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Using the Organix, Organic Acids Testing,
in Clinical PracticeDr. Rachel Marynowski
Stages of Energy
Extraction From Food
Food
CO2 + H2O + Urea
1. Actual values –
Examples include analytes such as lactate,
sulfate etc.
2. Functional markers –
These include analytes such as FIGLU, 5HIA
The Organix Profile Looks at:
C
ABB
A Intermediary metabolite
En Enzyme
CofactorE1
E2E2
© 2005 Metametrix Clinical Laboratory, Inc.
Urine
Functional Indicators of Nutrient Deficiency
Mitochondrial Function and Assessment B Complex Vitamin Markers Methylation Pathway Markers Neurotransmitters Metabolism Markers Oxidative Damage and Antioxidant Markers Detoxification Markers Intestinal Dysbiosis Markers
General Breakdown
1. Mitochondrial Function and Assessment Fatty Acid Metabolism Carbohydrate Metabolism Energy Production (Citric Acid Cycle)
Evaluation: Step 1
If Pyruvate is elevated consider: B-vitamins: B1 and B5 Lipoic Acid Under-eating
If Lactate is elevated consider: CoQ10 Biotin Lipoic Acid Excess Alcohol intake
Pyruvate dehydrogenase requires B-vitamin cofactors, thus an elevated pyruvate may be an indicator of a need for B-vitamins.
- Naito et. Al., 1998 Eur J Pediatrics
Co-enzyme Q10 supplementation has been found to be effective when lactate is elevated.
- Sobreira, et. Al., 1997 Neurology
Requirements…
Pyruvate Dehydrogenase Complex
High levels may suggest :1. Low carbohydrate diet2. Diabetic ketoacidosis3. Reduced caloric consumption
or Wasting diseases.4. Insulin resistance (also look at high
lactate/pyruvate)
(acid)
Buffer
NH4
Citrate3
-
Proximal Tubular Cell
NH4CitrateIsocitrate
Cis-aconitase
(Ammonia)
Citrate, Isocitrate, Cis-Aconitase(Excreted in the urine)
Elevated?Need for CoQ10
Mevalonic Acid
Cholesterol
Statins
CoQ10
Hydroxymethylglutarate (HMG)
1. Mitochondrial Function and Assessment2. B Complex Vitamin Markers
Thiamin (B1) Riboflavin (B2) Niacin (B3) Pantothenic acid (B5) Pyridoxine (B6) Lipoic Acid Biotin
Evaluation Step 2
B-Complex (B1, B2, B3, B5)
Each of these uses a similar dehydrogenase enzyme to move on…
Pyruvate a-ketoglutarate
a-ketoisovalerate a-ketoisocaproate a-keto-β-methylvalerate
The dehydrogenase enzyme requires vitamins: B1, B5, B2, B3 and lipoic acid
Vitamin B6 (Pyridoxine)
“One of the earliest markers for B6 deficiency was the urinary excretion of xanthurenic acid, which is normally a minor tryptophan catabolite. The major pathway of tryptophan catabolism proceeds via the PLP-dependent kynureninase reaction.” (Shane and Contractor, 1980)
The DRI for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and
Choline (1998 - IOM)
Biotin
Excretion of β-hydroxyisovalerate (3-HIA) and biotin are early and sensitive indicators of biotin deficiency.
(Mock et al., 2002)
The indicators of biotin status that have been validated to the greatest extent are an abnormally decreased urinary excretion of biotin and an abnormally increased urinary excretion of 3-hydroxyisovaleric acid.
(DRI Institute of Medecine 1998)
1. Mitochondrial Function and Assessment2. B Complex Vitamin Markers3. Methylation Pathway Markers
Cyanocobalamin (B12) Folic Acid
Evaluation Step 3
Methylmalonate
• Isoleucine• Valine• O3, O6, O9
B12
Urinary Excretion
Urinary MMA levels are a good indication of cobalamin distribution and function since they are directly related to a cobalamin-dependent metabolic pathway.
-EJ Norman, 1982; 59(6): 11-28-1131
Methylmalonic acid (MMA) is increased in blood and urine of patients with vitamin B12 deficiency.
-Clinical Chemistry. 2001;47:1993-2002
Methylmalonate was shown to be superior to serum B12
•
(FIGLU)
Degradation of histidine relies on assistance from folate
1. Mitochondrial Function and Assessment2. B Complex Vitamin Markers3. Methylation Pathway Markers4. Neurotransmitters Metabolism
Markers
Evaluation Step 4
Iron and BH4
Magnesium
Magnesium
Copper
Vitamin B6
Iron and BH4
B6
Vit C, Cu
Fe
SAMe
L-dopa
Dopamine
Norepinephrine
Epinephrine
Tyrosine
Homovanillate (HVA)
Vanilmandelate(VMA)
Low levels of HVA and VMA are associated with depression, fatigue, sleep disturbance. Clinicians should consider stress and cortisol levels, and may consider adding amino acid supplements.
B6
FeTryptophan
5-HTP
Serotonin
5-HIA
5-Hydroxyindoleacetate (5-HIA) is a degradation product of Serotonin. _________________________________________________________________
5-HIA will likely be elevated when L-Tryptophan, SSRIs or 5-HTP supplements are taken.
Interferon-gamma
Inflammation
• Viral or bacterial
source?
• Increased nociception
• Increased irritation
• Possible sleep disturbance
NMDA agonist
1. Mitochondrial Function and Assessment2. B Complex Vitamin Markers3. Methylation Pathway Markers4. Neurotransmitters Metabolism Markers5. Oxidative Damage and Antioxidant
Markers
Evaluation Step 5
P-Hydroxyphenyllactate is a marker for cellular mitosis. While a small amount of production is normal, indicating metabolic cell turnover, excessive production can indicate injury or possibly tumorogenesis.
8-Hydroxydeoxyguanosine (8-OHDG) is a residue resulting from free radical damage to guanosine in DNA. Levels correlate with the rate of DNA damage and repair.
1. Mitochondrial Function and Assessment2. B Complex Vitamin Markers3. Methylation Pathway Markers4. Neurotransmitters Metabolism Markers5. Oxidative Damage and Antioxidant Markers6. Detoxification Markers
Evaluation Step 6
Xylene exposure sources:• Cigarette smoke• New paint, spray paint, paint
thinners• New carpet• New cars• Dry cleaning products• Fuel & Exhaust fumes
Excessive ammonia production:• From gut-derived bacteria• Elevated Amino Acid catabolism
Conjugation & Elimination
Glucarate(remnant)
Glucuronic Acid
Glucose
Phase I
Phase II
1. Glucarate represents both accelerated Phase I activity…
(This process requires intervention from Phase I, leaving Glucarate behind as a
remnant.)
2. …and slow Phase II glucuronidation status
Glucarate
Alpha-hydroxybutyrate, Pyroglutamate and Sulfate… 3 clues
of glutathione status!
When pyroglutamate is being produced at a faster rate than it can be
recycled, it will appear elevated on the Organix
profile.
Cysteine lost in the urine will appear as urinary sulfate
With every molecule of cystathionine committed to making Glutathione,
one molecule of α-Hydroxybutyrate is made.
GlycineGlutamate
1. Mitochondrial Function and Assessment2. B Complex Vitamin Markers3. Methylation Pathway Markers4. Neurotransmitters Metabolism Markers5. Oxidative Damage and Antioxidant Markers6. Detoxification Markers7. Markers of Intestinal Dysbiosis –
Yeast/Fungal
Evaluation Step 7
Tyr
Phe
TrpTryptophan is converted to Indole in the gut – and subsequently excreted as Indican.
Candida yeast species overgrowth is indicated when, D-Arabinitol is high
The conversion of Benzoate to Hippurate is a glycine
conjugation step. Supplemental glycine may help with the conversion.
The markers are compounds created by organisms in the small bowel, that are
absorbed and excreted in the urine
Use of antibiotics Use of antacids Loss of digestive function
Gastric, pancreatic, hepatic Dietary intake (sugar, alcohol, etc.)
Jejuno-ileal bypass or resection Blind loop, physiological abnormality Celiac disease
Causes of Dysbiosis
L-Glutamine N-acetyl Glucosamine Botanicals:
Licorice Okra Aloe Leaf Slippery Elm Marshmallow
MSM MUCIN Butyric Acid Zinc-carnosine Pre & Probiotics High Fiber diet
Heal the GI Mucosal Lining
1.
2.
Guide to Supplementation from Organix™ Profile
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rg
© 2012 Metametrix