(Breather) This show covers an incredibly rich and informative article on DrJackKruse.com dealing with how our circadian clock affects our hormone function and all aspects of our biology. We’ll travel around the 24-hour clock and enjoy 21 different insights about hormone and metabolic function from extreme biohacker and anti-aging expert Dr. Jack Kruse. 

This guy is WAY out there at the extreme edge of health and that’s what makes him someone worth checking into. I understand that he has his critics and second guessers, but he is clearly highly advanced in his thinking, scientific research, and life experience as a neurosurgeon.

In this episode, I’ll detail how he turned his life around in 2007 when he injured his knee surgery at 357 lbs and decided to get healthy. He started studying like crazy, reading through thousands of research articles, and landed in the area that claimed, “Obesity is not the result of too many calories, not enough exercise or living a slothful existence. Obesity begins in the eye because of an altered spectrum of light.” No one understands how artificial light is the driving force behind modern neolithic diseases tied to mitochondrial dysfunction. That is Dr. Kruse’s sole focus now: he aims to teach people the world of quantum biology.

Dr. Kruse lost 133 pounds in one year and started curing patients at his Nashville clinic to eventually develop his “Leptin Rx Reset,” a protocol that acts as a brain surgery without ever using a blade, completely rewiring the hypothalamus by aligning with our natural circadian rhythms and mastering the “timing” of our evolutionary blueprint. His findings include:

• The timing of when you eat is more important than what you eat: seeing sunlight in the morning is critical.
• Snacking or eating “small meals” every 2-3 hours as commonly advocated by conventional medicine all but guarantees life-long obesity.
• Anyone can lose massive amounts of weight without ever counting a calorie.
• Rigorous cardio exercises (like long-distance running or chronic cardio routines) leads to stem cell reduction and shaves years off the end of your life.
• Eating fats, which conventional medicine told us to shun, is ideal for Optimal Health.

We will have to work through a ton of scientific terms and concepts, but my goal is to do my best to distill the message into simple and actionable takeaways that can improve your health as I go through 21 separate insights from this comprehensive article published at Dr. Jack Kruse’s longevity-focused website, taking you through a 24-hour day. 

First, ask yourself: How does your day begin, and how does it evolve? Here goes the story of the modern “warm adapted” human circadian cycle. Oh yeah, Dr. Kruse is a huge cold exposure enthusiast and takes his ice baths for up to an hour! We’ll learn about how cold therapy can positively impact metabolism and health, especially for post-menopausal women who feel like they’ve been tripping out!

You will hear a lot about a couple of hormones, so I want to define them right out the gate:

Leptin, a hormone released from the fat cells located in adipose tissues, sends signals to the hypothalamus in the brain. This particular hormone helps regulate and alter long-term food intake and energy expenditure, not just from one meal to the next.

Prolactin is most commonly known as what stimulates the production of breast milk but has a number of other important metabolic functions. It also regulates behavior, the immune system, metabolism, reproductive systems, and many different bodily fluids. This makes it a crucial hormone for overall health and well-being, for both men and women.

Production of prolactin is controlled by two main hormones: dopamine and estrogen. These hormones send a message to the pituitary gland primarily indicating whether to begin or cease the production of prolactin. Dopamine restrains the production of prolactin, while estrogen increases it.

Our brain wakes up with a morning surge of cortisol. That is what turns our brain on at 6 am. VIP (vasoactive intestinal peptide) helps do this in long light cycles. VIP is highest at 6 am, and lowest at 6 pm. 

Ghrelin is also highest in the morning. Ghrelin is a prominent hunger hormone made in the stomach that has a half-life of one hour. Ghrelin sends a signal directly to our pituitary gland and it influences our metabolism. This is why the circadian cycle in the stomach in the morning is critical to optimal health. Kruse talks about the Leptin Rx reset protocol on his blog. 

You’ll hear about leptin a lot in this story. It’s the prominent satiety, fat-storage hormone, and its main role is to prime you for reproductive fitness — our most basic and important biological drive. When leptin signaling is efficient between the brain and digestive system, you eat an optimal amount of calories. When leptin signaling is compromised due to assorted adverse lifestyle practices, you don’t get the satiety signal and you tend to store fat rather than burn it. I say ‘signaling’ rather than ‘low and high’ because it’s more nuanced than low and high.

Melatonin secretion increases after four hours of darkness. This allows plasma leptin to enter the hypothalamus if you are sensitive to its receptor. But, if you are leptin-resistant, this process can no longer occur.   

Now, onto the 24-hour tour of our circadian rhythm: 

1. Circadian cycles for the obese are dramatically altered compared to non-obese individuals in the morning. For non-obese people, ghrelin is high when cortisol is highest in the early morning. Ghrelin drops fast when food is eaten, too. But for the obese, ghrelin is much lower than expected in the morning. Moreover, once they eat food, ghrelin will stay elevated for an extended amount of time. This is why obesity is an inflammatory brain disorder causing hormonal imbalance. This happens because of the inflammation associated with the higher leptin levels in the morning in the obese. Melatonin is known to acutely decrease ghrelin (which is great for when you want to go to sleep). 
2. At 6:45am, we will expect to see the sharpest rise in blood pressure in the entire day. This is due to many activated systems in the body getting us ready to fully supply blood to all vital areas to get us motivated to begin our day and search for food. This period of rapid blood pressure rise is why we see so many cardiac deaths occur in early morning sleep or early wakefulness. This happens when cortisol is highest.
3. Sun hits the retina at daybreak, and the photic stimulus begins to shut off the secretion of melatonin from the pineal gland in the brain. Morning sunlight contains mostly IR light at daybreak and as we approach noon, UV light frequencies appear on the skin. When morning sunlight hits your retina and receptors in skin cells throughout your body, the signal travels through the optic nerve to other regions of the brain, including the pineal gland. The light cue prompts melatonin levels to fall and serotonin and cortisol to spike within 30 minutes of waking. Adenosine levels decrease steadily as you sleep, and are low when you awaken, increasing alertness. The adenosine-cortisol-serotonin effect is most effective closest to dawn, another reason to try to rise with the light of day!
4. At 7:30AM, usually after an hour of light, melatonin is completely shut off in the brain.
5. At 8:30AM, the gut has been awakened and peristalsis becomes more vigorous and bowel movements getting rid of yesterday’s food are very likely. This happens as protons flow to move serotonin sulfated (that means snuffed out, like a battery) by the light of the gut microbiome to get to get to the brainstem to become sulfated melatonin (serotonin converts to melatonin in the evening). Bowel movement is stimulated if food is eaten around this time as well. This is called the gastrocolic reflex. Cortisol, aldosterone, and ghrelin are all raised at this time to drive activity, increase our blood pressure and stimulate feeding. This is all yoked to AM sunlight stimulus. It is blocked when we wear clothes or at work in the AM.

6. Around 9-10AM, we have the highest secretions of the sex steroid hormones in humans and these pulsatile crescendos lead to our highest alertness at around 10AM in our day to allow us to explore our environment. So who knew the VIP time for sex was morning delight?
7. Our ideal muscle coordination occurs at 2:30PM, which adapts us best to hunt for dinner at this time. An hour later, we see our fastest reaction times develop from our motor systems in our CNS.
8. At 5PM, humans exhibit their greatest cardiovascular efficiency allowing for maximal exercising or hunting. This also occurs during a period of time when we have our best rates of protein synthesis in our body. This is why exercise should be optimally done in this window.
9. As the sun falls at 6PM, we begin to see a major change in the cardiovascular system about a half hour later.
10. At 6:30PM, we see our highest blood pressures due to changes in atrial natriuretic factor and antidiuretic hormone (ANF, ADH) in the renin-aldosterone axis.
11. Once this occurs over the next 30 minutes (7PM), we begin to see a gradual rise in our body temperature as leptin (and IL-6) is released from our fat stores, with agouti’s help, slowly after dinner is eaten to signal the brain about our fat mass and inflammatory status. Agouti is a furry little rodent but also a neuropeptide produced in the brain that has a powerful signaling effect to increase appetite, decrease metabolism and energy expenditure, which is why it is known as one of the most potent and long lasting appetite stimulators.
12. For the next two to three hours, leptin levels slowly rise as insulin levels fall. Adiponectin levels also fall during this time frame. These fat hormone signals are what activate the adenosine system in our bodies. Adenosine is created over the course of the day; you start in the AM with low levels, and as they build, high levels of adenosine lead to sleepiness.
13. Adenosine peaks at 10PM ,and then the circadian clock allows for melatonin secretion after 3-4 hours of total darkness. Serum leptin is rising quickly now (with agouti’s help) as it is released from the fat cells to enter the brain. Agouti is highest at this time of the day, even in a normal person.
14. As these trends continue, the GI tract is slowly shut down by the circadian clocks and around 11:30PM, bowel movements are shut down for the night. This means that the vagus nerve is quiet.
15. At midnight, leptin begins to enter the hypothalamus to bind to its receptor – it signals energy reserves (you burn stored energy during the night). In diurnal animals, sleepiness occurs as the circadian element causes the release of the hormone melatonin and a gradual decrease in core body temperature. This drop in temperature is the stimulus to change sulfated serotonin to sulfated melatonin.  This timing is affected by one’s chronotype.

16. It is the circadian rhythm that determines the ideal timing of a correctly structured and restorative sleep episode. Melatonin, the hormone from the pineal gland, called the “darkness hormone ” is of great importance in the functioning of the SCN – that’s the suprachiasmatic nucleus – located in the hypothalamus. Hypothalamus is the control tower for all hormonal and metabolic functions in the body, regulating body temperature, hunger, important aspects of parenting and attachment behaviors, thirst, fatigue, sleep, and circadian rhythms. SCN is the main arbiter of circadian rhythm in the body. Sunlight hits SCN and the hormonal cascades are kick started. The most important target of melatonin in humans appears to be the SCN, as the SCN contains the highest density for melatonin receptors. A double effect of melatonin in the SCN, namely, an immediate effect and long-term effect, has encouraged its worldwide use against the ill effects of jet lag. This may not be wise to do. As an immediate effect, melatonin is found to suppress neuronal SCN activity toward nighttime levels. During the daytime, the SCN neurons must run faster than normal.  This is possible because the retina has more DHA in it than the brain.  In terms of long-term effect, melatonin can phase shift and amplify circadian rhythmicity of the SCN. Melatonin application has been found to be useful in synchronizing the endogenous circadian rhythms not only in people who suffer from jet lag, but also in blind individuals, patients with dementia, and in shift workers.

17. After the 4 hours of darkness, melatonin secretion increases and this allows plasma leptin to enter the hypothalamus, if we are sensitive to its receptor. If we are leptin resistant, this process can no longer occur.
18. Once leptin enters and binds to its receptors, it affects the lateral hypothalamic tracts to immediately send a second messenger signal to the thyroid to signal it to up-regulate thyroid function and efficiency. This is how we can raise our basal metabolic rate when we are leptin sensitive. These coupled events, matched with leptin’s actions peripherally in muscles, occur at the UCP3 sites (these are mitochondrial uncoupling proteins) to burn fat as we sleep at a higher basal metabolic rate. This means electron chain transport does not make ATP as usual. When leptin allows this uncoupling to occur, we make heat (and not energy) from normal metabolism. This means we will burn off our excess calories as pure heat. This is one reason why the whole ‘calories in and calories out’ argument makes no biological sense once you understand how leptin works.  Humans are built to burn fat at night, as we sleep to lose excess weight we don’t need.

19. The timing of the leptin action is also critical. It usually occurs between 12-3AM, and is tied to when you last ate and how much darkness your retina (SCN) have seen. This generally occurs soon after our hypothalamus releases another hormone called prolactin, from our pituitary gland in the brain.
20. The surge of Prolactin is normally quite large in normal darkness, but is significantly diminished in artificially lit environments after sunset. The reason is that prolactin release is coordinated with sleep cycles where autophagy is at its highest efficiency and where Growth Hormone is released. If this is diminished, we generally see lower DHEA levels clinically and higher IL-6 levels on cytokine arrays. This is a measure of uncoupling of sleep from normal metabolism. I base every bio hack I do on this step in circadian biology because it is the most important.
21. The normal large circadian prolactin surge we should see at around midnight after leptin enters the brain, does not happen if the patient has leptin resistance, sleep apnea, or has eaten food too close (within 3-4 hours) to bedtime. This blocks leptin’s ability to enter the brain because of insulin spikes. As mentioned above, this step is usually impaired if you are a post-menopausal female as well. This is often why older women sleep badly and gain weight they can not seem to lose in the gym, even with a good paleo template and good habits. This is another reason I am a big advocate for bioidentical hormone optimization in women. This need is also greatest in women who are warm-adapted. The need is lowest in the cold-adapted females because their leptin levels are already low due to the cold. Post-menopausal women who are cold-adapted tend to do amazingly well clinically in most disease parameters in my clinical experience. The main problem they face is that their vanity and dogma keep them from using the cold pathways to become rockstars as they age.

Thanks for listening to this journey around the circadian clock, and stay tuned for part 2!

TIMESTAMPS:

In this podcast, Brad talks about the work of Dr. Jack Kruse who believes that obesity is not caused by eating too many calories and not exercising enough. [01:23]

Obesity begins in the eye…because of an altered spectrum of light. [03:28]

The timing of when you eat is more important than what you eat. [04:42]

Snacking or eating small meals every two or three hours all but guarantees lifelong obesity. [05:31]

People can lose massive amounts of weight without ever counting a calorie. [6:38]

Processed carbohydrates are the true culprit and disease driver of the modern diet. [07:37]

Leptin is a hormone released from fat cells located in the adipose tissues that send signals to the brain. [09:42]

Prolactin is the prompter of manufacturing breast milk but does much more. [10:49]

Our brain wakes up in the morning with a surge of cortisol, the fight or flight hormone. 

Another hormone that is high in the morning is ghrelin, the appetite signal. [12:00]

Leptin signaling is compromised by lifestyle practices, like too much artificial light after dark. [14:10]

In the obese, ghrelin is much lower in the morning than expected and when food is eaten, it stays elevated. [15:34]

As Brad goes through explaining the circadian rhythm process, we see that about 6:45 a.m. is when the blood pressure has the sharpest rise. [16:15]

Around 7:30 a.m., usually after an hour of sunlight, melatonin is completely shut off. [19:00]

The morning sunlight stimulus gets the other hormones going to increase activity. [20:45]

Although we are primed to consume calories in the morning, it is really popular these days to try fasting. [21:30]

Proceeding through the morning’s body rhythm, Brad points out that around 10:00 a.m. we have the highest secretion of sex steroid hormones. Ideal muscle coordination occurs at 2:30 p.m. [23:08]

Around 5:00 p.m. is the best time for exercise. [24:54]

It is important to have three or four hours of darkness in the evening.  [27:03]

At midnight, your body is still hard at work. [30:41]

Having artificial lights on so that it doesn’t get dark is a huge health hazard. [32:56]

If you don’t have a healthy metabolic function, you will not be burning fat as you sleep. [36:07]

The timing of leptin is critical. It usually occurs between 12 and 3:00 a.m. [37:10]

Post-menopausal women often find the timing of this evening meal impacts their ability to sleep well and they also gain weight regardless of their exercise and diet regimen. [39:07]

There are many ways you can become cold-adapted. [40:10]

LINKS:

• Brad’s Shopping Page
• Dr. Jack Kruse
• Jack Kruse Circadian Clock
• The Obesity Code
• Leptin RX Reset Protocol
• Dr. Panda
• Dr. Cate Shanahan
• Brad’s Cold Therapy
• Ghrelin
• Prolactin information

QUOTES:

• “Obesity is not the result of too many calories, not enough exercise, or living a slothful existence.”
• “The timing of when you eat is more important than what you eat.”

LISTEN:

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Get Over Yourself Podcast

Brad (1m 23s): Let’s take a journey around our circadian clock, 24 hours of fun and exciting action. This show covers an incredibly rich and informative article that I read on Dr. Jack Kruse.com, dealing with how our circadian clock affects hormone function and all aspects of our biology. So we’re going to put in some hard work here, people it’s going to be a pretty thick show with tons of scientific insights and concepts, and I’m going to do my best to work through these and distill the message into simple and actionable takeaways that can improve your health. Brad (2m 3s): And if you don’t know Dr. Jack Kruse check out that website, he’s a leader in biohacking, anti-aging live in life on the extreme edge of bio hacking and cutting edge anti-aging strategies, and he is way out there. And that’s what makes him someone worth checking into. He has some critics and second guessers. I understand, but he’s clearly extremely advanced in his thinking, his scientific research and tremendous life experience as a neurosurgeon. So in the article or in the website, you’ll learn that he turned his life in a different direction. Back in 2007, he injured his knee had to have surgery, and he was weighing in at 357 pounds. Brad (2m 44s): So he was disgusted that his health had gone to heck while he was operating and saving so many people’s lives. So that’s when he decided to immerse himself into the world of alternative health biohacking, studying like crazy, cranking through a bunch of research articles, cranking out a bunch of wonderful content on his own website. And he kind of landed on this concept that obesity is not caused by eating too many calories and not exercising enough. And this is an insight that’s been overturned really nicely by many other people. In recent years, I talk about Dr. Jason Fung insights a lot on the Obesity Code, where he’s talking about it’s the hormone imbalances, the excess insulin production. Brad (3m 28s): And then how do we get into this pattern of eating too much and producing too much insulin besides making bad food choices? Dr. Kruse is coming in from a different direction. Very interesting. So here’s a quote. And of course you can read a lot more about his it’s called the Leptin RX Reset Protocol. Obesity is not the result of too many calories, not enough exercise or living a slothful existence. Obesity begins in the eye, ah, because of an altered spectrum of light. No one understands how artificial light is the driving force behind modern neolithic diseases tied to mitochondrial dysfunction. And that is Dr. Kruse’s main focus. Brad (4m 9s): He wants to teach people about the world of quantum biology. So when he got into this game, he lost 133 pounds in one year. And he started curing patients at his Nashville clinic. And this is what led him to develop this Leptin RX Reset. It’s a protocol that acts as brain surgery without ever using a blade. I’m reading promo content from his website, completely rewiring the hypothalamus by aligning our natural circadian rhythms and mastering the timing of our evolutionary blueprint. Here are some of his findings. First, the timing of when you eat is more important than what you eat. Brad (4m 48s): Again, this stuff is now becoming a highly accepted, you know, Dr. Panda down at San Diego, the Salk Institute is being referenced a lot for his time-restricted feeding studies and showing that two groups eating the same amount of calories, but one group eating in a compressed eating window fares much better than the other group who has their calories consumed over a longer time period. So that’s the popularity of the time-restricted feeding, eating in a compressed time window. That’s a centerpiece of Sisson and I’s upcoming book. Two meals a day is just eating less frequently. Not snacking. Just having a couple of nice meals can turn your metabolic function around your fat loss goals, everything. Brad (5m 31s): So next on the bullet points of Dr. Kruse’s discoveries and the centerpiece of the Leptin RX Reset snacking or eating small meals, every two to three hours as commonly advocated by conventional medicine, all but guarantees lifelong obesity. Whew. Yes. The snacking is particularly problematic. Dr. Cate Shanahan explains this really well. And she talks about that in some of our past podcasts, but every time you snack, you shut down body fat burning in order to burn the calories that you just consumed. So even if you’re consuming a high fat snack, that’s favored by the keto community, as long as it meets the macros and doesn’t spike insulin it’s okay. Brad (6m 16s): But if you’re consuming fat bombs all day, keep in mind that you’re going to burn those fat calories rather than the body fat calories. And Dr. C.ate explains that anything you consume will cause an insulin response. So this snacking, this boosting blood sugar with the energy bars and the entire industry that’s built around snacking. Bad deal. Okay. Next insight from Dr. Kruse, anyone can lose massive amounts of weight without ever counting a calorie. Next rigorous cardiovascular exercise, like long distance running or other routines that are chronic in nature lead to STEM cell reduction and shave years off the end of your life. Brad (6m 56s): Again, a notion that seemed radical probably at the time when he was putting his message out there originally 2008, 2009. I remember people turning their heads going, what’s this guy talking about? And now this is being widely regarded as accurate and the extreme dangers of chronic cardio. I’m going to do a whole show pretty soon called why I ditched, jogging and transform my daily exercise centerpiece into something different that has broader fitness benefits and less downside risk associated with chronic cardio. Final insight from Dr. Kruse on the bulleted list from his website, eating fats that conventional medicine has told us to shun is ideal for optimal health. Brad (7m 37s): Again, widely regarded as a centerpiece of the ancestral health movement, lots of science turning those notions on their ear now. And finally realizing that processed carbohydrates are the true culprit and disease driver in the modern diet and that natural, nutritious fats, of course not the manufactured fats, like the industrial seed oils is what he’s talking about. Okay, here we go. People buckle your seatbelt. And again, we’re going to throw some science at you, but I’m hoping that you’ll be able to extract the, the basic insight of basic understanding that will help you make good decisions as we go around our circadian clock. So this is going to be a lot of quoting from this lengthy article on Dr. Brad (8m 21s): Kruse’s website, but also my editorializing and kind of twisting some of the words to, to make it more readable and compress the duration of the article a little bit. So how does our day begin and how does it evolve here? Go the story of the modern quote, warm, adapted human circadian cycle. So it should be noted that Dr. Kruse is a huge cold exposure enthusiast. He takes ice pass that lasts up to an hour. He was one of the first guys I’d ever heard about that, did this stuff. This is now at least 10 years ago. So when he says warm adapted, he’s also going to talk about in the article, the many, many benefits of becoming or her rekindling, our ability to be cold adapted. Brad (9m 5s): And so we’ll learn about how cold therapy can positively impact your metabolism, your health, your ability to burn body fat and especially in the category of post-menopausal females. So trip out on that, I keep telling Mia Moore, she’s got to jump in the chest freezer. She wouldn’t think of it, but maybe by the time you listen to this show, some of you post-menopausal females will be compelled intrigued. Okay? So during the show, you’re going to hear a lot about a couple of hormones. So I want to provide a definition out of the gate. So we can reference when we hear them mentioned in passing. First is leptin official definition. Brad (9m 45s): It’s a hormone released from fat cells located in the adipose tissues, and it sends signals to the hypothalamus in the brain. This particular hormone helps regulate and alter longterm food intake and energy expenditure, not just from one meal to the next. I come to understand leptin as the prominent satiety, fat storage, and reproductive fitness hormone. One of the most important hormones in the body right up there with insulin. Dr. Ron Rosedale, author of The Rosedale Diet. He’s a strong promoter of the importance of leptin and deep into the science of leptin. And he talks about it being the, the control tower for your metabolism and the prominent driving force of the human. Brad (10m 29s): The most prominent biological drive is to be fit for reproductive fitness, right? And leptin is a strong influencer of that. So it determines how much you’re going to eat and what you’re going to do with those calories, whether you’re going to store them as fat or whether you’re going to burn them all in the interest of achieving reproductive fitness. Okay. The next hormone that we’re going to talk about a lot is prolactin. Most commonly known as the prompter of manufacturing breast milk. But prolactin has a number of important metabolic functions. It regulates behavior, immune function, metabolism, reproductive systems, and many different bodily fluids. This makes it a crucial hormone for overall health and wellbeing for both men and women. Brad (11m 14s): So the production of prolactin is controlled by two main hormones, dopamine, you know that as the instant gratification, the pleasure seeking hormone, the burst of pleasure that gets from a dopamine hit. And then secondly, estrogen. So these hormones, dopamine, and estrogen send a message to the pituitary gland primarily indicating whether to begin or cease the production of prolactin. Dopamine restrains the production of prolactin while estrogen increases it. Okay. So that’s our advanced information. Before we go into these 21 different insights provided by Dr. Kruse taking us around the 24 hour clock, are you ready to rumble? Brad (11m 60s): Here we go. Number one out of 21, remember our brain wakes up with a morning surge of cortisol. That’s the prominent fight or flight hormone. We often talk about it in a negative context when we’re producing too much cortisol from overly stressful exercise or lifestyle patterns, or we’re staying up too late at night, blasting our eyeballs with artificial light. And this causes spikes in cortisol the brain, the hormonal system, thinking that it’s sunny thinking you need to stay awake. So you’re getting that surge of cortisol. Of course, first thing in the morning in association with sunrise, ideally, that’s the best time to wake up for a bunch of reasons that we’ll learn about as we dip into the story here. Brad (12m 43s): So this is a positive and desirable surge of cortisol. Yeah, this is what turns our brain on at 6:00 AM. And of course, when you hear these timestamps from Dr. Kruse’s article, these are going to be generalizations. Obviously your circadian rhythm is highly influenced by what latitude you live at and what time of year. So if you’re on the equator and your days only vary by an hour, hour and a half around the year, everything can fall into perfect place. But if you’re up in the Northern territories like Scandinavia, Canada, Alaska, you’re going to have a huge variation in seasonal and has a tremendous influence on your health and hormonal function. Brad (13m 25s): So we’re going to just go with these generalizations and let’s say we’re living in the main swath of the Northern hemisphere, where most of the world’s population is contained. And 6:00 AM is generally pretty close to sunrise. Okay? So VIP Vasso Active Intestinal Peptide. VIP helps do this in long light cycles. That is prompt. The surgery cortisol. VIP is highest at 6:00 AM and lowest at 6:00 PM. So another hormone that’s highest in the morning is ghrelin the prominent stimulator of hunger. Ghrelin is made in the stomach and it has a half life of one hour. Ghrelin sends a signal directly to our pituitary gland and it influences our metabolism. Brad (14m 10s): This is why the circadian cycle in the stomach in the morning is critical to optimal health. I have even more notes here about leptin. So I want you to really understand it. When leptin signaling is efficient between the brain and the digestive system back and forth, the signaling, you eat an optimal amount of calories. When leptin signaling is compromised due to distorted adverse lifestyle practices, especially that introduction of too much artificial light after dark. You don’t get the satiety signal and you tend to store fat rather than burn it. Notice I’m using the word signaling leptin. Signaling being optimal rather than high levels or low levels of leptin. So it’s a little more nuanced than let’s say insulin. Brad (14m 51s): You want to lower your insulin rather than have too much insulin. And what we’re really talking about as the signaling. So it’s different than high and low cause sometimes even with the example of insulin resistance, you’re producing a lot of insulin, but your body is not accepting that signal very well. So you’re over producing insulin and it’s not working as intended because your insulin signaling is off. Same with leptin signaling. Okay. Back to the story. Circadian cycles for the obese are dramatically altered compared to non obese individuals in the morning. In the normal person, ghrelin is high when cortisol is highest in the early morning. Then ghrelin drops quickly when food is eaten. Brad (15m 34s): Of course, the ghrelin being the hunger hormone, you eat food, you satisfy it and boom down goes, ghrelin Dr. Cate says ghrelin gets your stomach growling. So truly the sensations, the noise that you hear in your stomach when you’re hungry is ghrelin doing its thing. However, in the obese, ghrelin is much lower in the morning than expected. And when food is eaten ghrelin stays elevated for an extended amount of time. Okay. Due to the metabolic dysfunction caused by obesity, you eat a meal, you’re supposed to feel satisfied ghrelin supposed to drop down, but instead it stays elevated causing you to consume extra calories. Brad (16m 13s): Let’s move on to 6:45 AM. This is where we see the sharpest rise in blood pressure. In the entire day, this is due to many activated systems in the body, getting us ready to fully supply blood to all the vital areas, to get us motivated, to begin our day and in our ancestral example, to go searching for food. This period of rapid blood pressure rise is why we see so many cardiac deaths occur early in the morning. Well, still asleep or just waking up. This is also when cortisol is the highest, so high risk for heart attack. If you’re in bad shape to begin with. Okay, the insight number three is at daybreak. When sun hits the retina. The photonic stimulus begins to shut off the secretion of melatonin from the pineal gland in the brain. Brad (16m 59s): Remember melatonin is strongly associated with getting you sleepy, helping you go to sleep. It has many other important metabolic functions in the body. It’s a powerful antioxidant. And so it’s not just the sleep hormone, but it is what gets us ready for sleep in the evening. And then with sun, boom, that melatonin is shut down and converting over to serotonin, which is a mood elevating hormone. So morning sunlight contains mostly infrared light at daybreak. And as we approach noon, the ultraviolet light frequencies start to appear on the skin. That’s kind of an aside from Dr. Kruse, but it’s nice to know that the sunlight shuts down melatonin. Brad (17m 40s): So excerpt from Keto for Life, one of our books, just to further explain this transaction of sunlight, hitting your retina. When that morning sun hits the retina and receptors and skin cells throughout the body. Remember that that our entire body is light sensitive and triggering associated hormonal functions. So when you try to go to sleep with a blindfold on, but you still have the TV on or lights in the room, for whatever reason, your skin cells are still getting the message that it’s light out. So that’s why it’s so important to have a pitch dark room to sleep in. Okay. So when the light hits the retina and the skin cells, the signal travels through the optic nerve to other regions of the brain, including the pineal gland. Brad (18m 24s): The light cue prompts, melatonin levels to fall and serotonin and cortisol to spike within 30 minutes of waking. Adenosine. That’s another neurotransmitter levels decrease steadily as you sleep and are low when you awaken increasing alertness. Yes. The identity, yeah. Cortisol, serotonin effect is most effective, closest to dawn, which is another reason why you want to try to wake up in association with sunrise because it makes it so easy to get up and get energized naturally with all the hormones flowing and kicking into gear when the sun comes up. Okay. So number four, on the list of 21, are you hanging with me? Brad (19m 4s): How you feeling so far? All right. All right. At 7:30 AM. Usually after an hour of sunlight, melatonin is completely shut off in the brain. Number five at 8:30 AM. The gut has been awakened and Paracelsus becomes more vigorous. That’s the movement of your colon, right? To a prompt, a bowel movement. Peristalsis becomes more vigorous and bowel movements. Getting rid of yesterday’s food are likely, this happens by protons flowing to move serotonin sulfated sulfated meaning snuffed out like a sulfated battery. It’s protons flowing to move serotonin sulfated by the light of the gut microbiome to get to the brainstem, to turn into sulfated melatonin. Brad (19m 47s): So remember serotonin converts into melatonin in the evening. If that’s a little confusing, remember that you start your good night’s sleep in the morning by getting that serotonin boost in association with sunlight. And so you’re now setting yourself up 12 hours later to convert that serotonin into melatonin and initiate the go to sleep processes. So for contrasting example, if you’d like to sleep until noon and mess things up, and all this light has been happening, but you’re not really elevating serotonin because you’re still asleep under the covers. You’re going to have a difficult time triggering that beautiful dim light melatonin onset process in the evening, within the hours, a couple hours after it gets dark. Brad (20m 35s): Okay. So 8:30 AM. This bowel movement is stimulated. If food is eaten around this time as well, this is called the gastrocolic reflex. Cortisol aldosterone. That’s another hormone and ghrelin are all raised at this time to drive activity, increase our blood pressure and stimulate feeding. This is all tied to morning sunlight stimulus, and it’s blocked when we wear clothes or indoors at work in the morning. So not just getting up in association with sunrise, but getting out and exposing your skin cells and your eyeballs to direct sunlight, to achieve these wonderful hormonal processes that give you that natural energy, the adenosine cortisol, serotonin effect, as well as the gastrocolic reflex. Brad (21m 25s): So you want to get your digestive tract, your elimination system going as well. You heard a couple of comments that the ghrelin is high, and we are prepared to eat food first thing in the morning. So this is an optimal time to consume calories. We’re most insulin sensitive in the morning as well. However, we all know that it’s an extremely popular practice to try to fast for as long as possible in the morning and eat your first meal at midday, achieve this 16 hours fast at eight hours, compressed eating window pattern. Many other reasons that you might have heard in other shows and other the resources that it’s really healthy to fast in the morning. Brad (22m 5s): So those are not those two insights are not at odds. We are definitely primed to consume calories in the morning, but especially in modern life, I feel like a really popular goal is to try and reduce excess body fat. So we’re not operating as perfect metabolic humans anyway. So doing something like delaying that first morning meal until you really require calories is to continue to function well, you can’t take it anymore. You know what I mean? When your appetite is really high, that can be a healthy habit and can kick you into a high fat burning mode during those morning hours. So it’s a, it’s a good time to fast if you want to. Brad (22m 47s): And then there’s quite a few people that will take a nice nutritious morning meal taking advantage of that insulin sensitivity and perhaps fasting through the busy, stressful workday when there might not be an opportune time to create a relaxed environment to your food, completely enjoy that meal and then get right back to work. So it depends, I think, mostly on your daily schedule, your convenience factor and knowing that if you eat a nutritious meal in the morning, that’s certainly aligned with health as is fasting. Okay. So now we go to insight, number six, around nine to 10:00 AM. We have the highest secretions of sex steroid hormones in humans. Brad (23m 29s): And these also tile crescendos lead to our highest alertness okay. At around 10:00 AM. And this allows us, again, going back to the genetic ancestral example, it allows us to explore our environment. You can also infer that this is the time for sexual activity and arousal. So who knew that sex was the morning delight rather than the afternoon delight? Okay. Checkpoint ! And on we go with our day number seven, our ideal muscle coordination occurs at 2:30 PM and this adapts us best to hunt for dinner. Around that time. An hour later, we see our fastest reaction times develop from our motor systems in our central nervous system. Brad (24m 12s): So best time to exercise or perform a high intensity workout just from a circadian perspective, right? It doesn’t mean that you should go switch from your morning class to the 2:30 PM class or what have you. But it’s just an interesting insight to know that our physical body is primed for peak performance at 2:30 PM. 3:30 PM is the fastest central nervous system reaction time. Okay. Number eight on the list of 21, I know we’re cranking through this at 5:00 PM humans exhibit their greatest cardiovascular efficiency, allowing for maximum exercising or hunting. Okay. So we need to expand that window from 2:30 PM to 5:00 PM. Brad (24m 53s): So again, muscle coordination, 2:30. 5:00 PM, cardiovascular efficiency. So really that is a nice window to contemplate exercise. This 5:00 PM timeframe also occurs during a period of time when we have the best rates of protein synthesis in our body. This is the optimal time for exercise. Number nine. The sun falls at 6:00 PM, right? Give or take. We begin to see a major change in the cardiovascular system about a half an hour after sunset. 6:30 PM, highest blood pressures due to changes in atrial natural factor. And antidiuretic hormone, A N F and A D F respectively in the renin aldosterone access. Brad (25m 39s): So again, we had high blood pressure, first thing in the morning, and then we have a high blood pressure period at 6:30 PM. When this, these blood pressure changes occur over the next 30 minutes, from 6:30 to seven, we begin to see a gradual rise in body temperature as leptin and interleukin six is released from our fat stores with Agouti’s help, A G O U T I. After dinner is eaten, this signals the brain about our fat mass and our inflammatory status. If you haven’t heard of that term, Agouti? Google it and you’ll discover that it is a funny looking little rodent. Brad (26m 21s): That’s the first definition that comes up. But Agouti is also a neuropeptide produced in the brain that has a powerful signaling effect to increase appetite, decrease metabolism, and energy expenditure. Again, this is kicking into gear 30 minutes after the sunset. So it’s known as one of the most potent and long lasting appetite stimulators, I guess, ancestrally we were wanting to keep busy hunting, gathering, building our shelter. During the day we had the muscle coordination, the cardiovascular function, and then when the sun sets time to eat, relax, slow down. Okay. So for the next two to three hours, this is insight. Brad (27m 2s): Number 12, leptin levels slowly rise as insulin levels fall. Adiponectin levels also fall during this time. These fat hormone signals are what activate a adenosine system in our bodies. Adenosine remember is created over the course of the day. It’s low in the morning, which increases wakefulness. And then as you start to accumulate, high levels of adenosine will lead to sleepiness on cue in the evening as with melatonin as well. And that’s insight number 13 identizine peaks at 10:00 PM. And then the circadian clock allows for melatonin secretion after three to four hours of total darkness. Brad (27m 45s): Hm. Interesting there, huh. So we really want three to four hours of total darkness to get that familiar sensation of sleepiness, heavy eyes that wants us to go to sleep. Raise your hand if you’re achieving three, four hours of total darkness or as dark as possible with modern circumstances. Oh boy, that’s a tough one. And again, if that’s not happening for you every single day, you’re compromising some of these optimal hormonal processes, antioxidant repair functions that happen in association with melatonin’s rise and continued elevation overnight. So yeah, we’re going to try to achieve darker evenings for three to four hours. Brad (28m 28s): Okay. A serum leptin levels are rising quickly now too. The help of Agouti as it’s released from the fat cells to enter the brain. Agouti is okay. So highest at this time of night, even in a normal person. Number 14, these trends continue. And the gastrointestinal tract is slowly shut down by their circadian clocks around 11:30 PM. And bowel movements are shut down for the night. This means that the vagus nerve is quiet. Okay. So if you are interfering with that super, super bad deal to be shoveling down one more, a handful of popcorn or square of dark chocolate or a bowl of cereal binge late at night, while you’re watching TV and blasting your eyeballs with artificial light, suppressing, the important hormones that prompt sleepiness and getting a good night’s sleep. Brad (29m 19s): But that GI tract is closed for business. I’ve often heard from other sources that after the sunset, your GI tract is really wanting to mellow out, start to get some rest. And it’s not really a prime to digest a meal, especially a big meal. So we want to do the best we can there. Ben Greenfield has talked about this too, and says that, you know what, man, with my family, we’re busy during the day. And we quite often eat big meals after dark, so too bad. So if Ben Greenfield’s okay, prioritizing social times and family connection over the exact optimal time to eat a meal, maybe you can not worry too much about it, but especially in the summertime, when there’s more hours of light before it gets dark, we can make a better effort to try to get those meals in before it gets dark. Brad (30m 9s): On the earlier side of evening. Mia Moore and I were just talking about that the other day, because we went out to dinner and then took our evening walk and Lake swim after dinner because we went out to dinner so early to take advantage of happy hour, yo. And it was very nice to have the dinner done instead of the other way around where we’re out there, taking a walk, going, swimming, coming home, and then starting to prepare dinner. And it’s getting really late, especially in the summer. So if you can put that dinner earlier, great news. Now on to number 15. At midnight leptin begins to enter the hypothalamus to bind to its receptor there. Brad (30m 50s): It signals energy reserves. So I interpret this to mean that now your body’s going to kick over and start burning stored energy for the rest of the nigh. In diurnal animals, sleepiness occurs as the circadian element causes the release of the hormone melatonin and a gradual decrease in core body temperature. That’s another big reason or a big prompter of sleep is you’ve got to get that core temperature low. If you’re heated overheated, for whatever reason, your environment’s really hot in the summer. Take a cold shower before you go to bed. Works really well. I’ve jumped in the ice tub a couple, few times. Not very often. It’s a little bit of a shock to then try to go to sleep. Brad (31m 31s): Cause you are getting that desirable hormone spike that happens in the morning cold exposure. But a cool shower, nothing too troubling. That’s going to cause a stress hormone. Spike is a great prompter of sleep. This drop in body temperature is the stimulus to change. Sulfated serotonin to sulfate and melatonin. The timing is affected by one’s chronotype. Oh, okay. So there’s a little plug for night owls and whatnot. But again, we’re trying to optimize circadian function and get up near sunrise in the morning and wind things down after the sunsets. Number 16, it’s the circadian rhythm that determines the ideal timing of a correctly structured and restorative sleep episode. Brad (32m 14s): Melatonin. The hormone from the pineal gland is called the darkness hormone and it’s of great importance in the functioning of the SCN. That’s the super cosmetic nucleus, which is located in the hypothalamus. As you may know, the hypothalamus is the control tower for all hormonal and metabolic function in the body. It regulates body temperature, hunger, important aspects of parenting and attachment behaviors: thirst, fatigue, sleep, and circadian rhythms. So the SCN located in the hypothalamus is the main arbiter of circadian rhythm in the body. Sunlight hits the SCN and the hormonal cascades are kickstarted. Brad (32m 55s): So the most important target of melatonin in humans appears to be the SCN. The SCN contains the highest density for melatonin receptors. So this super duper effect that melatonin has on the SCN, it has both an immediate effect and a longterm effect, has encouraged its worldwide use against the ill effects of jet lag. Melatonin application has been found to be useful in synchronizing the indogenous circadian rhythms, not only in people who suffer from jet lag, but also in blind individuals, patients with dementia and shift workers with seasonal changes in night duration, there are parallel changes in the duration of melatonin secretion, and this leads to more secretion in the winter as compared to summer. Brad (33m 41s): In the cold environments of fallen winter melatonin couples to E N O S that’s endothelial NOS also known as nitric oxide synthase and not too light levels. Again in the cold environments of fallen winter melatonin couples to endothelial NOS instead of night levels. E N O S is an enzyme that generates vassal protective molecule and O nitric oxide, which serves as a major weapon to fight vascular disease in warm adapted humans in the tropics, the light remains the focus of S C N entrainment year round, potentially confusing there, but there’s a takeaway here that we’re now making this artificially lit year round life instead of actually having a cold fall and winter like our ancestors did. Brad (34m 35s): And so that could be compromising our production of the extremely important basil protective molecule nitric oxide. Now we’re tied to light year round with our melatonin production. And guess what? When we have those lights on all winter so that it doesn’t get dark at five, but rather at 10 or 11 inside our house, this is a, a huge health hazard. Number 17. I know we’re working through it pretty fast. And 21 is right around the corner. I’ll finish the show after we hit the 21, but then there’s going to be a whole nother followup show with insights about what happens when we screw things up and how we can make things better. So here we are with 17, after four hours of darkness, melatonin, secretion increases, and this allows plasma leptin to enter the hypothalamus. Brad (35m 24s): If we are sensitive to its receptor, if we are leptin resistant, which is associated with obesity and all kinds of disease States, this process can no longer occur. Number 18 once leptin enters and binds to its receptors, if we’re healthy. Affects the lateral hypothalamus tracks to immediately send a second messenger signal to the thyroid, to signal it to up regulate thyroid function and efficiency. This is how we can raise our basal metabolic rate when we’re leptin sensitive. These coupled events matched with leptins actions peripherally in the muscles occur at the UZP3 sites. Brad (36m 5s): These are mitochondrial uncoupling proteins to burn fat as we sleep at a higher basal metabolic rate. Again, I said, there’s going to be some science thrown in here, but Hey, if you want to just skip to the big picture insight, if you are not leptin sensitive, you are screwed because you’re not even burning fat. Well, while you sleep as would someone who has healthy metabolic function. So back to the description, this means the electron transport chain does not make ATP. As usual. When leptin allows this uncoupling to occur, we make heat and not energy from normal metabolism. This means we will burn off our excess calories as pure heat. Brad (36m 48s): This is one reason why calories in and calories out argument makes no biological sense once you understand how leptin works, humans are built to burn fat at nigh as we sleep to lose the excess weight that we don’t need. So it’s critically important to being leptin sensitive, to have these things take place in the middle of the night while we sleep. And this is why number 19 is a big one. The timing of leptin is so critical. It usually occurs between 12 and 3:00 AM and is tied to when you last ate and how much darkness your SCN, your super charismatic nucleus has seen this generally occurs soon after our hypothalamus releases another hormone called prolactin from our pituitary gland in the brain. Brad (37m 36s): Number 20, the surge of prolactin is normally quite large in normal darkness, but is significantly diminished in artificially lit environments after sunset. The reason is that prolactin release is coordinated with sleep cycles where autophagy is at its highest efficiency and where growth hormone is released. If this is diminished, by, guess it, artificial light and so forth. We generally see lower D H D A levels clinically. That’s the prominent sex hormone that prompts the healthy levels of reproductive hormones, testosterone, estrogen, so forth. We’re generally seeing lower DHDA levels clinically and higher interleukin six levels on cytokine arrays. Brad (38m 21s): That just means inflammation patterns rather than healthy sex hormone production. This is a measure of uncoupling of sleep from normal metabolism. I base every biohack I do on this step in circadian biology, because it is the most important. That’s the surge of prolactin that we want in total darkness at 12 to 3:00 AM. So that leptin will work efficiently. Number 21, this normal, large circadian, protract and surge, we should see at around midnight after leptin enters the brain It does not happen if the patient has leptin resistance, sleep apnea or has eaten food too close to bedtime. Brad (39m 6s): And that’s a three to four hour window that Kruse wants from our last meal to bedtime. These things that we just mentioned, block leptin’s ability to enter the brain because of the insulin spike from the meal. As mentioned above this step is usually impaired. If you are a post-menopausal female as well. This is often why older women sleep badly and gain weight. They cannot seem to lose in the gym, even with a good paleo template and good exercise habits. You’ve heard that complaint so frequently that after menopause, everything changes and their body composition goes to heck. Well, let’s look at these evening patterns. Brad (39m 46s): We want that leptin to enter the brain. We want it to do its thing to prompt the prolactin surge. So no eating within three to four hours of bedtime, no excess artificial light digital stimulation after dark and getting up in association with sunrise to get that adenosine surge, and serotonin cortisol, spike that needs to the melatonin release in the evening on cue. Okay. This is another reason why Kruse is a big advocate for bioidentical hormone optimization in women. This need is greatest in women who are warm adapted, and the need is lowest in cold adapted females because their leptin levels are already low due to the cold. Brad (40m 30s): Post menopausal women who are cold adapted tend to do amazingly well clinically in most disease parameters. The main problem they face is their vanity and dogma to keep them from using cold pathways. To become rock stars as they age. Oh my gosh. Ladies, go look at Brad Kearns, chest freezer, cold therapy, the YouTube video. I explained the whole thing about how to get started with a cold therapy practice. I know the cold tub is pretty hardcore. Maybe not the most appealing to that demographic of post-menopausal females, as opposed to super-duper biohacking males from the age of 24 to 45. Brad (41m 13s): But at least you could get started considering the practice of a cold shower and working toward a more cold exposure. And there’s all assortment of ways to become cold adapted. One of them is to underdress when you go out for an evening walk or just have some periods of time where you’re underdressed and getting yourself cold a little bit once in a while, instead, always being perfectly dressed and avoiding that icky cold water. Thank you so much for listening to part one of the journey around the circadian clock inspired by Dr. Jack Kruse. And we’ll come back with takeaway insights and what to do if some of this stuff is broken. All right, good work way to hang in there. Brad (41m 55s): Thank you for listening to the show. We would love your feedback at getoveryourselfpodcast@gmail.com. And we would also love if you could leave a rating and a review on iTunes or wherever you listen to podcasts, I know it’s a hassle. You have to go to desktop iTunes, click on the tab that says ratings and reviews, and then click to rate the show anywhere from five to five stars. And it really helps spread the word so more people can find the show and get over themselves because they need to thanks for doing it.

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