Category Archives: 7. Brain Health

Artificial Sweeteners and the Risk of Dementia

Artificial Sweeteners and the Risk of Dementia

References: StrokeObesityWashington Post,

Whoa, Nellie! Now artificial sweeteners are bad! Help, help, help. We’ve been telling everyone not to eat sugar, and now you turn around and point at sweeteners. What’s the deal? Better, what’s the evidence?
Ok, an observational study from the long-term, Framingham heart study prospectively followed 4,272 older adults for 10 years with follow-up for risk of stroke and dementia. They found 97 strokes and 81 cases of dementia over that time period and compared those outcomes to the frequency of sugar and artificial sweetener use. Compared to controls within those groups, after statistically accounting for the proper variables, they found a 2.97 times increased risk of stroke and 2.87 for increased risk of dementia by drinking one diet soda a day. One measly, little diet soda. Sugar didn’t show any negative effect.
Well, out come the critics in full force (from the soda industry, of course). They claim it was a lousy observational studies without any proof of causation. (True) They attacked because it wasn’t large enough. They griped because the sugar use wasn’t found to be dangerous when every other study shows it has. And the accompanying editorial in the journal pointed out that the risks go away when incident diabetes and vascular risk factors were taken into account.

Ok, ok, so the evidence isn’t perfect. But it is there. Is there a plausible mechanism we can construe that carries a tiny bit of credibility?
Well yes, there is. Here it is. First and foremost, drinking diet soda has been shown to lead to weight gain, not weight loss. The means by which that happens is thought to be by confusing your brain’s appetite sensor into thinking calories are coming because you taste sweet, and then you secrete some insulin, which lowers your sugar, and 4 hours later, you eat more. Presto, fatso.

It may be along this line that we will find an answer. The interplay of human hormones is so complex, it is extremely hard to parse out a single hormone in isolation. The breadth of knowledge is advancing in that direction. Here is one plausible bench research explanation: there is pretty good evidence that being fat makes you insulin resistant, and higher insulin with higher glucose leads to your tummy fat making more amyloid precursor protein (APP). And it’s APP that breaks off in your brain to make agglomerations of beta-amyloid plaque. Ok, so you drink diet soda, make a little extra insulin, get fatter and gain weight, make more beta-amyloid and there you have it. Diet soda makes for more dementia.
WWW.What will work for me. Well, well. Not the strongest of evidence but the gun is smoking never the less. I just drove for 4 hours yesterday and got a big gulp of 32 oz of diet Pepsi at a QuickTrip because I was sleepy. Bummer. I can feel the beta-amyloid crawling up my neurons. I’m weaning myself off sweeteners bit by bit. Sounds like it’s time to increase that effort. Is Stevia just as bad? Haven’t got a clue.

 

Pop Quiz

 

  1. If you believe this study, you triple your risk of dementia by drinking artificial sweeteners. T or F                                                           Answer: True unless you nit-pick over 2.87 fold vs 3.0
  2. Women who drink diet sodas stay thin. T or F                         Answer: False, they gain weight.
  3. Belly fat makes amyloid precursor protein, which is the protein that then calves beta-amyloid in your brain, the cardinal sign of Alzheimer’s. T or F                      Answer: Bingo
  4. Is sugar safe to put in your drinks?                                            Answer: No, not at all. In fact, to me, that was the weakest sign of this paper because, on every other front, more sugar is worse for you in ever so many ways. This study sort of absolved it.
  5. Now that you know belly fat makes APP, want to lose weight?                    Answer: oh my goodness, yes.

 

Blood Glucose and Cognitive Decline

Blood Glucose and Cognitive Decline

Reference: Crane, NEJMLancet NeurologyELSA StudyDiabetes Care,

Your HgbA1c is your most important blood test. Get to know it well. It is a simple concept. When blood sugar gets higher, more of it sticks to different proteins. Glucose is a very reactive molecule, ready to stick to anything. You know that from spilling a Coke on your car seat and having sticky goo for weeks thereafter. When you eat 4 scoops of ice cream your blood sugar shoots up for 6-8 hours. In that time it sticks to everything in sight, including your hemoglobin molecules in your red cells. That makes it a nice surrogate marker for glucose also sticking to the proteins in your blood vessels, your kidneys, your brain, your joints and on and on. You can sample your blood and there it is, a nice marker. Now, red cells live about 100 days more or less, so your A1c becomes the average of your glucose over the last 100 days. As fat cells get bigger, they require a higher insulin level to make them react to rising glucose, so A1c becomes a marker of how overweight your body thinks you are. Not your spouse, or your friends, your own internal body signal.

We define adult-onset diabetes as a blood sugar of 126 after an overnight fast. That leads to an A1c of about 6.4. But is that accurate? Is blood sugar healthy at 126? The answer is absolutely not. The Whitehall Study from England shows decreasing cardiac mortality down to a blood sugar of 85 before leveling off. Hmmm. Heart disease is one thing, but which would you rather die from, heart disease or dementia? I’m going for neither. I want old age to just spirit me away.
That’s what this week’s studies relate to. What is the risk of dementia from elevated blood sugar? Turns out, a lot. In fact, much lower than 126 or A1c of 6.4.
Crane’s study in the New England Journal is the hallmark study. The Adult Changes in Thought Study took 2067 elderly adults (average age 76) who yielded 524 folks with dementia. The simplest conclusion of the study was that a blood sugar of 100 compared to 115 raised risk of dementia by 18%. Going the other way, dropping blood glucose from 100 to 95 lowered risk 14%. One could extrapolate and say that dropping from blood glucose of 115 to 95 lowers dementia risk 32%.

There are now more studies following this seminal study that say the same thing. Lancet Neurology confirmed the danger in the ELSA Study.
There are some of us who spike our blood sugars quite high when we sneak that ice cream and that is even riskier. The science of that isn’t completely known but it can be measured with a nifty new test called 1,5-AG ratio that adds a layer of understanding to the risk. This may or may not play out. Something to watch. I want to know mine.
We don’t mean to belabor this point. The message is clear. The size of your fat cells matter. If you are overweight, your blood sugar will likely be higher, and your risk of dementia will be higher. Losing weight and lowering your A1c matters. What’s the target? A1c of 5.5 should be your minimum. 5.1 is perfection.
WWW. What will work for me? Well, with a mother with dementia and a father that had diabetes, my genes are in the crosshairs. I was running an A1c of 5.2 for a couple of years there then suddenly I popped up to 5.9 last year. (Nothing like a wedding in the family to gain a little weight and a broken food to cut the exercise.) I’ve been doing the fast mimicking diet for 5 months now and I’m back down to 5.6. This perfection stuff is a pain in the proverbial…..So, I still have a ways to go. Join me. I’m doing the FMD diet last week of the month. Every month until I’m below 5.5. Each month it gets easier.

Pop Quiz

 

  1. Your A1c reflects what?                                                         Answer: Your average blood glucose over the last 100 days.
  2. How can you lower it?                                                            Answer: Stop eating foods that make it go up like grains and sugar, and lose weight with the Fast Mimicking Diet.
  3. What blood sugar is an A1c of 5.1? (Google Blood Glucose A1c Table)             Answer: 5.1
  4. The current definition of diabetes is based on sound science. T or F               Answer: It was a committee decision that was made 40 years ago. Now way out of date.
  5. What’s the first step most folks need to do to lower their blood sugar?           Answer: Stop drinking it. The calories you drink are the calories your store. Sugared soda is the worst. Orange juice and energy drinks, ditto.

 

What’s the Big Deal with Homocysteine?

What’s the Big Deal about Homocysteine?

Reference: Amer Jr Clin NutritionNutrition JournalLIfe Extension,

We’ve known about the risks of homocysteine since the late 60’s when a Harvard researcher by the name of McCulley brought it to the world’s attention with his research. At that time there was a brutal PR war going on about lipids and cholesterol as being the cause of heart disease, which the pharmaceutical industry took up with enthusiasm (because there was so much money to be made). McCulley was essentially booed off the stage with his ideas and homocysteine was swept under the rug, despite continuing research showing that it had an association with headaches, heart attacks, strokes, osteoporosis, macular degeneration, and dementia. Ok, which of those don’t you have? This is the perfect portfolio of what we are getting sick from in this 21st century, and homocysteine is sitting right in the middle of it.
What does homocysteine do? Well, it is really just a shuttle bus moving methyl groups around inside your cell. It backs up when you don’t have enough. That simple. But what do you need methyl groups for? Ah, there’s the rub. (Poor Hamlet, thinking of suicide) Methyl groups are needed to label DNA so that you know which DNA to turn on and off. Having sufficient Methyl-FOLATE, one of the key sources of methyl groups is so powerful that women trying to get pregnant who take METHYL-FOLATE starting one year prior to conception will have as much as a 70% reduction in premature delivery. Wow! Throw in B12 (the other source of methyl groups in nature) with the methyl folate and spina bifida drops 5 fold during pregnancy. I could go for pages describing these effects in the literature, but you get the gist. You need methyl groups to tag and label DNA so that you can turn on the right genes at the right time. Add B6 and methyl glycine (a reservoir chemical to give methyl groups to folate and B12) and you will have pristine, perfect homocysteine levels.
The other thing methyl groups do is to be the first step in making “gunk” water soluble so you can excrete it through your kidneys. Lots of neurotransmitters are “methylated” on their way to excretion, as are all our hormones. Without sufficient methyl groups, we back them up and make more dangerous models.
Where do you get methyl-folate from? The foods are essentially all peas and green vegetables (spinach, asparagus, broccoli), foods we don’t eat anymore. If you eat lots of greens and black-eyed peas (yummy southern soul food cooking) you get lots of good folate.
The real problem is that we don’t measure homocysteine routinely. In fact, many health networks forbid measuring it because it’s not on their list of approved lab tests. Trust me. I know. I’ve gone to battle with one large local health care system only to be told by a nurse reviewer that it doesn’t meet their criteria.
And the irony is that it is ridiculously easy to lower to a normal range. Bredesen in his online training and his book, The End of Alzheimer’s, wants your homocysteine to be 7 or below. You lower it by taking B vitamins.
And that’s what this week’s studies show. B vitamins help slow cognitive decline in aging men. You can correlate that with high homocysteine. The average man in America has a level of 12 but I’ve seen as high as 42 now. For every 1 point above 7, you get a 16% increased risk of Alzheimer’s. Dropping your homocysteine from 12 to 7 halves your risk. Isn’t that just peachy! So simple, so easy, so elegant.
How did we get in this pickle? We evolved eating lots of green leafy vegetables in Africa. We lived to 35. It didn’t harm us then. Bruce Aime’s Triage Theory points out that until a nutrient deficiency makes a biological imperative for evolutionary pressure, it won’t cause trouble. We can skate along the edge of deficiency and not be affected until we fall over that cliff.

WWW.What will work for me. Well, the “cliff” appears to be about age 50 when we seem to get into trouble with sufficient B vitamins. I see very few folks with normal homocysteine. I had a level of 12 when I started and on daily B vitamins, I get down to about 9. I’ve just started with more methyl-folate and I’m waiting to test myself again. I’m bracing for paying the lab fee myself as I know my insurance may not cover it.

Pop Quiz

 

  1. What does homocysteine do?                                        Answer: It’s a passive amino acid shuttle that carries a methyl group off to attach to other chemicals. It’s simply a marker of sufficient methyl groups for everything else downstream.
  2. Soul food is inherently unhealthy? T or F                    Answer: Timeout. Probably the best way to get methyl folate through food. At least if you are eating greens and black-eyed peas.
  3. What should women wishing to become pregnant do in regard to methyl folate?                        Answer: Take it continuously for at least one year prior to pregnancy initiation in order to reduce their risk of premature delivery as much as 70%
  4. Why doesn’t lack of B vitamins hurt us more sooner? Answer: Bruce Ames triage theory explains that it does hurt us if we put on the right glasses to see it’s effect. It takes years of labeling DNA badly for the effect to show
  5. For every point increase in homocysteine over 7, my risk of dementia goes up how much? Answer: 16% You should know your homocysteine. Always.

 

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.