Monthly Archives: August 2017

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.