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IFM Study > Bioenergetics APM > Flashcards

Bioenergetics APM Flashcards

1
Q

What are 5 clinical conditions that may have underlying imbalances in mitochondrial function?

A 
Depression
Headaches
Neurodegeneration
Fatigue
Centralized pain
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2
Q

What are functions of the mitochondria?

A 
Buffering calcium ion flux
Maintainence of ion gradients
Generation of ROS
Cell Signaling
Growth regulation
Biosynthetic pathways
ATP synthesis
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3
Q

How much ATP do you make daily?

A

Your body weight in kg (on avg 70-80 kg)

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4
Q

What percentage of ATP does brain use?

A

22-25%

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5
Q

What process do fatty acids go thru to make ATP?

A

Beta oxidation

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6
Q

What process do carbohydrates go thru to make ATP?

A

Glycolysis

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7
Q

What percent of oxygen does mitochondria consume for oxidative phosphorylation?

A

90%

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8
Q

What is the final electron acceptor in the Electron Transport Chain to make ATP?

A

Oxygen

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9
Q

What are the 4 distinct parts of the mitochondria?

A

Outer membrane, intermembrane space, inner membrane, matrix

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10
Q

Is outer membrane porous or impermeable?

A

porous

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11
Q

Is the inner membrane porous or impermeable?

A

impermeable

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12
Q

What part of the mitochondria do enzymes involved in mito lipid synthesis sit?

A

Outer membrane

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13
Q

What is in the intermembrane space of mitochondria?

A

Hydrogen ions are pumped into here, so low pH
Enzymes that use newly made ATP to phosphorylate sit here, cytochrome C
Calcium ions, ATP

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14
Q

What are the cristae in mitochondria made of?

A

Cardiolipin

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15
Q

What are in the inner membrane of mitochondria?

A

Cristae
ETC protein complex
ATP synthase
Transport proteins that move molecules into and out of matrix(Ca, Na, HPO4, ATP, ADP, Adenine dinucleotides, etc)

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16
Q

What is in the matrix of mitochondria?

A 
Kreb cycle enzymes
mtDNA
ribosomes
GSH
mtRNA
Ca
Nitric oxide
1500+proteins of unknown function
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17
Q

What are the 2 parts of mitochondrial genome?

A

Genes inside nuclear genome

Genes inside the mitochondria

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18
Q

Why are mitochondrial genes not robust?

A 
Circular genome
Lack histones for protection
Highly susceptible to oxidative stress
Absent DNA repair
10 x mutation rate - reproduce rapidly
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19
Q

Which parent determines your mitochondrial DNA?

A

Mother

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20
Q

Which patients may have more mutations in their mitochondrial DNA?

A

Those born to older mothers than younger ones

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21
Q

Why are mitochrondia a genotoxic stress sentinel?

A

Damage to and release of mtDNA ellicits a protective signal for cells/tissues to repair their DNA

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22
Q

What mediates mito fission?

A

Drp1

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23
Q

What is mito fission triggered by?

A

Low GSH/GSSG(low antioxidant potential)

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24
Q

What does dysregulated fission lead to?

A 
More oxidative stress
increased mito depolarization
loss of ATP production
Reduced insulin stimulated uptake of glucose
inability for mitophagy to proceed
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25
Q

What happens if dysregulated fission becomes chronic?

A

leads to low cellular energy state

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26
Q

Which enzymes are needed for biosynthesis of mitochondria?

A

PGC-1alpha, PGC-1beta, TFAM, NRF-1

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27
Q

What enzymes participate in mitophagy?

A

Pink1, Parkin, ATG12, ATG3, Bnip3

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28
Q

What enzymes induce fission?

A

Drp1/Dnm1, DLP-1,
Fis-1, DJ-1
MTFP1

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29
Q

What enzymes participate in fused mitochondria?

A

Mfn1, Mfn2, OMM fusion

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30
Q

Mitochondrial dysfunction in what structure has been associated with anxiety and social competitiveness?

A

nucleus accumbens

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31
Q

How do benzo’s work?

A

increase dopamine in nucleus accumbens, regulating mito function by increasing respiration and ATP levels

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32
Q

How does mito induce AI disease?

A

Pore transport induction and small mitoDNA fragments entering the cytosol increase type 1 Interferon production. Type 1 IFN family of innate immune cytokines contributes to AI conditions.

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33
Q

Expression of what gene enzyme is master regulator of mitogenesis?

A

PGC-1alpha

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34
Q

Which pathway triggers mitophagy?

A

PINK1/Parkin pathway - PTEN induced putative kinase 1

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35
Q

What promotes mito fission?

A 
Meth, cocaine
Etoh, opioids, benzos
Palmitate
Rotenone, pesticides,
Amyloid beta
ischemia
Sedentary
glucose
nsaids
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36
Q

What promotes mito fusion?

A 
Exercise
Fasting/caloric restriction
Cold exposure
Omega 3 PUFAs
Sirtuin activation(IV NAD)
Melatonin
Betaine
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37
Q

How does beta oxidation work?

A

Fatty acids add 2 carbon to make acetyl CoA which then enters Krebs cycle

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38
Q

How does glycolysis work?

A

Glucose gets turned into pyruvate which then can bind to acetyl coA and go into kreb cycle

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39
Q

What are substrates that drive metabolome?

A

Fatty acids, amino acids, carbs

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40
Q

Is beta oxidation/krebs cycle the only way fatty acids can enter ETC?

A

No, it can enter directly via complex 3

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41
Q

What substances can pyruvate make?

A

Alcohol, lactate(when no oxygen), glucose, alanine, oxaloacetate which can be made into glucose, Acetyl CoA which can be made back into fatty acids.

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42
Q

What is Acetyl CoA made of?

A

ATP + Pantothenic acid + Acetyl

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43
Q

What is central to all acetyl transfers?

A

B5(Pantothenic acid)

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44
Q

What vitamin deficiency will lead to hypoglycemia and why?

A

B5, impaired insulin receptor downregulation by lack of palmitic acid acetylation of insulin receptor

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45
Q

2 AcetylCoA make…?

A

Beta hydroxy butyrate

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46
Q

How many Acetyl CoA can 1 BHB make thru ketooxidation?

A

2(plus an extra NADH)

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47
Q

What is necessary for ETC to make 34 ATP?

A

Oxygen

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48
Q

How much ATP can 1 molecule of palmitate make?

A

106-129

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49
Q

What nutrients are required for fatty acid oxidation?

A

Carnitine, FAD(riboflavin), NADH(niacin), CoQ10

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50
Q

What has more carbon-hydrogen bonds- fats or carbs?

A

Fatty acids

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51
Q

What provides 60-90% of energy for ATP synthesis?

A

Fatty acid oxidation

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52
Q

What happens if not enough carnitine?

A

You get omega oxidation instead of beta oxidation.

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53
Q

What is primary food source for carnitine and what patients may be at higher risk for deficiency?

A

Meat; vegans/vegetarians

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54
Q

What are key nutrients to support mito energy production from Carbs?

A

B1, B2, B3, B5, Lipoate

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55
Q

What are key nutrients to support mito energy production from fats?

A

Carnitine

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56
Q

What are key nutrients to support mito energy production from proteins?

A

B1, B2, B3, B5, Lipoate

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57
Q

What nutrients support the citric acid cycle?

A

GSH, Fe, Mg, Mn, B1, B2, B3, B5 Lipoate, CoQ10

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58
Q

What are key nutrients to support Energy transporters?

A

Niacin, Riboflavin

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59
Q

What are key nutrients to support the ETC?

A

CoQ10, Vit C, Vit K, Alpha lip acid, Mg, Phosphytidyl Choline

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60
Q

Decreases in what substances causes oxidative stress?

A

Folate, B vitamins, Mineral cofactors, CoQ10, GSH, Carnitine

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61
Q

How does NF-KB cause damage?

A

Increased ox stress leads to increase NF-KB which leads to upregulation of stress/inflammation genes including NOS which leads to RNS, NO, ONO2- which causes cellular damage

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62
Q

What is the best marker for monitoring intracellular oxidative stress?

A

GSH to GSSG ratio

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63
Q

How are PUFAs affected by free radicals?

A

It causes a kink/bend in the bond which disrupts membrane

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64
Q

What gets activated by mild-moderate amount of oxidative stress?

A

NrF2

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65
Q

What gets activated by high amount of oxidative stress?

A

NFkB - inflammation

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66
Q

What gets activated by extreme amount of oxidative stress?

A

AP-1 - Apoptosis

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67
Q

How does GPx reduce GSH?

A

Oxidizes NADPH

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68
Q

What inhibits Heme Synthesis pathway?

A

Heavy metals

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69
Q

What protects liver from chemo, arsenic and by how does it regulate mito function?

A

Metformin: inhibits mito resp chain complex 1, increases intracellular NADH/NAD+ ratio and decreases the intracellular ROS

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70
Q

What is the master regulator of mito biogenesis and homeostasis?

A

PGC-1alpha

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71
Q

What are mitochondrial rich tissues?

A

Skeletal muscle, brown adipose tissue, heart and some extent liver

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72
Q

What is effect of exercise on mitochondria?

A

Increases PGC-1a and Fusion happens more than fission, get better quality/quantity of mitochondria

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73
Q

What is effect of sedentary lifestyle on mitochondria?

A

Decreases PGC-1a which activates NFkB for protein degredation and Fission is greater than fusion so get fragmented and dysfunctional mitochondria

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74
Q

What activates PGC-1a?

A

Exercise, fasting/caloric restriction, cold temp, AMP-Kinase(alpha lipoic acid), Sirt1(activ by NAD), NO, MIto damage, T3

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75
Q

What inhibits PGC-1a?

A

Inactivity, high calorie, saturated fats, refined carbs, fructose, Inflam mediators(TNFa, excessive prooxidants, aging

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76
Q

What are top 10 mito therapeutic foods?

A 
Salmon
Pomegrante Seeds
Berries
Greens
Green Tea
Olive Oil
Cruciferous veggies
Seaweed
Avocado
Almonds
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77
Q

Increases in what causes oxidative stress?

A 
Oxidative stress,
Nitric oxide
Glucotoxicity
Toxins
Caloric excess
TNF alpha and inflammation
Propionate SCFA
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78
Q

What enzymes protects the body from ROS?

A

Catalase(Fe)
Superoxide Dismutase(Zn, Cu, Mn)
GPx(Se) and Glutathione reductase

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79
Q

What dietary antioxidants protects the body from ROS?

A

Vitamin C for aqueous compartments
Vitamin E for lipid compartments
Carotenoids, flavonoids
Albumin

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80
Q

What endogenous antioxidants protect the body from ROS?

A 
GSH
Cysteine
CoQ10
Lipoic acid
Uric acid
Cholesterol
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81
Q

What % of plasma does GSH account for?

A

1%

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82
Q

Where does most of GSH reside in?

A

Intracellular

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83
Q

What molecules are central to assembly of the ETC and catalase?

A

Heme Molecules

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84
Q

What are cofactors for the enzymes in the Heme synthesis pathway?

A

Antiox - lipoic acid
B vitamins - B2, B5, B6, B7
Minerals- Mg, Zn, Cu, Fe

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85
Q

Where in the heme biosynthesis does metal inhibition occur?

A

Pentacarboxyporphyrinogen to coproporphyrinogen via UROD and Coproporphyrinogen to protoporphyrinogen IX visa CPOX

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86
Q

What does organophosphate exposure induce?

A

Decreased NADPH cytochrome C reductase
Decreased succinate cytochrome c reductase
Decreased CcOX activity in mitochondrial respiratory chain
Reduction of mitochondrial transmembrane potential
Decreased ATP production
Increased ADP/ATP ratio
LDH release
Apoptosis/necrotic cell death
Increases ROS damage markers(protein, DNA, fatty acid oxidation)
Alter antioxidant enzyme function(GPx, CAT, SOD, GR)
Increase G6PD activity, impairing glucose metabolism
Induce cytochrome p450 enzymes

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87
Q

What is the antioxidant hub?

A

NRF-2

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88
Q

What is the genetic hub?

A

PGC-1 alpha

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89
Q

What are some plants and constituents that induce ARE via NRF2?

A 
Sulphoraphane
Curcumin
Ginger
Quercetin, polyphenols
Trans resveratrol
Alpha lipoic acid
Carnosol(rosemary)
Gingko
Garlic
Cinnamon
Green Tea
Milk thistle
Cofee(kahweol and cafestol)
Melatonin
Caffeic acid phenylether ester(CAPE from Bee propolis)
Wasabi
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90
Q

Food is ….

A

Medicine
Connection
Information
Energy

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91
Q

What primary nutrients activate NRF-2?

A 
Cucurmin
Green Tea
Resveratrol
Sulphoraphane
Garlic
DHA
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92
Q

What processes activate NRF-2?

A

Fasting
Caloric restriction
Carbohydrate restriction
Mild oxidative stress

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93
Q

What is important for the fluidity of mitochondrial membrane?

A

Fatty acids

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94
Q

How do fatty acids regenerate the mito membrane?

A

Fatty acids conjugate to Carnitine outside the mito, CPT1 transports this across mito membrane

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95
Q

What deficiency leads to inability to oxidates fats as fuel?

A

Carnitine

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96
Q

What is the ratio of fat to carbs on a keto diet?

A

4:1

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97
Q

What is mechanism of keto diet?

A

Unclear but attributed to ketone bodies, glycolysis and mito metabolism

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98
Q

What are effects of keto diet?

A 
Reduces inflammation
Enhances mito biogenesis
Enhances ATP production
Reduces ROS production
Increases insulin sensitivity
Increases leptin sensitivity
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99
Q

What are benefits of Intermittent Energy Restriction?

A 
Increased insulin sensitivity
Reduced levels of insulin and leptin
Increased mobilization fatty acids
Elevated BHB
Increased BDNF
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100
Q

What are principles of mito food plan?

A 
Phytonutrient density
Low Glycemic
Anti-inflammatory and antioxidant
Fats and oils
Cooking impact
Fasting; Calorie and/or Carb restriction
Organic and clean food
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101
Q

What are labs to order for mito function?

A 
CBC, ferritin
CMP, A1c, Insulin
NH4
Lactate and lactate:pyruvate ratio
CPK
Quan plasma amino acids
Quan urine amino acids
Plasma AcylCarnitine profile
CoQ10
Ox stress markers, Anti ox capacity
ETC and citrate synthase activity testing
genomic/metabolomic evaluation
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102
Q

What would lab show in lactate/pyruvate to indicate mito dysfunction?

A

> 20 in resp chain d/o

<10 pyruvate DH defect

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103
Q

What would you see on magnesium if mito d/o?

A

Low RBC Mg

104
Q

What would you see on amino acids if mito defect?

A

Elevated alanine, proline, glycine, sarcosine, tyrosine

105
Q

What would you see on microscopy to indicate mito dysfunction?

A

Red ragged fibers

106
Q

What would you see on urinary organic acids if mito defect?

A

TCA cycle intermediates
Ethylmalonate, Adipate, Suberate
3 methylglutaconate, 3 methylgluterate
Dicarboxylic acids

107
Q

What would you see on acylcarnitine if mito defect?

A

Low free carnitine

Elevated acyl:free carnitine ratio

108
Q

How would you tx mito dysfunction?

A 
MLF 
Metabolic support 
Membrane support
Oxidative stress mitigation
Detox interventions and inflammation
109
Q

How does exercise affect mitochondria?

A

Stimulates key stress signals that control skeletal mito biogenesis and function; Increases BDNF, balances BS; Perturbations in mito content and function can directly or indirectly impact skeletal muscle function and whole body health/wellbeing.

110
Q

What are some primary metabolic support for mito?

A

B vitamins, Fe, Mg, CoQ10, Carnitine

111
Q

What are some secondary metabolic support for mito?

A

Creatine, BCAA, SAMe

112
Q

What are primary lipid support?

A 
If fecal fat, dry skin, GI symptoms - pancreatic lipase, bile acids
PC
Fish oil
Flax Oil
EPO/Borage oil
113
Q

What is secondary lipid support?

A

IV lipids

114
Q

What are some direct ox stress tx?

A

Vit C, A, E
ALA, CoQ 10
NAC
Se, CU, Mn

115
Q

What are some indirect ox stress tx?

A 
Antiox induction agents:
Suphoraphane-Glucosinolate
Resveratrol/Red wine
Curcumin/Tumeric
EGCG/Green Tea
Pterostilbine/Blueberries
116
Q

What are detox enzyme inducers/substrates?

A

Sulphoraphane-Glucosinolate, Quercetin
Milk Thistle
NAC
TMG - Choline rescue to protect PC in membranes
SAMe - supports production of GSH from Hcy
Direct GSH(S-acetyl, liposomal, Intranasal, IV, Nebulized)

117
Q

What is pathophysiology of migraines?

A

Neuro-biologically based
Vulnerability to migraine - inherited for many
Vascular changes alone do not provide sufficient explanation of pathophysiology
Key pathways for pain are the trigeminovascular input from the meningeal vessels

118
Q

What are common nutrient deficiencies in migraines?

A

CoQ10, Mg, B6, EPA

119
Q

What is the maladaptive brain response to stress ?

A

the effects of repeated stress lead to alteration in brain networks both functionally and structurally. As a result brain responds abnormally to environmental conditions.

120
Q

What do you get with oxyphos dysfunction?

A

Decreased energy
Increased ROS
Altered redox regulation of gene expression and metabolism
Altered calcium homeostasis

121
Q

What are conditionally essential inputs to the metabolome?

A 
AA, Arginine
Betaine
Cysteine, Carnitine, CoQ10, Choline
DHA, EPA
GSH, Glycine, Glutamine
Vitamin K2
Lipoic acid
Serine
SAMe
Taurine
Tyrosine
122
Q

Oxidation of fatty acids require….

A

Carnitine
CoQ10
NADH(Niacin)
FAD(riboflavin)

123
Q

What products in urine will you see if you are undergoing omega oxidation?

A

Adipate
Ethylmalonate
Suberate

124
Q

How much ROS does human produce per year?

A

1 kg

125
Q

What percent of oxygen is used by mitochondria to make SOD and H2O2?

A

1-2%

126
Q

Free radicals, ROS and RNS react with and damage ….

A

Membrane and receptors which impair signaling
Enzymes/other proteins which impairs molecular conversions
Cellular DNA and RNA
Mitochondrial DNA and membranes

127
Q

What are some products of Heme biosynthesis?

A

Hgb, Myoglobin, Neuroglobin, Cytoglobin, Catalases, Endothelial nitric oxide synthase, TPO, Lactoperoxidase, Eosinophil peroxidase, MPO, CytP450, Cytochromes a,b,c Photsensitive proteins

128
Q

What drugs affect MPTP(mito permeability transition pores? And what is tx?

A

Nsaids, Acetaminophen, Valproic acid, Troglitizone, Disulfuram;
Tx is GSH(and precursors/regulators - SAMe, TMG, NAC, CoQ10)

129
Q

What drugs cause direct drug inhibition of beta oxidation? and tx?

A

Nsaids, Valproic Acid, Amiodarone, Tamoxifen, Acetaminophen; Tx: Omega 3 to stimulate PPARs and Butyrate to stimulate peroxisomal b-oxidation

130
Q

What drugs cause oxphos uncoupling? And tx?

A

Ibuprofen, ASA, Amiodarone, Tamoxifen, diclofenac; Tx - remove cause

131
Q

What drugs inhibit ETC?

A

Nsaids, Amiodarone, tamoxifen, diclofenac, TCN, cyanide, Rotenone, oligomycin, antidepressants

132
Q

What cause mitodna depletion or damage?

A

Acetaminophen, Troglitazone, AZT (usually severe, early onset, auto recessive)

133
Q

What is genetic hub for needing less injury from oxidative molecules?

A

NRF-2

134
Q

What is genetic hub for needing more and better mitochondria?

A

PGC1-alpha

135
Q

How is NRF-2 an antioxidant hub?

A 
Sequesters Iron
GSH utilization/production
Quinone detoxification
Txn production , regeneration and utilization
NADPH production
136
Q

What does SOD do?

A

It makes H2O2 and O2 from free radicals.

137
Q

Where is SOD found in the cell and what cofactors does it need?

A

Cytosolic(Zn & Cu)

Mito(Mn)

138
Q

What does Catalase do?

A

It takes H2O2 made by SOD and converts it to 2 water and O2

139
Q

What does GPx do?

A

If not enough SOD or CAT, then it will take 2GSH and H2O2 and convert it to 2 H2O and GSSG

140
Q

What is a primary dysfunction in dementia?

A

Calcium regulation. Impairments in intracellular Calcium handling. Overload promotes superoxides, met dysfunction and cell death.

141
Q

What enymes have altered expression in AD?

A

DLP1, OPA1, Mfn1, Mfn2 - decreased levels seen

Fis1 - increased

142
Q

What conditions can be seen with carnitine dysfunctino?

A

DM, Sepsis, Renal dz, CM

143
Q

What is unique about liver mito?

A

They are a hub that integrates hepatic metabolism of carbs, lipids, proteins

144
Q

What regulates nuclear and mitochondrial genes?

A

Estrogen

145
Q

What detoxification pathway is dependent on mito function?

A

Methylation. If mito dysfunction will be deficient in SAMe as you need ATP to convert methionine to SAMe.

146
Q

How does low SAMe lead to NASH?

A

Low SAMe -> low GSH -> low PC:PE ratio -> low membrane fluidity -> fat accumulation

147
Q

What supplement reduces liver failure/death or delays transplant in alcoholics?

A

SAMe but has to be on it for at least 12 months.

148
Q

What supplement is mito protectant in diabetic kidney disease?

A

Silymarin

149
Q

Why do obese people have less energy despite greater food intake?

A

Skeletal muscle have smaller mito, reduced contents of mito and impaired electron transport activity

150
Q

What is the mito pathophysiology of IR?

A

Mito dysfxn(inefficiency of ETC and B ox) -> increased ROS and damaged lipids -> disruptive signaling of insulin pathway -> IR

151
Q

What can you do to induce more white to brown adipose tissue?

A

cold exposure, polyphenols and alpha lipoic acid; all activate AMPK

152
Q

What are some features of alpha lipoic acid?

A

Cofactor in decarboxylation of alpha keto acids(pyruvate DH complex)
Blocks stress signaling pathways
Activates AMPK in periphery(brown fat) which activates PGC1-alpha
Activates PPAR gamma which increases insulin sensitivity, dec TGL synthesis
Decreases diabetic complications and DPN
Increases intracellular and mitochondrial GSH
Metal chelator

153
Q

What are findings on CBC with mito dysfxn?

A

Low hemoglobin, ferritin,

Low neutrophils, wbc, platelets with high ox stress

154
Q

What is elevated in urea acid or organic acid cycles?

A

Ammonia

155
Q

What becomes an essential nutrient in Urea acid cycle d/o, organic acid d/o?

A

Arginine

156
Q

What mitochondrial d/o will you have an elevated L:P ratio?(Lactate to pyruvate)

A

Inherited d/o of resp chain complex
Tricarboxylic acid cycle d/o
If acutely ill

157
Q

What mito d/o will you have low L:P ratio?

A

Inherited d/o of pyruvate metabolism

Defects in the pyruvate DH complex

158
Q

What is not sensitive nor specific marker of mito disease?

A

Serum lactate. Per Dr. Haase, urinary lactate can be useful for mito dysfxn.

159
Q

What will cause a false positive on organic urinary acids?

A

MCT oil, fasting

160
Q

What amino acids will be high on Plasma quant aa?

A

Alanine, proline, glycine, sarcosine, tyrosine

161
Q

What are functions of TCA cycle metabolites?

A

Signaling molecules regulating chromatin
DNA methylation
Immunity
Hypoxic response

162
Q

What are potential biomarkers for aquired mitochondrial disease in autism d/o?

A

Unique acyl:carnitine profiles

163
Q

What does elevated acyl:carnitine ratio tell you?

A

suggests downstream genetic defect

164
Q

What supplement lowers risk of sudden cardiac death?

A

CoQ10

165
Q

What are some ox stress markers of damaged DNA?

A

8OHDG

166
Q

What are some ox stress markers of damaged fats?

A

Lipid peroxidases, oxidized LDL, Isoprostane F2

167
Q

What are some ox stress markers of damaged sugars?

A

A1c, AGEs

168
Q

What are some ox stress markers of damaged proteins?

A

3 Nitrotyrosine

169
Q

How to test ETC and Citrate synthase activity?

A

Muscle biopsy

Buccal swab

170
Q

What serves as a marker of overall mitochondrial mass?

A

Citrate Synthase

171
Q

What is Trap1 related disease?

A

Triad of chronic pain, Gi dysmotility and fatigue due to Trap1 mutation which plays a role in antiox defense. Tx is to tx with antiox

172
Q

How is mood and stress affect associated with mito fxn?

A

Positive mood is assoc with higher mito health index, negative mood/stress is assoc with lower mito health index

173
Q

Which neurodegenerative d/o should you not use a keto diet in?

A

ALS

174
Q

What lipids are in the mito membrane?

A

PC, PS, PE, Phosphatic acid, cardiolipin

175
Q

What is diagnostic criteria for CFS?

A 
>= 6 months, not allev by rest and interferes with fxn, no other explanation; at least 4 of the 8:
Post exertional malaise
Impaired concentration or memory
Unrefreshing sleep
HA
Muscle pain
Joint pain
Sore throat
Tender cervical nodes
176
Q

What are some lab findings in CFS?

A 
Low serum acylcarnitine
muscle bx - abnl mito morphology
decreased GSH, increased lactate in brains of CFS pts
impaired recycling of ADP to ATP
ox damage
177
Q

What is peripheral fatigue?

A

Physical capacity and performance ability. Rises as linear function with exercise and reach a max value only at the point of exercise termination
Mito based

178
Q

How is peripheral fatigue measured?

A

Gait, strength and endurance testing

179
Q

What conditions is peripheral fatigue higher/lower

A

Higher - anxiety, depression, neuroticism

Lower - extroverted personality

180
Q

What improves peripheral fatigue?

A

Graded exercise

181
Q

What are some characteristics of peripheral fatigue?

A

1) Energy Depletion: ATP use > production, depletion of muscle glycogen, reduced availability of pyruvate, malnutrition/malabsorption
2) Metabolic by products: lactate and H+ d/t glycogen breakdown, Ammonia d/t aa breakdown
3) Dehydration - affects cardiac output and increased thermal strain

182
Q

What is central fatigue?

A

Perceived effort. Governed by neural networks, neurotransmitters, neuronal firings, thoughts, beliefs, emotions
A complex emotion
Neurotransmitter based

183
Q

What creates central fatigue?

A

consciousness producing structures in brain; conscious awareness of changes in the subconscious homeostatic control systems

184
Q

What is blue sclera associated with?

A

Iron deficiency

185
Q

What organ dz is Dupytrens associated with?

A

Liver dz

186
Q

What supplement attenuates strength loss and ROM after exericse?

A

EPA and DHA

187
Q

What cofactor does Tryptophan need to be converted into 5HTP?

A

Iron

188
Q

What cofactor does 5HTP need to be converted into serotonin?

A

B6

189
Q

What cofactor does Serotonin need to become melatonin?

A

SAMe

190
Q

What are neurotransmitters of fatigue?

A

Trypthophan
Kynuric acid(KYNA)
Quinolate(Quin)

191
Q

When is tryptophan released?

A

with mental and physical exertion

192
Q

What competes with Tryptophan to enter the brain?

A

BCAAs

193
Q

What enzyme converts Tryptophan to KYNA?

A

IDO(indoleamine dioxygenase)

194
Q

What does KYNA covert to?

A

Quinolate(QUIN)

195
Q

What is an NMDA glutamate channel antagonist?

A

KYNA

196
Q

What is an NMDA glutamate channel agonist?

A

QUIN

197
Q

What induces Tryptophan to go thru IDO pathway?

A

Excess Tryptophan, KYN, steroids, INFgamma, IL1, IL6, TNFalpha, NF-KB

198
Q

What downregulates Tryptophan to go thru the IDO pathway?

A

E2, NADPH(niacin)

199
Q

What depletes BCAAs?

A

Exercise

200
Q

How does exercise affect tryptophan?

A

Exercise depletes BCAAs and releases free fatty acids which displaces tryptophan from albumin so more free tryptophan in blood stream. Both drive up brain tryptophan and central fatigue.

201
Q

What decreases RPE(rate perceived exertion) in exercise?

A

BCAAs

202
Q

What levels are increased during sleep deprivation?

A 
Tryptophan
Serotonin
Taurine
8 acylcarnitines(short and long, not medium)
3 glycerophospholipids
3 sphingolipids
203
Q

What is a marker of mitochondrial function imbalance?

A

8 acylcarnitines(short and long) not medium

204
Q

What are the brain effects of LPS?

A

Increased glucose utilization in the right more than left insula
Increased glucose utilization in the anterior than posterior insula
Decreased metabolism in anterior cingulate(R>L)

205
Q

What does right insula regulate?

A

Sympathetic activity so stimulation leads to negative emotions
It receives input from skeletal muscle afferents therefore prevents us from exercising too much.

206
Q

What does anterior cingulate do?

A

Increases positivity; Inflammation will decrease metabolism in this area. But can be modulated by attention, willpower and intention

207
Q

Is it better to use controlled release 5HTP or immediate release and why?

A

Controlled to avoid cortisol spike

208
Q

How does interferon alpha cause fatigue?

A

via IL-6. Inhibits tyrosine hydroxylase conversion to dopamine in BG and decreases CNS homovanilic acid; Decreases THB(B4) by releasing NO - elevated phenylalanine/tyrosine ratio and low BH4 impairs 5HTP as well.

209
Q

How long do you have to instill MLF in neurodegenerative disease before gradually transitioning off meds?

A

12 months with good effect

210
Q

Why is sleep important for Neurodeg dz?

A

It helps to clear Tau proteins

211
Q

What can be an early sign of Neurodeg dz?

A

Sleep disturbance

212
Q

What neurodeg has abnormal REM sleep behavior prior to disease by several years?

A

Parkinsonism, Dementia

213
Q

What neurodeg has high rates of abnormal sleep/insomnia/osa/circadian rhythm problems, RLS

A

MS

214
Q

What neurodeg dz has rapid eye movement sleep behavior disorder?

A

Nonsynucleinopathy neurodeg dz

215
Q

What can be an early effective intervention in neurodeg and psych dz?

A

Improving sleep

216
Q

How does melatonin affect Alz D?

A

Improves sleep
Decreases sundowning
Slows progression of cognitive impairment
Protects against amyloid beta toxicity
Decreases amyloid beta production of amyloid fibrils
Serves as a neuro regulator hormone with various mechanisms of actions - free radical scavenger, antiox, antiinflam, immunosuppression

217
Q

What happens to melatonin and cortisol with poor sleep?

A

Melatonin decreases and cortisol increases

218
Q

Is morning light exposure associated with improved or worsened sleep quality?

A

Improved

219
Q

Which interleukin is effective for treating both symptoms and pathology of neuroimmune diseases in animal studies? How do you naturally increase this?What inflam markers are decreased?

A

IL-10 - exercise(studies done with 6 months of exercise) which decreases IL-6 and TNF alpha

220
Q

What is the impact of exercise on the functional and structural changes of the brain?

A 
Improved connectome
Neuroprotection
Neurogenesis
Oligodendrogenesis
Remyelination
221
Q

What type of diet led to a better QOL in mild to moderate RRMS patients?

A

Higher fat, greater intake of micronutrients - cholesterol, folate, iron and magnesium and reduced carbohydrate intake. This led to better ambulation, daily fxn

222
Q

What food intake has a higher correlation with MS?

A

Liquid cow milk(not cheese). Especially among women if they had high intake during adolescence.

223
Q

What IgG food sensitivities are high in Schizophrenia?

A

Gluten and Casein

224
Q

What can milk proteins be metabolized into and what is the effect of it?

A

Morphine like substances called Beta Casomorphin-7 with immune impact

225
Q

What foods are neuroprotective in PD?

A 
Carotenoids
Caffeine
Fruits
Genistein
Omega 3
Resveratrol
Tea
Veggies
226
Q

What food is neurodeg in PD?

A

Milk

227
Q

What are some pros of eggs?

A

If grass fed - DHA, choline, biotin, lutein, Vit A, D, K2, B3, B6, B9, B12

228
Q

What are cons of eggs?

A

Most common food allergen in IBD at >70%
60% allergy patients have IgG ab to eggs
13% of those with seasonal allergies have IgG ab to eggs

229
Q

What are most common food triggers to eosinophilic esophagitis?

A

Milk, wheat, eggs

230
Q

What are 3 sulfur rich foods?

A

Cabbage(Brassicas), mushrooms, onions(Allium)

231
Q

What components of mushrooms stimulate BDNF and NGF?

A

Lion’s mane(Yamabushitake), hen of the woods and cordyceps stimulate BDNF.

232
Q

How do mushrooms help immunity?

A

Stimulates natural killer cells; prime innate and adaptive immunity; associated with lower rates of cog decline and depression

233
Q

How do brassicas and alliums help protect against Neuro deg dz?

A 
Modulate NRF2 pathways
Improve detox
Increase GSH production
Increase Gaba production
Enhance neuroprotection
Improve endothelial function
Fermented sources - beneficial probiotics
234
Q

What foods are natural ACE inhibitors?

A

Fermented cabbage(kimchi, sauerkraut) and kefirs

235
Q

Consumption of what foods are associated with less COVID 19 deaths?

A

Fermented cabbage(kimchi, sauerkraut) and kefirs

236
Q

What probiotic does fermented foods provide?

A

Lactobacillus

237
Q

Why is vitamin K2 impt for brain?

A

Myelin protection
Neural stem cells
Calcium influx into bones/teeth

238
Q

Where is K2 produced?

A

Vitamin K1 is metabolized to K2 in the gut

239
Q

What nutrients to greens have in it?

A

K2, carotenoids. lutein, zeaxanthin, meso zeaxanthin, folate, Ca, Mg

240
Q

Which pigments are associated with improved cog performance and neuroprotection?

A

Blue/purple/black polyphenols

241
Q

What food is a good source of CoQ10?

A

Organ meats

242
Q

What vitamins/minerals/nutrients do organ meats have?

A

Ubiquinone, EFA, retinol, vitamin A, Vitamin K2-mk4

243
Q

Where is beta carotene converted to vitamin A and by what enzyme?

A

Intestine, BCMO1

244
Q

What nutrient biomarker patterns were associated with more favorable cognitive and MRI measures?

A

1) High plasma B1, B2, B6, B9(folate), B12, C, D, E

2) High plasma marine n-omega fatty acids

245
Q

How do fatty acids mediate cog fxn?

A

They modulate neuronal membrane fluidity;. Critical to PFC and visual cortex, Critical factor is ratio of omega 6:3(4:1 is best ratio); helps relapse rate in MS

246
Q

What can predict cognition at age 10?

A

Levels of EFAs at birth

247
Q

What are beneficial effects of EFAs on MS?

A

Inflam markers
Glutathione reductase
Reducing relapsing rate
Achieving omega 6:3 balance

248
Q

What are some finding of fat soluble vitamins and MS?

A

Retinol has inverse relationship with MRI outcomes in RRMS
MS pts had lower K2 blood levels than controls
Relapse risk reduced with Vitamin D at least 20ng
Vit E had inverse relationship with MRI disease activity in RRMS

249
Q

How does stress affect MS?

A

Increases MS relapse/severity of relapse
Increases risk for AD
Increases freezing of PD and worsening of PD gait
Increases risk of CVD and stroke

250
Q

What is a modifiable risk factor for development of AD?

A

Smoking

251
Q

What metals are associated with neurodegeneration?

A

Cd, Cu, Pb, MN, Fe, Methyl Hg

252
Q

What rx drug blocks progenitor cell differentiation inhibiting CNS remyelination?

A

Simvastatin

253
Q

What synergistic dz with ApoE4 increase risk of AD 5 fold?

A

DM

254
Q

How does LH/Sex steroid hormone ratio affect neurodeg dz?

A

Increased ratio drives up TNF alpha and amyloid beta

255
Q

Whats the best way to increase BDNF in PD?

A

Exercise, mushrooms and fasting/ketosis/metabolic switching

256
Q

What substance can rebuild myelin?

A

CDP-Choline by increase in oligodendrocyte precursor cells and oligodendrocytes
Upstream approach: Use PC blended with water

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