Bioenergetics Flashcards
How does energy dysregulation manifest in the neurological system?
Depression, neurodegeneration, migraines, seizures, neuropathic pain, dysautonomia, temperature instability
How does energy dysregulation manifest in the CV system?
CHF, tachycardia, POTS, heart blocks, oxLDL, cardiomyopathy, WPW syndrome
How does energy dysregulation manifest in the liver and kidneys?
Low BS, liver injury or failure, nephrotic syndrome, Type 2 DM, nephropathy
How does energy dysregulation manifest in the muscles and GI system?
Weakness, cramping, wasting, exercise intolerance
GI dysmotility, IBS, N/V/D, exocrine pancreatic failure, GERD
How does energy dysregulation manifest in the endocrine system?
Fatigue, CFS, fibromyalgia, apnea, DM, hypothyroid, decreased GH, parathyroid failure (low calcium), HYPOglycemia
What tests/markers are used in a mitochondrial function workup?
CBC, ferritin, chemistries, A1C, insulin, LFTs
Creatine kinase
Metabolic: B-vitamins, low Mg, CoQ10, low free carnitine (high acyl:free carnitine ratio), ammonia, lactate, Lac:Pyr ratio
Plasma amino acids
Urine organic acids
Oxidative stress markers: 8-OH-DG, LP, oxLDL
Toxins: RBC-metal, TGF-b
Genomic/metabolomic evaluation
How does energy dysregulation manifest in the ears and eyes?
Visual loss, ptosis, ophthalmoplegia, optic atrophy, hearing loss, acquired strabismus, retinitis pigmentosa
What values of lactate/pyruvate ratio suggest mitochondrial dysfunction?
>20 = respiratory chain disorder (ie lactate >> pyruvate) <10 = pyruvate dehydrogenase defect (ie pyruvate > lactate)
Which amino acids are ELEVATED in mitochondrial dysfunction?
Alanine Proline Glycine Sarcosine Tyrosine
What OAT abnormalities would be seen with mitochondrial dysfunction?
Increased TCA cycle intermediates, ethylmalonate, adipate, suberate
3-methylglutaconate, 3-methylglutarate
Dicarboxylic acids
What enzymes, dietary antioxidants and endogenous antioxidants protect the body from ROS?
Enzymes: catalase (Fe), superoxide dismutase (Zn, Mn, Cu), glutathione peroxidase (Se), glutathione reductase
Dietary antioxidants: vitamin C, E; carotenoids, flavonoids, etc
Endogenous antioxidants: glutathione, cysteine, CoQ10. lipoic acid, uric acid, cholesterol
What are common clinical findings associated with central sensitization of pain?
Fatigue, insomnia, IBS, interstitial cystitis, vulvodynia, neuroendocrine disorders, mood and anxiety disorders, brain fog, low back pain, headaches, TMJ
What are the mechanisms of pain?
Inflammatory mediators - cytokines, nerve growth factors, food reactions, toxins, injury/trauma, GALT activation, AGEs, LPS, medications
Neurotransmitter/receptor imbalances - pain amplification centers within the CNS, NMDA wind-up, imbalanced inhibition pathways
Microglial activation
Structure/function imbalances
Genetic influences
What are the foundation components of treating pain patients?
Food first
Mitochondrial support (nutrients, MITO food plan)
Healthy fats to stabilize nerve membranes
Improve glycemic responses
5-R gut healing (& rule out gram negative LPS activation)
Stress reduction and self-care
Purposeful movement
Kinetic energy modalities & structural care
What are some nutritional interventions for energy?
Low-GI Avoid dairy-based ketogenic Ketogenic: MCT/coconut oil, 60-80g/carbs Olive oil ketogenic Fasting FMD/IF/TRF; eat QD or QOD Seasonal ketosis
What are some triggers and mediators for migraines?
Blood sugar imbalance, nutritional deficiencies, food reactions, dysbiosis, toxins/heavy metals, infections, structural/spinal imbalances, cardio-sacral & TMJ imbalances, oral cavity issues, chronic stress, poor sleep, trauma, hormonal imbalances, inflammation, neurotransmitter imbalances, barometric pressure changes, genetic predispositions
What are some strategies & interventions for migraine?
Support micro- and macronutrients (Mito food plan)
Avoid hypo- and hyperglycemia
R/O anemia
Increase oxygenation w/deep breathing, movement, exercise
Assess for toxins
Address chronic inflammation and possible underlying autoimmunity
Gut repair
Mindfulness
What are some oral cavity considerations in migraines?
Periodontal inflammation
Mix metals
Toxic load
Possible infection (root canals, wisdom teeth cavitation)
Poor function of teeth/TMJ - chewing affects digestion & assimilation
Structural imbalances of the head, neck and jaw
What are some nutrients associated with depression?
EPA/DHA, vitamin D, Mg, Zn, vitamin B2, B6, B9, B12, SAMe, 5-HTP
Note: mitochondrial dysfunction and poor ATP production associated with depression
What are some potential etiologies for depression?
Gluten and food sensitivity Acid blockers and B12 deficiency Vitamin D deficiency Antibiotics and dysbiosis Lack of fish and EFA SAD and loving sugar and resulting insulin resistance Lack of love and connection Trauma Toxic exposures Family Hx
What are the physiological effect of a ketogenic diet?
Reduces inflammation (NFkB), enhances mitochondrial biogenesis, enhances ATP production, reduces ROS production, reduces apoptosis, increases insulin and leptin sensitivity
What are the 4 ingredients of a healing encounter?
- An emotionally charged relationship with a helping person
- A healing setting
- An explanation for the symptoms (control)
- A plan which involves active participation of both parties that each believes will restore the person (Belief and Action)
What are signs and symptoms of mitochondropathy?
Ptosis, ophthalmoplegia Kidney wasting, liver failure Cardiomyopathy DM, hypoglycemia; exocrine pancreatic failure Fatigue Migraine, HA Depression Neuropathy, muscle wasting
What are key nutrients that support mitochondrial energy production?
ETC (6) CAC (6+), Carbs/proteins (5), Acetyl-CoA (1)
ETC: CoQ10, vitamins C & K, ALA, Mg, phosphatidylcholine
Carb/protein metabolism: vitamins B1, B2, B3, B5 & lipoate
CAC: glutathione, Fe, Mg, Mn, B1/2/3/5/lipoate, CoQ10
Acetyl-CoA: B5/pantothenic acid
How does the body protect against ROS?
3 Enzymes
3 Dietary
6 Endogenous
Enzymes: catalase (Fe), SOD (Zn, Cu, Mn), Glutathione peroxidase (Se) & reductase
Dietary: vitamin C, E, carotenoids
Endogenous: GSH, cysteine, CoQ10, lipoid acid, uric acid, cholesterol
What are cofactors needed in heme synthesis?
Anti-oxidant - lipoate
B vitamins - B2, B5, B6, B7
Minerals - Mg, Zn, Cu, Fe
(heme needed for ETC cytochromes and catalase)
How is NRF-2 involved in antioxidant activity?
NRF-2 is involved in:
Iron sequestration, GSH utilization, quinone detox, GSH production and regeneration,
TXN production, regeneration and utilization,
NADPH production
What are some evidence of mitochondrial dysfunction in CFS (chronic fatigue syndrome)
Low acylcarnitine
Abnormal mitochondrial morphology in muscle
Decreased glutathione and increased lactate in brain
Impaired recycling of ADP to ATP in mitochondria
Oxidative damage
How can you tell if fatigue is peripheral?
Measure gait, strength, endurance (graded exercise improves performance ability and peripheral fatigue)
Energy depletion: If ATP use > ADP production = muscle glycogen depletion
Lactate and H+ buildup due to glycogen breakdown
Ammonia buildup due to amino acid breakdown
Dehydration
How can you tell if fatigue is central?
Central fatigue is more psychic (perceived effort)
Influenced by neural system, emotions, thoughts
What are some triggers and localizers for fatigue?
Travel and infections/vector exposures
Immunosuppressive drugs
Tick/Lyme
IVDU/unprotected sex, HIV, Hep C
Sleep deprivation, sedentary
CV risk factors
GI complaints
Sore throat - EBV, recent viral infection
Menometorrhagia, anemia
Polyuria, polydipsia, dyspnea
Visual field defect (MS), weight loss, blood in stool
Cold/heat intolerance, arthralgia, rashes
Paresthesias, blurred vision, psychiatric changes, cognitive decline, ataxia (heavy metal toxicity)
What are foundational biomarkers to look for when investigating fatigue?
CBC, CMP, GGT, ferritin A1C, fasting insulin hsCRP, Hcy TSH, FT4, TT3, rT3, Anti-TG, Anti-TPO RF, ANA Vitamin D, B12/MMA, folate N3:N6 ratio
What are expanded tests that could be done when investigating fatigue?
Communication: 4-point salivary cortisol, LH, FSH, sex steroids, prolactin, GHm IGF, leptin
Inflammation: celiac screening, endotoxin Ab’s, food sensitivities, TGF-beta
Oxidative stress: 8OHdG, OxLDL, lipid peroxides
Nutrients: Mg, CoQ10, L-carnitine
Metabolites: ammonia, Lactate/pyruvte
Infectious: EBV, TB, RPR, Lyme ELISA, Toxo, brucellosis
Neuro: CT, MRI
Toxic: RBC toxic metals
OAT, amino acids, fatty acids, acyl-carnitine, mitochondrial labs, zonulin/DAO, hydrogen breath test, auto-antibody screen, mycotoxins, HRV, toxin assessment for PCB, OC, OP, VOC, metabolomics, genetics
What are key nutrients for fatigue?
B-vitamins, Omega-3, CoQ10 (30-1200mg)
Vitamin K, iron, Vitamin C
Mg, L-carnitine (up to 2g), ALA
nicotinamide riboside (NAD precursor)
How should exercise Rx be approached for fatigue?
For rejuvenation
Lower intensity, low impact, <60% MHR
Diaphragmatic breathing
What antioxidants may benefit CFS?
Selenium, GSH, NAC, ALA, CoQ10, ginkgo, bilberry, oligomeric proanthocyanidins
How can BCAA help with fatigue?
Competes with Trp entry into brain (Trp may contribute to fatigue)
Exercise depletes BCAA - administration with BCAA decreases perceived exertion
How can LPS be reduced (helpful for fatigue and depression)?
Probiotics (Bifido, Lacto)
Prebiotics (to make SCFA)
Reduction of GI dysbiosis, GI healing w/glutamine
Oral immunoglobulins or Abx
How can Trp metabolism to quinolinic acid be minimized? (activates NMDA, lipid per oxidation -> neurotoxicity)
Reduce IDO activation: 5-HTP, estradiol, niacin
What are treatment options for fatigue?
If muscle fatigue, poor exercise recovery: free form amino acids; high BCAA and arginine 5g BID
If suspect low B6 - give P5P up to 50mg/day
Reduce oxidative burden - sulphorophane, curcumin, ALA, resveratrol, NAC, MCT oil, BCAAs, reduce carbs
Fix HPA dysfunctions - adaptogens, B vitamins, DHEA
Sympathetic up regulation - HRV, biofeedback
How long should modifiable lifestyle factors be instituted (with food effect) before attempting to gradually reduce drug therapy for patients with MS or any neuroimmune condition?
Modifiable lifestyle changes x 12-36 months with good effect before even attempting to reduce drug therapy
What are strategies to increase sleep and relaxation to reduce symptoms associated with psychiatric and neurodegenerative diseases?
AM light, no UV light in the PM Melatonin Taurine Magnesium Epsom salts Essential oils Massage OSA treatments as needed
How does sleep/sleep problems impact Parkinson’s disease?
Sleep helps to clear Tau proteins; abnormal REM precedes onset of PD and dementia for several years
Poor sleep: decreased melatonin, increases cortisol
Reduced morning light associated with poorer sleep quality
Melatonin & light treatment can be helpful
What are the benefits for mushrooms (e.g., Lions Mane) on neuroimmune diseases?
Increase and stimulate production of nerve growth factors
Activate natural killer cells
Prime innate and adaptive immunity
Protect neurons from neurotoxicants
What are the benefits of brassica and allium for neuroimmune diseases?
Improve detox, increase GSH production, increase GABA production, enhance neuroprotection, improve endothelial function
What are the benefits of leafy greens on neuroimmune disease?
Contain vitamin K1 (which is metabolized to K2 [ MK-7] in the gut)
K2 is important in myelin production, neural stem cells, calcium influx into bones and teeth
Also contain carotenoids, magnesium
What color polyphenols are associated with improved cognitive performance and neuroprotection?
Deeply pigmented plants, especially blue/black/purple
Eg. blueberry powder (=1 cup blueberries) vs placebo showed improvement in cognition and brain function
What metals are associated with neurodegenerations?
Cd, Cu, Pb, Mn, Fe, Methyl-Hg
How does ApoE4 SNP impact metabolic diseases and AD?
Increased: brain atrophy, neuronal toxicity, beta-amyloid aggregation, tangle formation, aberrant brain activity
Decreased: synaptic function, glucose metabolism, neurogenesis, beta amyloid clearance, vascular function, mitochondrial function and lipid/cholesterol metabolism
How can BDNF be increased? (as per Dr. Wahls)
Exercise, mushrooms (Lions Mane, hen of the woods, cordyceps), caloric restriction/ketosis
What supplements may be used for remyelination?
CPD-choline 500mg-1g BID or upstream phosphatidylcholine
How does ApoE status related to Alsheimer’s risk?
E2/E2 or E2/E3 - 40% less likely E3 - avg risk E2/E4 - 2.6x more likely E3/E4 - 3.2x more likely E4/E4 - 14.9x more likely
What are potential underlying causes of depression?
Disruption of social fabric Increased comorbid conditions Poor nutrition Electromagnetic pollution Endocrine abnormalities Increased inflammation
What are childhood RFs for anxiety and depression?
*Most impt: childhood maltreatment (trauma, neglect, abuse) Family hx, genetics Temperatment Parenteral depression Dissolution of family Family dysfunction/reactivity Academic stress Sociodemographic factors Obesity Sleep Excessive social networking
(note balance between limbic (emotional) brain and prefrontal cortex control, as modeled by parent is impt for childhood emotional regulation
What are the main differences between melancholic agitated depression and atypical/CFIDS depression?
Melancholic agitated: worse in the morning, cortisol is high throughout the day, M>F; less sleepy, less weight gain; agitation and panic
Atypical/CFIDS: worse in the evening, cortisol of low-normal, F>M; psychomotor retardation
What are the effects of sugar on mood and anxiety?
Decreases BDNF, increases pro-inflammatory cytokines, increases utilization of B vitamins, stresses autonomic nervous system, inhibits Krebs
What are ingredients necessary for neurotransmitter function?
Vitamins B6(P5P) B12 C
Zinc, Cu, tyrosine, tryptophan
Tetrahydrobiopterine
SAMe
Tyrosine - > -> Dopamine -> NE -> E requires BH4, vitamin C, Cu SAMe
Trp -> 5-HTP -> 5-HT requires BH4, P5P
What micronutrients have been used as adjunctive therapy with antidepressants?
SAMe, Zinc, methylfolate, omega-3, vitamin D
Others: Cr, Ca, Mg, Se, B12, B6, B2, carnitine, inositol, biotin, antioxidants, serine, inositol (9g BID)
Which is the preferred omega-3 for depression?
EPA >DHA
What are some clinical indications of Cu>Zn ratio?
Anxiety, nervousness, agitation, aggression, female hormone-related mood disorders; women on BCPs
What are some functions of methylation?
Silencing of genes (epigenetics)
Modulation of neurotransmitter systems (NE, E, 5-HT, DA)
Metabolism of estrogen
Production of energy (carnitine, creatine, ATP)
What nutrients are involved in the methylation cycle?
folate, B12, B6, SAMe, B2 (activates MTHFR), TMG/betaine/choline
When mitochondria are in chronic fission state (vs. fusion), what does this result in?
Low energy state
Lots of small mitochondria
(Fused mitochondria - more mass and ATP production; better)
What are 5 common clinical presentations of mitochondrial dysfunction (on energy tree)?
Depression, headaches, fatigue, pain, neurodegeneration
What promotes mito fusion?
exercise, fasting, cold exposure, omega-3, sirtuin activation (eg. bioflavonoids), melatonin, betaine
What promotes mito fission?
Drugs of abuse, palmitate, pesticides, sedentary, glucose, indomethacin, etc
What are the key nutrients to support mitochondria energy production?
Carbs: B1, B2, B3, B5, lipoate
Fat: L-carnitine
Proteins: B1, B2, B3, B5, lipoate
CAC: GSH, iron, Mg, Mn, B1, B2, B3, B5, lipoate, CoQ10
Energy transporters: Niacin, riboflavin
ETC: CoQ10, iron, ALA, vitamin C, vitamin K, Mg, phosphatidyl choline
Acetyl CoA - B5 (pantothenic acid)
What are some sources of oxidative stress?
increased: caloric excess, nitric oxide, propionate (as SCFA), TNF-alpha, inflammation, glucotoxicity, toxins
Decreased: folate, B-vitamines, mineral co-factors, CoQ10, GSH, carnitine
How does oxidative stress cause cell damage?
Activates NFkB -> up-regulation of stress and inflammation, iNOS -> production of RNS, NO, etc -> cell damage
Also, ROS siphon FADH2 and NADH from the ETC and reduces ATP production
What nutrients are necessary for heme synthesis for ETC and catalase? (ie for cytochrome C)
Antioxidant: ALA
B-vitamins: B2, B5, B6, B7
Minerals: Mg, Zn, Cu, Fe
What heavy metals and toxins are associated with mitochondrial toxicity?
Pb, As, Hg
Organophosphates, organochlorines, cyanide, carbon monoxide
What medications may impair mitochondrial function?
valproic acid, anti-retrovirals, statins, ASA, aminoglycosides, acetaminophen, platinum chemo, metformin, beta-blockers, steroid
How to treat mitochondrial permeability transition pore injury? (ie from NSAIDs, APAP, VPA, troglitazone, disulfiram)
glutathione & its precursors
SAMe, TMG, NAC, CoQ10
What medications could directly inhibit the ETC?
NSAIDs, tamoxifen, antidepressants, amiodarone, diclofenac, tetracycline, cyanide
What can induce NRF2 (anti-oxidant hub)?
Sulforaphane, curcumin, ginger, t-resveratrol, quercetin, ALA, carnosol (rosemary), gingko, garlic, cinnamon, green tea, milk thistle, coffee, melatonin, bee propolis (caffeic acid phenylether ester), wasabi
How to activate PGC-1alpha? (regulates mitochondrial biogenesis)
(anything that signals need for more energy) Exercise (fusion>fission) Fasting/calorie restriction Cold AMP-kinase (ALA) Sirt1 (activated by NAD) NO Mitochondrial damage T3
What inactivates PGC-1alpha? (regulates mitochondrial biogenesis)
inactivity, caloric overload, saturated fats, refined carbs, TNF-alpha, excessive pro-oxidants, aging
Which 4 organs consumes 60% of resting energy expenditure?
Heart, kidneys, brain, liver
brain works 5x as hard as heart mitochondria
What is TRAP1 and its associated disease?
TRAP-1 encodes for a mitochondrial chaperone involved in antioxidant defense
SNPs can lead to TRAP1-related disease: chronic pain, fatigue, GI dysmotility, tachycardia, dizziness (improves greatly with aggressive antioxidant therapy)
For which condition should the ketogenic diet NOT used?
ALS (data suggests it may not be beneficial)
What are some detox enzyme inducers and substrates?
Sulforaphane, milk thistle (silymarin), NAC, TMG (choline rescue to protect phosphatidyl choline in membranes), SAMe (to support GSH production from HCY), direct glutathione
What are some lipid supports? (to support cell and mitochondrial membrane structure)
Pancreatic lipase, bile acids Phosphatidyl choline EPA/DHA ALA GLA
What is the recipe for the “Clinician Effect”?
Create space Create patient expectations Be fully present and listen to the story Offer support and collaborate Create a plan
