Does Your Home's Plumbing and Your Vitamin Pill Cause Alzheimer's

Does Your Plumbing and Your Vitamin Pill Cause Alzheimer's?

In America, 30% of folks show cognitive decline in their 80s. Did you know that in rural India the incidence is 1.07% for those over age 65?   In Nigeria, the rate is 0.52% for those aged 75-84. That's fact 1.

Fact 2 is that Alzheimer's is a recent disease. It was not described prior to World War 2 despite there being multiple, reputable, rigorous reviews of brain pathology. For example, William Osler, the founder of Johns Hopkins, the originator of residency specialty training, the author of the first textbook of medicine, did not describe Alzheimer's. Freud didn't describe it. Boyd, a famous brain pathologist who published a textbook of brain pathology as late as 1938 didn't describe it. And there were plenty of old folks who should have been sufficient to have the disease noticed prior to World War II.

What is your conclusion from these two facts? Alzheimer's is a new disease, not a given of human biology. And it happens in some, but not all advanced societies. We are doing this to ourselves. What are we doing? Read on.

What happened in World War II? We developed a massive copper industry to fuel the manufacturing of bullets and shells. Copper was so cheap after WWII that houses had their roofs sheathed in copper sheeting. The industry was desperate to stay alive, and thus it innovated and made copper tubing. Pipes for homes. In just a decade, the entire home building industry shifted from iron pipes to copper pipes. Your home likely has copper plumbing.

A home with copper pipes will shed about 0.1 ppm of divalent copper. Cu-2. The EPA claims that 1.3 ppm is safe. That is a 10-fold margin of safety. But is it safe? A famous study of rabbits showed that pure drinking water results in no amyloid plaque in the rabbits’ brains. But add in .1 ppm Cu-2 and bingo, plaque and memory problems. So, no, 0.1 ppm of Cu-2 is not safe.

The problem comes down to some simple chemistry. There is a huge difference between the copper in your body, Cu-1 (chemically +1) versus what comes off the pipe in your home, Cu-2 (chemically +2). In mammalian intestines, there is a Cu-1 receptor. Biological copper is always, always, Cu-1. Period. That copper is absorbed and carefully processed in the liver. There is no Cu-2 receptor. That copper does not exist in normal biological systems. That copper goes directly into your blood and causes all sorts of havoc. It is unregulated by your biological control systems. You can prove all that by using radioactive Cu-1 or Cu-2 and see where it goes. It's easy to prove. Cu-2 shows up immediately in your blood. Cu-1 takes days to show up, and is then bound to carrier proteins.

Copper is an incredibly important trace mineral. It is extremely bioactive. It plays a pivotal role in protecting our bodies from redox reactions, helping neutralize peroxide made from escaped electrons in the mitochondrial electron transport chain. It is so bioactive that it's management is tightly regulated. And that regulation depends on you ingesting Copper-1. Not copper-2. That's it. That's the problem. In a study of 280 random homes in America, 30% of the homes had Cu-2 levels above 0.1 ppm, the level that causes damage in animals. 

The Japanese have a low rate of Alzheimer's. Only 6.7%. After WWII, they were offered copper pipes to rebuild all their bombed-out homes. They politely declined, claiming it had not been studied. They use iron pipes. 6.7% versus 30%. Hmmm. What do you read from that?

We now know the precise site of trouble. Amyloid precursor protein tries to get rid of Cu-2 and reduce it down to Cu-1. It does that. But it makes a free oxygen radical is so doing. That goes out and causes damage. And it makes Beta-amyloid accumulate. Throw in diabetes and too much glucose, and you get glycation. Add Cu-2 with glycation and it just explodes with more free radicals and beta-amyloid formation.   That's the diabetes, Alzheimer's link with copper.

With the explosion of free radicals, we deplete our plasmalogens. Our synapses start disappearing because we can't protect ourselves from the oxidizing damage of Cu-2. And we use up our plasmalogens at our peril.

The good news is that we can fix all this. What a mess we have made of our biochemistry.

www.What will Work for me. Every home in America from 1950-2010 was built with copper pipes. My 1978 home has copper pipes. Every vitamin pill and mineral supplement has Cu-2 in it. I am taking poison what I take a routine vitamin pill and drink it down with tap water. And that is something I can do something about. I now understand the chemistry right down to the molecules on the membranes of my cells. In my brain, Cu-2 is poison. It never existed in human history in our ecosystem until we made copper pipes and devised copper-containing supplements. I will be reading every supplement I ever take hereafter. And I will be measuring my copper and zinc levels twice a year. I am so happy I bought a RO water system from my drinking water. And to demonstrate my OCD, I even now distill my own water. It's cheaper than buying it from the grocery store.

References: Exp Biol and Med., Neurology, Am J Psych, PNAS, Stroke,J Biol Chem, J Biol Chem, Biochemistry, Biofactors

Pop Quiz

1. Copper is a necessary trace mineral. What form does it exist in nature?               Answer: It's called copper-1 and has a +1 electrical charge.

2. What copper ion comes out of our copper pipes?                             Answer: Copper-2 that has a +2 charge.

3. What level of Cu-2 is safe according to the EPA?                               Answer: 1.3 ppm

4. What level of Cu-2 comes out of 30% of American homes' pipes?                     Answer: Higher than 0.1

5. What happens to animals when they ingest 0.1 ppm Cu-2?                            Answer: they get amyloid plaques and memory problems. Just like humans

6. In natural systems, there are biological proteins to carry copper. What type of copper can they absorb?                                 Answer: Cu-1 only. No impact on Cu-2

7. How often should we check our Zinc-Copper levels?                          Twice a year. And please, please, please examine your vitamin pills and stop taking any that have copper in them.  Vitamin pills always have Cu-2 only.

8. What form of copper is in your vitamin pill?                      Answer: Cu-2. Oops. Poison.

This column was written by Dr John E Whitcomb, MD, Brookfield Longevity, Brookfield WI.

Benign Incidentalomas of the Adrenals are Common and Cause Trouble

"Benign" Incidental Tumors on Adrenal Glands are Common

This is a hugely important study that may go a very long way to explaining puzzling conundrums in menopausal women. Most notably, "Why can't I lose weight?" or "Why do I have high blood pressure suddenly out of the blue?". You may have never heard of an "adrenal incidentalomas" but it is what its name sounds like: an incidental nodule or "mass" on the adrenal gland, found, by chance with a CT or MRI of the abdomen that includes the adrenal glands. As CT and MRI scanning has become more widespread, more of these incidental adenomas (lumps) have been found. A surprising number of them (2/3rds) appear to be in post-menopausal women.

It's the link to MACS (Mild Autonomous Cortisol Secretion) that was the impetus to this study. Cushing's Disease is most commonly caused by a "benign" tumor that excretes unregulated cortisol. Those folks show a classic picture of high blood pressure, weight gain, stretch marks, buffalo humps on their backs, and muscle weakness: all effects of too much cortisol. The question to be answered was whether there is a continuum of this archetype disease to a milder form, MACS, associated with these incidental "swellings" that hadn't become a defined mass or tumor.

They found 1305 of incidentaloma patients and evaluated them for MACS and sure enough, there was a very strong association between the tumors and the cortisol, particularly if the women had resistant diabetes needing insulin and high blood pressure needing extra medications.

In fact, the numbers were striking. In Great Britain alone, the results of this study suggested that some 1.3 million women might be affected. This becomes one of the first considerations to review if post-menopausal women have high blood pressure and diabetes. Added to their evaluation should now be a screening for MACS which essentially comes down to collecting a 24 hour urine for adrenal steroids. So, it is a continuum with Cushing's. There is a milder form. And the "milder" form may not be so benign or mild.

What has yet to be determined is whether these women all need CT/MRI's of their adrenal glands. We need clear guidelines as to what are acceptable limits of cortisol production on 24 hour urine tests. A lot of health care system training is in order.

Cushing’s disease gets severe osteoporosis. Does MACS? Yes! Do we need to checkevery woman with osteoporosis? That same thread is going to now arise with diabetes, high blood pressure, sarcopenia, weight gain.......on and on. This is a seismic shift. Huge advance. Good work, team!

WWW.What will work for me? It's not often that a major shift in disease management comes along. This is one. My ears are burning with memories of women who I have seen who have asked the question, "Might I have Cushing's?" and on standard testing, they fell through the cracks. Now we have new criteria and a new "syndrome", a complex of tests to explain. Once again, the "patient" was right. Fortunately, someone in Great Britain paid attention. It just has to be part of our workup in standard internal medicine.

References: Science Daily, Annals of Internal Medicine Jan 22,Jr Clin Endo Metab, Endocrine Connections,

Pop Quiz

1. MACS stands for what?                     Answer: Mild autonomous cortisol secretion.

2. Where is it found?                      Answer: For now, it is found in post-menopausal women who have high blood pressure and or diabetes which are slightly treatment-resistant.

3. How common is this?                      Answer: In women in Great Britain, the guestimate is 1.3 million women (2% at age 50 rising to 10% at age 70). That would translate into 8 million + women in the USA. A lot.

4. What are other symptoms that might be part of the syndrome? (Think what symptoms go along with Cushing's disease?).                     Answer: Osteoporosis, stubborn obesity particularly in the core body, sarcopenia, besides the resistant high glucose and blood pressure.

5. How do we diagnose MACS?                         Answer: A one-time cortisol won't define it. We will have to get 24-hour urine collections to see the totality of cortisol production, and then be more open to further testing with more nuanced parameters for the rest of the testing.

6. What's the treatment?                       Answer: Surgery to remove it? Yet to be determined. We don't know what is the chicken and what is the egg. What caused it? Can that be reversed? Are their effective, non-toxic drugs? Will lifestyle changes work?

Written by Dr. John Whitcomb, MD at Brookfield Longevity, Brookfield, Wisconsin

Monolaurin Prevents COVID Mortality

COVID Metabolomics Finds Monolaurin as a Predictor of Mortality

We have referenced this before, metabolomics, and here it is again around COVID. It becomes more important to understand. With Omicron surging at 5-7 times infectivity rate, you may want to pay attention to this idea.

What is metabolomics? It is the study of everything in your "metabolome", or everything that your genes make in your blood. Your genome is the genes you have inherited. Your metabolome is the result of those genes in the environment you are living. When you activate genes, your DNA makes messenger RNA to manufacture new proteins. That you know. Your messenger RNA gets sent out all over your body in exosomes and to adjacent cells via pores so that individual cells communicate with their near neighbors and with distant cells. That makes for a coordinated, system-wide response to environmental challenges.

This method of science is actually a reversal of the usual method for studying disease. Instead of looking at COVID patients the old-fashioned way, trying one treatment after another based on prior experience, metabolomics looks at many patients with COVID and measures everything in their blood. Everything. Like the human genome project that measures every gene, and then looks at what genes are associated with what illnesses, metabolomics looks at every molecule made and present in the blood that represent a successful response to any given illness.

In this case, the illness being examined was COVID. In Italy, 51 health care workers at high risk for getting COVID had their blood examined by this method. As reported in Nature Magazine, health care workers are at high risk for developing COVID. They are real heroes. And in fact, of the 51, half-developed COVID within the month. This was at the beginning of the pandemic, prior to adequate PPE when everyone was scrambling, trying to discover just what it was that put folks at risk, and how to properly protect our precious health care workers.

Metabolomics is not an easy or inexpensive method. You aren't performing a "Chem 12", the standard blood test looking at traditional risk measures. A metabolomics test is essentially a "Chem 25,000", measuring everything in the blood. That takes huge computing power, and more importantly, it takes a lot of exploration to figure out what all those compounds are in the blood. This is the same process Goodenowe did in his cohort from Rush-Presbyterian with aging Catholic clergy. That takes time. The investigators found 322 "small molecules" that they went to work on to see what was helpful. (This did not look at much larger proteins, antibodies, and other complex compounds.)

But what popped out was monolaurin. Monolaurin is basically a product of coconut oil. It is known for having antiviral effects, but even WEB MD states that it "needs further study". Monolaurin blood levels were highly correlated in these health care workers with not getting sick from COVID. It is known to "dissolve" the viral membrane of viruses very effectively. N,N dimethylglycine, an amino acid, also popped out. Finally, higher levels of cholesterol appeared as a risk factor. This correlates with statins that also appear to be partially protective against COVID.

This study is the first to show the scientific process of metabolomics on COVID. It adds to a recent report in MedRxIV from Englandfollowing some 327,000 folks that people taking probiotics, Vitamin D, fish oil and multivitamins, did better against COVID. Now we can add monolaurin or just straight-up coconut oil. In fact, the authors suggest that the use of topical coconut oil may also confer some benefit.

www.What will Work for me? With the looming threat of a third wave of COVID, we are all a bit off balance. I am. I'm vaccinated three times and I wear a mask everywhere I go. But adding coconut oil to my regular cooking is pretty easy. I can order monolaurin as a supplement, and in fact, just did. I can take one more pill for a couple of months without choking to death from too many pills. I do have a small nostalgic moment for my childhood in India where, in my teenage desire to look cool like Americans, I greased my hair with coconut oil. Made my glasses fall down as is melted down behind my ears. I have no photos from the 60s with my glasses up. But at least my hair looked like Elvis...well, vaguely.

References: Nature, Jr Food Safety, MedRxIV, Med MD

Pop Quiz

1. What is monolaurin?                     Answer: part of coconut oil. It is basically a 12 carbon fatty acid attached to glycerol. Humans store energy as 16 carbon fatty acids.  It's in the medium chain fatty acid family, which may explain why it "dissolves" viral coat membranes.

2. What is my metabolome?                  Answer: the sum of all the products your body makes that is floating around in your blood outside of your cells.

3. How can you test it?                            Answer: If you read the paper in Nature, they took a mass spectrometer to find every product they could in 51 health care workers and ended up with 322 "small particles". It would have taken far longer to explore larger proteins, peptides, and hormones. But is there a blood test for monolaurin? No.

4. What else was associated with better survival with COVID?                                       Answer: N,N dimethyl glycine, an amino acid and lower cholesterol. (Those topics will have to wait for another day.)

5. Are there other supplements proven by population studies you can take that help COVID survival?                                  Answer: Yes. A review of 327,000+ British folks showed that Vitamin D, probiotics, omega-3 fats, and multivitamins all were associated with better survival. Sounds like a pretty good handbook.

Heterochronic Parabiosis, a Path into Exosomes

Heterochronic Parabiosis - It's Longevity Right in Your Blood

If I were to tell you that I could take an old mouse and make it suddenly perform like a much younger mouse by exchanging half its blood with a young mouse, you would raise an eyebrow. And if I showed you the data that you could prove increased muscle repair, better hippocampal stem cells, and reduced fatty liver (all the standardized examples of more youthful tissue) you would probably sit up and pay attention. Welcome to the concept of "heterochronic parabiosis". Yup. Take out the old blood and put in the new, and those mice look younger by any measure you can come up with.

The experiments have actually been a bit more complicated than that. Open up cloned old and young mice and stitch together two veins so they are constantly interchanging their blood. Then, observe how the older mice becomes younger, and the younger, older. Heterochronic parabiosis. Blood swapping.

That means there is something in the blood that is making them older. What is it?

The first insight came from a research project at Harvard by Kenyon back in the 90 where she found just one gene in roundworms, that when altered, doubled their lifespan. That was cool. The idea was hatched that aging is programmed into our genes.

Now, the experiments have now gone further. Conboy has shown that in cell culture you can identify two systems that can replicate the same process: TGF-beta which activates ALK5/pSmad and goes up with age, and oxytocin which activates MAPK and diminishes with age. From the same lab at Stanford, Villeda showed that brain learning gets better too. That caused lots of excitement and motivated multiple other labs to confirm those findings. The race was on. What was it?

Next step: take out half the blood from an old mouse and replace it with saline and 5% albumin. Same effect. No transfusion reactions between competing immune systems. Its something smaller than visible red cells.

What is smaller that carries all that effect. Exosomes. Let's introduce exosomes and basic cell biology. Exosomes are one of the hottest topics on the longevity market right now. What are exosomes? Every cell in your body, when exposed to some environmental stimulus responds by activating some new DNA. That makes messenger RNA. Many copies. All cells are connected to the tissue around them, and that mRNA gets transported across the pores connecting the cells. And some of it is exported into the blood in tiny, tiny vesicles called exosomes. Exosomes are about the size of LDL particles. Tiny. And there are millions of them in every milliliter of your blood. Wikipedia has a nice intro article that is quite up to date. Your blood is filled with mRNA, instructing you as a whole being, to respond to that stimuli in a structured, coordinated fashion through exosomes. That's what is hidden in your blood that is coded to make you older, or younger. You can react to malaria, sepsis, trauma by messaging all over with those exosomes. And they can make you "younger" or "older".

The implications for aging and longevity is interesting and significant. Our biology is destined for senescence. We pass on our genes and then fall apart in a structured fashion. We are programmed to get out of the way so that the next generation can have a go at it. The exosomes in our blood are passing out "nasty" signals. "Get white hair". "Get arthritis". "Lose muscle". "Lose brain." We are beginning to be able to read that code in our exosomes, the code of our DNA being spread out over all our bodies and exemplified in that circulating mRNA. The crude stitching together of two mice has opened quite a door. If we get it right, we can understand how to actually reverse that structured falling apart.......

www.What will Work for me. This exosome idea is probably going to be the next frontier in anti-senescent work. It is my belief that heterochronic parabiosis is a crude way with relevant results of revealing the power of exosomes. We can repair your membranes and make a safer environment for your cells by managing your plasmalogens. That story is still playing out. Now, how do we manage your exosomes? Stay tuned. I'm very interested.

References: Aging - Conboy, Harvard Review, Aging - Medhipour and Conboy, Conboy and Medhipour in Aging, Nature Medicine, Wikipedia

Pop Quiz

1. What is heterochronic parabiosis?                           Answer: Fancy name for sharing blood between two animals that have been stitched together like Siamese twins - of different ages but with identical genetic make up.

2. What role does in play in the history of medicine?                            Answer: It has carried the torch of that idea that aging is not inevitable, but rather programmed into our biology.

3. What are the implications of this programming?                      Answer: If it's programmed in, we can program it out.

4. What are exosomes?                              Answer: Ah, that is what has been causing the effect of heterotropic parabiosis. Tiny, LDL-sized, vesicles carrying messenger RNA to instruct your body to behave in various fashions.

5. Can I make myself younger by getting exosome infusions?                         Answer: I'm going to find out.....and if it's feasible, we will be doing it. This is way too interesting.

L-theanine and the Curious Longevity of the Japanese

L-theanine and the Curious Longevity of the Japanese

The Japanese live longer than any other G7 nation. In part, that is because of lower rates of obesity. They have less heart disease, prostate, and breast cancer. They eat more fish and seaweed (iodine). And they drink green tea. As they immigrate to America, those differences go away in proportion to their maintaining their Japanese lifestyle and diet.

Ah, Green tea! What makes green tea different from other teas is the amount of L-theanine. L-theanine is a non-essential amino acid that plays a role in producing many beneficial neurotransmitters. And green tea has been found to be inversely correlated with Japanese cardiovascular disease and mortality. In fact, the more they drink, the longer they live. One cup a day has detectable differences, but five cups a day is proportionately better.

There is a lot written about the effects of green tea and its L-theanine. It appears to reduce anxiety and helps mellow you out. There is pretty good evidence that it tips the balance to beneficial neurotransmitters in your brain. That helps you get to sleep, and sleep a little longer. We know that longer sleep is associated with better brain health as it gives you more time for your brain to be flushed out of its accumulated toxins.

We also know that brain volume and size correlates with all-cause mortality. We want a healthy, large brain. As a general rule, we all have a gradually shrinking brain for which the loss of 50,000 neurons a day is the butt of Saturday Nite Live comedy. But that loss is not inevitable. It is a problem of brain chemistry.

Might there be another solution? With the advent of knowledge of plasmalogens, we know that plasmalogens are the antioxidant of first resort in your cells. They have a vinyl-ether bond right on the surface of the cell membrane. That chemical structure is what soaks up and neutralizes peroxide. Peroxide is the chemical a stressed-out, dying cell releases as it frantically tries to balance its overburdened, broken, internal energy systems. It's the sign that the NAD+/NADH ratio is all out of whack. That peroxide gets excreted and damages other cells around it. One zombie cell damages other cells around it. Your immune system can identify those damaged cells by "lipid peroxidation" on the surface. That's a polite way of saying they have used up all their plasmalogen protection and can't protect themselves anymore. They have used up their plasmalogens and peroxide is tagging the lipids as "damaged". Your immune cells than kill off that zombie cell, quickly before it damages too much else.

What does green tea do to that formula? The antioxidant quality of l-theanine has been shown to be able to neutralize 0.4 ppm peroxide. This allows your cells to not deplete their plasmalogens. Over time, that contributes to your brain not shrinking. Plasmalogens make up some 70% of your axons and synapses, so you have quite a reservoir, but not an endless one. Gradually shrinkage over decades sounds normal. It's not. Shrinkage correlates with death. And we are back to the formula, large brain = long life. Maintaining brain volume is maintaining lifespan.

www. What will Work for me? Goodness, gracious. I like drinking hot liquids as something to sip on while I work. Green tea is easy to substitute. And 200 mg of L-theanine at bedtime. That's easy too. I had seen the evidence before of Japanese having less cancer while living in Japan and I knew about their longevity. Now, the link to green tea and the connection to plasmalogens fits and makes good sense. I look back on a trip to China I made 10 years ago and was lectured by a "professor of tea-ology" about the benefits of green tea. He was right. Pompous, and taken with himself, but right.

References: Feel, Prevention Watch, Pharmcogn Mag, Ann Epidemiology, Jr Polish Biochem Society, Researchgate,

Pop Quiz

1. What is the key difference between green and black tea?                          Answer: L-theanine

2. There are different kinds of green tea. Is any one particularly better?                Answer: well, matcha green tea is shaded prior to harvest. That makes for more L-theanine. (Quite a lot more-so make guide your choices.)

3. What does green tea do to my sleep?                           Answer: It probably will help a little by calming you and producing beneficial neurotransmitters.

4. And how does it help me live longer?                      Answer: This is hypothesis so far, without clear proof, though all the elements are in order. It has potent antioxidant qualities and is shown to help preserve plasmalogens. Loss of plasmalogens has been shown to be the pathway to brain shrinkage and earlier mortality.

5. How much green tea should I drink?                             Answer: Some. More is better. The Japanese who drink 5 cups a day showed proportionately higher benefits.

Phosphatidylcholine Prevents Diabetes

Phosphatidylcholine Prevents Diabetes

You have no idea what cognitive dissonance this study evokes! This might be a whole new field of inquiry opening up, or it may be sloppy research and bad statistics. The Finns have done pretty impressive, evidence-based medicine in their research. For being a country off on the edge of Europe, they are "researching above their weight" and turning out ideas that end up being right, though never previously investigated. Example: their investigational work on saunas.

This might be another. The Kuopio Heart Disease Study, done in the city of Kuopio, tucked in close to Russia, was designed to look at the risks of heart disease. 2332 men, ages 42-60, were followed for 19 years. Of that cohort, 432 developed Type II diabetes based on the standard criteria. Food surveys were done by doing a 4-day precise measurement of food intake. What leaped out of the statistical results was phosphatidylcholine intake and Type II diabetes. And it was no small difference. In measure quartiles of intake, those with the highest intake had a 41% lower risk of developing diabetes. This becomes the number one risk factor for diabetes. That's huge! We should be rushing out ......

Just what is phosphatidylcholine, if you can even pronounce it? IT makes up a huge proportion of biological membranes. It is the precursor template for making plasmalogens. Plasmalogens are 70% of the membranes in nerve axons and synapses. Animals central nervous systems could not have evolved without the biological features of plasmalogens. And maybe just as importantly, they constitute the majority of the membranes inside your mitochondria and other intracellular organelles. They are the backbone of allowing your cellular machinery to run.

What is the cognitive conflict? Ah! Here's the rub. Choline is found in most animal products like meat and dairy and particularly in eggs and liver. These are all high on lists of "heart disease problem foods." But choline also plays an important role in our core biology as a methyl donor, a precursor for neurotransmitter acetylcholine and a component of plasmalogens. But, choline has been fingered as a major dietary precursor for gut microbiome-derived trimethylamine, which is converted in liver to trimethylamine N-oxide (TMAO). Elevated TMAO is being thought to be the new, most accurate predictor for cardiovascular disease, kidney disease and mortality, and........ for type 2 diabetes. 

You can't have it both ways. One study says it reduces diabetes, the other says it increases. What's an egg-eater to do? (Eggs being one of the best sources of choline).

Here is my hunch and see if I can coax you along with it. The "cholesterol" theory of heart disease is broken. It does not predict who gets sick accurately enough. We know too many farmers who have spent their lives eating three eggs for breakfast and liver for supper and dying at 94 with no heart attacks.

There is a difference between plain choline and phosphatidylcholine. Choline is only one part of the whole molecule. It is the whole molecule that is valuable. The choline, by itself, is a minor player. Phosphaditidylcholine is just one vinyl-ether bond away from being a plasmalogen. And plasmalogens are are real deal in making mammalian membranes, and nervous systems, advanced.  They are the key to having a functioning brain with sensory components that can see, and hear, taste and smell, think and talk.......and remember.

With the publication of research on renal dialysis patients showing that plasmalogen deficiency explains heart disease risk better than cholesterol excess, we may have a crack in the "statin empire" opening and our obsession with cholesterol being challenged.  With cholesterol we may be looking at a tangential problem, but not the core defect.   From the several hundred measures of phosphatidylcholine that I have done, I suspect we have a whole new dimension to investigate.  Dysfunctional membrane structure from plasmalogens deficiency is what causes cholesterol abnormalities.   It's the root problem.  At least 90% of folks over age 60 are low on choline and phosphatidylcholine. This study turns on the light. Repairing and mending our broken membranes and restoring our phosphatidylcholine is core biology in our mitochondria and in every cell in our bodies.  This gets us to the root and core issues that really helps us. 

That the folks who eat a lot of phosphatidylcholine get less diabetes is contrary to our current way of thinking. Fortyone percent reduction in diabetes is massive. There must be something fundamental to cellular function going on. But that is what good research does. It challenges you to think differently and go back to your sources to try and figure out WHY? Now we need some follow-up studies that duplicate the findings and add to them by folding in more details. What's the mechanism? Who knows? Yet....that's what we need more research to tease out.

www.What will Work for me? If you want healthy plasmalogens, you have to make sure you have healthy peroxisomes, the site of manufacturing them. The only way to have that is to exercise, limit calories for at least 12 hours a day (longer is better), and get rid of fatty liver. I've bought lecithin. Nature provides abundant phosphatidylcholine in sunflower seeds. Lecithin is what we call it. You can buy it for cheap and take it every day. You only need about a tablespoon a day of lecithin to double what the Finns were eating. That's what I'm doing.

References: European Jr Nutrition, J Am Coll Cardiology, Am Jr Clin Nutrition, Nephrology Dial Trans,

Pop Quiz

1. What is phosphatidylcholine?                               Answer: a critical building block for making plasmalogens and a key component, in its entirety of many cellular membranes.

2. And what do you have to do to phosphatidylcholine to make a plasmalogen?            Answer: You have to add a precious vinyl-ether bond in the peroxisome.

3. What does that "vinyl-ethyl" bond do?                         Answer: It sits on the surface of your cellular membranes and protects them from oxidation. Your plasmalogens are the antioxidant of first resort, protecting your brain from foreign stressors.

4. What's the best way to combat getting adult type II diabetes?                     Answer: Keep your BMI between 22 and 25. No sugar. No processed foods. No ground up flour. Exercise and intermittent fasting. And now, increase your intake of phosphatidylcholine.

5. I'm 65 years old? What is my chance for being "prediabetic" or actually full blown diabetic living in America?                               Answer: Probably close to 80%.

Vitamin K2, Vitamin D, and COVID Revisited

Vitamin K2 and COVID Revisited

We have written a column on the curious resistance of the Japanese to COVID-19 being associated with the consumption of natto. Natto is a unique Japanese dish, eaten mostly for breakfast, and made from fermented soybeans. The Fukushima prefecture eats the most natto and has had the least COVID. That effect was thought to be from a yet unidentified protein because heat treating natto inactivated the effect. Otherwise, COVID-19, on exposure to natto could not enter cultured lab cells at all.

But it might not just be the protein. It might be the K2 as well. Natto turns out to be the highest food source of K2 known to humankind. Take 150 folks infected with COVID and measure the protein in their blood that K2 activates, K–dependent dephosphorylated uncarboxylated matrix Gla protein. Just call it Matrix GLA protein. It depends on K2 to be activated. High levels mean there isn't much K2 around. Turns out that the folks who got seriously ill had very high levels of Matrix GLA protein. Or, no K2. And independently, folks with low Vitamin D (< 20 ng) also had worse COVID infections. For every 1 Log unit increase of Matrix GLA protein, the risk of death or severe disease doubled. For every 1 log unit decrease in blood Vitamin D, the risk of death tripled.

What's the mechanism behind all this? We aren't quite sure yet because measure K2 is nigh impossible, to date. Our intake is so low, blood levels are hard to obtain. But Matrix GLA protein can be measured. With just the tiniest amount of K2, high levels of Matrix GLA protein come down dramatically.

Bruce Ame's argued for the "triage theory" of evolution whereby we react to environmental stressors based on those internal nutrients, vitamins, and minerals whose absence becomes the rate-limiting step of survival. There are many nutrients of which we have just barely enough. We don't get ill/impaired until that particular nutrient is needed. Low Vitamin D allows you to squeak by until you fall and a bone breaks, or until influenza shows up and you can't mount an immune response. We have that model with Vitamin D. Now, we recognize K2 as a synergistic partner with D.

We used to have K2 in our food chain when we ate animals raised on grass. Those animals made K2 in their gut. With our current animals all fed corn and beans with precious little grass, our K2 intake has plummeted some 90%. Bruce Ame's triage theory would then consider K2 a critical nutrient that then becomes the nexus of trouble when COVID shows up. Without sufficient K2, for reasons still undefined, we die.  That's how natural selection works.  I don't want to be naturally selected out.  

Is it the Vitamin K2? Is it the mystery protease in natto? All that is unknown. Good science allows leads to more questions. And good science is showing that more people die if their K2 intake is insufficient.

www.What will Work for me. Hmmm. With Omicon lurking out there, it is important that every person you know is encouraged to be on Vitamin D and Vitamin K2. Babies included. Two thousand units of Vitamin D a day is safe for infants. And it comes with K2 in it. Buy the combination.  Super K for Life Extension is easy to find on line.  As an adult, I'm doubling up on my K2 for the foreseeable future. No harm in it. And I just started my next batch of homemade natto. It will last me a month, at least.

References: IDSA Open Forum, Scand Jr Clin Lab Invest, NutraIngredients, Biochem Biores Comm, Inter Jr Endocrinology,Jr Immunology,

Pop Quiz

1. Where do you naturally get K2 from?                           Answer: GRASS-raised animals. Only. Or from natto, fermented soybeans. (There is precious little comparative research but one example I found: Dutch Gouda cheese, advertised as grass raised, has 10 iu of K2 per ounce whereas an American Gouda had 2.

2. What does K2 do?                                       Answer: We know it "carboxylates", or adds a carbon-oxygen group, to two proteins that upon activation make bones stronger and arteries stretchier. Matrix GLA protein is one of them. Osteocalcin is in your bones.

3. And what does the research study today show?                                    Answer: folks with low K2 had a doubled risk of death from COVID.

4. What's enough Vitamin D?                                           Answer: We know that you don't produce your natural antibiotic, cathelicidin, until your D level is above 32. Hence, the minimum D level should be 33. The benefit curve appears to say optimum is 50-80.

5. What's enough K2?                                               Answer: We don't know how to measure it. But we know its absence is bad. So, take some. I'm taking a double dose for the next year or so. Bought some Dutch Gouda at Sendiks. Yummy.

Taurine and the Longevity of the Japanese

Taurine, and the Longevity of the Japanese

If I told you that I can explain the major reason some folks didn't get strokes or heart attacks, you would push me away and challenge me. No way! I get asked that question all the time. Why do women live longer? Why are the Japanese so resilient? Taurine is at least one of the answers. We should know about taurine.

It is an amino acid. Simple. But we don't use it to make proteins. Instead, it appears to be a crucial signal modulation chemical. It does contain sulfur atoms and carries a negative charge. That gives it some unique functions. Deficiency in taurine leads to cardiomyopathy in many animals, and likely in humans. Supplementation of it appears to naturally help resolve atrial fibrillation. It plays a role in modulating osmolality, the concentration of serum. It has anti-oxidant functions. It plays a huge role, and some argue primary, in bile acid excretion, thereby reducing serum cholesterol. And last, but probably not least, it modulates the balance and role of plasmalogen lipids. And that may be the key!

Seaweed has been shown to have >600 mg per 100 grams of taurine. Compare that to oysters (396 mg), fish (130 mg), beef (43.1 mg), chicken (17.8 mg), pork (61.2 mg), and lamb (43.8 mg), and virtually zero from most vegetables. Some seeds and nutshave levels below 10 mg per 100 grams. If you then examine the societies that eat lots of seaweed and seafood (Japan and Korea) and heard that the Japanese average seafood consumption in Japan is up to 580 g/week compared to the Western world (USA: as low as 63 g/week) you start to understand a critical nutrient difference between the two that might have a salutary effect. When examining the epidemiological effect of taurine, some 61% of the beneficial variation from stroke or heart attach can be explained by the "taurine, salt, BMI, cholesterol" variables, with taurine being the uniquely Japanese issue. It should be noted that the Mediterranean diet is also a high taurine diet, perhaps explaining their cardiac benefit as well.

Where do you want to get your taurine from? Well, you can get lots of it in all sorts of energy drinks. But at the end of the day, the best sources are seafood, with shellfish being the champions. If you are a vegan, taurine deficiency is a real issue. Nuts and seeds have tiny levels, and some beans carry a little tiny bit.

And can we really ascribe just what taurine does that makes those plucky Japanese hang around so long? No, we can't just yet. It I were to guess, I would posit the beneficial effect on plasmalogens. What else?

The effect on heart attach and stroke is not insignificant. This is roughly 10-100 times the beneficial effect of statins. The Japanese are living some 5-10 years longer than their western counterparts. If taurine is 60% of that, you have a 4-6 year benefit. Statins will add 1 week to your life, if you haven't had a heart attack.

www.What will Work for me. I love scallops and pick them any time I have a choice. Looks like I can now explain why seafood is so good for us. I'm affronted by the energy drink industry with their taurine manipulation. But maybe I should just get over it. And buy some taurine. If I were to choose, I would get the magnesium taurate and get my magnesium along with the taurine.

References: ResearchGateJr BioMed Sci, ResearchGate, Arteriosclerosis, Med Hypothesis, Nutrients, Adv Res Dev Biol,

Pop Quiz

1. What is taurine? Answer: It is an amino acid not used in making proteins. It has many other uses in our metabolism yet to be fully understood.

2. What uses? Answer: Helps excrete bile acids. Helps hearts have normal rhythms. Antioxidant. Balances plasmalogens.......

3. Where do we get it from in our diet? Answer: Seafood. Scallops, clams, oysters, fish. And seaweed The level is regular meats is about 10% of seafood. Vegetables and fruits have none. Seeds and nuts, tiny amounts.

4. What percent of the longevity of the Japanese can be explained by their intake of taurine (this is some 10 fold what Westerners eat)? Answer: About 60% when combined with cholesterol, BMI, salt and magnesium intake.

5. And what is the plasmalogen connection? Answer: Well, we don't really know except that there appears to be a positive correlation with more taurine intake and membrane phospholipid levels (that include plasmalogens.). That raises the tantalizing spector that you can raise your plasmalogens by taking more taurine. (Complete conjecture supported only by other conjectures, so far. )

Brain Volume and Cognitive Decline

Brain Volume and Cognitive Decline

It's a cardinal feature of Alzheimer's. A shrunken brain. In fact, we have known since Rosser's Study in Neurology that the volume of the brain correlates directly with the level of cognitive function, and the rate of decline of volume is directly matched to the rate of brain shrinkage. Ok, so you want a nice, big brain. Seems obvious.

Well, it is. But we have had it backward on its etiology. We have looked at amyloid plaques and neurofibrillary tangles as the problem. They are the two pathological features you see on autopsy of Alzheimer's. They must be the cause and addressing their accumulation should be how we approach repairing or preventing Alzheimer's. Right? Actually, dead wrong. All backward.

It is impaired cognition that is toxic to the brain. First and foremost, impaired cognition comes first. Yes, I said that. It's the impaired brain function that causes everything else. When you understand this, you will then understand how to keep your brain healthy. It's actually much simpler than you think. (Little pun there).

Here is the nugget. The act of thinking, the process of activating a synapse in your brain, is absolutely defined by the secretion of acetylcholine. Period. The ability to process and make acetylcholine is the whole story. And here is the driving force: the ability to secrete choline is determined by the adequacy of plasmalogens in your synaptic membrane. That's it. You must have sufficient plasmalogens. They are the sole membrane lipids that can shapeshift, and thereby merge the neurotransmitter-containing vesicle with the synaptic membrane. It's that core function, merging with the membrane, that allows our brains to function rapidly. That function depends on plasmalogens. Adequate plasmalogens. In fact, multicellular life with neurological systems depends on those key features that plasmalogens alone have: they can shapeshift, they are the most liquid of membrane lipids, and they protect the nerve cell from oxidation with their vinyl-ether bond.

Inadequate plasmalogens set in motion a deadly and inevitable cascade. Without sufficient plasmalogens, you get insufficient secretion of acetylcholine. The nerve must function. Its only survival strategy to create acetylcholine when plasmalogen levels are inadequate is to cannibalize the synaptic membrane of choline plasmalogens. Less plasmalogen in your synaptic membranes, less fluidity, less secretion. Your plasmalogens are made with choline as an integral component. And if you don't have enough acetylcholine as a neurotransmitter, you can snitch a plasmalogen molecule from your membrane and make another acetylcholine from it. But that destroys that one plasmalogen molecule. Round and round it goes. And as that process continues to happen, the synapse collapses, shrivels up, and disappears. Each neuron has some 4,000 synapses, so you can lose one or two, but not four thousand. Lose 4000 and you have lost the neuron. Lose neurons and you have lost brain volume.

That's what comes first. The brain shrinks from the inside out, It is that simple. Without sufficient plasmalogens, you can't make sufficient acetylcholine, and your nerves can't fire. Now, what happens next? The details are then what you would expect. With the loss of a synapse, you don't need the cables of intracellular transport. Those "wires" or cables aren't needed. They pile up. We call them neurofibrillatory tangles. They didn't cause the problem, they are a marker of the problem.

And if you were paying attention, you would have intuited the means to subvert that whole deadly spiral. You need to maintain your plasmalogens. You need to maintain your choline supply in your diet. You need to maintain your neurotransmitter distribution system which is based on methylation. And you need to keep your peroxisomes healthy. That's it. Healthy plasmalogen levels can completely circumvent dementia, even the APOE4 gene. We can measure your plasmalogens and we can replace them.

Your brain has amazing resiliency and redundancy. You have many pathways to remember every word, every emotion, every map, every regret you ever had. The "Nun's Study" from Elm Grove, Wisconsin has demonstrated for us that the writing style of women, 60 years before the diagnosis of dementia, could be identified as "at risk". Losing synapses and memory isn't a 6-month affair, it is a lifetime affair. Losing a synapse here and there all adds up. Your brain always wants to rebuild resiliency and redundancy, if it has the tools. That is in your hands.

www.What will Work for me. I've measured mine, knowing my mother died of Alzheimer's. I was sort of average, maybe a tiny bit below. My risk of cognitive decline would come out to 20% or so if I did nothing. If I raise my plasmalogens up to 1 SD above the mean, I'm at 7% risk. If I raise my level to 2 SD above the mean, I'm down to 2% risk. And I've done the math. At $ 2,000 a year to replace plasmalogens, I'll spend $ 40,000 over 20 years. At age 90, I will still have a working brain and be recognizing my family. My mother, at age 90, didn't. It cost her $ 10,000 a month (in today's dollars). It's cheap to fix, compared to that.

References: Neurology, Lipids in Health and Disease, Frontier in Cell Devel Bio, Human Mol Gen, Nature, New York Times,

Pop Quiz

1. When I forget a word or overlook an errand, what might be going on?                         Answer: in the aggregate, the loss of some prior neuronal connection.

2. The diagnosis of Alzheimer's means what?                    Answer: Not covered above but likely the recognition of severe damage and impairment. On the order of 70% of synapses being lost. It's the end stage of at least a 25-year process.

3. The driving force of Alzheimer's is what?                 Answer: Loss of cognitive function.

4. What does that entail?                         Answer: Insufficient acetylcholine, driven by insufficient choline.

5. If your neuron doesn't have enough choline to make acetylcholine, what does it do?            Answer: scavenges choline from plasmalogen molecules, leading to the eventual collapse of that synapse or neuron.

Triglycerides Predict Longevity And We Know How

Triglycerides and Longevity

Yup! Your triglycerides tell a lot about you. In fact, they might be the most important part of your cholesterol profile. Here is the physiology, and the implications it has. Note, cholesterol isn't the main story.

First of all, we now recognize that high triglycerides come about because of peroxisome dysfunction. We see high triglycerides most commonly in diabetes and worry endlessly about how to lower it with statins (they don't work). Essentially, what is happening in diabetes is the flooding of your mitochondria with too many calories in the form of carbs and fats. In a desperate attempt to keep up, your peroxisome, which is meant to be feeding chopped-up fat into the mitochondria, stresses out and can't chop up fat at all. Your triglycerides go up. Your peroxisome is all jammed up and flooded, just like your gasoline-car engine.

The question arises, what is the best way to modulate those triglycerides? Ah! Easy, peasy. Cut the calories. Clean up the logjam of calories. Intermittent fasting will do it. In a lovely study from Pakistan during Ramadan, 40 volunteers with high triglycerides agreed to not eat for 12 hours every day (That's easy: that's what Ramadan does for Muslims every year). Guess what happens to the flow of calories into the peroxisome! It drops to "tolerable levels". The peroxisome can start chopping up fat, like it's meant to. Guess what happens to the triglycerides? They get chopped up. Their level drops like a rock. (You can prove this for yourself: try intermittent fasting and measure your own.)

That's what intense exercise does too! It uses up the stored carbs and forces you to start burning fats. That wakes up the peroxisome to solicit more proteins so that it can provide you with the calories you need (in this case from burning fat instead of glucose). A mitochondrion has 29 genes of its own to manufacture new, essential proteins, on a minute-by-minute basis. It can burn glucose or fat, depending on what is presented to it on a minute-by-minute basis, but will go for glucose first until it is used up. The peroxisome, right next to the mitochondria, is the entity that is tasked with chopping up those triglyceride fats to feed into the mitochondria, can't respond so quickly. It takes a couple of days to ramp up. It too has to call for the nucleus to manufacture new proteins, but it has no DNA of its own, and it takes a little longer to ramp up. If you go on a very stringent fast right away without inducing the peroxisomal "biogenesis", you will become hypoglycemic and feel awful. You stopped eating carbs and run out in just 12 hours, and you can't make fat. You feel like you are going to die. Your diet will fail.

You have to wake up those nascent genes in your cell nucleus and export some mRNA out to the ribosomes to make new peroxisomes. And you do that best by little stages. Each day, nudge your metabolism for an extra hour of fasting. Do it overnight. Don't eat for 12 hours (depleting your glycogen to zero and beginning to burn a teeny bit of fat). Then, stretch it to 13 hours....14....15. Skip breakfast and go for 18 hours. Your triglycerides will disappear. You don't have to call me, you can measure them yourself. It takes some 4-5 days to get them properly turned on. If you have extreme discipline and put up with the "keto-flu", you can muscle your way through it. Or, you can gradually accommodate to it by stretching out your intermittent fasting to longer time periods.

But that's not the meat of this week's email. You live longer? Why? Ah...healthy peroxisomes also make more plasmalogens. Higher plasmalogens are then associated with larger brain size. Larger brain size correlates with larger muscle mass and longevity.

That is the key. Low triglycerides and high plasmalogens even trump APOe status. APOe4 becomes a problem only if you are insufficient plasmalogens. Peroxisomes also need the right building blocks to make plasmalogens, like choline and ethanolamine, DHA, and B12/B6/folate. Just look at the figures in Goodenowe's study. Healthy plasmalogens result in longer life. Period. And you can't have healthy plasmalogens in your brain when you have high triglycerides in your blood.

www.What will Work for me. Triglycerides are a quick and dirty peek at peroxisome function. It's easy to measure. Sure enough, the folks with healthy, low triglycerides will tell you they eat very little sugar, white flour, and tons of vegetables. And very likely exercise. We now know that some 60-70% of the calories from green vegetables arrive in the form of Beta-hydroxybutyrate after the gut bacteria break the plant cell wall down. Peroxisomes LOVE beta-hydroxybutyrate. When you eat a salad with olive oil dressing, you are getting a perfect peroxisome soothing diet. I've stopped looking at total cholesterol. In fact, the data now has convinced me that the healthiest cholesterol is 210-250, not less than 200. But it's the triglycerides that matter for good health.

References: Brain Sci, Molecular Metabolism, Frontiers Nutrition, Frontiers in Cell and Develop Bio, Nature - Experimental Med,

Pop Quiz

1. What is going on with triglycerides? What is really happening down in the gearbox of your cell?       Answer: High triglycerides suggest your peroxisome is all backed up, in conjunction with the mitochondria from getting too many calories all at once. Fast food, highly processed, floods your peroxisomes. Sugar is the worst.

2. How can you modulate that?                                 Answer: Change the way you deliver calories to your cells. Cut the sugar, cut the processed foods. Add more vegetables.

3. What's the key strategy you can start, even today?                         Answer: Go 12 hours every day without eating anything. So start with no late evening snack. Then, stretch out breakfast and make it a little later. Gradually extend that time all the way out to lunch. "Compact your calories" or "Intermittent fasting".

4. What else do peroxisomes do besides chop up fat (thus lowering triglycerides)?                 Answer: They make plasmalogens for your nervous system.

5. What predicts long life with plasmalogens?                  Answer: The more of them, the better. An average person who is two standard deviations below normal, compared to two standard deviations above, drops dementia risk by some 90% in improves longevity by some 15 years.