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Institute for Functional Medicine exam > Environmental > Flashcards

Environmental Flashcards

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1
Q

What does “PURE” stand for in the context of detox?

A

Pattern recognition
Undernourished
Reduce exposures
Ensure a safe detox

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2
Q

How is Total Toxic Load determined?

A

Total toxic exposure MINUS ability to biotransform + excrete toxins
(TTL=total of body burdens of exogenous chemicals, heavy metals, and toxic endogenous compounds)

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3
Q

What are the phase 1 (CYP P450) detox reactions?

A

Oxidation, reduction, hydrolysis

introduce or expose a functional group to render the compound more polar

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4
Q

What are the phase II detox reactions?

A

Glutathione conjugation (glutathione-S-transferase) - mostly into bile
Amino acid conjugation (taurine, glycine, arginine, glutamine)
Methylation (methyltransferase/eg COMT)
Sulfation (sulfonyltransferase) - excreted into urine (low substrate concentrations)
Acetylation (N-acetyltransferase)
Glucuronidation (UGT enzymes)

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5
Q

What are the Neuro & psych manifestations of poor detox?

A 
Concentration and memory issues
ADHD, autism
Chronic headaches, insomnia
Peripheral neuropathies, tremor
Autonomic dysfunction
Neurodegenerative disease - ALS, Parkinsons, AD
MS
Mood disorders 
Pain
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6
Q

What are the immune manifestations of poor detox?

A

Atopy
Autoimmune disease - Hashimoto’s, IBD, RA, SLE, psoriasis, Sjogrens
Chronic inflammatory disease
Recurrent/chronic infections
Chronic dermatitis
Adverse food reactions
Multiple chemical sensitivities (MCS): TILT

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7
Q

What are the mitochondrial and metabolic manifestations of poor detox?

A 
Obesity and abnormal weight gain
Metabolic syndrome & type 2 DM
Atherosclerosis
Fatigue, CFS
Fibromyalgia, muscle aches, weakness
Osteoporosis
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8
Q

What are the endocrine manifestations of poor detox?

A 
Hormonal and HPA axis imbalances
Thyroid issues
Met Sx & Type 2 DM
Females: premature puberty, PMS, PCOS, infertility, endometriosis, fibroids
Males: oligospermia, sperm dysmotility
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9
Q

What are nutrients and foods which support phase 1 detoxification?

A

Riboflavin (soy, spinach, cremini, eggs, asparagus, almonds, turkey)
Niacin (fish, meat, brown rice)
Pyridoxine (meat, fish, sweet potatoes, potatoes, sunflower seeds, spinach, banana)
Folic acid (legumes, broccoli, turnip greens)
B12 (fish, meat)
Glutathione (undenatured whey protein, asparagus, curcumin, broccoli, avocado, spinach, garlic, citrus, Brazil nuts)
BCAAs (whey protein, fish, chicken, eggs)
Flavonoids
Phospholipids (soy, sunflower seeds, eggs)
Mg, Zn, Cu, Fe, molybdenum

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10
Q

What are nutrients which protect against overproduction of toxic phase I metabolites?

A

Carotenes/vitamin A
Vitamin C
Vitamin E (sunflower seeds, almonds, spinach, chard, avocado, asparagus)
Selenium (Brazil nuts, fish, meat)
Copper (sesame seeds, cashews, soy, mushrooms, walnuts, lentils, lima beans)
Zinc (meat, pumpkin seeds, lentils, quinoa)
Manganese (cloves, oats, brown rice, beans, pineapple, pumpkin seeds)
CoQ10 (meat, fish)
Thiols (garlic, leeks, onions, chives)
Flavonoids
Silymarin (milk thistle, artichokes)
Pycnogenol (skins of grapes, blueberries, cherries, plums)

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11
Q

What are nutrients and foods which can support phase II detox?

A

Glycine - beef, chicken, lamb
Taurine - fish, meat
Glutamine - beef, chicken, fish, eggs, cabbage, beets, beans, spinach, parsley
N-acetyl cysteine - meat, garlic, crucifers
Cysteine - meat, fish
Methionine - eggs, sesame, Brazil nuts, soy, chicken, tuna, legumes, almonds, brown rice

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12
Q

What are lab measures of antioxidant capacity?

A

Whole blood GSH (reflects tissue levels and correlated with NK function)
Glutathione peroxidase (Se dependent)
SOD (Cu/Zn cytosol and Mn mitochondria)
CoQ10

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13
Q

What are biomarkers of toxic susceptibility in the stool?

A

Dysbiosis and reduced diversity
beta-glucuronidase
Intestinal permeability (ie low lactulose or mannitol recovery)
Malabsorption markers:

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14
Q

List some oxidative stress tests

A

oxLDL
8-OH-dG - DNA damage (note: minimally affected by chemical antioxidants - A,C,E, beta-carotene)
Thiobarbituric acid reactive substances (TBARS)
Oxygen radical absorbance capacity (ORAC) - measures antioxidants in blood
Lipid peroxides
F2-Isoprostanes - formed from free radical attack of AAs, GLA & formed from COX

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15
Q

How can body burden be assessed?

A

Biomonitoring:
Measurement of exogenous agents in blood, stool, urine, hair, nail & adipose tissue
Measure markers that indicate presence or effects of toxin

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16
Q

What metals can be measured in hair?

A

Pb, Hg, Mn, Cd, As, Cr (WITH blood/urine markers)

Note:
Autism associated w/antimony, Pb, Hg, As
ADD, oppositional defiant disorder assoc w/Mn, Pb, Hg, AI
Chronic depression assoc w/Pb

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17
Q

What are some potential sources of oral toxicity?

A

Metals (Hg amalgams, crowns, titanium implants, orthodontic appliances)
Plastics (BPA, BPS, phthalates from fillings; resins in night guards)
Infections
Oral health products - triclosan, SLS, propylene glycol, titanium dioxide, fluoride

Note: mechanisms include galvanism, leaky mouth, sublingual absorption, swallowing, microbiome disruption -> leads to immune dysregulation, inflammation & oxidative stress

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18
Q

What are the components of safe mercury amalgam removal?

A

Pt pre-treatment with ingested charcoal and chlorella rinse
Nasal air supply & eye protection for the patient
Non-latex dam and nitrile gloves
Saliva ejector under dam
“Clean-up” suction devices
Auxiliary suction devices with mercury filters
Protective gowns and mercury vapor respirator masks for dental staff

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19
Q

How can we prevent oral toxicities?

A

Diet: remove food sensitivities, nutrients to support detox
Daily physical biofilm disruption
Choose safe ceramic and BPA-free dental materials
Eliminate toxic oral health products
Probiotics

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20
Q

What is the difference between toxin, toxicant, xenobiotic and persistent organic pollutant (POP)?

A 
Toxin = produced by living organism (animal, plant, fungi, bacteria)
Toxicant = result of human activity
Xenobiotic = chemical compound foreign to the body
POP = substances that persist in the environment and bioaccumulate through the food chain
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21
Q

Define body burden

A

The quantity of an exogenous substance or its metabolites that accumulates in an individual

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22
Q

What are population RFs which increase risk of POP burden?

A

Poverty, BMI, age, gender, race

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23
Q

Why do some people retain or are more sensitive to toxins?

A 
Increased or ongoing exposure
Nutrient deficiencies (B vitamins, antioxidants, Mg, Se, etc)
High refined food intake
Inadequate protein
Stress, emotional trauma
Intestinal dysbiosis
Genetic variations in phase I/II
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24
Q

What are characteristics of biotransformation?

A 
Constantly active
Inducible
Energy dependent
Micronutrient dependent
Genetically polymorphic
Additive (affected by total load)
Redundant
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25
What organs & biochemical processes are involved in absorption and first pass metabolism?
``` Stomach (HCl) Intestines (digestive enzymes) Gut wall (CYP3A4, P-glycoprotein anti-porter pumps) Liver (P450s, transferases) Colon (bacterial metabolism, excretion) ```
26
Where are p-glycoprotein pumps located?
Intestines, BBB, kidneys, liver (biliary) | - antiporter which decreases intracellular [substances]
27
What medications induce p-glycoprotein?
Chemotherapy, dexamethasone, rifampin, SJW
28
What medications inhibit p-glycoprotein?
tamoxifen, ketoconazole, cyclosporine, erythromycin, verapamil, grapefruit juice, berberine
29
Which CYP enzyme has the greatest genetic variation?
CP2D6 (codeine, dextromethorphan, tamoxifen, TCAs, SSRIs) Absent/poor: 6-10% Caucasians, >10% blacks, 1-2% Asians Ultra-Rapid: 30% of Middle Eastern, North Africans
30
Which CYP enzyme is responsible for metabolism of ethanol, acetaminophen, nitrosamines, food mutagens, ketones, benzene?
CYP2E1
31
A genetic SNP in which enzyme would impact caffeine, aflatoxin and arylamine metabolism?
CYP1A2 Eg. Slow Metabolizer - coffee drinking increases risk of MI
32
Which enzymes do cigarette smoking, charbroiled beef & dioxins induce?
CYP1A2; therefore cigarette smokers often have high caffeine tolerance Also CYP1A1, 1B1
33
SNPs or chemicals that up-regulate which CYP enzyme can lead to autoimmune diseases and increased risk of prostate & breast CA?
CYP1B1 Responsible for bioactivation of pro-carcinogens, estrogen to 4-OH Note: inhibited by DHEA, polyphenols, resveratrol, red clover
34
What factors can impact CYP450 phenotypic variability?
Drugs SNPs Age: variable in children, may decline w/age Inflammation and liver disease reduce activity Induced by nuclear receptors: AhR (aromatic hydrocarbon), PXR (pregnant X), CAR (constitutive androstane), VDR, PPAR (note: which in turn activate XREs - xenobiotic response elements) Hormones (glucocorticoids, GH induce 3A4, T3 inhibit 3A4) fasting alters many phase I enzymes
35
Gilbert's Syndrome is a SNP in which detox enzyme?
UGT1A1 Impaired ability to conjugate bilirubin with glucuronic acid, therefore elevated unconjugated bilirubin after fasting - especially noticeable with phenytoin, irinotecan (Note UGT1A1 can be induced by suforaphane, flavonoids)
36
Which enzyme is inhibited by red wine anthocyanins, catechins, quercetin, genistein, red food dye, annatto and alcohol, leading to excessive monoamines?
SULT1A3 - deactivates catecholamines SULT1A1 - deactivates xenobiotics, estrogens, phenolics, iodothyronines (therefore, PAHs which inhibit this can lead to estrogen and thyroid disruptions)
37
Which Phase II enzymes are subject to common SNPs?
UDP-glucuronosyltransferases (UGTs) Sulfotransferases (SULTs) NAD(P)H:quinone oxidoreductases (NQO1s) Methyltetrahydrofolate reductases (MTHFR)
38
SNPs in which enzymes can increase the risk of cancer with consumption of well-done meat?
Rapid NAT2, CYP1A2
39
What are common causes of impaired biotransformation?
Overwhelming toxic load, impaired elimination, imbalanced macronutrients, deficiency of detox substances, dysregulation of detox enzymes, bacterial uncoupling of conjugation
40
What are substrates of glucuronidation?
Insecticides, herbicides, BPA, sulfonamides, acetaminophen, naproxen, opioids, cannabis Bilirubin (think Gilbert's), steroid and thyroid hormones, retinoids, prostaglandins, bile acid, dietary polyphenols
41
What phytonutrients upregulate glucuronidation (UGT enzyme)?
Quercetin (in apple, onion, cherry, kale, beans, broccoli), citrus, luteolin & chrysin (honey, propolis, broccoli, chili peppers, celery, rosemary, parsley), glucosinolate (watercress, crucifers) + EFAs to support membrane-bound enzyme + magnesium
42
What botanicals induce UGT enzymes?
Milk thistle, gingko, grape seed extract, Hawthorne, noni, SJW, valerian, cranberry, resveratrol, Curcumin
43
What phytonutrients reduce beta-glucuronidase?
``` plant protein & fiber carotenoids (note: vit A deficiency inhibits UGT1A1, 1A6) Silymarin Strawberry, black current Reishi Licorice Lactic acid probiotics Inulin, prebiotics Caloric restriction Calcium d-glucarate (2000-4000mg/day) ```
44
What tests could be used to diagnose glucuronidation deficiencies?
Dysbiosis - stool beta-glucuronidase, stool culture, OAT Thyroid issue - usual thyroid tests + assess Se, Zn, Fe, I A, E, B2, B3, B6, C, D, tyrosine UGT gene SNPs
45
What phytonutrients, nutrients, etc can induce sulfotransferases?
Genistein, glucosinolate (cabbage), vitamin E, vitamin A, selenium, caffeine
46
What are the cofactors for sulfite oxidase? (transforms sulfite to sulfate)
B6, molybdenum (in adzuki beans, grains, nuts)
47
What are conditions associated with SULT SNPs?
Environmental/chemical sensitivity, AD, PD, motor neuron disease, RA, delayed food sensitivities (ie phenol, tyramine foods), diet-responsive autism, acetaminophen intolerance
48
What sulfur compounds can support sulfation?
SAMe, GSH, taurine, NAC, MSM, glucosamine & chondroitin sulfate
49
What tests can be used to diagnose insufficient sulfonation?
Blood sulfate Sulfur amino acids (plasma Met, cystathionine, cysteine, taurine) Transulfuration - CBS gene SNP (B6 coenzyme) SULT gene SNPs
50
What plant foods are highest in sulfur?
Corn, sunflower seeds, oats, chocolate, cashew, walnuts, almonds, sesame seed
51
What enzymes are associated with methylation SNPs?
MTHFR (support w/5-methyfolate), MTR (support w/B12), MTRR (B12), BHMT (TMG/betaine), COMT (Mg, SAMe, hydroxyB12), CBS (B6), AHCY
52
What tests could be used to determine methylation insufficiencies?
Methionine metabolism: plasma homocysteine, SAMe, SAH, SAMe/SAH, methionine & cysteine Methylmalonate (B12) Gene SNPs Monofilament and tuning fork for vibratory and light touch testing on feet/toes (can be due to toxic metals - Pb, Hg, Cd, As & also methylation issues, insulin resistance & EtOH) (note: Serum B12, folate, pyridoxine less helpful)
53
What are dietary sources of nutrients for methylation support?
Methionine - meat, fish, shellfish, eggs, nuts, seeds, spirulina B12 - meat, fish, shellfish, eggs B6 - meat, nuts, garlic, whole grains, seeds, legumes Betaine - quinoa, beets, spinach, whole grains, sweet potato, meat Folate - beans, legumes, liver, nuts, seeds, spinach, asparagus, mustard greens, avocado Mg - seeds, beans, nuts, whole grains
54
How does TMG impact NASH?
Increases SAMe, resulting in reduced hepatic enzymes, steatosis and fibrosis in NASH patients (SAMe is the major methyl donor and primary precursor to cysteine)
55
What supplements could be considered to support methylation?
``` 5-MTHF 0.4-10g Methylcobalamin 0.4-5mg pyridoxine, P5P 10-50mg B2 10-50mg TMG/betaine 500-2000mg Mg 200-1200mg Fish oil 1-5g SAMe 400-1200mg if clinical tolerance ```
56
What nutrients are needed for GSSG reductase and GSH peroxidase, respectively?
B2, FADH2, NADPH - GSSG reductase (GSSG -> GSH) | Selenium - GSH peroxidase. (GSH->GSSG)
57
What is the product of glutathione conjugation (phase 2 detox)?
Mercapturic acids (excreted in urine)
58
What nutrients may be used to increase glutathione levels?
NAC, glycine, lipoic acid, GSH, magnesium, vitamin D3, vitamin C, methyl-folate, methyl-B12, milk thistle SAMe, niacinamide, zinc, vitamin E, selenomethionine, whey protein isolate, phytonutrients (curcumin, hydroxytyrosol, sulphorophane, resveratrol, berry extracts, nuts)
59
What tests may be used to diagnose glutathione deficiencies?
RBC reduced glutathione Blood glutathione peroxidase Serum/plasma cysteine Urine mercapturic acids
60
Which amino acids are involved in conjugation detox?
Taurine, glycine, arginine, glutamine Also serine, proline, ornithine Note - this is a minor metabolic pathway for most xenobiotic carboxylic acids & neurotransmitter metabolism (substrates include bile acids, BCAAs, herbicides, benzoate's, ASA (glycine), ibuprofen (taurine), VPA)
61
What is the function of taurine in detox and what can it be used for?
Contains sulfonate group as reducing agent Crosses BBB and protects against glutamate excitotoxicity Potentiates Pb and As chelation w/DMSA May be used for: hyperactivity, anxiety, sleep disturbance, seizures, autism, cholestasis 1-6g/day
62
What are clinical applications of glutamine?
IBD, intestinal permeability, healing wounds, low muscle mass & chronic immune weakness, wasting syndrome, cancer patients on chemo 5-40g/day or 0.5g/kg body weight (25-30g/day for adults <110lb)
63
What are contraindications for glutamine?
Neurodegenerative diseases - ALS, MS, PD - Gln conversion to Glu can be excitotoxic * Glu levels in blood don't increase with moderate Gln doses (ie 5g single doses)
64
What type of conjugation is usually slow in people who are chemically sensitive?
Acetylation (ie attachment of acetyl-CoA) Substrates include histamine, serotonin, sulfa drugs
65
What nutrients enhance acetylation? (ie pyruvate conversion to acetyl-CoA via pyruvate dehydrogenase and N-acetyltransferases/NAT)
B1, B2, B3, B5, lipoate, vitamin C, Mg | Also - quercetin upregulates NAT
66
What labs can reflect detox gene SNPs?
GST SNPs: blood GSH and/or oxidative stress (cysteine, SOD, sulfate, GSH-Px, peroxides) MTHFR, MTRR, MTR SNPs: methylation labs CYP1A2, 1B1 - estrogen metabolites (4,16,2)
67
What are the clinical emphases for detox? | ie optimize glucoronidation, sulfonation, methylation, glutathione conjugation
Lots of phytonutrients Glucuronidation: carotenoids, glucuronidase support, thyroid, dysbiosis Sulfonation: sulfur AAs, sulfate/MSM Methylation: folate, B12, B6, TMG, EPA-DHA Glutathione conjugation: NAC, lipoate, GSH, Mg, D3
68
What are the roles of Zn in detox?
Displaced by Hg, Pb, Cd Induces metallothionein genes Protects sulfhydryl groups against oxidation (support membrane strength) Complexes with phospholipid to block membrane oxidation SODs require Zn, Mn, Cu; Zn stabilizes it
69
What are RFs for zinc deficiency?
Infants, children, older adults; pregnancy & breastfeeding Diarrhea, malabsorption, IBD Strict vegetarians (high grain/legume phytate content can increase zinc needs by 50%) Liver disease, renal zinc loss increases Malnourished Zn deficiency = impaired development of acquired immunity
70
What are clinical signs of Zn deficiency?
Dermatitis, hair loss, frequent infections, glossitis, nail dystrophy Labs: low plasma & RBC Zn, low ALP, check for high Cu, low vitamin A/beta-carotene ratio Zinc taste test
71
What are S&Sx of Mg deficiency?
Early signs: constipation, HA, muscle cramps, fatigue/weakness, numbness, tingling Progressive: HTN, arrhythmia, N/V, seizures, personality changes, tremors
72
What are the top 3 CYP450 enzymes for drug metabolism?
CYP3A4 - 40-45% CYP2D6 - 20-30% CYP2C9 - 10%
73
What is the role of GGT and its significance in detox assessment? (gamma-glutamyl transferase)
GGT catalyzes transfer of the gamma-glutamyl moiety of glutathione to water (forming glutamate), to amino acids or peptides Its function is central to GSH metabolism, xenobiotic and drug detox. Sensitive indicator of liver disease (esp fatty liver and biliary disease) and surrogate marker for toxic exposure. *good early marker of liver toxicity, possible marker for oxidative stress, and may be a marker for increased CV/metabolic risk
74
How does glyphosate impact microbiome and detox?
Gut microbiome disrupter, impairs serum sulfate transport, and suppresses P450 enzymes, thereby enhances toxicity of other toxins
75
How is toxicity reflected on a CBC?
Leukopenia - sign of chronic toxic exposure | - due to Rx (CBZ, clozapine, TMP/SMX), benzene, As, strontium, hexavalent chromium (also causes leukocytosis)
76
What increases 8OHdG?
Cigarette smoking, PAH exposure Increases with total calorie and/or carb intake, PUFA intake Note: it is higher in PD and lung CA; minimally affected by chemical antioxidants (A,C,E, beta-carotene)
77
What decreases 8-OHdG?
Exercise, MUFA | A,C,E, beta-carotene?
78
What influences blood lead concentration?
``` Recent exposure (iw 4-6wks) Bioavailable internal stores (eg. bone) Individual differences in lead toxicokinetics ```
79
What are acute and chronic symptoms of Pb toxicity?
Acute: N/V, GI pain, renal dysfunction, convulsions Chronic: ongoing GI & renal, HTN, infertility, developmental delays, neurological issues (e.g. poor concentration, consciousness changes, encephalopathy in kids), anemia (inhibits heme synthesis), Burton's line (black lines around teeth). paresis, wrist drop
80
Which route to test for toxicity?
Blood or urine metals
81
How does dry heat impact development of AGEs?
>10-100-fold more AGEs than uncooked state across food categories, esp animal-derived foods (vs. carb-rich foods and milk tend to contain few AGEs even after cooking)
82
What are some dietary phytochelators?
``` Fibers (esp insoluble, rather than soluble) - flaxseed meal shown to increase Cd absorption Modified citrus pectin Chlorella Sulfur-containing foods Cilantro, coriander EGCG Quercetin Turmeric Matcha Green veg/chlorophyll ```
83
What can be used to support bile flow and reduce cholestasis?
Vitamin C, B6, folate, B12, Mg, choline, inositol, taurine, methionine (building block for bile salts), betaine HCL Artichoke leaf extract and other bitters (take at mealtime) *might worsen gallstones
84
What are some chemoprotective phytonutrients? (ie for breast CA)
Green tea 3+ cups/day Quercetin Mediterranean-style diet w/>5 F&V, legumes, olive oil Organosulfur compounds (crucifers, garlic) Also: regular exercise and optimize 2/4/16-OH-E ratio
85
How can we support xenoestrogen clearance?
P450 hydroxylation: I3C, DIM, soy/clover isoflavones, lignans Methylation, COMT - Mg, B12, methylfolate, choline, TMG, SAMe Sulfate conjugation (SULT) - genistein, vitamins E & A, Se, crucifers Glucuronide conjugation (UGT) - glucosinolates, Mg, curcumin, quercetic, calcium d-glucarate, carotenes, probiotics, retinol, optimal T3
86
What are some bi-functional phytochemical modulators?
Pomegranate, turmeric, green tea, crucifers, beet, garlic
87
What are baseline phytonutrients to emphasize for detox?
Frequent consumption of: | Crucifers, curry, berries, garlic, onions, beets, carotenoid rich produce, EVOO, green tea, pomegranate, green leaf veg
88
What's the protocol before & after dental amalgam removal?
1 week prior: CBC, CMP, GFR ``` 1 week before and for 14 days after: 8-10 glasses of water/day Vitamin C 2-3g/day GSH 0.5-1g/day B-complex CoQ10 100-300 Se 200-300mcg Vitamin E 200-400IU Mg 400+mg/day ``` Procedure day and post: Activated charcoal 2 caps right before and 2 caps immediately after; next day take 1-2 capsules in AM & PM Chlorella swish x 30sec immediately before and after; Swallow 2-4 capsules immediately after and continue 2-4 capsules BID for 2-5 days Optional IV vit C + plenty of rest
89
What strategies to prevent dental-related toxicities?
Diet: identify food sensitivities, nutrients to support detox Biofilm disruption at least once per day Choose safe and BPA-free dental materials Eliminate toxic oral health products Add probiotics
90
What are some potentially toxic ingredients in oral health products?
Triclosan - impedes thyroid function, likely endocrine disruptor SLS - can cause chronic oral lesions & sloughing of mucosa Microbeads - can imbed in gums (+environmental issue) Artificial sweeteners (saccharine, aspartame) Propylene glycol - considered an irritant Alcohol based - disrupts microbiome Fluoride - accumulates in tissues leading to neurological effects and endocrine disruption (controversial)

Institute for Functional Medicine exam (7 decks)

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