Nitric Oxide, The Fulcrum of Life

Nitric Oxide - The Fulcrum of Life


A fulcrum is something on which a process pivots. Ah! That's how important NO is. All three theories of aging, stem cell collapse, oxidation, telomere shortening all pivot on the fulcrum of NO and are actuated and prevented with sufficient NO. NO is so important, that mother's breast milk has more Nitrites and Nitrates (the precursors for NO) in it than any other food, and supplies way over WHO recommendations of consumption for safe health. That's how misunderstood Nitric oxide is. Hence this series on NO. First, we need to debunk its "danger". So, today we just learn what it is. I want to know this.


First of all, what is it? NO is a gas. It is an unstable molecule with an extra electron to give away. That make's it a free radical. But this is the definition of a good free radical. Don't confuse NO with nitrous oxide (N2O, an anesthetic gas) or nitrogen dioxide (NO2, a major dangerous environmental poison). It was named "Molecule of the Year" in 1992 and provided the reason for the Nobel Prize in Medicine in 1998 for the role it plays in vascular health.


Nitric oxide plays a huge role in blood flow. In fact, it has been argued that the delivery of oxygen to tissue is more dependent on nitric oxide levels and blood flow than on oxygen concentration. Levels of nitric oxide predict an athlete's ability to perform more accurately than any other indicator (presuming the same amount of training and hard work!). Levels of nitric oxide predict recovery from a heart attack, blood pressure, stroke, Alzheimer's.


And that's the conundrum. Our ability to make NO declines with aging by about 12% a decade. Hence if you are 60 years old, you only have 30% of the capacity you had as an infant. Without the soothing effect of NO on your vascular tree, you are going to have coronary artery disease. Guess what else won't work? Correct. There is a very high degree of correlation between erectile difficulty and coronary artery disease..... and low nitric oxide.

Here is the nugget of how we make it. There is a nitrogen cycle in nature with atmospheric nitrogen that is oxidized by lightning into nitrates that plants can then use. There is also a nitrogen cycle in humans. It goes as follows. First, we eat nitrates and nitrites from vegetables, mostly green leafy ones. The bacteria in the crypts at the back of our tongues reduce it to nitrites. In our acidic stomach, at least below pH 4, nitrite gets changed into the gas NO. The remaining nitrates are absorbed by the gut into the blood and return, in large quantities to our salivary glands. With our salivary as the main repository of nitrates, we then make saliva and the bacteria in the back of our tongues do their job, reducing nitrate to nitrite. We swallow and our saliva proceeds to our stomach where we make the final end product, NO.


Then, there is a second pathway that makes NO through the breakdown of arginine. That pathway feeds into the nitrogen cycle as well. Curiously, the effort to make more NO through arginine supplementation has not been a resounding success.

Guess what happens when you take mouthwash? Yup. You kill the bacteria in your crypts and your NO goes down and within a week, your blood pressure rises.


Guess what happens when you take PPIs, the most prescribed medication in the world, and make the pH of your stomach neutral with no acid? Yup. In the next three years, your risk of heart attack rises some 20%. Makes sense to be on a PPI and a statin all at the same time, huh!


www.What will Work for me. I'm just learning this. I've seen the pathways for aging that all have NO and the various enzymes that are activated by in cellular oxidation or telomere shortening. But this ideas is boots on the ground in everyday life. I ordered an NO test kit for myself and sure enough, my level was modestly low. So, I ordered Beet Root extract, took two pills and two hours later, sure enough, my level was much higher. My mouthwash just got pitched. I suspect NO and its levels will become one of the most important markers of good health we can follow. And you can test yours at home, cheaply. One minute. And now I understand why the DASH diet and the Mediterranean diet work. They both emphasize lots of leafy, green vegetables, the type that makes more NO. And it has been measured and proven to be the case with both.


References: Wikipedia, The Nitric Oxide Solution, Blood Pressure, PLOS One, Nutrition & Metabolism, Nature Reports,

Pop Quiz


1. What is Nitric Oxide?                 Answer: A gas containing one Nitrogen and one Oxygen.

2. What does it do chemically?                   Answer: It is an electron donor.

3. What role does NO play in aging?                 Answer: All three processes of aging have NO as the key instigator/modulator. (Oxidation, telomere shortening, stem cell fatigue)

4. What happens to our NO levels as we progress through the decades?                    Answer: We lose about 12% per decade. By age 40, we are down 50%.

5. What happens when you carefully rinse your mouth with bacteria killing wash after you floss?      Answer: You successfully kill all the bacteria on your tongue that are helping you make NO. Your blood pressure will rise over the course of the next week. We suspect that same effect happens everytime you take antibiotics for anything. And did you catch that last paragraph above about PPIs?


One Type of Exercise Helps Your Brain the Most

One Type of Exercise Protects Your Brain the Best


In the era of FitBits and ultrasensitive measuring devices, we can now monitor just about exactly whatever you do, all day long. Using that for a useful purpose becomes the next stage of lifestyle research. Wouldn't you like to know if there is any benefit to taking the stairs instead of the elevator? How about walking the dog briskly, or slowly. How about jogging, or folding laundry? Is there a benefit to emptying the dishwasher? Ah! We can now tell you. 


This week's study from the BMJ was all over CNN because it was designed to answer just that question. Movement measuring devices were attached to the thighs of 4,500 mid-life British subjects in the longitudinal cohort study starting in 1970. At age 46, they were offered the opportunity to participate and did. They were studied for 7 days around the clock. They were also tested for verbal memory and executive function. 


Here is the "good news". Moderate activity, of just 6-9 minutes a day, could be shown to assist in better memory, problem-solving and executive function. Moderate activity is something that gets your heart rate up. Biking on the flat doesn't count. Uphill does. Stairs do too....6-9 minutes worth. Aerobic dancing, running, jogging, and swimming all work. Just plain standing, walking around, making the bed, cooking dinner,... those don't do it. It takes a threshold of getting your heart rate up. Now, that explains why 6 minutes of High-Intensity Interval Training works too.


Now, it we can talk you into 20 minutes, that's better yet. But the bottom line, the take-home message, is that your brain will function better with just 6-9 minutes of anything that gets your heart rate up and makes you a bit breathless. (No, that wasn't mentioned.).  And you can tell the difference in just a week.


www.What will Work for me. This is the first study that I've seen that measures mid-life exercise and its effect on "executive function"...decision making. Your brain needs something that exercise provides, and likes a bit more than most of us get. Osteocalcin, the protein that binds calcium and binds it into bone also is known to turn on muscle growth and brain growth. I suspect that is an important link. If you want to go down that rabbit hole, you might be intrigued to understand that osteocalcin is activated by Vitamin K2 (Not K1!). If you can do 40 pushups (men), walk a brisk 3 minute mile (either gender), get up from the ground without touching the floor with your hands, you will live longer. Being fit matters for your longevity, and for a brain to accompany you on the way. My experience is that 25 deep knee bends really gets me winded. I can't do 30 quite yet, but I'm working on it.


References : BMJ, Facty.com, Women's Health, Cell Metabolism, Nat Rev Endocrin, Jr Bone Miner Res.,


Pop Quiz  

1. You can prove your memory is better with how many minutes of moderate exercise?                       Answer: 6-9 minutes 

2. And that can be measured in normal 46 year olds in how long a period of time?                      Answer: Just 7 days will show a measurable difference 

3. Watching TV and cheering for the Packers counts, doesn't it.                         Answer: No 

(at least not this season). Sedentary couch time, sleeping, standing, folding laundry, may all be noble deeds and worthy of being done...but don't help your brain like exercise 

4. How do I know my exercise is good enough?                                     Answer: Gets your heart rate up and may get you sweaty if the weather isn't too chilly. 

5. Do weights and heavy lifting help?                                         Answer: Indeed it does, just work it enough to get sweaty. Cross Fit can be designed for anyone where ever they are on life's path. Repeated exercise, enough to get you winded and your heart rate up. Your brain will benefit from it.

Vitamin K2 Might be the Holy Grail for Your Heart

Vitamin K2 Might Just be the Holy Grail for Your Heart


The two scourges of modern civilization, osteoporosis, and coronary artery disease. They seem to have skyrocketed together over the last 100 years, concurrently with our remarkable extension of life span. Are we getting more of these two wicked demons just because we are living longer, or has something changed in our environment? Maybe a little bit of both?

Or maybe our world changed. After World War II, virtually every meat producer in America moved their animals off of pastures onto feedlots. Animals that eat grass make Vitamin K2 in their gut from the K1 found in green leaves. There is no K1 in corn and beans. We don't have any measurements from before, but the resultant change is likely hugely significant, probably in part because even with grass-raised animals in our food chain, our prior K2 intake was just barely sufficient, and not enough to be "therapeutic". There is a vast difference between recommended minimum daily requirement and optimal therapeutic requirement.


One of the most common questions I get is "How can I reverse my coronary artery calcium score?" or "How can I fix my osteoporosis?" So, when I come across a story in which an inventive engineer with severe left main calcification completely reversed his calcification with Vitamin K2, I have to pay attention.

Pat Theut, a paper engineer from Up-North, Wisconsin, found severe coronary calcium on an executive physical at the Mayo Clinic. He tried the traditional role of statins and AHA-type advice to no avail. So, he struck out on his own and started reading. Over the next few years, he came up with his own program, centered around much higher doses of K2 (and including regular K1 as well) and reversed his coronary artery disease. Reversed. Gone. Nada. Fixed. And in the process, gave the high dose of Vitamin K2 to his aunt only to see her osteoporosis go away.

K2 activates matrix GLA protein in your arteries. It also activates osteocalcin, the key calcium binder in your bones. Matrix GLA protein binds calcium and pulls it out of your arteries. In fact, there are now emerging studies from Europe showing the more K vitamins you consume, the lower your rate of coronary calcium and coronary artery disease.


The literature is extensive. Even the obverse now seems clear. Take warfarin to prevent blood clots, (a Vitamin K2 antagonist) and observe your arteries turning into rigid, calcified stone.

The implied effect is that the amount of calcium in your arteries predicts the risk of coronary artery disease. And that is true. You don't need an expensive catheterization and its potential risks. You just need a 64-slice CT scanner and 5 minutes. A score of 0 has "0" risk for heart attacks. A score of 400 is dangerous. Getting rid of the calcium starts with Vitamin K2, at least 5 times what is currently available by standard supplement providers. With that in hand, Pat Theut started a company called Koncentrated K at www.k-vitamins.com and will sell you just that: 500 mcg of MK7 and 25 mg of MK4 in addition of 5000 mcg of K1. You can't take warfarin with that as the K1 will promptly reverse the blood thinning effect. Read his "Story" and his "Cardiac Manifesto". It's more than just K2. Weight loss, exercise, stress management, and sleep all matter too.


www.What will Work for me? I have been touting the benefit of K2 for 10 years now and feel vindicated by this remarkable anecdote. He is just one person but he emboldens me to push this harder. We have not been successful at reliably reversing osteoporosis or coronary calcium with Super K. It has just 100 mcg of MK7. Not enough. I've even made my own natto so that I can get the benefit of K2 from natural sources (natto is the highest food source of K2) but its flavor is tough to enjoy unless you are born and bred Japanese. But I'm now officially changing my advice for anyone on K2. You are not getting enough with 100 mcg a day. That may meet RDA-type standards, but it is not therapeutic. We are all in a deep, physiologic mess and need MORE. Thank you, Pat Theut.


References: Japanese Natto Association, AJCN, Eur Jr Nutrition, K-Vitamins.com, Cells, J Am Coll Card. ,


Pop Quiz


1. Vitamin K1 and K2 are really, just the same. T or F?                             Answer: Related to some degree but with a completely different side chain, have completely different physiological targets. That is how nature works. Once it finds a working vitamin or hormone, it builds on that base and branches out over time with different effects.

2. If you block K1 with warfarin, what is your chest X-ray likely to look like after about 5 years?               Answer: That's easy. You can see every artery in your entire chest outlined in calcium. I've been in the ER for 25 years and have seen it 100s of times.

3. Where is our food source of K2?                          Answer: It is made in the gut of animals that eat grass.

4. How much of the normal American diet is based on grass-raised meat?                            Answer: It must be in the low single digits.

5. This column suggests we need more K2. How much?                        Answer: Probably 500% more. 5 times. Right. You read it here. Give Pat Theut a high-five after you have read every word of his personal story. Consider that your informed consent.


Create More Happiness for Yourself - Channel Your Inner Finn

Create More Happiness - Channel Your Inner Finn


Ok, ok, not everyone in Wisconsin came from Germany...there have been boatloads of Swedes, Italians, Ukrainians, Poles, Norwegians, and Finns too. But when we hear that Finland just landed "the happiest country in the world" for the fifth year in a row, you might be tempted to ask just what it is that they do. Is our "Finnish" heritage part of why Wisconsin is considered such a welcoming place? Add to their internal happiness, their immigrants end up being the happiest of any immigrants. Something is working right in Finland.


In pursuit of that answer, ask Finland's premier happiness researcher, Frank Martela, just what it is that Finns do to make their country and themselves happy. Here is the list recently published on CNBC.


1. “Kell’ onni on, se onnen kätkeköön.” In English, it means: Don’t compare or brag about your happiness. What that translates into in everyday life in Finland is less showy displays of possessions. You can't tell a millionaire by their clothes or their car. They might be on the bus with you. They certainly won't brag about the neighborhood they live in. Finland has enough lakes and shorelines for just about everyone to live close to water and next to nature. So, you don't have to boast about your place "up north". Finland, after all, is up north.


What that really means is to set your own standards of happiness that you can achieve and be content with who you are. Don't compare yourself to others. You are good enough. And can you help your friends feel the same way? Encourage them to be enough just as they are. Make it infectious.

2. Get close to nature and savor it. Surveys show that 87% of Finns think nature is particularly important. Getting outdoors and taking the 4 weeks of summer holiday that most Finns get away from cities is highly prized. But a walk will do in the park, even in January. Grow a plant indoors. If you can't grow anything, get a bird feeder.  Just notice and enjoy the natural world we live in.

3. Do what you can to increase public trust. Research shows the higher the level of public trust in a society, the happier everyone is. Practice absolute honesty in everything you do. Consider courtesy as your operating system. Drive with kindness and tolerance in your heart. Don't judge the people around you with your first impressions. Practice trusting their goodwill. Let the other guy into your lane. Let the other person go through the door first. Wait your turn in line with patience. Notice how it makes you feel part of the larger whole.


Do you know what happens when you lose a wallet in Finland? You get it back over 90% of the time, with the money in it (11 of 12). (Best of 16 cities studied). Mumbai, India came in at 9/12. New York was only 8/12. Presume goodwill when you speak to the beleaguered customer service person on the phone. Go ahead, be kind, and see if you don't get what you wanted more often. And mostly what you want is a sense of trust and relationship with everyone you meet. Public trust. Nurture it. It's good for all of us.


www.What will Work for me. I've had a lost computer returned to me at Chicago's train station. I remember that as acutely as the time I was mugged in college (The mugger returned my wallet, empty but for my student ID). You know what happened me when I found myself late at night on the train station in St Louis, with only two large, obvious maintenance men there with me, and I didn't have the change to get the train ticket? One of the men gave me a dollar in change. How I wish I had his name. Opportunities to create public trust come up all the time. Be prepared in your heart to give a minute, give a dollar, speak up in kindness, show deference...you will be happier.


References: Finland's Characteristics, Wisconsin Historical Society, World Happiness Report, NBER, Reader's Digest, CNBC,


Pop Quiz


1. The happiest countries in the world have the lowest taxes? T or F. Answer: Not asked and not studied, but it could be noted that the highest-taxed countries in Europe are all in the top happiest places to live.

2. Can you think of three ways you can participate in increasing public trust?

3. Can you think of ways that you can feel ok about the choices you make to spend time with your family or friends?

4. What can you do to enjoy nature as we roll through the coldest and darkest days of the year?

5. Will you really be happier in an expensive car?

 
Autism May be Diagnosed with a Hair Sample

Diagnose Autism with a Hair Sample


Want to know if your one-year-old child might develop autism with 81% accuracy? That's the test currently being fast-tracked with the FDA. Since we typically don't diagnose autism until age 3-5, knowing your risks ahead of time might allow preventative or interventional efforts to be taken. That's new and meaningful.


Developed first in Japan and Sweden, a 1 cm stretch of hair was removed from 220 Japanese 1-month-old children and stripped of its outer lining. Three years later the 100,000 children included in the survey were randomly narrowed to a 220-child study for follow-up to assess for features of autism. The hair samples were then measured by mass spectrometry at 650 points looking for a variety of substances, including toxic heavy metals like aluminum, arsenic, lead, and cadmium as well as normal nutrients like zinc and copper. The study designers used machine learning and statistical analysis to narrow down the risk features. This method is like Goodenowe's discovery of plasmalogens: that measured everything by mass spectrometry and then parsed out responsible biochemical features. You can imagine the amazing detail when you conceive of 650 measurements in 1 cm of hair!


81% accuracy! That is huge. 75 % of children were correctly given the all-clear. And to do so 3 years before clinical diagnosis gives a window of opportunity to make changes. Of course, 81% isn't perfect, so "larger studies" are needed, but this justifies a 2,000-child study that has now been started.


What's the read on this? The authors state that their "prediction" is based on proprietary measurements of 567 separate features that showed statistically valid variability. They aren't exactly revealing just what it was they measured. It's only a teaser to say they measured heavy metals, copper, and zinc. (560 others not revealed to us). That suggests a broad dysregulation of biochemistry. Their test will likely be marketed by a company for future medical use.


We do know that population studies looking at A1 milk predict autism with spooky reliability. The 7 amino acid fragment in A1 milk is biologically active on themorphine receptor in the brain and is found to be about 1.6 times higher in children with autism. Wisconsin cows, mainly Holsteins are all A1. Brown cows are A2, as is goat milk and human milk

.

We also know that copper is higher in autistic kids, and drops with zinc therapy. With 90% of American homes made with copper pipes, copper is a new chemical in our environment. It drives zinc lower, and zinc is the. most important mineral in the brain. This same dynamic has play in Alzheimer's which burst onto the American medical scene only after the introduction of copper pipes.


What this all means is there is likely no single entity that can claim causation with autism, but rather a broad shift of metabolic dysregulation. That fits precisely with the plasmalogen hypothesis that we entertained last week. Plasmalogens are the antioxidant of first resort. When there is inflammation in the gut, and the immune system is broadly activated, inflammatory markers and cytokines are everywhere. The brain becomes inflamed and there are not enough plasmalogens to tip the balance back to normal.....and white matter becomes irrevocably damaged.


Just like in Bredesen's approach to Alzheimer's, children with autism probably need a multimodal approach to repair: avoid wheat, avoid A1 milk/dairy, add Vitamin D, add K2, add zinc, nurture the gut......add plasmalogens. If that were all started after a positive predictive test, perhaps we would reverse this awful trend.


www.What Will Work for me. This is the functional medicine approach to autism in a nutshell. The anecdotal news that autism is significantly helped with plasmalogens gives out a hint that we need to turn off the raging fire in the autistic brain, and then pull out the burning embers one by one: (repair copper), remove A1 dairy, remove wheat, repair gut....more and more plasmalogens. Send the kid to school and catch up when her/his precious brain starts to work.


References: J Clin Metabolism, International Jr Mol Sci, Nutrients, Nutr Metab Insight, Goodenowe,


Pop Quiz


1. How many measurements are made in this study on 1 cm (0.4 inches) of hair from a 1-year-old baby?         Answer: 650

2. What is a mass spectrometer?                      Answer: No fair, you didn't mention that. Well, it is a machine that can measure precisely every molecule present in a sample by vaporizing it and weighing it with electronic wizardry. You will have thousands of ingredients, some of which shouldn't be there. And you will get some read about how much of each. Nifty technology.

3. This study showed how many ingredients in hair are off kilter with abnormal measurements in autistically prone kids?                             Answer: Some 560 (Which we are not told about. The study only showed the results. Coy. Obviously planning to market their proprietary results.)

4. Average age of diagnosis of autism in the USA is? Answer:                        Age 4

5. If you had a positive test in your 1 year old infant, what would you do?                              Answer: Add plasmalogen supplements, measure zinc and copper and balance them with appropriate levels, chelate out heavy metals, avoid A1 dairy, avoid wheat, get better probiotics and prebiotics into the food chain, Vitamin D and K2, fish oil....... breastfeed some more if still possible. Maybe all children should be on this trajectory and avoid the test.   Maybe get a reverse osmosis filter in your house.


Autism May be a Plasmalogen Deficiency Syndrome

Autism May Be a Plasmalogen Deficiency Syndrome


Autism is one of the most devastating diagnoses for a growing child, and for the involved family. Its increase has been a puzzle of monumental proportions with few clues to date. Its incidence continues to increase dramatically. (6.7/1000 in 2000 and now 23/1000 - just 20 years later).


It is not an infectious disease. No evidence there. It is not caused by trauma. It is not racially or genetically based that we can tell. (To date). What is it?


What we do know are some incontrovertible facts about food and nutrition. In the last 100 years we have altered our diet with massive shifts in micronutrients. Many of those changes involve the nutrients needed to make proper levels of neurotransmitters and neuro-lipids, otherwise known as plasmalogens. When we had grass-raised animals, we got omega-3 fats in our food chain. Now, all our animals are raised on corn and beans and our intake of omega-three fats has dropped precipitously. You can't make a plasmalogen molecule without the omega three fatty acid called DHA

.

Our sugar intake has skyrocketed. Sugar shifts our metabolism to inflammation and crowds out other vital nutrients. The proportion of our food made up of ultra-processed food (packaging using many unrecognizable ingredients to sustain shelf life, flavor, color) has also skyrocketed. There is now clear evidence in adults that ingestion of ultra-processed foods results in cognitive decline. Could autism be the result of a lousy ecosytem of food in pregnancy and early childhood? That's what this author believes.


What we do know is that fetuses can't make plasmalogens and depend on them from their mother. The ability to manufacture plasmalogens prenatally only starts about week 30 of pregnancy. The central nervous system is growing rapidly and the demand soars at birth in the neonatal brain. Trillions of axons and synapses have to be manufactured for a newborn brain to start working. The content of plasmalogen lipids in synapses is about 70%, meaning there is a massive demand for that specific nutrient at birth. Each synapse and axon is composed of plasmalogen lipids. Breast milk, particularly colostrum, is a very rich source of plasmalogen lipids. Infant formula has none. And indeed, here is our first clue. Breastfed children have less autism. In fact, meta-analyses of breast feeding studies show, "more breastfeeding, less autism".


Is there other evidence? Well, yes. MRI studies of autistic kids suggest that their brains have a dramatically reduced quality and quantity of white matter. That's the part of the brain composed of all the axons, the wires and links between nerve cells. That is a direct indication of plasmalogen deficiency. We also know that if you experimentally deprive rats of plasmalogens, baby rats are born with all sorts of cognitive trouble.

The link that is still missing are studies that show improvement in clinical status of children with autism when they are given plasmalogen lipids, or in mothers who take plasmalogens as supplements when they are pregnant. But we do have a report of intriguing evidence that children with RDCP (severe genetic plasmalogen deficiency) get better with plasmalogen supplementation.


We also know that autism is highly correlated with brain inflammation. And this may be the Achilles heel that drives autism. Plasmalogens have a vinyl ether bond that helps battle inflammation. That, however, then depletes the plasmalogen molecule. That would then become a feed-forward, self-sustaining loop that continues to promulgate ongoing deficiency and never-ending inflammation.

But this is simple. We know our food chain has altered and deprived us of critical building blocks like fish oil and Vitamin D. Fish oil is a critical component of plasmalogen lipids. Without it, your body can't make plasmalogens. Without adequate B12, choline, folate, and Vitamin D we are in worse shape. Without plasmalogens, a baby can't hook up their growing brain to all the connections that need to be made. Once deficient, the inflamed brain can't repair itself, and the ongoing deficiency becomes self-sustaining.


www.What will Work for me. All the pieces of the puzzle are there, but for a randomized, placebo-controlled trial. But plasmalogens are just food. No toxicity, no side effects, critically important, and currently Missing In Action. Proper research and proof require randomized, placebo-controlled trials that take years. I believe there is an ethical constraint that prevents careless research when there are concerns about toxicity and drugs that are foreign to humans. But here we are talking about food and simple nutrients with no toxicity....what on earth are we waiting for? If I had an autistic family member, I would be buying plasmalogen supplements and trying it out. The risk-benefit ratio is too favorable to ignore. (Along with Vitamin D, B12, folate, choline, fish oil.......)


References: Biological Psych, Jr NeuroSci, CDC-Autism Data, Nutrients, Autism Parenting, Asian Jr Psychiatry, Med Life Discoveries, Pharmaceuticals.


Pop Quiz


1. What is a plasmalogen lipid?                                 Answer: the super-fluid, super-fragile membrane lipid that makes up some 70% of the brain's synapses and axons (links and wires).

2. What do MRI scans of children with autism show?                     Answer: damaged white matter that correlates with severity of symptoms.

3. Can we take plasmalogen supplements safely?                            Answer: Yes. That's like asking if you can eat eggs safely. (Eggs are loaded with choline, a critical component of plasmalogens)

4. Can I just buy plasmalogens off the internet?                             Answer: Well, not quite. You get plasmalogens whenever you eat any animal food. They get digested. Dayan Goodenowe, a brilliant biochemist, has discovered a method of manufacturing plasmalogen precursors that survive your gut and get into your bloodstream and thereby raising your plasmalogen levels. That's the scientific advance of which we can now take advantage. www.Prodrome.com

5. Is this proven to be safe and effective?                        Answer: No, not proven. Just a glimmer of hope and we need randomized, placebo-controlled trials to prove it.


How Memories are Made

How Making Memory Works - Silent Synapses


Sitting down to a Holiday Dinner with your family? What a memorable event! Want to make sure you remember it? You need filopodia, or silent synapses. This MIT study has just unpacked a huge mystery, how we learn and keep those memories.

Your brain has some 600 trillion - 4 quadrillion synapses, links between neurons. Each neuron is like a computer chip, connected to some 3,500 -4,000 other neurons by long, slender wires called axons with a synaptic endplate. That synapse is where the electrical impulse that travels down the axon is converted into a chemical message through neurotransmitters that are secreted in little packets into the space between the two neurons called the synaptic cleft. We now know that plasmalogen lipids make up some 70% of the membranes of the synapse. Plasmalogen lipids are the only membrane lipids that can shape-shift, allowing the vesicles filled with neurotransmitter to merge with the endplate of the synapse and disgorge their contents into the synaptic cleft. That's how neurons work. Memories are composed of complex webs of neurons utilizing thousands of synapses between them.

This column reported earlier this year on a study from Yale where a novel imaging technique demonstrated that the density of synapses correlates with cognitive function. This validates Goodenowe's research that shows the loss of plasmalogens is predictive of cognitive decline and mortality. You lose plasmalogens, you lose synapses. Your brain shrinks. You lose memories. We call that Alzheimer's.


What's the reverse? How do we make memories? Ah! That's what this study showed. In mouse brains, using a novel method of examining one synapse at a time, the researchers at MIT were able to approximate that roughly a third of synapses (in mouse brains) are actually immature, "filopodia" that are not yet active. They are just out there, waiting to be activated. They already have NDMA receptors in them, but not AMPA receptors. For a synapse to work, it must have both. They start as tiny little branches called dendrites off of axons that are everywhere in the brain in great numbers, as much as 30% of the brain content. You don't want a mature synapse to be altered by new inputs because you want old memories to stay preserved. But you do want a new memory to make a link, and then to be reinforced and made more durable on exposures. That's exactly what this model allows. Very elegant.


www.What will Work for me. This study explains the means and methods of how memory can be built and maintained. The adage, "Learn something new every day" makes sense when you see it in the context of keeping your brain making new memories and reinforcing those immature, early links into more mature, secure links. And to do that, it has to have means and mechanisms for making those links. The primary building blocks are sufficient plasmalogens to build the membranes and sufficient methylation capacity to manufacture neurotransmitters and pump them down axons. That's B12, B6, and folate. The Bs. And finally, you need choline, choline, choline. Eggs and liver. And then you have to have the willingness to expose yourself to the new event. Push yourself to do something new. It's the number one attribute of "super-agers".


References: Nature, MIT News, Yale News, CNBC,


Pop Quiz


1. What is a synapse?                          Answer: The link between two nerve cells.

2. How many do you have?                      Answer: Between 0.6-4.0 quadrillion. Lots

3. What are synapses composed of?                     Answer: Their walls of made of plasmalogen lipids and inside they have packets (vesicles) of neurotransmitter.

4. What is a filopodia?                     Answer: A tiny, immature branch off an axon with partial formation for a synapse, waiting for a new memory to be formed and for it to be activated.

5. What percentage of synapses of mouse brains are made of filopodia?                   Answer: Some 30%


Watch the Youtube video:  https://youtu.be/coaWbDwrTXo


Understanding Ultra-Processing of Our Food

Understanding "Ultra-processing" of Our Food


Now that we know that 80% of us eat at least 20% of our food in "ultra-processed form", which increases the rate of cognitive decline by 25%, it becomes incumbent on us to learn how we can change that. We need to understand processing and what that means. This new construct has emerged in the last decade and is now gaining momentum. Instead of focusing on individual ingredients like protein, fat, and carbs, we look at the whole product and how it has been altered from the original ingredients used to make it. What is processing?


Start with that. Unprocessed food is picked by you from the tree, or dug up from the garden. Then you eat it as is. The vegetable aisle at the grocery store will do. Minimal processing is the simplest next step. Remove the inedible parts. With grains, knock off the hull. With apples, cut out the seeds in the core and the stem.

Secondary processing includes grinding up a grain into a powder we call flour and then baking it. You might include freezing, but then there are those who will argue that freshly frozen vegetables capture their peak nutrient value, so freezing isn't so bad for vegetables. But popsicles? Fermentation adds wonderful probiotic effects but is also on the secondary processing spectrum. Frying vegetables? Now you are cooking at high heat and adding fat to the food.

The third stage turns the grains into edible products. Baking, frying, microwaving....and all those raise new questions. What used to be three groups has now been made into four.

The NOVA classification now groups foods into those four categories. The third category, processed foods, were defined as “Generally produced to be consumed as part of meals or dishes or may be used together with ultra-processed products to replace food-based freshly prepared dishes and meals.” Typical foods described for this category were canned or bottled vegetables and legumes preserved in brine; peeled or sliced fruits preserved in syrup; canned whole or pieces of fish preserved in oil; salted nuts; unreconstituted processed meats such as ham, ham bacon, and smoked fish; and cheese. (Sounds a lot like what we eat every day.)


There there is category 4, "ultra-processed." Even Category 4 has evolved over the last decade through 4 stages. Stage 1: The first definition alludes mainly to the use of both food additives and salt in food products. Stage 2: The second introduces the putative impact of ultra-processed foods on accessibility, convenience, and palatability of ultra-processed foods. Subsequently, the definitions become longer and include more elements. Stage 3: The third definition built on previous definitions but introduced 2 new angles. One is the nonavailability of ingredients used in ultra-processed foods from retail outlets such as supermarkets, and the second introduces food additives as the most widely used ingredients, in numerical terms, in the manufacture of ultra-processed foods. 

The next definition now introduces the role of food fortification as a defining element of ultra-processed foods. Further definitions introduce new elements such as the importance of foods synthesized in a laboratory, based on organic materials such as oil- and coal-based additives and flavoring compounds, a specification for the minimal number of ingredients to be found in these foods, and then an emphasis on the inclusion of salt, sugars, oils, and fats as a starting point for defining ultra-processed foods.

That is what brings us today to what we buy in the grocery store. Over 60% of American calories come from ultra-processed foods. They are in packages, with long shelf life, with more than 5 ingredients including sugar, fat, preservatives and many things you can't pronounce. You can see for yourself. Go to your pantry and read the labels just for the number of ingredients. If there are more than 5, it meets the simplest criteria for Category 4, "Ultra-processed". It isn't original food anymore. There is something about that mix of additives that is meant to be preserving and enhancing the food product to increase its shelf life, its taste, its addictive qualities....that's killing us.


www.What will Work for me. I picked up an Atkins bar I had on my shelf. Good for me? Right? Keto, after all!! Hmmm. Just 2 grams net carbs. But I counted. 13 ingredients. Do you know what vegetable glycerin, polydextrose, maltilol, sodium caseinate, soy lecithin, sodium metabisulfate, and "natural flavorings" are? Me neither. But that's more than 5 things I can't buy in the store. I thought it was a coconut bar with a shell of chocolate. It qualifies as ultra-processed. My takeaway is that if it comes in a package of any kind, and has any sugar, fat, salt, flavoring, color or preservative, it flunks. And 10 minutes in my pantry: everything flunked. Bummer.


References: Healthline, BMJ Open, Current Dev Nutrition, Educhange


Pop Quiz

1. Name three unprocessed foods you ate today? Answer: Avocado, lettuce, ...... (couldn't get to three)......

2. Name three minimally processed foods you ate today? Answer: Boiled egg......no, it was deviled egg with Mayo and Sriracha sauce.......(14 and 27 ingredients on the label). My answer...Zero

3. Can you define what ultra-processing means? Answer: Designed to have a long shelf life, with sugar, salt, fat and multiple secondary colorings, flavorings, preservatives, with more than 5 added ingredients,

4. What is the impact of your eating ultra-processed foods? Answer: 25% faster cognitive decline than those who eat less than 20% of their calories from such foods.

5. Average folks eat how much ultra-processed foods? Answer: > 60% of calories.


Ultraprocessed Foods Damage Your Brain

Ultraprocessed foods damage your brain


This is a well done study from Brazil that answers a question not looked at before. What happens to upper-income folks who have resources to buy whatever food they fancy? You see, as we get wealthier, we choose more ultra-processed foods. Or, as we get poorer and more urbanized, we can only afford the most egregiously ultra-processed foods. Everyone knows that living on a tiny farm in Sicily and eating lots of olive oil, vegetables and some fish results in great health outcomes. The Mediterranean Diet has been shown to be good for you. But do we eat it? Or do we choose to go to the deli or fast food place on the way home and pick up a quick burger and fries? Pizza is, after all, the #5th most popular food in America, Burgers are #1, Fries are #3.... are so convenient.


The participants in this study were all civil servants from across Brazil. There were 10,775 participants, 55% women, 53% Caucasian, average age 52. They were followed for 8 years on average and tested at regular intervals for immediate and delayed word recall, word recognition, and phonemic and semantic verbal fluency tests. Their food choices were collected and noted.

The findings are quite remarkable. If the subjects ate more than 20% of their daily calories from "ultra-processed foods" the subjects showed a dramatic increase in cognitive decline. Anyone above the first quartile in the population of ultra-processed food consumption had a 25% increased rate of cognitive decline. Let's repeat that, in case you had some pizza before you read this. Three-quarters of folks, the top three quartiles, were all in trouble because they had more than 20% of their calories from ultra-processed foods. Ouch!!!


This raises the question, what is ultra-processed? Essentially it comes down to foods that start with food-like ingredients but then has a majority of ingredients being flavorings, preservatives, colors, binding and thickening agents, all not routinely sold at retail. Read the FAO report from the UN.

This is a sea change. We have talked about foods being "Whole Foods" but really we have split our thinking into carbs, fats, and proteins. This categorization changes that construct back into how much the food has been altered from its native, original self. A Peruvian potato is quite a different thing from a modern potato that is pulverized into a paste, soaked in oils, saturated with fat and preservatives, and sold in a cardboard tube.


"The most important factor now, when considering food, nutrition and public health, is not nutrients, and is not foods, so much as what is done to foodstuffs and the nutrients originally contained in them, before they are purchased and consumed. That is to say, the issue is food processing—or, to be more precise, the nature, extent, and purpose of processing, and what happens to food and to us as a result of processing". That puts it in nicely.


And this study is the first, large study to take that clarion call of alarm and examine it in a population and for effects of ultra processing. They are stark.


www.What will Work for me. This is so important, we will talk more about it next week. I wanted to catch your attention with this story so that you learn this as urgently and thoroughly as I do. We should all know all the categories so that we can evaluate everything we eat, every day by that classification and make our choices accordingly. Stop thinking about proteins, carbs and fats and start thinking about the 12 ingredients on the package you never heard of and can't buy anywhere. And then, the Mediterranean Diet will make pretty good sense.


References: JAMA Neurology, In the Kitchen, Current Devel Nutrition, FAO, Public Health Nutrition,


Pop Quiz

1. What is the definition of Ultraprocessed foods?                   Answer: Foods that have more ingredients than their native, original food composed of preservatives, colorings, flavors, and conditioning chemicals. (more details to follow next week.)

2. What did this study show?                    Answer: Folks who ate more than 20% of their calories (75% of this population sample) from ultraprocessed foods had a 25% increased rate of cognitive decline.

3. This data matches what we see when we eat "Keto" or "Vegan". T or F                       Answer: Mixed picture. It changes the conversation from protein, carb and fat to how much the food has been "prepared" and altered from its original self. Mostly this has to do with making products with long shelf lives that have enhanced, more intense flavors from added salt, sugar and other flavors. Think pork loin versus bologna. Think white bread versus whole grain cereal. Think energy bar versus a banana.

4. It's easy to calculate how much we eat ulltraprocessed foods. T or F                   Answer: It's a whole new paradigm. We have to learn to think differently.

5. America's number 1 food is...?                     Answer: a hamburger followed by hotdogs, french fries, Oreo cookies and pizza. And which of these would be considered ultraprocessed? Read next week to understand why all of them qualify.


More Fish Oil, Better Brain

More Fish Oil, Better Brain


I bet you knew that. But here's proof. And it makes perfect sense. This is where it is coming from. The Framingham study is just about the largest, longest-running survey of a group of average Americans we have. We are, in fact, on the third generation of participants. And this study was on those on those in mid-life. That's the key here.

What this study found was in 2,183 dementia- and stroke-free participants (mean age 46 years, 53% women, 22% APOE-e4 carriers that red cell omega three index predicted better cognitive function. The red cell index indicates the sufficiency of omega-3's in your diet. Humans can't make omega-3 fatty acids so we have to eat them. They are made by green plants. Wild caught animals, deer, elk, moose, rabbit, fish all have omega three's in them. The APOE-e4 gene is the one that predicts severe risk for Alzheimer's and 22% is about the normal representation in the population. They also showed better hippocampal volume on MRI, which correlates with less cognitive trouble. It's that simple. Conclusion, more fish oil, (omega-3 fats we can't make ourselves), better brains.

This doesn't have to sound like gobbledegook. Let's explain. Your brain is fundamentally made of plasmalogen lipids. They make up some 70% of the lipid coating in the membranes of brain cells and much the same in the interior of the 5,000 mitochondria each brain cell has. Plasmalogen lipids are the most liquid of lipids which makes our brains fragile (hence you get concussions easily and we evolved a brain floating in water and suspended by delicate little stretchy cables to cope with that.). That liquid quality allows the membranes of your brain to be able to change shape rapidly. That means you can think rapidly. See the world in real time. Hear rapidly. Use language. Indeed, we would not have evolved a central nervous system without plasmalogen lipids. That simple. And that fluidity all depends on omega fats incorporated into the plasmalogen molecule.

Omega-3 fats, you see, have 5 double bonds in them, all in cis-conformation. The cis-conformation is actually a tad unstable. If they could only flip to "trans" formation, they would be much more stable. But we all know "trans" fats are bad. That instability allows each of those double bonds to swing around. That swinging allows shape-shifting which is integral to a vesicle of neurotransmitter fusing with the synapse membrane and disgorging its contents into the synapse. All in a few nanoseconds. And each double bond confers a 30-degree bend in the molecule. With 5 double bonds, you have a virtual spiral shape. That shape can't pack tightly, which leads to more fluidity. And where do those omega fats go? They are incorporated into the plasmalogen molecule. That's where they go.

 

Without omega fats, you can't make plasmalogens. Humans actually incorporate more and more plasmalogens into their brains until age 50. Peak brain is age 50. But from 50 to 70, the average human loses some 20% of their plasmalogen content. (Remember, nature isn't interested much in you once you have passed on your genes, and age 50 is pretty much done with doing that.)

We know that Icelanders who eat the most omega-3 fats in the world have very low rates of depression and many other markers of healthy brains. But this study is the first for looking at mid-life french fry-eating Americans. That's when you want to be building up your brain. Once you are over 60, measuring and repairing your plasmalogens will be central to preventing cognitive decline. I'm betting on that. I'm not betting on that antibody on the news today doing anything meaningful.


www.What will Work for me. Just wait. 10 years from now Plasmalogens will finally make it to the mainstream and be acknowledged as the real way to prevent cognitive decline. All the silly drugs that are being introduced right now will be flashes in the pan. But you want to be on all the ingredients that make for a healthy plasmalogen supply. That included fish oil, lecithin, B12 and folate, NAC, and acetyl-carnitine. It takes a 30-year study to prove the effect, and that is what makes the Framingham study so valuable. That level of proof was long in coming. But your life is not a flash in the pan. We want your long life to be fulfilling, and memorable.


References: Neurology, The Atlantic, Lipids in Health and Disease,


Pop Quiz


1. Where does fish oil end up?                        Answer: At the SN-2 position on a plasmalogen.

2. What quality does that confer on the plasmalogen?                       Answer: Fluidity and the ability to shapeshift. The fundamental properties needed to make a neurological system. Rigid membranes would not do.

3. At what age do we have the highest amount of plasmalogen lipids in our brains?               Answer: Age 50. Peak brain.

4. Does it make sense that more fish oil makes for better brains?                       Answer: That's just what this study showed.

5. To make memories and keep them, you have to have a web of synapses all linked together. What is the cause of Alzheimer's?                                 Answer: the loss of synapses secondary to the loss of plasmalogens. Maintain the fish oil and the plasmalogens and your brain always wants to rebuild the memories from what you are doing and remembering each day.


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