EP231: Lipid Biology, Plasmalogens, and Neurodegenerative Prodromes - Part 2 - Dayan Goodenowe, PhD
In a Nutshell
Dr. Dayan Goodenowe explains chronic diseases (autism, Alzheimer's, MS, Parkinson's, ALS, Long COVID, ME-CFS) as acquired losses of biochemical resilience due to entropy, mitochondrial/peroxisomal dysfunction, and plasmalogen deficiencies, detectable via prodromes like low HDL (<50-60), total cholesterol (<200), high triglycerides (>100), and elevated homocysteine. Restoration prioritizes plasmalogen precursors (omega-3 for gray matter/synapses, omega-9 for white matter), phosphocholine from animal sources, methyltransferase support (B12, methylfolate, TMG, NAC), niacin for NAD, and mitochondrial boosters (carnitine, acetylcysteine) over toxin removal alone, reversing neurodegeneration, improving brain structure/function, and building adaptability. Daily practices include resistance training, hormetic stress, purpose-driven service mindset, and simplified protocols via ProdromeScan/Biometrics for monitoring progress toward longevity escape velocity.
These notes were generated by AI and may contain inaccuracies.
Welcome to the Better Health Guy podcast, exploring complex chronic conditions to build resilience, improve vitality, and achieve better health. Sign up for Scott's newsletter in show notes for updates and support options. Subscribe, rate, or review to help reach more listeners. Content is informational only, not medical advice; consult personal medical authority.
Continuing part two with Dr. Dayan Goodenowe on lipid biology, plasmalogens, and neurodegenerative prodromes. Listen to episode 230 part one first for foundation. Jumping into chronic illness and neurodegenerative prodromes through Goodenowe lens.
Discussing chronic illness and neurodegenerative prodromes, patterns from lab testing, root causes, and support approaches including plasmalogen precursors, phospholipids. Question: How similar or dissimilar are modern chronic diseases like autism spectrum, PANS/PANDAS, chronic Lyme, mold illness, Alzheimer's, MS, Parkinson's? Environment drives via toxicity, non-native EMFs, terrain disruption, chronic infections, immune dysregulation, poor food quality, nutrient density, air/water quality, stress.
Dr. Goodenowe: More similarities than differences. Human body designed to work unless born with severe genetic metabolic disorder; these are acquired. Not attacked by external pathogen; philosophical fault to seek protagonist. No child born with autism—neurodevelopmental delay from reduced health. MS, Parkinson's, ALS, dementia are loss of function from failure to maintain health. Similar stresses proliferate diseases like canary in coal mine; what breaks varies by individual.
Prodromes: How lost resilience becomes observable health deviation. Restoring health same across diseases despite different deviation paths.
Aging not disease—entropy. Body deeply organized; requires energy to maintain order against dispersion. Analogy: Making bed daily, smoothing wrinkles from daily activities. Body burns calories (carbs, proteins, fats) to CO2/water, generates energy, uses building blocks to restore order.
As older, accumulate entropy opportunities like house scars/baseboards. Maintenance restores: repaint house, tune Model T. Body made of living cells that self-fix with right materials/stimulation. Aging from lower function adaptation: less exercise, atrophy. Predictable milestones like car parts failing (brakes at 65,000 miles)—not programmed, but predictable from use/genetics.
Genetics predispose: one to Parkinson's, another ALS/MS like car models to bad brakes/transmission.
Prodromes in biochemistry: deviations like low plasmalogens, methyltransferase system, mitochondrial function. Bundled indicators of system failure. Analogy: Smoking car exhaust predicts engine failure/carbon buildup; poor glucose processing predicts negative outcomes.
Source of disease: biochemistry inability to maintain order due to insufficient energy/building materials; unchecked entropy proliferates until failure.
Loss of life: inability to adapt to changing environment; immortality is successful adaptation.
Top stressors: chronic infections, toxicants, others. Balance supporting adaptability (plasmalogens, phospholipids) with removing/mitigating stressors.
Core biochemical systems:
- Metabolic sufficiency: metabolize sugars/fats (triglycerides, HDL cholesterol, glucose regulation, fasting insulin).
- Energy creation: ATP efficiency, mitochondrial biomarkers.
- Building materials: proteins/amino acids, lipids (30 trillion cells with phospholipid bilayers, intra-organelle membranes). Membranes fuse, store resolvins/fatty acids/signaling molecules, house receptors/ion channels. Body makes cholesterol (large membrane portion), plasmalogens, fatty acids (via synthase, e.g., oleic/saturated), essentials (omega-6/3), methyltransferase (phosphorylcholine, homocysteine).
- Lipids oxidizable like house paint/rancid butter; manage oxidative stress (malondialdehyde, oxidized phospholipids, C-reactive protein).
- Immune response (interleukin-6, etc.).
Build reserve capacity: B vitamins, higher-dose plasmalogens, animal-based phosphocholine, leucine-enriched protein, niacin—provide ready-made materials energetically demanding to produce.
Need constant slight stress to overcome (hormetic). Low-stress life undesirable; overcome stresses sequentially. Life milestones (school, dating, marriage, kids, job) build resilience. In 50s-70s+, milestones fade (empty nest, retirement), atrophy ensues. Body in constant motion (heart/brain always on); needs continual stimulation/challenge for higher function.
Two components: function/purpose—reason to get up, positive outlook, invigoration by challenge, biochemical sustainability. Natural lifespan milestones exist; for 150-300 years, rethink life (e.g., limited golf). Reinvest high-functioning seniors into society.
Programmed cell death/adaptations to lower function.
Key: Measure death/dying, restore immortality, measure structure/function of perpetual health. Deviation from health unambiguous—prodrome of disease/death.
Prodrome Scan: Simpler, measures plasmalogens, phosphocholines, cholesterol, inflammatory markers, methyltransferase (80%+ needs). Good starting point.
Biometrics Bioscan: Deeper complexity, harder to interpret (needs skilled practitioner like Perpetual Health team/Dr. Grinnell). Advanced: sphingomyelin panel, oxidative stress markers.
Both inescapable for biochemical weaknesses; used for monitoring recovery. Research approach: overall blood interpretation vs. siloed medical cutoffs. Fix system via biochemical/methyltransferase/plasmalogen/phosphocholine support. Track visually/symptomatically (better sleep, strength, cognition, mobility).
Tests cover lipids, methylation, mitochondria impacting health/adaptability.
They're looking at inflammation, oxidative stress, metabolic function. Protome scan and biometrics bioscan are tools for assessment. For someone who hasn't done these, traditional LabCorp-type testing can indicate potential plasmalogen deficiency. Elevation of triglycerides may suggest supporting plasmalogens.
Plasmalogens are made in peroxisomes. Peroxisomes and mitochondria are catabolic systems that break down fat. Mitochondria process palmitic acid for pure energy: carbon dioxide, water, and ATP. Peroxisomes do partial beta oxidation of fats, producing building blocks for other molecules like cholesterol and plasmalogens. Peroxisomes are critically related to the neuromuscular system. People with peroxisomal issues have elevated triglycerides.
Biomarkers that track together:
- Total cholesterol under 200
- HDL under 60 or under 50
- Triglycerides over 100
These indicate compromised peroxisomal function and low plasmalogens. Healthy plasmalogen levels correlate with high HDL, good total cholesterol, low triglycerides, and low C-reactive protein.
Other tests:
- Creatinine for muscle mass
- Uric acid for NAD and oxidative stress
- Homocysteine ideally around 8
If these are off, metabolic restoration is needed.
Cholesterol below 200 may be a concern, e.g., 140 or 150, even if doctors say medication is working well.
Spermidine supports autophagy for damaged cells via polyamine system (putrescine pathways). Urolithin A relates to mitochondrial fusion. Resolvins and protectins are made naturally if the system works. These are secondary. NAD core precursor is niacin. NAD is the main energy transfer molecule.
Burning carbohydrates or fat breaks down to acetyl-CoA, burned in mitochondria like methane in a furnace: carbon dioxide, water via Krebs cycle. Electrons from sunlight energy stored in hydrocarbons are captured by NAD as NADH+, the body's electricity, transferred to electron transport chain with oxygen to water.
Precursors are critical due to compartmentalization: niacin for NAD, N-acetylcysteine for glutathione, plasmalogen precursors cross blood-brain barrier (intact plasmalogens do not). Strategic biochemical engineering is key.
Two key biochemical mechanisms in Alzheimer's:
- DHA plasmalogen depletion in brain impairs membrane fusion and cholesterol regulation.
- Causes amyloid accumulation via shift from alpha secretase (pro-neurogenesis) to beta secretase (amyloidogenic).
- Impairs neurotransmitter release, especially acetylcholine system.
Acetylcholine impairment starves cells of choline, impairing reabsorption via high-affinity transporter, leading to autocannibalism: cells digest membranes for acetylcholine, causing shrinkage.
Cells make phosphatidylcholine from scratch via phosphatidylethanolamine N-methyltransferase (PEMT), overloading leads to elevated homocysteine, shutting down methylation. PEMT defects link to neurofibrillary tangles.
Neurofibrillary tangles (inside neurons) from phosphorylated tau defects in dephosphorylation, dependent on methyltransferase. Tau (matrix-associated proteins, MAPs) involved in organelle transport down axons (phosphorylation pushes, dephosphorylation relaxes). Impaired lipid transport affects axons (critical for Parkinson's).
Amyloid plaques (outside neurons) directly from plasmalogen deficiency; tangles indirectly via methyltransferase.
Amyloid is not causative of Alzheimer's or dementia; it's definitional pathology (plaques + tangles). Dementia is functional (memory, speed); amyloid/tau indicate unhealthy brain.
Amyloid forms when system overwhelmed: excess Aβ42, limited clearance. Not protective; plaques not toxic per 90s studies. Tangles more directly related to axonal dysfunction (occur inside neurons).
Amyloid removal trials (early 2000s, multiple technologies) failed to improve function; approved drugs delay progression 18 months, require MRIs for brain bleeds. Plasmalogens reduce amyloid: high DHA plasmalogens correlate with low amyloid in postmortem brains, cell culture.
Choline essential nutrient (recognized 1990s). Deficiency reproducibly causes cancer (liver, pancreas). Body makes it energetically via methylation, but dietary best.
Sources:
- Alpha-GPC, CDP-choline fine.
- Best: phosphatidylcholine from animal sources (eggs, liver) with fats.
Enters brain via lyso-phosphatidylcholine system for membranes and acetylcholine. Plasmalogen precursors indirectly improve fusion, release, reabsorption.
p-tau 217, GFAP (glial fibrillary acidic protein, astrogliosis/microgliosis), NfL (neurofilament light chain, axonal integrity), Aβ42/40 ratio.
Anecdotal: NfL drops dramatically; GFAP less precise. p-tau outperforms amyloid markers.
Neuroquant MRI for volumetrics (mold illness, CIRS): inflammation (hypertrophy), degeneration (atrophy). VIP nasal spray used.
Volumetrics crude: brain swells/shrinks from water. Measure hippocampus, ventricles (grow with age), but not intervenable.
Key sensitive markers:
- Cortical thickness (gray matter band, sensitive to change).
- White matter density: diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) measures axons, cell bodies, free water per voxel.
- Blood flow: arterial spin labeling, vascular reactivity (BOLD).
Volumes contain gray/white; need longitudinal analysis. Can mislead (e.g., autism head circumference increase from swelling).
All injuries (MS, Parkinson's, age decline, COVID, concussion, CTE): brain (made of fat) must make own cholesterol, plasmalogens, phosphocholine internally. Needs resilience under stress.
Support: plasmalogen precursors, phosphocholine, methyltransferase support, mitochondria (acetylcysteine, carnitine). Missing link often plasmalogens.
MS: lesions + "normal-appearing white matter" need reinforcement.
Reversed brain aging; reached brain longevity escape velocity: stop/reverse aging via plasmalogen precursors (omega-9 white matter, omega-3 gray/synaptic), environmental stimulation, mitochondrial support.
- Methyl-B12, methylfolate, trimethylglycine (TMG)
- N-acetylcysteine prevents methionine depletion
- Good protein for methionine
- Phosphatidylcholine (animal-based)
- Creatine 4-5g/day (methyl load; NAC helps)
Reduces load, supports system.
Four things:
- mRNA vaccines enable cells to produce spike protein without killing cell, leading to chronic production post-infection.
Spike is mitochondrial toxin (complex I electron transport chain), reducing function body-wide. Core of long/acute COVID.
Core component of long COVID, acute COVID, and turbo cancers is mitochondrial dysfunction. When mitochondrial function is impaired, cells create ATP outside mitochondria, core to all cancers. This extra-mitochondrial ATP production prevents the body from staying in fasting state, leading to plasmalogen deficiencies. COVID heavily relates to plasmalogen deficiencies. Mitochondrial dysfunction causes inflammation and chronic inflammatory syndrome due to poor mitochondrial function, oxidative stress, and hyperimmune activation. Brain fog in long COVID results from microglial inflammation.
Recovery from long COVID has two components: removing spike protein (tools exist) and enabling body recovery, regeneration, and thriving even with spike protein present via enhancing mitochondrial function, restoring membrane structure with mitochondrial support, supplementation, plasmalogens, and phosphocholines (lipid restoration). This returns system to normal. However, body adapts to lower mitochondrial function, like being locked in a room for two years, requiring retraining and reactivation. Boost mitochondrial function with omega-3s; DHA plasmalogens are stimulating. Build energetic resilience gradually.
Restoring brain structure and function is biochemical. Myocarditis challenge in COVID era: heart is high in plasmalogens. Increasing plasmalogens helps recovery; heart loses plasmalogens under oxidative stress to neutralize peroxides—plasmalogens are most used antioxidant due to abundance in membranes. Normally, body rebuilds them, but prolonged fire depletes to chronic deficiency level without supplementation. Plasmalogen precursors improve heart structure and function in myocarditis, reducing C-reactive proteins.
Most strokes are ischemic (oxygen deprivation from restricted blood flow), preceded by atherosclerosis: thickening artery walls, thinning caps, impaired endothelial/muscle flexibility from oxidative stress and oxidized phospholipids. Impairs vasodilation, baroreflex, parasympathetic acetylcholine system. Plasmalogen deficiency, especially omega-3 plasmalogen, causes vascular stiffness.
Pre-stroke: healthy mitochondrial/lipid composition, good HDL removes soft plaque; plasmalogens improve vasodilation.
Post-stroke: extreme oxidative stress in blocked brain areas requires N-acetylcysteine, carnitine, niacin, riboflavin, thiamine, plasmalogens for survival and revascularization.
All fatigue relates to mitochondrial insufficiency. Fatigue during illness (flu, cold) from immune/inflammatory activation consuming mitochondrial energy. MS patients have fatigue improved by acetylcarnitine.
Balance removing toxic load and building resilience. Sufficient mitochondrial boosting can overcome toxic load, aiding clearance over time. Photobiomodulation directly stimulates mitochondria. Omega-9 critical early for resolving inflammation; omega-3 plasmalogens reactivate, clear brain fog, restore energy.
For chronic infections/mycotoxins, prioritize restoration first—sufficient restoration lets body clear itself by reducing secondary inflammation perpetuating autoimmune cascade. Eliminate secondary inflammation via restoration; primary may calm without detox. Then add detox.
In toxic world (pesticides, chemicals, heavy metals, micro/nanoplastics), limit exposures. Human resilience high; animal studies show massive toxin doses (e.g., cuprizone causes demyelination/microgliosis/astrogliosis; MPTP causes Parkinson's) prevented by plasmalogen precursors.
Focus on biochemical resilience pre-exposure for longevity, like building entropy-fighting capacity against unpredictable events. Plasmalogen precursors mitigate toxin effects preventatively and reverse damage post-occurrence (limits exist, e.g., can't fully regrow 80-year-old brain or Parkinson's substantia nigra). Restore viable cells, make smaller cell numbers function like larger ones, maintain indefinitely. Brain has excess capacity; elite practitioners have age-shrunken brains but high function. Lesions in MS: brain repathways around them.
Plasmalogen insufficiency is huge, overlooked contributor to aging/disease. Autism is mitochondrial deficiency disorder causing inflammation/neurological load, delaying myelination (critical for learning/development)—most reproducible: reduced white matter integrity.
Developing brain's job is development/learning/connection; external load (inflammation, infection, metabolic weakness) impairs it. Exclusive breastfeeding first 12 months improves development via plasmalogen precursors in human breast milk.
Neurosupport program: 200+ families, 95% parents report improvements in children/adults. Protocol: omega-9 plasmalogens for remyelination, anti-inflammatories (curcuminoids), methylation support, phosphocholine plasmalogens, proper diet. Improves food variability. In PANS/PANDAS, reduces acute hyperinflammation/aggression; calms brain, increases engagement.
Increased autism incidence from pro-inflammatory environment and nutrition.
Our environment is more inflammatory. Nutrition contributes, like looking down grocery store aisles at ingredients or infant formula, which is horrible. These factors increase inflammation risk, leading to delayed development.
To dial back neuroinflammation, prioritize practical interventions. Omega-9 plasmalogens are key. A special curcuminoid called BDMC shows good results as a potent anti-inflammatory that crosses the blood-brain barrier. B vitamins from diet or supplements, phosphatidylcholine from egg sources, and methyltransferase support cover 95% of needs. Avoid giving parents lists of 20 supplements for children; triage for highest impact.
In children with autism who regress after normal development and a medical procedure, higher plasmalogen levels would likely allow healthier response to inflammatory stress. For concussions, use omega-9 plasmalogens before high-risk activities like soccer or hockey to build resilience. Start in pregnancy with maternal health for biochemical resilience, continuing through life.
MS is environmental, potentially from mold, infections like Epstein-Barr virus, with autoimmune components. In research, cuprizone induces demyelination. MS is fundamentally mitochondrial dysfunction, like autism in a fully developed midlife female. Oxidative stress from mitochondrial insufficiency leads to peroxidated membranes, microglial activation, and autoimmune cascade.
Each MS patient creates specialized immune T-cells from memory B-cells targeting damage epitopes, storing a personalized immune reaction. Flare-ups occur with new insults due to predisposed response, linked to oxidized LDL-type molecules. Advanced MRI shows normal-appearing white matter in MS is less dense, in prodromal state, explaining random lesions.
Restore myelination with omega-9 plasmalogens and mitochondrial support as ground zero. Early intervention after optic neuritis or numbness restores neurological function. MS progresses slowly over 20-30 years, leading to complacency. B-cell depleting therapies reduce relapses but not brain shrinkage or neurodegeneration, tricking patients into false security; relapses are not the driver.
Parkinson's involves toxic exposure affecting substantia nigra specifically, possibly 20 years prior. Normal movement requires 20% functioning; symptoms appear after significant loss. Aging reveals prior damage as general degeneration unmasks it. Cumulative toxicity over time, revealed in 60s-80s.
L-DOPA enhances dopaminergic function but causes secondary issues like impulse control due to dopamine's multiple roles. Minimize L-DOPA toxicity, keep lowest dose, or eliminate it. Restore to 20-22% dopaminergic function via round numbers (protocol). Stimulate neurite growth for higher function from fewer cells.
Methyltransferase is critical as Parkinson's is a tauopathy. Omega-3 plasmalogens (DOPLESMALOGENS) stimulate neurogenesis, sAPP alpha, new axonal projections. Patients improve progressively over years, e.g., better writing after two years. Brain regeneration and remapping take years, like childhood development from birth to age 8.
ALS is paroxysmal toxicity from toxic exposure, impairing D-amino acid oxidase, elevating D-serine, causing hyper-glutamate toxicity at NMDA receptors in gigantopyramidal motor neurons. Leads to intracellular hyper-oxidative stress, misfolding superoxide dismutase (SOD). Genetic mutations in D-amino acid oxidase cause early ALS.
Misfolded SOD exports as gain-of-function toxin, infecting adjacent cells, driving rapid progression unlike other diseases' loss-of-function. Strategy: aggressive plasmalogen (deficient), mitochondrial, paroxysmal support. Successes exist but labor-intensive to sustain. Add photobiomodulation, counterpulsation for muscle mitochondria, manage exercise recovery.
Reduce glutamate toxicity by increasing clearance: leucine enrichment detoxifies glutamate, counters muscle wasting. Muscle wasting is independent of neurological function post-neuromuscular junction. Neurological restoration effective; focus on muscle side.
Trehalose is a slow-release glucose dimer (alpha bond), anti-diabetic, prebiotic for bifidobacteria, reduces glycemic load. ALS is hypermetabolic: high caloric demand, weight/muscle loss despite eating more. Suppresses acute glucose load; excess glucose co-transports with glutamate, exacerbating ALS. Glucose insensitivity (type 2 diabetes) reduces ALS risk; favor high-fat/protein, low-glucose/ketogenic diets.
Plasmalogens connect indirectly via peroxisomal stimulation. Diabetes is mitochondrial/glucose metabolism insufficiency. Fed state: high glucose/triglycerides, low free fatty acids; body stores as fat. Fasting state: fat cells release free fatty acids for energy.
Peroxisomal dysfunction impairs free fatty acid processing, leading to overload, insulin resistance, elevated fasting glucose. Improve with muscle maintenance, exercise, time-restricted eating. Plasmalogens (especially omega-3s) stimulate peroxisomal function.
DHA plasmalogens have a proximal stimulating effect and help lower triglycerides. Anything that lowers triglycerides helps diabetes.
Every day you do the work you do is like living in a toy store.
Future goals focus on simplifying infrastructure: MRI technology, blood testing, supplementation, biochemical restoration in a packaged process so people can go on with their lives. Adding photobiomodulation as an important modality. Building centers across the country for local access, as currently people fly to California for MRIs. Setting up infrastructure in Canada with a community health program.
Passionate about community public health to improve health amid crippling healthcare expenditures and economics. Excessive high-price drugs like Alzheimer's drugs create a huge drag. Need to improve health, reduce system load by incorporating into community, lifestyle, and mechanisms for larger populations—not just motivated subclass. Make technology accessible to the general public. Not everyone has to come to Moose Jaw.
Generously offered discount for Prodrome products (in show notes).
Rinse and repeat supplement protocol: omega-3 plasmalogens in the morning, mitochondrial support supplements, omega-9s at night.
Basic resistance training: push-ups, deep knee bends, dumbbells to maintain skeletal muscle mass—critical.
Maintain positive service mindset.
If you dedicate your life to service, like you're here to help and not to build an island, that creates a sense of peace. You can get up in the morning, do your work, and create a level of purpose that never ends.
Purpose to help others never ends. As you get older, maintain purpose by treating every day as a new day, Groundhog Day—accomplishments yesterday are done, focus on today. At end of day, go to bed. Avoid comparing to others; it doesn't matter.
Maintain biochemical support structure, community (staff, employees, family), push yourself with healthy hormetic stress—enough to overcome but not too much to shut down.
This was a four-hour masterclass; brain went to the gym. Thank you for work, creating new tools and approaches to healing, being a light in the world. Incredible pleasure to interview and learn from you, Dr. Goodenowe.
Thank you, Scott. We'll see you again soon.
Dr. Goodenowe, thank you for having me.
Keep BetterHealthGuy in your library
Save the videos and channels worth coming back to, and find them again in one place.
