Evaluation for Toxins

Question 1

Elevated fasting unconjugated bilirubin (Gilbert’s phenotype

Answer 1

• UGT1A1*28

SNP)

Question 2

• Low HDL-cholesterol

Answer 2

(surrogate for low PON1)2 = ↑CVD/T2DM risk; ↑OP
toxicity2

PON protects against lipid oxidation

Question 3

Biomarkers of susceptibility - impaired nutritional status

Answer 3

B vitamins, homocysteine, methylmalonic acid 
RBC minerals (magnesium, zinc)
Antioxidants (CoQ10—total and reduced,
retinol, tocopherols, glutathione)
RBC essential fatty acids(Omega-3/6)

Question 4

-

Answer 4

arsenic tox

with betaine also helps with alcohol

Question 5

lab measures of antioxidant capacity

Answer 5

Glutathione (GSH) – whole blood
Glutathione peroxidase
Superoxide dismutase
CoQ10 (plasma)

Question 6

Optimal ubiquinone level

and how to achieve

Answer 6

> 2

mcg/mL: requires supplementation to achieve]

Question 7

Glutathione Peroxidase

Answer 7

if too high - sign of oxid stress

Question 8

Superoxide Dismutase

Answer 8

if too high, sign of oxid stress

Question 9

glutathione peroxidase dependent on what mineral

Answer 9

Se

Question 10

Biomarkers of Susceptibility:

GI: Stool analysis

Answer 10

• Decreased diversity index (DNA based)
• Dysbiosis – overgrowth of potential pathogens
• Fecal β-glucuronidase
• Intestinal permeability

Question 11

toxins: -expect to see high or low? 
RBC
WBC
uric acid
LFTs (esp GGT, ALT)
kidney function

Answer 11

• Hematopoetic: WBC, RBC
• Liver function tests (esp ALT, LDH, GGT)
• Uric acid (PCBs, dioxin & dioxin-like chemicals)
• Kidney function: BUN, creatinine, cystatin C

Question 12

Persistent leukopenia - think…

Answer 12

toxic exposures to:
Pharmaceuticals
Organic Pollutants
Heavy Metals

Question 13

GGT function central to

Answer 13

Function is central to glutathione metabolism, xenobiotic and drug detoxification

Question 14

GGT Level of concern (men/women)

Answer 14

• Men: 30-40 IU/L (upper quartile) increased suspicion;
>50 IU/L significant
•Women: >30 IU/L significant

Question 15

Toxins - biomarkers of effect

Answer 15

• Oxidative stress markers1,2
• Urinary porphyrin profile (mercury)3
• Urinary D-glucaric and mercapturic acids4
• Hormonal imbalances (eg elevated 4-OH-estrogen)5,6
• Elevated serum insulin (insulin resistance)7

Question 16

Oxidative stress tests:

Answer 16

• oxLDL
• 8-Hydroxy-Deoxyguanosine (8-OH-dG)
• Thiobarbituric acid reactive substances (TBARS)
• Oxygen radical absorbance capacity (ORAC)
• Lipid Peroxides
• F2-Isoprostanes

Question 17

what are Lipid peroxides

Answer 17

• Unstable oxidative product of polyunsaturated fats

Question 18

Isoprostane F-2-alpha

Answer 18

• Measured in plasma or urine
• Formed as result of free radical attack on AA & GLA (lipid peroxidation)
• Isomer of enzymatically formed prostaglandins (e.g., PGF2)
• Chemically stable but can also be formed from COX.

Question 19

ORAC (Oxygen Radical Absorbance Capacity)

Answer 19

• Measures overall water-soluble antioxidants in blood;

* Used to measure antioxidant properties of foods.

Question 20

8-Hydroxy-DeoxyGuanosine
what is it?
increased by
- 
-
increased in
-
not affected much by 
-

Answer 20

(8-OH-DG, urine)
• Indicative of damaged DNA, especially mitochondrial
• Markedly increased by cigarette smoking and environmental
toxin (PAH) exposure
• Increases with total calorie and/or carbohydrate intake
• Increases with PUFA intake; lowered with MUFA
• Elevated in Parkinson’s disease & lung cancer
• Reduced by physical exercise
• Minimally affected by chemical antioxidants
(A, C, E, beta carotene)

Question 21

bikers/exhaust have more

Answer 21

ox LDL

Question 22

round up (glyphosate) disrupts what part of detox?

Answer 22

gut bacteria/AA production

CYP 450 enzymes