You Can Make Your Brain Bigger
The cardinal sign of Alzheimer's is a shrunken, withered brain. Science has progressed from recognizing the shrinkage on the macro level to understanding the engine that is driving it. Yale was the first to show by PET scanning with a unique marker of synapses that synaptic density correlates with cognitive function.
That just makes sense when you realize that the preserving of memory is bound up in multiple neurons making thousands of links to generate any single memory.
Goodenowe was the first to identify the culprit at the molecular level. He invented the field of "metabolomics", measuring everything in the blood over time with aging Catholic clergy. He discovered that the fatty membrane lipids called plasmalogens are the cardinal component of synapses (70%) and axons (70%) that decline and cause the progress loss of synapses and the progressive degradation of white matter. White matter is composed of all the cables wrapped up in the insulating plasmalogen membranes wherein all the communications are carried between the neurons of gray matter and every cell in the body.
What this week's study reveals is MRI evaluation of an aging population with MRI scans taken at regular intervals. There were 653 subjects who were followed for some 12 years and had over 7000 exams of their brains. They showed that aging is linked to a shrinking brain at a steady pace over age 40, and this is linked to reduced cognitive function.
This study reinforced a similar study from Hamburg that confirmed the loss of cortical thickness. This all builds on the finding of Kristine Walhovd from Norway in 2011.
Fair enough. It's a given. As you get older, your brain shrinks. That's just normal aging. Or is it? Has anyone ever reversed it? Of note, there were no brains in any of these studies that got larger. Maybe stay close to the same, but that -1 to -2% slope appears to be universal.
What has changed is the ability to manufacture plasmalogen supplements that can augment the normal healing the human body wants to do, and will do, given the chance. We know that that is what is missing.
Now, reported at a national meeting (World Peptide Conference) Dr Goodenowe reported on his own experiment on himself. He gave himself 100 mg per kg per day of Prodrome Neuro and Glia for 18 months with before and after fMRI exams.
His brain got 8% larger in that time. That would be a +76% slope positive. No one has ever done that before. He reversed the effects of 17 years of "normal aging". Furthermore, diffusion studies of his white matter showed a 10% improvement. He had no indication before his experiment that any of this would have been abnormal. It has never been done before. No toxicity. No side effects.
This is big.
www.What will Work for me? Well, I had a mother who died of Alzheimer's and I'm anxious for my brain. I'm taking 50 mg per kg per day of plasmalogen supplements. I feel subjectively that I'm getting sharper. Fortunately, three years ago I got an MRI just for the purpose of checking things out. That was before diffusion studies were widely available. Time to go back for a repeat.
References: JAMA Network Open, Frontiers, Neurobiology of Aging,
Pop Quiz
1. Is a shrinking brain normal with aging? Answer: It is happening to everyone. Those who have a slightly steeper slope get Alzheimer's. If you live to 95, you have a 50% chance of dementia. Normal means it is happening to everyone, but it doesn't mean that has to be accepted as healthy, or ok.
2. What happened to our first recorded, documented brain supplementation program of 18 months of 100 mg per kg per day? Answer: An 8% increase in brain size and 17 years of "normal " aging reversed.
3. What was the observed toxicity of such high-dose treatment? Answer. None
4. Can one consider a study with an N of 1 credible? Answer: Depends how you look at it. The first single human heart transplant triggered a revolution.
5. To repair a broken brain with symptoms of memory issues, how long does it take to repair? Answer: We are doing research on our car while driving it. We don't know the answer, but it appears that 1 year of 100 mg per kg per day reverses the "normal" shrinkage that would occur over 17 years.
What Causes Schizophrenia?
Schizophrenia is an odd disease. It strikes teenagers (most often) who have otherwise been normal. They often present with a characteristic prodrome of disordered thinking. That prodrome is better treated with fish oil than any other pharmaceutical, reducing the odds of flipping into full fledged schizophrenia by some 50-70%. That is a very interesting clue (We will get back to this). Supposedly the cause is unknown, though many conjectures exist. Separated twins continue to have an increased risk so there is some acknowledgement that there is a genetic risk involved.
Schizophrenia’s symptoms are myriad. Disorder thinking, troubled relationships, hallucinations all can be part of the symptom mix. It’s a catastrophe for the person involved. They frequently end us unable to hold a job, finish school, engage in healthy relationships or all the other hallmarks of a fulfilling life.
There is hope here. Follow this thread. We have known for almost 20 years that Schizophrenia shows disrupted white matter on MRI diffusion studies. That means the myelin in the brain has been degraded. Instead of nice, neat 10-15 layers of myelin, there is too much water and too little plasmalogen lipid in the myelin. Plasmalogens make up 70% of myelin. They are the antioxidant of FIRST RESORT designed to protect the precious brain cells from damaging chemicals. Hence, when reactive oxygen species show up and overwhelm the normal defenses, plasmalogens are damaged and need replacement.
Microglia are the garbage trucks of the brain, tasked with cleaning up damaged cells so that the regular undamaged cells can get on with the work to be done. Evidence of microglial activation is also well established. “Upon activation, microglia release key proinflammatory cytokines and free radicals, which are well-recognized neurotoxic factors contributing to cognitive decline.” Microglia are sloppy. In the release of those inflammatory cytokines, they damage the region around the damaged axon, making a falling domino effect. They then have to clean up the next cell, and the next, and the next.
That domino effect occurs because the cells responsible for making myelin, called oligodendrocytes, have got themselves in a biological corner. The surface area of membrane they are responsible to maintain is massive. Each oligodendrocyte has multiple pseudopods extending out to make multiple layers of myelin around the axons. That myelin works best if there is very little water in it. That feature allows it to insulate the axon for electrical conductivity. A well-myelinated brain will conduct electricity at 100 meters a second. A newborn baby with virtually no myelin has a conduction speed in their brain of 1-2 meters a second. If you imagine a regular cell being a football (it is the season, after all). A regular cell has a membrane around the football. That’s not hard to maintain. If damage happens, it can send a repair team out to fix it. An oligodendrocyte has a membrane the size of a football field, compared to its football. Maintaining that is no small task. To send out repairs, when there is no water to work with, ties its hands behind its back. You might call that the Plasmalogen Bottleneck. The Oligodendrocyte can’t repair the damaged membranes without a lot of help, if at all because of those sloppy microglia that keep damaging the next cell over.
Is there evidence of plasmalogen damage in schizophrenia. Yup, yup, yup. When peroxide or the dreaded OH- ion meet up with the vinyl ether bond on the surface of the myelin, the double bond is degraded and destroyed, making a byproduct called malondialdehyde. Guess what we find in schizophrenia? High malondialdehyde.
This speaks to the cause of schizophrenia. Some unrecognized mitochondrial failure initiates a cascade of reactive oxygen species. They overwhelm the normal defenses and reach the white matter ecosystem. Oxidative damage happens and axons no longer function properly. That’s where fish oil comes in. Gray matter plasmalogens are where DHA from fish oil ends up. If we give the poor, struggling brain cells just a modicum of help, they get better. They are just burning up from the oxidative stress and need a whole raft of support mechanisms to fix them.
That’s where plasmalogen supplementation comes in. It hasn’t been proven yet, but all the features are there. What has changed is the beginning ability to manufacture replacement plasmalogens. Mitochondiral support, methylation support are all easy to accomplish. Just flood the zone and give the poor brain a chance!
WWW.What will work for me. I’ve heard of one anecdote of a psychotic break with hallucinations given 200 mg/kg of plasmalogens a day resulting in a complete remission of symptoms in just 7 days. That is just mind boggling, to coin a phrase. What I’m wrapping my brain around is the concept of the Plasmalogen Bottleneck in the oligodendrocyte. That makes sense to me. We evolved such an amazing brain with so many fantastic capabilities, but in so doing, opened up a key vulnerability. That football field of membranes is a bear to maintain and just doesn’t do it very well when ongoing oxidative stress happens. Well, now we can fix it. Probably, hopefully. Turning off the oxidizing stress source may be key. More research to follow
References:
Lipid Health Dis., Mayo Clinic, Neuropsychopharmacology, Nature, Noro Psikiyatr Ars, Nature,
Pop Quiz
1. What is the MRI finding in the white matter of brains with folks suffering from schizophrenia? Answer: White matter diffusion defects.
2. How can you prove that there is widespread microglial activation in the brains of schizophrenia sufferers? Answer: High malondialdehyde
3. Why do presenting schizophrenics often improve with extra fish oil? Answer: Fish oil, DHA, its integral to making plasmalogens. That's where fish oil is used in the human body. The brain is begging for building blocks so it can function properly.
4. What is the Plasmalogen Bottleneck? Answer: My label for an observed phenomenon. Oligodendrocytes, the cells that make myelin has a responsibility to maintain many times their own natural surface area of membrane that is wrapped around axons to insulate them and allow them to conduct electricity rapidly. That wrapping is hard to access because, of a necessity, all the water is squeezed out. When myelin is damaged, the cell responsible to repair it just can't.
5. Will schizophrenics improve with plasmalogen therapy? Answer: It is a tantalizing hypothesis that addresses all the physiology properly with no toxicity. Nothing else has worked to date. We are just waiting for proof.
Chronic Lyme has MRI Scan Changes Consistent with Demyelination
Chronic Lyme Disease is a mystery, much like Chronic COVID. There is clearly a similarity with Chronic Lyme and CIRS. We, in the CIRS community, contend that chronic Lyme disease is a cause of about 10% of CIRS with 80% of CIRS being caused by mold/actinomycetes toxins from water-damaged buildings. Brain fog is high on the list of aggravating symptoms. Additional symptoms like “difficulty concentrating”, “learning new knowledge”, and “remembering” all fit under the rubric of “brain fog”.
Now we know why. This is a very meaningful study that lies in the nexus of multiple threads of scientific discovery. As reported in PLOS 1, 12 patients with well-characterized and documented Lyme disease compared to 18 controls had MRI scans with diffusion tensor studies. There were clear differences between the controls and the Lyme patients.
MRI diffusion tensor studies are looking at the distribution of water in white matter. White matter is basically all the cables (axons) between the computer servers (neurons) in your brain. Myelin is over 70% plasmalogens made with oleic acid (olive oil) made by brain cells called oligodendrocytes. Each oligodendrocyte services dozens of axon cables around it by gradually growing its membrane around and around the axon. There are many, many layers of membrane. Each layer makes for faster, more consistent conductivity of the axon. Your brain is being myelinated continuously into your late 40s. Yes, a 40-year-old has more myelin than a teenager.
If you do a cross-section of human white matter at autopsy, you see millions of cables in cross-section, each of which is surrounded by layer upon layer of myelin. Like onions, there are multiple layers of insulation or wrapping. The more the better. Those myelin layers are made of fat. Fat repels water. Very little water is between the myelin layers. There is so little that most of it lines up with each other in a characteristic pattern because of the tiny bipolarity of water.
You are now getting the picture. MRI scans work by activating that polarity of the water molecule with a huge magnet. Then, let it go. The magnet makes a loud banging as it releases the magnetic field, making MRI scans noisy events. The pattern you see in healthy brain white matter is exactly that….very little water, all neatly lined up.
That’s not what you see in chronic Lyme disease. You see alterations in the diffusion studies reflecting damage to the myelin. That’s a hugely important finding.
The reason that’s huge is because we know all the steps short of that. This is exactly what happens in autism, though autism strikes a much more immature brain that hasn’t laid down many memories or layers of myelin.
Inflammation in the brain only has one pathway to express itself. Reactive oxygen species escape stressed mitochondria and generate free peroxide. Peroxide overwhelms glutathione and then goes on to do more damage to any double bond it can find. Plasmalogens are designed to protect the precious nerve fiber with a double bond right on the surface of the myelin membrane. That way it can gobble up the peroxide, or worse, the OH- hydroxyl ion, before any damage can happen to the axon. With that, the plasmalogen molecule is destroyed and has to be replaced. That puts a huge stress on the oligodendrocyte, which has to make more plasmalogens to repair the damaged membrane. That’s the plasmalogen bottleneck.
Lyme disease creates an ongoing generation of oxidizing stress on the white matter of the brain. It is exhausting the ability of the white matter to repair itself, and indeed, the MRI is here proving that it is not succeeding at so doing. Each oligodendrocyte has a huge surface area because it serves dozens of axons with many layers of myelin. All that is well and good until an oxidizing environment comes along. Chronic infection from Lyme meets that criteria.
The problem is the ongoing oxidizing stress. Like a circle of dominos, as soon as you put up one side of the circle, the falling dominoes come around again. Once you have oxidizing stress and damage some membranes, the garbage trucks of the brain come to clean up. Microglial cells come to kill what they think is an infection invader. In their well-meaning efforts to knock off the “invader,” they damage the axon membranes around the injured axon, making for more damage and calling in more microglia. Around and around, you go.
There is only one way to cure this. Treating with antibiotics and hoping it will get better won’t do it. Of course, you have to kill the Lyme disease but that’s not a forever thing. You have to interrupt the circle of dominoes. You have to break through the plasmalogen bottleneck. That takes treating the oxidizing stress and flooding the zone with sufficient plasmalogen replacements should fix it. Giving your oligodendrocytes adequate building blocks to repair the white matter is a necessary and relevant step. We don’t have proof of that yet, but we have all the requisite intermediate steps proven in the scientific literature. This article seals the deal.
What has now changed and offers hope is the ability to manufacture plasmalogen replacement supplements. With Prodrome Glia, we can replace the missing piece of the jig saw.
WWW. What will Work for Me? I’m going to try this experiment on any Lyme patient in the future. It makes perfect sense. We are repairing other forms of plasmalogen damage. It takes an agonizing long time to fix, but fix it does. Goodenowe just reported that he measured his own brain, while in a healthy state. His MRI of his brain showed normal diffusion status when he started but after one year of Prodrome Glia, it improved dramatically. That was unexpected.
References: PLOS One,
Pop Quiz
1. What happens to the brains of Lyme Disease patients as shown on MRI? Answer: Dymelination of the axons
2. Why is that a problem? Answer: Lose a layer or two, you get brain fog, trouble remembering, etc. Your brain slows down.
3. Why is this demyelination happening? Answer: The common pathway of oxidative stress that causes too many loose electrons, causing activation of catalase and the manufacturing of peroxide to get rid of the electrons. That depletes glutathione. If still overwhelmed, peroxide and the hydroxyl ion attack the plasmalogen double bond, designed for just that purpose, so be the final line of defense against oxidative stress. Microglia come to clean up the damage but they are sloppy and damage the surrounding cells, which then need repair, and that becomes self-perpetuating.
4. What is the "plasmalogen bottleneck"? Answer: The oligodendrocytes, tasked with making and maintaining the myelin end up way overextended. Each oligodendrocyte has multiple axons it is covered with many layers of myelin, resulting in a surface area of membranes that is impossible to keep up with under the burden of ongoing oxidative stress. They can't catch up.
5. Is there a fix for that? Answer: Not proven but probably yes. Prodrome Glia is the precursor plasmalogen molecule found in mother's breast milk. Newborn babies get 30 mg/kg per day while breastfeeding. It accelerates remyelination. This might be huge and may be the cure for long Lyme's.
Skin Wrinkles Drive Aging
We age. Our skin ages. Bummer. Our skin is our largest organ and provides an amazing protection from all the nasty things in our environment. It has collagen providing firmness, elastin adding elasticity and rebound, and glycosaminoglycans to maintain hydration. They are all abundant in young, healthy, unwrinkled skin. It should be noted that under a microscope of a biopsy of a wrinkle, there are no obvious indications that you are looking at a wrinkle. What gives?
There are two types of aging to skin. Intrinsic aging is going on inside the cells. Collagen drops by about 1% a year. Skin cholesterol decreases with aging and correlates with reduction of production of Vitamin D. Sweat and oil glands make less product, elastin production drops, and glycosaminoglycans are diminished. Older skin is naturally dryer. All this leads to mild, fine wrinkles.
Extrinsic aging occurs on top of intrinsic aging. Exposure to many forms of environmental damage will suffice. Excessive sun, tobacco use, and any number of environmental pollutants will do. Extrinsic aging shows up as thickening of the cornified layer, precancerous changes such as lesions called actinic keratosis, skin cancers, freckles, and upregulated loss of collagen, elastin, and glycosaminoglycans. These processes layered onto intrinsic aging make skin look rougher, with uneven tone, brown patches, thinner skin, and deep wrinkles
With advances in our understanding of senescent cells and the processes they go through, skin senescence is gaining greater understanding. The process that limits the cell division number is termed cellular or replicative senescence. That is thought to be a powerful, albeit imperfect, tumor suppressive mechanism. It is also thought to contribute to organismic aging. Senescent cells undergo three types of changes: they irreversibly arrest growth, they acquire resistance to the natural recycling call apoptosis, and they acquire altered differentiated functions.
It's that "altered differentiated function" that may be the root problem. That's a polite way of saying "They become zombies". The problem with zombies is that they freak out their neighbors. The skin, being such a large organ (#1 in size, competing with our vascular tree) is that when it misbehaves, the rest of the organism is affected. Senescent cells affect the cells around them and convert them into senescent cells. The general principle of aging is to keep cells "quiescent". Like soldiers on parade, dressed with rifles over their shoulders. quiescent cells are dressed up and ready to go. Senescent cells are like soldiers in their barracks, no rifles, wearing only their underwear, deep into a poker game with a beer in their hands, and not paying any attention to the enemy.
How do we affect that? That's the anti-aging rub. David Sinclair's research with metformin and NAD kicked off this idea. Tartary buckwheat is probably next on the list. It has been proven to lower epigenetic age. What we don't have is a direct measured link between skin wrinkles and aging. We just have teaser questions and epidemiology. Vitamin D is so intrinsic to aging, the loss of cholesterol in skin and subsequent loss of Vitamin D production suggests there is some link there. (Your natural D production has dropped some 80% by age 70)
www.What will Work for me. Well, well. It's the end of summer and the end of Vitamin D production. I am sloppy about sun block but I don't seek out sunlight. I don't smoke. But I'm wrinkled. As the famously old French woman, Jeanne Calmet, said, "I only have one wrinkle, and I'm sitting on it." She was very wrinkled, but at least had a sense of humor. I have started adding senolytic therapy to my regimen. Tartary buckwheat is a not topic. My only complaint is the number of pills I take. Oh well, .... I do take my 5,000 IU of D a day. That may be the simplest, most bang for your buck.
References: New Scientist, Scientific American, JBC, Jr Investigative Dermatology, Int Jr Mol Sci,Food Chem, Derm Surg, CNBC,
Pop Quiz
1. How much Vitamin D do you lose with aging? Answer: About 80% by age 70.
2. Why do you lose Vitamin D? Answer: Because we have lost the cholesterol content of our skin, which correlates with wrinkles.
3. What is wrong with a senescent cell? Answer: It acts like a zombie and damages the cell around it.
4. Why is skin senescence such a big problem? Answer: Because our skin is so big, it affects everything underneath. Instead of being a passive marker, it may be a driver of aging.
5. Do we have proof of this idea? Answer: No, it's just a conjecture, based on a lot of physiology that lines up. But an interesting point never the less.
Live Longer with Selenium and CoQ10
This sounds like a little fluff study that doesn't have much relevance. Let me argue that it is quite an important study in that it reveals important principles that are quite interesting. We are looking at one of the core "Hallmarks of Aging", namely telomere shortening. Your telomeres are the DNA sequencing that isn't copied into useable proteins, but which marks the end of the chromosome and from which there is a steady loss off the end with each duplication of DNA. It is as though the DNA duplicating enzyme occupies so much space on the end of telomere DNA template that can't be copied. That explains the Hayflick limit that holds that we can only live through so many generations of divisions of cells.
Confounding that is an enzyme called telomerase that actually lengthens the telomere. Lengthening your telomeres is a hot topic of current aging research and there are many labs around the world doing just that. We do know that stress, emotional, and oxidative can hasten telomere shortening. Throw that whole salad together and look at some of the key mechanisms of calming oxidative stress and see what pops out.
That's what this study is about. Europe, in general, tends to have low selenium intake. Selenium plays a huge role in generating glutathione, your ultimate antioxidant/mitochondrial protector. This study was done in Sweden with 118 folks aged 70-80 low in selenium. They were given CoQ10 (an important mitochondrial agent that helps reduce oxidative stress and selenium, that helps neutralize oxidative stress. The intervention period was 4 years with 10 years follow-up to monitor those who died. Telomere length was measured by PCR before and after the study.
The results were very interesting, and not expected. Those two supplements resulted in less telomere shortening. Those who died, particularly from cardiovascular disease had dramatic telomere shortening. Their conclusion was that preservation of telomere length after selenium and coenzyme Q10 supplementation was associated with statistically significant reduced cardiovascular mortality. With just 118 subjects, statistical significance from the major cause of death in such a small number of subjects is a big deal.
We have talked about NRF-2 activation for having a significant impact on telomere shortening and virtually all the hallmarks of aging. Fahy, in Aging Cell, reported that DHEA, Metformin, and Growth Hormone can lengthen your telomeres. This adds to that body of work. We will continue to refine this idea.
www.What will Work for me. Well, I've measured selenium in some 100+ folks and if you aren't on the supplement, you are likely low if you live in the midwest. Just like Swedes in Sweden. I'm going to kill myself with choking on supplements, but there isn't another way to get selenium and CoQ10. We just make less CoQ10 as we age. Dr Sinatra used CoQ10 15 years ago as the cornerstone of his congestive heart failure program. He was ahead of his time.
References: Nutrients , Biogerontolgy, Aging Cell, Wikipedia, Nat Lib Medicine,
Pop Quiz
1. Why is selenium important for longevity? Answer: We have some 25 "seleno-proteins" that use selenium as their active core. Five of those are involved in making glutathione, your most important internal antioxidant.
2. Why is selenium a problem? Answer. There isn't much selenium in American soils in many areas. Along the Great Lakes is one of them. Most plants don't have much anyway.
3. What percentage of Americans are selenium deficient? Answer: Depends where you live. Along the Great Lakes, it's quite low in our soils. One billion people worldwide are low.
4. CoQ10 does what? Answer: It plays a huge role in making energy in mitochondria. Without sufficient CoQ10, electrons aren't passed on properly and thereby escape, making reactive oxygen species and starting the oxidative stress pathway.
5. Why does the combination of CoQ10 and selenium result in less telomere shortening and longer lifespan? Answer. The whole portfolio of oxidative stress and NRF-2 activation is still shrouded in some mystery. Selenium and CoQ10 are intricately intertwined. Sirtuin proteins are meant to be the guardians of your epigenome. What's their role? Its complexity and interconnectedness is daunting. One of the mysteries to be elucidated with more science. I want to live long enough to see it understood. Stay tuned. When I took Tartary Wheat supplements for 6 months, my epigenetic age dropped 8 years. This is all part of the same puzzle. This is like a 2000-piece, pure white jigsaw puzzle.
What's Your Ageotype?
Ok, I'm not used to manufactured words. Age "o" type is meant to mean there is a typing methodology to how we age. At least, that is the proposal made by Michael Snyder's Genetics team out of Stanford. There is more under the surface.
What this really reveals is the maturing of metabolomics, the methodology Goodenowe pioneered by measuring "everything" in the blood of people as they age. In that process, no one particular item is targeted. Instead, it is accepted that there is a complex interplay between all the items present that changes over time. The key is not one measure but measurements over time with different outcomes revealing themselves by the nature of the changes revealed. This process reverses the methodology of science and medicine. The old-fashioned way, what we deem as traditional medicine, you could call "top-down". You identify an illness or a symptom and study that symptom/illness to identify everything your imagination can find about it. For example, with tuberculosis, we culture the bacteria and find its sensitivity. We take X-rays and CT scans to see what organs may be involved. You are used to all that. That's how the house of medicine "works up" an illness.
Metabolomics is "bottom-up". There is no target and no disease being studied. Everything is being studied. This creates massive databases and requires huge computing power to process. And, at the end of the day, detailed statistical analysis. From that, magic emerges. Patterns not seen by any other method are revealed. Instead of questions looking for an answer, we have answers looking for a question.
What Dr. Snyder did was to take 106 individuals, ages 29 to 75, and follow them longitudinally. Their primary focus was to assess the risk of prediabetes and metabolic syndrome's effect on aging. Despite aging being a huge topic of interest, we really don't know much about how it happens. In this study, subjects were followed between 3-4 years of time with quarterly visits and assessments. Proteomics (every protein measurable), metabolomics on plasma samples, transcriptome analysis on mononuclear cells, targeted cytokine assays using serum, nasal and gut microbiome analysis using 16S rRNA sequencing, exome sequencing (measuring all the circulating messenger RNA), and 51 clinical lab tests were acquired on each visit. There were 18 million data points to analyze. Even in that small time frame, and with that small a group of people aged that far apart....seemingly random and not much in common....some very interesting patterns emerged.
The team found 608 distinct molecules, bacteria, and genes that changed significantly over just four years. Those changes occurred in four distinct patterns associated with four organ systems - kidneys, liver, immune, and "general". Most of the subjects aged along all four pathways, with one predominating. Some had two more dominant. Like an aging car, the whole gets older together but some parts actually wear out faster.
What this really offers are possible new insights into how we address aging. If you are a "kidney ager" you may well benefit from more water. A liver ager would do well to lay off alcohol and Tylenol. A metabolic ager needs to lose weight more urgently than others.
There are probably more patterns and types to be revealed. This may be a valid means of identifying risk, or not. Some of the subjects in this study improved their markers of aging by losing weight, drinking more water, or whatever. Are those efforts statistically valid? Time will tell. It does reveal that bottom-up science is a new field that is revealing a new method of looking at ourselves. As it matures we will find insights we haven't seen before.
www.What will Work for me? Good science starts by asking a question, or a hypothesis, and goes looking for an answer, which always leads to more questions. When you do it "backward" and gather all the answers, you go looking for all the answers and then ask the questions. We will have to learn that "good science always leads to more answers", so what are the questions? What do I need to do for now? I have problematic diabetes genes. That I know. Losing weight and keeping it off is a devil. This test isn't available publically, nor is it mature enough to use in that fashion. Goodenowe, who measured 25,000 items in a cohort of 1,500 aging Catholic clergy discovered plasmalogens with this method. I think more discoveries are waiting in the wings. I'm taking my plasmalogens.
References: Natural Medicine ,
Pop Quiz
1. What is metabolomics? Answer: The measurement of "everything you can find" in someone's blood. The metabolome is what your metabolic processes make.
2. How is the metabolome different from the genome? Answer: Your genome is your genetic code. That's your hard wiring. Your metabolome is what your genes make after being read and interacting with your environment.
3. What is your "exome"? Answer: For another day. That is the reading of all your circulating mRNA carried in exosomes. Your circulating mRNA reflects the DNA that has been activated. You have read about it recently regarding COVID as it has been used to reveal the activity of your COVID response. (Research so far.) You could argue that your exome is halfway between your genome and metabolome.
4. What is your biome? Answer: At 100-1000 times the amount of genetic diversity over you, your biome is all the bacteria living in you. We have recently learned that the biome of your tongue is distinct and tasked with making nitric oxide. Your gut biome is a critical component of your healthy self. When you are full of it, that's a good thing!
5. Can you test for your Age-o-type. Answer: Not yet, and maybe never. Let's watch and wait.
Your PPI Stomach Acid Drug May be Killing You
The PPI class of drugs (proton pump inhibitors) are the main drugs used to treat GERD in America. They are very effective at reducing stomach acid. The pH of your stomach, designed to be pH 2 in order to efficiently digest protein, essentially goes to pH 7 (neutral) and relieves the burning sensation of GERD. They are very popular for that reason. The problem is.....
The biology of making nitric oxide (NO) is dependent on a pH of <3 in the stomach to convert the nitrites in saliva into nitric oxide. When you eat vegetables, you get a dose of natural nitrates which are then concentrated in your saliva. Unique bacteria to the crypts of your tongue convert those nitrates into nitrites. But that's only the first step. The second, essential step is the conversion of nitrites in the saliva into NO, nitric oxide, in the stomach. A normal pH will stop that process cold. Just like mouthwash will completely stop the process.
Several studies have now confirmed the problem. Nitric oxide is critical to the health of your endothelium, the lining of your arteries. It is arguably the largest organ in your body. The health of the endothelium depends on your blood level of nitric oxide. We lose about 12% of nitric oxide per decade, so the aging process is already setting up our arteries to be NO deficient. Without sufficient NO, the endothelium falls apart and more easily ruptures, allowing underlying plaque to be exposed. That sets off platelet aggregation and clotting in the artery, a heart attack.
I believe NO may be the single most important supplement you can take to prevent aging other than plasmalogens. The drawback right now it cost. At $ 80 a month, it's a bit pricey. There will be competitors who make a similarly effective product, so waiting a year may be rational.
What is one to do if they have GERD and can't stand the pain at night? The answer, in my opinion, is to find a way to take BPC-157 pills. BPC is the natural compound found in the human gut to protect us from the naturally caustic effect of stomach acid. Great apes, eating 99% plant material, don't need to digest animal protein and have a stomach pH of 4. Humans prove their meat-eating proclivity by having evolved a stomach pH a hundred times lower. pH 2. That pH of 2 is hard to protect against. We had to also add BPC-157 to heal our gut from the extreme acidity we needed to digest protein properly. It can be ordered from a wide variety of sources off of the internet. Manufacturing peptides is still in its infancy and there is some risk of less-than-pure product. Reputable compounding pharmacies run the nascent peptide through several passes down the gel column. Each pass loses 10% of product but increases purity by 90%.
And you may have intuited another problem with PPI therapy. Yup, you do a miserable job digesting protein and may become protein deficient. It is clear you become B12 deficient as B12 is absorbed with a protein binder made in the same cells that make the acid. Throw in calcium, iron, magnesium, and Vitamin C and PPIs reduction of acid results in a whole raft of deficiencies.
www.What will Work for me? The Peptide Society has BPC-157 as a key ingredient in the anti-aging portfolio. I take it every day. My GERD has virtually disappeared unless I get foolish and overeat a huge curry dinner within an hour of bedtime. If I stop eating 3 hours before bed, I'm good. No PPI for me.
References: Forbes, PLOS One , Ther Adv Drug Safety,
Pop Quiz
1. What do PPIs do? Answer: They stop the production of stomach acid perfectly.
2. Name one unintended consequence! Answer: Dramatic reduction in B12 absorption, for the most obvious and flagrant effect.
3. Name the peptide that can cure your GERD with no side effects. Answer: BPC-157
4. Bonus question. Where was BPC first recovered from? Answer: The human stomach. What was found was actually a larger protein, but the action part is the smaller protein called BPC-157. You can make the argument that BPC-157 isn't exactly neutral.
5. What is the proper functioning pH of the human stomach? Answer: pH 2.0
The REAL Cause of Post-Partum Depression
It was all over the news. CNN, and others, all announcing the discovery of a new drug to treat post-partum depression. Zuranolone has been approved by the FDA to be marketed under the name Zurzuvae. Zuranolone is a positive allosteric modulator of GABA-A receptors. GABA functions as the primary inhibitory neurotransmitter for the central nervous system. It slows down and inhibits neurotransmission. Here's the catch. It will cost around $ 34,000 for treatment for the some 400,000 women who have it each year. That's one in 7 women who have just delivered a baby.
With my curiosity regarding plasmalogens and brain diseases, I have to ask the question, "What is going on around birth that makes a woman so vulnerable to depression? Is there a core mechanism we can get to?" We know from basic biology that every indication is that the fetus gets nutrients first. Mom is just the passive entity that is donating all those good things to the developing fetus. Iron, folate, protein, etc etc...and plasmalogens to the newborn. We also know that a fetus has virtually no myelination of their brain until about the 37th-38th week. Then, it starts myelinating nerve fibers (axons) and that then activates neurons as they sense incipient nerve conduction. You can witness it for yourself. A newborn baby won't make eye contact at birth. It can't. Its neurons aren't myelinated yet. They aren't sending any messages. Brain speed, measured in a brand-new baby comes out at 2 meters/second. A mature adult human measures 100 meters a second. That's a fifty-fold increase in speed. Speed is dependent and the numbers of plasmalogen dominant (70%) layers of myelin. A newborn baby has the massive task of myelinating all of its neurons as fast as it can go. Where does it get all that myelin from?
Mothers' breast milk turns out to be the highest food source of myelin precursors from which the baby can then make myelin for itself, and get its brain up and running. Yup, mothers' milk is number one. Cow milk? Zip. Zero. Nadda. Formula, also a big zero. At the time of birth, a newborn needs plasmalogen precursors in abundance. Lots and lots.
Here's the rub. Humans can only make plasmalogens slowly. Everything has to be just perfect to make enough for Mom. What happens if she can't make enough? Well, you borrow from Peter to pay Paul...or from Alice to pay Alisha.
Do we have any proof of that? Well, yes, we do. Type in for yourself "Post Partum Depression, MRI scan brain, diffusion defects." You will find multiple articles that all say much of the same. There are measurably damaged tracts of white matter in the brains of post-partum mothers. White matter is myelin. Their myelin appears depleted. It's certainly damaged.
We know that white matter damage is what is going in in MS, ADHD, autism, migraine....and now we add post-partum depression? Would that make sense?
Of course, it makes sense. The hypothesis, (completely unproven yet) is that at birth there is a huge demand for brain development and growth that rests precisely on plasmalogen supply. The largest (and actually only) reservoir of plasmalogens is in membranes, most notably the brain. We also know that as a general rule, baby comes first and mom is just "chopped liver". That's how nature works. The ultimate value of passing on that DNA and next-generation gets priority. Mothers' breast milk has about 30 mg/kg of plasmalogen building blocks. Is the baby robbing mom's brain of plasmalogens? That is what has not been proven, but that is what those abnormal MRIs suggest. There certainly is observable damage that looks just like the damage in major depression. Can we supply plasmalogens back? Well, yes. They are easily supplemented.
We also know that children with the most breastfeeding don't get the horrible, dreaded RDCP until they stop breastfeeding, including if they are breastfed until age 5. We know ADHD/autism kids have the exact same white matter MRI defects as postpartum mothers. We also have compelling hints that they get better with plasmalogen supplementation.
That's what the product Prodome Glia is. It is mother's milk in a pill. It is the plasmalogen precursor, what's in women's breast milk, with an extra tweak to allow it to survive gut digestion and show up in the blood. It is exactly what's missing in those conditions with white matter changes. Now we see the MRI data showing it's there in postpartum depression too.
Finally, we also know that kids with MRIs of their brains showing healthy, properly structured white matter tracts do better in school, and are more socialized and developmentally stable. We all need more plasmalogens. And Mom is the one left holding the bag. No wonder her brain is screaming for help.
Do we need to wait for randomized, placebo-controlled trials to prove it? Well, yes. That will take 10 years. And guess how enthusiastic organized medicine will be to do it? (Hint, no profit at $ 300 total per mother). It will likely not happen soon. The ethics of trying it without an RCT revolve around whether there is any risk of harm. To that the reply is, "How dangerous is mother's breast milk?" No, there is no risk or possible harm.
www.What will Work for me? Prodrome Glia is just that, the building block for the white matter tracts. If I had postpartum depression, I would be taking it by the handful. And even more so if I was choosing to breastfeed. In fact, I'm predicting that 10 years from now, it will be given to every mother starting 3 months before delivery so that she never gets post-partum depression and her baby never gets autism/ADHD. Total cost per mother would be roughly $ 300 total, and then add in some other vitamins and fish oil. Way, way, way less than $ 34,000 for a drug that has to be given IV.
That, to me, is the real cause of postpartum depression: the cannibalizing of Mom's brain to start baby's brain just right. Baby thrives. Mom tanks. An artificial GABA stimulator doesn't get to the root cause.
References: Neuropsychopharmacology, CNN, Washington Post, Behavioral Neurology, JMRI, Human Brain Map,
Pop Quiz
1. What does zuranolone do? Answer: It is a novel neurotransmitter that is a novel modulator of the GABA receptor in the brain.
2. Its cost is? Answer: $ 34,000 per person, and we haven't added up the side effects that may show with wider use.
3. What are the effects seen in the brain on MRI with folks experiencing major depression? Answer: Diffusion defects of white matter tracts signifying plasmalogen loss and inflammation.
4. How does post-partum depression relate to major depression on MRI? Answer: Identical
5. How can one repair the damage of major depression/autism/ADHD? Answer: Plasmalogen supplementation is the emerging answer.
Sugar Changes Your Gut Biome - And Makes You Fat
I bet you have never heard of microbiota-induced or commensal Th17 cells. Well, you should know about them because they are what you are fighting over in your struggle to not be fat. It's not simple, but the evidence is there. Here is the story.
Your microbiome is a complicated system with at least 100 to possibly 1,000 times the DNA of your own genome. That's if we have a healthy biome in our colon. There is constant cross-talk between your gut, immune system, and brain. All are interdependent on each other. Scientists have now found a separate class of white blood cells called commensal Th17 cells that do some very interesting work. Commensal gut bacteria are those that live alongside the gut lining and do not initiate disease under normal conditions. There they "show" antigens that can be detected by the organism’s immune system and give rise to commensal-specific lymphocytes. When that goes awry, you get the rise of autoimmune diseases. The T cells that are made start in the thymus gland, but their generation of commensal T cells is dependent on the type of commensal microorganism present in the gut. Scientists have now found that segmented filamentous bacteria are particularly good at stimulating them. The study of those segmented filamentous bacteria is all the cutting edge of biome research right now.
What happens when you eat sugar? Aha, there's the rub. A high-fat, high-sugar diet (think donuts, ice cream...) promotes metabolic disease by depleting those commensal Th17-inducing microbes. When they come back the commensal Th17 cells restored protection. Microbiome-induced Th17 cells provide protection by controlling lipid absorption across intestinal gut lining in an IL-17-dependent manner. The number of commensal Th-17 cells defines the absorption of fat, inversely. You want lots of Th-17 cells. Much less fat absorption. Sugar depletes them. And fat goes into the circulation to be added to your hips. That simple.
Table sugar, notably fructose, is not that great a friend. It is easy to show that fructose starts metabolic syndrome by overwhelming the liver, driving uric acid up, NAD down, and fatty liver to develop. Now we know that fructose adds to its Darth Vader reputation by knocking off those beneficial commensal Th17 cells.
www.What will Work for me. You get a modest amount of fructose in fruit. It becomes concentrated when to throw out the fiber and make it into fruit juice. The average American is eating 10-12% of their calories in the form of sugar. Any food in a package likely has some sugar added to it. Ultra-processed foods (more than 5 ingredients some of which you can't recognize, can't buy in the grocery store) almost always have sugar in some fake name form or another. Carob syrup or maltodextrin caught my eye this week. Yup,both on the sugar list.
References: Cell, J Inflam Research, Frontiers Microbiology, 56 Names for Sugar, Nutrients,
Pop Quiz
1. What's the name for the white blood cells that appear to block the absorption of fat, if they are living in a health gut? Answer: Commensal Th17 cells
2. They have a conversation back and forth between themselves and what type of bacteria in the gut? Answer: Segmented filamentous bacteria
3. What does sugar do to his equation? Answer: A dramatic loss of the Commensal Th17 cells.
4. What happens when you stop eating sugar? Answer: The Th17 cells reappear.
5. Taking probiotics will make up for my eating a donut? T or F. Answer: Ha Ha.
Good Hydration May Be a Longevity Key
You are likely sick of ads for electrolyte drinks, filled with sugars, for rehydrating yourself. Beautiful/handsome sweaty young athletes swilling down bottles of sugar water, made from high fructose corn syrup and a shake of salt just don't do it for me. I tend to turn off to those ads.
The concept of hydration though, is interesting. The core idea is that every membrane in your body has to move various nutrients across the membrane against a gradient of some sort. For example, sodium is the most common electrolyte in your blood. It should be at 135-140. Inside the cell, it is around 5. Potassium is the reverse. It is only 3.5-4.5 in the blood, but 140-150 inside most cells. That makes potassium in the blood only 2% of your body's total. Those gradients take energy to maintain.
When you are dehydrated, the amount of energy it takes to maintain those gradients becomes greater. It's not just the electrolytes that matter. You have to excrete all sorts of end products of metabolism, (cellular garbage), and it you make the gradient higher for that excretion, your cells start living with a bit more garbage. Makes sense that you get into trouble for that.
The difficulty comes in studying that concept. It's a devil to pin down which of 100,000 breakdown products of metabolism you need to study when the difference between good and bad is just a few milliequivalents.
So, this week's study from the Lancet decided to just look at sodium in folks being followed for 25 years in the Atherosclerosis Risk in Communities study. They had 15,752 middle aged people with 25 years of follow-up. Good, solid, big study.
What they found was that those with a sodium >142 mmol/l were associated with a 39% increased risk to develop chronic diseases, and >144 mmol/l with 21% elevated risk of premature mortality. People with serum sodium >142 mmol/l had up to 50% higher odds to be older than their chronological age. A higher biological age was associated with a 70% increased risk of chronic diseases and a 59% increased premature mortality. Goodness. Those are big numbers.
We don't know whether the chicken or the egg comes first. Can we reverse it with an intervention of hydration? Can we get your sodium down below 142 meq? Will that result in us living longer? Did the disease we already have come first? We have always brushed off the sodium level as "within normal limits" if it was 145. This brings a whole new field of scrutiny to bear.
Can we rehydrate ourselves? Well yes, but it's hard to drink and hang onto water if you drink just plain water. What happens if you add a wee bit of flavor to it? And some electrolytes? Still don't hang onto the fluids very well. So, let's sit down 72 young men with no medical problems and give them 1 liter of 13 different fluids. Guess which one comes out on top for retaining the most fluid? Milk! Cola, diet cola, hot tea, iced tea, coffee, lager, orange juice, sparkling water, and sports drinks were no different than water. Dioralyte from Sanofi was almost as good as milk. Skim milk was as good as full fat. Hmm.
A tiny bit of protein appears to add a rehydration benefit. Glutamine and alanine are the amino acids that dissolve the easiest. The explosion of commercial products with a few amino acids in them is beyond description. It's hard to find the actual science for all the "Sponsored Content" on Google.
Dr. Seeds, of the International Peptide Society, might be the most forward-looking body to craft scientifically based methods of cellular health. Here is their formula.
Here’s a quick and easy recipe:
1. Fill a half-gallon or gallon jug, over-sized water bottle, or other large container with purified water.
2. Then add:
o One Scoop of each of these four amino acids to create the best synergistic effect:
L-glycine -3 grams
L-Glutamine- 5 grams (slowly increase over a few weeks to 15-20 grams)
L-alanine -4 grams
Creatine- 5 grams (made up of methionine, arginine, and glycine)
3. A shot (¼ cup) of coconut water ( coconut water is a great, sweet-tasting electrolyte without added sugar!)
4. A squeeze of lemon for taste
www.What will Work for me? Well, I just bought all four of those amino acids off of Bulk Supplements.com where you can get 250 grams of any amino acid for a reasonable cost. I don't want to add any sugar with fructose in it so I added a touch of Trehalose, a molecule made of two glucose hooked together with an unusual link, so it digests much slower. It ends up making glucose, which your body can use as energy, just much slower. And it's sweet. The drink didn't taste too bad. I'm going to give it a try on my biking.
References:Lancet, Kidney Disease, Amer Jr Clin Nutr., IOP Science.
Pop Quiz
1. Drinking extra water helps you live longer. T or F. Answer. False. Water by itself doesn't seem to do it
2. What is the best liquid to help you hang onto total water. Answer. Milk, or many water with some extra amino acids.
3. If my serum sodium is above what number, should I be concerned about risk for chronic disease? Answer: 142
4. Why should I be concerned? Answer. When you're dry, every single cell in your body has to work harder to maintain itself. Death by a thousand cut
5. Where can I find a good commercial rehydration formula? Answer: Spare me. There are thousands of them. Be picky and find one you like. Avoid fructose. Make sure there are some amino acids in them. Or drink skim milk.