Statins Add 5 Days to Your Life

Statins Add 5 Days to Your Life

There are cracks in the "statin empire". The $ 18 billion industry has reached out as far as it can possibly go, even to the extent of advocating that virtually all adults should be on statins. But does it make sense and are we really treating a disease or a symptom?

The first crack appeared about 9 years ago around the simplistic rule of 200. Cholesterol above 200, you need statins. Below 200, "You're fine". Well, the Norwegians tested that in 2012 with the HUNT Study and followed some 50,000 folks for 10 years. They found that women with cholesterol over 200 lived longer than under 200. Oops! Is there a problem here? Of course, there is. The real problem is that you get into trouble in your arteries from small, dense LDL particles that have been oxidized. They occupy less volume. You can have a "low" cholesterol and not really be protected. Taking a statin, ironically, reduces the number of large, fluffy, harmless LDLs and not the dangerous small LDLs. That "magic" number of 200 doesn't make sense. It is simply a super easy tool that advertisers and patients can glom onto and believe that sounds like it makes sense. (Statins do have some helpful effect, probably as an anti-inflammatory nature.

Ask the question. Are you interested in how long you live, or how low your cholesterol is? I would contend you want to live longer. If I showed you a study of 12.6 million people, followed for some 10 years and having 694,000 deaths, you would say, "Sounds like a pretty good study to me - it's got big numbers." Well, they found that the ideal cholesterol was between 210 to 249. Sounds like the crack is getting bigger.

Ok, so just what benefit do I get from statins? Let's look at that. A study published in the British Medical Journal looking at 6 primary prevention and 5 secondary prevention studies (all they could find that included mortality and had sufficient scientific rigor) showed a surprising finding. The median survival advantage is just 4-5 days. Not much, considering cost, side-effects, and inconvenience. In fact, perhaps just plain nuts except for in very focused situations, like smokers who have had a heart attack. But folks with negative calcium CTs of their heart being advised to take a statin? That's just plain nuts. (Just look at that study. Folks with score of zero had zero mortality.)

Don't get me wrong. Cardiac disease remains the number one killer in America. It's worthy of being addressed. Just find for me the right tools. I would contend that you want to turn off oxidation and the production of small, dense LDLs. Well, now that's a worthy challenge. Once you understand what's happening, you can shape your own strategy to change it for yourself. We have to dive down into your mitochondria and the membranes of your cells. I can't fit it into this column so it's coming next week. In the meantime, consider cutting out sugar and white flour for the whole week. (Hint: if you measured the volume of your LDLs before and after the week, your LDL volume would have gone up. Your oxidized LDLs would have slipped into "safe" territory and your oxidation count would have gone down.). So next week, we will put the icing on the cake (sorry, wrong image), the olive oil on the avocado, and walk you through how oxidation gets started and how that leads to leaky endothelium in your arteries....and that's what we need to be treating. Stay tuned.

www.What will Work for me. I started my monthly 5-day fast mimicking diet this week. My first-morning fasting glucose after a 13 hour fasting period was 103. Ugh. I have such lousy genes. The Whitehall Study shows that every point over 85 on your fasting glucose results in a 6% increase risk of diabetes. Indeed, my father died of diabetes. The fast-mimicking diet will drop my glucose to the 70s by day 5, which gets me briefly into the safe zone. But insulin resistance and diabetes is all wrapped up in leaky artery endothelium, which is all wrapped up in oxidized, small dense LDLs. I'm intensely interested in this topic. And my physiology represents just about 50% of folks who think they are pretty ok and don't have much trouble, until they do. That's why this is such an important topic. But I'm not convinced a statin will help me. I am going to avoid fructose, sugar, and white flour.

References: BMJ Open, Stat News, Sci Reports, JACC Cardiovascular Imaging, Lancet,

Pop Quiz

1. Statins are an important part of cardiac care and prevention? Answer: Oh, such a loaded question. Yes, for a small number. No, for probably most people, particularly for those with a negative cardiac calcium scoring test.

2. And even if I have risk, how much extra life do I get by taking statins? Answer: 4-5 days. If that comforts you. Make sure you use those 4 days well.

3. My muscle aches and brain fog that I get with statins are worth it, aren't they? Answer: You have to decide

4. What is the level of cholesterol correlated with the longest life-span? Answer: between 210-250. Now, oxidized, small dense LDLs, that’s another story.

5. Did you know that the vast majority of primary care physicians have review of their medical decision-making around statins with economic consequences in their salary for not treating people with cholesterol over 200? Answer: Sad, isn't it? Guess who designed those "quality guidelines"? Yes, statin compensated doctors. The problem: you get caught in the cross-hairs.

The Trouble With Diabetes Isn't the Glucose, It's the Insulin

The Problem with Diabetes Isn't the Sugar, It's the Insulin

We have had an increase of diabetes in America and around the world of unprecedented magnitude. We are increasing at about 10% a year, and our health care system has been helpless to decrease it. Some 60% of people in America are on the path to getting it. What gives?

The clue comes in a unique experiment done almost twenty years ago by Ron Kahn's lab at the Joslin Clinic. The core idea from his experiments was that blood glucose is actually a red herring. It's not the problem. The problem is INSULIN resistance. Blood glucose is just a symptom. Your blood insulin is only partially related to your glucose level. The experiment was to genetically knock out insulin receptors in different tissues in lab mice, and then watch what subsequently happened. Every tissue has insulin receptors. Brain, fat cells, brown fat, muscle, pancreas beta-cells, blood vessels, and kidneys were the tissues they chose. All the mice got sick in one way or another, but only the liver and brain knock-outs got high blood sugar. Only the brain knock-out became obese and developed metabolic syndrome. And to put the final irony, the kidney knockout didn't get high blood glucose but got the kidney disease of diabetes anyways.

WHOA! This has huge implications. The logic is a bit complex but nevertheless compelling. It's not the glucose. It's the insulin that causes the illness.

If you think it through, we see the same effect in humans. Insulin deficient type I diabetics take 20 plus years to get kidney disease. But type II adult-onset diabetics already have the kidney disease before they get the high blood sugar. Why? Because they have had surreptitious insulin resistance for years that was not diagnosed. Their insulin level was over 5 and no one blew the whistle.

Why this dichotomy? Insulin is a two-edged sword. It helps control blood glucose, that's one edge. But it also serves as a proliferative agent. It increases the growth of cells. In the heart and kidney, those cells are the smooth muscle cells in the walls of the arteries, and you get heart attacks and kidney failure as a result. (This has been proven in every intensive insulin program ever done: you reduce blood glucose but raise risk of chronic disease. Bummer.)

What causes insulin resistance? We've known this for 20 years, but it somehow doesn't quite bubble up to the top. Finally, a recent review acknowledges that fructose, half of table sugar, (sucrose is glucose and fructose stuck together) is the real enemy. It drives metabolic syndrome starting with insulin resistance in the liver. Soon thereafter, hypertension shows up too.

Fructose is the enemy. But fructose is in every liquid calorie you drink that is manufactured using high fructose corn syrup. Fructose is in almost every prepared food you eat, every mouthful of ice cream you eat, and on and on. Fruit is some 6% fructose, so even that contributes a little but our body appears to be able to handle the quantity that comes with fruit. But more than two servings of fruit a day and LDLs will go up.  But fructose was never in any food prior to this century.  Real food does not have fructose in it.  Period.

What is so awful about fructose? You can't slow it down. It floods into your liver and demands attention. You have no controls or gates that limit how quickly it gets into your liver. It has to be labeled with a phosphate group from ATP, which exhausts your ATP supply. You get an oversupply of acetyl-CoA in the liver and the liver cell panics and switches to making fatty liver. The fat globules accumulate. And that's the beginning of insulin resistance. Guess how badly Big Food wants you to understand this. Guess how much lobbying money goes into not regulating it?

How do you reverse diabetes? It's not weight loss per see, though that may be extremely helpful. You reverse diabetes by focusing on the insulin resistance and your insulin level. This is where the power of intermittent fasting works. By compressing calories into an 8 hour window, your body has burned up it's glycogen stores in 10-12 hours and you then have at least 4 hours of running on ketones, which means the pressure on your insulin evaporates. The first ketones to go are from your fatty liver. As you reduce fatty liver, your metabolic syndrome fades. Or, once a month fast mimicking. Same thing. But you start by stopping the sugar, high fructose corn syrup in particular.

www.What will Work for me. I've measured my insulin on day 5 of my fast mimicking behavior when I eat 800 calories a day for 5 days: 50% fat and 50% green vegetables. It's been as low as 2. Otherwise, my insulin runs 7-8. I'm tip toeing along the edge of metabolic syndrome. So, I'm close to trouble. For the last month I've started skipping breakfast and eating my first meal at least 10 am. I want to see if I can get my A1c down below 5.6, where it appears to have been permanently parked. And no sugar, no sugar, no sugar.

References: Ann Rev Physiology, Critical Rev Clin Lab Sci, Nutrition and Metab, Penn Med News,

Pop Quiz

1. Through most of human history, when did we get sugar? Answer: Only in the fall when fruit ripened which we could get for a couple of weeks. Or, if we found a beehive. Sugar has shown up in our food supply only in the last 100 years in quantity.

2. And just what does sugar (fructose in particular) do to make metabolic syndrome? Answer: Insulin resistance.

3. Which comes first for adult-onset diabetics, the high blood glucose or high insulin? Answer: Insulin is way first. If you had observed the range of "normal insulin" in our labs in Southeast Wisconsin over the last 30 years, you would have noted that the "range of normal" has been creeping up every couple of years. The supposed normal range is now typically 3-29, depending which lab you use. It used to be 1.9-19 about 15 years ago. What happened in the interim? We have eaten more HFCS, ice cream, sugared sodas, ketchup....etc.

4. What is the cardinal first step in lowering your insulin? Answer: It starts in your fatty liver begging you to stop the fructose. Then, give your liver a break and let it burn up all the energy you stuffed into it with fructose by lengthening the time you don't eat each day. Get to 16 hours, your fatty liver will go away.

5. What is a healthy insulin level? Answer: Less than 5. Measure it. Pay heed if it's higher.

6. Can you take enough meds for diabetes to reverse the harm of fructose? Answer: No. Meds are just a bandaid to cover the symptom of high blood sugar. High blood glucose is the symptom. High insulin is the disease.

Plasmalogens and Parkinson's disease

Plasmalogens and Parkinson's Disease

Parkinson's is the number two horrible neurological disease plaguing the elderly and has been increasing as the population ages. It is classically known as a loss of dopamine-producing cells in the substantia nigra, a tiny little nucleus at the base of the brain. Its symptoms include a mask-like face, rigid walking and movements, a pill-rolling tremor, and eventually cognitive decline. It's miserable.

Giving dopamine back as a medication, or stimulating more release of dopamine helps for a while, but the real problem is the inexorable depletion of those precious few remaining cells in the substantia nigra.

In the 1980s, a couple of California folks were trying to make designer heroine. They stumbled onto a drug called MPTP, which unfortunately gave them Parkinson's in a real fast sort of way. The drug, MPTP, turned out to be a perfect model for creating Parkinson's in lab animals. Over the years researchers have been able to drill down to the exact chemical steps that happen. The MPTP is a poison to your mitochondria all over your body. But it is preferentially taken up by dopamine neurons, so they get a super boost of it, and it kills their mitochondria off. The dopamine-producing cells die and the lab mice get Parkinson's in a dose-dependent fashion. But wait, there's more. It turns out the MPTP has been a perfect study drug to elucidate the electron transport chain, which MPTP poisons in Complex A. That's where you are meant to turn NADPH (a source of free radicals) to NAD+, safe. With MPTP around, NADPH backs up and you make boatloads of free oxygen species, which your cells desperately try to get rid of by making peroxide. (If you want to be a biochemistry snob, you can quote that the NOX enzyme on the surface of your cell is what captures that extra NADHP and spits out the peroxide outside the cell.) Peroxide in your blood activates glia cells and those activated glia turn into cookie monsters and gobble up the injured cells.

Ok, what's the big deal? The big deal is that is the precise mechanism for cell death in the brain from all causes that make too many reactive oxygen species for all sorts of reasons, and which is fixed by having more plasmalogens. Like Alzheimer's. Like ALS. What did I just say? Fixed by more plasmalogens. Plasmalogens are the membrane lipids with a "vinyl ether bond" that gobbles up peroxide and neutralizes it. It is the backup protection for overloads of reactive oxygen species. It is the reservoir of protection that allows you to have a short-term bump in reactive oxygen species, and recover. And when you run out of that reserve pool, you are more vulnerable to getting Alzheimer's and ALS if you don't get Parkinson's.

So, just what do we know about plasmalogen blood levels in folks with Parkinson's? From Dr. Goodenowe's study at Rush in Chicago, we know that blood plasmalogen levels are incredibly predictive. Healthy blood levels and Parkinson's is a rare disease. Low levels and risk skyrockets. Everyone with Parkinson's has lower levels. Very similar to Alzheimer's and ALS.

Ok, what are the plasmalogen's doing? Well, Goodenowe has now completed multiple lab mice studies of MPTP. If you give extra doses of Plasmalogens to the mice before they get exposed to MPTP, they never get the expected Parkinson's. If you give the MPTP and wait 5 days, they still don't get it, or at least much less.

Alright, one final study. Let's take monkeys that have been given MPTP and had Parkinson's induced. They are now down the road with bona fide Parkinson's, on L-dopa, and being successfully treated. Just like with humans they are beginning to get the typical dyskinesias of long-term L-dopa therapy. Give the monkey's plasmalogen replacement therapy and guess what happens? Some 30-50% reduction in the dyskinesias. This means the plasmalogens are acting beyond just being protective by sucking up peroxide. They are making the remaining neurons function better because they play a role in the synaptic membrane of helping the packets of dopamine to be released faster and better. That's a neuroactive function in itself.

Where are we in human Plasmalogen research? It's just emerging. A study from Japan showed improvement in Parkinson's symptoms when given oral plasmalogens derived from scallops. Their dose was 1 mg a day, which is hard to reconcile, being such a low dose.

But everything is lined up. First and most important, plasmalogens are fats that are just food. They are not toxic in any way. You just have to get a form of them that gets into the body. The normal, animal-based plasmalogens, are digested in your stomach. Almost 100%. Goodenowe has invented a product that delivers a bio-active template that gets into your body, allowing you to make the right stuff.

www.What will Work for me. Again, we are seeing how plasmalogens play roles in the core functions of our neurological systems. The point is not to treat the disease necessarily, but to catch people as soon as they might be at risk and normalize levels so that they aren't prone to the subsequent risk. I now know that plasmalogens play many, unique and critical roles: they are your body's main depository for omega-3 fatty acids, they help your hormonal vesicles merge rapidly by shape-changing, they neutralize hydrogen peroxide and finally, they are the most liquid of membranes, allowing proteins embedded within them to move rapidly and smoothly. Pretty impressive. We are down to the very core of how our bodies work. This is "membrane science", a new and critical field of inquiry that undergirds just about every aspect of our medical spectrum. Interesting.

References: Parkinson's Disease, Br J Pharm, Behavioral Brain Research, Jr of Neuroinflammation, Free Rad Biol Med, Free Rad Biol Med, Aging Research Reviews,

Pop Quiz

1. If I have low blood plasmalogens, what happens to my risk for Parkinson's? Answer: Much higher.

2. If I have Parkinson's, what happens when I raise my plasmalogens with supplements? Answer: Early results show improvement

3. What is happening in my brain cells if I take Plasmalogens? Answer: they are the lipids that can shape change, a critical feature for membrane fusion: a fancy term for what it takes to put neurotransmitters into the synaptic junction.

4. Why do my plasmalogens get low? Answer: Likely an environment of elevated oxidizing compounds. Some folks must be more vulnerable. Research pending.

5. Is there any risk to taking plasmalogen supplements? Answer: Nope. No more risk than eating a teaspoon of olive oil. It's food.

Plasmalogens and Cancer

Fight Bowel Cancers and Inflammatory Bowel Disease with mRNA-148 and Curcumin

Ok, the title is a mouthful. But the story is amazing. If you understand this, you may conclude that we are at the threshold of detecting bowel cancers much much sooner, and more importantly preventing/treating it more effectively. So this is big. Having had several family members diet of colorectal cancer, I've got skin in this game. (And very likely, ALL cancers.....)

The first concept to understand is that your gut makes very, very-long-chain fatty acids (GTAs-gastrointestinal tract acids). Not the run of the mill 18 carbon-long fatty acids stored in your fat cell, I'm talking 28-36 carbons long. Super long. And they are strongly anti-inflammatory and very cancer-protective. If you have tons of them, you are a lucky devil. Your risk of GI cancers is very low. And they are low years before colon cancer develops. That makes them very effective screening tools. If you are low, you are at a much higher risk of getting colon cancer. Curiously, carving out the cancer with surgery doesn't lower their level. Their low level PRECEDEs the cancer. You want a higher level, or else a second cancer has fertile soil to grow in.

What are these GTA's doing? Well, for one, they are incredibly potent anti-inflammatory compounds. If you look at the activity of folks without GTAs in their blood, their NFkappaB is much higher. There are about a dozen markers of inflammation that are downregulated. You may have heard about LPS caused inflammation? Yes? LPs are the lipopolysaccharides off the walls of bacteria that get into your blood and set off inflammation. Guess what GTAs do? Yup - cut them off completely. Cool, huh!

Want to get better? You've heard about how curcumin cuts off LPs inflammation? (Say yes and pretend you have.). Well, it does. Particularly in the brain. We have known that South Asians who eat curcumin breakfast, lunch, and dinner have much less Alzheimer's and many fewer cancers than Americans until they leave South Asia and adopt diets without the curcumin. Now, not all curcuminoids are equal. Of the three known curcuminoids, I and II have very little effect but III, which has two "methoxy" groups carved off is the real deal. It turns on miRNA148 like crazy. And that's the secret sauce that fights cancer, inflammation, and inflammatory bowel disease. The problem is is that it is only 1-1.5% of curcumin. You want MORE. Micro RNAs are short messenger RNA that are only some 22 bases long. They act like genetic switches turning on and off different genes. Learning how to manipulate them is the next huge frontier ahead of us in medicine. And miR-148a appears to be a champion cancer killer. You want it on your side with colon cancer, pancreatic cancer. Like the GTAs, miRNA-148 is low as an inherent part of the cancer. It's like the cancer can't behave like a cancer without first suppressing mi-RNA-148. Then, when it's suppressed it can migrate and spread and be wicked.

Now, let's talk colitis and inflammatory bowel disease. The inevitable and dreaded consequence of that is colon cancer. Guess what happens to mice with the lab model of colitis who get their miRNA-148a stimulated? You got it. Cancer is stopped almost completely back to normal healthy mice. Read that again! Click the link. Guess what stimulates miRNA-148a? Turmeric, particularly the type III (the 1% stuff.)

Now, round out the portfolio of risks for colon and pancreatic cancer and Goodenowe has found the inevitable. Lower production of healthy plasmalogens by choline-deficient diets with more inflammatory arachidonic acid instead of DHA caused by too much omega 6 fatty dietary fats (fried food with vegetable oils), and you shift the whole membrane biology towards more cancer. You can reverse that too by making sure you have sufficient choline in your diet and less O-6 fats.

www.What will Work for me. Put this all together and we are talking a strategy that will reduce your risk of cancer may be on the order of 10 fold total. No kidding. I have low GTAs in my blood. That means I am at higher risk for colon cancer. I will be taking that turmeric-3 product for the rest of my life. Goodenowe has gone on to manufacture the Type III Tumeric molecule under the name Prodrome GTA. You can't buy it directly but if you are an active client, just use my name and we will back you up when they call. You will get a discount. When I go over the results of Goodenowe's metabolic scan of various clients, he has repeatedly pointed out various profiles that are at high risk of ovarian, colon, pancreatic cancer. Doesn't mean those folks have it, but it is something that can be reversed, and dramatically proven by the published science. This will be the future of cancer prevention: detect the biochemical phenotype earlier in life and in those with abnormal findings, much more frequent screening tests, or better yet, more aggressive supplementation with neutralizing dietary compounds.

Summary of better diet: turmeric as often as you can eat it. Less vegetable oil and more fish oil. More choline. (Eggs, chickpeas...)

References: BMC Gastroenterol, BMC Medicine, International Jr of Cancer, J Ex Clin Can Res, Oxidative Med and Cellular Longevity, Frontiers in Pharmacol, Progress in Preventative Medicine, BMC Genomics, Human Cell, Onco Letters, Exp Ther Med,

Pop Quiz

1. Just what are GTAs? Answer: Super long-chain fatty acids made in your gut. They are anti-inflammatory and anti-cancer compounds.

2. What can you do to make more of them? Answer: We don't know right now.

3. What can reverse their absence? Answer: Turmeric, specifically Type-3 with the two methoxy groups off it.

4. Can I alter my profile? Answer: Yes. Eat like a South Asian. Lots of curry, every chance your get. If you want to push the envelope, buy Prodrome GTA which is 50% bisdemethoxycurcumin)from the Prodrome company. Cut down your fried food. Eat more fish and chickpeas and eggs. (Or take alpha-GPC)

5. If I have a cancer, can I suppress it with turmeric? Answer. Yes, 1% with the normal stuff. I would personally be all over the Prodrome GTA and Prodrome Neuro supplements. They are precision food for naturally fighting cancer.

Plasmalogen Loss Drives Coronary Artery Disease

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.

References: Nephrol Dial Trans, Atherosclerosis 2017, Atherosclerosis 2015, Biochem Biophys Acta, Biochemical J,

Pop Quiz

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 .......

Feeling Tired All The Time: Blame Ceramides

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.

References: JAHA, Nutr Met CV Dis., Nature Metabolism, FASEB, American Coll Cardiology, Mol Nutr Food Res. , Circulation, Biochem Biophy Acta,

Pop Quiz

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. (

How Low Plasmalogens Cause Cancer

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,

Pop Quiz

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 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

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.

References: JAHA, EuroHeartJournal, Cell, Frontiers in Medicine, Trends Endocr Metab., Cell Death Dis.,

Pop Quiz

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 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.

Do Genomics and Metabolomics Solve Cancer? Maybe!

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)

References: Lipids in Health and Disease, JAMA, American Jr Human Genetics, ProdromeSciences, Biochem and Biophys Acta, Biochemie, IUBMB Life,

Pop Quiz

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: Fixing Homocysteine

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.

References: NEJM, Acta Biochem Pol.,

Pop Quiz

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.