The ApoE4.Info Podcast: Episode 3

Dayan Goodenowe, PhD: Plasmalogens & Neurological Health (Part 2)

Dr. Dayan Goodenowe joins Julie Gregory to discuss his new book, Breaking Alzheimer’s: A 15 Year Crusade to Expose the Cause and Deliver the Cure. He talks about how his research lead him to plasmalogens and how they relate to neurological health. He explains what goes wrong biochemically as dementia develops and highlights age-related diminishing plasmalogen levels as a major driver of disease. He outlines his research showing that ApoE4 carriers may require more plasmalogens to maintain cognition, and he identifies tests and supplements to support plasmalogen levels. Finally, they discuss the unprecedented results of Dr. Goodenowe’s newly completed clinical trial that he just reported on at the Alzheimer’s Association International Conference.


Podcast Part 1: Plasmalogens & Neurological Health

Educational Seminars: free registration

Prodrome Sciences: supplements and tests

Breaking Alzheimer’s book: direct / Amazon

More info:

For pre-publication discussions of clinical trial results sponsored by the Alzheimer’s Association and presented at the Alzheimer’s Association International Conference (AAIC) in July 2021, watch episodes C105 and C106 at Dr. Goodenowe’s Educational Seminars site after free registration.

Show Notes

0:22  Julie’s introduction of Dr Goodenowe :  This is a longer podcast, almost 1.5 hours, but full of information, including results of his recent clinical trial.

Dr. Goodenowes’ research into biochemical mechanisms of disease started in 1990.  His curiosity on the biochemistry of life remains insatiable.  In the last 30 years he invented and developed advanced diagnostic in bioinformatic technologies, designed and manufactured novel and natural biochemical precursors, and identified biochemical prodromes of numerous diseases including Alzheimer’s Disease,   other dementia’s, Parkinson’s Disease,  multiple sclerosis, ALS, and many more.

Dr Goodenowe is now going beyond disease and the detection of biochemical dysfunctions to diagnose and move toward correction of biochemical dysfunctions to treat disease.  His new focus is to defeat the entropy of aging by creating strategic biochemical and biofunctional reserve capacity in advance of known disease risk so the body can maintain the physical and biological functions of life indefinitely and without disease.

2:06 Julie:  Welcome Dr Goodenowe.  So much has happened since last podcast, a recent achievement includes the publication of a new book, Breaking Alzheimer’s.   It was an excellent read and as a layperson you made it very accessible.

3:04 Dr G:  I’m a generalist in many areas.  My value is to consolidate research from multiple avenues, even though I’m an expert in specific fields, particularly biochemistry.

It’s easy for scientist to get enamored with the complexity of science.  There are basic organizing principles that are common in everyday life.  People get intimidated by science, that it’s complicated. But most of the things in science follows general logic that we see in everyday situation.  The words change, get more complicated, but the basic underlying principles are the same.  I really wanted to break down this fear of science.  I try to teach people how to learn these principles.

The last chapter goes into why we don’t have cures for these diseases, the structural reasons. Not to blame anybody, but to understand the organizational infrastructure of medicine and how private industry works vs public industry, and why universities aren’t doing public work anymore.  Many supplements have been clinically validated over the years yet they’re not implemented into routine care.  Why?  I explain that and if you want to change this reality, you have to understand what it takes to implement change.

I come from large clinical trial work, I also come from the pharmaceutical industry.  There are certain rules of the pharmaceutical industry and certain aspects of clinical trial work that have real validity, we can’t throw that out when we get into nutritional based medicine.

My interest is population medicine.  Medicine that can be applied to entire populations to change the percent of people who get dementia, or cancers, or autism.  That’s my passion.

I’m like a farmer of humans and giving them the appropriate fertilizer.

7:31  Julie:  You’re doing an amazing job of bridging several camps, we need more like you.

In your book you describe yourself as a biochemical detective.  You discuss the mass spectrometry technology platform that you invented that ultimately led you to identify plasmalogens as a major player.  Tell us how plasmalogens emerged from among the thousands of other biochemicals that you were studying.

8:04 Dr G:  I fundamentally view our living world through the lens of chemistry.  There are three large organization principles:  biology, chemistry, and physics.

We live in a world of chemistry.  We’re controlled by very simple laws.  The first law of thermodynamics is that energy or matter can neither be created or destroyed.  We just move things around.  Sunlight comes in, it converts carbon dioxide and water into glucose in plants. Then we take that and we burn it up with carbon dioxide and water.  We’re just moving electrons around, we’re moving atoms around.   That’s chemistry.

When the genetics revolution occurred in the 90s people sequenced entire genomes of plants and animals, thus understanding how these systems work.  Chemistry is really that core.  We needed a technology that could measure comprehensively all these small molecules so that we could see these transformations, so we could see this first law of thermodynamics in action.

Disease simplified is that something changes, there’s a cause and effect.   The technology that I invented was called nontargeted metabolomics, using high field mass spectrometry.  This allowed us to measure thousands and thousands of molecules simultaneously.   The original concept was to study biology, chemistry, and the effects of genetic modification of plants and animals, then apply it to human biology in human diseases.  When we started to apply it in the clinical trial world we looked at different disease states, what’s different.  Because if I can physically see a phenotypic difference, for example, you’re healthy but your sister has ovarian cancer I can ask what is different?  If I can physically see something different there has to be a chemical signature that matches that difference.


Over many, many diseases we started to see very powerful diagnostic capabilities.  Virtually every single human disease is diagnosable with this type of technology, the prodrome scan technology.

When it was applied to Alzheimer’s Disease, we saw these molecules called plasmalogens decrease.  Not just plasmalogens, many others too.  That’s the challenge of science, the cause and effect relationship can be quite diverse.  The farther you get away from an event, the harder it is to identify the actual cause.  For example, radiation disease in people from Nagasaki or Hiroshima 20 years after the nuclear bomb.  If you didn’t know about the nuclear bomb you’d have a very difficult time figuring out why the damage occurred.  The farther you get away a causation event the more complicated the situation gets.  With one insult in the human body, you get primary effects and secondary effects and over time you have thousands and thousands of changes.  The challenge is to work your way back up to that simple event.

It became reproducibly observable that plasmalogens were deficient in Alzheimer’s disease and cognitive impairment.  The low levels of plasmalogens correlated with the severity of the cognitive impairment.  It correlated with the rate at which it declined.  It also correlated with who got dementia in the future versus those who did not get dementia in the future.

From that clear observation the question is why?  What is it about plasmalogen deficiency?  Also is it linked or is it just a symptom?  With more and more research it became obvious it was core.  Even post-mortem analysis of brains the plasmalogen association with cognition is the most strongly associated.  It is the closest to the event we’re measuring, which reduced cognition of anything else in the human body.  That’s how it came to be.


This revealed that biochemical deficiencies precede our diseases.  They are prodromes, they are predictive of future events. The body can tolerate dysfunction for a certain period of time but eventually it turns into disease.

14:56 Julie:  You describe Alzheimer’s as a plasmalogen deficiency.  Is it really that simple?  Can we just replenish our plasmalogen levels and be protected?

15:10  Dr G:  To a certain degree, yes.  Obviously, there are other aspects that contribute.  When we get older, we’re talking 50s and 60s, our brain starts shrinking.  We get focused on Alzheimer’s as being the main event, but it isn’t the main event, it’s brain shrinkage, neuropathologies, reduced brain health.   Alzheimer’s is just a symptom.  Alzheimer’s is not a disease at all.

Your body is designed to work in a certain balance.  Your body must make your own plasmalogens and you make a lot of them.  Probably 20% of all lipids in the body are plasmalogens.  When you lose plasmalogens you don’t just lose plasmalogens.

For example, you want to bake your favorite cake.  Your recipe calls for 2 cups of milk, 4 eggs, and a pound of flour.  But you don’t have enough milk, only 1 cup.  So instead of a whole cake you make half a cake with the 1 cup of milk, 2 eggs, and a half pound of flour.   You adjust because of the situation.  That’s what your body is doing every night when you sleep.  It’s making “cakes”.  When you’re baking something, that’s chemistry.  You’re chemically transforming something from one form to another.  The egg that’s in the shell is very different chemically than the egg that’s been baked in the cake.  That’s what your body does.  We have trillions of cells in the body and every single cell has “bakers” in them.  These “bakers” are making membranes, proteins, etc.  They can only make what they need to make from what’s in their pantry.   When you lose plasmalogens in the human brain, you don’t just lose plasmalogens. Those “bakers” can’t make things appropriately.  You lose other things:   phosphocholines, ethanolamines, cholesterol, and hormones.  Those all come down because your body will adjust to the materials available to it.  That’s why brain shrinkage occurs.  There’s obviously other aspects, but plasmalogens are a critical component of brain health in terms of synaptic function, membrane modulation, etc.


The human body is really a very simple design biologically, two core things that must work to live.

This first core aspect is energy generation.  We breathe in molecular oxygen to burn hydrocarbons, much like the car uses oxygen to burn hydrocarbons. We eat fuel: carbohydrates, fats, proteins we burn those into carbon dioxide.  Our lungs are gas exchangers, we breathe in oxygen, we breathe out carbon dioxide.  That oxygen gets neutralized to water in the energy process and is peed out.  That process generates high energy electrons.  We’re basically returning the electromagnetic energy from the sun back.  Plants absorb electromagnetic energy and we release it back.  When the mitochondria of our cells don’t do that properly, we get oxidative stress and these electrons leak out.  One of the consequences of this oxidative stress is inflammation.  Inflammation comes from oxidative stress not the other way around.

The second thing is your lipid membranes.  The human body is made of lipid membranes, that’s why we’re not soup, it’s what gives us physical structure.  We have trillions of cells and each of these cells are defined by their three-dimensional structure and what puts the walls together are these lipid membranes.  The proteins in your body are embedded in these membranes.  Virtually everything lives in lipids in the human body.

Imagine walking on solid ground versus walking in mud.  In mud you can’t move properly.  Walking in mud changes how we walk, how fast, and such.  When we lose plasmalogens your membranes become like walking in mud, nothing works properly.  It’s more than just plasmalogens, there can be other deficiencies, but plasmalogens are critical.

It takes a triage perspective.  You want to first identify the most critical component first, then move on to the next one, and on. So if you’re a gardener, the first thing when you need with a plant is nitrogen and water, not fungicide or sulfur.  After the most important components are taken care of, then you can move on to other things for optimization.  It makes no sense to focus on the minor esoteric issues until you deal with the core issues first.

23:28 Julie:  And that’s plasmalogen levels.

23:31  Dr G:  Plasmalogens are core.  If you don’t have sufficient plasmalogen levels, you’re really wasting your time on a whole bunch of other things.  If you don’t have proper mitochondrial utilization, you’re wasting your time.  You’re fixing windshield wipers on a car that has no oil, it won’t help you drive any farther.

23:53  Julie:  I love your analogies. That’s a very hopeful answer, so yes it really is that simple.  We can replenish our plasmalogen levels, we’ll talk about that later.

In your book, you emphasize the importance of identifying and addressing the APOEε4 mechanism that increases our risk.  You say that’s an impaired cholesterol transport system.  The antidote you suggest is to rebalance the cholesterol transport weakness through high levels of plasmalogens.  Can you explain how that works.

24:38 Dr G:  I really put time toward the ε4 community because it is such a confusing world out there.  This definitive lecture series that I’m launching, the first lecture is on APOEε4.  In the book there three chapters dedicated to the ε4 scenario.  It’s easy to get caught up in the noise.  Just like plasmalogens, you have to identify what is it about ε4, ε3 and ε2 that changes the risk profile.  Everyone with the APOEε4 genotype should understand is that the ε4 genotype itself has no increased risk of mortality in the nature of the genotype difference.  There’s no reason for an ε4 carrier to live less than an ε2 or ε3.  Similarly, people with the BRCA gene with regard to breast cancer, BRCA does not change your mortality risk, it just changes your disease risk.  It’s the disease that provides the mortality.  I go through that in the book.

The most proximate issue as a consequence of the ε4 genotype is accumulation of amyloid.  So ε4 carriers accumulate more amyloid than non-ε4 carriers.   ε2 carriers will accumulate less amyloid than ε3 carriers.  If you know the amyloid level of an individual, their genotype is irrelevant.  It’s the risk of accumulating amyloid.

Why do we have amyloid?  It’s a marker of brain health.  It’s all related to cholesterol transport.  Your body transports cholesterol on lipoproteins.  Cholesterol is a big piece of fat that isn’t soluble in water.  So how do you transport it because the body, blood, intracellular space are all made of water.  The body sticks it to highly water-soluble proteins called lipoproteins.  These lipoproteins are fat transporters.  The APOE gene codes for one of those proteins, the Apolipoprotein type E (ApoE).  It’s a very minor protein, we’ve known about it since the 70s.  The genotype has been known for many years but it wasn’t until 1993 that it was published that 50% of the people who had Alzheimer’s in their family history had the APOEε4 genotype.

In the United States about 25% of the population has one or two ε4 alleles.  Around 60% to 65% have two ε3s, and 10% to 15% have an ε2 allele.  These are the three main groups (ε4, ε3 and ε2) and there’s a high prevalence of Alzheimer’s in those with the ε4 genotype.  Why is that?

The ε4 lecture goes into this in greater detail with literature references.  But if you’re an ε4 carrier and you get a blood test, you’ll notice you typically have higher levels of LDL versus others.  If you’re an ε2 genotype you’ll typically have lower levels.  That is not bad, that is completely irrelevant to your health.


The reason isn’t the circulating ApoE4 levels, less than 5% of the lipoproteins in the periphery of the body is ApoE, virtually none of it is in LDL particles, but in Apolipoprotein B (ApoB), which is LDL.  Apolipoprotein A (ApoA) is HDL.  A little bit of ApoE is found in HDL particles, a little bit in very low density LDL, and a little bit in chylomicrons.  What makes ApoE unique is because whereas it makes up only 5% of the lipoproteins in periphery: lungs, liver, blood supply, etc., most is in the brain, it’s the only lipoprotein that the brain makes.  The brain has a totally separate cholesterol regulation system.  None of the cholesterol from your liver and blood supply gets to the brain.  Your brain makes all its own cholesterol and all its own transportation of cholesterol.  In the periphery we have an interstate system called the circulatory system: blood, veins, and arteries, that distributes material all around the body.  The liver makes most of the cholesterol and distributes it on LDL particles.  The cells will absorb the cholesterol that they need from the blood supply.  When you get a blood test it’s measuring total cholesterol, HDL, LDL.  Every single cell in the body can make its own cholesterol and the body will balance it, redistribute it.  If it’s making a lot, it won’t pull much from the blood supply, if it’s hungry, it will pull from the blood supply.

The reason why APOEε4 carriers have higher levels of LDL cholesterol is that they’re cholesterol conservers, which means your cholesterol efflux is lower.  Imagine your house has solar panels on an electrical grid.  The electrical grid from the power company is the circulating LDL.  The electrical grid in your house powered by the solar panels, that’s your individual cell.  If you’re a APOEε4 carrier, you’re very energy efficient, you don’t require much energy from the power company, so you absorb less, you conserve cholesterol.  Since you conserve cholesterol, you don’t require as much from the blood supply, so LDL levels will elevate because the cellular demand of cholesterol is less in an ε4 carrier than in an ε3 carrier.  ε2 carriers are the opposite, they efflux cholesterol, they can’t hold their cholesterol, they’re always absorbing cholesterol from the blood supply which makes their LDL levels low.  ε4 carriers have low cholesterol efflux, they hold their cholesterol better.

33:34 Julie:  They hold cholesterol better in the periphery, what about the brain?

33:38 Dr G:  That’s where it gets interesting.  They do the same thing in the brain, but the brain is very different.  In the periphery you have the interstate system of large arteries.  The brain is like Chinatown, it’s a whole lot of little streets, there’s no real circulatory system.  There’s a bit of a tidal system with the cerebral spinal fluid.  Everything in the brain is local.  What makes ApoE such a unique molecule, it has equal LDL and HDL qualities.  It can act as an LDL so it can deliver cholesterol and it can act as HDL for exporting cholesterol.  Your brain uses ApoE for both functions.  Instead of the liver making cholesterol, in the brain your astrocytes make cholesterol and your neurons and everything else absorb cholesterol.  It’s all about cholesterol efflux.  How the brain uses one single protein (ApoE) to do all of this is with different transporters.  You have LDL transporters which are generic, but how cholesterol gets out of the cell requires three main transporters called ATP binding cassettes (ABC): ABCA1 (A1), ABCG1 (G1) and a ABCG4 (G4).  Three separate transport proteins the control the efflux, some are on neurons, some are on astrocytes, and they work in conjunction with each other.  The APOEε4 genotype is involved in the efflux from A1.

The APOE genotyping is called Single Nucleotide Polymorphisms (SNPs – pronounced snips).  There are two amino acids that are changed.  They change from either a cysteine, which is a sulfur containing amino acid, to arginine, which is a very polar amino acid.  What’s important about cysteine, as a sulfur amino acid, is it creates disulfide bridges, dimers, which are like two magnets that stick together.  APOEε4 carriers cannot do that, they can’t create dimers.  The ε2 carrier will have two cysteines, two free sulfurs.   ε3 carriers will have one sulfur cysteine and one arginine.  ε4 carriers will have two arginines, which means they have no cysteines at all, they cannot create dimers.  It’s the dimerization of the ApoE4 protein that modulates its cholesterol efflux capacity through A1, and it’s a dose dependent effect.

The difference between the genotypes is the ability for cholesterol to leave the cell through the ABCA1 transporter.  That A1 transporter is in a certain part of the membrane, in the phospholipid rich region.  The other system that modulates this A1 transporter is an enzyme called ACAT (Acetyl-CoA acetyltransferase), it’s what esterifies cholesterol for export.  That’s used in the periphery as well.  What happens is that protein is controlled by plasmalogen levels, so if you increase cholesterol esterification it increases transport.  You have a three-legged race with ApoE on one side, plasmalogens on the other side, and the A1 transporter in the middle.  If one is weak, the other can compensate.  So when we’re young with lots of plasmalogens, APOEε4s are protected, it only becomes a risk factor later in life when plasmalogen levels become depleted, then the counterbalance of the ε4 on the ABCA1 transporter is missing.  When that happens, the levels of cholesterol in your membranes increase and with that amyloid, the Amyloid Precursor Protein (APP) is shifted from its normal process which is the formation of soluble APP to Amyloid Beta 42 (Aβ42), a major component of amyloid plaque.

That’s why ε4 carriers have an association with amyloid.  ε2s will have less amyloid than ε3s, ε4s will have more amyloid than ε3s (ε2 < ε3 < ε4). It’s 100% related to cholesterol efflux.

If an ε4 carrier does not accumulate amyloid, that person is just like anyone else.  An ε3 carrier can have other cholesterol problems, have more amyloid, and be worse than an ε4 carrier.  Even an ε2 carrier can have amyloid issues.  It’s just that odds are, all things being equal, and the individual is ignorant of what controls their genotype, then ε4s will have cholesterol membrane problem.

So ε4 carriers that have high plasmalogens in the brain have normal amyloid levels. If the blood plasmalogen levels are high, the ε4 genotype is silenced, no increased risk.  That was published a year and a half ago.  It all comes down to that one protein the ABCA1 protein, it’s related to the dimerization, specifically the SNP mutation in ε4.   ε4 carriers don’t need to know anything more than that.

The LDL in your blood makes no difference, there’s nothing wrong with that, in fact it’s a measure of health.  The worse thing is to have low cholesterol because it shows your cells are unhealthy.  If your cells are unhealthy, they need cholesterol and they suck cholesterol from the blood supply, or your liver is not making enough cholesterol.

When the A1 protein doesn’t work properly the problem is distribution.  Everything in the brain is localized.  The neurons share with each other.  If one neuron has a little extra cholesterol, a little extra phosphorylcholine, it will export it.  It’s like a solar panel network.  The power is redistributed as needed, but if you can’t redistribute, you can’t optimize.  That’s what happens with APOEε4 carriers, the reserve, or buffer, of redistribution is not as good.  We’re very dependent on having adequate plasmalogen levels whereas the ε2 carrier can be sloppier.  It’s like how one person can eat and remain skinny whereas another person can look at food and gain weight.

42:16 Julie:   It’s actually very hopeful.  So as an APOEε4 homozygote (ε4/4) as long as my plasmalogen levels are high, my cholesterol efflux in my brain will be optimized, and I will not collect amyloid beta.

42:25 Dr G:  You’ve made it this long; your body has the right compensation mechanisms.  That’s the other problem with have with medicine and diseases, they get focused on excesses.  But that’s not how health works, 100% of human disease is caused by a deficiency.  Excesses come from deficiencies.  If you have a deficient transport of the A1, that creates the excess of cholesterol.

43:34 Julie:  That’s what I don’t understand.  I’m thinking of a Type 2 diabetic taking in an excess of glucose, isn’t that what’s causing disease?

43:45 Dr G:  No actually, it’s because they have an impaired ability, it’s insulin insensitivity.  The reason why they have elevated blood glucose is because they have a deficiency in glucose regulation, that deficiency causes the excess.

The world is very stingy.  Biochemistry doesn’t waste anything.  Excess isn’t created freely, if there’s excess, it’s because there’s nowhere else for it to go.  The root cause of all toxic excesses comes from a deficiency of some system.

45:02 Julie:  I’m going to go back to cholesterol because I think a lot of people in our community are uber focused on their cholesterol.  There’s something you say in the book that’s every encouraging.  In terms of all-cause mortality, you say total cholesterol in the 220 to 240 range as being the healthiest.

45:30 Dr G:  240-250 is where you want to be.  That’s not me saying that, that’s 164 country epidemiology data, 12 million people in Korea, these are huge studies.  The optimal blood cholesterol level for longevity, lowest rates of all-cause mortality occur in individuals with cholesterol levels in the 240 range, 220 to 260.  As soon as your cholesterol levels get below 200 all-cause mortality starts going up quite dramatically, it’s an indicator of reduced health.

46:12 Julie:  It fits with your stingy analogy.

46:16 Dr G:  Cholesterol is critically important to the human body.  We want to regulate it, too much in the wrong place is not good. For instance, what we talked about with too much in the membrane of the brain.  Typically, if people have low levels of cholesterol in their blood it indicates something is not right. Either they have a liver problem in that they can’t make enough cholesterol, often it’s a phosphatidylcholine deficiency that’s causing it, or they have cellular issues.  If they’re taking a statin, basically a statin is a mitochondrial toxin, it turns off your solar panel, it forces the cells in your body to get their cholesterol from the blood supply.  Since the cells can’t make their own cholesterol, they’re forced to get it from the blood supply, which lowers blood cholesterol levels.  Where statins got their main purpose is in cardiovascular disease.  Oxidized LDL is associated with atherosclerosis and heart disease.  The theory with statins is if you lower LDL, you lower the pool of peptide of proteins that can be oxidized.  That’s logical and it’s true.  The clinical data on statins is if you have underlying oxidative stress, if you have high C-reactive protein levels and high LDL, then you’re at increased risk.  But if your oxidative stress markers are low, you can have cholesterol of 300 and it’s not going to hurt you.

48:07  Julie:  Wow, that’s very encouraging.

48:11 Dr G:  Cholesterol is not a toxic molecule, it’s benign, your cells need it, by itself it has no toxicity.  If it gets oxidized then it becomes an inflammatory mediator, it creates foamy macrophages, atherosclerotic plaque, etc.  The issue is really oxidative stress, it’s keeping C-reactive protein levels down.  That was another outcome of the clinical trial is that people who take plasmalogen have low levels of oxidative stress.

48:42 Julie:  That’s so exciting.  Before we get to the clinical trial results you recently presented, I want to tie this in a neat bow so our listeners know.  We’ve talked about plasmalogen levels and that we can increase levels, I want to tell them how to do it.  You’ve created a Prodrome Scan that can be very helpful in learning plasmalogen levels and other things as well.

49:12  Dr G:  The Prodrome Scan is the beginner’s kit of your own personal biochemistry.  It identifies the key issues of biochemical health that you want done first.  It’s really basic stuff.  Looks complicated the first time you see it, but it’s really basic. It’s organized into two pages, 14 sections.  One section deals with the phospholipids of the body, part of that is the plasmalogens.  The other is phosphocholines, people talk about lecithin, it’s another major issue in society that people, especially vegetarians don’t get enough good fat.  Choline deficiencies are really bad, that’s one of the reasons you have low cholesterol, it causes liver disease, pancreatic cancer and so on.   You don’t want to become choline deficient. It’s also linked to your homocysteine system.  We look at phosphocholines and ethanolamines the stuff that makes up all the membranes of the body.

Then we look at fatty acid ratios in the lipids.  We know about omega-3s and omega-6s and omega-9s and saturated fats.  The same part of the call that makes plasmalogens makes your own DHA, which is your long chain omega-3.  You want to make sure your cells have sufficient DHA or actually high levels of DHA in relation to arachidonic acid (AA) which is your omega-6 version.  We measure those levels in the membrane lipids, so that your cells are pre-loaded for low inflammation.  You’re going to get inflammation, that’s natural, you want that inflammation to stay localized and then disappear after it does its job.  The problem with the inflammation that people are experiencing with autoimmune diseases is that inflammation doesn’t stay localized to that site of inflammation, it grows.  Part of that is making sure your DHA to arachidonic acid ratio profiles are right.  It’s also very important for cancers, especially for reducing breast cancer risk.  Also cardiovascular risk.


Then we check iron levels.  If you’re iron deficient, then you become deficient in other key metals.  We need iron for oxygen transport.  All the cells, the mitochondria, need iron.  Most of the mortality from COVID in hospitals are from people who have a pre-existing iron deficiency.  When you get inflammation, your body is making a whole bunch of new cells, in the brain it’s called microglia, and in the blood it’s your macrophages and T-cells.  Those are brand new cells.  For every cell that your body makes there has to be materials to make them, you need “bakers” all those cells need mitochondria, peroxisomes, etc.  Those cells need iron. Mitochondria need iron.  When you get inflammation, it starts sucking iron out of your reserves. If your inflammatory cells need iron they take it out of the other cells. You don’t want to become iron deficient or deficient in the other metals that follow such as like selenium and copper that I don’t measure, but there are other tests can measure for that.


I check gastrointestinal (GI) health.  There are biomarkers that have been studied for colon and pancreatic cancers extensively.

Then we get into the key issues of your body we look at the methyltransferase system.  This is one system people think of B vitamins: B-12, B-6, methylated folate that most people who are health conscious are taking.  The reason you’re doing that is to make sure you have methyltransferase.  Amyloid formation in the brain is also methyltransferase dependent, not just membrane.  The other component that causes abnormal amyloid is methyltransferase deficiency which is caused by homocysteine.  Same thing with phosphorylated Tau, neurofibrillary tangles in the brain, those are driven by methyltransferase issues in the brain. The definitive lecture series goes through each of these things in detail.  You can reduce your Tau tangle formation.  I explain how phosphorylated Tau works in the brain.  We measure methyltransferase, homocysteine, sphingomyelins and ceremide ratios.


We check mitochondrial health to make sure your mitochondria are tuned up.  These are all easily fixable.  If your mitochondria aren’t working properly, you can easily take carnitine and other supplements.

We check peroxisomal function which is where plasmalogens and DHA are made and helps regulate fasting triglyceride levels.  Everyone should have fasting triglycerides under 100.   If fasting triglycerides are over 100 something is not right, but it’s fixable.

We check cholesterol levels make sure your not cholesterol deficient.  Check HDL levels.


Then a couple other markers that are old school markers like creatinine.  People think of creatinine for kidney disease, but actually when you get older the biggest issue for people with low creatinine is you’re in a muscle wasting space.  Muscle wasting, sarcopenia, is a critical issue as we get older, but it’s also fixable. In the clinical trial, more powerful than the cognitive changes was the sarcopenia and muscle wasting.  We had dramatic improvements in muscularity in only four months.

We also check uric acid levels.  People think of uric acid for gout but low levels also indicate inflammation and other diseases.

The scan hits all the main areas.  We have certified doctors that understand it and there’s educational materials on the website for individuals.

For example, if cholesterol is 150, you ask why is the cholesterol so low.  You look up the chart and you see phosphocholine is at the 20% percentile, that’s the reason.  You can fix that with lecithin supplementation.  With choline levels up I can fix cholesterol levels.  If my fasting triglycerides are too high, I can fix that too, by increasing intermittent fasting level, ProdomeNeuro (supplement sold by Prodrome Sciences) will improve peroxisomal function, also moderate exercise with resistance training.

Just like your phone that you use all day, it expends energy so you put it on the charger at night.  Your car uses energy so you fill up the tank.  Your body does that every day, it switches from the fed state to the fasting state.  During the day you’re typically in the fed state, you’re up and active.  At night you’re on recharge and that’s when you’re in the fasting state. It’s in the fasting state that’s when you build.  It’s lipogenic.  During the day your body runs on glycolysis, it takes glucose/sugar that generates the energy but our rebuilding processes are shut down.  At nighttime, your body switches from glycolysis to lipolysis, which means it breaks down fatty acids from your fat cells.

58:21  Julie:  That’s when you’re in ketosis, at night.

58:24  Dr G:  Right.  The natural way for your body to get into ketosis is caloric restriction.  Typically, at night, you’re not eating so eventually you come into lyposis, you’re keto.  During the day your stomach digests food for energy.  At night your fat cells digest food for energy.  That’s when you’re building, that’s when you make your steroid hormones, your membranes, when you rebuild/fix all the stuff from during the day.  When you get older, we don’t consume as much energy during the day as we did when we were younger, it takes longer to get into that fasting state.  Late night snacking is especially really unhealthy because it prevents the body from getting into that fasting state and rebuilding.  You can do keto, but you should do both, your body is designed to switch back and forth.

59:31 Julie:  In our community, most of us do keto through fasting, exercise, we know healthy ways of getting into it, as well as our low carb diet.

This Prodrome Scan, everybody should get one, figure out what your plasmalogens are, get a snapshot of your health.  I’ve got two kits sitting in my kitchen, I can’t wait to do it.  Our show notes have a link on how to get the Prodrome Scan.

Also important, you’ve also created a plasmalogen precursor supplement that can essentially replenish plasmalogen levels.  We’ve identified that Alzheimer’s is a deficiency of plasmalogen. Tell us how we can increase our plasmalogen levels.

1:00:12  Dr G:  This is really exciting.  We’ve known about plasmalogens about 100 years now.  We know they’re obligate to human life.  If born with a genetic mutation that stops you from making plasmalogens either you will die in the womb or die before reaching your 10th birthday.  The consequences of plasmalogen deficiencies are severe.

The body has lots of plasmalogens, but it has different plasmalogens for different reasons.  Diseases like Multiple Sclerosis and ALS, those are white matter diseases.  The plasmalogen that’s in your white matter are protective, they’re the “plastic coating around the copper wire”.  They’re very impervious to oxidative stress.  That’s plasmalogens containing an Omega-9, like oleic acid from olive oil, but it has a plasmalogen backbone.  We have a product called ProdromeGlia which delivers 100% Omega-9 plasmalogens.  (The other product is called ProdromeNeuro).

1:01:25 Julie:  So how does someone know which supplement to buy?  Is it the result of their prodrome scan?

1:01:33 Dr G:  The simplest way is to know is ProdromeNeuro is for performance.  ProdromeNeuro has Omega-3 DHA in it, that’s critical for neuromuscular junction for muscularity and for cholinergic neurons in the brain.  The same neuron that handles cognition in the brain is the same neuron that handles muscle activity.  DHA plasmalogens are the ones that ApoEε4 carriers need, the DHA plasmalogens modulate the cholesterol efflux.  They also improve cognition in the synaptic cleft of neurotransmission.  Omega-3 DHA is a performance enhancing plasmalogen.  The omega-9 oleic acid is for protection, mostly for younger people: autism, multiple sclerosis, concussions, stroke.  You can use both the molecules will share each other.  As we get older, we typically need more of the DHA.  But they’re both extremely healthy for different reasons.

The problem with plasmalogens is the very last step in their manufacture is that they create what’s called a vinyl ether bond.  This is what gives it its special powers.  It’s packing power in the white matter protective sheath and it gives it its membrane fusion, neurotransmitter release, membrane modulation power for performance.  It’s also why it’s a very powerful antioxidant.  It neutralizes peroxides.  That process makes that molecule very sensitive to exposure in acidic environments.  So when you eat something that has plasmalogens in it, like a steak, when it hits the stomach acids, those plasmalogens break down.  Dietary sources of plasmalogens are very minimal compared to what we need.  We get insignificant levels from our diet.   As a chemist, I needed to design a molecule that can survive the stomach acids.  These are natural precursors, they’ve been around forever, they’re called alkyl-acylglycerols.  The problem with the natural sources is you can’t get them without other things, you can’t target specific neurons, you can’t get purified versions. What I’ve designed is purified alkyl-acylglycerols, two types, everything is 100% vegan, no risk of environmental contaminants in any of our products.  The DHA is from an algae source.  We make a free fatty acid form and put that on a plasmalogen backbone.

Your body needs lots of it.  The small dose is 900 mg.  Your body has grams.  You need to make sure you’re taking enough of it to have an effect.  I designed plasmalogen precursors that are 100% natural, they are part of the natural human biochemistry, so not only does it get absorbed in your blood, it elevates your overall blood plasmalogen levels, it’s designed to go into each of the cells of the body as a precursor.  This idea of the power grid vs your own capability, it does two things, it increases the entire grid of plasmalogens and every day you take a plasmalogen supplement it pulses itself into your neurons. It actually goes into every single cell of the body and lets the cell do the final two steps, they don’t even need to get plasmalogens from the blood supply anymore.  That’s what was interesting from the clinical trial, we didn’t segregate anyone for their baseline plasmalogen levels and we had the same clinical effect from those who had high plasmalogens at baseline vs people who had low plasmalogens.

1:06:29 Julie: Did you get baseline plasmalogen levels for the clinical trial?

1:06:40 Dr G:  Yes, it was a very controlled.

1:06:42 Julie:  Let me back up for a second.  So Dr Goodenowe just presented at the Alzheimer’s Association International Conference (Jul 26, 2021 – Jul 30, 2021).  This is not published.

1:07:04 Dr G:  Yes, this is what we presented in Denver.  This was a clinical trial approved and financed by the Alzheimer’s Association. The Alzheimer’s Association paid for this.

1:07:14 Julie:  That’s very encouraging.

1:07:19 Dr G:  We did it in collaboration with a group in Santa Monica, Dr Sheldon Jordon, neurologist.  We did a very simple, straightforward, open label.  The goal was to know how much plasmalogen precursor we needed and what was the effect of adding plasmalogens to blood levels.  We had a hodge-podge of individuals.  We had 22 people, all had cognitive impairment, a clinical dementia rating scale (CDRS) of 0.5, 1.0, or 2.0.  There are four scales on that rating scale:  0.5 is mild cognitive impairment, 1.0 is moderate, 2.0 is semi-severe, and 3.0 is very severe.  Fourteen had mild cognitive impairment.  Four had a CDR of 1.0, and four had a CDR of 2.0.  Everyone had cognitive impairment, there was no control.  We had as young as 37, some had Lewy Body Disease, most had Alzheimer’s dementia.  Dementia comes in many flavors, we have vascular dementia, Alzheimer’s dementia, Frontotemporal lobe dementia, Lewy Body dementia.  Dementia is reduced cognitive function but there are different types of cognition.  We did no selection, this was a random group of people.

We got blood baseline levels. Cognition at baseline.  Looked at their mobility, a 30 second sit-stand which is stand and sit as many times as can in 30 seconds, it’s a measure of mobility and muscle strength.  That was done every month.  So we had a baseline.  In the first month, they took 1 ml a day of the ProdromeNeuro, or one bottle lasting one month.  At the end of the first month they were tested cognitively, mobility, and blood samples drawn.  Then they went home with two bottles of ProdromeNeuro, so they doubled the dose, 2 ml a day.  We did that for two months.  At the end of the second month we tested cognitively, mobility, and blood samples drawn.  Then we gave them 4 bottles of ProdromeNeuro, one bottle a week, 4 ml a day.  That’s the dose from animal trials for complete neuro protection for neurodegeneration.

We have a number of people who are on the high dose that have had dramatic improvements in Parkinson’s and Alzheimer’s.  We had people with a CDR of 3.0 who are down to 1.0 now since they’ve been on the high doses of the Plasmalogens.

1:10:53 Julie:  Wow

1:10:55 Dr G:  Then we did a wash out phase for a month and took tests at the end.  So four people had a CDR of 2.0, which is the most severe of the people in this trial, three of those four improved by more than an entire CDR score, they went from a 2.0 to a 1.0 or a 0.5, a dramatic improvement.   Half of the people with a CDR of 1.0 improved.  Remember, Alzheimer’s is a disease you’re not supposed to improve from.  When you do a clinical trial what you’re doing is trying to do is ask the question, “can we reduce the rate of decline” no one ever talks about improvement.

1:11:43 Julie:  Absolutely.

1:11:55  Dr G:  I know Dr Dale Bredesen talks about improving.  There are others out there who are not satisfied with just reducing decline, we can get better.   We had significant cognitive improvement in individuals.  The other thing that was the mobility improvements were quite dramatic, 4-5 increased sit-stand, so the sit-stand improvement was actually more robust than the cognitive improvement.

1:12:29 Julie:  Wow

1:12:30  Dr G:  From my own experience it is muscle enhancing, it improves your exercise capability.

1:12:43 Julie:  At what dose did you see the most improvement?  4 ml?

1:12:50  Dr G:  About 2 ml is probably where most people will be.  For some of the severe people, the 4 ml helped.  Remember these are people who already have cognitive impairment, the blood test is designed to understand biochemical health.  If you have a neurological disease, if you have symptomology, then biochemically you want to supplement in an appropriate way for that disorder regardless of the blood test.  The blood test is designed to make sure there’s no boogey man under the bed that you don’t know about.

1:13:38 Julie:  That’s actually very encouraging because that’s a step some people could skip if budget is tight, skip the Prodrome Scan and go directly to the supplement.

1:13:50  Dr G:  I’m going to create a Breaking Alzheimer’s package that I’ll be coming out with later.  Because the other thing with Alzheimer’s and supplementation is it becomes pretty complicated.  It’s hard for us to send 10 bottles of supplements out to people.  We’ll be packaging things in a much better way.  There will be a designed supplement biochemically engineered package for people.

1:14:26 Julie:  When you went to the washout period, did people lose the gains they incurred?

1:14:36 Dr G:  The plasmalogen levels came down. The gains stayed for most people.  We had a couple people that within two weeks, these were the more severe cases, they opted not to complete the trial, they started to dose again. It’s individual dependent.  Symptomatically, the plasmalogens have actual physiological effect in improving cognition.  Anyone who takes the supplement will typically experience that, feel a sense of awareness.

1:15:17 Julie:  My understanding is the people need to take the supplement for life.

1:15:23 Dr G:  Pretty much.  It’s kind of like a Vitamin D story, there are natural ways to increase Vitamin D, plasmalogens are the same, there are lifestyle practices that improves it, like fasting, exercise.  When you get in your 60s, 70s, 80s and 90s you’re not dealing with what happened last year, you’re dealing with what happened for 30 years.  You can’t fix 30 years of decline in 2 weeks.  If you want to push time back, you have to create the biochemical reserve, that will take a while.  It’s like a game of musical chairs, we want our players around the chairs so we have our guy ready to sit in the empty chair. Biochemical reserve capacity has excess plasmalogens available.  The brain has a slow rate of turnover, for us to restore neuronal membrane structure it takes time.  So yes, it’s something you will want for the rest of your life for prevention and optimal health.

1:17:02 Julie:  This is so incredibly exciting.  When are you going to publish the results of the trial?

1:17:09 Dr G:  We’ll write it up pretty soon.  I put a video together on the results.

The other thing we measured was antioxidant biomarkers, this was the second part of the trial. We measured malondialdehyde, these are aldehyde levels, we measured catalase function, we also measured superoxide dismutase levels.  We had a very powerful correlation, really exciting to me, hopefully to readers as well.  When you get oxidative stress there’s many mechanisms.  The first phase is this super oxide radical is formed that normally gets neutralized by an enzyme called super oxide dismutase (SOD). When that gets mutated we have diseases such as ALS.  That takes the super oxide radical and converts it to hydrogen peroxide, which is less damaging than the super oxide radical but still not good.  Then this hydrogen peroxide gets neutralized either by glutathione peroxidases, catalase, or plasmalogens.  But if that doesn’t happen those peroxides will eventually oxidize lipid membranes, you get peroxidated lipids, that’s the nasty stuff that causes inflammation, vascular disease and so on.  Malondialdehyde (MDA) is a more sensitive biomarker.  C-reactive protein is a biomarker for oxidative stress, but malondialdehyde is much more specific.  We had a very powerful correlation, P value of 10-7 in a small trial, crazy.

1:18:46 Julie: Wow

1:18:47  Dr G:  We looked at people with high MDA levels vs low MDA levels, and everyone who had high MDA levels the plasmalogens neutralized them.  We neutralized the aldehyde levels so oxidative stress levels really went down.  Catalase is an enzyme, it’s a protein it works to neutralize hydrogen peroxide. When we reduced peroxide load with the plasmalogens, catalase levels started recovering.  We also had improvements in SOD.  Very powerful mechanistic data.  Our average plasmalogen levels doubled and more, a dose dependent effect.

That video is live now, that data is available.

1:19:47 Julie:  Fabulous.  This is astounding news.

1:19:58 Dr G:  The first time in human history we’ve been able to target and elevate blood plasmalogens.

1:20:09 Julie:  How was your presentation received?  I’ve been following the news out of the AAIC and I’ve been disappointed they’re not reporting on this.

1:20:34  Dr G:  I’m disappointed but it’s a tough world out there, these institutions need to live, they’re funded by donations, their ability to get things done.  They’re between a rock and a hard place.  They funded this trial, so they’re doing this kind of work, the challenge is in the delivery mechanisms.   What do you do with a trial like this afterward?  The pharmaceutical industry has a very simple delivery mechanism.  They get the FDA approval, pharmacy delivers, doctor can prescribe, it can get distributed very quickly.  The Alzheimer’s Association has to be an open tent for all people.  They do a lot of epidemiological studies, they do nutritional studies.  The problem with the nutritional work and the stuff we do, as exciting as it is, is that we need to solve the delivery problem.  How do we get it to everybody?  That’s my biggest focus.

1:21:53 Julie:  You have an educational hurdle.  You need to explain to people all about plasmalogen levels.  Doctors aren’t getting this.

1:22:07 Dr G:  No, but they’re getting there.  Our network of doctors is growing dramatically.  In the end the proof is whether it works or not. Doctors are really excited because they’re seeing dramatic results in their patients.  The anecdotes we get from patients and their loved ones.  One of the biggest problems we’ve had to break down is people don’t expect health anymore. They expect to live with disease.  We’ve convinced people they can’t recover from disease.

1:22:49 Julie: There needs to be a paradigm shift.

1:22:52 Dr G:  People have to realize you shouldn’t be sick.  The human body is designed to work.  If it’s not working, it’s not balanced properly.  That’s what we do with biochemical engineering, we deal with very simple, straightforward biochemical stuff.  You can measure it, before and after, you can fix it.  It will become mainstream, we are in the beginning of a major shift.  The pharmaceutical industry is imploding.  This new Alzheimer’s drug, $35,000 a year for amyloid lowering.

1:23:42  Julie:  It’s actually more than that, $56,000.

1:23:46  Dr G:  It’s crazy and it doesn’t even work. Actually, the drug works perfectly.  What it’s designed to do is to lower amyloid and it absolutely does that.  It does exactly what it supposed to do.  Just like statins, statins work, cholesterol levels will go down, the question is whether that’s useful or not. Pharmacologically the drugs do exactly what they’re designed to do, the question is if what they’re designed to do have any positive health consequences.

1:24:31  Julie: They have nine years to gather more evidence, so we’ll see.

1:24:41  Dr G:  There are many scientists out there and it takes years to get government grants.  Changing trajectories in public research is not trivial and it’s very competitive.  They get one little advancement at a time.  You can’t suddenly switch gears when you have thousands of scientists studying tau and amyloid and esoteric proteins.  It takes a while.

1:25:28 Julie:  You’ve got a great attitude.  I’ve been in this space about nine years now and what you’ve accomplished is nothing short of amazing and I’m so excited to share that.  I feel badly we’ve taken so much time.  I want to thank you so much for sharing your work.  We’ll share links in the show notes.

1:26:16  Dr G:  The APOEε4 lecture series especially, it gets to the root of the matter.

1:26:22 Julie:  I have one last question, where can people get a copy of your book.

1:26:26 Dr G:  You can go to, it’s also on Amazon.

1:26:35  Julie:  Wonderful.  Breaking Alzheimer’s, I love the title.   I can’t thank you enough for sharing your time and your work.

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