Using the Organix, Organic Acids Testing, in Clinical Practice Dr. Rachel Marynowski.

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

www.metametrix.comwww.metametrixinstitute.o

rg

© 2012 Metametrix