Category Archives: 7. Brain Health

Neural Exosomes: Diagnosing Alzheimer’s Early

Neural Exosomes

References: Alzheimer’s DementScience Direct,

Neural Exosomes? Sound like Greek to you? Ever heard of them? You should have. Here’s the scoop. First, they aren’t rare. You have about some 1.2 billion of them per ml of blood. They are tiny little spheres of membrane that have budded off of neural cells. Much like the tiny vesicles that bud off a nerve cell to transmit nerve impulses between cells, exosomes are 2-3 times the size of those packages, and designed to travel further to other cells. Instead of neurotransmitters, they carry RNA instructions. Many come from the brain, but many come from other organs.

What makes them unique is the surface markers on them and the RNA in them, including messenger RNA, mircoRNAs, DNA and signaling proteins. They are not fully functional cells, they are tiny little spheres of membrane, lined/filled with all these unique markers. The range of function that is being proposed for them is that of signaling between cells, moving cellular components, like amyloid precursor protein or messenger RNA. What is known is that you can measure them in quantity and specificity way before you come down with disease. In particular, they show up as much as 10 years before your develop Alzheimer’s. Did you get that? They give you the markers of advance warning.
Now, it’s not just that advance warning they give you. Each exosome has within it a unique pattern of micro RNA and messenger RNA. What are those doing? Did you know that your own chromosomes are actually only 2% coded for your unique genes? That’s it. But did you know that the other 98% isn’t junk? It’s your instruction manual. Messenger RNA is how you send out genetic code about what to do when. This is how your body responds to development as you move from a single egg into a fantastically complicated human. Some of that code is good for you and builds you up. Some of it is like napalm, and attacks the enemy, tearing you down. And,…..here is the critical point. The messenger RNA is also how you send out instructions on how to respond to disease/threat/illness. All disease. Each condition merits different sets of instructions. That means Alzheimer’s will have different proteins in its exosomes than Lyme disease, or pancreatitis, or rheumatoid arthritis, or pneumonia. Another example function, we believe that exosomes are how we clear Amyloid Precursor Protein, APP. Lousy clearance results in accumulation of amyloid in your brain. We call that Alzheimer’s If we can learn how to interpret our Alzheimer’s exosome and how they are different, we can learn how to anticipate and react proactively. Learning how to read exosomes gives us the code to our “instruction manual”.
Now, what is coming is the next miracle. There are companies developing the software to interpret these tests who are just months away from commercial release. With that, we will be able to tell you just what you need to do next. Remember Star Trek’ Dr McCoy and the Magic Wand that would diagnose everything? Yup. That’s it. We are almost there. Maybe not a wand, but an exosome reader. It’s complicated. It is the epitome of “Big Data”.

A point of trivia: do you know how much DNA is in you? Here goes. One cell’s human DNA would stretch out about 2 meters. And considering that we have some 20 trillion cells, one human’s DNA would stretch from the sun, way beyond Jupiter. That’s a lot of DNA. Now, consider that over 99% of the DNA we carry around is actually in our gut in the bacteria of our colonic biome, now we are talking a lot of code that could be in exosomes.
WWW.What will work for me. I’ve finished Bredesen’s Certification Course this week and am just blown away by the possibilities of what we can do to reverse this wicked evil disease. It’s thrilling. And its sad. My 92 year mother with Alzheimer’s is too late to be helped. It makes this Mother’s Day bittersweet. I hope you are able to celebrate with your Mother. In a few months, we will be able to keep her safe from Alzheimer’s. In the meantime, I’m focusing on getting a good night’s sleep. You clear Amyloid much more effectively with good sleep. Maybe that’s why you feel so refreshed when you wake up.

Pop Quiz

 

  1. What is an neural exosome? It’s a little bud off a nerve cell, a bit bigger than the bud that sends neurotransmitters between nerve cells, that travels further between cells, sending messages.
  2. How many neural exosomes do you have? Answer: LOTS. 1.2 billion per milliliter of blood.
  3. What do they carry inside them? Answer: Signaling instructions in the form of RNA, microRNA, proteins.
  4. Is there a different set of exosomes for Parkinson’s versus Alzheimer’s? Answer: YES! A different set for every disease
  5. How much sooner a warning will I get if my exosomes say “Alzheimer’s Condition: Red Alert”? Answer: About 10 years, as best we know now. Much more to come, of course.

 

Fast Mimicking Diet 8: Alzheimer’s and Neurological Disease

Fast Mimicking Diet 8: Neurological Disease

References: The End of Alzheimer’sAgingJAMA Internal MedicineScience DailyCell Metabolism,

What we most fear in aging is Alzheimer’s disease, in particular because it we live to be 85 years old in America, 50% of us develop dementia. In England, Alzheimer’s beats heart disease as the number one cause of death. It is the penultimate marker of aging, and its prevention is a high priority. Bredesen has developed a unique program in which he believes “No One” should get Alzheimer’s. It should be noted that the very first step in his program is a low carbohydrate diet, and the second is 12 hours of nightly fasting. These are both cardinal features of the Fast Mimicking Diet.
Longo has taken his own unique approach to the problem be starting with mice having the same genetic defects that lead to dementia in humans. Mice can be genetically manipulated to have clean experimental models for Alzheimer’s, and they develop it in much shorter time periods. He conducted an experiment in which every other week, the study mice received very low essential amino acids, mimicking a protein deficient fasting diet. He found a 75% reduction in IGF-1, the growth factor that strongly correlates with cancer, that persisted months after the fast mimicking period. And those mice performed better on cognitive testing.

The next sep was to examine the features of healthy human diets that resist Alzheimer’s. Mediterranean diets that are rich in olive oil show resistance to Alzheimer’s. 447 study participants were randomized to getting extra olive oil and 1 oz of nuts a day or a regular diet. The extra nuts and fat made a difference with less cognitive decline, albeit modest on the order of 13%. Bredesen takes this further and advises that people eat coconut oil every day and add extra olive oil to their diets.

We don’t have huge human studies yet on the FMD but Bredesen has now added intermittent fasting, along Longo’s admonitions to his protocol as foundational to the life style changes we need to make in his Alzheimer’s ReCode program. It is all part of tipping the balance in the human brain towards building new cells and stop making beta-amyloid.

To summarize, the Fast Mimicking Diet requires a 5 day stretch each month of 1,100 to 800 calories. The calories are 7% protein and at least 50% fat – mostly from nuts and coconut.  In between the 5 day cycles, you should have at least 12 hours a night of fasting, 14 hours if you have 2 APOE4 genes and keep shifting your calories towards vegetables and away from animal (cheese, yogurt, milk, meat). Consider fish a twice a week treat. Two key things happen with this: a) you turn on your vacuum cleaner (called apoptosis) that cleans up unhealthy, dead cells and b) your stem cells surge and stay up for months every time you do it. Your brain needs stem cells.

www.What will Work for me. Well, I start month three on my own experiment today, Monday. I’ve been assembling snacks and kits of alternative foods so that I can figure out how to do this without buying the kits, as I intend to do this the rest of my life, at least every 3 months. And the walking season is upon us. The snow is gone (almost) so time to get my 10 k day.

Pop Quiz

 

  1. What happens in mice’s memory who do the FMD?                         Answer: they get better memory and their IGF-1 dropped 75%
  2. Do mice give us a good model for humans?                                      Answer: Unfortunately, no.
  3. Longo has published a great article on Fasting and its Mechanisms?               Answer: Yes: Homework!
  4. What two core beneficial effects occur with 5 days of Fast Mimicking?            Answer: a) Your vacuum cleaner and b) New Stem Cells to replace the gunk
  5. How many hours a day should you NOT eat?                                     Answer: 12 is a minimum, 14 is better, and mandatory if you have two APOE4 genes.

 

glutathione

Biotoxin Illness Part III: The Role of Glutathione

References: Toxins (2014)SciWorldJr,

So, you know about your immune system having two layers, the innate or lizard system, and the adaptive or precise mammalian system. A good analogy is like a bomb going off by a terrorist. Your city reacts with a curfew, 911 is activated, the police clear the streets, sirens are wailing. This is your innate immune system – “all hands on deck, but who is it that we are fighting?”. Nonspecific, system wide, reactive. Then, surveillance cameras pick up a suspicious character and his license plate is put out there with a sketch of what he looks like. Then his picture shows up from the driver’s license bureau. This is slower, your adaptive system, but it has precision and accuracy.

What are you using to clear the toxin, once you know what it is? The answer is glutathione. Glutathione is simply three amino acids tagged together but they have sulfur atoms in them, making it able to soak up loose electrons. Every cell in your body has it. It’s your natural defense, in effect, part of your 911 mop up system. It’s sort of like your fire hose cooling off the burning embers of the fire. And as you age you make less of it. Dramatically less.

Turns out, it is a critical player in Biotoxin illness. It enables your body to tag and dispose of mold toxins. The paper we review this week details how we make glutathione through a delicate dance with Nrf signaling and the protein GST or Glutathione S transferase (GsT) . There are 7 GsT types inside a cell, and the first and most common has many genetic variants. Half the adult population has a polymorphism that is dramatically less active. This has been associated with oxidative stress all over the body, most notably in the brain with Alzheimer’s. Mold toxins wreak some of their havoc by down regulating the level of glutathione production. And as we age, our levels of glutathione drop dramatically.

Well, well! If that’s what mold toxins do, what would happen if we gave glutathione to someone with all the symptoms of biotoxin illness, and positive markers of biotoxin disease? Here are two stories. A middle aged woman with three years of asthma symptoms not responsive to typical asthma therapy and cleared of asthma by the traditional medical system becomes symptomatic again. Treatment with one gram of IV glutathione for three days completely reverses her symptoms. In fact, her oxygen saturation surged from 95% to 98% within 10 minutes of treatment.
A second story. Multiple insect stings. A mid seventies women with over 15 hornet stings, treated with traditional Benadryl with only partial success. Insect stings are known to be another entry into the Biotoxin pathway. Two treatments with 1 gram IV glutathione result in dramatic and almost immediate, complete recovery.

Did you get that? Now, you can’t take oral glutathione easily as it is digested in your stomach like any other protein. And not everyone has access to IV glutathione. (It is just 3 amino acids long). But you can take it in “liposomal form” which is widely available in Supplement stores and on the net. And, more importantly, you can take N-acetyl cysteine or NAC and give yourself the rate limiting cysteine combination. NAC is a revolutionary supplement that has been around for 40 years. 40 years ago it revolutionized Tylenol overdoses. Prior to NAC, a Tylenol overdose was a guaranteed death sentence or liver transplant. NAC is so powerful that folks with Tylenol overdoses are now sent home from the hospital with NAC to take a couple of times a day. No wonder NAC makes Bredesen’s supplement list for Alzheimer’s prevention.

WWW.What will work for me. Well, I take NAC in my daily supplement list. If I was still an emergency physician, I would find a way to study glutathione for folks with nasty insect stings. But I’m now adding IV glutathione to my treatment regimen for everyone with Biotoxin illness. The jury is out about randomized, placebo controlled trials. But considering that glutathione is in you already, just less because you are old, means you and I should consider paying attention to our glutathione levels as we age.

Pop Quiz

  1. Glutathione is my natural antibody booster. T or F                                          Answer: False. Nothing to do with antibodies as that is the adaptive, more precise immune system. So called “glut” is your innate immune system’s fire hose. Just calming things down.
  2. As we age we make more glutathione. T or F                                                    Answer: Again, false. Testing to see if you actually red the article. Much, much less.
  3. Biotoxin illness down regulates your production of glutathione. T or F       Answer. Ok, we will give you a true
  4. There is a simple supplement that gives you the amino acid pieces to make your own glutathione. And it is called……………..                                                                 Answer: NAC or N-acetyl cysteine
  5. We all make pretty much the same amount of glutathione. T or F                 Answer: surprisingly false. There are 7 different forms of glutathione converting enzyme inside the human cell, and the first and most dominant one comes in form that is much less active in 50% of us. Why, we don’t know. But every protein has many slight alterations that we inherit in our gene mix called polymorphisms. That happens to be one that is curiously dysfunctional.

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.

The Trouble with Iron – Part II – Your Brain on Iron

The Trouble with Iron – Part II Iron and Your Brain

References: The MindSpan DietNeuromolecular Medicine, Nature CommunicationsJournal Biol ChemUCLA Newsroom,

Ok you got it. You know the “AP” rule, antagonistic pleiotropy, from last week: what’s good for you at one age isn’t so good later. Young women need lots of iron to have babies. Young men need iron for their brains to develop. Young. As we get older, that changes and becomes “ANTAGONISTIC”.

What’s the trouble with iron? First of all, epidemiology. Men accumulate iron faster than women, and get Alzheimer’s younger than women. Women who have hysterectomies start accumulating iron sooner, and get dementia sooner.

Then there is pathology. All major brain diseases (Parkinson’sALSAlzheimer’s) are shown to accumulate iron in their region of damage. Iron is very reactive. With oxygen it’s a deadly combo. On our cars, we call it rust. In our brains, it wreaks havoc.
There are many mechanisms now being understood wherein iron is a problem in the brain. In essence, beta amyloid accumulates as a net effect of excess iron. And chelating that iron, in animal models, reduces the damage.

What do we see in human populations who have very little Alzheimer’s disease and who live to be 100 with healthy brains? First, they eat foods low in iron and live in parts of the world where there aren’t “fortified” grains (added iron). Their average serum ferritin is 20. In America, we call that deficient. More and more research is showing that ferritin in spinal fluid and blood predicts risk for AD. This is the perfect example of Estep’s “AP” rule. The iron we needed in youth to make babies isn’t so good for us as we age. Those, whose scales are tipped to eating more iron by intention or serendipity, are at greater risk.

The question arises, how do I get rid of excess iron? Rule #1: when in a deep hole, the first thing you do is stop digging. Stop eating iron rich foods. That included fortified wheat products. Cereals like Total contain 18 mg of iron per serving. Don’t. Steak. Don’t. Find flour that is not fortified. Find bread that is not fortified. Consider taking supplements that deplete iron. Wheat grass juice is uniquely good. Go to the Blood Center and give a pint. Often. Let them have double red cells. Get your serum ferritin to 20. AKA: KNOW YOUR FERRITIN.

www.What Will Work for Me. I’m changing my meat eating. I’m looking for unenriched flour. I just measured my ferritin and I’m over 100. Hmmm. I just might give some blood away. I threw out our red colored ibuprofen (iron coating).

 

Pop Quiz

 

  1. Iron is good for your brain. True or false                                    Answer: Ha, Trick question. It appears to be important for you when you are young, but too much is a deadly toxin as you get old. That is the AP Rule: Antagonistic Pleiotropy.

 

  1. We have added iron to many of our foods on the belief that it is good for us. T or F        Answer: True.

 

  1. People around the world who have the best functioning brains, the longest, have much lower blood iron in the form of ferritin than we have thought was safe. T or F                  Answer: Yup. Average ferritin of 20

 

  1. Beta amyloid in the brain might be accumulating as a side effect of our brain’s attempt to get rid of extra iron. T or F                                                        Answer: Again. Yup

 

  1. Getting rid of excess iron might be the only way to reduce our risk for the dangers of iron. The easiest way to do that is……?                                 Answer: Donate blood.

 

 

 

The Trouble with Iron

The Trouble with Iron

References: The Mindspan DietEndocrine Society MeetingHow Much Iron in My CerealJr of Nutrition,

Ready to blow your mind with a whole new set of ideas? Want to live a lot longer and have your brain survive with you? Want to have an organizing principle that explains much of the trouble with modern nutrition, that is a complete curve ball from anything you have ever heard before? Here goes. Please read the next couple of weeks of The News with great attention to the details in this column.
Dr Person Estep is not am MD, he’s the smart kind, a PhD at Harvard Medical School, in Genetics and Health Science. HIs research is into those populations of people whose brain survives into their later years, and why. I’ve just devoured his book, and if you want to preserve your brain, you should too. This is a must read.
Let me start with a few core principles and ideas that he presents. First, the concept of MIND SPAN. I want my brain to survive longer than my body. My LIFE span makes me nervous, if it’s longer than my brain span. That’s Alzheimer’s (AD). Get that? Of course your do. We all do, and right now 50% of are getting it if we have the “good fortune” of living to 85. That’s idea #1.
Concept #2 for us to all know is the idea of Antagonistic Pleitropy. (Wow, if you get this, you can skip medical school.) It’s actually a simple idea. What it means is that your bodies needs change as you age. What was good for you once, becomes bad for you later. Biology works by natural selection, and reproduction is the driving force. If you can’t pass on your genes, they can’t change. So, natural selection works only until you stop reproducing. Nature is not interested in you once the pressure of natural selection is over. Get it? What is good for you before passing on your genes, may be bad for you later. Women have to give iron to their babies. The human body needs iron for it’s blood making. And through most of human history, our guts were filled with tiny worms that made us lose iron. In this mix, men have to make sperm. Trillions of them. But sperm doesn’t involve the losing of iron. Making babies does. Lots of iron. The human species has resulted in a model that generally, in both genders, accumulates iron easily. That’s good for women, while they are making babies. And its good for all of us when we keep losing iron from intestinal parasites. What happens to us after we stop reproducing? Well, nature has no way of repairing or changing that tendency to accumulate iron after our reproductive years. What happens if we keep accumulating iron? What happens when we get good plumbing and sanitation and stop getting pin worm? Our iron leak stops.
What happens, if we decide that our society is across the board iron deficient and we add iron to all of our grains? (Look at your breakfast cereal and see how much iron you are getting. Look at your “fortified bread” and see how much iron you are getting. Consider that the USDA says that we need 18 mg of iron a day, and good science shows that actually you probably need much less, like 4 mg a day, once you hit 50. What’s happened is that in America, we have added abundant iron to our diet, to our baby formula, to our grains, our breakfast cerealsour rice, to our whole food chain. And that may be a big problem.
What if I told you that accumulating ferritin in your pancreas pushes you into diabetes? What if I told you that amyloid plaque in your brain may be a side effect of a desperate attempt to get that toxic iron out of your brain. We’ll get to that in the coming weeks.
For now, think about these two core ideas and please, look at your “fortified” flour on your shelf and read the labels for your source of iron. Think about how red meat provides you lots of iron. And next week, we’ll have more details.

WWW.What will work for me. My mind is being totally turned upside down. I can’t wait to tell you the rest. This is a whole new way of exploring the metabolic problems we face with aging. But for now, stop taking any iron in your diet. STOP. Trust me. Stop. Stop your vitamin pill with iron. Stop your fortified cereal. Get skeptical about red meat. I’ll prove it to you. Or else buy the book. Next week.

 

Pop Quiz

  1. The human body accumulates iron easily, too easily. When is that good, and when is it bad?                                                                        Answer: It’s good if you are a young female, having lots of babies and with lots of intestinal parasites – like humans were until 100 years ago when we cleaned up our toilets, our guts and stopped having so many babies. It’s bad when you are male, have a clean gut, live longer than 35 years.
  2. What is this effect called?                                     Answer: Antagonistic Pleiotropy. (Go straight to your third year in medical school.) What’s good for you at one age or circumstance, becomes bad for you later.
  3. We decided, as a society, that every one should have how many milligrams of iron a day?                                                                             Answer: 18
  4. How many milligrams do mature adults, past the age of child bearing need? Answer: Probably around 4.   Certainly no more than 8.
  5. Should I worry about the red color of my ibuprofen pill?                              Answer: Yes, that is actually oxidized iron. Buy another brand. The ibuprofen is good for your brain. The Iron is not.

Nine Risks for Cognitive Decline

Nine Risks for Cognitive Decline

References: The Lancet, July 2017BBC News

This week, in London, the Alzheimer’s Association International Congress, just met. One of their presentations was a publication in the Lancet detailing the current best evidence of risk factors for developing cognitive decline. The over arching principle is that the brain does show changes with time that eventually lead to withdrawal and loss of cognitive function. It shows up as short term memory loss, but starts with other risks. Prevention should be focused on building a “cognitive reserve” earlier in life. If there is to be an inevitable downward slope, change the grade of the slope.
Your brain is constantly tasked with decided what to keep and what to throw away. It is not a hoarder. It repeatedly questions what memories to discard, what are important, and which are less important. The stop sign you passed on the way to work may not be all that important to remember. It gets tossed. Where you put your keys is important, only in the short term, but can be forgotten. Your spouses birthday, now, that is important. Your brain has to sort those out. Routine and repetition can lead to letting go.

In order to do all that sorting, your brain needs data. It needs to be exercised, flexed, challenged, used. Knowing that, the list presented at the meeting makes sense. They estimated that approximately one third of dementia was amenable to prevention by early intervention. That starts with mid life hearing loss. This is the first paper that I have seen with a meta- analysis of multiple high quality studies of hearing loss as a risk for cognitive decline. It accounted for 9% of the risk. Following that was lack of a completed high school eduction (8% risk), smoking (5% risk), failure to seek early treatment for depression, (4%), physical inactivity, 3%, social isolation (2%), high blood pressure (2%), obesity (1%), Type II diabetes (1%). These all add up to the 35% percent of modifiable risk factors.
Continuing life long learning keeps your brain working with new data. Doing something “hard” every day, keeps your brain solving problems. Staying socially engaged with humans keeps all your filters of human interaction functioning. These factors appear to be important, and make sense. They flatten the slope of decline.
What is quite new in this examination is the consideration that diabetes accounts for only 1% of risk, obesity 1%, smoking 5% and physical inactivity 3%. These are far lower than prior estimates and suggest that there was no attempt or discussion about reduction and change of lifestyle risk factors. That is likely because the prior model of weight loss is all about low fat, which doesn’t work. Hence, no one has been able to succeed with weight loss, diabetes reversal, high blood pressure reversal etc. With the proper use of low carb for weight loss, modifiable risks for cognitive decline will appear to be more meaningful and effective.
WWW.what will work for me. I’m paying attention to the hearing loss concern. This is the first study that shows it to be so high on the list. It’s never been so high in any prior study. I’m going to find a time to get myself checked. I haven’t seen any other study like this, so this could be a statistical blip, but it sure catches my eye. Pay attention.

Pop Quiz

  1. The current article suggests that as much as 35% of dementia can be prevented. T or F                                              Answer: That’s there data from statistical analysis. I think the number can be much high.
  2. Mid life hearing loss can be postponed until you are on Medicare. T or F                Answer: False. It leads to social isolation.
  3. Cognitive decline is a natural process. T or F                                     Answer: Sadly true if you live long enough. Age is the strongest risk factor. What is not discussed here but is quite intriguing is that dementia may be the result of a protective or natural process going awry.
  4. Hearing loss may be far more important a risk factor than we care to acknowledge. T or F Answer: Yup
  5. The combination of diabetes, high blood pressure, obesity are all one parcel of common problems best reversed with a low fat American Heart Diet. T or F Answer: It’s true they are all one parcel, it’s false that the AHA diet will help you.

 

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.