium-chain triglycerides? These were very popular in the health and biohacking space a few years ago — the whole bulletproof coffee notion, MCTs, butter coffee. That's more or less faded away. What are some of the known benefits of MCTs, where do you find them, and what brought you to them as a research topic?
Dr. St-Onge: This was a topic for my PhD dissertation. My PI had done prior work on this. What we did was use purified MCT oil — a liquid oil that contains 8-carbon and 10-carbon chain fatty acids, which are not very common in our general food source. We created a functional oil that also contained flaxseed oil to get some omega-3 fatty acids, and we added plant sterols because that was a big focus of my lab at McGill — plant sterols for cholesterol reduction and reduced risk of cardiovascular disease. The idea was to evaluate the impact on energy expenditure, because the way we process medium-chain triglycerides is different from how we process long-chain triglycerides — the 12, 14, 16, and up carbon chains. Medium-chain triglycerides travel directly to the liver and get metabolized. We burn them off more readily than long-chain triglycerides, which travel in peripheral circulation and get deposited in adipose tissue.
We did two separate studies — in men and in women — and in both, there was an increase in the thermic effect of food. You burned slightly more calories from the meal that contained medium-chain triglycerides compared to the meal that contained standard fat.
For my PhD, the first study we did was in women, and we were trying to match the saturated fat content of the diets, because medium-chain fatty acids are by default saturated. So we compared to a saturated-fat-matched control using beef tallow. It was a lot of beef tallow. Participants were not happy with that diet. We put it on mashed potatoes. Half of the total fat of the diet came from either the medium-chain-containing oil or the beef tallow. There was also the issue of the laxative effect of MCT oil — we had a few participants who initially felt a lot of gastrointestinal discomfort from consuming MCT because it was a lot early on. It resolved after a few days. It was a four-week study, so after a few days no one dropped out for GI issues.
Andrew Huberman: That's reassuring.
Dr. St-Onge: Beef tallow, because it has a lot of saturated fat, is solid at room temperature. So as soon as your food started to get a little colder, it would kind of gel on your plate. A couple of women felt it gave them a headache just from the smell of it.
With the MCTs, there was a statistically significant increase in the thermic effect of food — about 45 to 60 calories.
Andrew Huberman: Oh, I thought you were going to say a percent increase.
Dr. St-Onge: No, it's a small change. But if you're going to use this versus that, you're getting a little boost. If you repeat this a few times in a day — because when we measured the thermic effect of food, we measured it only after one meal — but repeated over three meals per day over a certain period of time, we did find changes in body composition, improvements in weight status with medium-chain triglyceride consumption, lean mass to fat mass.
Then we did a follow-up weight loss study with medium-chain triglycerides. This time it was just purified MCT oil versus olive oil, which is much more acceptable, and found greater weight loss with MCT.
Andrew Huberman: Based on what you're saying, it's reasonable if somebody wants to improve weight loss — I'm hearing a constellation of things: shift your meal timing to the first two-thirds or so of your day, which sounds like it will also improve sleep, which will also improve appetite regulation, satiety, and hunger signals. What is it — a tablespoon or two of MCT per day?
Dr. St-Onge: Yeah, about that.
Andrew Huberman: In place of some other oil, not in addition.
Dr. St-Onge: Not in addition. Correct.
Andrew Huberman: Some ginger. Are they additive? Are they synergistic?
Dr. St-Onge: I think they could probably be additive because the impact is through different mechanisms. Obviously no one's tested that. It makes me think of David Jenkins and the portfolio diet, which actually made the New York Times in December. The portfolio diet was a diet he designed for maximal cholesterol reduction. It was initially designed to have four specific foods: high in soy protein, nuts, plant sterols, and soluble fiber.
Andrew Huberman: It's going to be a tough one to get past most of the American public. People hear soy — nuts they like but are easy to overeat — and they hear plant sterols and they're somewhere else.
Dr. St-Onge: This diet went head-to-head with a lipid-lowering agent — a statin — and had the same cholesterol reduction.
Andrew Huberman: As a statin. Interesting. They've expanded it?
Dr. St-Onge: They've expanded it to be more flexible. It's not just soy protein now — it also includes legumes. They've added monounsaturated fats, so olive oil. When I look at a diet like the portfolio diet, or the current food suggestions by the FDA that emphasize unprocessed and minimally processed food, I think that's a step in the right direction.
The issue that always comes up for me is that in a more plant-based, grain-heavy, nut diet, it's very easy for people to overeat calories based on the amino acid protein foraging hypothesis — this idea that we eat until we get enough of the amino acids we want. A chicken breast or a couple of eggs is very satiating, whereas we can eat a lot of grains and nuts before we say that's enough. There seems to be this issue of how do you ensure cardiometabolic health while quelling hunger — and we can't have people walking around hungry all the time.
Andrew Huberman: And the GLPs help with that. It does get down to whether you include animal-based foods or not. How do you reconcile this from a public health perspective? Clearly the highly processed food diet is not going to work. But now there's this polarization — mostly plants, grains, nuts, lower saturated fat, improving blood lipids, or more protein for satiety. Do you see where I'm getting at?
Dr. St-Onge: I think there's no reason to pit one against the other. Having a diet that's more plant-based has higher volume — it's filling. It's hard to eat a lot of food when your food volume is high but doesn't provide as many calories. Then you put in some nuts, which helps prolong satiety because you get some protein and some healthful fats. I'm not saying animal products are bad. I think they're important for a diet and for health. It's just a matter of portion size and making sure there's not an overemphasis on animal products over plant-based products, because we know that plant-based products are so much healthier in terms of heart health, reduction of type 2 diabetes, cancer risk, and other metabolic diseases.
Andrew Huberman: I love fruits and vegetables. I do eat meat — half Argentine, you know. But I don't eat them in excess. The things that are very easy for people to overeat are starch-fat or starch-sugar-fat combinations. The stop signals are all pushed down and the go signals are all go. So reducing white foods as much as possible.
Dr. St-Onge: Yes. The white flour, white rice, white pasta — things that are not as colorful. If you're eating a slice of bread and it just dissolves in your mouth, it's not so good.
Portion sizes, food culture, and the American diet
Andrew Huberman: I was looking at the history of nutrition in this country. You're Canadian by birth, right? If you look at the history of food in the United States, it's never been particularly healthy. The foods we consider American — hamburgers, hot dogs, French fries, corn dogs, fried chicken, donuts — we've never been healthy about food. People probably just moved a lot, ate less, smoked a lot more, which is an appetite suppressant but gives you cancer. Maybe food volume was more in check, but if you look at traditional food in Europe, or in Canada — what sort of traditional fare is there? I think we're in this delusion that we were once healthy about food in this country.
Dr. St-Onge: I think portion size has a lot to do with it. Moving from Canada to the US, you go to a restaurant and the portion sizes are so big. It would never have occurred to me to take a doggy bag at a restaurant ever. Here it's like you kind of have to, or else you're throwing away half your plate or finishing the whole thing.
Also, the foods are different. When I moved to the US, the first thing the dietitian at my work told me was: do not buy bagged bread. Go to the grocery store, go to the bakery section, they'll cut it up for you. Apparently she was talking about too many additives, too much sugar. And then yogurt — I eat yogurt quite a bit, and the yogurt here in the US tasted sweeter to me. The same yogurt, same name, same everything — it was sweeter. Foods are formulated in different ways in different countries to appeal to the population of that country. Yogurt was a little less sweet in Canada than in the US, and less sweet in Europe than in Canada and the US.
Andrew Huberman: We love our sugars and fats in the United States and I think we've paid a substantial health debt as a consequence. Now, with Ozempic, Wegovy, and the other GLPs — a lot of people are finding it much easier, if not easy, to lose weight that they just couldn't before. They just could not control their appetite, and they're just not as interested in these foods. There's this argument that maybe they're not as interested in everything in life, and that's an important question that needs to be resolved.
Dr. St-Onge: Things are changing. There are a lot more plain yogurt options than there were when I first moved to the US. There's been a lot of resistance — sociological resistance to people being healthy. There really has. This idea that if you're eating clean, you have an eating disorder. Or if you're not going to drink alcohol, there's something wrong with you. I think the contrast to Europe is interesting — there's a lot of social convention built up around food that was healthy. In the United States, the social conventions built up around food and alcohol were pretty unhealthy. When people start making choices in the direction of their health, there's this quieter undercurrent of "are you being restrictive? Are you really going to live like that?" But then you look at the health outcomes.
Industry-funded research and the problem of null results
Andrew Huberman: There's a paper on your CV that I could not help but ask about: "Snack chips fried in corn oil alleviate cardiovascular risk factors when substituted for low-fat and high-fat snacks." What?
Dr. St-Onge: Yes.
Andrew Huberman: Tell me the data.
Dr. St-Onge: This was funded by Frito-Lay. At that time they had changed the oil they were using to fry their corn chips — Doritos, Fritos, Cheetos, and Tostitos. They had changed to corn oil, which is higher in polyunsaturated fats. The question was: does it make a difference? Is it going to improve health if people choose those snacks compared to other snacks?
We had three arms in that study. Each person went through each of the three arms for 25 days. The question was: if you have a choice for a snack and you go to the vending machine, do you eat a low-fat high-carbohydrate snack, a high-fat higher-saturated snack, or those chips? We gave two snacks a day for 25 days, rotating through four different chips. The better lipid profile was the one from the corn chips. They also had less lipoprotein(a), which is another cardiometabolic risk factor.
Andrew Huberman: In the head-to-head comparison of seed oils with saturated fat, there are many studies showing that when you substitute saturated fat with seed oils, cardiometabolic risk factors go down. I avoid seed oils actively because I like olive oil and butter — mostly olive oil. I love olive oil. And there's some health effects of olive oil. When you look at the studies that compare saturated fat to seed oils, you do see better outcomes for seed oils. But then there's this crowd that says: that's on a backdrop of reasonably high carbohydrate intake. When you start replacing some of those carbohydrates with lower carbohydrate, higher protein intake — not keto, but lower-ish starch and sugar — then maybe that balances out. The big contention seems to be around the processing of these seed oils — this idea that when you take fats and combine them with carbohydrate and heat them up a lot, you create factors that are not good for the body. What is the evidence for or against that?
Dr. St-Onge: Different oils have different smoke points. Each oil should be used for its appropriate usage and cooking process. Some oils, like flaxseed oil, you wouldn't heat up to very high temperatures. Oils that remain liquid at room temperature — that should be your barometer for what's better to use. I'm not saying people should avoid butter like the plague. All in moderation is okay. Depending on how you want to use your oil — some people find olive oil imparts a stronger taste in baked goods. Some are more flavorful and more fragile and will impart flavors to different foods where they're not supposed to be.
Andrew Huberman: You're not seed-oil averse, nor are you pro-seed-oil personally?
Dr. St-Onge: No. The seed oil debate has been very contaminated by the issues I mentioned, but also because many processed foods contain seed oil — they're much less expensive than using grass-fed butter or olive oil or even just ordinary butter. What's important is being nutrition-facts literate. When you're talking about processed foods, as much as possible cooking at home — but a lot of people don't really know how to do that, feel they don't have the time for it. Going to the grocery store, looking at the nutrition facts panel, comparing products to one another, and knowing what's relevant for your own health — because what's relevant for my health may not be what's relevant for your health. Some people are very salt-sensitive. Some people are very active and need to replace salt, so salt is not an issue for them. Being able to know what to pay attention to — because otherwise it just gets overwhelming.
Andrew Huberman: You mentioned the study was paid for by a company, and earlier you mentioned companies. I think this is an important issue. Anytime I cover a paper, I look at whether there are financial conflicts of interest. What's the difference between a company funding a study and a financial conflict of interest, if any? When a company funds research on something like the snack chips study, I think everyone would like to assume there's no explicit nor implicit pressure for a particular outcome. How does this stuff come about?
Dr. St-Onge: I'm glad you're asking that, because people often have a knee-jerk reaction to industry-sponsored studies. There are people who are very vocal against industry-sponsored research. But as scientists, we do research to the best of our abilities. We draft the research question, get the data, analyze it, publish it. Some of the studies I haven't been able to publish have been funded by industry and had null results. We wrote the paper, we wrote the report, we provided it to our sponsor out of courtesy — "This is the paper, we're going to submit it for publication, do what you need to do." They gave us the green light to submit. The companies aren't short-circuiting this. That's in the contract — your right to publish. Because otherwise, why would you do research? There's no point doing research if you're not going to be able to publish it.
That one paper I'm referring to — I must have tried five different journals. The findings are not exciting. They show there's no effect on our outcomes. It got rejected, rejected, rejected, rejected. I'm pretty persistent. I ran out of steam. So if I run out of steam, I can imagine so many other scientists who have null results running out of steam much quicker.
Andrew Huberman: So that's a null-result issue. It's not necessarily unique to industry-funded studies.
Dr. St-Onge: Not unique. Industry-sponsored studies — I often also say there are NIH reports of scientific misconduct. Reports of scientific misconduct can be found from NIH-sponsored studies where they find that the principal investigator falsified data. So to me, if you're not an honest scientist, it doesn't matter who's sponsoring your research.
Andrew Huberman: Doing science for any other reason than trying to find real answers is just insane. These people who do this are legitimately sick. It never ends well — these things always come out in the wash. So I'm hearing that negative outcomes are hard to publish. When you take on funding from a company to address a particular question about a product they sell, it sounds like you don't feel any explicit or implicit pressure. Why are they funding studies? Companies are selfish and they should be — they have shareholders. Why are they funding research?
Dr. St-Onge: They wanted to know if it had a health benefit so they could market a health benefit. And then if they don't find a health benefit, maybe they could switch to something else.
Andrew Huberman: I'm very sympathetic to the reality that there isn't a lot of research funding coming through NIH and NSF these days. Are you taking money from companies to do this work because it's a great way to fund studies? If NIH had more money to study nutrition, could you imagine just taking money from NIH to do it?
Dr. St-Onge: If you could get an NIH grant, that's the ultimate goal. Or USDA or other governmental grants. But sometimes there are specific foods or products that would be kind of hard to study without industry support because you need to get access to that specific food or product.
Andrew Huberman: My fairly frequent check-in on the at least stated goals of the now-being-revised NIH includes creating a forum and even some incentive for publishing negative or null results. Jay Bhattacharya, who's been on this podcast, has put that out publicly — we need those results. They're important. They steer people away from certain things that need to be steered away from. And there seems to be more and more interest in nutrition as a research topic. People are eating every day. There should be more federal funding for these things, and then there's no chance of bias.
Dr. St-Onge: I think people assume that if industry funded a study — especially on food — something's not to be trusted. I don't know why for food in particular. If you think about it, food and drugs — drug companies do research on their own products, and most of the R&D for drug companies is done in-house. We don't see the null results. I actually would prefer if it took on a different shape. I don't think outright scientific fraud — people making stuff up — is very rare.
Andrew Huberman: Very rare. But I do think there are a lot of questions about people, because of the incentives to publish. As you described, it's hard to publish null results. We will never know — and this is when you run a lab — you want to create a culture where graduate students and postdocs feel very comfortable saying "there's nothing here." You always have to teach the students well. You have a student who comes to you and says, "Hey, this is lower, this is better than this," and you look at the numbers and you say, well, it's 25 versus 27 and the standard deviation is 10. No — 25 is the same as 27. You have to make sure you teach them that even numerically different effects may not be statistically significantly different.
Dr. St-Onge: The ideal situation is when the student or postdoc doesn't believe their own results — they're like, "It's not really..." and then you have to convince them, "Actually, you have something interesting." That's a good situation.
Andrew Huberman: That's a good situation. I think this whole field of nutrition is contentious for some of the right reasons — it's so very important. And it's contentious also for a lot of unfortunate and unnecessary reasons. Among students and postdocs and the general public, when you interact, what are people most interested in with respect to nutrition? What's coming? What are your antennae picking up?
Dr. St-Onge: I think "what should I eat?" or "have you heard about XYZ fad?" — "have you heard that whatever product cures everything in the world?" It's often very specific to a product.
Andrew Huberman: Peptides are really big right now.
Dr. St-Onge: It's always something else.
Supplements, fiber, and whole foods
Andrew Huberman: You won't be held responsible for your answer, but do you supplement your diet with minerals like magnesium or anything like that, or do you just rely on careful food choices?
Dr. St-Onge: I prefer careful food choices. I think it's more pleasurable to eat a complete food diet. That said, I think there are some people who may need to supplement their diets, but I think people should strive to get their nutrients from whole foods.
Andrew Huberman: Fiber recommendations are really growing. Many people's doctors are now telling them to take a little bit of psyllium husk. I always thought psyllium husk was like you were going to eat seed husks — it's actually ground into a powder. I'm still afraid to take it, but I should. Doctors are now prescribing supplemental fiber at a pretty high rate from what I understand.
Dr. St-Onge: That's interesting. People don't want to eat their fruits and vegetables, but there's so much more in them — all sorts of polyphenols, all sorts of non-nutrient components that themselves may have benefits for health that we don't fully understand yet, that feed your gut, that may enhance fiber's impact on health.
Andrew Huberman: I love fruits and vegetables. Well, thank you so much for taking time out of your schedule. You have a very unique research program. Very few people can work on as many different things and find their points of intersection. I'm grateful that you're exploring these things. I appreciate your openness about industry-funded research — this is something that I think people need to know about. I certainly learned about that from you today. And based on your work, I think it's fair to say that we shouldn't just be encouraging people to get great sleep. We should be encouraging people to eat at times and eat foods that allow them to get great sleep, which will allow them to make better food choices, and so forth.
Dr. St-Onge: Yes. I talk often about a vicious cycle where you don't sleep well, you don't eat well, then that makes you not sleep so well. And I'm really hoping for people to get into a healthful cycle — where you get good sleep, where you can make good food choices that then help you get better sleep, to keep propelling this cycle of better health.
Andrew Huberman: I love it. It's true integrative medicine and science. I can also attest that when you sleep well, you make better food choices. When you eat well, you sleep better. Thank you so much for coming, for taking time out of your schedule. I've learned a ton.
Dr. St-Onge: Thank you.