Plasmalogen Loss Drives Coronary Artery Disease
At last, we are down to the basic, basic biology and understanding of how coronary artery works! Dr. Dayan Goodenowe in his discovery and development of plasmalogens in human disease has opened a door of understanding that finally is creating a construct we can wrap our brains around and bring understanding to the very core of human illness. This is like the Unified Theory of particle physics. It's all about the balance of your "redox" capacity and health down at the molecular level. Let me see if I can explain it in understandable language and how that relates to your arteries in your heart.
You first have to start with the "endothelium" of your arteries. That is the inner cell layer surrounding every artery. It is pretty stupid. It only has three jobs. One: constrict or squeeze in. (We call that high blood pressure or endothelial dysfunction). Two: it relaxes. (This is normal blood pressure and that's good - healthy, optimal.). Three: it can call for help. It has millions of TLR's (tiny little radars) that are constantly monitoring to see if you have been invaded by germs. Ok, and all of that depends on the endothelium being intact. By intact, I mean all the cells are tightly connected to each other. The very first step in coronary artery disease is the advent of "leaky endothelium". That is caused by hydrogen peroxide being released from a variety of sources. There is good proof on this account in that we can see the damaging effect of homocysteine being broken down to uric acid and making peroxide on the way. And blood tests of higher uric acid and higher homocysteine both correlate, sure enough, with more artery disease.
Well, what happens when you get that leaky endothelium? Ah! That's when oxidized LDLs can wiggle their way into the wall of the arteries. That starts the accumulation of more LDLs and the generation of foam cells. Eventually, that plaque builds up and plugs arteries up, causing a heart attack, or the plaque ruptures and gunk flows downstream and causes trouble there. This is how strokes get started.
How do we know plasmalogens are involved? Multiple studies from a variety of sources have demonstrated this effect. A very elegant publication on dialysis patients showed that those who died from heart disease had much lower plasmalogens than those who didn't. Plasmalogen levels are a pretty good indicator of "oxidative stress" and low levels are dangerous. Low plasmalogens, you get a heart attack! High plasmalogens, you don't. Simple. That's one.
Another great study was in Atherosclerosis in 2017. In that study, they showed that folks with peripheral vascular disease have very high risk of heart attacks in the next few months, and that risk is proportionate to how low their plasmalogen levels are. Doing an angioplasty on or bypass surgery on your narrowed arteries doesn't fix the "endothelial dysfunction". Repairing your plasmalogens does! This is huge!
We can go on! Another study from another angle, also in the journal, Atherosclerosis from 2015, looked at HDLs, high-density lipoproteins. They are meant to be protective against heart attacks. They exert their effect partially by protecting those precious "endothelial cells" lining your arteries from dying through the process called apoptosis. With low plasmalogens, they don't protect them from apoptosis.
You can have an angioplasty of every artery in your body but you haven't reversed the disease, you have only repaired the short-term symptom. Come back in 6 months for a second angioplasty. Fix the plasmalogens and you have gotten to the core disease process. Then, you don't come back. Fixing blocked arteries is big business and big bucks, and doesn't really work. Fixing plasmalogens is cheap compared to one angioplasty, and it works.
The basic disease is the loss of plasmalogen "redox" capacity, the ability to soak up and neutralize reactive oxygen species by that precious vinyl-ether bond built into the plasmalogen. What causes the depletion of plasmalogens? Ah, there is the mystery of modern civilization. In biochemical terms, it's loading too much NADPH into the mitochondria and leaking out too many reactive oxygen species. In lay terms that we understand it means too many calories, too much sugar, too little exercise, too many environmental toxins, too little sleep, not enough exercise......If you want to go down that rabbit hole, read Biochem Biophys Acta article on Aging Peroxisomes and how they make less catalase. Less catalase means more hydrogen peroxide floating around in your blood. What does that do? If you get that right, I've succeeded in introducing you to this topic. ............(Did you get it?) Catalase breaks up hydrogen peroxide and thereby protects the lining of your arteries from getting leaky. What do plasmalogens do? They are the fatty acid molecules in every membrane that have the ability to soak up damaging "oxidants". But they get used up when can't make them as fast as we use them up.
www.What will Work for me. I'm getting older which means like it or not, my peroxisomes are not as robust as they used to be. I'm walking every day. I'm doing intermittent fasting and avoiding sugar as best I can. But darn it, this last week I had a birthday and I had a little cake. Life happens. But I am taking Dr. Goodenowe's Plasmalogen replacement supplements every day. My bet is that this keeps me away from the cardiologist's angioplasty suite. Fish oil is one of the key building blocks of these precious plasmalogens. That's why you want sufficient fish oil in your diet. But old peroxisomes, where plasmalogens are made, remain old and less functional. You can't un-age them, yet. You can take plasmalogen replacement therapy. That should be a slam dunk.
1. What is "endothelial dysfunction"? Answer: The first step towards artery disease with fatty lipids being deposited as the end marker. You get a leaky endothelium with the subsequent ability of oxidized LDL's to seep in.
2. What is the root cause of it? Answer: Too much hydrogen peroxide in your arteries, caused by insufficient catalase to neutralize it.
3. Where does catalase come from? Answer: It is an enzyme made in your peroxisomes. Your peroxisomes are in every cell of your body, right next to your mitochondria. Their job is to make plasmalogens and catalase, and feed mitochondria their basic, preferred fuel of fatty acids.
4. What's the best way to fix the disease called "heart attack or stroke"? Answer: If you are having those, the best treatment is to immediately go to a hospital and repair the damage that's happening ASAP. But that is just symptom repair. The long-term cure is to fix your plasmalogens.
5. Is this the end of coronary artery disease? Answer: Are you kidding? The power of the sugar lobby, the couch potato lobby, the trans fat, the pesticide, the toxin, the .......
Energy a Bit Low? Blame Ceramides
Do you feel washed out and tired after a meal, or at the end of the day? Dragging around, wishing you had a pick-me-up to get some get-up-and-go? Is your energy level curiously just rotten? Read this.
We are beginning to get a better understanding of how our energy flow works through understanding core metabolic processes right down in our mitochondria, our local energy factories. (Remember, you are 10% mitochondria! Your heart and brain are closer to 30%.). Mitochondria make energy in the form of the molecule ATP. So far, so good. But here are some guiding principles in making energy I bet you weren't aware of. Did you know that your mitochondria are really happiest if they can switch back and forth between running on fat or running on glucose? Did you know that they do better when you are on just one pure source of energy (glucose - carbs) or fat ( beta-hydroxybutyrate.) and not mixed. When you mix sources of fuel, it's like having two hoses filling your gas tank on your car. Something overflows. You get more reactive oxygen species (ROS) and that makes for more damage? Did you know that you start to drift into ketosis if you don't eat for 12 hours? Yup, and more ketones at 14 and even more at 16. But too much of fat, carbs, protein all at once, a typical American big meal, and your mitochondria get overwhelmed with too much fuel. And some of if is just plain bad.
Bad fuel #1 is fructose. Now, through most of human history, we got ripe fruit (hence fructose at about 5-6% of ripe fruit) only in September for a few weeks. Or, for any of us with a mulberry tree in their yards, you can imagine snarfing down mulberries all day long for about a week in July. We only got sugar, half glucose, and half fructose, in about the year 1500 or so, and only ramped up to 120 pounds a year each in the last 40 years with the addition of high fructose corn syrup. Fructose at such quantities is a new phenomenon to our mitochondria. The problem with fructose is that we don't have a way to slow it down. It goes straight to your liver, kabam! Your liver cannot turn it away. We exhaust our liver cells that frantically try to protect themselves by making fat and scavenging ADP into AMP and then uric acid. If you have fatty liver or high uric acid, you are probably well-served if you seriously examine your sugar intake because you are tip-toeing along the edge of liver failure. If you don't believe this, watch the movie "Super Size Me" and see someone who almost died from eating at MacDonald's three times a day for a month.
We now know how your liver cells protect themselves. They make ceramide fats and palmitic acid (16 carbons long) from all that fructose. Ceramides are stiffer molecules than most fats, making your cell walls more rigid and less capable to taking up arriving nutrients. Ha! Short-term strategy works. It saves the cells. But another, more insidious event happens. Ceramides block the insulin receptor, in part because of their stiffening effect on the cell membrane. And that, my friend, is how insulin resistance gets started. Your rising level of insulin corroborates with inflammation, and you now have adult-onset diabetes off to the races. With high levels of insulin in your blood, your fat cells get the message not to open up and share their fat. You have the perfect double whammy to blocked glucose uptake (so less energy) and locked fat cells (less energy).
You are in a dilemma. You have plenty of stored energy. Just check out your fat tissue. But you can't get to it. And the only, only way to feel good is to eat enough glucose to get huge swings in blood sugar and then plunges thereafter. See-saw, see-saw. And you are exhausted to boot.
Once you understand the mechanisms, you can find the way how to climb down off this cliff and get your mitochondria back to working. You can measure your ceramides if you are curious. You can certainly measure your A1c to see how "diabetic" you are. You can measure your insulin level. It should be below 7 at the worst. Five would be better.
Key principles to fixing yourself is stopping the fructose and slowing way down processed carbs. Then, focus on rebuilding your mitochondria's ability to be metabolically flexible by stretching out the time between meals, particularly at night. That way you burn up all your carbs and get practice at switching over to fat. Add more green vegetables that also make beta-hydroxybutyrate and you ease away from glucose carbs. Add olive oil. Reduce your protein down too. And all those together will get you back to metabolically flexible, with more energy and fewer ceramides. You can do it.
Did you know that ceramides predict your risk of heart disease more accurately than LDL cholesterol? Yup...but that's for another day.
www.What will Work for me. How to lower ceramides? Well, well....that's the question. Start with cutting the sugar out of your diet. If you wanted to really cut the sugar, that means you have to take on ketchup and peanut butter too! Eating extra olive oil in a Mediterranean diet has been shown to reduce heart disease commensurate with its ability to lower ceramide blood levels. More green vegetables in your diet delivers more beta-hydroxybutyrate to your mitochondria, slowly. Intermittent fasting, compressing your calories into 8 hours does it too. Hmm. I'm fasting for 5 days a month. Perhaps I need to learn to navigate past breakfast too. I found a ceramide blood test on Goodenowe's plasmalogen test. Mine was higher than I like. Bummer.
1. What are ceramides? Answer: they are a rigid fat that makes membranes firmer, or stiffer. (Not good)
2. What is the key means by which you make them? Answer: Eating fructose in the form of too much HFCS, table sugar, hidden sugar, fake names for sugar (like dehydrated orange juice), and forcing your liver to make palmitate, which then hits your mitochondria hard.
3. What would your mitochondria prefer? Answer: Mitochondria want to get back to metabolic resiliency and the ability to flex between carbs and fat. You can do that by compressing calories into 8 hours a day. You naturally do it when you exercise to exhaustion. You get there faster if you eat more vegetables and more olive oil.
4. If your mitochondria get overwhelmed and your cell responds by making ceramides, what happens to your ability to make ATP energy? Answer: It goes down. So do you.
5. Can I measure ceramides? Answer: Just emerging. Not yet in the major labs and certainly not in your regular clinic. The Mayo Clinic is all hot on it and has it. Goodenowe measures them with his blood panel. (www.Prodrome.com).
How Low Plasmalogens Start Cancer
Did you get that? We have a screening test in Plasmalogens around cancer that is emerging. Why didn't we know this earlier? Explain all this? Well, here goes. For starters, it is well known that many cancers have dramatically different rates between countries, and more importantly, over time. You can compare countries to each other and see huge variability. For example, data from the Global Cancer Observatory will show you that America has 15 times the rate of thyroid cancer in India. There must be something in the environment. Ok, let's follow that thread.
We have also known for some 40 years that there is a curious connection in cholesterol synthesis, export, and blood lipids in cancers. In fact, lipid synthesis disorders are far more consistent in cancers than blood glucose disorders. When you give cancer-causing chemicals to experimental animals, the first thing that happens is dysregulation of lipids, with abnormal LDLs and changes in LDLs and HDLs way before the cancer shows up, with those changes being predictive of cancer coming down the pike. Hence, the possibility of a screening test. Again, as an example, breast cancer is strongly associated with very high HDLs and lower LDLs. (Sort of the opposite of what you are used to thinking of protection from heart disease). To prevent breast cancer, you want HIGHER, yes HIGHER LDLs, and lower HDLs. Wrap your brain around that one. (We will get to the explanation: hang in there.). You see the exact same pattern in Chinese men with lung cancer. Danger from high HDLs and low LDLs. I mean a 347% increased risk with that pattern. That's huge. What's amiss?
If you don't mind my geeking out a little bit: here it is. Tiny changes in the content of cholesterol in your membranes results in massive changes in glucose transport into a cell. We've known that for 40 years, and it got lost in the pile of other research. All cancers must make that change. They need glucose, hence, they also must, must, must alter their membranes to put more cholesterol molecules into their cell walls. The mitochondria of cancer cells have three times the cholesterol in them compared to normal cells. That makes the membranes much more rigid, and much more open to importing the glucose that cancer cells thrive on. It also makes the membranes much more prone to exporting citrate, the baseline fuel that cancers get most of their energy from. Energy in cancer cells, instead of going into making ATP gets diverted into making more cholesterol and exported in HDL particles. (See how cancer cells got to high HDLs?). The normal feedback look inside normal mitochondria is lost, and that feedback loop is dependent upon the membrane content of plasmalogens and cholesterol. Cholesterol goes up, plasmalogens go down. There you have it. Low plasmalogens are staring us in the face.
Cancer cells get only 20% of their energy from glucose. Where do they get the rest of their energy from? If you want to do a deeper dive, you can go down that rabbit hole and find that cancer cells have to get glutamine as an energy source and from which they make aspartate and polyamines. Blah, blah, blah. I love and now understand it, but it is complicated. The nexus it turns on is the plasmalogen levels in your membranes.
Pull back out and take the bigger view. Follow the dominoes as they drop. The plasmalogens in your membranes are the key feature here. Cancer cells can't get more cholesterol into their membranes until you lose control of cholesterol manufacturing and exporting. That takes lower plasmalogens. Once you have that, you can start bulking up the cholesterol in your mitochondrial membranes and in your blood with high HDLs. That allows you to change your mitochondria to making more citrate and lactate, and off you go. More extramitochondrial acetyl CoA and citrate in your cells, the faster the cancer grows. Want to slow a cancer down? Well, in bench research, we can do it by replacing plasmalogens. More plasmalogens in your membranes, better cholesterol control.....better cancer control. The tip of the spear is low plasmalogens.
www.What will Work for me. That data shows that virtually every cancer has low plasmalogens for years prior to the cancer showing up. We aren't quite sure why plasmalogen content of your membranes drops. But there it is. Low plasmalogens in your blood are like a prepared garden for cancer to thrive in. Do we have proof that you can hold cancer off by taking plasmalogens? Not yet. We sure have bench research showing it slows them down. Now, can we measure them in you? YES! Can we replace them? YES. Are they dangerous to take? NO! NO! NO! It's just food. It's just fish oil placed in just the right places with just the right chemical bonds. At the heart of it, plasmalogens play a huge role in making every membrane in your body work properly. And if you look at folks with normal plasmalogens in their blood, they simply don't ever get cancer, dementia, or just plain die. They are the few chosen who get to live to 100 with a working brain. I want to be on that team. I measured mine. I was in the moderately low group. My garden was all rototilled and ready for cancer to grow. For Alzheimer's to blossom. You know how long it takes to get your blood level to normal? One dose. I'm putting my nickel down on that bet: normal plasmalogens dictate a long and healthy life.
References: Global Cancer Observatory, Critical Reviews in Biochemistry, Jr Natl Cancer Instit, Int Jr of Cancer, Brain Sci, Biochemistry, Science Direct,Euro Jr Biochem, Science Direct, Membrane Anomalies of Tumor Cells, Lipids in Health and Disease, Plos One, Lipids in Health and Disease,
1. What are plasmalogens? Answer: They are the lipids that have very unique characteristics of being able to capture free radicals (making them the neutralizer of first choice in your body). They are also uniquely extremely liquid which makes membranes with embedded proteins work better, thereby allowing regulatory functions, like the control of cholesterol to work better.
2. What happens if I have low plasmalogens? Answer. You won't know it. You don't feel anything. But your cells begin to struggle. You have a fertile field in which trouble can happen. Bit by bit, your neurons give up and collapse. Your links in your brain start declining. On and on. Here you heard about cancer. We haven't gotten to all-cause mortality yet. (Debbie Downer has her way with you.)
3. Why didn't we know this sooner? Answer: This has been a whole new field of science developing by starting from the opposite end of research. Instead of studying a disease, Dayan Goodenowe developed and discovered the process of examining every measurable compound in your body that was in trouble over time as people got sick. That required supercomputing power and long-term epidemiological research.
4. Is it dangerous to take plasmalogens as supplements? Answer. No, they are just food. It's just the right food. You can't take oral plasmalogens as they get digested in your stomach. Goodenowe has been a unique genius in developing and patenting the chemical process of manufacturing plasmalogen precursors that survive your gut.
5. Where can I get tested? Answer: You can get it directly from Prodrome.com or any doctor affiliated with Dr. Goodenowe's lab. We do it at Brookfield Longevity and give you a price break because our volume allows discounts.
Natural Gas is Your Best Friend
No, no, no! NOT the stuff that comes out of the ground and heats your house. We are talking about the stuff that you make in your gut and about which you make a funny face and blame the dog. This is deadly serious and was in fact the topic of a Nobel Prize in Medicine. The gases you make in your gut is hugely important to managing your body. (Many kinds of gas.) You want more of it/them. The evidence is mounting and very interesting.
The Nobel Prize story is all about NO and how it dilates blood vessels and the discovery of it being a gas that did the messaging. It's now common knowledge that that's how Nitroglycerin works on your heart and relieving angina by dilating blood vessels. And if you weren't aware that men think NO is a really cool thing, you haven't been watching all the hawkers on TV and their promises of "new awakenings" in what was once dead. The field of gut-produced gases being important signaling messages was born.
Another example. Did you know that we can now measure the ability of the bacteria in your mouth, in your gums, and under your plaque to make NO? That NO lowers your blood pressure a couple of points. Almost as much as any blood pressure medication. Swish your mouth with alcohol mouth wash and the benefit goes away. Hmm. You might consider not so much swishing.
In 2019, in the journal Cell, came the study showing that NO produced in the gut attaches to thousand of proteins in the blood by a process called S-nitrosylation, which subsequently turn genes on and off. The researchers worked with the roundworm, C. Elegans, and showed the phenomenon by feeding developing worms bacteria that produce nitric oxide. They then selected one very important protein--argonaute protein, or ALG-1--that is highly conserved from worms to humans and silences unnecessary genes, including genes critical for development. More nitric oxide, some organs stopped developing completely! Whoa. The bacteria in the gut were turning off host genes. Interspecies communication and genetic manipulation!
Well, it's not just NO. Methane joins the fray. You know, the stuff you lit when you were a teenager so that you wouldn't contribute to global warming. Methane. Common natural gas. Did you know there is now intense interest in how methane impacts mitochondria and your production of energy? Yup. Methane turns out to be a modulator of inflammation too. Again, a gas starting in your gut and changing how you make energy, whether you are inflamed or normal.......
Hearing about NO and methane, you shouldn't be surprised when we add Hydrogen to the list. Simple H2. Again, hugely important in inflammation. It activates the Nrf2-Keap1 pathway, one of the main inflammatory pathways. Implications might be huge. For example, Parkinson's patients are known to have less H2 production in their gut biome. You heard that! A horrible disease shown to have less anti-inflammatory gas production because of an alteration in the bacteria of their gut. So, which came first, the bacteria or the gas or the disease?
Do you want to add hydrogen sulfide to the list? Another gas, another emerging field of research that affects inflammation. Stay tuned. More to learn.
What this constellation of research is leading to is an increasing awareness of how the biome in our gut manages us and is important for us to care for. You can't just take your "biome" for granted. We need to take care of that "organ" that you so carefully dispose 30% of every day. It needs to be fed the right food, and avoid the wrong toxins.
www.What will Work for me. I'm all over this. I love this type of research. I bought a hydrogen generator for home and office so that my water is now hydrogen water. And at the grocery store, I had to buy some "Sun Chokes", the name now applied to Jerusalem artichokes, mentioned in every list of good prebiotics. (They are a native American plant, cultured and eaten by Native Americans for millennia, and have nothing to do with Jerusalem. They look like sunflower plants. It's their root that looks like a potato you want to eat more of. Bake them with olive oil, salt, and garlic and they taste great. Lose the potatoes. Substitute "sunchokes". ) What I really want to learn is how to increase my NO, sulfur, and methane while still living in proximity to other humans. That may take some careful negotiations. Or, just a healthy gut that isn't leaky.
1. What natural gases are present inside our bodies? Answer: oxygen, O2, nitrogen, N2, Methane, NO, CH4, H2, SO2.....a lot of them
2. Why is the gut so important to these gases? Answer: because that is where they are made.
3. Can you name one effect on our bodies by these gases? Answer: H2 turns off inflammation. NO dilates blood vessels and lowers blood pressure. And makes men happy. NO also tags proteins that turn on and off many genes. ....
4. How can we manage these gases? Answer: heath healthier diets and avoid gut toxins......like sugar, wheat, glyphosate. (Buy organic and lose 80% of pesticides)
5. What is one thing I can do today to tip towards a healthier gut? Answer: more fiber of all sorts. More prebiotic, more raw, more vegetables, more vegetables, more vegetables.
Genomics, Cancer and Metabolomics - Big Words but May Solve Cancer
Just say the word, "Solve Cancer" and everyone perks up and pays attention. But the current method we are following hasn't worked. Chemotherapy of solid tumors only delays the cancer, for the most part. Surgery works, some of the time if you catch it early enough. Why are so many of us getting cancer, so young in life? Well, let's see what the field of Genomics and Metabolomics might offer.
First of all, genomics. If a woman has the BRCA gene, her risk for breast cancer/ovarian jumps a lot. (72% by age 80). But that's only 2% of breast cancers. Let's look into the human genome and measure all your SNPs, (genetic mutations we all carry which increase risks for various diseases. For example, having CYP 19A1 results in lower estrogen in postmenopausal women and better response to aromatase inhibitors if chemotherapy is warranted. You can take a deep dive into Vitamin D, inflammation, MTHFR, and many other genes to paint a picture of benefit or risk from various SNPs. Genes point to potential risk.
Metabolomics points to what is actually happening. What proteins and compounds does your body actually make in the environment you are living? That's metabolomics. With that in mind, here is the cutting edge of research right now, an edge that might offer a thread of hope.
The hypothesis: we start life in a healthy state, and our bodies were programmed to always try to get back to that state of optimal health. Our bodies were also programmed to stop being fertile, and then decline and get out of Dodge to allow the next generation to take over. Throughout most of human history, we lived to about age 35, with only 5-10% of humans living into their 50s or 60s. We now recognize that we have three stages of disease. 1) Healthy, no disease. 2) Apparantly healthy but measurable defects - a prodrome state. The prodrome state has "pressure" or "guidance" to swerve us away from optimal health towards illness and disability. 3) Disease. The treatment of disease by our modern health system returns us to 2) not 1). That's the problem. You cut out your cancer with surgery, and you are still in "Prodrome", even if you actually cut out every single last cancer cell. Getting back to 1 is the key to "Longevity".
Here is the example. Plasmalogens. Did you know that EVERY cancer victim can be shown to have very low plasmalogens? Control groups with no cancer have normal plasmalogen levels. If you cut the gastric, colon, pancreas cancer out, your plasmalogens are still low.
Here is the series of dominoes that the hypothesis entertains. The first step is our activation of a change in "oxidants", our "redox balance" if you will. This probably happens for a variety of reasons, the first being the over-availability of calories, particularly refined grains and sugars. We always have extra pressure on our mitochondria, pushing calories in instead of sucking them out. (This is why intermittent fasting and fast-mimicking have such power, we change that dynamic to giving our mitochondria a daily/monthly break to catch up on all that extra redox imbalance.
The second step is the tipping away from redox health by consuming the largest pool of antioxidant presence in our bodies: plasmalogens. Ah! That's where the prodrome comes in. Plasmalogens make up some 70% of our axon and synapse membranes, making them incredibly fluid and capable of rapid response and action. Our nerves are so precious and so delicate that we surround them with this halo of protection. Plasmalogens have an incredibly powerful antioxidant role because of a very special bond called a "vinyl-ether" bond. It stops the oxidizing effect of free oxygen radicals cold and doesn't let it propagate. But it depletes that one plasmalogen molecule. A new one has to be made to replace it. We become plasmalogen deficient, allowing the redox state to damage other processes in our body, setting off the pathway to cancer.....and a host of other illnesses.
That vinyl-ether bond is made in the peroxisome and nowhere else. The peroxisome is so valuable, every cell has them, making tons of plasmalogens when we are young. A mysterious process degrades the activity of the very first enzyme in that manufacturing, Dihydroxyacetone phosphate acyltransferase (DHAP-AT). It is the rate-limiting step of making new plasmalogens. As we age, DHAP stops working. Follow that thread? We don't make enough plasmalogens. They are the means by which we cool off inflammation. The needle tips to out-of-control metabolism. Cancer gets started.
Let's make it a little easier. It all started when you got that bowl of extra chips when Virginia got drubbed by Ohio at the NCAAs last night. You spent 4 hours n the couch watching TV instead of walking, and worse, you only had 8 hours of no calories. Your mitochondria get getting waves and waves of calories, never being calorie deficient so they could flush out those extra reactive oxygen species. You were in a constant state of "oxidation", as was Virginia. They looked rusty.
www. What will Work for me. Bummer. The direct link isn't quite there yet but the evidence for all the steps is. Can I take plasmalogens as a supplement? Yes. Do they help prevent cognitive issues? Yes. Do plasmalogens help the course of MS and ALS? Yes. Can I take plasmalogens to prevent cancer? Ah....unknown. Can I shift my redox balance with exercise? Yes, going for a walk in about 5 minutes. (Two stars). Can I intermittently fast every day for 13 hours? Yes. (Two stars). Can I do a monthly fast mimicking diet? Yes (four stars)
1. What is the metabolite in our blood that we can measure that is low in every cancer? Answer: Plasmalogen fats
2. Where are plasmalogens made? Answer: In the cellular body called the peroxisome. Every cell has peroxisomes. You can measure their function by measuring the ratio of plasmalogens and other biochemical compounds.
3. What makes plasmalogens so valuable? Answer: They are the stop sign for radical oxygen species that damage the cell so badly.
4. As we age, what happens to our peroxisomes? Answer: for reasons yet unknown the first, rate-limiting step of making plasmalogens slows down. The enzyme Dihydroxyacetone phosphate acyltransferase (DHAP-AT) just runs out of gas. If you can say that with a mouthful of chips, I give up.
5. Why would a cancer form from low plasmalogens? Answer: Ah, there is a Nobel Prize waiting in that answer. And that is where many labs are probing and looking right now. Stay tuned. At least this column has given you the insight.
Genomics 2: Figuring out how to Repair Homocysteine
This is no joke! Homocysteine is a huge risk for developing Alzheimer's and cognitive decline. A rise from 7 to 12 means some 40% incremental risk as shown by a landmark paper in the New England Journal of Medicine that followed the aging population in the famous Framingham Study. The average American male is at 12, making the lowering of homocysteine to 7 a top priority. And a lot of people have that risk.
It should be easy, right? Traditional Internal Medicine shows the homocysteine cycle to be all about sufficient vitamins B12 and methyl folate. Take those two and you should be all fixed. Those are the two vitamins that provide methyl groups (a single carbon atom with 3 hydrogens on it) for your body to "methylate" which is a critical step in manufacturing neurotransmitters, digesting used-up compounds, and many more functions. You need methylation. Only problem, it didn't work. Many folks get halfway there, but not all the way. Double the dose of methyl-folate and B12, and still no progress. What to do?
This is where the frontier of medicine shows up. Genomics is the emerging science of observing your genes and seeing what SNPs, (single nucleotide polymorphisms) you have. A SNP is a gene with one amino acid changed that alters the functional efficiency of the gene. The methylation family of genes, known as MTHFR has been bandied about as the key. These are the proteins that convert homocysteine back into methionine, the amino acid that is the actual donor or methyl groups. You can measure your genes and see if you have a SNP in one or two of them. The response to those deficits is to take much more B12 and folate, or B6. And that is what hasn't worked. You might say this has been "push" therapy for homocysteine. Time to try "pull".
This is where the field of "Metabolomics" comes along. In measuring all the actual compounds that are present in your blood, which reflect how active the total balance of your genetic profile is, we have learned all sorts of new insights. And the summary on homocysteine is eye-opening. The simplest understanding is as follows. Homocysteine is not the problem. It's demand for (that's the "pull") methyl groups, probably in your muscles, and membranes that is the real driver. Homocysteine is the gas gauge, not the gasoline. Goodenowe, the genius behind discovering plasmalogens, found that.
The real problem with high homocysteine is that it is an indicator that your methyltransferase system is shut down. The feedback loop of homocysteine does that. A low homocysteine means your methyltransferase system is open for business. High means it's closed. It's backing up because of too much demand, too much "pull". And if it's closed, B12 and folate won't fix it. You can understand how to fix homocysteine if you examine it from the point of "methylation demand". There are two enzyme systems that produce homocysteine: the ones that make creatine for your muscles, and phosphatidylcholine for your nerve membranes make 75% of your homocysteine.
It is that step before homocysteine that matters. Methylation demand produces a homocysteine precursor called SAH (S-adenyl homocysteine). SAH is the potent feedback loop that turns off methylation when demand is high and too many methyl groups are being used up. Get that? It's methylation demand that drives up homocysteine. That means methylation is turned off. Off. Off. Can't fix it with more B12 and folate. It's turned off. You have to lower demand! How so?
In a slight of organic chemistry magic, you can take the two compounds whose production drives demand, creatine, and phosphatidylcholine. Provide those from outside and you reduce methylation demand. If you reduce demand, you make less SAH. Less SAH, less homocysteine. Finally, if you take NAC (N-acetyl cysteine), you force the homocysteine you do make down to glutathione, using up homocysteine via cysteine, and again, preserving methionine. The reserve sources of choline are the fats in your nervous system membranes: your sphingomyelin. Your plasmalogens will start stealing choline from your nerve cells if you turn off methylation with high SAH. As you steal sphingomyelin, you make ceramides that you can measure. And your brain deteriorates. Does this sound like gobble-di-gook to you? Well, me too. So, let's make it simpler. Get me to the bottom line.
The puzzle was solved by Metabolomics, the study of what's in your blood. It has been metabolomics that tells us exactly how fast some enzymes work and how much of any given compound they produce. That has been the genius of Goodenowe and his plasmalogen test. He has studied the contents of peoples' blood and determined the balance of what's healthy and what results in harm and reduced down to understandable and actionable events. Look at your genes and see where your enzyme difficulties are. Look at your blood and see what the genes you inherited are actually doing, and I can show you how to lower your homocysteine to normal.
www.What will Work for me. Homocysteine is oddly one of the pinnacle markers for risk of cognitive decline. Lowering it should be one of all of our key "wellness" actions. It is easily as important as A1c. Mine has stubbornly been above 10, down from 15 but still 9-10. I did the IntellxxDNA test and found I have a SNP in the choline pathway called PEMT that lowers my production of choline. I create high methylation demand with that SNP. Ah! I get it now. I need more choline and creatine, in addition to the B12 and folate, I faithfully take every day. Every single person I've seen an IntellxxDNA test on has revealed one "secret" or another. The PEMT SNP that I'm short of, well, it's actually present in 45% of us. So, I'm not so special as I thought.....or we are all in a leaky boat together. The good news is, with knowledge we can fix it before we are in too much trouble.
1. Are you completely confused by this? Answer: Yes!! Sorry....let me make it simpler.
2. Just get this right. What is Genomics? Answer: The study of the variability of your genes from normal. Each of us has several hundred SNPs that have some clinical implications. By chance, most of them are not so bad because you only had one from one of your parents. But if you get the same SNP from both parents, you may have problems. PEMT is considerably softened by taking B12 in much higher doses. That may be why some folks just get better with B12 shots.
3. What is Metabolomics? Answer: An examination of what your genes actually make and do. How fast and how efficiently they work.
4. What is the real driver of high homocysteine? Answer: Methylation demand. You aren't getting enough creatine in your muscles, so you are trying to make more creatine, producing more SAH. Or your nerves don't have enough phosphatidylcholine, so you are trying to make more of that, creating more demand.
5. How can you lower that demand? Answer: Creatine is a cheap supplement. Phosphatidylcholine is also pretty inexpensive. NAC is safe and effective. Simple food items, if you need them, when targeted effectively, work. Then, take the standard B12 and folate. And you get fixed. Read the paper.
Genomic Medicine 1: Vitamin D Deficiency Explained!
In the year 1900, some 50% of Wisconsin children had variations of rickets. My mother had rickets as a little girl. There is pretty good proof that neonatal jaundice comes from too low of Vitamin D. (The only negative study showed levels of 14 in the non-jaundiced group and 10 in the jaundiced group: both are way, way too low.) Vitamin D controls 10% of the human genome and we don't get much (actually any) in Wisconsin, in winter. The sun is now back up to 42 degrees, and soon will be high enough to provide enough UVB radiation for you to start making Vitamin D, if you are outside during 10-3 period of time of intense sunlight. 10% of the human genome controlled by Vitamin D! That's huge. Vitamin D is important.
I've been intrigued by Vitamin D for 20 years now, ever since I found my level to be 7 when I first measured it. How could I be so low? I've found the answer.
Genes. Genomic medicine has arrived. The ability to check your genes and, more importantly, how to convert that information into actionable effects is now at hand.
You have 8 billion base pairs in your DNA. We all do. Three base combinations of the 4 DNA "letters" or bases code for the 20 amino acids that make up the magical compounds called proteins. Proteins are hundreds and often thousands of amino acids long, folded in careful shapes and activated by differing cross-links or metals in their active domains. The coding for a protein that is 600 amino acids long would be DNA that has 1800 base pairs, and the coding regions for activating the DNA transcription or "interpretation".
What happens if you have a "mistake" or misinterpretation of a single base pair? That is called a SNP, or "snip". Single Nucleotide Polymorphism. One SNP in black cows makes for A1 milk as it alters the casein protein at amino acid 67 and makes for a 7 amino acid fragment humans can't digest. Just by chance. Brown cows don't have that. Humans that eat A-1 milk have their immune system "jiggled" or nudged just a bit: enough to induce insulin-dependent diabetes, for starters.
What about Vitamin D SNPs? We can now measure them. Each of us has some 4-5 million SNPs in our 8 billion base pairs. Maybe more. That's a guestimate. And companies are racing to be the first to make it useable information. IntellxxDNA is "Best in Class" so far. I got my DNA examined and I looked at my Vitamin D SNPS. I have a boat-load of them in my Vitamin D domain, mostly in my conversion of cholesterol in Vitamin D. The two proteins that help sunlight make 25-hydroxyvitamin D3 (25(OH)D) have identifiable SNPS, and I have both of them. You get one copy of DNA from each parent, so having 1 copy of the SNP is potentially troublesome. Having two is a slam dunk big problem. My DNA shows that I have two copies of both SNPs. I have a huge reduction in my ability to make Vitamin D. The only solution for me is to take it as a supplement. The odds ratio of being deficient for me with my SNPs is 2.12 x 10 -27th power. Now, Vitamin D needs a carrier protein to transport it to the liver, and then to the kidney to manufacture the final useable product. Those SNPs I've got too but only 1 of each, so I can still transport D, just a little slower. And finally, my intracellular D receptor, where you actually activate the 10% of your genes with Vitamin D, I've got those covered with normal proteins. Whew, dodged that bullet.
All that wisdom right in front of my eyes. I can read my genes and have actionable behaviors that help me decide how to manage my Vitamin D.
The implications of D are huge. Osteoporosis is the classic. But heart disease, cognitive function, diabetes, mood disorders, immune function, cancer all have relatable issues for which D is relevant. That means everybody.
www.What will Work for me. This is such a huge topic. I'm mesmerized. Bear with me as I take you on the journey over the next few weeks of discovering how to turn this dry information of DNA coding into actionable behaviors. This is the future of all medicine: measuring your DNA and identifying precisely how to manage it. No wonder my mother got rickets. And now knowing the prevalence of these SNPs in the population, no wonder half of Wisconsin had rickets in 1900. These are not rare genes. My set is nasty. Some 15-20% of folks are in the same boat as I am.
References: Science Direct, Palomar EDU, Medline Plus,
1. What are your "genes" composed of? Answer: 8 billion base pairs of DNA.
2. How do you translate DNA into your proteins? Answer: Proteins are made of 20 different amino acids. Like snap beads on a necklace. Each amino acid is coded for by a different triplet of DNA base pairs. For example, the amino acid glycine is coded for by GGT. Glutamine is coded for by CAA.
3. Is your DNA perfect? Answer: Well, actually not. We probably have many millions of DNA fractures happen every day and have a whole set of proteins tasked with repairing that damage. Every now and then, a mistake happens that you don't/can't fix. You then have a SNP: single nucleotide polymorphism. You pass that on to your kids. Most of those mistakes make for an amino acid change that doesn't do much damage to its parent protein. But some do alter behavior a little. Some do a lot. Two copies of an alteration that is harmful leads to genetic disease.
4. Can we alter our "fate" if we know our genes? Answer: Yes, dramatically. You don't need a gene transplant. You need to know the tools to modulate those risks.
5. How can you modulate Vitamin D SNPs? Answer: We now can manufacture Vitamin D very inexpensively. You can take more. We can also upregulate the Vitamin D receptor proteins inside the cell dramatically by increasing your blood level of magnesium, curiously enough. That is part of how magnesium has so many beneficial effects.
Extra Olive Oil Helps Women with Breast Cancer Lose Weight
Breast cancer is the number one cancer in women in America. In other cultures, diets based on olive oil and more plants (Mediterranean Diet) have lower rates of breast cancer. With that in mind, a randomized, controlled diet trial was instigated offering the traditional National Cancer Institute Diet versus a plant-based diet with extra EVOO (Extra Virgin Olive Oil)(3 Tablespoons a day). It was small, yes, but it's still useful. The author's labeled it a "pilot" study.
Being overweight is also a risk for breast cancer, so weight loss is part of the program to lower overall risk. The goal was to lose 5% of body weight. Forty-four women were enrolled in the program that alternated the NCI lower-fat diet (between 15-30% fat) and the olive oil-enriched diet. Randomized to the diets for eight weeks, the completing women were then offered either for the remaining 6 months of the program. Of the 22 that completed the first segment of the trial, 19 chose the extra EVOO plan. Twelve of the fifteen (80%) women assigned to the olive oil arm lost their 5% body weight goal target versus four of thirteen (31%) (p<0.01) in the NCI diet.
This should be understood widely and followed more carefully. What it is telling is brazenly clear. Just because it was small doesn't mean it's not true. The "P value" of 0.01 means less than 1% chance this was from statistical fluke. We need healthy fats that don't turn on insulin. Insulin is not your blood sugar hormone, it is your storage hormone, designed to be used only in the short period of the year when carbohydrates are in abundance (autumn - harvest). And worse, for cancer, insulin is a potent growth hormone that stimulates cancer growth. Its reduction is a high priority. Weight loss will do that. Yes, weight loss is an important goal for women with breast cancer. It's just the method.
What implications does this have for all of us? Pretty big. You might consider having a nice vial of lemon-flavored olive oil sitting in your pantry to take a snack treat on a daily basis. Can you do that?
You are expertly managing your physiology when you do that. Other ways of getting that olive oil dose: can you buy some tasty olive and just have a daily dose of olives? You are turning off insulin by providing a food that doesn't touch insulin. The second you secrete insulin, your fat cells go into storage mode for 8-16 hours. Animal protein will also stimulate insulin. Saturated animal fat is not a healthy food.
Other healthy fats include sesame oil, macadamia, or avocado but not corn, soy, peanut, or canola. Don't even buy any of the mainstream oils. Just don't.
Now, if you think this study is interesting, and every person who wants to lose weight will, wait till next week and learn out 1 L of olive oil a week that knocks it out of the park. (Little teaser here)
www.What will Work for me. Well, I just but some very tasty olive oil. Fresh, glass container, small bottle so I use it up quickly and burns my throat when I have a spoonful. One big T a day of EVOO as a snack. Sometime during the day.
References: Jr Women's Health,
1. Ok, so just a brief synopsis. How much EVOO do I need to take a day to successfully lose weight? Answer: 3 Tablespoons, along with a plant-based diet.
2. What is the amount of weight I have an 80% chance of losing if I do that? Answer: 5% of my current weight over 8 weeks.
3. Why do I lose weight when I eat healthy oils? Answer: Your body gets calories it can use without turning on insulin, which locks up your fat cells and turns them into storage mode. Without being in storage mode, your fat cells share calories. That's called losing weight.
4. How can I prove I'm losing weight? Answer: Easy. Buy a ketone meter that measures your blood ketones. Ketones are present ONLY when your fat cells open up due to lack of insulin, and share calories. That's called weight loss.
5. Is there a nuance about what plants I can eat to lose weight? Answer: YES, you can't eat insulin inducing plants and lose weight: potatoes, rice, grains, beans, peas. What works are green leaves, cabbage, cauliflower, broccoli, Brussels,....
Fluoride and Cognitive Decline
It's almost a sacred given that fluoride in public water supplies reduced childhood cavities. The CDC website says it's good for you, calling it one of the 10 greatest health care advances of the 20th century. But hold on a little. Good, rigorous scientific review suggests that the original proponents of fluoridation were a little over-enthusiastic. A 15% reduction might be closer to the truth. Even a Cochrane review suggests the scientific underpinnings of fluoridation are not as rigorous as previously entertained. A little too much enthusiasm on the part of dentists to promote their profession and a touch too much enthusiasm on the part of the fluorine industry to sell their product. Hmmm.
So, what would you say if you saw an article in JAMA Pediatrics that shows for every 1 mg/L increase of fluoride in drinking water during pregnancy results in 4.9 less IQ points in children? Anyone want to sign up to drink that? That study was done in Canada, and published with some caution because of its controversy. The Europeans promptly dismissed it with a study of their own. But the study stands!
If I came back and said that a carefully controlled study of mice's ability to learn while being given fluoride shows significant deterioration in just 12 weeks upon exposure to the same fluoride level we get in our water, then what would you say? Granted, those mice had some prearranged mutations that made them more vulnerable to cognitive decline but still! "The lower levels of synaptic proteins and enhanced oxidative stress detected in the hippocampus of APP mice were aggravated by fluoride".
This is concerning! If you do a deeper dive into the biomechanics of energy in the brain, and the damage caused by fluorine to mitochondria, you might just come away a bit shaken. It appears there is bench research showing that fluorine causes multiple problems at the molecular level that would give plausibility to the hypothesis that the presence of fluoride exacerbates many of the conditions that lead to cognitive decline.
Face it! Bottom line. It is a potent neurotoxin. We have been cautiously dancing around it for decades, trying to be nice for the dentists, the same crowd that told us that mercury in our mouths was ok. We need to respectfully ask our dental colleagues to prove fluoride to be safe before promoting it any further.
I'm not an "anti-vaxer" and I have always felt the "anti-fluoride" crowd was something cut from the same cloth. But when I read that Bredesen insists that all of his cognitive decline patients avoid fluoride, my feelings tipped. I think it's time to get on that train.
www.What will Work for me. I don't have city water so I'm not in the position to worry about that. I do have grandchildren who live in places where their water is fluoridated. I do have a Keurig for which we buy distilled water. But I just started using fluoride-free toothpaste. And no more painting my mouth with fluoride treatment after cleaning. I'll floss. I'll water-pik. But no fluoride. I believe the decades it takes to develop cognitive issues hide the danger. It's too hard to prove.
1. What do we think the "real" dispassionate effect on cavities in children is true with fluoride? Answer: Probably about a 15% reduction.
2. For every 1 mg/L of extra fluoride, what happens to children's IQs? Answer: A 4.9 point decrease.
3. f it has that effect on kids, what about seniors worried about memory? Answer: Same problem - appears to accelerate it.
4. Where is your daily exposure to fluoride? Answer: Your toothpaste, your drinking water, your use of Teflon coated cookware......
5. Is it possible to lower your exposure? Answer: Over 77 cities in America have voted to have fluoride taken out of their water. Were they crazy or are you late to the show? Juneau studied it and found that kids got about 1 cavity a year extra. So, would you rather pay your dentist extra or pay the memory unit for long term memory care? Hmmm. Sophie might have something to say about that.
COVID-19 and Cognitive Decline
One of the most common symptoms of COVID-19 is that folks report loss of smell. It is known that the virus invades the brain through smell receptors in the top of the nose which gives it a direct and short pathway straight into the hippocampus. Loss of smell, taste and headaches are all high on the list of COVID-19 symptoms. These are all signs of brain involvement. What is more disturbing is that functional MRI scanning has shown consistent and disturbing trends with alterations in the volume of multiple brain nuclei. This tracks the disturbing historical precedence following the 1918 Flu epidemic resulting in a tripling of the incidence of Parkinson's in the years following in those who contracted it and survived it. In the same fashion, there is growing awareness that the herpes viruses are more prevalent in Alzheimer's brains, and their suppression with chronic anti-viral therapy results in better outcomes. Bredesen uses anti-virals as part of his Alzheimer's protocol for anyone with chronic cold sores and believes that results in observably better outcomes.
Molecular biology has progressed enough to know that the COVID-19 virus makes a dramatic block of energy production in the mitochondria of afflicted cells, diverting potential energy production into viral coat lipids. Taking Ketone Esters as a therapy for COVID results in many folks who have been bedridden with fatigue and shortness of breath to virtually recover function in miraculously short times. These ketones drop right into the mitochondria past the block the virus imposes. We do know that we Western Diet humans have our brain accommodated to glucose as the dominant source of energy and that our brains are vulnerable to glucose deficit. The addition of a virally imposed block in the mitochondrial energy production makes intuitive sense that folks with vulnerable brains are further injured by COVID.
In that light, 40 medical centers around the world are banding together to study 1000 patients each and follow them prospectively to examine the ongoing effect of COVIDon subsequent cognitive decline. They haven't proved it yet, but there is enough smoke in the air for them to start looking for the fire. Their expectation is that there will be serious and long-term complications from COVID and that it accelerates Alzheimer's. Oh, dear. Hope they are wrong.
What implications does that have for you? We are doing research on the fly in the middle of battle. These aren't ideal conditions for long-term, prospective research. But now is not the time to delay. You do the best you can with the tools you have.
www.What will Work for me. To me, this is another compelling reason to encourage you to get your vaccination. If you are worried about your own cognitive abilities, or aware that you have had some risk for cognitive issues like an affected family member, use this as a reason to get over your reticence. And if you have had COVID and lost your sense of smell, and still haven't got it back, consider getting some sort of treatment for that. Thymosin A may be useful. Ketone esters are worth a trial. To my ears, prolonged loss of smell says you have already developed damage in the gearbox of your brain.
1. COVID-19 is primarily a respiratory virus. T or F. Answer: Emphatically false. It hitchhikes between people via respiratory droplets but it is a systemic illness that affects virtually every organ system in one person or another.
2. What is one of the most common symptoms that it is affecting your brain? Answer: Loss of smell or taste. Brain fog and headache come in close thereafter.
3. What other viruses have been proven to be involved in prolonged brain damage after infection. Answer: None, prospectively. That is too high a bar to demand. But associations studies show that the Influenza of 1919 resulted in a huge wave of Parkinson's 50 years later with a tripling of incidence. And HSV6 and 1 both appear to have associations.
4. Is there anything I can do about this? Answer: Yes. You can add this to your risk-benefit calculation going forward and get vaccinated. The vaccines are not whole viruses and can't in any fashion alter or change your DNA, as some misinformation anti-vaxers claim. They are messenger RNA molecules that are end products. Messenger RNA cannot in any fashion reverse manufacture DNA.
5. Can I take other medications to prevent the virus? Answer: yes, there are all sorts of prevention and immune boosting strategies. Start with Vitamin D, 5000 a day. Please, do all of them.....