Category Archives: 16. Sleep

Leptin Resistance and Inflammation

Leptin Resistance and Inflammation

References: Am Jr Coll CardVitamin HormonesCurr Immunol ReviewCell,

Leptin is the hormone that has several important functions. One is that it is secreted when your fat cells say they are full. It is a feedback loop that tells you that you have had enough to eat, so stop. Fine and dandy. But like everything else in your body, there are layers and layers of delicate complexity far exceeding the first layer of functionality. Another layer is that it essentially mediates the release of fat from fat cells, making it the guardian of your energy stores. When all is well and working properly, your leptin level falls when you don’t have food and your fat cells open up and share their calories. Women have more leptin than men. As a general rule, gaining weight results in a higher leptin level which should result in your feeling full and not eating. Something strange happens, however, when you get inflamed.
The fly in the ointment here is that there is an intersection between metabolism and inflammation. The leptin receptor in your hypothalamus appears to be a critical link. It turns the Proopiomelanocortin system and has you produce melanocortin. MSH. MSH is a potent down-regulator of appetite. With a nice high MSH, you don’t feel like eating. Low MSH, you don’t have a feedback loop. And just what happens with inflammation? Leptin plays a role in that it has a critical effect on innate and adaptive immune response. It promotes the secretion of cytokines like IL-6 and Tumor Necrosis Factor, and there you have it. It sets up the link between metabolism and inflammation. What you see is a dramatic dysregulation of inflammation in folks who become overweight, and thereby establishing the first step in increasing risk for Alzheimer’s, heart disease, cancer, autoimmune disease and just about everything else that ails us. The “Common Soil Hypothesis” is the concept that metabolism and inflammation came from the same source in evolution, way, way back. Here again, we see that nexus and it makes for problems.

What you see happen is as follows. Folks with inflammation, like low-grade mold exposure, have low MSH and high cytokines that damage the leptin receptor in the hypothalamus. Leptin drifts higher in response, trying to bring about control of calorie balance. The person gains weight. Leptin goes higher, but the receptor is damaged and the higher leptin then mediates more inflammation. Around and around you go. If you feel overweight and have chronic pain or chronic fatigue, you likely fit this model. Forget trying to lose weight until you lower your leptin.

How can you lower your leptin most effectively? I suspect the fast mimicking diet will do so, but that is not yet proven. The one good study that shows regeneration of the pancreas beta cell used mice with a genetic defect in their leptin receptor, so they couldn’t be used to proven leptin repair. Right now we can use pioglitizone (ACTOS) which is an old fashioned diabetes drug that has lots of side effects when used for too long, but is dandy at lowering leptin and MMP-9, two mold effects.

Can we reduce leptin with our own lifestyle? Well, quite a lot. If you focus on several key items, you can guide your leptin lower. Keep your daily sleep cycle to a regular pattern. That plays into your POMC system being played every day at the same time. Avoid sugar. Increase fat in your diet. Cut down on your evening meal and increase your daytime eating, making for at least 12 hours of fasting each night. Exercise. Sleep at least 8 hours, starting with at least 3 hours of no food before bed. Consider training yourself to enjoy a cold shower, particularly if you get a nice hot sauna just before. (The Finns had it right.)

WWW.What will work for me. I’m fascinated with leptin and mold illness. I keep seeing women in particular with not only high leptins but super high leptins levels. Just about every one of them has had low MSH levels, meaning some sort of mold or biotoxin exposure. Throw in stress, sugar, lack of exercise, lousy sleep and we make for a perfect storm to elevate leptin, and keep everyone overweight and inflamed.


Pop Quiz.

  1. Leptin helps you make MSH which suppresses your appetite. T or F                Answer: Almost right but backward. LACK of leptin results in hight MSH, and then weight loss and lack of appetite.
  2. Inflammation turns on leptin. T or F                                                                      Answer: I’m into backward today. It makes for leptin resistance, which then elevates leptin.
  3. Name a few means by which you can lower your leptin with lifestyle changes. Answer: Regular schedule, exercise, sleep, 12 hours of fasting, weight loss, less sugar….
  4. Leptin allows the release of MSH. What does MSH do?                                     Answer: It’s a potent appetite down-regulator.
  5. The cause of fibromyalgia is likely?                                                                    Answer…….. /biotoxin illness leading to damaged leptin receptors.



Sleeping on your Side Washes Your Brain the Best

Sleeping on your Side Lowers Risk for Alzheimer’s

Reference: Jr Neuroscience August 2015, New York Times

August 17, 2015

Sleeping on your side may reduce your risk for Alzheimer’s!   How so? Well, the above referenced study was done in rats, so we aren’t certain it works in humans, but it appears to reflect what happens in all mammals. The evidence of what happens when we sleep is increasing.

Sleep is your brain on “flush”. It’s cleaning itself and washing away accumulated toxins. When you are awake, your brain is using up to 50 different neurotransmitters to conduct its business of thinking and surviving.   Those neurotransmitters are sent out along very long, tiny thin wires called axons to connect with other cells all over your brain.   Little packets of those chemicals are secreted on one side of synapse to cause a reaction on the other side. The chemicals may be picked back up, or may be digested.   At the end of the day, you are left with a lot of chemical breakdown products a long way away from where they were manufactured. The wires (axons) are so thin that there is a big problem transporting the waste products back.   You feel tired and ready to sleep.   If you don’t get sleep, you start to slow down your thinking, make errors and within a few days, hallucinate before you die.

That’s where the glymphatic system comes in.   It was described only in the last few years when it was discovered to actually connect the lymph system to the brain. What is more dramatic is what happens when you sleep.   The glymphatic system swells in size (as much as 60%) and the axons shrink in size. This allows for a huge increase in the flow of lymph fluid while you sleep. The amount of flow that can be accommodated by that change in fluid size is as much as 10 fold.

It’s as though your brain can either play in the band, or dance to the music, but it can’t do both at the same time. It can think and function as what we call awareness, or it can flush and cleanse itself in what we call sleep.   But toxins are building up every second you are awake, and eventually have to be flushed out.

So, just what did this study show?   Rats, when sleeping on their sides, are much more efficient at cleansing their brains than when they sleep on their backs or stomachs. Now all mammals naturally sleep on their sides predominantly.

What gets flushed out is not just the chemical break down product but also β-amyloid, the protein that is found concentrated in Alzheimer’s.   Dr. Helene Benveniste used MRI technology with kinetic modeling to measure the exchange rate of the cerebrospinal fluid with the glymphatic system fluid.   With fluorescence microscopy and radioactive tracing, they were able to see the change in fluid flow during wakefulness and sleep by looking directly at the brains of the anesthetized rats.   This is another study confirming the existence of the glymphatic system, and building on that to show that it is most efficient when you lay on your side.

Lots of dementia related diseases have sleep disorders as part of their pathology. Alzheimer’s is no exception.   And there appears to be links between chronic sleep loss and Alzheimer’s.

WWW. What will work for me.   I like sleeping on my side but my shoulder aches if I don’t have two pillows to support me.   I’m going to pay attention to see if I get more restful sleep when I lay on my side or on my stomach, and avoid my back.


Pop Quiz

  1. During sleep, the fluid flow of your brain’s drainage system increases 60%. T or F

False. The size of the vessels increase in cross section 60% but that means the flow can increase as much as 10 fold.

  1. Your brain can either cleanse itself or think, but can’t do both at the same time. T or F


  1. Your brain has a system of fluid channels that are connected to the lymph system out of which fluid flows during sleep, now called the glymphatic system. T or F


  1. Lack of sleep means toxins are building up? T or F

True. That may be sleep’s most important action.

  1. Sleep flushes out β-amyloid, the protein that accumulates in Alzheimer’s. T or F




Sleep is your Brain on Drain

Sleep is Your Brain Drain

Reference:   Science Daily June 2015,

What a great feeling to wake up in the morning and feel really refreshed!   You can get stuff done. You have ideas. You feel full of vitality and energy. What just happened?   Your brain got scrubbed, washed, flushed and reset!

Sleep is dangerous.   Mammals get eaten during sleep.   Yet every mammal does it. It must be so important that it is worth the risk.   So, just what is happening? We have reported on it before, so here is a second article building on the first .

In the Journal of Experimental Medicine, Dr Aspelund now reports that he was able to demonstrate the connection of the lymphatic system of the adult human brain to the rest of the lymphatic system.   The lymph vessels are so delicate, and they collapse so completely when not flowing that finding them takes painstaking searching.     And that’s what Dr Aspelund did.   He found the links and anatomical connections.

When you are awake, there is very little flow in the “glymphatic system”. But when you sleep, something dramatic happens. Your neurons begin to shrink and the spaces between cells increases dramatically.   Flow of the brains lymphatic system increases as much as 3 fold during sleep.   More interesting is that when the Alzheimer’s associated protein beta=amyloid is injected into a mouse’s brain, it can be shown to clear more rapidly when the brain is then asleep.

Our brain is a very busy organ, using as much as 25% of our total energy. Just being awake and taking care of business, you are accumulating breakdown products of brain messaging.   The synapses, or connections between brain cells, are often quite far away from the body of the cell.   The wires that connect the cells to their synapses are, of a necessity, long and very delicate. For a small, compact cell, the simply diffusion of chemicals inside the cell allows for breakdown products to be excreted and metabolized.

But what do you do when you have very delicate, long, slender pipes that send chemicals inches away from where they were manufactured?   Of a necessity that stuff is going to accumulate.   For example, we do know that adenosine accumulates during wakefulness.   Adenosine is a break down product of energy useage. It comes from ATP, our cellular gasoline.   When awake, adensosine levels in the brain rise. When we sleep, adenosine gets flushed out and ATP levels get recharged.

What happens if you don’t get enough sleep? A lot. Total sleep deprivation will kill you. Less than 7 hours a night and you start showing higher stress hormones and get on the road to becoming overweight. Less than 6 hours and we can show you start having risks for diabetes.   There may be much more to sleep than just flushing the brain as all these other endocrine disruptions suggest a very intricate balance of functions. But maybe all of them depend on getting a chemical flush.

You thought that sleep was all about your brain getting reorganized and consolidating energy. That’s what we have all been taught.   Now we know differently. Sleep is there to clean out the gunk, to flush out the poison.   It is only with unconsciousness that our neurons shrink, allowing the lymph system to start flowing and the waste products to be washed out. The effects of poor sleep are awful.

WWW. What will work for me.   I just had a great night’s sleep. It feel wonderful. I feel full of energy.   I can write this column.   Try to get at least 7 hours.   Take 3 mg of melatonin at bedtime.   Don’t watch disturbing TV before bed. Turn the lights down lower later in the evening.   Don’t go to bed mad.


Pop Quiz

  1. The lymphatic system of the brain is called the glymphatic system. T or F

T (Open book – open internet makes for great testing, doesn’t it!)

  1. The brain’s lymphatic drainage in humans has been proven to both exist and connect to our other lymphatic system. T or F


  1. Your brain neurons shrink in size when you sleep.

That’s it

  1. Your brain’s lymphatic drainage increases when you sleep

Right on

  1. You build up adenosine, a breakdown product of energy production during wakefulness. T or F


Sleep Apnea – A Cure?

Reference: Science Daily, Sleep Medicine 2014

Sleep apnea is increasingly being recognized as a huge risk for men. It keeps climbing up the risk ladder as causes of heart disease.   What is it? It’s the subtle collapse of the upper airway that blocks normal, effortless breathing while asleep. What ensues is a tug-of-war between effort to break that blockage by increasingly rigorous efforts at breathing, and need for deep, restful sleep. In its most classical form, the person breaks through their apnea with a sudden snort or loud snore after a variable period of silence. Observing the sleeping person in that silent period will show someone who almost looks like they are gagging, as they make an effort to breath in, but have it arrested by being unable to force open the collapsed airway. The net effect is awakening, every 2-5 minutes, all night long. Guess who well rested that person feels the next day! If you have an issue of fatigue, and you snore, you likely have some measure of sleep apnea and are not getting restorative, restful sleep. (Mild sleep apnea = 5-15 episodes per hour, moderate is 15-30, severe > 30)

It is intuitively obvious that extra weight makes sleep apnea worse. The need for effortless, easy breathing is impaired by extra weight on the chest and abdomen. The diaphragm has more work to do. There is more weight in the neck area. Extra fat provides less room for muscles to move it. But it has never been studied as a means to cure.   This is the first study looking at weight loss as the solution.

That’s what this study provides. For the first time, obese men and women were taken and carefully instructed to make meaningful life style changes so that real weight could be lost.   They started with 81 subjects, and finished with 47.   They all had sleep apnea. They were followed for 5 years while being counseled. Those who achieved 5% weight loss were considered successful (n=20) versus those that didn’t achieve meaningful weight loss. (n=27) The risk of progression to more severe sleep apnea was reduced by 80% in the weight loss group compared to the other group.   Some men were cured completely. The dietary intervention was to increase the consumption of lean meats, fish, fruit and vegetables and to avoid desserts, dairy fats and saturated fat. (No wonder only 20 men lost weight.)   Exercise was counted when men exercised 30 minutes three times a week.

The main finding, that sleep apnea gets better with weight loss, is huge. But this is a very small study, and only a tiny bit more than 50% could finish it. An 80% reduction of progression when you have only 20 participants might be a very small number. What is more interesting to me is that they found 20 folks who could lose 5% weight on a low fat diet. We now know that these folks will fail in time and regain their weight. The only weight loss that is long lasting and successful has the consumption of fat as central to its mechanisms. Eating carbs turns on insulin and insulin stores calories: that’s how you gain weight.

WWW. What will work for me. I think it’s time to take this knowledge and press the advantage. In my practice, I have dozens of folks in just a few years who have dramatically improved their weight, and sleep, and very likely their snoring. We don’t need more studies of low fat weight loss, we need a high-fat, low carb (>20 grams/day) weight loss study. That will show folks to be cured.

Pop Quiz

  1. Sleep apnea can be cured with 5% weight loss? T or F


  1. This cure applies to men and women. T or F


  1. Snoring is a cardinal symptom of sleep apnea. T or F


  1. Sleep apnea will get worse over time if you don’t lose weight. T or F


  1. Sleep apnea is a huge risk for heart attack, diabetes, high blood pressure. T or F