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[00:00:00.000 --> 00:00:14.720] The episode you're about to listen to is a presentation I gave at the American Academy of Anti-Aging Medicine Conference in Palm Beach, Florida last May of 2024, where I discussed my top three strategies for optimizing metabolic health.
[00:00:14.720 --> 00:00:18.320] Number one, high-intensity interval training, or HIIT.
[00:00:18.320 --> 00:00:21.360] Number two, circadian timed eating.
[00:00:21.360 --> 00:00:24.560] And number three, optimizing good sleep.
[00:00:24.560 --> 00:00:30.480] So I'd also discuss how to implement these and the powerful effects they have on metabolic health.
[00:00:30.480 --> 00:01:00.080] In the presentation, I cover why high-intensity interval training outshines moderate intensity exercise for improving metabolic health, how lactate accumulation from higher training intensity benefits glucose homeostasis, the optimal high-intensity interval training conditions for improving body composition, how vigorous exercise boosts mitochondrial repair through a process called mitophagy, evidence-based HIIT protocols like Tabata, Wiengate, one minute on, one minute off, and the Norwegian 4x4.
[00:01:00.080 --> 00:01:07.120] How just 10 reps of doing squats are more powerful at improving glucose homeostasis than a 45-minute walk.
[00:01:07.120 --> 00:01:11.040] How to improve prostpranial glucose regulation with exercise snacks.
[00:01:11.040 --> 00:01:13.600] Why you should stop eating three hours before bed.
[00:01:13.600 --> 00:01:17.600] Why high normal glucose levels might accelerate atrophy in the hippocampus?
[00:01:17.600 --> 00:01:22.720] How even mild sleep restriction creates a metabolic profile similar to type 2 diabetes.
[00:01:22.720 --> 00:01:25.760] Why just one hour of extra sleep might help you lose weight.
[00:01:25.760 --> 00:01:31.600] How to ameliorate the increased mortality risk associated with sleeping less than seven hours a night, and much more.
[00:01:31.600 --> 00:01:40.880] As you listen to this presentation, one of the lifestyle strategies that I don't cover but still think has an outsized benefit for our longevity is omega-3 supplementation.
[00:01:40.880 --> 00:01:52.000] Omega-3 fatty acids are essential not only for neurodevelopment and cognitive function, but also for reducing cardiovascular mortality, dampening chronic inflammation, and generally supporting healthy aging.
[00:01:52.000 --> 00:01:58.240] Yet, more than 90% of the global population does not meet the recommended intake levels for omega-3s.
[00:01:58.240 --> 00:02:01.480] The easy solution for most people is to take a supplement.
[00:02:01.480 --> 00:02:05.800] However, choosing a quality supplement can be a daunting task.
[00:02:05.800 --> 00:02:27.960] That's why we've prepared a 13-page comprehensive guide on omega-3 supplementation that covers how to choose a quality omega-3 supplement, including factors like purity, freshness, the bioavailability of the different forms of omega-3, and dosing strategies that can elevate the omega-3 index to a level that's linked to a five-year increase in life expectancy.
[00:02:27.960 --> 00:02:40.120] We also provide a selection of a handful of omega-3 supplement brands that have scored positively on consumer, third-party consumer tests, which were evaluated based on key factors like oxidation and concentration.
[00:02:40.120 --> 00:02:45.640] You can download this free guide at fmfomega3guide.com.
[00:02:45.640 --> 00:02:50.920] One more time, that's fmfomega3guide.com.
[00:02:50.920 --> 00:02:53.960] On that note, I hope you enjoy this presentation.
[00:02:54.440 --> 00:02:55.640] So glad to be here.
[00:02:55.640 --> 00:03:00.440] I want to thank the organizers at A4M for inviting me to speak.
[00:03:00.760 --> 00:03:03.480] I spoke at Longevity Fest last December.
[00:03:03.480 --> 00:03:09.800] It was amazing, so I'm super pumped to be here today talking all about metabolic health.
[00:03:09.800 --> 00:03:22.600] And we're really gonna focus on what I think are three major lifestyle factors that can play a pretty big role in metabolic health.
[00:03:22.600 --> 00:03:29.400] So we're gonna be talking about sorry, is this not working?
[00:03:31.320 --> 00:03:32.600] All right.
[00:03:32.920 --> 00:03:47.840] We'll be talking about high-intensity interval training, which is a very time-efficient way to get your heart rate up, to improve insulin sensitivity, glucose homeostasis, glucose transport, mitochondrial function.
[00:03:48.160 --> 00:03:56.480] And we're going to talk a little bit about exercise snacks that can be strategically timed and how that can play a profound role in glucose homeostasis.
[00:03:56.480 --> 00:04:09.120] We're going to talk about circadian-timed eating, so why it's important to avoid late-night eating, what the effects of melatonin are on insulin, time-restricted eating, and circadian misalignment.
[00:04:09.120 --> 00:04:22.400] And then we're going to jump into sleep and the profound metabolic effects of sleep restriction on metabolic health, as well as some behavioral changes that can be implemented to improve metabolic health.
[00:04:25.600 --> 00:04:28.240] So let's start with high-intensity interval training.
[00:04:28.240 --> 00:04:34.320] So as I mentioned, this is a very time-efficient way to get your heart rate up and exercise.
[00:04:34.320 --> 00:04:38.320] So it involves very short bouts of intense exercise.
[00:04:38.320 --> 00:04:46.240] One, we're talking about heart rate up at at least 75% max heart rate, followed by periods of recovery.
[00:04:46.240 --> 00:04:58.560] There's a lot of different protocols we're going to discuss, but there have been lots of studies talking and showing that high-intensity interval training can improve glucose homeostasis, insulin sensitivity.
[00:04:58.560 --> 00:05:04.080] It also decreases fat mass, improves body composition, and enhances mitochondrial function.
[00:05:04.080 --> 00:05:14.400] So a meta-analysis of 50 different randomized control trials compared high-intensity interval training to moderate intensity continuous exercise.
[00:05:14.400 --> 00:05:25.280] So this would be exercise that's at a lower intensity, the kind of intensity where you can have a conversation, but you're maybe still breathy, sometimes called zone 2.
[00:05:25.280 --> 00:05:28.880] And this is a longer duration type of exercise.
[00:05:28.880 --> 00:05:37.720] So high intensity interval training outperforms moderate intensity continuous exercise at decreasing insulin resistance.
[00:05:38.040 --> 00:05:44.840] It also improves HBA1C levels, so the long-term biomarker for elevated blood glucose levels.
[00:05:44.840 --> 00:05:50.920] It leads to a decrease in body weight and also significantly lowers fasting blood glucose levels.
[00:05:50.920 --> 00:05:54.520] Again, this is 50 different randomized controlled trials.
[00:05:54.840 --> 00:06:23.880] And another systematic review of many different randomized controlled trials has found that again, high-intensity interval training outperforms moderate intensity continuous exercise at improving cardiorespiratory fitness, improving diastolic and systolic blood pressure, improving HDL, triglycerides, and fasting glucose, lowering oxidative stress, improving adiponectin and insulin sensitivity as well as beta cell function to produce insulin.
[00:06:23.880 --> 00:06:30.520] It increases PGC1 alpha, which is a biomarker for mitochondrial biogenesis, which we'll be discussing in a little bit.
[00:06:30.520 --> 00:06:36.280] And it also improves cardiac function, and this is all better than moderate intensity continuous exercise.
[00:06:36.280 --> 00:06:45.720] So it really provides an opportunity for people to have a time-efficient way of improving metabolic health.
[00:06:46.360 --> 00:07:00.200] And part of that is because when you get your heart rate up high, when you are putting in the effort, you're putting a strong stress on your mitochondria and your muscle.
[00:07:00.200 --> 00:07:07.320] And your mitochondria are unable to produce energy quick enough to keep up with the demand.
[00:07:07.320 --> 00:07:14.760] And so your muscle cells shift to using glucose as a source of energy through glycolysis.
[00:07:15.040 --> 00:07:21.920] And that ends up producing lactate, which was thought to be a byproduct, a metabolic byproduct.
[00:07:21.920 --> 00:07:24.640] Well, decades, a couple of decades ago, Dr.
[00:07:24.640 --> 00:07:37.360] George Brooks at the University of California in Berkeley was one of the pioneers to find that lactate generated from exercise is anything but a byproduct.
[00:07:37.360 --> 00:07:41.440] So steady-state lactate levels are less than one millimolar.
[00:07:41.760 --> 00:07:49.040] When you crank up the intensity of exercise, you can go anywhere up to 15, 17 millimolar.
[00:07:49.040 --> 00:07:54.480] And that lactate gets in circulation and it's consumed by other organs.
[00:07:54.480 --> 00:08:00.240] It goes into the brain, it goes into the heart, it goes back into the muscle, it goes to the kidneys, it goes to the liver.
[00:08:00.240 --> 00:08:04.880] And it's serving a very utilizable source of energy.
[00:08:04.880 --> 00:08:12.400] So lactate can be used and converted into acetyl-CoA and used by energy, by the mitochondria.
[00:08:12.400 --> 00:08:16.560] But probably one of its most important roles is as a signaling molecule.
[00:08:16.560 --> 00:08:22.480] It's a way for your muscle to connect, to communicate with other organs and other tissues.
[00:08:22.480 --> 00:08:34.800] And one of its signaling roles is back in the muscle, it's increasing the translocation of glucose-4 transporters to the cell surface of the muscle, glute-4 transporters.
[00:08:34.800 --> 00:08:37.840] And so lactate gets back into the muscle.
[00:08:38.320 --> 00:08:45.360] It's basically telling the muscle, hey, we're using a lot of glucose here for energy, so we need to bring more glucose in.
[00:08:45.360 --> 00:08:50.080] And the way it does it is by increasing glute-4 transporters at the muscle.
[00:08:50.080 --> 00:08:55.120] And I mentioned lactate levels go up during this intense exercise.
[00:08:55.120 --> 00:08:56.320] That's very transient.
[00:08:56.320 --> 00:09:06.920] So after about 20 minutes, when exercise stops, your lactate levels go back to baseline because all these other organs, including the muscle, are consuming it so quickly.
[00:09:06.920 --> 00:09:18.040] However, the increase in glucose 4 transporters stays elevated for up to 48 hours, with the first 24 hours being the most robust.
[00:09:18.040 --> 00:09:25.640] So you're getting a long-term effect from that signaling from lactate back to the muscle to increase glute-4 transporters.
[00:09:25.640 --> 00:09:33.800] And that is why high-intensity interval training is so potent and powerful at improving glucose homeostasis.
[00:09:33.800 --> 00:09:44.040] So there was another meta-analysis of 36 randomized control trials that were looking at optimal conditions of high-intensity interval training for improving body composition.
[00:09:44.040 --> 00:09:53.640] And so it's been identified that the duration of the HIIT workout, high-intensity interval training workout, eight weeks is optimal for improving body composition.
[00:09:53.640 --> 00:09:57.160] The frequency is at least three sessions a week.
[00:09:57.160 --> 00:10:08.760] And the intervals are 60 seconds of, 60 seconds or less of the robust, intense interval, followed by about 90 seconds of recovery.
[00:10:08.760 --> 00:10:13.320] And this leads to improvements in reducing fat mass.
[00:10:13.320 --> 00:10:17.000] Cycling and running was the best at doing that.
[00:10:17.000 --> 00:10:23.240] Also, improving percent body fat, so body fat reduction, and that was the best with running.
[00:10:23.560 --> 00:10:30.040] And then increasing fat-free mass, which includes muscle, and the best at that was actually cycling.
[00:10:30.040 --> 00:10:37.160] So, these are some of the optimal conditions for improving body composition with respect to high-intensity interval training protocols.
[00:10:37.800 --> 00:10:58.560] We're going to talk about how high-intensity interval training can regulate mitochondrial function, but before we talk about that, I think it's important to recognize that people with metabolic syndrome, insulin resistance, obesity, and type 2 diabetes have been identified to have pretty profound dysregulated mitochondria.
[00:10:58.560 --> 00:11:16.880] So, the mitochondria and skeletal muscle from people with type 2 diabetes and obesity have been found in multiple studies to respire about 40% less than skeletal muscle cells from people that do not have type 2 diabetes or people that are lean.
[00:11:16.880 --> 00:11:20.400] So, their mitochondria are dysfunctional.
[00:11:20.720 --> 00:11:26.480] And subsequent studies have also identified structural defects in the mitochondria.
[00:11:26.480 --> 00:11:30.560] So, mitochondria from people with type 2 diabetes are fragmented.
[00:11:30.560 --> 00:11:38.080] So, mitochondria are typically, they form a very connected network, this sort of look like vermicelli spaghetti.
[00:11:38.400 --> 00:11:49.360] And that's a really beautiful network of mitochondria that are able to undergo respiration and do their functions quite robustly.
[00:11:49.840 --> 00:12:05.760] When mitochondria become really fragmented, they are dysfunctional, they can't utilize or even produce energy very well, and they're on their way to basically dying and causing cells to die.
[00:12:05.760 --> 00:12:13.440] So, there's a very intricate connection between structure of mitochondria and the function of mitochondria.
[00:12:13.440 --> 00:12:27.440] And that's important because vigorous exercise, high-intensity exercise, has been shown to increase this repair process in mitochondria known as mitophagy.
[00:12:27.440 --> 00:12:39.000] So, when exercise is intense enough, it increases the nutrient-sensing protein, AMP kinase, AMPK.
[00:12:39.320 --> 00:12:40.840] It activates it.
[00:12:40.840 --> 00:12:48.200] And this causes the mitochondria to send the signal that they need to repair themselves.
[00:12:48.200 --> 00:12:54.200] And so mitochondria can be sort of dysfunctional or they can be really dysfunctional.
[00:12:54.200 --> 00:13:04.200] So mitophagy can clear away an entire dysfunctional mitochondria to be used and recycled, or it can clear away pieces of a dysfunctional mitochondria.
[00:13:04.200 --> 00:13:16.600] So when you're doing that acute exercise, your mitochondria, if you have a dysfunctional one, the mitophagy pathway gets activated and the mitochondria fizzes off.
[00:13:16.600 --> 00:13:25.560] It kind of goes through this mitochondrial fission process, and that damaged part of the mitochondria then goes and is recycled through the lysosome.
[00:13:25.560 --> 00:13:40.600] And then what you have is a long-term effect of after doing routine high-intensity exercise, you then have more healthy functional mitochondria because you're just getting rid of the damaged part of the mitochondria.
[00:13:40.600 --> 00:13:44.360] If the mitochondria is dysfunctional enough, you're going to get rid of the whole mitochondria.
[00:13:44.360 --> 00:13:49.880] And by the way, the AMP kinase pathway, many of you are probably thinking, oh, well, that's a nutrient-sensing pathway.
[00:13:49.880 --> 00:13:52.840] It's activated during periods of fasting.
[00:13:52.840 --> 00:13:54.200] And that is true.
[00:13:54.200 --> 00:14:02.440] AMP kinase is activated during periods of fasting, and fasting is a powerful signal for inducing autophagy and mitophagy.
[00:14:02.440 --> 00:14:14.280] However, in this particular study, people that did this high-intensity, vigorous exercise for 30 minutes, it did not matter if they had fasted for 16 hours or not.
[00:14:14.280 --> 00:14:16.240] There was no difference in the mitophagy.
[00:14:16.400 --> 00:14:27.520] So, in other words, the exercise itself was such a strong signal for activating mitophagy that it didn't matter if they had not fasted for 16 hours because it was so powerful.
[00:14:27.840 --> 00:14:37.680] On top of the repair process, high-intensity interval training is one of the most robust exercise modalities that can increase mitochondrial biogenesis.
[00:14:37.680 --> 00:14:42.240] So, the growth of new mitochondria, increasing mitochondrial volume.
[00:14:42.240 --> 00:14:52.960] So, you're having this double whammy effect where you're getting repairing of the mitochondria, getting rid of the unhealthy parts, and then you're increasing the growth of new mitochondria.
[00:14:52.960 --> 00:15:19.040] So, one of the reasons high-intensity interval training is very good at increasing mitochondrial biogenesis compared to, let's say, moderate continuous exercise is because lactate that's generated from that vigorous exercise is a signaling molecule to activate the protein that very much regulates mitochondrial biogenesis in skeletal muscle, PGC1-alpha.
[00:15:19.040 --> 00:15:21.840] So, again, lactate is playing that signaling role.
[00:15:22.240 --> 00:15:27.200] It's generated by the muscle, it's taken back up by the muscle, and then it's communicating with the muscle.
[00:15:27.200 --> 00:15:35.840] It's saying, hey, we can't make energy fast enough because this exercise is so intense, we need more mitochondria to be able to do that.
[00:15:35.840 --> 00:15:52.240] So, it's an adaptation to the vigorous intensity exercise, and that adaptation is making more mitochondria, which is obviously very beneficial for not only people with type 2 diabetes, metabolic syndrome, obesity, but also everybody.
[00:15:52.880 --> 00:16:05.240] So, mitochondrial biogenesis improves energy efficiency in mitochondria, and also is associated with other benefits like decreased atrophy and improved exercise endurance as well.
[00:16:05.560 --> 00:16:10.200] So, there's a whole host of benefits with increasing mitochondrial biogenesis.
[00:16:10.200 --> 00:16:20.200] So, a lot of the high-intensity interval training protocols that were used in these systematic analysis and these meta-analyses were evidence-based HIIT protocols.
[00:16:20.200 --> 00:16:21.800] So, Tabata is one that's used.
[00:16:21.800 --> 00:16:28.120] That's a 20-second on, 10-second off interval, 20 seconds at the highest intensity you can do.
[00:16:28.120 --> 00:16:35.320] You're going all out and then you're resting for 10 seconds, and that's repeated eight times for a total of a four-minute workout.
[00:16:35.320 --> 00:16:39.880] In some cases, the Tabata protocol was repeated twice.
[00:16:39.880 --> 00:16:55.320] The Wingate HIT protocol is another very commonly used one, and that is a 30-second all-out sprint followed by four minutes of active recovery where you're low-intensity, and then you do that four to six times.
[00:16:55.320 --> 00:16:57.640] That's about a 20-minute or so workout.
[00:16:57.640 --> 00:17:01.400] And then there's the conventional workout, it's the one-minute on, one-minute off.
[00:17:01.400 --> 00:17:09.800] So, you're going as intense as you can for one minute, and then you have one minute of very light active recovery, and then you repeat that 10 times.
[00:17:09.800 --> 00:17:11.640] So, that's a 20-minute workout.
[00:17:11.640 --> 00:17:18.280] It is hard, but it's very, very effective at improving a variety of metabolic parameters.
[00:17:18.280 --> 00:17:29.560] And then there's the clinical workout, also known as the Norwegian 4x4, which I like to call it because the Norwegian ski team often uses this hit protocol for their training.
[00:17:29.560 --> 00:17:37.160] It's a four-minute interval where you're going as intense as you can for four minutes, and then you have light recovery for three minutes.
[00:17:37.160 --> 00:17:41.400] So, you're going very, very light, getting your heart rate down, and that's repeated four times.
[00:17:41.400 --> 00:17:44.120] So, it's about a 25-minute workout.
[00:17:46.800 --> 00:17:54.960] So let's just talk a little bit about exercise snacks, which is a type of high-intensity neural training workout.
[00:17:54.960 --> 00:18:04.720] It involves doing something at vigorous intensity, you know, a vigorous intensity heart rate for one to two minutes.
[00:18:04.720 --> 00:18:10.320] And they're often called exercise snacks because you can just do them whenever throughout the day.
[00:18:10.320 --> 00:18:30.480] And I think this is very relevant because I just came across a study a couple of weeks ago that showed 10 body weight squats, okay, 10 for every 45 minutes was more powerful at improving glucose homeostasis than a 30-minute walk.
[00:18:30.480 --> 00:18:39.520] So I feel like that is, it's just, it kind of puts it in context because how easy is it to get up and do 10 body weight squats, right, every 45 minutes?
[00:18:39.520 --> 00:18:42.080] I mean, it doesn't get easier than that.
[00:18:42.720 --> 00:18:55.600] And there's also a reason to strategically time these exercise snacks either 30 minutes to an hour before a meal or 30 minutes to an hour after a meal.
[00:18:56.560 --> 00:19:08.400] So the timing of these exercise snacks has been shown in several studies, people with type 2 diabetes or insulin resistance, to really improve their glucose regulation after a meal.
[00:19:08.400 --> 00:19:13.920] So their post-praanial glucose regulation and their glucose disposal was improved.
[00:19:13.920 --> 00:19:27.360] Again, because getting that high-intensity exercise where you're generating some lactate, it's increasing glute-4 transporters at the muscle, and that is then causing glucose to come into the muscle.
[00:19:27.360 --> 00:19:34.440] It's lowering the burden of your pancreas to have to produce insulin, and it's improving glucose homeostasis.
[00:19:34.440 --> 00:19:43.320] So, exercise snacks around meals is an easy way to improve post-praneial glucose regulation and glucose homeostasis.
[00:19:43.320 --> 00:19:49.800] It's obviously very relevant for people with type 2 diabetes, but also I think for everyone.
[00:19:49.800 --> 00:19:55.800] Exercise snacks has also been associated with a decrease in all-cause mortality.
[00:19:55.800 --> 00:20:13.800] So, there have been very large studies out of the UK Biobank data where people are wearing accelerometers and they're part of the vigorous intensity, sorry, vigorous intermittent lifestyle activity studies that have been done, VILPA, they're called.
[00:20:13.800 --> 00:20:26.760] And what those studies have identified is that people that do one to two minutes of vigorous intensity exercise, and these are things like just sprinting up the stairs rather than taking the escalator or walking up the stairs.
[00:20:26.760 --> 00:20:32.680] And they do this, this is like a one to two minute high-intensity burst, and they do this three times a day.
[00:20:32.680 --> 00:20:38.200] That's associated with a 50% reduction in cardiovascular-related mortality.
[00:20:38.200 --> 00:20:40.120] 50% reduction.
[00:20:40.120 --> 00:20:45.640] It's also associated with a 40% reduction in cancer-related mortality and all-cause mortality.
[00:20:45.640 --> 00:20:54.920] So, cancer, cardiovascular disease, these are all diseases that are associated with metabolic dysregulation.
[00:20:55.240 --> 00:21:11.480] So, implementing exercise snacks, I think, is one of the easiest ways to get, you know, get a little bit of exercise, get your heart rate up, get that lactate generated, increase your glucose transporters, but also just improve your mood to break up your sedentary time.
[00:21:11.480 --> 00:21:21.760] You know, so being sitting at your desk for a couple of hours is sedentary, and being sedentary is an independent risk factor for certain diseases like cancer.
[00:21:21.760 --> 00:21:25.920] So, I mean, we've all been sitting here for what, an hour at least.
[00:21:25.920 --> 00:21:30.640] I say we get up and we do a minute of body weight squats.
[00:21:30.640 --> 00:21:32.000] Body weight squats.
[00:21:32.000 --> 00:21:34.000] All right, ready?
[00:21:35.200 --> 00:21:37.520] Okay, I'm gonna get this timer going.
[00:21:37.520 --> 00:21:38.800] We're gonna do a whole minute.
[00:21:38.800 --> 00:21:40.880] I'm saving you the high knees.
[00:21:41.200 --> 00:21:42.160] All right, here we go.
[00:21:42.160 --> 00:21:44.160] So, we're gonna do body weight squats.
[00:21:44.160 --> 00:21:49.680] We're gonna try to get the heart rate up, and we're gonna do it for one minute.
[00:21:50.000 --> 00:21:52.080] Try to go low if you can.
[00:21:52.080 --> 00:21:58.080] You wanna feel the burn in your quads?
[00:21:58.480 --> 00:22:00.240] Go sideways there.
[00:22:01.520 --> 00:22:04.000] Keep going.
[00:22:04.320 --> 00:22:07.280] We're not even at 30 seconds yet.
[00:22:11.440 --> 00:22:13.440] Okay, we're halfway.
[00:22:14.400 --> 00:22:16.000] Are you guys getting your heart rate up?
[00:22:16.000 --> 00:22:17.280] Are you feeling it?
[00:22:28.640 --> 00:22:37.680] 15 seconds left.
[00:22:37.680 --> 00:22:44.160] Five, four, three, two.
[00:22:46.800 --> 00:22:47.680] All right.
[00:22:51.840 --> 00:22:56.240] So, a little out of breath, feeling good.
[00:22:56.240 --> 00:22:58.880] Increase the blood flow to the brain.
[00:22:59.200 --> 00:23:07.880] But, but more importantly, glute four transporters.
[00:23:07.880 --> 00:23:20.200] Okay, so we're gonna shift gears and we're gonna talk a little bit about circadian meal timing.
[00:23:22.760 --> 00:23:37.800] All right, okay, so as everybody here knows about circadian rhythm, we're all diurnal creatures here, more active during the day, less active in the evening, right?
[00:23:37.800 --> 00:23:41.160] Our metabolism is also on a circadian rhythm.
[00:23:41.160 --> 00:23:49.400] We are more insulin-sensitive earlier in the day and later in the evening, less insulin-sensitive.
[00:23:49.400 --> 00:24:01.000] Part of that, so let me talk about a study that I think is pretty telling in terms of insulin sensitivity and glucose regulation throughout the day.
[00:24:01.000 --> 00:24:08.920] So, participants were given the same exact meals in the morning, in the afternoon, or in the evening.
[00:24:08.920 --> 00:24:13.880] Okay, so same macronutrient composition, same caloric content, everything the same.
[00:24:14.200 --> 00:24:22.760] And participants were much more insulin-sensitive in their first meal, given in the morning, compared to their evening meal.
[00:24:23.080 --> 00:24:33.320] And I think part of this has to do with our circadian rhythm, and as we get later in the day, melatonin.
[00:24:33.640 --> 00:24:59.920] So, back in like the early 2000s, about 2009, a lot of studies started coming out in the genetics world where the variation, a very, a certain variation in the melatonin receptor 1B was identified to be a pretty high risk factor for developing type 2 diabetes and for having basically insulin dysregulation.
[00:24:59.920 --> 00:25:03.920] So, people were not producing insulin correctly.
[00:25:03.920 --> 00:25:15.520] And it was very perplexing to scientists at the time because melatonin was thought to be just this hormone that is produced by the pineal gland that is regulating our sleep.
[00:25:15.520 --> 00:25:20.400] It's quieting down our brain, telling us it's time to get sleepy, right?
[00:25:20.400 --> 00:25:22.160] It's making us tired.
[00:25:22.160 --> 00:25:32.480] Well, it turns out, after more studies started to investigate this, that we have melatonin receptors on our pancreas, on our pancreatic beta eyelid cells.
[00:25:32.480 --> 00:25:38.720] And the melatonin receptors, the 1B receptors, are sensitive to melatonin.
[00:25:39.040 --> 00:25:47.200] People with that gene variation had a hypersensitive receptor where little bits of melatonin were enough to really kind of activate it.
[00:25:47.200 --> 00:25:56.000] And so it turns out melatonin is also quieting down our pancreas at night and telling our pancreas, we don't have to produce so much insulin.
[00:25:56.000 --> 00:25:56.720] It's nighttime.
[00:25:56.720 --> 00:25:58.560] We're not going to be eating.
[00:25:58.560 --> 00:26:10.960] And so there's a systemic effect of melatonin, not only on our brain, but also on our other organs that are important for metabolism.
[00:26:11.280 --> 00:26:25.040] And I think this is a really good reason to think about when you're going to have your last meal and why it is detrimental to engage in late night eating.
[00:26:25.040 --> 00:26:33.160] So, our bodies naturally produce melatonin about three or so hours before our natural bedtime.
[00:26:33.480 --> 00:26:41.800] So, it's a good rule of thumb to make sure that you have finished your last meal, you have finished eating, before that time.
[00:26:41.800 --> 00:26:50.600] So, before three hours before your natural bedtime, it's really just a good rule of thumb to kind of make sure you're done eating that.
[00:26:50.600 --> 00:26:57.560] When you wake up in the morning, you're also still producing some melatonin for about the first hour.
[00:26:57.560 --> 00:27:05.880] Now, bright light exposure can inhibit that, so it can hasten the clearance of the melatonin.
[00:27:05.880 --> 00:27:14.200] But also, I think it's a good idea to wait about an hour after you first wake up before you start taking in your meal.
[00:27:14.200 --> 00:27:21.080] So, bright light exposure we'll talk about also is very important for regulating our circadian rhythm, and that's important for sleep.
[00:27:21.080 --> 00:27:37.080] But generally speaking, I think just aligning your meals with your circadian rhythm, it makes sense when you think about the role of melatonin in quieting down our brain and also our pancreas, it makes a lot of sense why you don't want to be eating late at night.
[00:27:37.400 --> 00:28:00.600] So, just as a, you know, I think an aside here, having glucose levels in the normal range, but on the high normal range, so high normal glucose, was associated in UK biobank data with higher incidence of atrophy in the hippocampus, so the part of the brain involved in learning and memory.
[00:28:00.600 --> 00:28:09.640] So, people that just had higher than, they were on the high end of normal had more atrophy in their hippocampus than people on the low end of normal.
[00:28:09.640 --> 00:28:22.000] So, this is in the absence of any clinical type 2 diabetes, really sort of highlighting the importance of everyone considering their metabolic health, even if you don't have type 2 diabetes, even if you're not, you know, pre-diabetic.
[00:28:22.240 --> 00:28:28.480] You just, you want to make sure that your glucose regulation is the best it can be.
[00:28:29.760 --> 00:28:31.280] Circadian misalignment.
[00:28:31.280 --> 00:28:42.240] Now, so many of you may have come from, like me, the West Coast, or perhaps Europe, and you're out of sync with your circadian rhythm.
[00:28:42.240 --> 00:28:51.680] So circadian misalignment refers to when your natural internal clock is out of sync based on a behavioral pattern.
[00:28:51.680 --> 00:28:54.560] So this is very common with jet lag.
[00:28:54.560 --> 00:29:00.880] It's very common in shift workers who are up in the night, in the evening, working and eating.
[00:29:01.200 --> 00:29:05.280] It's also very common in people with erratic sleep behaviors.
[00:29:05.280 --> 00:29:11.520] So there's been studies done where people, our participants, are their circadian misaligned.
[00:29:11.520 --> 00:29:13.520] So they're out of sync.
[00:29:13.520 --> 00:29:18.560] So they're basically their sleep and meals are shifted by about 12 hours.
[00:29:18.560 --> 00:29:22.480] And when that happens, people have about a 6% increase in their glucose.
[00:29:22.800 --> 00:29:25.280] They make 22% more insulin.
[00:29:25.280 --> 00:29:27.200] They have decreased leptin levels.
[00:29:27.200 --> 00:29:30.800] So that's the hormone involved in being satiated.
[00:29:30.800 --> 00:29:42.080] And their postprandial glucose levels are in the pre-diabetic range, only by shifting their circadian clock by 12 hours.
[00:29:42.080 --> 00:29:46.320] So it has a profound effect being circadian misaligned.
[00:29:46.320 --> 00:29:53.760] Exercise can help with that, especially high-intensity interval training, but also time-restricted eating.
[00:29:53.760 --> 00:30:03.480] So, time-restricted eating refers to eating all your food in a restricted window of time instead of just eating ad libdum, right, throughout the day.
[00:30:04.120 --> 00:30:13.160] And typically, time-restricted eating is anywhere between six to ten hours of an eating window, and the rest is fasting.
[00:30:13.160 --> 00:30:14.600] There's been a lot of work done by Dr.
[00:30:14.600 --> 00:30:19.000] Sachin Panda on time-restricted eating in shift workers.
[00:30:19.320 --> 00:30:36.600] He's done some work on firefighters showing, you know, these firefighters that are up all night, if they eat their food in a time-restricted eating window, you know, eight hours, ten hours, that it improves their metabolic biomarkers.
[00:30:36.600 --> 00:30:43.480] So, there's been a lot of meta-analyses done on time-restricted eating and how it improves metabolic health.
[00:30:43.480 --> 00:30:48.520] Now, time-restricted eating does not mean you have to reduce your calorie intake.
[00:30:48.520 --> 00:30:59.400] But we're going to talk about in a minute, people that are naturally doing time-restricted eating tend to do that because they're skipping snacks, so they're skipping their dessert or they're skipping a meal.
[00:30:59.400 --> 00:31:09.000] So, when people do end up reducing their calorie intake along with time-restricted eating, they end up losing weight and losing fat.
[00:31:09.320 --> 00:31:21.560] But, independent of calories, so if they do not change their caloric intake but they are practicing time-restricted eating, it can improve glucose regulation, insulin sensitivity, it can lower blood pressure.
[00:31:21.880 --> 00:31:27.640] And so, there's a lot of metabolic parameters that are improved with just the time-restricted eating.
[00:31:27.960 --> 00:31:38.120] Now, as I mentioned, people that do practice time-restricted eating, so there's been multiple studies looking at even just a 10-hour window, which isn't even that restricted.
[00:31:38.120 --> 00:31:48.880] People that are doing a 10-hour time-restricted eating window, not a controlled trial, but just like you tell them to do it, they end up reducing on average about 200 calories a day.
[00:31:49.200 --> 00:31:52.880] Again, because typically people are skipping snacks or meals.
[00:31:52.880 --> 00:32:10.000] And so, that does lead to weight loss and it reduces waste size, body fat percentage, and also reduces visceral fat, which is the deep fat that surrounds your organs that's secreting pro-inflammatory cytokines and hormones that play a role in type 2 diabetes, metabolic syndrome.
[00:32:10.000 --> 00:32:16.080] But also, you know, emerging evidence indicates visceral fat plays a role in cancer as well.
[00:32:16.560 --> 00:32:24.720] Time-restricted eating also lowers blood pressure, it improves lipid profiles, and improves the HbA1C glucose biomarker.
[00:32:26.000 --> 00:32:31.680] Early time-restricted eating, so this is typically people that end their last meal at about 4 p.m.
[00:32:32.000 --> 00:32:38.560] Usually, early time-restricted eating is about a six-hour window, so it's a shorter eating window.
[00:32:38.560 --> 00:32:47.440] People that do early time-restricted eating without reducing their calorie intake dramatically improve a variety of metabolic parameters.
[00:32:47.440 --> 00:32:53.120] Insulin levels are improved, insulin sensitivity is improved, beta cells are more responsive to glucose.
[00:32:53.440 --> 00:33:01.040] The improvements in blood pressure were so profound that they were equivalent to some anti-hypertensive treatments.
[00:33:01.040 --> 00:33:02.960] So, that was a big finding of that study.
[00:33:02.960 --> 00:33:05.600] And then, X oxidative stress levels were also improved.
[00:33:05.600 --> 00:33:08.240] And this is early time-restricted eating.
[00:33:08.240 --> 00:33:14.480] There's been a meta-analysis of about 12 randomized controlled trials looking at early time-restricted eating.
[00:33:14.480 --> 00:33:19.920] Again, this was defined at stopping your last meal at about 4 p.m.
[00:33:20.560 --> 00:33:23.440] And then comparing it to late, later time-restricted eating.
[00:33:23.440 --> 00:33:27.120] So, people that were stopping their meals not at 4, but a little bit later.
[00:33:27.120 --> 00:33:32.120] And all the eating windows were either 4 to 10 hours.
[00:33:32.440 --> 00:33:43.880] And early time-restricted eating does have more profound effects on glucose regulation, largely because, again, we're more insulin-sensitive earlier, less insulin-sensitive later.
[00:33:44.040 --> 00:33:49.160] Once the melatonin starts to kick in, again, that just gets much worse.
[00:33:49.160 --> 00:33:58.680] So early time-restricted eating can improve fasting blood glucose levels and insulin resistance more than late, later time-restricted eating.
[00:33:58.680 --> 00:34:04.200] But it also has a more profound effect on the blood pressure regulation, so lowering blood pressure.
[00:34:04.200 --> 00:34:10.760] Late time-restricted eating can sort of maintain blood pressure, but it doesn't improve it like the early time-restricted eating.
[00:34:10.760 --> 00:34:16.440] And both early and late improve lipid profiles as well as fasting glucose and insulin resistance.
[00:34:16.440 --> 00:34:19.320] Just early does it a little bit more robustly.
[00:34:19.320 --> 00:34:47.080] So I think there's pretty strong evidence that if you are circadian misaligned, jet lagged, for example, if you're a shift worker, or just people that are, you know, wanting to sort of try to optimize their glucose homeostasis as much as possible, certainly people with metabolic dysfunction may benefit from time-restricted eating, along with the high-intensity enabled training and the 10 body weight squats every 45 minutes.
[00:34:47.720 --> 00:35:08.280] Okay, so let's talk about the last topic I want to discuss this morning, and it has to do with poor sleep and how most of us, I think, are aware when we don't get a good night's sleep, we don't feel cognitively on game, our mood is affected, we feel lethargic, we don't have as much energy.
[00:35:08.280 --> 00:35:19.200] But I'm not sure that most people realize the profound effect that even mild sleep restriction has on our metabolic health and glucose regulation.
[00:35:19.200 --> 00:35:32.560] And this is extremely relevant because about one-third of people in the United States do not meet the recommendations, which is seven to nine hours of sleep per night for sleep.
[00:35:32.560 --> 00:35:35.760] And again, this is very relevant for jet lag.
[00:35:35.760 --> 00:35:41.360] I mean, there's a lot of relevance here for poor sleep.
[00:35:41.360 --> 00:35:48.400] So mild sleep restriction, this is one to three fewer hours of sleep per night.
[00:35:48.400 --> 00:35:50.320] So I mean, one, it's not a lot.
[00:35:50.320 --> 00:35:54.960] Doing that three nights in a row can increase fasting insulin levels.
[00:35:54.960 --> 00:36:03.680] It can lead to higher insulin concentrations, elevated fasting glucagon levels, and also it decreases insulin sensitivity.
[00:36:03.680 --> 00:36:09.120] Again, this is just getting one hour less of sleep a night for three nights.
[00:36:09.120 --> 00:36:12.480] I mean, how many of us have probably even done that at this conference, right?
[00:36:12.480 --> 00:36:19.200] I mean, it's very easy and very applicable, and it's having a profound effect on metabolism.
[00:36:19.200 --> 00:36:23.760] Sleep debt is the cumulative effect of sleep restriction, right?
[00:36:23.760 --> 00:36:27.120] So this is when you're having multiple days of the sleep restriction.
[00:36:27.120 --> 00:36:33.600] So in this case, it was four, sorry, three days of four hours less sleep per night.
[00:36:33.600 --> 00:36:46.000] That lets you 40% slower glucose clearance, 30% decrease in glucose effectiveness, so this is independent of insulin, similar to diabetes, and 30% lower insulin response.
[00:36:46.000 --> 00:36:48.000] So, this is really indicating early diabetes.
[00:36:48.000 --> 00:36:49.360] And these aren't healthy people.
[00:36:49.360 --> 00:36:55.280] This is healthy people after just three nights of having four hours less sleep a night.
[00:36:55.280 --> 00:36:58.800] Very profound effect on metabolism.
[00:37:00.200 --> 00:37:08.840] There's been large meta-analyses done on longitudinal studies looking at type 2 diabetes risk and sleep duration.
[00:37:08.840 --> 00:37:17.720] And it's been identified that the optimal range of sleep for the lowest type 2 diabetes risk is seven to nine hours of sleep a night.
[00:37:17.720 --> 00:37:24.040] So going below seven hours or above nine hours were both associated with an increased risk for type 2 diabetes.
[00:37:24.360 --> 00:37:40.760] So the seven hour threshold, getting less than seven hours of sleep a night, was associated with increases in fasting insulin, increases in glucose levels, homo IR was elevated, higher HbA1C, and then also visceral fat was increased as well.
[00:37:40.760 --> 00:37:46.200] So again, getting less than seven hours of sleep a night, which a lot of people do routinely.
[00:37:46.200 --> 00:37:50.520] And speaking of the elevated Hb1A1C, I think this is really important.
[00:37:50.520 --> 00:38:01.640] Most of you probably realize this, but when you are constantly having elevations in blood glucose levels, this leads to advanced glycation end products, or ages, as they're called.
[00:38:01.640 --> 00:38:11.000] And it's certainly a huge problem in people with type 2 diabetes because they are constantly having glucose dysregulation in their elevated blood glucose levels.
[00:38:11.000 --> 00:38:25.000] But generally speaking, when you have the HbA1C high, you are talking about glucose reacting with lipids and proteins through the maillard reaction, including collagen.
[00:38:25.000 --> 00:38:33.560] And this is all inside of our blood vessels, our arteries, you know, our myocardium making, you know, surrounding our heart.
[00:38:33.560 --> 00:38:38.560] When you have those advanced glycation end products forming, it stiffens that collagen.
[00:38:38.440 --> 00:38:38.960] Okay, college.
[00:38:39.080 --> 00:38:43.000] HbA1C levels turn over after about what, 120 days?
[00:38:43.000 --> 00:38:45.280] Your collagen is in there forever.
[00:38:44.680 --> 00:38:49.520] So what happens is you have those advanced glycation end products.
[00:38:50.560 --> 00:38:57.360] If it's in your blood vessels, it stiffens the blood vessels and this leads to hypertension, plays a big role in hypertension.
[00:38:57.360 --> 00:39:09.760] When it's happening in the arteries and the myocardium, this decreases cardiovascular compliance and it really plays a role in the stiffening of your heart with age.
[00:39:10.080 --> 00:39:17.760] And so these advanced glycation end products increase the risk of cardiovascular disease, heart attacks, and hypertension.
[00:39:17.760 --> 00:39:30.960] So having these elevations in your blood glucose levels and subsequently the HBA1C biomarker, which biomarks that, is so much more than just type 2 diabetes risk.
[00:39:31.360 --> 00:39:33.280] It's cardiovascular health.
[00:39:33.280 --> 00:39:39.280] And it's really a cumulative effect that plays a role as we age.
[00:39:40.560 --> 00:39:50.480] There are a variety of mechanisms that have been identified for how short sleep and mild sleep restriction can cause dysfunctional metabolism.
[00:39:50.480 --> 00:39:53.840] So we're going to talk about decreased insulin signaling in adipocytes.
[00:39:53.840 --> 00:39:57.120] We're going to talk about lower beta cell sensitivity to glucose.
[00:39:57.120 --> 00:40:03.120] We're going to talk about impaired glucose absorption in muscle and liver and then changes in satiety hormones.
[00:40:03.120 --> 00:40:06.800] So there's been some studies looking at sleep restriction.
[00:40:06.800 --> 00:40:10.400] This is about four hours of sleep a night for four days.
[00:40:10.400 --> 00:40:14.560] It decreased insulin signaling in adipocytes by 30%.
[00:40:14.560 --> 00:40:21.760] So I mean your adipocytes are one of the major sinks, aside from muscle, for glucose disposal, right?
[00:40:22.400 --> 00:40:24.640] Storing it as fat, you know, for energy.
[00:40:24.640 --> 00:40:32.440] But a 30% reduction in cellular insulin signaling in adipocytes is, I mean, you're talking about these aren't healthy people.
[00:40:29.600 --> 00:40:41.640] This is like a healthy person immediately becoming obese or immediately becoming type 2 diabetic after just four days, right, of sleep restriction.
[00:40:41.640 --> 00:40:45.240] So it's very profound in terms of metabolic health.
[00:40:45.560 --> 00:40:52.120] Sleep loss, so mild sleep loss, even, it does promote an obesogenic profile.
[00:40:52.120 --> 00:41:01.320] And so a lot of work has been done out of Yves Van Coucher's lab, and she's looked a lot at these hunger hormones, satiety hormones.
[00:41:01.320 --> 00:41:07.800] So after two days of four hours less sleep, leptin levels go down.
[00:41:07.800 --> 00:41:13.640] So people are not feeling satiated by their food because leptin regulates satiation.
[00:41:14.280 --> 00:41:16.040] And their ghrelin levels increase.
[00:41:16.040 --> 00:41:17.400] So it's a double whammy.
[00:41:17.400 --> 00:41:18.920] Ghrelin is the hunger hormone.
[00:41:18.920 --> 00:41:19.960] It tells you you're hungry.
[00:41:19.960 --> 00:41:23.000] And so they're getting this continual hunger.
[00:41:23.000 --> 00:41:27.240] So global hunger ratings go up, global appetite goes up.
[00:41:27.240 --> 00:41:32.680] So people are not satiated by their food and they're hungry throughout their day.
[00:41:32.680 --> 00:41:49.080] And again, Eve Van Coucher's work has shown that people eat more and they're consuming foods and have cravings for processed foods, highly refined sugars, salty foods, processed fats and fatty foods.
[00:41:49.080 --> 00:41:57.000] So they're eating up to 45% more of those processed, unhealthy foods, and their hunger ratings are 24% higher.
[00:41:57.000 --> 00:42:01.720] So they're eating even more than they would if they were getting a good night's sleep.
[00:42:04.280 --> 00:42:11.160] So I think it's pretty clear that sleep restriction, poor sleep, does cause dysfunctional metabolism.
[00:42:11.160 --> 00:42:15.000] And so the question is: can you fix your sleep and improve metabolic health?
[00:42:15.680 --> 00:42:19.840] So there's a couple of evidence-based ways we're going to talk about improving sleep.
[00:42:19.840 --> 00:42:22.640] Both of them involve good sleep hygiene.
[00:42:22.960 --> 00:42:27.040] So good sleep hygiene is really the foundation of good sleep.
[00:42:27.040 --> 00:42:30.400] And there's a variety of factors that are like a checklist of it.
[00:42:30.400 --> 00:42:37.200] And I didn't include all of them, but some of the main ones here are using light smartly.
[00:42:37.200 --> 00:42:50.000] So bright light exposure, first thing in the morning, at least 30 minutes, is one of the most important ways to reset your circadian rhythm so that you become sleepy at a normal time.
[00:42:50.000 --> 00:42:57.200] Very, very important for resetting circadian rhythm, but also important for stopping that melatonin production when you're first waking up, right?
[00:42:57.840 --> 00:43:04.240] Also, avoiding bright light, blue light exposure in the evening after sunset, right?
[00:43:04.240 --> 00:43:08.800] Blue light is what is inhibiting melatonin production in our eyes.
[00:43:10.000 --> 00:43:20.560] It's through our eyes, actually not in our eyes, but it's inhibiting melanopsin, which then is involved in the signaling of producing melatonin to make us sleepy.
[00:43:20.560 --> 00:43:26.880] And so you want to avoid blue light either by having light dimmers or different color lights, maybe red or orange.
[00:43:26.880 --> 00:43:29.920] Also, glasses you can wear to filter it out.
[00:43:29.920 --> 00:43:34.400] But also realize that screens are full of bright light, blue light as well.
[00:43:34.400 --> 00:43:39.120] So turning down the screens, maybe avoiding screens at night is another good idea.
[00:43:39.120 --> 00:43:45.840] Also, making sure your room is dark because there's been studies showing that even a little bit of ambient light coming in disrupts sleep.
[00:43:45.840 --> 00:43:47.920] Managing temperature is important.
[00:43:47.920 --> 00:43:54.640] So part of what melatonin is doing, besides making you sleepy, is it's lowering your core body temperature.
[00:43:54.640 --> 00:43:56.400] And this is part of the circadian rhythm.
[00:43:56.400 --> 00:43:58.560] It's important for good sleep.
[00:43:58.560 --> 00:44:01.960] And so you want to make sure you're not sleeping in a really hot room.
[00:43:59.840 --> 00:44:06.040] And there's many ways that you can obviously maintain your bedroom temperature.
[00:44:06.360 --> 00:44:09.160] Optimizing meal timing is also important.
[00:44:09.160 --> 00:44:19.240] So in addition to the importance of avoiding eating, you know, like three hours before your bedtime because of melatonin production, it also improves your sleep.
[00:44:19.240 --> 00:44:21.160] So this has actually been some work by Dr.
[00:44:21.160 --> 00:44:23.960] Sachin Panda at the Salk Institute as well.
[00:44:23.960 --> 00:44:32.600] He's identified from large studies that he's done that people that stop eating three hours, at least three hours before their bedtime, sleep better.
[00:44:32.600 --> 00:44:36.120] And that's also partially because you're not digesting.
[00:44:36.360 --> 00:44:39.640] I mean, digesting is a lot of, it's an energy consuming process, right?
[00:44:39.640 --> 00:44:41.720] That's happening while you sleep.
[00:44:41.720 --> 00:44:46.520] So it makes sense that it would also disrupt sleep somewhat.
[00:44:46.840 --> 00:44:48.120] Regular exercise.
[00:44:48.120 --> 00:44:50.680] So again, this is all, these are all tied together.
[00:44:50.680 --> 00:44:54.520] So the exercise is also a very powerful zeitgeber.
[00:44:54.520 --> 00:45:03.640] So, you know, just routine exercise is also really important for resetting the circadian rhythm and helping you just get on that rhythm and go to bed at a normal time.
[00:45:03.640 --> 00:45:05.320] And then monitoring caffeine intake.
[00:45:05.320 --> 00:45:09.000] Caffeine shifts the circadian clock by 45 minutes.
[00:45:09.000 --> 00:45:13.560] So if you're drinking a cup of coffee, that's 45 minutes of a circadian shift.
[00:45:13.560 --> 00:45:17.160] And then you have another cup of coffee, that's 45 minutes of a circadian shift, right?
[00:45:17.160 --> 00:45:24.280] And so you're going to be going to bed hours later if you're drinking four cups of coffee, particularly if it's afternoon.
[00:45:24.280 --> 00:45:28.760] Obviously, there's a lot of individual variation between the way we metabolize caffeine.
[00:45:28.760 --> 00:45:37.880] So yeah, there's some individual variation, but generally speaking, it still shifts circadian rhythm by about close to an hour.
[00:45:38.520 --> 00:45:47.360] So, sleep extension is one of the evidence-based ways that's been shown to improve sleep, and this involves really just adjusting your bedtimes to increase the sleep time.
[00:45:44.680 --> 00:45:50.560] So, either going to bed earlier or sleeping in both of those.
[00:45:50.880 --> 00:45:57.360] It also involves a lot of consultations with sleep experts and then sleep hygiene recommendations, like we just discussed.
[00:45:57.360 --> 00:46:06.160] And so, there's been meta-analyses looking at sleep extension in people that are short sleepers, so they're getting fewer than seven hours of sleep per night.
[00:46:06.160 --> 00:46:20.640] And when they undergo this type of behavioral change, when they're engaged in sleep extension, for every hour additional that they're sleeping per night, they improve their insulin sensitivity regardless of their body weight.
[00:46:20.640 --> 00:46:23.760] They improve and normalize their hormones, leptin and ghrelin.
[00:46:23.760 --> 00:46:25.280] They have reduced appetite, right?
[00:46:25.280 --> 00:46:26.880] They're not getting so hungry.
[00:46:26.880 --> 00:46:31.920] Their sugar intake goes down and their caloric reduction goes down and they lose weight.
[00:46:31.920 --> 00:46:48.000] So, all these things, of course, the sugar intake and the reducing the calories, is all regulated by the satiety hormones, which again, if you're increasing your sleep, you can basically flip that switch to kind of help regulate them back and normalize them back.
[00:46:48.640 --> 00:46:56.560] The other type of evidence-based way of improving sleep is a certain type of cognitive behavioral therapy for insomnia, CBTI.
[00:46:56.560 --> 00:47:01.840] This is probably one of the most used, well-known, and effective ways to improve insomnia.
[00:47:01.840 --> 00:47:04.000] It involves a variety of factors.
[00:47:04.000 --> 00:47:07.520] I'm not going to go in depth on, but stimulus control is the main one.
[00:47:07.520 --> 00:47:11.280] So, that means the bed is only associated with sleep.
[00:47:11.280 --> 00:47:18.160] So, no watching TV in your bed, no scrolling on your phone, no doing anything, screens on your bed.
[00:47:18.320 --> 00:47:19.680] Bed is for sleeping only.
[00:47:19.680 --> 00:47:20.960] So, that's stimulus control.
[00:47:20.960 --> 00:47:25.760] It involves sleep restriction, which is a little ironic, paradoxical.
[00:47:26.080 --> 00:47:41.560] So, that means if you're laying in your bed and you're tossing and turning and you're up for an hour or two or three, it means getting out of your bed and going into another room, dark room, like your living room couch, and laying there and you do some relaxation techniques that you learn about.
[00:47:41.560 --> 00:47:44.120] and then wait till you get sleepy and then go back into the bed.
[00:47:44.120 --> 00:47:46.360] So again, bed is for sleep only.
[00:47:46.360 --> 00:47:54.120] It also involves implementing a variety of the sleep hygiene factors that we talked about, sleep education, and again, some relaxation techniques.
[00:47:54.120 --> 00:48:04.120] So meta-analyses of CBTI have also been shown to improve metabolic health in people with insomnia, including improved HBA1C, improved blood pressure.
[00:48:04.120 --> 00:48:08.680] Of course, their sleep quality and insomnia factors and all those things improve as well.
[00:48:08.680 --> 00:48:21.240] So it's pretty clear that people that have poor sleep, that have insomnia, that are short sleepers, if they work on fixing their sleep, they improve their metabolic health.
[00:48:22.520 --> 00:48:34.600] But there are situations where it is challenging to sleep longer, stay, you know, to sleep in, to do, to all these things, because maybe you're a new parent, right?
[00:48:34.600 --> 00:48:37.320] And you have to wake up and your sleep will be compromised.
[00:48:37.320 --> 00:48:39.560] There's absolutely nothing you can do because of it.
[00:48:39.560 --> 00:48:41.320] There's other things as well, right?
[00:48:41.320 --> 00:48:43.960] I mean, jet lag, things like that.
[00:48:44.280 --> 00:48:50.840] So there is another way to improve metabolic health, even when you're not sleeping optimal.
[00:48:50.840 --> 00:48:55.640] And that takes us full circle back to the beginning of the talk with high-intensity interval training.
[00:48:55.640 --> 00:49:03.080] So high-intensity interval training has shown to be a very robust way to improve metabolic health when you are sleep-restricted.
[00:49:03.720 --> 00:49:23.840] So, there's been studies that have shown that high-intensity interval training, if you do three sessions over five days of also being sleep-restricted, so sleeping four hours less a night, you can still improve your circadian rhythm, you can still improve your glucose tolerance, your mitochondrial function, and biomarkers of mitochondrial function and mitochondrial biogenesis.
[00:49:23.840 --> 00:49:29.760] And you know, I mean, this is important because, again, the glucose regulation, so you're doing that high-intensity interval training.
[00:49:29.760 --> 00:49:39.840] Well, part of the way that high-intensity interval training, I mean, part of the way that sleep restriction impairs glucose regulation is it makes your muscle less responsive to glucose.
[00:49:39.840 --> 00:49:42.240] And so, what is high-intensity interval training doing?
[00:49:42.240 --> 00:49:43.760] It's doing the exact opposite, right?
[00:49:43.760 --> 00:49:47.440] It's increasing glute-4 transporters, and it's bringing the glucose into your muscle.
[00:49:47.440 --> 00:49:55.360] So, you're really countering some of that negative effect of poor sleep on your muscle.
[00:49:55.680 --> 00:50:00.160] Even doing high-intensity interval training before you know you're going to be sleep-restricted.
[00:50:00.160 --> 00:50:02.080] So, I got on my Peloton yesterday.
[00:50:02.080 --> 00:50:04.480] I went hard right before I got on my flight from California.
[00:50:04.480 --> 00:50:07.920] I knew I was going to lose some sleep because it's three hours ahead in Florida.
[00:50:08.640 --> 00:50:20.160] Doing high-intensity motival training before you're going to be sleep-restricted still mostly rescues the high blood glucose and acute insulin resistance that's caused by sleep restriction.
[00:50:20.160 --> 00:50:32.400] So, yet again, just really important with respect to tools that we have at our disposal to help mitigate some of the effects of chronic sleep loss or even acute sleep loss, both.
[00:50:34.000 --> 00:50:43.280] And a lot of those protocols, again, are the ones we've discussed: the Tabata, the Wingate, conventional one-minute on, one-minute off, and the Norwegian 4x4 HIP protocol.
[00:50:43.760 --> 00:50:47.840] A lot of HIIP protocols out there that people can do, or you just do your exercise snacks as well.
[00:50:47.840 --> 00:50:55.040] I mean, that also has been shown to increase glucose homeostasis, as I mentioned, the 10 body weight squats.
[00:50:55.040 --> 00:51:18.760] And I do want to mention one last study before we end on time, and that is, again, there's lots of data out there to be harvested from the UK Biobank data, and there's been studies that have identified people that sleep fewer than seven hours or greater than nine hours a night have a higher all-cause mortality.
[00:51:19.080 --> 00:51:34.920] However, if those people are physically active and they're getting, and they're meeting the guidelines for physical activity, 75 minutes a week of intense, vigorous exercise or 150 minutes a week of moderate intensity exercise, they do not have a higher all-cause mortality.
[00:51:34.920 --> 00:51:38.040] They have the same mortality risk as someone that's getting good sleep.
[00:51:38.040 --> 00:51:46.840] Yet again, exercise can forgive a lot of sins, and there's no reason to not do a time-efficient type of high-intensity interval training workout.
[00:51:47.000 --> 00:51:49.560] It's, you know, time-efficient, it's easy.
[00:51:49.560 --> 00:51:52.760] Exercise snacks, I mean, there's all the evidence there.
[00:51:52.760 --> 00:51:53.960] We just have to implement it.
[00:51:53.960 --> 00:51:55.400] Make it part of your hygiene.
[00:51:55.400 --> 00:51:58.680] Like you brush your teeth every morning, you do your hit.
[00:51:59.640 --> 00:52:05.560] So, in conclusion, I think there's three really powerful tools we have to improve our metabolic health.
[00:52:05.560 --> 00:52:11.720] I talked about the vigorous intensity exercise, high-intensity interval training, making it part of your personal hygiene.
[00:52:11.720 --> 00:52:20.040] Also, trying to eat your meals in accordance with your circadian rhythm, a good rule of thumb, stop eating three hours before bed because of that melatonin production.
[00:52:20.040 --> 00:52:24.600] It's nice to have a pretty restricted time window, eight, ten hours.
[00:52:24.600 --> 00:52:42.360] And then also making sure we optimize our sleep and having good sleep, and that can be anything from the bright, you know, good sleep hygiene and all those things we talked about to people that have problems and doing things like CBTI or sleep extension, and certainly back to the exercise again to help.
[00:52:42.360 --> 00:52:46.800] And with that, thank you so much for staying here and listening to me talk for an hour.
[00:52:44.680 --> 00:52:51.520] I hope you guys enjoy the rest of the conference, and thanks again.

Prompt 2: Key Takeaways

Now please extract the key takeaways from the transcript content I provided.

Extract the most important key takeaways from this part of the conversation. Use a single sentence statement (the key takeaway) rather than milquetoast descriptions like "the hosts discuss...". 

Limit the key takeaways to a maximum of 3. The key takeaways should be insightful and knowledge-additive. 

IMPORTANT: Return ONLY valid JSON, no explanations or markdown. Ensure:
- All strings are properly quoted and escaped
- No trailing commas
- All braces and brackets are balanced
Format: {"key_takeaways": ["takeaway 1", "takeaway 2"]}

Prompt 3: Segments

Now identify 2-4 distinct topical segments from this part of the conversation.

For each segment, identify:
- Descriptive title (3-6 words)  
- START timestamp when this topic begins (HH:MM:SS format)
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Most important Key takeaway from that segment. Key takeaway must be specific and knowledge-additive.
- Brief summary of the discussion

IMPORTANT: The timestamp should mark when the topic/segment STARTS, not a range. Look for topic transitions and conversation shifts.

Return ONLY valid JSON. Ensure all strings are properly quoted, no trailing commas:
{
  "segments": [
    {
      "segment_title": "Topic Discussion", 
      "timestamp": "01:15:30",
      "key_takeaway": "main point from this segment",
      "segment_summary": "brief description of what was discussed"
    }
  ]
}

Timestamp format: HH:MM:SS (e.g., 00:05:30, 01:22:45) marking the START of each segment.

Prompt 4: Media Mentions

Now scan the transcript content I provided for ACTUAL mentions of specific media titles:

Find explicit mentions of:
- Books (with specific titles)
- Movies (with specific titles)  
- TV Shows (with specific titles)
- Music/Songs (with specific titles)

DO NOT include:
- Websites, URLs, or web services
- Other podcasts or podcast names

IMPORTANT: 
- Only include items explicitly mentioned by name. Do not invent titles.
- Valid categories are: "Book", "Movie", "TV Show", "Music"
- Include the exact phrase where each item was mentioned
- Find the nearest proximate timestamp where it appears in the conversation
- THE TIMESTAMP OF THE MEDIA MENTION IS IMPORTANT - DO NOT INVENT TIMESTAMPS AND DO NOT MISATTRIBUTE TIMESTAMPS
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Timestamps are given as ranges, e.g. 01:13:42.520 --> 01:13:46.720. Use the EARLIER of the 2 timestamps in the range.

Return ONLY valid JSON. Ensure all strings are properly quoted and escaped, no trailing commas:
{
  "media_mentions": [
    {
      "title": "Exact Title as Mentioned",
      "category": "Book",
      "author_artist": "N/A",
      "context": "Brief context of why it was mentioned",
      "context_phrase": "The exact sentence or phrase where it was mentioned",
      "timestamp": "estimated time like 01:15:30"
    }
  ]
}

If no media is mentioned, return: {"media_mentions": []}

Full Transcript

[00:00:00.000 --> 00:00:14.720] The episode you're about to listen to is a presentation I gave at the American Academy of Anti-Aging Medicine Conference in Palm Beach, Florida last May of 2024, where I discussed my top three strategies for optimizing metabolic health.
[00:00:14.720 --> 00:00:18.320] Number one, high-intensity interval training, or HIIT.
[00:00:18.320 --> 00:00:21.360] Number two, circadian timed eating.
[00:00:21.360 --> 00:00:24.560] And number three, optimizing good sleep.
[00:00:24.560 --> 00:00:30.480] So I'd also discuss how to implement these and the powerful effects they have on metabolic health.
[00:00:30.480 --> 00:01:00.080] In the presentation, I cover why high-intensity interval training outshines moderate intensity exercise for improving metabolic health, how lactate accumulation from higher training intensity benefits glucose homeostasis, the optimal high-intensity interval training conditions for improving body composition, how vigorous exercise boosts mitochondrial repair through a process called mitophagy, evidence-based HIIT protocols like Tabata, Wiengate, one minute on, one minute off, and the Norwegian 4x4.
[00:01:00.080 --> 00:01:07.120] How just 10 reps of doing squats are more powerful at improving glucose homeostasis than a 45-minute walk.
[00:01:07.120 --> 00:01:11.040] How to improve prostpranial glucose regulation with exercise snacks.
[00:01:11.040 --> 00:01:13.600] Why you should stop eating three hours before bed.
[00:01:13.600 --> 00:01:17.600] Why high normal glucose levels might accelerate atrophy in the hippocampus?
[00:01:17.600 --> 00:01:22.720] How even mild sleep restriction creates a metabolic profile similar to type 2 diabetes.
[00:01:22.720 --> 00:01:25.760] Why just one hour of extra sleep might help you lose weight.
[00:01:25.760 --> 00:01:31.600] How to ameliorate the increased mortality risk associated with sleeping less than seven hours a night, and much more.
[00:01:31.600 --> 00:01:40.880] As you listen to this presentation, one of the lifestyle strategies that I don't cover but still think has an outsized benefit for our longevity is omega-3 supplementation.
[00:01:40.880 --> 00:01:52.000] Omega-3 fatty acids are essential not only for neurodevelopment and cognitive function, but also for reducing cardiovascular mortality, dampening chronic inflammation, and generally supporting healthy aging.
[00:01:52.000 --> 00:01:58.240] Yet, more than 90% of the global population does not meet the recommended intake levels for omega-3s.
[00:01:58.240 --> 00:02:01.480] The easy solution for most people is to take a supplement.
[00:02:01.480 --> 00:02:05.800] However, choosing a quality supplement can be a daunting task.
[00:02:05.800 --> 00:02:27.960] That's why we've prepared a 13-page comprehensive guide on omega-3 supplementation that covers how to choose a quality omega-3 supplement, including factors like purity, freshness, the bioavailability of the different forms of omega-3, and dosing strategies that can elevate the omega-3 index to a level that's linked to a five-year increase in life expectancy.
[00:02:27.960 --> 00:02:40.120] We also provide a selection of a handful of omega-3 supplement brands that have scored positively on consumer, third-party consumer tests, which were evaluated based on key factors like oxidation and concentration.
[00:02:40.120 --> 00:02:45.640] You can download this free guide at fmfomega3guide.com.
[00:02:45.640 --> 00:02:50.920] One more time, that's fmfomega3guide.com.
[00:02:50.920 --> 00:02:53.960] On that note, I hope you enjoy this presentation.
[00:02:54.440 --> 00:02:55.640] So glad to be here.
[00:02:55.640 --> 00:03:00.440] I want to thank the organizers at A4M for inviting me to speak.
[00:03:00.760 --> 00:03:03.480] I spoke at Longevity Fest last December.
[00:03:03.480 --> 00:03:09.800] It was amazing, so I'm super pumped to be here today talking all about metabolic health.
[00:03:09.800 --> 00:03:22.600] And we're really gonna focus on what I think are three major lifestyle factors that can play a pretty big role in metabolic health.
[00:03:22.600 --> 00:03:29.400] So we're gonna be talking about sorry, is this not working?
[00:03:31.320 --> 00:03:32.600] All right.
[00:03:32.920 --> 00:03:47.840] We'll be talking about high-intensity interval training, which is a very time-efficient way to get your heart rate up, to improve insulin sensitivity, glucose homeostasis, glucose transport, mitochondrial function.
[00:03:48.160 --> 00:03:56.480] And we're going to talk a little bit about exercise snacks that can be strategically timed and how that can play a profound role in glucose homeostasis.
[00:03:56.480 --> 00:04:09.120] We're going to talk about circadian-timed eating, so why it's important to avoid late-night eating, what the effects of melatonin are on insulin, time-restricted eating, and circadian misalignment.
[00:04:09.120 --> 00:04:22.400] And then we're going to jump into sleep and the profound metabolic effects of sleep restriction on metabolic health, as well as some behavioral changes that can be implemented to improve metabolic health.
[00:04:25.600 --> 00:04:28.240] So let's start with high-intensity interval training.
[00:04:28.240 --> 00:04:34.320] So as I mentioned, this is a very time-efficient way to get your heart rate up and exercise.
[00:04:34.320 --> 00:04:38.320] So it involves very short bouts of intense exercise.
[00:04:38.320 --> 00:04:46.240] One, we're talking about heart rate up at at least 75% max heart rate, followed by periods of recovery.
[00:04:46.240 --> 00:04:58.560] There's a lot of different protocols we're going to discuss, but there have been lots of studies talking and showing that high-intensity interval training can improve glucose homeostasis, insulin sensitivity.
[00:04:58.560 --> 00:05:04.080] It also decreases fat mass, improves body composition, and enhances mitochondrial function.
[00:05:04.080 --> 00:05:14.400] So a meta-analysis of 50 different randomized control trials compared high-intensity interval training to moderate intensity continuous exercise.
[00:05:14.400 --> 00:05:25.280] So this would be exercise that's at a lower intensity, the kind of intensity where you can have a conversation, but you're maybe still breathy, sometimes called zone 2.
[00:05:25.280 --> 00:05:28.880] And this is a longer duration type of exercise.
[00:05:28.880 --> 00:05:37.720] So high intensity interval training outperforms moderate intensity continuous exercise at decreasing insulin resistance.
[00:05:38.040 --> 00:05:44.840] It also improves HBA1C levels, so the long-term biomarker for elevated blood glucose levels.
[00:05:44.840 --> 00:05:50.920] It leads to a decrease in body weight and also significantly lowers fasting blood glucose levels.
[00:05:50.920 --> 00:05:54.520] Again, this is 50 different randomized controlled trials.
[00:05:54.840 --> 00:06:23.880] And another systematic review of many different randomized controlled trials has found that again, high-intensity interval training outperforms moderate intensity continuous exercise at improving cardiorespiratory fitness, improving diastolic and systolic blood pressure, improving HDL, triglycerides, and fasting glucose, lowering oxidative stress, improving adiponectin and insulin sensitivity as well as beta cell function to produce insulin.
[00:06:23.880 --> 00:06:30.520] It increases PGC1 alpha, which is a biomarker for mitochondrial biogenesis, which we'll be discussing in a little bit.
[00:06:30.520 --> 00:06:36.280] And it also improves cardiac function, and this is all better than moderate intensity continuous exercise.
[00:06:36.280 --> 00:06:45.720] So it really provides an opportunity for people to have a time-efficient way of improving metabolic health.
[00:06:46.360 --> 00:07:00.200] And part of that is because when you get your heart rate up high, when you are putting in the effort, you're putting a strong stress on your mitochondria and your muscle.
[00:07:00.200 --> 00:07:07.320] And your mitochondria are unable to produce energy quick enough to keep up with the demand.
[00:07:07.320 --> 00:07:14.760] And so your muscle cells shift to using glucose as a source of energy through glycolysis.
[00:07:15.040 --> 00:07:21.920] And that ends up producing lactate, which was thought to be a byproduct, a metabolic byproduct.
[00:07:21.920 --> 00:07:24.640] Well, decades, a couple of decades ago, Dr.
[00:07:24.640 --> 00:07:37.360] George Brooks at the University of California in Berkeley was one of the pioneers to find that lactate generated from exercise is anything but a byproduct.
[00:07:37.360 --> 00:07:41.440] So steady-state lactate levels are less than one millimolar.
[00:07:41.760 --> 00:07:49.040] When you crank up the intensity of exercise, you can go anywhere up to 15, 17 millimolar.
[00:07:49.040 --> 00:07:54.480] And that lactate gets in circulation and it's consumed by other organs.
[00:07:54.480 --> 00:08:00.240] It goes into the brain, it goes into the heart, it goes back into the muscle, it goes to the kidneys, it goes to the liver.
[00:08:00.240 --> 00:08:04.880] And it's serving a very utilizable source of energy.
[00:08:04.880 --> 00:08:12.400] So lactate can be used and converted into acetyl-CoA and used by energy, by the mitochondria.
[00:08:12.400 --> 00:08:16.560] But probably one of its most important roles is as a signaling molecule.
[00:08:16.560 --> 00:08:22.480] It's a way for your muscle to connect, to communicate with other organs and other tissues.
[00:08:22.480 --> 00:08:34.800] And one of its signaling roles is back in the muscle, it's increasing the translocation of glucose-4 transporters to the cell surface of the muscle, glute-4 transporters.
[00:08:34.800 --> 00:08:37.840] And so lactate gets back into the muscle.
[00:08:38.320 --> 00:08:45.360] It's basically telling the muscle, hey, we're using a lot of glucose here for energy, so we need to bring more glucose in.
[00:08:45.360 --> 00:08:50.080] And the way it does it is by increasing glute-4 transporters at the muscle.
[00:08:50.080 --> 00:08:55.120] And I mentioned lactate levels go up during this intense exercise.
[00:08:55.120 --> 00:08:56.320] That's very transient.
[00:08:56.320 --> 00:09:06.920] So after about 20 minutes, when exercise stops, your lactate levels go back to baseline because all these other organs, including the muscle, are consuming it so quickly.
[00:09:06.920 --> 00:09:18.040] However, the increase in glucose 4 transporters stays elevated for up to 48 hours, with the first 24 hours being the most robust.
[00:09:18.040 --> 00:09:25.640] So you're getting a long-term effect from that signaling from lactate back to the muscle to increase glute-4 transporters.
[00:09:25.640 --> 00:09:33.800] And that is why high-intensity interval training is so potent and powerful at improving glucose homeostasis.
[00:09:33.800 --> 00:09:44.040] So there was another meta-analysis of 36 randomized control trials that were looking at optimal conditions of high-intensity interval training for improving body composition.
[00:09:44.040 --> 00:09:53.640] And so it's been identified that the duration of the HIIT workout, high-intensity interval training workout, eight weeks is optimal for improving body composition.
[00:09:53.640 --> 00:09:57.160] The frequency is at least three sessions a week.
[00:09:57.160 --> 00:10:08.760] And the intervals are 60 seconds of, 60 seconds or less of the robust, intense interval, followed by about 90 seconds of recovery.
[00:10:08.760 --> 00:10:13.320] And this leads to improvements in reducing fat mass.
[00:10:13.320 --> 00:10:17.000] Cycling and running was the best at doing that.
[00:10:17.000 --> 00:10:23.240] Also, improving percent body fat, so body fat reduction, and that was the best with running.
[00:10:23.560 --> 00:10:30.040] And then increasing fat-free mass, which includes muscle, and the best at that was actually cycling.
[00:10:30.040 --> 00:10:37.160] So, these are some of the optimal conditions for improving body composition with respect to high-intensity interval training protocols.
[00:10:37.800 --> 00:10:58.560] We're going to talk about how high-intensity interval training can regulate mitochondrial function, but before we talk about that, I think it's important to recognize that people with metabolic syndrome, insulin resistance, obesity, and type 2 diabetes have been identified to have pretty profound dysregulated mitochondria.
[00:10:58.560 --> 00:11:16.880] So, the mitochondria and skeletal muscle from people with type 2 diabetes and obesity have been found in multiple studies to respire about 40% less than skeletal muscle cells from people that do not have type 2 diabetes or people that are lean.
[00:11:16.880 --> 00:11:20.400] So, their mitochondria are dysfunctional.
[00:11:20.720 --> 00:11:26.480] And subsequent studies have also identified structural defects in the mitochondria.
[00:11:26.480 --> 00:11:30.560] So, mitochondria from people with type 2 diabetes are fragmented.
[00:11:30.560 --> 00:11:38.080] So, mitochondria are typically, they form a very connected network, this sort of look like vermicelli spaghetti.
[00:11:38.400 --> 00:11:49.360] And that's a really beautiful network of mitochondria that are able to undergo respiration and do their functions quite robustly.
[00:11:49.840 --> 00:12:05.760] When mitochondria become really fragmented, they are dysfunctional, they can't utilize or even produce energy very well, and they're on their way to basically dying and causing cells to die.
[00:12:05.760 --> 00:12:13.440] So, there's a very intricate connection between structure of mitochondria and the function of mitochondria.
[00:12:13.440 --> 00:12:27.440] And that's important because vigorous exercise, high-intensity exercise, has been shown to increase this repair process in mitochondria known as mitophagy.
[00:12:27.440 --> 00:12:39.000] So, when exercise is intense enough, it increases the nutrient-sensing protein, AMP kinase, AMPK.
[00:12:39.320 --> 00:12:40.840] It activates it.
[00:12:40.840 --> 00:12:48.200] And this causes the mitochondria to send the signal that they need to repair themselves.
[00:12:48.200 --> 00:12:54.200] And so mitochondria can be sort of dysfunctional or they can be really dysfunctional.
[00:12:54.200 --> 00:13:04.200] So mitophagy can clear away an entire dysfunctional mitochondria to be used and recycled, or it can clear away pieces of a dysfunctional mitochondria.
[00:13:04.200 --> 00:13:16.600] So when you're doing that acute exercise, your mitochondria, if you have a dysfunctional one, the mitophagy pathway gets activated and the mitochondria fizzes off.
[00:13:16.600 --> 00:13:25.560] It kind of goes through this mitochondrial fission process, and that damaged part of the mitochondria then goes and is recycled through the lysosome.
[00:13:25.560 --> 00:13:40.600] And then what you have is a long-term effect of after doing routine high-intensity exercise, you then have more healthy functional mitochondria because you're just getting rid of the damaged part of the mitochondria.
[00:13:40.600 --> 00:13:44.360] If the mitochondria is dysfunctional enough, you're going to get rid of the whole mitochondria.
[00:13:44.360 --> 00:13:49.880] And by the way, the AMP kinase pathway, many of you are probably thinking, oh, well, that's a nutrient-sensing pathway.
[00:13:49.880 --> 00:13:52.840] It's activated during periods of fasting.
[00:13:52.840 --> 00:13:54.200] And that is true.
[00:13:54.200 --> 00:14:02.440] AMP kinase is activated during periods of fasting, and fasting is a powerful signal for inducing autophagy and mitophagy.
[00:14:02.440 --> 00:14:14.280] However, in this particular study, people that did this high-intensity, vigorous exercise for 30 minutes, it did not matter if they had fasted for 16 hours or not.
[00:14:14.280 --> 00:14:16.240] There was no difference in the mitophagy.
[00:14:16.400 --> 00:14:27.520] So, in other words, the exercise itself was such a strong signal for activating mitophagy that it didn't matter if they had not fasted for 16 hours because it was so powerful.
[00:14:27.840 --> 00:14:37.680] On top of the repair process, high-intensity interval training is one of the most robust exercise modalities that can increase mitochondrial biogenesis.
[00:14:37.680 --> 00:14:42.240] So, the growth of new mitochondria, increasing mitochondrial volume.
[00:14:42.240 --> 00:14:52.960] So, you're having this double whammy effect where you're getting repairing of the mitochondria, getting rid of the unhealthy parts, and then you're increasing the growth of new mitochondria.
[00:14:52.960 --> 00:15:19.040] So, one of the reasons high-intensity interval training is very good at increasing mitochondrial biogenesis compared to, let's say, moderate continuous exercise is because lactate that's generated from that vigorous exercise is a signaling molecule to activate the protein that very much regulates mitochondrial biogenesis in skeletal muscle, PGC1-alpha.
[00:15:19.040 --> 00:15:21.840] So, again, lactate is playing that signaling role.
[00:15:22.240 --> 00:15:27.200] It's generated by the muscle, it's taken back up by the muscle, and then it's communicating with the muscle.
[00:15:27.200 --> 00:15:35.840] It's saying, hey, we can't make energy fast enough because this exercise is so intense, we need more mitochondria to be able to do that.
[00:15:35.840 --> 00:15:52.240] So, it's an adaptation to the vigorous intensity exercise, and that adaptation is making more mitochondria, which is obviously very beneficial for not only people with type 2 diabetes, metabolic syndrome, obesity, but also everybody.
[00:15:52.880 --> 00:16:05.240] So, mitochondrial biogenesis improves energy efficiency in mitochondria, and also is associated with other benefits like decreased atrophy and improved exercise endurance as well.
[00:16:05.560 --> 00:16:10.200] So, there's a whole host of benefits with increasing mitochondrial biogenesis.
[00:16:10.200 --> 00:16:20.200] So, a lot of the high-intensity interval training protocols that were used in these systematic analysis and these meta-analyses were evidence-based HIIT protocols.
[00:16:20.200 --> 00:16:21.800] So, Tabata is one that's used.
[00:16:21.800 --> 00:16:28.120] That's a 20-second on, 10-second off interval, 20 seconds at the highest intensity you can do.
[00:16:28.120 --> 00:16:35.320] You're going all out and then you're resting for 10 seconds, and that's repeated eight times for a total of a four-minute workout.
[00:16:35.320 --> 00:16:39.880] In some cases, the Tabata protocol was repeated twice.
[00:16:39.880 --> 00:16:55.320] The Wingate HIT protocol is another very commonly used one, and that is a 30-second all-out sprint followed by four minutes of active recovery where you're low-intensity, and then you do that four to six times.
[00:16:55.320 --> 00:16:57.640] That's about a 20-minute or so workout.
[00:16:57.640 --> 00:17:01.400] And then there's the conventional workout, it's the one-minute on, one-minute off.
[00:17:01.400 --> 00:17:09.800] So, you're going as intense as you can for one minute, and then you have one minute of very light active recovery, and then you repeat that 10 times.
[00:17:09.800 --> 00:17:11.640] So, that's a 20-minute workout.
[00:17:11.640 --> 00:17:18.280] It is hard, but it's very, very effective at improving a variety of metabolic parameters.
[00:17:18.280 --> 00:17:29.560] And then there's the clinical workout, also known as the Norwegian 4x4, which I like to call it because the Norwegian ski team often uses this hit protocol for their training.
[00:17:29.560 --> 00:17:37.160] It's a four-minute interval where you're going as intense as you can for four minutes, and then you have light recovery for three minutes.
[00:17:37.160 --> 00:17:41.400] So, you're going very, very light, getting your heart rate down, and that's repeated four times.
[00:17:41.400 --> 00:17:44.120] So, it's about a 25-minute workout.
[00:17:46.800 --> 00:17:54.960] So let's just talk a little bit about exercise snacks, which is a type of high-intensity neural training workout.
[00:17:54.960 --> 00:18:04.720] It involves doing something at vigorous intensity, you know, a vigorous intensity heart rate for one to two minutes.
[00:18:04.720 --> 00:18:10.320] And they're often called exercise snacks because you can just do them whenever throughout the day.
[00:18:10.320 --> 00:18:30.480] And I think this is very relevant because I just came across a study a couple of weeks ago that showed 10 body weight squats, okay, 10 for every 45 minutes was more powerful at improving glucose homeostasis than a 30-minute walk.
[00:18:30.480 --> 00:18:39.520] So I feel like that is, it's just, it kind of puts it in context because how easy is it to get up and do 10 body weight squats, right, every 45 minutes?
[00:18:39.520 --> 00:18:42.080] I mean, it doesn't get easier than that.
[00:18:42.720 --> 00:18:55.600] And there's also a reason to strategically time these exercise snacks either 30 minutes to an hour before a meal or 30 minutes to an hour after a meal.
[00:18:56.560 --> 00:19:08.400] So the timing of these exercise snacks has been shown in several studies, people with type 2 diabetes or insulin resistance, to really improve their glucose regulation after a meal.
[00:19:08.400 --> 00:19:13.920] So their post-praanial glucose regulation and their glucose disposal was improved.
[00:19:13.920 --> 00:19:27.360] Again, because getting that high-intensity exercise where you're generating some lactate, it's increasing glute-4 transporters at the muscle, and that is then causing glucose to come into the muscle.
[00:19:27.360 --> 00:19:34.440] It's lowering the burden of your pancreas to have to produce insulin, and it's improving glucose homeostasis.
[00:19:34.440 --> 00:19:43.320] So, exercise snacks around meals is an easy way to improve post-praneial glucose regulation and glucose homeostasis.
[00:19:43.320 --> 00:19:49.800] It's obviously very relevant for people with type 2 diabetes, but also I think for everyone.
[00:19:49.800 --> 00:19:55.800] Exercise snacks has also been associated with a decrease in all-cause mortality.
[00:19:55.800 --> 00:20:13.800] So, there have been very large studies out of the UK Biobank data where people are wearing accelerometers and they're part of the vigorous intensity, sorry, vigorous intermittent lifestyle activity studies that have been done, VILPA, they're called.
[00:20:13.800 --> 00:20:26.760] And what those studies have identified is that people that do one to two minutes of vigorous intensity exercise, and these are things like just sprinting up the stairs rather than taking the escalator or walking up the stairs.
[00:20:26.760 --> 00:20:32.680] And they do this, this is like a one to two minute high-intensity burst, and they do this three times a day.
[00:20:32.680 --> 00:20:38.200] That's associated with a 50% reduction in cardiovascular-related mortality.
[00:20:38.200 --> 00:20:40.120] 50% reduction.
[00:20:40.120 --> 00:20:45.640] It's also associated with a 40% reduction in cancer-related mortality and all-cause mortality.
[00:20:45.640 --> 00:20:54.920] So, cancer, cardiovascular disease, these are all diseases that are associated with metabolic dysregulation.
[00:20:55.240 --> 00:21:11.480] So, implementing exercise snacks, I think, is one of the easiest ways to get, you know, get a little bit of exercise, get your heart rate up, get that lactate generated, increase your glucose transporters, but also just improve your mood to break up your sedentary time.
[00:21:11.480 --> 00:21:21.760] You know, so being sitting at your desk for a couple of hours is sedentary, and being sedentary is an independent risk factor for certain diseases like cancer.
[00:21:21.760 --> 00:21:25.920] So, I mean, we've all been sitting here for what, an hour at least.
[00:21:25.920 --> 00:21:30.640] I say we get up and we do a minute of body weight squats.
[00:21:30.640 --> 00:21:32.000] Body weight squats.
[00:21:32.000 --> 00:21:34.000] All right, ready?
[00:21:35.200 --> 00:21:37.520] Okay, I'm gonna get this timer going.
[00:21:37.520 --> 00:21:38.800] We're gonna do a whole minute.
[00:21:38.800 --> 00:21:40.880] I'm saving you the high knees.
[00:21:41.200 --> 00:21:42.160] All right, here we go.
[00:21:42.160 --> 00:21:44.160] So, we're gonna do body weight squats.
[00:21:44.160 --> 00:21:49.680] We're gonna try to get the heart rate up, and we're gonna do it for one minute.
[00:21:50.000 --> 00:21:52.080] Try to go low if you can.
[00:21:52.080 --> 00:21:58.080] You wanna feel the burn in your quads?
[00:21:58.480 --> 00:22:00.240] Go sideways there.
[00:22:01.520 --> 00:22:04.000] Keep going.
[00:22:04.320 --> 00:22:07.280] We're not even at 30 seconds yet.
[00:22:11.440 --> 00:22:13.440] Okay, we're halfway.
[00:22:14.400 --> 00:22:16.000] Are you guys getting your heart rate up?
[00:22:16.000 --> 00:22:17.280] Are you feeling it?
[00:22:28.640 --> 00:22:37.680] 15 seconds left.
[00:22:37.680 --> 00:22:44.160] Five, four, three, two.
[00:22:46.800 --> 00:22:47.680] All right.
[00:22:51.840 --> 00:22:56.240] So, a little out of breath, feeling good.
[00:22:56.240 --> 00:22:58.880] Increase the blood flow to the brain.
[00:22:59.200 --> 00:23:07.880] But, but more importantly, glute four transporters.
[00:23:07.880 --> 00:23:20.200] Okay, so we're gonna shift gears and we're gonna talk a little bit about circadian meal timing.
[00:23:22.760 --> 00:23:37.800] All right, okay, so as everybody here knows about circadian rhythm, we're all diurnal creatures here, more active during the day, less active in the evening, right?
[00:23:37.800 --> 00:23:41.160] Our metabolism is also on a circadian rhythm.
[00:23:41.160 --> 00:23:49.400] We are more insulin-sensitive earlier in the day and later in the evening, less insulin-sensitive.
[00:23:49.400 --> 00:24:01.000] Part of that, so let me talk about a study that I think is pretty telling in terms of insulin sensitivity and glucose regulation throughout the day.
[00:24:01.000 --> 00:24:08.920] So, participants were given the same exact meals in the morning, in the afternoon, or in the evening.
[00:24:08.920 --> 00:24:13.880] Okay, so same macronutrient composition, same caloric content, everything the same.
[00:24:14.200 --> 00:24:22.760] And participants were much more insulin-sensitive in their first meal, given in the morning, compared to their evening meal.
[00:24:23.080 --> 00:24:33.320] And I think part of this has to do with our circadian rhythm, and as we get later in the day, melatonin.
[00:24:33.640 --> 00:24:59.920] So, back in like the early 2000s, about 2009, a lot of studies started coming out in the genetics world where the variation, a very, a certain variation in the melatonin receptor 1B was identified to be a pretty high risk factor for developing type 2 diabetes and for having basically insulin dysregulation.
[00:24:59.920 --> 00:25:03.920] So, people were not producing insulin correctly.
[00:25:03.920 --> 00:25:15.520] And it was very perplexing to scientists at the time because melatonin was thought to be just this hormone that is produced by the pineal gland that is regulating our sleep.
[00:25:15.520 --> 00:25:20.400] It's quieting down our brain, telling us it's time to get sleepy, right?
[00:25:20.400 --> 00:25:22.160] It's making us tired.
[00:25:22.160 --> 00:25:32.480] Well, it turns out, after more studies started to investigate this, that we have melatonin receptors on our pancreas, on our pancreatic beta eyelid cells.
[00:25:32.480 --> 00:25:38.720] And the melatonin receptors, the 1B receptors, are sensitive to melatonin.
[00:25:39.040 --> 00:25:47.200] People with that gene variation had a hypersensitive receptor where little bits of melatonin were enough to really kind of activate it.
[00:25:47.200 --> 00:25:56.000] And so it turns out melatonin is also quieting down our pancreas at night and telling our pancreas, we don't have to produce so much insulin.
[00:25:56.000 --> 00:25:56.720] It's nighttime.
[00:25:56.720 --> 00:25:58.560] We're not going to be eating.
[00:25:58.560 --> 00:26:10.960] And so there's a systemic effect of melatonin, not only on our brain, but also on our other organs that are important for metabolism.
[00:26:11.280 --> 00:26:25.040] And I think this is a really good reason to think about when you're going to have your last meal and why it is detrimental to engage in late night eating.
[00:26:25.040 --> 00:26:33.160] So, our bodies naturally produce melatonin about three or so hours before our natural bedtime.
[00:26:33.480 --> 00:26:41.800] So, it's a good rule of thumb to make sure that you have finished your last meal, you have finished eating, before that time.
[00:26:41.800 --> 00:26:50.600] So, before three hours before your natural bedtime, it's really just a good rule of thumb to kind of make sure you're done eating that.
[00:26:50.600 --> 00:26:57.560] When you wake up in the morning, you're also still producing some melatonin for about the first hour.
[00:26:57.560 --> 00:27:05.880] Now, bright light exposure can inhibit that, so it can hasten the clearance of the melatonin.
[00:27:05.880 --> 00:27:14.200] But also, I think it's a good idea to wait about an hour after you first wake up before you start taking in your meal.
[00:27:14.200 --> 00:27:21.080] So, bright light exposure we'll talk about also is very important for regulating our circadian rhythm, and that's important for sleep.
[00:27:21.080 --> 00:27:37.080] But generally speaking, I think just aligning your meals with your circadian rhythm, it makes sense when you think about the role of melatonin in quieting down our brain and also our pancreas, it makes a lot of sense why you don't want to be eating late at night.
[00:27:37.400 --> 00:28:00.600] So, just as a, you know, I think an aside here, having glucose levels in the normal range, but on the high normal range, so high normal glucose, was associated in UK biobank data with higher incidence of atrophy in the hippocampus, so the part of the brain involved in learning and memory.
[00:28:00.600 --> 00:28:09.640] So, people that just had higher than, they were on the high end of normal had more atrophy in their hippocampus than people on the low end of normal.
[00:28:09.640 --> 00:28:22.000] So, this is in the absence of any clinical type 2 diabetes, really sort of highlighting the importance of everyone considering their metabolic health, even if you don't have type 2 diabetes, even if you're not, you know, pre-diabetic.
[00:28:22.240 --> 00:28:28.480] You just, you want to make sure that your glucose regulation is the best it can be.
[00:28:29.760 --> 00:28:31.280] Circadian misalignment.
[00:28:31.280 --> 00:28:42.240] Now, so many of you may have come from, like me, the West Coast, or perhaps Europe, and you're out of sync with your circadian rhythm.
[00:28:42.240 --> 00:28:51.680] So circadian misalignment refers to when your natural internal clock is out of sync based on a behavioral pattern.
[00:28:51.680 --> 00:28:54.560] So this is very common with jet lag.
[00:28:54.560 --> 00:29:00.880] It's very common in shift workers who are up in the night, in the evening, working and eating.
[00:29:01.200 --> 00:29:05.280] It's also very common in people with erratic sleep behaviors.
[00:29:05.280 --> 00:29:11.520] So there's been studies done where people, our participants, are their circadian misaligned.
[00:29:11.520 --> 00:29:13.520] So they're out of sync.
[00:29:13.520 --> 00:29:18.560] So they're basically their sleep and meals are shifted by about 12 hours.
[00:29:18.560 --> 00:29:22.480] And when that happens, people have about a 6% increase in their glucose.
[00:29:22.800 --> 00:29:25.280] They make 22% more insulin.
[00:29:25.280 --> 00:29:27.200] They have decreased leptin levels.
[00:29:27.200 --> 00:29:30.800] So that's the hormone involved in being satiated.
[00:29:30.800 --> 00:29:42.080] And their postprandial glucose levels are in the pre-diabetic range, only by shifting their circadian clock by 12 hours.
[00:29:42.080 --> 00:29:46.320] So it has a profound effect being circadian misaligned.
[00:29:46.320 --> 00:29:53.760] Exercise can help with that, especially high-intensity interval training, but also time-restricted eating.
[00:29:53.760 --> 00:30:03.480] So, time-restricted eating refers to eating all your food in a restricted window of time instead of just eating ad libdum, right, throughout the day.
[00:30:04.120 --> 00:30:13.160] And typically, time-restricted eating is anywhere between six to ten hours of an eating window, and the rest is fasting.
[00:30:13.160 --> 00:30:14.600] There's been a lot of work done by Dr.
[00:30:14.600 --> 00:30:19.000] Sachin Panda on time-restricted eating in shift workers.
[00:30:19.320 --> 00:30:36.600] He's done some work on firefighters showing, you know, these firefighters that are up all night, if they eat their food in a time-restricted eating window, you know, eight hours, ten hours, that it improves their metabolic biomarkers.
[00:30:36.600 --> 00:30:43.480] So, there's been a lot of meta-analyses done on time-restricted eating and how it improves metabolic health.
[00:30:43.480 --> 00:30:48.520] Now, time-restricted eating does not mean you have to reduce your calorie intake.
[00:30:48.520 --> 00:30:59.400] But we're going to talk about in a minute, people that are naturally doing time-restricted eating tend to do that because they're skipping snacks, so they're skipping their dessert or they're skipping a meal.
[00:30:59.400 --> 00:31:09.000] So, when people do end up reducing their calorie intake along with time-restricted eating, they end up losing weight and losing fat.
[00:31:09.320 --> 00:31:21.560] But, independent of calories, so if they do not change their caloric intake but they are practicing time-restricted eating, it can improve glucose regulation, insulin sensitivity, it can lower blood pressure.
[00:31:21.880 --> 00:31:27.640] And so, there's a lot of metabolic parameters that are improved with just the time-restricted eating.
[00:31:27.960 --> 00:31:38.120] Now, as I mentioned, people that do practice time-restricted eating, so there's been multiple studies looking at even just a 10-hour window, which isn't even that restricted.
[00:31:38.120 --> 00:31:48.880] People that are doing a 10-hour time-restricted eating window, not a controlled trial, but just like you tell them to do it, they end up reducing on average about 200 calories a day.
[00:31:49.200 --> 00:31:52.880] Again, because typically people are skipping snacks or meals.
[00:31:52.880 --> 00:32:10.000] And so, that does lead to weight loss and it reduces waste size, body fat percentage, and also reduces visceral fat, which is the deep fat that surrounds your organs that's secreting pro-inflammatory cytokines and hormones that play a role in type 2 diabetes, metabolic syndrome.
[00:32:10.000 --> 00:32:16.080] But also, you know, emerging evidence indicates visceral fat plays a role in cancer as well.
[00:32:16.560 --> 00:32:24.720] Time-restricted eating also lowers blood pressure, it improves lipid profiles, and improves the HbA1C glucose biomarker.
[00:32:26.000 --> 00:32:31.680] Early time-restricted eating, so this is typically people that end their last meal at about 4 p.m.
[00:32:32.000 --> 00:32:38.560] Usually, early time-restricted eating is about a six-hour window, so it's a shorter eating window.
[00:32:38.560 --> 00:32:47.440] People that do early time-restricted eating without reducing their calorie intake dramatically improve a variety of metabolic parameters.
[00:32:47.440 --> 00:32:53.120] Insulin levels are improved, insulin sensitivity is improved, beta cells are more responsive to glucose.
[00:32:53.440 --> 00:33:01.040] The improvements in blood pressure were so profound that they were equivalent to some anti-hypertensive treatments.
[00:33:01.040 --> 00:33:02.960] So, that was a big finding of that study.
[00:33:02.960 --> 00:33:05.600] And then, X oxidative stress levels were also improved.
[00:33:05.600 --> 00:33:08.240] And this is early time-restricted eating.
[00:33:08.240 --> 00:33:14.480] There's been a meta-analysis of about 12 randomized controlled trials looking at early time-restricted eating.
[00:33:14.480 --> 00:33:19.920] Again, this was defined at stopping your last meal at about 4 p.m.
[00:33:20.560 --> 00:33:23.440] And then comparing it to late, later time-restricted eating.
[00:33:23.440 --> 00:33:27.120] So, people that were stopping their meals not at 4, but a little bit later.
[00:33:27.120 --> 00:33:32.120] And all the eating windows were either 4 to 10 hours.
[00:33:32.440 --> 00:33:43.880] And early time-restricted eating does have more profound effects on glucose regulation, largely because, again, we're more insulin-sensitive earlier, less insulin-sensitive later.
[00:33:44.040 --> 00:33:49.160] Once the melatonin starts to kick in, again, that just gets much worse.
[00:33:49.160 --> 00:33:58.680] So early time-restricted eating can improve fasting blood glucose levels and insulin resistance more than late, later time-restricted eating.
[00:33:58.680 --> 00:34:04.200] But it also has a more profound effect on the blood pressure regulation, so lowering blood pressure.
[00:34:04.200 --> 00:34:10.760] Late time-restricted eating can sort of maintain blood pressure, but it doesn't improve it like the early time-restricted eating.
[00:34:10.760 --> 00:34:16.440] And both early and late improve lipid profiles as well as fasting glucose and insulin resistance.
[00:34:16.440 --> 00:34:19.320] Just early does it a little bit more robustly.
[00:34:19.320 --> 00:34:47.080] So I think there's pretty strong evidence that if you are circadian misaligned, jet lagged, for example, if you're a shift worker, or just people that are, you know, wanting to sort of try to optimize their glucose homeostasis as much as possible, certainly people with metabolic dysfunction may benefit from time-restricted eating, along with the high-intensity enabled training and the 10 body weight squats every 45 minutes.
[00:34:47.720 --> 00:35:08.280] Okay, so let's talk about the last topic I want to discuss this morning, and it has to do with poor sleep and how most of us, I think, are aware when we don't get a good night's sleep, we don't feel cognitively on game, our mood is affected, we feel lethargic, we don't have as much energy.
[00:35:08.280 --> 00:35:19.200] But I'm not sure that most people realize the profound effect that even mild sleep restriction has on our metabolic health and glucose regulation.
[00:35:19.200 --> 00:35:32.560] And this is extremely relevant because about one-third of people in the United States do not meet the recommendations, which is seven to nine hours of sleep per night for sleep.
[00:35:32.560 --> 00:35:35.760] And again, this is very relevant for jet lag.
[00:35:35.760 --> 00:35:41.360] I mean, there's a lot of relevance here for poor sleep.
[00:35:41.360 --> 00:35:48.400] So mild sleep restriction, this is one to three fewer hours of sleep per night.
[00:35:48.400 --> 00:35:50.320] So I mean, one, it's not a lot.
[00:35:50.320 --> 00:35:54.960] Doing that three nights in a row can increase fasting insulin levels.
[00:35:54.960 --> 00:36:03.680] It can lead to higher insulin concentrations, elevated fasting glucagon levels, and also it decreases insulin sensitivity.
[00:36:03.680 --> 00:36:09.120] Again, this is just getting one hour less of sleep a night for three nights.
[00:36:09.120 --> 00:36:12.480] I mean, how many of us have probably even done that at this conference, right?
[00:36:12.480 --> 00:36:19.200] I mean, it's very easy and very applicable, and it's having a profound effect on metabolism.
[00:36:19.200 --> 00:36:23.760] Sleep debt is the cumulative effect of sleep restriction, right?
[00:36:23.760 --> 00:36:27.120] So this is when you're having multiple days of the sleep restriction.
[00:36:27.120 --> 00:36:33.600] So in this case, it was four, sorry, three days of four hours less sleep per night.
[00:36:33.600 --> 00:36:46.000] That lets you 40% slower glucose clearance, 30% decrease in glucose effectiveness, so this is independent of insulin, similar to diabetes, and 30% lower insulin response.
[00:36:46.000 --> 00:36:48.000] So, this is really indicating early diabetes.
[00:36:48.000 --> 00:36:49.360] And these aren't healthy people.
[00:36:49.360 --> 00:36:55.280] This is healthy people after just three nights of having four hours less sleep a night.
[00:36:55.280 --> 00:36:58.800] Very profound effect on metabolism.
[00:37:00.200 --> 00:37:08.840] There's been large meta-analyses done on longitudinal studies looking at type 2 diabetes risk and sleep duration.
[00:37:08.840 --> 00:37:17.720] And it's been identified that the optimal range of sleep for the lowest type 2 diabetes risk is seven to nine hours of sleep a night.
[00:37:17.720 --> 00:37:24.040] So going below seven hours or above nine hours were both associated with an increased risk for type 2 diabetes.
[00:37:24.360 --> 00:37:40.760] So the seven hour threshold, getting less than seven hours of sleep a night, was associated with increases in fasting insulin, increases in glucose levels, homo IR was elevated, higher HbA1C, and then also visceral fat was increased as well.
[00:37:40.760 --> 00:37:46.200] So again, getting less than seven hours of sleep a night, which a lot of people do routinely.
[00:37:46.200 --> 00:37:50.520] And speaking of the elevated Hb1A1C, I think this is really important.
[00:37:50.520 --> 00:38:01.640] Most of you probably realize this, but when you are constantly having elevations in blood glucose levels, this leads to advanced glycation end products, or ages, as they're called.
[00:38:01.640 --> 00:38:11.000] And it's certainly a huge problem in people with type 2 diabetes because they are constantly having glucose dysregulation in their elevated blood glucose levels.
[00:38:11.000 --> 00:38:25.000] But generally speaking, when you have the HbA1C high, you are talking about glucose reacting with lipids and proteins through the maillard reaction, including collagen.
[00:38:25.000 --> 00:38:33.560] And this is all inside of our blood vessels, our arteries, you know, our myocardium making, you know, surrounding our heart.
[00:38:33.560 --> 00:38:38.560] When you have those advanced glycation end products forming, it stiffens that collagen.
[00:38:38.440 --> 00:38:38.960] Okay, college.
[00:38:39.080 --> 00:38:43.000] HbA1C levels turn over after about what, 120 days?
[00:38:43.000 --> 00:38:45.280] Your collagen is in there forever.
[00:38:44.680 --> 00:38:49.520] So what happens is you have those advanced glycation end products.
[00:38:50.560 --> 00:38:57.360] If it's in your blood vessels, it stiffens the blood vessels and this leads to hypertension, plays a big role in hypertension.
[00:38:57.360 --> 00:39:09.760] When it's happening in the arteries and the myocardium, this decreases cardiovascular compliance and it really plays a role in the stiffening of your heart with age.
[00:39:10.080 --> 00:39:17.760] And so these advanced glycation end products increase the risk of cardiovascular disease, heart attacks, and hypertension.
[00:39:17.760 --> 00:39:30.960] So having these elevations in your blood glucose levels and subsequently the HBA1C biomarker, which biomarks that, is so much more than just type 2 diabetes risk.
[00:39:31.360 --> 00:39:33.280] It's cardiovascular health.
[00:39:33.280 --> 00:39:39.280] And it's really a cumulative effect that plays a role as we age.
[00:39:40.560 --> 00:39:50.480] There are a variety of mechanisms that have been identified for how short sleep and mild sleep restriction can cause dysfunctional metabolism.
[00:39:50.480 --> 00:39:53.840] So we're going to talk about decreased insulin signaling in adipocytes.
[00:39:53.840 --> 00:39:57.120] We're going to talk about lower beta cell sensitivity to glucose.
[00:39:57.120 --> 00:40:03.120] We're going to talk about impaired glucose absorption in muscle and liver and then changes in satiety hormones.
[00:40:03.120 --> 00:40:06.800] So there's been some studies looking at sleep restriction.
[00:40:06.800 --> 00:40:10.400] This is about four hours of sleep a night for four days.
[00:40:10.400 --> 00:40:14.560] It decreased insulin signaling in adipocytes by 30%.
[00:40:14.560 --> 00:40:21.760] So I mean your adipocytes are one of the major sinks, aside from muscle, for glucose disposal, right?
[00:40:22.400 --> 00:40:24.640] Storing it as fat, you know, for energy.
[00:40:24.640 --> 00:40:32.440] But a 30% reduction in cellular insulin signaling in adipocytes is, I mean, you're talking about these aren't healthy people.
[00:40:29.600 --> 00:40:41.640] This is like a healthy person immediately becoming obese or immediately becoming type 2 diabetic after just four days, right, of sleep restriction.
[00:40:41.640 --> 00:40:45.240] So it's very profound in terms of metabolic health.
[00:40:45.560 --> 00:40:52.120] Sleep loss, so mild sleep loss, even, it does promote an obesogenic profile.
[00:40:52.120 --> 00:41:01.320] And so a lot of work has been done out of Yves Van Coucher's lab, and she's looked a lot at these hunger hormones, satiety hormones.
[00:41:01.320 --> 00:41:07.800] So after two days of four hours less sleep, leptin levels go down.
[00:41:07.800 --> 00:41:13.640] So people are not feeling satiated by their food because leptin regulates satiation.
[00:41:14.280 --> 00:41:16.040] And their ghrelin levels increase.
[00:41:16.040 --> 00:41:17.400] So it's a double whammy.
[00:41:17.400 --> 00:41:18.920] Ghrelin is the hunger hormone.
[00:41:18.920 --> 00:41:19.960] It tells you you're hungry.
[00:41:19.960 --> 00:41:23.000] And so they're getting this continual hunger.
[00:41:23.000 --> 00:41:27.240] So global hunger ratings go up, global appetite goes up.
[00:41:27.240 --> 00:41:32.680] So people are not satiated by their food and they're hungry throughout their day.
[00:41:32.680 --> 00:41:49.080] And again, Eve Van Coucher's work has shown that people eat more and they're consuming foods and have cravings for processed foods, highly refined sugars, salty foods, processed fats and fatty foods.
[00:41:49.080 --> 00:41:57.000] So they're eating up to 45% more of those processed, unhealthy foods, and their hunger ratings are 24% higher.
[00:41:57.000 --> 00:42:01.720] So they're eating even more than they would if they were getting a good night's sleep.
[00:42:04.280 --> 00:42:11.160] So I think it's pretty clear that sleep restriction, poor sleep, does cause dysfunctional metabolism.
[00:42:11.160 --> 00:42:15.000] And so the question is: can you fix your sleep and improve metabolic health?
[00:42:15.680 --> 00:42:19.840] So there's a couple of evidence-based ways we're going to talk about improving sleep.
[00:42:19.840 --> 00:42:22.640] Both of them involve good sleep hygiene.
[00:42:22.960 --> 00:42:27.040] So good sleep hygiene is really the foundation of good sleep.
[00:42:27.040 --> 00:42:30.400] And there's a variety of factors that are like a checklist of it.
[00:42:30.400 --> 00:42:37.200] And I didn't include all of them, but some of the main ones here are using light smartly.
[00:42:37.200 --> 00:42:50.000] So bright light exposure, first thing in the morning, at least 30 minutes, is one of the most important ways to reset your circadian rhythm so that you become sleepy at a normal time.
[00:42:50.000 --> 00:42:57.200] Very, very important for resetting circadian rhythm, but also important for stopping that melatonin production when you're first waking up, right?
[00:42:57.840 --> 00:43:04.240] Also, avoiding bright light, blue light exposure in the evening after sunset, right?
[00:43:04.240 --> 00:43:08.800] Blue light is what is inhibiting melatonin production in our eyes.
[00:43:10.000 --> 00:43:20.560] It's through our eyes, actually not in our eyes, but it's inhibiting melanopsin, which then is involved in the signaling of producing melatonin to make us sleepy.
[00:43:20.560 --> 00:43:26.880] And so you want to avoid blue light either by having light dimmers or different color lights, maybe red or orange.
[00:43:26.880 --> 00:43:29.920] Also, glasses you can wear to filter it out.
[00:43:29.920 --> 00:43:34.400] But also realize that screens are full of bright light, blue light as well.
[00:43:34.400 --> 00:43:39.120] So turning down the screens, maybe avoiding screens at night is another good idea.
[00:43:39.120 --> 00:43:45.840] Also, making sure your room is dark because there's been studies showing that even a little bit of ambient light coming in disrupts sleep.
[00:43:45.840 --> 00:43:47.920] Managing temperature is important.
[00:43:47.920 --> 00:43:54.640] So part of what melatonin is doing, besides making you sleepy, is it's lowering your core body temperature.
[00:43:54.640 --> 00:43:56.400] And this is part of the circadian rhythm.
[00:43:56.400 --> 00:43:58.560] It's important for good sleep.
[00:43:58.560 --> 00:44:01.960] And so you want to make sure you're not sleeping in a really hot room.
[00:43:59.840 --> 00:44:06.040] And there's many ways that you can obviously maintain your bedroom temperature.
[00:44:06.360 --> 00:44:09.160] Optimizing meal timing is also important.
[00:44:09.160 --> 00:44:19.240] So in addition to the importance of avoiding eating, you know, like three hours before your bedtime because of melatonin production, it also improves your sleep.
[00:44:19.240 --> 00:44:21.160] So this has actually been some work by Dr.
[00:44:21.160 --> 00:44:23.960] Sachin Panda at the Salk Institute as well.
[00:44:23.960 --> 00:44:32.600] He's identified from large studies that he's done that people that stop eating three hours, at least three hours before their bedtime, sleep better.
[00:44:32.600 --> 00:44:36.120] And that's also partially because you're not digesting.
[00:44:36.360 --> 00:44:39.640] I mean, digesting is a lot of, it's an energy consuming process, right?
[00:44:39.640 --> 00:44:41.720] That's happening while you sleep.
[00:44:41.720 --> 00:44:46.520] So it makes sense that it would also disrupt sleep somewhat.
[00:44:46.840 --> 00:44:48.120] Regular exercise.
[00:44:48.120 --> 00:44:50.680] So again, this is all, these are all tied together.
[00:44:50.680 --> 00:44:54.520] So the exercise is also a very powerful zeitgeber.
[00:44:54.520 --> 00:45:03.640] So, you know, just routine exercise is also really important for resetting the circadian rhythm and helping you just get on that rhythm and go to bed at a normal time.
[00:45:03.640 --> 00:45:05.320] And then monitoring caffeine intake.
[00:45:05.320 --> 00:45:09.000] Caffeine shifts the circadian clock by 45 minutes.
[00:45:09.000 --> 00:45:13.560] So if you're drinking a cup of coffee, that's 45 minutes of a circadian shift.
[00:45:13.560 --> 00:45:17.160] And then you have another cup of coffee, that's 45 minutes of a circadian shift, right?
[00:45:17.160 --> 00:45:24.280] And so you're going to be going to bed hours later if you're drinking four cups of coffee, particularly if it's afternoon.
[00:45:24.280 --> 00:45:28.760] Obviously, there's a lot of individual variation between the way we metabolize caffeine.
[00:45:28.760 --> 00:45:37.880] So yeah, there's some individual variation, but generally speaking, it still shifts circadian rhythm by about close to an hour.
[00:45:38.520 --> 00:45:47.360] So, sleep extension is one of the evidence-based ways that's been shown to improve sleep, and this involves really just adjusting your bedtimes to increase the sleep time.
[00:45:44.680 --> 00:45:50.560] So, either going to bed earlier or sleeping in both of those.
[00:45:50.880 --> 00:45:57.360] It also involves a lot of consultations with sleep experts and then sleep hygiene recommendations, like we just discussed.
[00:45:57.360 --> 00:46:06.160] And so, there's been meta-analyses looking at sleep extension in people that are short sleepers, so they're getting fewer than seven hours of sleep per night.
[00:46:06.160 --> 00:46:20.640] And when they undergo this type of behavioral change, when they're engaged in sleep extension, for every hour additional that they're sleeping per night, they improve their insulin sensitivity regardless of their body weight.
[00:46:20.640 --> 00:46:23.760] They improve and normalize their hormones, leptin and ghrelin.
[00:46:23.760 --> 00:46:25.280] They have reduced appetite, right?
[00:46:25.280 --> 00:46:26.880] They're not getting so hungry.
[00:46:26.880 --> 00:46:31.920] Their sugar intake goes down and their caloric reduction goes down and they lose weight.
[00:46:31.920 --> 00:46:48.000] So, all these things, of course, the sugar intake and the reducing the calories, is all regulated by the satiety hormones, which again, if you're increasing your sleep, you can basically flip that switch to kind of help regulate them back and normalize them back.
[00:46:48.640 --> 00:46:56.560] The other type of evidence-based way of improving sleep is a certain type of cognitive behavioral therapy for insomnia, CBTI.
[00:46:56.560 --> 00:47:01.840] This is probably one of the most used, well-known, and effective ways to improve insomnia.
[00:47:01.840 --> 00:47:04.000] It involves a variety of factors.
[00:47:04.000 --> 00:47:07.520] I'm not going to go in depth on, but stimulus control is the main one.
[00:47:07.520 --> 00:47:11.280] So, that means the bed is only associated with sleep.
[00:47:11.280 --> 00:47:18.160] So, no watching TV in your bed, no scrolling on your phone, no doing anything, screens on your bed.
[00:47:18.320 --> 00:47:19.680] Bed is for sleeping only.
[00:47:19.680 --> 00:47:20.960] So, that's stimulus control.
[00:47:20.960 --> 00:47:25.760] It involves sleep restriction, which is a little ironic, paradoxical.
[00:47:26.080 --> 00:47:41.560] So, that means if you're laying in your bed and you're tossing and turning and you're up for an hour or two or three, it means getting out of your bed and going into another room, dark room, like your living room couch, and laying there and you do some relaxation techniques that you learn about.
[00:47:41.560 --> 00:47:44.120] and then wait till you get sleepy and then go back into the bed.
[00:47:44.120 --> 00:47:46.360] So again, bed is for sleep only.
[00:47:46.360 --> 00:47:54.120] It also involves implementing a variety of the sleep hygiene factors that we talked about, sleep education, and again, some relaxation techniques.
[00:47:54.120 --> 00:48:04.120] So meta-analyses of CBTI have also been shown to improve metabolic health in people with insomnia, including improved HBA1C, improved blood pressure.
[00:48:04.120 --> 00:48:08.680] Of course, their sleep quality and insomnia factors and all those things improve as well.
[00:48:08.680 --> 00:48:21.240] So it's pretty clear that people that have poor sleep, that have insomnia, that are short sleepers, if they work on fixing their sleep, they improve their metabolic health.
[00:48:22.520 --> 00:48:34.600] But there are situations where it is challenging to sleep longer, stay, you know, to sleep in, to do, to all these things, because maybe you're a new parent, right?
[00:48:34.600 --> 00:48:37.320] And you have to wake up and your sleep will be compromised.
[00:48:37.320 --> 00:48:39.560] There's absolutely nothing you can do because of it.
[00:48:39.560 --> 00:48:41.320] There's other things as well, right?
[00:48:41.320 --> 00:48:43.960] I mean, jet lag, things like that.
[00:48:44.280 --> 00:48:50.840] So there is another way to improve metabolic health, even when you're not sleeping optimal.
[00:48:50.840 --> 00:48:55.640] And that takes us full circle back to the beginning of the talk with high-intensity interval training.
[00:48:55.640 --> 00:49:03.080] So high-intensity interval training has shown to be a very robust way to improve metabolic health when you are sleep-restricted.
[00:49:03.720 --> 00:49:23.840] So, there's been studies that have shown that high-intensity interval training, if you do three sessions over five days of also being sleep-restricted, so sleeping four hours less a night, you can still improve your circadian rhythm, you can still improve your glucose tolerance, your mitochondrial function, and biomarkers of mitochondrial function and mitochondrial biogenesis.
[00:49:23.840 --> 00:49:29.760] And you know, I mean, this is important because, again, the glucose regulation, so you're doing that high-intensity interval training.
[00:49:29.760 --> 00:49:39.840] Well, part of the way that high-intensity interval training, I mean, part of the way that sleep restriction impairs glucose regulation is it makes your muscle less responsive to glucose.
[00:49:39.840 --> 00:49:42.240] And so, what is high-intensity interval training doing?
[00:49:42.240 --> 00:49:43.760] It's doing the exact opposite, right?
[00:49:43.760 --> 00:49:47.440] It's increasing glute-4 transporters, and it's bringing the glucose into your muscle.
[00:49:47.440 --> 00:49:55.360] So, you're really countering some of that negative effect of poor sleep on your muscle.
[00:49:55.680 --> 00:50:00.160] Even doing high-intensity interval training before you know you're going to be sleep-restricted.
[00:50:00.160 --> 00:50:02.080] So, I got on my Peloton yesterday.
[00:50:02.080 --> 00:50:04.480] I went hard right before I got on my flight from California.
[00:50:04.480 --> 00:50:07.920] I knew I was going to lose some sleep because it's three hours ahead in Florida.
[00:50:08.640 --> 00:50:20.160] Doing high-intensity motival training before you're going to be sleep-restricted still mostly rescues the high blood glucose and acute insulin resistance that's caused by sleep restriction.
[00:50:20.160 --> 00:50:32.400] So, yet again, just really important with respect to tools that we have at our disposal to help mitigate some of the effects of chronic sleep loss or even acute sleep loss, both.
[00:50:34.000 --> 00:50:43.280] And a lot of those protocols, again, are the ones we've discussed: the Tabata, the Wingate, conventional one-minute on, one-minute off, and the Norwegian 4x4 HIP protocol.
[00:50:43.760 --> 00:50:47.840] A lot of HIIP protocols out there that people can do, or you just do your exercise snacks as well.
[00:50:47.840 --> 00:50:55.040] I mean, that also has been shown to increase glucose homeostasis, as I mentioned, the 10 body weight squats.
[00:50:55.040 --> 00:51:18.760] And I do want to mention one last study before we end on time, and that is, again, there's lots of data out there to be harvested from the UK Biobank data, and there's been studies that have identified people that sleep fewer than seven hours or greater than nine hours a night have a higher all-cause mortality.
[00:51:19.080 --> 00:51:34.920] However, if those people are physically active and they're getting, and they're meeting the guidelines for physical activity, 75 minutes a week of intense, vigorous exercise or 150 minutes a week of moderate intensity exercise, they do not have a higher all-cause mortality.
[00:51:34.920 --> 00:51:38.040] They have the same mortality risk as someone that's getting good sleep.
[00:51:38.040 --> 00:51:46.840] Yet again, exercise can forgive a lot of sins, and there's no reason to not do a time-efficient type of high-intensity interval training workout.
[00:51:47.000 --> 00:51:49.560] It's, you know, time-efficient, it's easy.
[00:51:49.560 --> 00:51:52.760] Exercise snacks, I mean, there's all the evidence there.
[00:51:52.760 --> 00:51:53.960] We just have to implement it.
[00:51:53.960 --> 00:51:55.400] Make it part of your hygiene.
[00:51:55.400 --> 00:51:58.680] Like you brush your teeth every morning, you do your hit.
[00:51:59.640 --> 00:52:05.560] So, in conclusion, I think there's three really powerful tools we have to improve our metabolic health.
[00:52:05.560 --> 00:52:11.720] I talked about the vigorous intensity exercise, high-intensity interval training, making it part of your personal hygiene.
[00:52:11.720 --> 00:52:20.040] Also, trying to eat your meals in accordance with your circadian rhythm, a good rule of thumb, stop eating three hours before bed because of that melatonin production.
[00:52:20.040 --> 00:52:24.600] It's nice to have a pretty restricted time window, eight, ten hours.
[00:52:24.600 --> 00:52:42.360] And then also making sure we optimize our sleep and having good sleep, and that can be anything from the bright, you know, good sleep hygiene and all those things we talked about to people that have problems and doing things like CBTI or sleep extension, and certainly back to the exercise again to help.
[00:52:42.360 --> 00:52:46.800] And with that, thank you so much for staying here and listening to me talk for an hour.
[00:52:44.680 --> 00:52:51.520] I hope you guys enjoy the rest of the conference, and thanks again.