Category Archives: 24.Basic Physiology

Copper, Another Cause of Alzheimer’s

References: Dr. WeilJ. Biological and Inorganic ChemistryFront Aging NeurosciJr Nutr Health AgingPro National Acad Sci., NeurologyEuro Biophy Jr,

We have established that iron is a problem in Alzheimer’s Disease (AD). That’s clear. But are there other links? What else has changed in Western Society? One example is clean water, delivered through sterile pipes made of………copper. That is new in the last 100 years.
Wast AD rare 100 years ago? Yes. In 1900 it wasn’t even mentioned in Osler’s compendium of medical diseases. That was at a time we had over 3 million folks over age 60, and at today’s rate of AD, there should have been 36,000 cases in the USA, enough to have been noticed and commented on by Osler. So, it’s new and it’s common.
Sparks and Schreurs published an article in 2003 looking at free inorganic copper added to rabbits drinking water at a concentration of 0.12 parts per million caused AD like pathology in their brains and damaged their memory. The EPA allows 1.3 ppm of free copper in our water. That’s allegedly safe. Singh confirmed the exact same results in a mouse model of AD in 2014.
The key here is the difference of “free” copper, loose in your blood and lightly bound to albumin and organic copper, tightly bound and regulated attached to a protein called ceruloplasmin. The free copper is a problem. Squitti showed that free copper is elevated in AD, but not in vascular dementia and its ratio of free copper to bound copper predicts the range of dysfunction. Free copper comes from copper pipes. Organic copper comes from food. Don’t confuse the two, they are different in their biological behavior. Organic copper is bound to proteins, carefully guarded and processed. Free copper is not bound and is not in the protection system of the body.

Where do we get “free” copper from. Our plumbing. 90% of American homes have copper pipes in them. The use of copper took off after WWII as did the incidence of AD. It should be noted, the Japanese were hesitant to use copper and didn’t use copper in internal plumbing. They have had MUCH less AD. When Japanese move to Hawaii, they lose that advantage and develop AD just like everyone else.
What does copper do in the brain? It appears to be part of the APP and APOe protein pathology. It certainly causes oxidative stress on brain cells. It may be simpler than that. The APOe 2 gene has 2 binding sites for copper, the APOe3 gene has 1, and the APOe 4 gene (the bad one) has no binding sites for copper.

Here is the proposed sequence for copper
1. You live in a home with copper pipings.
2. Your brain copper rises as you get too much in your water
3. Your copper removal system kicks into gear, the APP system works on copper like it does on iron.
4. You have an APOe 3 gene (lousy with only one binding site) or worse, an APOe4 with no binding sites – so you can’t get rid of it at all
5. Your brain churns and churns, trying to get rid of copper with the APP protein, and it just can’t do it because you have too much copper in relationship to your APOe risk.
6. You overwhelm your brain cells. They die. You slow down.

You can’t change your genes. You can change your water. Brewer studied several hundred American homes for copper levels. He found that about a third had copper levels above 0.1 (damages rabbits and mice), about a third had levels below 0.01 and a third were in-between.. Your pipes are killing your brain.

www.What Will Work for me. I’ve been startled by checking zinc and copper levels for the last year. I have had two or three couples whom I have seen who have normal zinc and copper ratios. To a person, they have all had normal zinc copper ratios. (Remember, zinc and copper work like a teeter-totter. As copper goes up, zinc goes down and vice versa.) Healthy brains have more zinc than copper. Everyone else has low zinc and very high copper. When I went to Burma last spring and asked about AD at a nursing home we visited, I was met with curiosity and confusion. They had never heard of it. Thirty residents over 70 should have had some dementia. Their water source: a single iron pipe, outside in the courtyard. Hmmm. For now, I’m taking zinc every day. I’m thinking about how to get my water checked.

Pop Quiz

  1. Copper works on the same channels in your brain as iron causing formation of amyloid protein plaques? T or F                                                                                 Answer: That, my friend, is true.
  2. Copper is tightly regulated by nature with a protein called ceruloplasmin where it is safely sheltered. T or F                                                                                               Answer: That’s what we measure and presume.

 

  1. Alzheimer’s patients have high levels of “free copper” relative to bound ceruloplasmin copper. T or F                                                                                                    Answer: See the pattern we are building?     True

 

  1. What percent of American homes have copper pipes, and what percent have levels of copper enough to create plaques in brains (in rabbits – 0.1 ppm)?                        Answer: 90% and 30%

 

  1. Zinc levels balance copper, so one strategy to soften copper’s damage is to take zinc. T or F Answer: True. Get your serum zinc higher than your copper

 

The Trouble with Iron: Part IV The Nitty Gritty of What Happens in Your Brain!


References: The MindSpan Diet, Nature Communications, Front Aging Neurosci, Maynard: Jr Biological Chem, Annual Review of Neurosci,

Bear with me. I need to know the details of just what happens in your brain that makes iron so destructive. So here goes. You can get a wonderful synopsis by reading the MindSpan Diet book, or if you want a deep dive, I’ve got links here to some of the most meaningful literature.

For starters, what is the role of the APOe -4 gene? Having one copy doubles your risk of Alzheimer’s (AD), but two copies is a 10 times risk. Only 2% of Americans have two copies, but they are 15% of AD. Just two years ago, the AD Neuroimaging Initiative published a very strong paper showing that the APOe gene drives iron into the brain, and the level of iron in the brain, (as measured by cerebrospinal fluid ferritin) correlated with cognitive decline.

Along comes gene number 2, the APP gene. It was found in Down’s folks, who inevitably get dementia, and who have 3 copies of the APP gene. (It’s on chromosome 21 which Down’s folks have 3 copies of instead of two.)

Now, here is the key. We have 20,000 genes. Only 20 of them are responsive to levels of iron in our environment. It’s called the Iron-Response Element. It gets turned on when there is more iron, turning on the production of the APP protein. APP protein has the job of exporting the extra iron out of the brain.

The importance and centrality of the IRE system and the APP gene comes from population research in Iceland. There, a small and homogenous population allows genetic research to flourish. There are Icelandic folks who have a genetic variation of the APP gene, and they get about 10 years of brain protection out of it. Or, they have a 7.5 times less likely to get AD at age 85 than the rest of Icelanders. Lucky devils. It completely negates the danger of the APOe-4 gene. That really fingers the APP system as being in the forefront of causing AD. There it is.

So, let’s just simplify the sequence.

1.   You have too much iron, either because you ate too much red meat, took too many iron pills, or had two copies of the APO-e 4 gene. (Bad luck or bad environment.)

2.  The IRE system turns on, like your sprinkler system in your building in response to a fire.

3.   The production of APP protein turns on. (The sprinklers are blasting water everywhere, trying to douse the flame of too much iron.)

4.  The brain equivalent of Servrpro comes along to clean up the mess and ends up clipping a piece off the APP protein that gets left behind. That piece ends up accumulating in plaques, called beta-amyloid.

5.   As amyloid pieces accumulate, the clean up crew has to work overtime, using up its ability to duplicate  (the cells can only duplicate themselves so many times, each time shortening their telomeres and finally being unable to clean up at all).  Clean up slows.

6.  AD accelerates and the brain falls apart.  You slow.

Well, you can’t control your genes. You got what you got. You also can’t control the other elements of the breakdown process. But you can control your iron. That’s what is in your power.

WWW.What will work for me. It’s all about lowering your ferritin. What we haven’t talked about yet is the roll of copper. That may be as bad as iron, and that is coming next week. For now, I’m thinking about how to get rid of my iron. I’ve got too much and I now have the supplies in my office to do “phlebotomy” – cleaning and carefully draining blood out of you. If you can’t give it to the blood donation center. Please, please, please, do that first. Remember – you are aiming for a ferritin of 40. Give yourself a year to get there. Each time you give blood, your ferritin will drop about 20-40 points.

Pop Quiz

  1.   The APP protein is responsible to get extra iron out of your brain? T or F              Answer: True

2.     The Iron Responsive Element is one of 20 proteins in our genome that turns on in response to too much iron, and it turns on the production of more APP? T or F                             Answer: In a nutshell, you got it

3.   Your iron level in your spinal fluid reflects what’s in your brain. T or F                      Answer: Right again. True

4.   Blood donation will lower your ferritin. T or F                                                                 Answer; True. Isn’t that just too easy?

5.   We have tried our best to make sure people have enough iron. That is good for…..?                   Answer: Young menstruating women. Not so good for those of us over age 50.

The Trouble with Iron Part III Diabetes

The Trouble with Iron Part III Diabetes

References: Cell MetabolismJ of Diabetes Research,

You were trained to think of iron as absolutely necessary to help fatigue. “Build up your blood!” and other such phrases are deep in our subconscious. We see blood and know it is the red of iron. Iron is critical for life, because it’s the key to carrying oxygen to the tissue so that we can make energy. No doubt, iron is important. But carrying oxygen is no mean feat, as it is such a reactive chemical, it needs the strong chemical bond of iron in heme to transport it. What happens when you get too much iron?

Two conditions of too much iron are thalassemia and hemochromatosis. Guess what happens to those folks? Hemochromatosis is also known as bronze diabetes. They fill up the islet cells of their pancreas with iron, and their insulin producing capacity fails. This can be reversed with removal of the iron.

And what happens to normal folks? Well, here again we find that the tendency to being diabetic goes along with the tendency to be iron overloaded. And the devil is in the details. It’s not just the total load of iron that causes damage. It’s not just the accumulation of iron in the islets of your pancreas. It’s the whole ecosystem effect of iron. Iron plays a role in every tissue that mediates energy metabolism, particularly the fat cell. There is a whole host of signaling that occurs when iron is present with intracellular and extracellular messaging. The nuance of it is still not anywhere close to being understood, but you can get a sense for its complexity by the review in Cell Metabolism.
And what have we done, with all of our good intentions, in America. We have devised guidelines for iron supplementation that serve young, pregnant women, well. We add iron to all our grains. It is the fortification you see on the label of every kind of flour product. When you eat most breakfast cereals, particularly the ones that claim to have you supplemented with great vitamins and minerals, you will find 18 mg of iron added to each serving. But it will also be in the flour of your bagel, your hotdog bun, your Danish, your french toast. And it interferes with your metabolism of carbs, immediately. On the spot.

This raises a fascinating conjecture. Is it the iron added to carbs that makes them so problematic for weight gain, insulin resistance and diabetes? Hmmm. There is enough evidence around iron to make it a perfectly reasonable hypothesis. That also explains a few conundrums that the pure carbohydrate hypothesis doesn’t solve. For example, why is red meat so insulogenic? You eat a large bloody red steak, dripping with heme, and you get a huge spike in insulin. And it may not be just the red meat per se, because we see a stronger effect with processed meats. The evidence seems to lean towards more complicated and nuanced reasons, like the amount of AGE’s and ALEs. (If you knew what those were before you read this: you are a star. AGE’s are Advanced Glycation End Products – made by roasting meat with sugared sauces and ALEs are Advanced Lipo-oxidation Products, that occur with food preparation of meats with protein and high fat content.) However it occurs, iron is in the middle of it.
Here are some tests this hypothesis. First, one must look for high ferritin in folks who have high cholesterol, moderate blood glucose and elevated insulin: all the people we thought were overindulging in carbs. So far, I’m three for three. The last one had a ferritin over 600. Another test…..why can’t women lost weight after menopause? Answer: They stop losing iron with menses after menopause, accumulate iron and have their insulin go up. That makes them gain weight. Hmmm. Ever seen that happen? They go carb free and eat more meat, and don’t lose weight. Hmmm. I’m about 400 for 400 on that one.

WWW: What Will Work for Me. I’ve paid a lot of attention to this topic in my own life. Right now I’m reading labels and finding secret iron everywhere. At the picnic last night, I avoided the hamburger offering and had two olive oil salads instead. I had just read that the iron in spinach is tightly bound by oxalates. And what about Vitamin C? It increases iron absorption 400%. Complex, isn’t it?

Pop Quiz

  1. Too much iron in you can cause you to become insulin resistant, thereby leading to diabetes risk and obesity? T or F                                                                              Answer: Bingo. True
  2. The mechanism for this cause is well known. T or F                            Answer: Well, it’s well known now but the mechanism is still murky. Too complex. The phenomenon has been observed. And ferritin is deposited into insulin cells in the pancreas, but the cellular mechanism is much more nuanced, probably because iron is so tightly regulated and bound.
  3. You should know your iron level and it should be?                              Answer:  Ferritin of 40 or so.
  4. If your ferritin is too high, you can reduce it by?                                   Answer: giving blood to the Red Cross. Come on in and we will phlebotomize for you if the Blood Donor Center won’t or can’t do it.  (Leaches.  Blood letting.  Hand to hand combat.)
  5. This iron topic is a whole new way of interpreting the problem with carbohydrates, because………..?                                                                                           Answer: we added iron to virtually all carbs in Western societies. It may be the iron, and not the carbs.  This is conjecture for now, but it sure fits.

LifeSpan versus HealthSpan

LifeSpan Versus Healthspan

References:  WEForum 2017Compreh Physiology 2012,  Med Sci-Fi Sport Exercise,

We are living longer. But are we living better? In the 20th century, we doubled our life expectancy with the miracle of antibiotics, clean surgical technique, X-rays, immunizations and clean water.  Babies being born today in advanced societies have a 50:50 chance of living to be 100. But living longer isn’t necessarily better. There have been some disturbing trends lately. Obesity has managed to reverse the climb to longer lifespan in some societies, namely the USA.

As we live longer, we have more choices about lifestyle, making research into factors affecting confoundingly complex. It becomes impossible to do “randomized, placebo controlled” studies over decades without limiting free choice and spending more money than could be allocated. This article, from the World Economic Forum this year, offers insight into the laboratory of fitness, namely masters athletes. I have a dozen or so men and women older than 60 in my practice who would qualify as exceptionally fit. And I see their lab results and their vitality. They are aging differently than those of us who are less active.

Sedentary behavior is being increasingly recognized as the driver of many of our modern conditions. Part of this discernment comes from the recognition that athletes, (high end performers) have a disproportionately share of good health. They don’t get in trouble. They still die, but their time of end-of-life disability is markedly compressed, compared to the majority of the sedentary population. They become a unique research cohort, one that we couldn’t duplicate with “randomized research”. In effect, what happens with athletes is that they reach their peak in their 30s, like all of us, but then don’t show much decline until close to the very end. The rest of us show inexorable, linear decline. “Patch, patch patch, after 40!,” we say.

At every age in life, starting exercise of any kind has benefit. And the risk of complications from exercise is far lower than the risk of remaining sedentary. The real risk is sitting. Considering computer games at home, TV, computers at work and cell phones in-between, we are mesmerized by electronic distractions that leave us sedentary. In fact, research in 2009 of 17,000 Canadians of all ages showed a dose relationship of sedentary behavior to all cause mortality, regardless of levels of exercise. That means 30 minutes in the gym does you no good if you are sitting the rest of the day. Bother.

The Author cites four strategies with references on each: 1) Move More (Just get started and move more), 2) Move Slow, (Aim for 10,000 steps a day) 3) Move Fast (Add some high intensity something, even for just 10 minutes) and 4) Move Heavy (Add some weights). Read those hyperlinks. It’s the best of our knowledge.

WWW.What will work for me. Sedentary behavior is the new smoking. If you want to live better, longer, you have to do it. Build it in every day. A day without exercise is as bad as a day of smoking.

Pop Quiz

1. Our grand-kids are likely to live to be 90+. T or F Answer: False if they are sedentary, but true if they get the exercise bug and take care of their diet.
2. Our society is becoming more active. T or F Answer: Mixed picture. But as a general rule, false. Bless those who make the answer slightly true.
3. 30 minutes at the gym has beneficial effects? T or F Answer: Sure, it helps. Its benefit may be completely erased by an 8 hour day of sitting.
4. There is a dose relationship between exercise and good health. T or F Bingo
5. Getting sweaty isn’t necessary. T or F Answer: False, if you want optimal results. Getting sweaty 3-4 times a week is much better for you.

 

Sulfate: Maybe it All begins with Sulfate

Sulfate: Maybe it All begins with Sulfate

References:  Holistic Primary Care,  Theor Biol Med Model,

You’ve probably heard the term -sulfate added on to many medical terms. For example: chondroitin sulfate. You might have shrugged it off like it was just an add on salt, and no big deal. In that, you may be very, very wrong. At least, you are if Stephanie Senneff from MIT is right. At last March’s Clinical and Scientific Insights Conference in San Francisco Dr. Senneff had a breakout session on sulfate and it’s importance. In sum, she argues this is one of the foundational causes of most diseases. Whoa! That’s big. How can she claim that?

Here is her logic based on proven experimental literature and known chemical principles. The sulfate anion, a combination of sulfur and oxygen, is the fourth most common anion in out bodies. It plays many critical roles detoxing drugs, digesting food, building our intracellular matrix, preventing blood from coagulating when passing through tiny capillaries. Lots and lots of roles. And where does it start? Ironically, in your skin with exposure to sunlight. A combination of red cells, cholesterol, sunlight and vitamin D are all necessary ingredients to make the sulfate anion. Senneff describes our skin as our solar powered battery because it extracts the energy of sunlight through the enzyme Endothelial Nitric Oxide Synthetase that turns the energy of sunlight into the sulfate anion in your skin.
At this point, sunlight and sulfate make two new and unrecognized molecules, vitamin D sulfate and cholesterol sulfate. The Vitamin D sulfate is water soluble and can travel everywhere. The Vitamin D you take in a pill doesn’t have the sulfate attached, so can’t dissolve in water (blood) so doesn’t have near the effectiveness of the sulfated form. But ditto for the cholesterol. It’s hard to get sufficient Vitamin D from oral supplementation alone, making sunlight a critical link for good health. Hmmm….don’t you just plain feel better when you get sunlight. The principle remains, many hormones, vitamins, fats have to be sulfated to be transported in the blood.

The foundational necessity of sulfate comes down to the physics of fluid flow in your blood and blood vessels. Cholesterol sulfate lines the outside of red blood cells creating a negatively charged field so that red cells repel each other, allowing them not to stick together as they travel through all your tiny capillaries and not rupture. That same negative charge carried by sulfate creates a behavior of water atoms on the surface of blood vessels that make them super slippery, almost like a teflon surface. In fact, that effect of sulfate may be central to the actual biology of how heart disease gets started. That’s for next week.

WWW.What will work for me. If sulfate is important, where can I get it in my diet? Well, ever wondered why garlic is such a potent herb? Loaded with sulfate! And the whole broccoli, kale, cabbage family. Loads of it. Eggs. Ditto. And sunshine? Yeah, I know the dermatologists goes nuts over too much of it. But without it, you don’t make the sulfate ion in your skin. This may be another clue why Vitamin D studies haven’t always panned out. You can’t just take the pure D3. It’s sulfated D3 that’s the portable form. Like cholesterol sulfate, the portable form. That role of sulfate making our blood vessels slippery makes sulfate central to our bodies being able to be multicellular. It allows us to distribute energy and get rid of gunk. After all, glutathione is based on sulfur. On and on and on. Eat more garlic.

Pop Quiz

1. Sulfate ions are key to making water insoluble compounds soluble and that has its impact felt on what crucial vitamin/hormone?                                Answer: Vitamin D

 

2. Humans can live without sunlight? T or F                                    False. We get sick, not just from lack of Vitamin D,but also lack of sulfate creation by sun in our skin.

 

3. Human red cells don’t stick to each other because they have a halo of?                      Answer: Negatively charged sulfate atoms.

 

4. Blood vessels are slippery because they have a surface layer of water atoms set up by…?                    Answer: Negatively charged sulfate atoms

 

5. I can get more sulfate in my diet by eating what foods?                                   Answer: Kale, garlic, eggs, broccoli, Brussel’s sprouts.

 

ProOpioMelanocortin

POMC: The God Protein

References: Wikipedia, Uniprot,

Proopiomelanocortin. Repeat after me. Proopiomelanocortin. Bet you never heard of that before. What is it? It’s the protein that runs you. It’s a large protein that is in your pituitary gland that is made from pre-pro-proopiomelanocortin, a 285 amino acid long peptide that is activated once the 44 amino acid activating fragment is removed. Then it is ready for activation. It’s all in its name, at least part of it. Opio – it has opioid activity in part of it. Melano – it has melatonin activity. Cortin – it has cortisol activity. The devil is in the details. It is the prototype-hormone that can be split in many directions, depending on what enzymes attack it and chop it up into other pieces. It is those other pieces that become the hormones that run your body. ACTH heads off to the adrenal glands, giving you cortisol for energy and stress response. MSH has all sorts of appetite and sexual activity implications. The appetite part works through leptin. Generally it suppresses appetite as does leptin, when you aren’t leptin resistant. Beta-endorphin manages pain perception and immune function.

The devil is in the details. POMC can be chopped up into at least 10 different hormones, depending on where it is chopped. All the regions are overlapping with each other so any one hormone that is created might nix the making of another. It all depends on which chopping enzyme gets activated, and the activation is managed by adding or subtracting marking sugars or acids attached on certain sites.

An example of how it works goes as follows. You go to the gym and exercise like crazy. Imagine a good Cross Fit workout, or a great tennis match, or a hard 5mile run. Your body is demanding more fuel so you put out the call for more cortisol to mobilize more fuel. To make more cortisol, you need ACTH. First you chop the pre-pro-proopiomelanocortin into proopiomelanocortin. From that you then chop it into ACTH. When you make ACTH, you also, by chance make beta-endorphin. That’s your natural opioid. Presto: you feel a warm glow of happy feelings. The runner’s high.

That’s what happens when it works well. Guess what happens when it gets screwed up? The CIRS (Chronic Inflammatory Response Syndrome) as typified by black mold attacks you right at POMC. By downregulating the natural ebb and flow of POMC, you block beta-endorphin, ACTH and leptin which results in your being utterly unable to lose weight, not sleeping well, hurting all over and having no energy. Sound like anyone you know? We shy away from all those folks because it is to awfully overwhelming. We call people with that “Chronic Fatigue” or “Fibromyalgia” and give them pain pills and usher them out as fast as possible.

It might be kinder to investigate why they are feeling so awful. Ritchie Shoemaker, the author of the web site www.survivingmold.com claims that 80% of folks with chronic fatigue actually have CIRS, and positive markers for mold. They represent as many as 25% of the population when you do genetic testing for those who are susceptible to mold toxins. All they need is repeated exposure. 2% of folks are exquisitely sensitive, and 5 minutes in a sick water damaged building will set them off. If you can fix their POMC and get it back to normal function, their suffering will be over and they will claim you were the dispenser of a real miracle: the God Protein.

WWW.what will work for me. I’m totally fascinated with POMC and have started working on being certified as a Black Mold specialist. It’s a couple hundred articles and pages of reading, but if I come out being able to fix those folks who have been blown off by 8 other physicians and given nothing but symptom relief, I’ll be pleased. I am getting awfully hyper about any water leaks in my house. There are roofers up on our roof right now making sure our house stays dry. Mold will happen anytime you let water leak in your house, and don’t fix it promptly.

Pop Quiz

‪1. POMC is the prohormone that modulates your sex drive. T or F

Well, part of it does. There are implications for sexual function in MSH but more of it’s components go to energy and pain control

‪2. POMC can be chopped up to make how many hormones?

A: At least 10 and maybe more

‪3. Can they all be made at the same time?

No, any given combination will only make 2 or 3 depending on where you cleave the protein. This means there is lots of overlap.

‪4. The toxins of mold do their dirty deed by disrupting POMC. T or F

A: Bingo

‪5. Mold illness is rare. T or F

Are you kidding? Probably as many as 25% of our population has the genetic tendency to be affected. Likely only 2% are exquisitely sensitized, but that is still a huge number. (6-7 million exquisitely sensitive, 90 million partially sensitive.)

Connexins and Diabetes

Connexins and Diabetes

References: J. Cell Biology, J Biol Chemistry, FEBS Letter,

Connexins. What we learned last week was basic. Connexins are the proteins that make for connections between cells. They exist in every creature with more than a few cells. For multicellular organisms to exist, connexins have to become part of the picture. And the management of fuel for cells in central to an organism that has specialized digestive processes. To have a gut, blood, central nervous system, bones, muscles and everything else means you have to have a centralized control system for fuel allocation. That central traffic cop is the pancreas gland with its beta cells. They produce insulin, and insulin is the key hormone used to signal storage of calories for future use. Traditional medicine calls insulin your blood sugar controlling hormone. A more inclusive vision would be to say that insulin rises in response to rising blood sugars which occurs during the time of year of calorie excess, just before the time of year of calorie deficit. It’s a good time to store calories.

The storing of calories as insurance against future starvation is a key feature of human survival (and all creatures). That’s insulin’s job. How do connexins play a part in all that? These articles this month go right to the heart of that role. When you knock out the ability of pancreas beta cells to make connexins, their ability to make insulin drops proportionately. This means for us to have a sensible, balanced and nuanced control of glucose, we have to have proper connexin function.

What happens in humans when we get overweight, and become diabetic? Our fat cells get bigger and we demand more and more insulin to keep glucose in a tight range. We can produce that extra insulin for a while, but eventually exhaust our ability to produce sufficient insulin to control blood glucose adequately enough. Glucose is a very reactive chemical. Granted, it is fuel to burn, which is why being reactive helps, but high levels of it stick to all sorts of places where it’s not meant to be. And that leads to disease too. Our body doesn’t like high glucose, and we frantically put out more insulin to regulate that. And what happens when we can’t make enough insulin any more? You got it, the first step is connexons between cells dropping off as we produce fewer and fewer connexins. This makes connexin dysfunction the first step in diabetes development. The ability of our beta cells in our pancreas to talk to each other via their connecting connexins is the first step to developing diabetes.

And guess what happens in heart disease, brain disease, muscle disease, kidney disease?…..Name an organ and I can show you references that demonstrate that connexins fall off and connexons (the name for the actual channel between cells) between cells decrease. The level to which all your organ types are connected to each other is the level to which you are healthy. This loss of intracellular connections via these proteins called connexins is the basis of much illness.

The $ 64 k question is, what can we do to alter our connexins? Is that something we have control over? And the answer is yes! Next week.

www.What will work for me. All right. I’ve learned that connexins are the protein channels between cells that allow communications between similar cell types, allowing different cells to act as coordinated organs. Muscles can contract together. Liver cells and digest together. Brains can think… etc. Sounds like this is at the heart of life of multicellular organs. I love getting down to the very basic facts. But I’m eager to know how I can alter it with my own behavior. I guess for that, I have to wait till next week.

 

Pop Quiz:

‪1. Connexins are the key mechanisms of different cell type to function as independent organs. T or F

Right on.

‪2. In diabetes, our pancreas beta cells have more connexins functioning with higher blood glucose. T or F

False.     That’s backwards.

‪3. Virtually every illness with organ dysfunction can demonstrate lousy connexins of the organ that’s not working. T or F

T.  Isn’t that fascinating?

‪4. Earth worms have connexins. T or F

True. They have muscles that work in a coordinated fashion. That wouldn’t happen without those links.

‪5. Our gut has connexins that get discombobulated with gluten. T or F

Bingo. You intuited that and you were right. Gluten disrupts connexins between gut cells.

 

Connexion Connection

Connexin Connection

References: Wikipedia, Molecular Fitness,Cell Science,

Ever heard of Connexins? I hadn’t. Until I read Darrell Tanelian’s book. Here is what they are. They are the proteins that make up the connecting channels between cells. Different organs in your body act together in concert because they know they are the same as their neighbor. A liver cell knows it is a liver cell because it has hundreds of connecting little passageways between itself and it’s neighbor. Those protein bridges are constructed of 6 identical proteins that fit together to make a cohesive channel that connects one cell to another. A brain cell knows it is a brain cell because it’s connections tell it that it is in a brain environment. Same with pancreas, gut, muscle, heart, kidney, bone…..you get the drift.

That channel can relax and open up, letting stuff through, or it can shut down and close off passage of any signaling messages. A healthy cell has a lot of connecting passages/links between itself and its neighbors. And an unhealthy cell has less and less connecting sites.

You will get the drift of the power of connexins with gut cells. Your intestine has a one cell layer between your food (the outside world) and your inner self, your immune system and blood supply. That cell layer is held together with three tiny bridges of connexins. Inflammatory bowel disease appears to be an illness of uncontrolled inflammation, in part because of dysfunctional connexin activity. This appears to be the cutting edge of gut research right now, as the functions of connexins, and their cousins, panexins, appears to be the mechanism behind most gut diseases. There are even some commercial companies selling the agents that pass back and forth between gut cells in their communications through their gap junctions as a means of fixing gluten and glyphosate injury to the gut.

The bottom line of connexins is that they allow multi-cellular organisms to exist. Without different tissues being able to differentiate themselves into organs with separate form and function, we wouldn’t benefit from being anything more than a big algae. The process of cellular evolution from single cell to human beings is founded on connexins. They had to come very early in the game of life on earth. Being that fundamental to human form, the well being of connexins and understanding their role in health for the greater organism might be a critical link to understanding. And that is about as state of the art as we can get.

WWW.What will work for me. I want to know more. I love getting down to the details, especially it it’s something I can change with lifestyle choices. I found the topic getting a sense that being overweight and insulin intolerant starts with dysfunctional connexins. I’m fascinated. More next week.

Pop Quiz

‪1. Connexins are proteins that allow cells to communicate with each other. T or F Bingo

Right on the money.

‪2. The ability of different tissues to act differently from other tissues depends on cells working together in a coordinated fashion, which requires connexins? T or F

Ok, now you are on a roll.

‪3. If I understand it, connexins might then be part of organ tissues repairing themselves, and keeping them selves happy? T or F

You are getting ahead but you got the drift. We are now researching how to repair damaged heart tissue with stem cells. Their ability to develop into new heart cells requires that they get their connexins right.

‪4. Single cell organisms have connexins. T or F Nope.

It’s connexins that define multi cell organisms, up to and including you.

‪5. Every organ in the human body has connexins. T or F True.

And their health depends on their having a good population of them.

 

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