How to Cure Migraine: Forever!
"Dad, I've got the worst headache I've ever had. It came on suddenly." My own son, calling me from the mid-Atlantic on a plane from Switzerland, coming to a family reunion. This is the worst possible thing you can tell a parent. He must have an aneurysm that's leaking. He needs a CT scan and probably surgery.
"When do you land? We'll be there."
He was coming with his family from Switzerland, to land in Boston in 90 minutes. We had minutes to get on the road, but it was Memorial Day weekend. We were at the resort on Cape Cod getting prepared for our reunion. Two of us rushed for the car and got on the road....to meet 100,000 people leaving the Cape at the end of the weekend. Traffic was backed up for miles. There is only one major bridge off the cape and everyone was going home. That's why there are signs all over the cape saying, "Plan your departure, expect delays 4-7 pm." His life depended on speed, and we were stuck...
They landed. We were 5 miles closer, but still 40 miles away. They made it to baggage control. We were 3 miles closer. Almost to the bridge. They were at the rental car. We were still 35 miles away.
"Don't pick up any suitcases....Let Laura drive......We'll meet you at MacDonald's at .....exit". I watched the car on Google Live inch closer. There was the car...they had made it to our car. He looked awful. We switched drivers and in my own head I decided he would get faster service at Cape Cod Hospital than a huge city hospital, even if Mass General is the best in America if not the world.
Forty precious minutes later with him lying back and making no exertion, we pull into the ER arrival bay. I was about to witness the best of American ER medicine. Triage in 1 minute, CT scan ordered from the triage desk. The ED doctor examined him while rolling. Into the CT scanner to see if his brain was filled with blood from an aneurysm.....results in 5 minutes. Negative. No blood. No aneurysm.
Just a horrible, first migraine. "Worst pain I ever had in my life." IV cocktail of Reglan, Benadryl, and Decadron.....and the pain gradually eased away. What a relief! What a scare. Post-Covid migraine? Are they linked? He had C0vid a year ago and had long Covid for 6 months. Is that linked? Yes, they are linked.
Does migraine have the same defects in white matter showing demyelination that we see in long Covid, autism, ADHD, manic depressive disease, MS....? Yes! Yes! Yes!It's all the same pathway of excessive inflammation overwhelming the mitochondria, making too much peroxide, overwhelming glutathione and eventually making the dreaded OH- hydroxyl ion that damages myelin. Microglia, the garbage trucks of the brain then try to clear up the mess and start demyelinating white water. So-called white matter are the axons covered in myelin that link all the neurons to each other. With damage to myelin and decreased myelination, speed of nerve conduction slows down. Victims experience brain fog. And that damage shows up on MRI diffusion studies. You can see it with the newer, MRI 2 Tesla machines. Wait till we get 4 Tesla machines! Imagine the detail.
If you look at 44 patients with chronic migraine and measure their malondialdehyde, the chemical you make when the OH- hydroxyl ion damages the cis-bonds of plasmalogens (proving that you have the inflammatory pathway common to autism, ADHD, long COVID, MS, etc), it is statistically much higher than it should be. The brain is on fire. And MRI scans confirm it. Migraine sufferers have detectable white matter defects in their brain. You can see the excessive white matter water that is linked to uncontrolled inflammation and the chemical changes that confirm the process.
That gives us a pathway to repair the damage and turn off the chronic activation of OH-. Address all of the pathway mechanics and chemical imbalances. Give NAC, Acetyl-carnitine, lecithin, B12, B1, B6, B9 and most importantly, Prodrome Glia so that you can repair the white matter and stop the microglial activation that is wreaking the havoc.
www.What will Work for me. So that's what I did. I first asked David if I could use his story. He said sure! Because he got better so quickly. This is an important story. It expands the reach of Goodenowe's autism study. I gave him 50 mg per kg of Prodrome Glia and his headache disappeared in 12 hours. He was still a 4 on return from the hospital. It dropped to a "1" with the Glia and then after 24 hours was zero. It was a first migraine after long COVID, but headache is clearly linked to COVID and can last for months with debilitating pain. We can interrupt this whole vicious cycle. We now have a tool for understanding the pathophysiology of migraine (MRI diffusion studies), and address the root cause....some sort of inflammation that overwhelms mitochondria, allowing electrons to escape at such a rate that they overwhelm the control mechanisms. The hydroxyl ion escapes and we end up with damaged white matter, elevated malondialdehyde. Support each and every control mechanism, and provide plasmalogen support, and we may have the demon migraine in a corner and controlled. How fortunate we are to live in a time with the expansion of scientific discovery. We plan to "fill up his tank" for the next 6 months with the Glia and all the support chemicals that address all the antioxidant control pathways. Exhale. He is ok. "Just" a migraine.
References: BMC Neurology, Frontiers, Jr Headache and Pain,
1. A description of one patient is sufficient to make conclusions with? T or F. Answer: Absolutely not. But it does confirm data and needs to be further tested.
2. The pathophysiology of migraine being similar to long COVID, MS, ADHD and autism comes as a surprise. T or F. Answer: False. That's how medicine works. It should follow established, testable pathways. So far we have 44 patients being reported with exactly this pathway. Just not with the treatment arm attached to that study.
3. What was missing from the 44 patient series? Answer: An action plan for cure. The ability to manufacture the plasmalogen molecule chassis called Prodrome Glia is new in the last 6 months, so still not widely tested.
4. What is the key ingredient in the action plan? Answer: Addessing each of the four critical support systems and finally, supplying the building blocks of myelin replenishment, Prodrome GLIA.
5. Why is migraine so persistent and keep relapsing? Answer: Like ADHD, autism, manic depression, long COVID, all share the same conundrum. Our brains have expanded to such a degree that our capacity to add extra plasmalogens to the mix is limited. It's as if we have a vulnerability/bottleneck in that the human body can only supply so much new plasmalogen. When we get a huge insult of inflammation, we can never recover back to "sufficiency" much less resilience and redundancy. We need outside help. Prodrome Glia gives that help. Without that help, we continue to tip-toe along the edge of recurrent symptoms with ongoing, low grade damage. The symptoms come and go with mysterious exacerbations from the tiniest of insults. We can never escape it...... until now. Now, we can.
Crohn's Disease is caused by Atypical Tuberculosis from Your Milk
Fifteen years ago, as I started my journey into functional medicine, I was intrigued by Vitamin D and its effects. I read an article in the Journal, Science that indicated you did not put out the peptide cathelicidin, (your natural internal antibiotic that kills viruses and bacteria by puncturing a hole in their cell walls) until your level of Vitamin D was 30. Below 30, no cathelicidin, and TB flourishes. Above thirty, you kill TB. There it was! That's why the age-old method of sending TB patients off to the mountains for "fresh mountain air" was actually to get more UVB radiation and make more D.
At that time, Aurora Health Care's "normal D level" was considered 5-50 ng because that was what we saw in the population.
I called up the Aurora pathologist to request a reconsideration of that level. I argued that "normal" should be considered medically sufficient to make that key ingredient, cathelicidin. Hence, a level above 30. He replied by saying, "Did you know that Crohn's disease is the #1 admission to Children's Hospital?". I thought that was a bit off the wall. I asked why that was relevant. He informed me that Crohn's had increased in incidence dramatically in the last 40 years. He was curious about Crohn's because as a pathologist, he knew that Crohn's is an illness with "granulomas" in the wall of the intestine. Only two other diseases make granulomas, tuberculosis, and sarcoidosis.
He asked, "Are you aware of Johne's disease". I had never heard of Johne's. It is basically atypical tuberculosis in cows. About 70% of dairy herds have at least one cow affected, and its hard to find. You have to culture the bug for over a year for it to be detected. Eventually, it kills the cow, but not before it infects other cows. Here's the rub. Pasteurization does not kill it completely. Some bacteria get through, especially in cheese production.
Now, there are increasing journal publications that are directly addressing the issue and using PCR (Polymerase chain reaction can detect just a few molecules of DNA and amplify it, thus permitting identifying its source.) and statistical methods to finger atypical TB with Crohn's. It's a very difficult illness to treat. Very indolent and persistent. There is virtually no cure. Did you know that one study showed that 100% of lactating women with Crohn's have atypical tuberculosis in their milk?
What's the rational conclusion? Every glass of milk you drink comes from 500 cows as milk is collected in large tanker trucks that mix the output of many cows. You will be drinking milk, eating cheese, yogurt, kefir or sour cream that is not completely sterilized for atypical tuberculosis. Johne's disease is not completely wiped out because we don't have a rigorous enough detection system in Wisconsin, or anywhere. There is broad consensus that some genetic predisposition exists. Vitamin D insufficiency is also clearly associated.
www.What will Work for me. I feel vindicated and frustrated. We have been talking about this topic for decades. The advent of PCR gives even more definitive proof. When will our suffering be enough? The only way to reduce our risk of Crohn's is to ask our elected government to insist on stronger identification of Johne's. PCR on cows would find it. It costs a little money. It saves huge medical costs and life-long misery for those affected. Otherwise, you are playing roulette with every dairy product you consume. It costs $ 37 to PCR test one sample for a cow. Wisconsin has a great lab. Politics makes it too expensive. Please, please take your Vitamin D and keep your level above 30....5000 IU a day will do it 99% of the time.
References: Science, World Jr Gastroenterology, J Immunology, Thera Adv Gastro., USDA, J Food Products, Inflamm Bowel Disease, Eur Resp Journal, MedRxIV, Wisconsin Vet Lab,
1. Crohn's disease is caused by what? Answer: Atypical tuberculosis in the small bowel.
2. The primary source of it is? Answer: Infected dairy products.
3. We have proof that you can't kill regular tuberculosis if your Vitamin D level is below. Answer: 30. The more skin pigment, the more sunlight you need to make sufficient D, African Americans in Wisconsin, not on D, will have levels of 5 ng in the winter and 20 in the summer....never sufficient. They have more Crohn's.
4. How long does it take to culture atypical tuberculosis? Answer: 1 year
5. Wisconsin requires that all its cows be tested for TB? T or F. Answer: False. It's voluntary. Bummer.
You can contact the Wisconsin Johne's Disease Lab and express your dismay by clicking here: Wisconsin Johne's Program. Better yet, contact your elected congressman. Make it an issue.
Myelin and IQ
The MRI scanner excites water molecules and uses that excitement to create its images. A very powerful magnet makes protons (a positive electrical charge) line up and then when the magnetic field is relaxed, the protons release their lining up with a smidgeon of released energy. The MRI scanner can read that. It is excellent at defining "soft tissue" in the body which has a lot of water in it.
The brain is floating in water but is mostly made of fat. Fat and water have quite different densities. The nerve cells of the brain are all connected to thousands of other nerve cells with some 4 quadrillion (estimated) connections called synapses. Each neuron cell is linked to some 3500-4000 other nerve cells with those synapses. The wires in between the cells and synapses are called axons. A naked axon conducts an electric impulse quite slowly. Eight weeks prior to birth, an infant human has very little myelin. All this can be proven by advances in MRI technology that can measure the quantity and quality of myelin. The human brain can't "afford" to be myelinated too much as that would make it "too large" for the exit canal. The brain has to wait for the last minute to be myelinated. Hence, babies are born with a huge myelin deficit and a big plasmalogen demand.
From the time to birth to age 3 months, the myelin doubles, and then doubles again in the next 6 months. There are many, many more wires laid down in the brain that are "needed" and the brain has a sorting process of discovering which axons are active, and conduct electricity and thereby need to be "hooked up" and connected. All that takes sorting out and pruning, wrapping, and wiring. A myelinated nerve that is sending signals conducts those signals at speeds in proportion to the density of myelin. Mothers paying attention see that maturation process as their infants learn to focus their vision and recognize their face. That happens early and is an important developmental event. Same with voice. Infants don't figure out their hands till later.
The axons in the brain are wrapped with progressively more layers of myelin. Like an onion, they mature, with efficient axons having many, many layers of myelin wrapped around and around the axon, making it faster and faster. The oligodendrocyte, the cell that does the wrapping, actually has pseudopods that reach out to multiple axons to wrap. That wrapping process doesn't happen in just a week or two. It is ongoing well into the 3rd and 4th decade of life, with "peak myelin" being achieved between 40-50. (Yes, children, your parents are smarter than you.). The more myelin, the faster the transmission speed.
The analogy with computers is compelling. Faster computers are better. They compute faster. We want to make quantum computers so that we can catapult computing time massively allowing us to solve heretofore unsolvable problems, like your bank account password.
That's what the frontier of MRI scanning is now achieving. As the layer upon layer of myelin is laid down around the axon, a tiny bit of water is trapped between the lipid layers. A tightly wrapped axon will have just a tiny bit of water. It is detectable as a tiny bit. A damaged axon, for any number of reasons, will have more water. And that variation is also detectable. Multiple sclerosis, concussions, autism, manic depression, ADHD, all have shown vhttps://www.medicalnewstoday.com/articles/adhd-brain-vs-normal-brainariable alterations of myelin density on MRI. This is obviously a developing field and more information is to follow.
But what about a high-functioning brain? Is a brain that is perfectly myelinated better than one that isn't? Here is the dilemma. The answer is probably yes, but not quite proven yet. Making myelin requires having sufficient plasmalogen lipids, the building blocks for constructing all those onion layer upon layer of myelin lipids. Making plasmalogen lipids is a delicate task that is put off by anything that damages cells' mitochondria and peroxisomes (where the plasmalogen backbone is constructed. MRI scans of twins suggest there is some genetic link with intelligence.....or is that link because the twins ate the same food? But preliminary studies are now beginning to confirm, more myelin, thicker axonal layers all correlate with better IQ. Hmmmm. Want your child to have one up on the competition?
www.What will Work for me. Prodrome Glia is the first compound to be on the market that has been proven to act as an engine to drive myelination in the brain. It has been proven to repair RDCP, the rare genetic disease of absolute plasmalogen production failure. This story has legs. We can fix the badly broken brain. Can we optimize it as well? Goodenowe's autism study is predicated on resolving the lack of healthy myelin easily documented in the brains of autistic folks, as well as in ADHD. It is clear that one of the "choke points" of human metabolism is the ability to manufacture plasmalogens. Yet, they play a massive role in the ability of our brains to function optimally. We can treat brain injuries of any source, including post-concussion syndrome. We are going to repair autism. Alzheimer's is next. Can we optimize our kids' brains with a little boost? (Answer? Probably yes)
References: Neuroimage , NIH, Frontiers In NeuroSci, ScienceDirect, eNeuro, Cell, Dev Neurobiol, KJR, WJP, Medical News Today, Intelligence, Brain Pathology,
1. A newborn baby has a fully functioning brain? T or F. Answer: Absolutely false. It is just starting to wrap its axons. Huge deficit in plasmalogens at birth.
2. The richest food source for newborns is what? Answer: Mother's breast milk. It provides about 30 mg/kg per day of plasmalogens. Cow's milk and formula provide zero.
3. The more breastfeeding, the less autism. T or F. Answer: True as proved by many, many studies.
4. If giving plasmalogen supplements repairs a disease called autism, what does giving, even more, do for otherwise normal kids? Answer: It makes sense to believe that it fixes a lot. SAT tests to follow.
5. Is there any toxicity to taking plasmalogen-building supplements? Answer: They are GRAS, generally recognized as safe. No toxicity.
Muscle Mass Defines Type 2 Diabetes
What does muscle mass have to do with diabetes? Very simple. You take up glucose in your muscles. If you lose muscle mass, you run out of places to put the glucose, so the glucose level in the blood starts to climb. Your insulin level then starts to climb. But as Grandma used to say, "You can't put five pounds of sugar in a four-pound bag." Insulin resistance ensues. Insulin is damaging to your kidneys and stimulates you to hang on to sodium. Blood pressure goes up. Metabolic syndrome develops. Voila. And it all started because you lose muscle mass. Conclusion: Muscle mass loss causes diabetes.
Does that sound too simplistic? What's the data? Actually, recently quite a lot. Studies have been conducted around the world, surprisingly, less so in the USA. From Japan, for example. In this study, two groups with 198 men, one with diabetes and one that was normal, had bioelectrical impedance analysis of their body to measure muscle mass. The men with diabetes had significantly less muscle mass. The loss was most pronounced in their legs.
A much larger study from Korea was comprised of 113,913 men and 89,854 women who were free of Type 2 diabetes at baseline. During 589,098 person-years of follow-up, 4,264 individuals developed Type 2 diabetes. Comparing quartile groups to relative risk, the next quartile still had a 2.2 fold increased risk for women and 2.0 increased risk for me....and dropping off with increasing muscle mass.
All of these studies speak to a more simple, global observation from the last 20 years. Muscle mass predicts longevity. The first research came out in just 2011 by Dr. Rosenberg indicating that "sacopenia" was a strong indicator of mortality. Loss of muscle makes for loss of places for glucose to be use. Blood levels of glucose rise. Insulin rises in response. Muscles become stuffed with glucose and insulin resistant.
This observation may explain why being "obese" isn't always so bad for you, if you have kept your muscle mass. It is bad for you the extra weight has increased your risk for diabetes, which it frequently does. But the core observation remains, more muscle, longer life. Muscle gives a place for glucose to go. Muscle burns calories around the clock shifting metabolism from glucose driven to ketone driven. Glucose helps you gain weight, make inflammation, make babies, but it doesn't help you live longer. Ketosis is always anti-inflammatory and supportive of building more plasmalogens. Plasmalogens are another strong indicator of longevity. And it all comes down to the amount of muscle you have.
www.What will Work for me? This line of logic makes physiological sense. The number one "anti-aging" activity we can all do is some form of exercise. All forms. Cardio has its own benefits. Weight lifting and resistance has its particular help with building muscle. And, as the time honored Hawaiian Retired Men's Study from 1998 showing that men who walked just 1.2 miles a day had a 20% reduction in mortality. Bike riding up an incline can be pretty cardio. We're going this afternoon. It's summer. Find a way to get out and do whatever that stretches your ability to exert.
References: Metab Syn Related Disorders, Open Access Govt, PLOS One, Am Jr Medicine, Sci American, NEJM, Clin Inter Aging,
1. Which comes first, muscle mass loss or diabetes? Answer: That is not apparent in these studies.
2. Muscle mass is dependent upon what main feature? Answer: Use it or lose it. Without use, your muscle shrink. With use, they grow
3. Why is muscle mass helpful for diabetes? Answer: it gives a destination for glucose.
4. Might I be correct in saying that diabetes is an indication of inadequate muscle? Answer: Yes. And inadequate exercise. Particularly in legs.
5. What can I do to change all that? Answer: Start. Do something. Every day. Consider Exercise Your #1 Anti-Aging Strategy.
How To Fix Autism: The Program, Part 4
We have reviewed the critical metabolic problems that promote autism.
1. Mitochondrial distress from an overload of elections and NADH leads to loose electrons that make reactive oxygen species. Cause of this? Anything that causes inflammation, reduces Nitric Oxide. High fructose corn syrup and table sugar are both right up there. Those reactive oxygen species make peroxide.
2. Too much hydrogen peroxide overwhelms all the safety systems to neutralize and we end up making too much OH-, the hydroxyl anion. The final evil ion.
3. The hydroxyl anion damages plasmalogen lipids that are the coating of your nerve fibers, and axons. You make malondialdehyde, and you lose plasmalogen coating and protection of your nerve fibers. (Remember this key factor because this is how we get to cure.)
4. Malondialdehyde activates microglia which attack the damaged axons and demyelinate the "white matter" in the brain. That can be seen and proven on MRI in autistic "victims". The microglia damage the methylation system by flooding the damaged cells with glutamate. Brain cells suffer and may die, but certainly don't have their wires communicate the way they were meant to. Autism ensues. (Or, if less affected, ADHD, manic depressive disease, or long COVID.....all have similar pathology.
5. Young children are most often affected because they have the least myelin. As children age and eat healthy food, they progressively develop more layers of myelin in their brains. The more layers of myelin, the faster your brain transmits signals. And yes, the more myelin, the faster and smarter your brain is. Eventually, the brain becomes so myelinated that autism doesn't happen in its fullest forms, but other lesser forms occur that are called ADHD, manic depressive disease, etc
There you have it. That's the physiological process of making a healthy kid's brain into an autistic brain. Knowing that, what are the steps to fix it?
A caveat. An autistic child has been deprived of normal brain function for a period of time. Their brain hasn't learned how to process language, emotions (love and trust), culture properly. Their learning has been delayed. Fixing all the metabolic problems doesn't repair that deficit and the child will need to learn to love, and be loved, to read and talk normally, to trust and be trusted.
We are going to learn how long all that takes....but a healthy brain can do that.
Step 1. Consider avoiding problematic foods containing sugar (particularly fructose), fried food using vegetable Omega 6 oils, A1 milk, and ultra-processed foods (more than 5 ingredients, wheat).
Step 2. Support the Mitochondria. Carnitine, CoQ10, B1, B2, B3, NAC
Step 3. Methylation Support. Creatine, egg yolk lecithin, B12, folate, betaine, B9, NAC
Step 4 General Nutritional Support. Sugar in the form of trehalose, Egg yolk oil, Whey Protein, Vitamins A, E, D3, K2, B6
How do we get all of those supplements into a child? Special Milk available to all children in the Autism Trial and generally available later this year. Or dig in and give it a try.
Step 5. Plasmalogen replacement and Myelin Repair. Prodrome Glia, 8 capsules a day (This has been the missing link. Now we have it. Everything else is part of the orchestra. This is the Maestro.). The whole program depends on this foundation. Prodrome Glia is essentially the basic skeleton building block for the brain to get to work and remyelinate those damaged neurons.
www.What will Work for me. I am awaiting the start of the trial. Families will get 4 bottles of Prodrome Glia for free, that will last a month and a reduced rate thereafter for participating in the trial. This is the missing link we have not had available to us until now. Now, we can prove that Prodrome Glia gets into the brain and stops the demyelination very rapidly. Days to weeks. Then, with metabolic repair in progress, it will take time, love, and caring to teach the child to love, trust, learn, remember....and all that happens in time.
References: PLOS1, Eur Rev Medpharm Sci, Epigenetics, Amino Acids, Goodenowe, Int Journal Mol Sci, Cell Metabolism, Nutr Res,
1. It has been proven in the lab that each step of the metabolic pathway of autism can be addressed, resolved, and repaired. T or F. Answer: True
2. It has been proven in large, placebo-controlled trials of autism that Prodrome Glia cures autism. T or F. Answer: False. Very exciting anecdotes holding promise.
Hence starting an open-label study as it was deemed unethical to withhold treatment when the real option of success was so close.
3. Prodrome Glia is toxic and should be studied further. T or F. Answer: false. No toxicity. Generally recognized as safe and sold as a supplement. It's essentially the core building block you make yourself to coat your own nerve cells. Prodrome Glia has been proven to safely reverse and repair the metabolic defect of RDCP children that are born without the ability to make any plasmalogens. Very rare condition but nature's example of absolute and complete plasmalogen deficit. That has been published in the peer-reviewed literature.
4. A treated autistic child will recover in weeks into a normal child. T or F. Answer: False and not claimed by the program. Early adapting parents report that it only takes weeks to notice calmer behavior, beginning play with siblings, less repetitive motions. The "computer" that is the brain has to get its wires insulated and functioning properly before it can create memories, culture, trust, language. That's a complex task.
5. More myelin in a brain makes for faster functioning? T or F. Answer: True. Hmmm. Do you want your child to have a better functioning brain. Will Prodrome Glia become brain food for all children? (Next week: Myelin and IQ)
Autism is a Disease of Microglia Activation that Damage Nerve Fibers - Part 3
Ok, last week we learned the incontrovertible proven fact that kids with autism have mitochondria that are being overwhelmed and are unable to handle the volume of electrons they are being presented. Some escape and make reactive oxygen species that cascade down to the hydroxyl ion. All the salvage steps in between; superoxide dismutase, catalase, and glutathione, get overwhelmed, as can be proven by lab tests showing dramatic alterations in autistic kids' blood.
All of those natural "anti-oxidants" are not sufficient to protect against the making of the hydroxyl ion (OH-). The hydroxy ion attacks the double bonds in the plasmalogen molecules and makes malondialdehyde, which is elevated in autistic kids as well. Now we have damaged membranes in the axons of our nerve cells. That malondialdehyde is a potent stimulator of microglia. Microglia are the garbage trucks of your brain, your macrophages, tasked with fighting invading germs, cleaning up unused synapses, dead cells, and damaged axons.
Wups! Cleaning up damaged axons? Yes. They are just doing what microglia are meant to do. When they see a damaged axon, that speaks to a diseased cell that needs to be tidied up and cleaned out before it sets off more inflammation that damages other cells. In autism the microglia just got sucker-punched by an internal problem of too many electrons and inadvertently started attacking the wrong thing.
Malondialdehyde is elevated in autistic kids' siblings too, just not as much as in the affected child. That is what argues for some genetic susceptibility in autism, or common environmental exposure. The microglia kill the cells they attack by flooding them with excess glutamate. At the same time, astrocytes in the brain frantically try to suck up the extra glutamate to calm the fire down. All of those phenomenon have been proven in lab tests.
An epic struggle ensues. Younger children have much less myelin in their brains, giving them a much smaller reservoir of reserve to battle oxidizing events, followed by microglial attack. (This is why autism starts in early childhood when the least bit of extra inflammation sets it off.). In the experimental model of autism induced by the chemical cuprizone, you can identify that females get much less demyelination in their brains to the same dose of cuprizone, accounting for the 3:1 ratio of autism in boys to girls. And yes, in the animal model of cuprizone-induced mouse autism, the tiny bit of estrogen that female baby mice have over baby male mice is sufficient to protect the females. What levels do human boys have compared to girls? Human girls, 0.6 pg and boys 0.08. Human adult women have 100-175 pg.) And estradiol is especially protective against glutamate toxicity.
Aha! It's glutamate secretion by microglia that kills off the neuron. It gums up and stops the methyltransferase system (B12, folate, homocysteine) and makes homocysteine jump. The cell starves to death and dies. Kids with autism have horrible methylation problems and need a ton of supportive supplements to get over the hump and fix the defect. More B12, folate, Betaine, B6, choline, creatine, and finally.....the kid's brain can calm itself down and get back to normal behavior.
Take-home summary. Autism is the endless cycle of microglia activation set off by overwhelmed redox systems. Microglia activate and attack the damaged, plasmalogen-deficient axon, thereby activating more microglia. Round and round, never escaping. The overwhelmed brain needs extra plasmalogens to rebuild and protect the nerve fibers, methylation support, and extra mitochondrial support to put out the fires....and that is all possible.
Guess what happens when you give plasmalogen precursors to make more myelin? Just guess. Yup! The Lone Ranger comes riding over the hill. You can almost instantly (within weeks) turn off demyelination in every mouse and animal model ever studied. This turns out to be the key. More plasmalogen building blocks. Pulls the rug out on all the extra stress and vicious cycles the brain is in.
That is Goodenowe's genius. He designed and is now making the plasmalogen precursor to make more myelin. It turns off microglial activation just like that. It's called Prodrome Glia. In effect, it provides sufficient building blocks for the brain to repair itself and break the neverending cycle of reinforcing microglia activation and demyelination.
www.What will Work for me. I am all in. Goodenow is launching his nationwide Autism study with his collaborating doctors, of which I am one. We are just waiting the details of how to sign people up. And all the "drugs" we sure are actually just supplements. GRAS. Generally recognized as safe. We just haven't had the Prodrome Glia until now. Now we do.
And it's not just autism. This mechanism is probably also what ADHD is actually all about, but with a slightly more mature brain that has just enough materialto stay a little bit ahead. Many are beginning to argue they are just different parts of the same spectrum. Got that? ADHD too....
References: Biomarker Insights, Annual Review of Immun, Neurosci., MDPI, Neurobio of Disease, Jr Clin Investigation, J Neurosci, J Immunology, PLOS One, Molecular Autism, Spectrum News,
1. Ok, keep it simple. What happens when you get too much hydroxyl ion? Answer: You damage plasmalogens in the myelin sheath around nerve axons and you make malondialdehyde and lose plasmalogens.
2. Autistic kids have more or less malondialdehyde? Answer: Way more (meaning dramatic loss of total plasmalogen pool)
3. Malondialdehyde is a potent trigger for what? Answer: Microglia (brain's garbage trucks) activation. You turn on the garbage trucks that come and attack the damaged membranes, stripping off the myelin and killing the cell with flooding glutamate.
4. Glutamate does what? Answer: Too much of it and you shut down the methylation cycle, and you starve the cell to death.
5. Can I fix that? Answer: Yes. You can give the plasmalogen building blocks to rebuild myelin and methylation vitamins and building blocks to give all the extra nutrition the autistic kid needs.
6. Wait, wait, wait.....I have more questions. Is ADHD and Autism part of the same spectrum? Answer. YES. and Prodrome Glia will probably help both syndromes in a similar fashion. Maybe even faster for ADHD as it is a milder form.
7. Wait, wait...... Answers: next week. (See why I argue that Goodenowe is going to get a Nobel Prize in Medicine? This is a major emerging story.)
Autism is a Condition of Mitochondrial Insufficiency - Step One
This is a bit geeky but if you dive into this and understand it, you actually are getting the foundation for almost all brain diseases. Really, All! I want to learn and take you along for the ride. Here is the science.
We have known this for decades. Studies from the 1970s first showed some of the data. Let me explain.
If your mitochondria are overwhelmed and can't process the calories being pushed into them, your mitochondria can't handle all the electrons being thrust at them with no ADP to pull the electrons away. Where that backs up is with TOO much NADH, instead of NAD+. This explains why sugars and easily digested white flour products make autism worse. Those electrons spin away outside the mitochondria and attach themselves to Oxygen Molecules that get changed into peroxide. That will damage membranes if not contained. Measuring the mechanisms of containment all show that kids with autism are fighting that battle and losing. For example, the first line of defense with free electrons is a protein called superoxide dismutase (SOD). It gets induced and autistic kids have much higher levels of it in their blood, meaning they are losing the battle. The next enzyme of protection is called catalase. It is not inducible and it just gets used up. SOD wasn't enough and now catalase levels have dropped in half. Guess what happens to autistic kids? Yup, they have low, low levels of catalase. They are fighting a mighty battle, and not keeping up.
The next line of defense against those overwhelming electrons is glutathione. It too can suck up and repair too much peroxide. But it too can't match the flood of excess oxidizing electrons. The poor autistic brain is off balance and glutathione levels plummet. What is a unique finding from this study in Syrian kids was that their siblings, without autism, were also low in glutathione, suggesting some level of genetic risk that hadn't presented clinically yet. Those siblings are on the verge of symptoms are for whatever reason aren't affected.
The final defense of brain membranes is plasmalogens. They can neutralize peroxide, but the price is high. You lose a whole plasmalogen molecule and deplete your brain's ability to myelinate the axons. Considering that plasmalogens make up 70% of the myelin lipids protecting axons, losing them results in less myelin.
Now we get to the final step into trouble. All the defenses against those free electrons are overwhelmed, and OH- now attacks nerve membranes. OH- will damage a double bond in cellular membrane plasmalogens and make malondialdehyde. What do you find in autism? Instead of a level of 5 found in normal kids, autistic kids will have a malondialdehyde of 20. Their asymptomatic siblings will be just a tiny bit lower.
Once you have damaged membranes and high levels of malondialdehyde, you start to activate microglia, the attack dogs of your central nervous system. They go to work to do what they are meant to do, clean up what they think is a mess. But it's not a mess. It's a little kid's brain. And that child can't break the cycle.
There you have it. This is irrefutable science, clearly documented with well-done research. It just feels overwhelming. Next week I will explain the microglial activation and how it plays out. And hang in there. The week after will be the protocol of how to go about addressing it.
You can download Goodenowe's very elegant chapter on the biochemical basis of autism and read it in great detail, if you so wish.
www.What will Work for me. I want to learn this in detail and share it as far and as wide as I can. I think this is thrilling science. What I find unique is the commonality of the pathway with almost all brain diseases. Autism is what happens in kids. Long COVID and brain fog is an adult brain on its way to autism if the cycle isn't broken. But sugar has a clear pathway to causing NADH disruption...as do any foods that make your glucose go up too fast. The commonality with Multiple Sclerosis, Parkinson's, ALS, Alzheimer's is startling. In fact, if you look at manic depressive disease, ADD, drug addiction....you find the same pathway and pathology. I can help my burdened mitochondria by avoiding sugar and white flour. Taking Acetyl-L-carnitine, glutathione, CQ10, B12, B6 and folate are all mitochondrial support supplements. Now you know part of why they are good for you too.
References: Frontiers Nutrition, Free Radic Biol, Med, Maedica, Goodenowe, Eur Arch Psychiatry Clin Neurosci, Biomarker Insights, J. Nutrition,
1. What is the first step in the autistic brain to making damage? Answer: The failure of the mitochondria to manage the flood of calories in the form of too many glucose molecules. Like your gasoline siphon for your spare gas tank overflowing because the gas station pump pumps too fast.
2. Is someone to blame for that? Answer: NOOOOO! There is obviously some genetic component but the increase in incidence of autism tracks our nation's consumption of sugar pretty closely. 80% of our packaged foods have added sugar. We live in a dangerous sea of calories.....with sugared drinks high on the list. Any "blame" to be had is the food industry that stuffs sugar into everything.
3. How come I haven't heard this before? Answer: It is overwhelming in its complexity. There are hundreds and thousands of articles. Pulling it into focus is Dr. Goodenowe's gift.
4. Are there easy blood tests I can get on my family to prove they are safe? Answer. Well, yes. You can now measure glutathione and malondialdehyde.
5. Is there something I can start with right now for my affected child, or my nephew with OCS, or Asberger's, or manic depression, or, or or. Answer; Yes. Start with finding ways around sweet foods and white flour. Dairy probably sets off brain inflammation as well if it is from A1 cows. Only A2 milk or cheese.
Autism - We Can Fix It
Autism has increased in prevalence over the last forty years by some counts as much as 10 fold. That may be due to better diagnosis and improved testing methodologies, but no one denies the massive impact the illness has on families, not to mention the economic impact on society of lost wages and lifetime disability. In 1930, autism was diagnosed in 1/100,000 children. Now,in Scotland, one in 36 children are being diagnosed. Genetic diseases do not behave in this fashion. Genetic diseases remain relatively constant in given populations. This speaks to environmental pressure and an altered ecosystem. And if it is environmental, and we can understand the root causes of it, we can fix it. That is what this series is about.
The CDC states on its web site that we don't know the causes of autism. That may technically be true, we don't know those initial triggers of overwhelming oxidative stress, but we do know the pathophysiology, and we have the tools to interrupt that pathophysiology and reverse it. Probably the sooner we learn how to diagnose this catastrophic affliction, and intercede with our therapies, the better it will be for all involved. Rather than quibble about what "sets it off", which we may not be able to determine, we should be focusing on how to make the interventions that catch it and reverse it.
Dayan Goodenowe, Ph.D. is leading the charge to run a clinical trial of interventions that use commonly available foods, supplements, and targeted plasmalogen therapies to accomplish this goal. And I'm all in.
The summary of the next few newsletters will be:
a) Show how mitochondrial stress and failure to process NADH results in the overproduction of reactive oxygen species.
b). Those reactive oxygen species go on to damage membranes of neurons which results in the activation of microglia, the cells that clean up damage.
c). Activation of microglia results in demyelination in the brain, which results in all the symptoms of autism.
d). A steady state of ongoing activation of microglia, demyelination and reactive oxygen species keeps the involved brain damaged and unable to return to its normal state. We can intercede in each of those steps.
And it is important to note that "cure" involves two steps. The physiology and inflammation can be normalized and reversed. Remyelination of the brain and rebuilding lost development takes more time. So cure is not an instantaneous event of a single intervention but rather a patient process.
www.What will Work for me. I'm optimistic. I believe this is a Nobel Prize in Medicine, waiting to be demonstrated. The several hundred physicians who have signed on to Dr. Goodenowe's research institute program have already demonstrated multiple anecdotal examples of dramatic improvement that I have personally witnessed. What I am fascinated by is learning the root physiology that has a common overlap with many other brain diseases. Long COVID, for example, is likely the same process going on in a more mature brain that doesn't devolve into frank autism or quite complete disability, but shares the steady state of not being able to return to normal, and improves and repairs with the same interventions. As does manic depressive disease, multiple sclerosis.... We can all start by keep our own brains healthier by avoiding sugar, making sure we have B vitamins and reducing our consumption of omega-6, pro-inflammatory fats (canola, corn, soybean oil)
References: Annals of Child Neurology , Jr Autism Dev Disorders, CDC, Goodenowe,
1. How is autism first recognized? Answer: No fair, not mentioned. Well, it's usually the recognition of delayed speech that takes a child to see a doctor.
2. What age does that happen? Answer: Average age for boys is 3-6.
3. Why do girls have 1/3 the rate of autism? Answer: Because estrogen, even at the tiny levels seen in prepubescent girls, is protective.
4. Are there racial disparities in autism? Answer: No, it appears to be worldwide, but notably in "advanced societies"
5. What is the first step in developing autism? Answer: The failure of mitochondria to adequately control the production of NADH, resulting in the escape of extra loose electrons that activate reactive oxygen species (ROS). These ROS start the cascade of damaging membranes, thereby activating microglia, leading to demyelination and reactivation of more inflammation. Around and around.
Erythritol: Is it Really Bad for Me?
Headlines, headlines......"Common Sweetener Tied To Higher Risk of Stroke and Heart Attacks". Goodness, is that true? Well, maybe. It certainly is something we need to think about and watch. We are all exposed to a lot of it.
What is erythritol? It is a 4-carbon sugar you naturally make on your own, in tiny amounts. You can find it in human blood and even in amniotic fluid at very low levels. When you use it as a sweetener, it shows up in your blood in minutes, and takes as much as 3-4 days to fully excrete. 78% is gone in one day. Once erythritol is in you, the vast majority of it is excreted through your urine. None of it gets turned into energy. The Japanese were the first to find out how to make it in bulk by fermenting a portfolio of yeasts. It was brought to market in the US in 2001 and generally recognized as safe (GRAS) in the US and in some 50 other countries. Its use currently is to supplement stevia and monk fruit sweeteners with which it is frequently the number 1 ingredient, albeit it with Stevia or Monkfruit taking the lead advertising. But we have only been exposed to it for 22 years now. This study is the first to find harm.
What did the researchers do? They first analyzed blood samples from 1,157 participants for multiple compounds linked to cardiovascular risk. In that analysis, erythritol showed up as one of the strongest links to the risk of cardiovascular type disease. That includes stroke.
A second group of subjects (2149 from the United States and 833 from Europe) undergoing cardiac evaluations were then analyzed for plasma levels of erythritol and for the presence of cardiovascular disease. That's where the association popped up. They found that participants in that second group with the highest 25th percentile erythritol blood levels were 2.5 (US) and 4.5(Europe) times more likely to have a cardiovascular event than those in the lowest 25 percentile. On face value, that makes erythritol one of our highest risks for cardiovascular disease. Is this credible?
Not everyone agrees that it is credible. It was not a randomized group of people. And it was blood levels that were measured, not what was consumed. The assumption that your blood level comes only from what you eat may be false, as humans make a tiny bit on their own. But it may be a marker of diseased arteries, or some other internal biological pathway yet unexplained.
www.What will Work for me. What is one to make of all this? The level of disease associated with this observation is startling. Observational studies are just that. They call to your attention a possible finding. What is a prudent person to do? I'm on the search for an alternative sweetener. I've been using "Stevia" from Cargill, only to note that its first ingredient is erythritol. Hmm. I order some Monk Fruit sweetener to try out, only to discover the big E as ingredient # 1 again. (Splenda Monk Fruit). Nature's Best1 Sugar Replacement has allulose. Hmm? Any better? I bought a bag of Trehalose as a sweetener. It works. And appears to be less bioactive at stimulating insulin. Heart disease? Unstudied. I'm now on a liquid Monk Fruit sweetener. We'll see how it goes.
References: Nature, Montreal Gazette, MedicalNewsToday, Yeast, Inter Jr Mol Sci, Nutrients, Crit Rev Food Sci,
1. What does erythritol do to folks with heart disease? Answer: Trick question. We don't know for sure. There is an association with higher use of erythritol and cardiovascular events.
2. What could be causing those "events" with erythritol? Answer: It could be the erythritol or it could be the heart condition making the erythritol.
3. How do we sort that out? Answer: Long-term, randomized, placebo-controlled trial measuring the amount consumed. (This will never be done as there is no money in it.)
4. How do I make my own decisions in a messy world when I hear information like this? Answer: Prudent folks can find alternatives until they see better science. Or not.
5. Is trehalose any better? Answer: We don't know. We do know that table sugar (glucose and fructose bonded together) and HFCS is 10-15% of our calories and added to 80% of prepared foods in one hidden fashion or another. And it's harmful. In one month on a fast food diet, you can prove someone is near death from fatty liver. (Small study: the movie "SuperSize Me.")
How To Engage your Inner Nerf
"...Nrf2 ...may well become the most extraordinary therapeutic and most extraordinary preventive breakthrough in the history of medicine."
How's that for a bold statement? The authors aren't kidding, and the volume of research on Nrf2 is becoming staggering. Almost all diseases originate with some dysfunction around "oxidate stress", and the Nrt-2 system is at the nexus of its repair. This review article details how all of our "health-promoting activities" have a common means of activation: the Nrf2 system. The Okinawan and Mediterranean Diets make their magic via Nrf 2. Exercise activates Nrf2. Intermittent fasting does it. Astaxanthin does it. Vitamin E (the gamma delta version), works. And our modern American Diet is almost the antithesis. Sugar and white flour, metabolic syndrome, and ultra-processed foods don't work.
That is how central the Nrf2 system is to virtually all of our modern diseases and "hallmarks of aging". In fact, there are now authors claiming that "Nrf2, ..(is the).. guardian of healthspan and gatekeeper of species longevity."
The diseases that have been identified as Nrf2 affected include cardiovascular, neurodegenerative, pulmonary, cancer, metabolic, and gastrointestinal...... which includes just about everybody.
There are identified foods that Okinawan and Mediterranean Diets use that are now known to be beneficial because of their NRF2 activation. For example, the phenolic antioxidants in olives (Mediterranean) and purple sweet potatoes (Okinawans) activate Nrf2 pathways. Carotenoids from green leafy vegetables are abundant in Mediterranean and Okinawan diets. Lots of fish oil. Lots of allium family (onions and garlic). Isothiocyanates from crucifers and terpenoids from eggplant and citrus all participate in both cuisines. That provides the scientific underpinning for the benefit of each of those cuisines.
And that's where rosemary comes in. The lovely, pungent Thanksgiving spice, rosemary has lots of carnosic acid in it. There are over 200 points of impact in the NRF2 pathway that has been identified. No one food or spice activates Nrf2 all by itself. However, once you hit 3-4 critical junctures in the complex pathway, you get synergies. Carnosic acid activates some of the most important, rate-limiting steps. Rosemary (carnosic acid), luteolin, and ginger are one powerful combination sold in a product called PB-125. Rosemary, by itself, is pretty good, but you get a 5-6 fold increase in Nrf2 activation with ginger and luteolin added in.
www.What will Work for me? I feel like I just found a missing piece in the jigsaw puzzle of aging. Nrf-2 activation works on just about everything, right at the very beginning of the problem. Without Nrf2 activation, stressed blood vessels get smooth and exposed, losing the glycocalyx coating that protects them from sheer stress. Without that glycocalyx, sheer stress starts injuring the artery. With Nrf-2activation, the complex, protective coat (Look like sea grass swaying in the current) comes back. PB-125 is one powerful, synergistic compound based on rosemary. There will be others. The evidence we want to watch for is the measured benefit proven by lab testing. The cool thing is that almost all spicy Asian cuisines are champion Nrf2 activators. We just need the lab science to show us which is best. Right now, it's PB-125 from Pathways Bioscience. I'm taking it. You should too. One pill a day. And keep up the exercise, the green leafy diet, the fish oil, the spices, the intermittent fasting.....and lose the donuts.
References: Acta Physiologocial Synica, Nutrition, IntegrativeCompBio., FreeRadBiolMed, Redox Biol, Int Jr Mole Sci, J Neurochemistry,
1. What role does the Nrf2 system play in ALL systemic diseases? Answer: Just about all diseases come about because of Oxidative Stress from some imbalance the human body can't keep up with. Nrf2 activation prevents that stress.
2. What happens to the Nrf2 system with aging? Answer: you know that answer. Just try jumping out of bed in the morning without an ache or pain. Nrf2 declines precipitously over age 40.
3. I can turn on my Nrf2 system by eating lots of rosemary? T or F. Answer: Slightly true. Any one food or spice will activate the complex Nrf2 pathway in only 2-3 places. Considering that there are now about 200 points of influence, you need more than one activation. Multiple components provide the threshold of synergy.
4. What is the active agent in rosemary which will likely play a role in most activators going forward? Answer: Carnosic acid, 20% is the magic threshold.
5. Name some lifestyle features that by themselves also activate and support the Nrf2 system. Answer: Exercise, fasting, ketogenesis, green leafy vegetables, omega-3 fats, onions, and garlic, purple Okinawan sweet potatoes, olives, fruits and vegetables of all kinds, and not so many grains and not so many sugars.