Insider's Guide 37

Functional Medicine Universitys
Functional Diagnostic Medicine

Training Program
INSIDERS GUIDE
Interpretation and treatment:
Organic acid Energy and
oxidative markers and treatment
By Ron Grisanti, D.C. & Dicken Weatherby, N.D.
http://www.FunctionalMedicineUniversity.com
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We have designed this book to provide information in regard to the subject matter covered. It is made available with the understanding that the
authors are not liable for the misconception or misuse of information provided. The purpose of this book is to educate. It is not meant to be a
comprehensive source for the topic covered, and is not intended as a substitute for medical diagnosis or treatment, or intended as a substitute
for medical counseling. Information contained in this book should not be construed as a claim or representation that any treatment, process or
interpretation mentioned constitutes a cure, palliative, or ameliorative. The information covered is intended to supplement the practitioners
knowledge of their patient. It should be considered as adjunctive support to other diagnostic medical procedures.
This material contains elements protected under International and Federal Copyright laws and treaties. Any unauthorized reprint or use of this
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Functional Medicine Training Program Page1 of 18

Insiders Guide Interpretation and treatment: Organic acid
Copyright 2008 Sequoia Education Systems, Inc
Table of Contents
A VERY BRIEF DIDACTIC OVERVIEW .............................................................. 3
Summary of the Citric Acid Cycle and the Significance of Organic Acid .......................................................... 3
ORGANIC ACIDS SIMPLIFIED ........................................................................... 4

DETAILED EXPLANATION OF ORGANIC ACIDS ............................................. 6
DEFICIENCY OF CARNITINE AND COQ10 ..................................................................................... 6
LACTATE AND PYRUVATE .......................................................................................................... 7
KETOGLUTARATE, A-KETOISOVALERATE, A-KETOISOCAPROATE, AND A-KETO--METHYLVALERATE . 8
-HYDROXYBUTYRATE .............................................................................................................. 9
CITRATE, CIS-ACONITATE AND ISOCITRATE ............................................................................... 10
SUCCINATE, FUMARATE, AND MALATE ...................................................................................... 11
HYDROXYMETHYLGLUTARATE (HMG) ...................................................................................... 11
XANTHURENATE ..................................................................................................................... 12
-HYDROXYISOVALERATE ........................................................................................................ 12
METHYLMALONATE ................................................................................................................. 13
FORMIMINOGLUTAMATE (FIGLU) ............................................................................................. 14
P-HYDROXYPHENYLLACTATE ................................................................................................... 14
8-HYDROXY-2-DEOXYGUANOSINE ............................................................................................ 15
2-HYDROXPHENYLACETIC ACID ............................................................................................... 15
4-HYDROXPHENYLPYRUVIC ACID ............................................................................................. 15
HOMOGENTISIC ACID ............................................................................................................... 16
A-KETOADIPIC ACID (AKAA) ................................................................................................... 16
GLUTARIC ACID ...................................................................................................................... 16
OROTIC ACID ......................................................................................................................... 17
PYROGLUTAMIC ACID .............................................................................................................. 17
ADIPIC ACID ........................................................................................................................... 17
B-OH-B-METHYGLUTARIC ACID (HMG) .................................................................................... 18
B-OH-BUTYRIC (BHBA) ......................................................................................................... 18

A Very Brief Didactic Overview
Summary of the Citric Acid Cycle and the Significance of Organic Acid
Diagram by MetaMetrix- www.metametrix.com

The citric acid cycle, also known as the tricarboxylic acid cycle (TCA cycle) or the Krebs cycle
occurs in the matrix of the mitochondrion.
The citric acid cycle is the all important metabolic pathway which uses a series of enzyme-
catalysed chemical reactions involved in the conversion of carbohydrates, fats and proteins
into carbon dioxide and water to generate a form of usable energy.
Other relevant reactions in the pathway include those in glycolysis and pyruvate oxidation
before the citric acid cycle, and oxidative phosphorylation after it.
Glycolysis is the sequence of reactions that converts glucose into pyruvate with the
concomitant production of a relatively small amount of adenosine triphosphate (ATP).
Pyruvate decarboxylation is the biochemical reaction that uses pyruvate to form acetyl-CoA,
releasing reducing equivalents and carbon dioxide.
Oxidative phosphorylation is a metabolic pathway that uses energy released by the

oxidation of nutrients to produce adenosine triphosphate (ATP).
Adenosine-5'-triphosphate (ATP) has been coined the "molecular currency" of intracellular

energy transfer. ATP is considered by biologists to be the energy currency of life.
It is the high-energy molecule that stores the energy we need to do just about everything we
do.
As food in the cells is gradually oxidized, the released energy is used to re-form the ATP
so that the cell always maintains a supply of this essential molecule
In short, the Citric Acid Cycle supplies the body with its primary energy needs. Any metabolic
glitches or blocks in the citric acid cycle or impairments in any of these processes may lead to
chronic fatigue, muscle pain and fatigue, accelerated cell breakdown, and unhealthy aging.
Because enzyme cofactors are involved in virtually every system in the body, insufficiencies in
these vitamins or minerals can affect a wide range of functions, including immunologic,
endocrine, musculoskeletal, and metabolic.
Organic Acids Simplified

The Organic Acid Profile is like an emission test performed on your car. The exhaust is
examined to see how efficiently the engine is burning fuel. Similarly, certain compounds called
organic acids in your urine reveal the efficiency of your bodys machinery.
Many organic acids result from the metabolic pathways, or chemical reactions, your body uses
to transform food into energy, growth, maintenance, and repair of body tissue. Like spark plugs
that ignite fuel in a car engine, vitamins and other essential nutrients are necessary for these

chemical reactions that power your metabolic machinery. Thousands of these reactions occur
in your body every second and are the basis of your level of health and vitality.
The figure below illustrates a well-functioning metabolic pathway. Molecule A is converted to

Molecule B by the enzyme AB. Molecule B is converted to Molecule C by the enzyme BC and
so on all the way down the metabolic pathway. Many enzymes require nutrients such as
specific vitamins and minerals in order to perform their functions in converting one molecule to
another.
Adapted from Metametrix interpretation guide for Organic Acids- metametrix.com

If specific nutrients are not available in adequate amounts, important reactions cannot occur as
well as they should. The illustration below shows what happens when the nutrient is not
present in adequate amounts so that enzyme AB functions inefficiently. A small amount of
Molecule A is converted to Molecule B and the remainder builds up and spills into the urine.
Notice that Molecules B through D downstream are also affected.

Visualize this process as a dam blocking a stream very little water flowing downstream and
an overflow occuring upstream. The Organic Acid test measures the overflow of certain
organic acids in the urine to determine what blockages may be occurring in the metabolic
pathways due to nutrient insufficiencies or other issues.
High levels of many organic acids can indicate which nutrient insufficiencies may be affecting
your patients health.

Detailed Explanation of Organic Acids
Deficiency of Carnitine and CoQ10
Adipate, Suberate, and Ethylmalonate are all functional markers for deficiency of carnitine
Carnitine is needed to move fatty acids into the mitochondria where they are converted to
energy using vitamin B2. When insufficient levels of carnitine or vitamin B2 slow down this
process, other parts of the cellular machinery take over and make adipate and suberate. A
similar block in another pathway causes high ethylmalonate. Since most of your bodys energy
is produced from the burning of fatty acids, your muscles and brain suffer when this cellular
energy pathway is blocked.
Anything that interferes with the normal fatty acid oxidation may reveal high levels of these
metabolites. Rule out environmental toxin exposure, excessive aspirin use
If HIGH
Consider supplementing with carnitine and vitamin B2. Lysine being a precursor of carnitine, it
may also be of value. Carnitine supplementation has been documented to improve
Alzheimers, age-related cognitive decline, and cardiac function.

Lactate and Pyruvate
Lactate is the principal product of glucose metabolism in skeletal muscle and is a major player
in anaerobic energy production and gluconeogenesis. High levels are commonly associated
with coenzyme Q10, biotin and lipoic acid deficiencies. The following should be ruled in or out
to determine the underlying reason why lactic acid is elevated: overwhelming infection,
hypoxia, high intake of acetaminophen, increased consumption of alcohol, cocaine, increased
iron levels, drug side effects (metformin). Rule out diabetes. High lactate can cause muscle
cramping, fatigue and brain fog.
If HIGH
Consider supplementing with CoQ10, Vitamin B1, B2, B3, B5, Lipoic acid and Biotin.
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-
carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino
acids.
Pyruvate is another major player in anaerobic energy production and gluconeogenesis. May
be elevated when B1, B5 and lipoic acid are insufficient.
Suspect lipoic acid deficiency when the combination of lactate and pyruvate are high. Many
studies have shown that lipoic acid is helpful in treating diabetes and for assisting the liver with
removing toxins from the body.
When the pyruvate marker is high, it is important to quickly scan to see if alpha-ketoglutarate,
alpha-ketoisovalerate, alpha-ketoisocaproate, and alpha-keto-beta-methylvalerate are
also high. All of these analytes share a common enzyme complex all relying on the same
coenzymes: Vitamin B1, B5, lipoic acid, B2, and B3. (in descending order of significance).
Lactate elevations, alone (meaning, not in combination with elevated Pyruvate) suggests
CoQ10 deficiency.

Ketoglutarate, a-Ketoisovalerate, a-Ketoisocaproate, and a-Keto-
-methylvalerate
Vitamins B1 (thiamin), B3 (niacin), and B5 (pantothenic acid) are necessary for energy
pathways of all of the cells in your body. As your food is broken down, specific compounds are
formed at steps that require B vitamin assistance. Ketoglutarate, a-Ketoisovalerate, a-
Ketoisocaproate, and a-Keto--methylvalerate are some these compounds. Alpha-
ketoisovaleric Acid, Alpha-ketoisocaproic Acid and Alpha-keto-betamethylvaline
Acid are metabolites of amino acids valine, leucine, & isoleucine, respectively. The production
of these metabolites require vitamins B1, B3, B5 and lipoic acid.
If HIGH
Impaired metabolism due to cofactor insufficiencies or toxic metals; OR maple syrup urine
disease (if markedly elevated).
Supplement cofactors (vitamins B1, B2, B3, B5, Mg, cysteine, or lipoic acid); remove toxic
metals (As, Hg, Sb, Cd)
If LOW
Possible low B6; OR secondary to low branched-chain amino acids.
Clinical Note: If patient is on Clofibrate (Clofibrate is a lipid lowering agent used for controlling
the high cholesterol) this marker might have diminished sensitivity.
Acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its

main use is to convey the carbon atoms within the acetyl group to the citric acid cycle to be
oxidized for energy production. In chemical structure, acetyl-CoA is the thioester between
coenzyme A (a thiol) and acetic acid (an acyl group carrier). Acetyl-CoA is produced during the
second step of aerobic cellular respiration, pyruvate decarboxylation, which occurs in the
matrix of the mitochondria. Acetyl-CoA then enters the citric acid cycle.

-Hydroxybutyrate
-Hydroxybutyrate is a metabolic marker of blood sugar utilization and insulin function.

Elevated -Hydroxybutyrate is a sign that extra chromium and vanadium may be warranted.
It is also a byproduct of ketosis. Ketosis occurs when cells do not get a steady supply of sugar
from dietary carbohydrate, so they burn fat instead. If you do not eat carbohydrate-rich foods
or if your insulin is not working, then you can have metabolic ketosis. It is not necessarily a
serious matter, but your doctor may need to find out just what the cause is.
Beta-hydroxymethylbutyrate is a ketone body.
If HIGH
Consider supplementing with chromium, vanadium, and lipoic acid.

Citrate, Cis-Aconitate and Isocitrate
If HIGH
Impaired metabolism due to toxic metals (Fl, Hg, As, Sb) OR low cofactors (Fe, GSH
depleted in oxidative stress); OR high amounts of dietary citric acid; OR metabolic acidosis (if
mildly increased cisaconitic acid but markedly increased citric acid).
High Citrate and Cis-aconitate can indicate arginine insufficiency for ammonia clearance
through the Urea Cycle
Consider supplementing with arginine
Rule out toxic metals; glutathione, N-acetylcysteine, Mg, or L-glutamine; consider anti-
oxidants; rule out pancreatic insufficiency (can lead to metabolic acidosis from deficient
bicarbonate).
If LOW
Low or high pyruvic acid or low acetyl CoA (from fatty acid oxidation)
Arginine is a conditionally essential amino acid that is critical for your cardiovascular health
and detoxification functions. The amino acid, arginine, is used to make the powerful blood
vessel regulator, nitric oxide. Nitric oxide acts to lower blood pressure. Too little arginine can
lead to high blood pressure.
If HIGH
Impaired metabolism due to low cofactors (B3, Mg, Mn) or inhibition by aluminum.
High Isocitrate can indicate arginine insufficiency for ammonia clearance through the
Urea Cycle
Consider supplementing with arginine
Rule out Al toxicity; consider vitamin B3, Mg, Mn supplementation.
If LOW
2 to subnormal upstream metabolites; OR same causes of high cisaconitic acid

Succinate, Fumarate, and Malate
Succinate, Fumarate, and Malate are used in the bodys metabolic pathway that generates
cellular energy the Citric Acid Cycle. Higher levels of these compounds in urine indicate
inefficiencies in energy production. If ketoglutarate is elevated along with succinate, malate,
and fumarate, you may need additional CoQ10.
Succinate, Fumarate, and Malate are all involved in mitochondrial oxidation. Succinate,
Fumarate are metabolites of the amino acids leucine & isoleucine and phenylalanine &
tyrosine respectively.
Common symptoms of high levels of the above may include: fatigue, weakness, myocardial
degeneration, neurological degeneration.
If HIGH
Consider supplementing with CoQ10, riboflavin (B2) and magnesium.
SPECIAL CONSIDERATION
Succinate metabolism may be impaired due to low cofactors (Fe or B2); OR bacterial
degradation of glutamine.
If LOW
Consider over-utilization of the Citric Acid Cycle. Fatigue and weakness are common
symptoms.
Consider supplementing with L-Leucine, L-Isoleucine and Vitamin B12 with low succinate,
tyrosine & phenylalanine with low fumarate and balanced amino acid blend with low malate.
Hydroxymethylglutarate (HMG)
Hydroxymethylglutarate (HMG) is a metabolic precursor of cholesterol used by your cells to

make CoQ10, a nutrient that enables the body to use oxygen to generate large amounts of
energy. Cholesterol-lowering statin drugs block this process, causing HMG to become
elevated and inhibiting the production by the cells of CoQ10. While there can be other causes
for this metabolic block, high levels of HMG generally indicate need for CoQ10
supplementation. Since your body can make coenzyme Q10, it is not called a vitamin. If you
are making enough to meet the demands of your tissues, you do not need to take any extra.
However, many people do not make enough coenzyme Q10. Elevation of
Hydroxymethylglutarate can reveal a block in your bodys synthesis of coenzyme Q10.
Other functional markers such as Lactate, Succinate, Fumarate, and Malate, indicate
whether your body is able to produce energy efficiently by utilizing coenzyme Q10.

Xanthurenate
Xanthurenate is a functional marker of B6 (Pyridoxine) and is a metabolite of the amino acid

tryptophan. High levels can indicate an insufficiency of B6, a vitamin critical for all protein
metabolism. Use of medications such as oral contraceptives, anti-hypertensives, and
bronchodilators and exposure to tobacco smoke as well as pesticides and other agricultural
products can all contribute to insufficiency of vitamin B6. Problems with balance, fatigue, and
mental/emotional stability (such as PMS and ADHD), high homocysteine, peripheral
neuropathy, lymphopenia are frequently found in patients with inadequate vitamin B6.
Research has shown that symptoms of autism can be ameliorated with vitamin B6
supplementation. Additionally, xanthurenate can prevent insulin from performing its vital role in
blood sugar regulation, which can contribute to diabetes.
If HIGH
Low B6; may also indicate low vitamin B3 and/or picolinic acid.
Supplement vitamin B6, possibly also B3 and picolinic acid
-Hydroxyisovalerate
-Hydroxyisovalerate is a sensitive indicator of biotin deficiency and is a metabolite of the

amino acid isoleucine. Until recently, biotin deficiency was very difficult to determine in humans
because this vitamin deficiency affects health in ways that mimic many other conditions.
Doctors were likely to overlook biotin deficiency until this test was discovered. Beta()-
hydroxyisovalerate is a specific and sensitive metabolic marker for functional biotin deficiency.
As your biotin intake decreases, your -hydroxyisovalerate excretion increases.Biotin
deficiencies develop for a number of reasons, including pregnancy, antibiotic use, dysbiosis
and anticonvulsant therapy. It is important to remember that raw egg whites are rich in the
glycoprotein, avidin which binds with biotin leading to a deficiency. Symptoms can include hair
loss, skin rash, dermatitis, immune deficiencies, gait disturbances, tremors and muscle
weakness.
If HIGH:
Consider supplementing with biotin. Include biotin rich foods such as cooked eggs, fish, dairy
products, legumes, cruciferous vegetables, sweet potatoes and lean beef.
Address dysbiosis

Methylmalonate
Methylmalonate is a functional marker of vitamin B12 and a metabolite of the amino acid
valine. High levels indicate insufficient vitamin B12. Increased alcohol consumption, dysbiosis,
aging and HIV infection will all have a detrimental impact on B12 absorption.
Common symptoms may include: Anemia, fatigue, elevated homocysteine, ischemic heart
disease, stroke, deep vein thrombosis, paresthesias and GI disorders
Consider supplementing with B12 sublingual or IV B12 (if oral is ineffective). Stop alcohol and
address dysbiosis.

Formiminoglutamate (FIGLU)
Formiminoglutamate (FIGLU) is a functional marker of insufficiency of folic acid and is a

compound made from the amino acid histidine. High levels indicate insufficient folic acid.
Increased alcohol consumption, excessive consumption of processed foods, oral
contraception, smoking and pregnancy will all have a detrimental impact on folic acid
absorption.
Common symptoms may include: Anemia, fatigue, elevated homocysteine, ischemic heart
disease, stroke and deep vein thrombosis. Pregnant women especially need to have adequate
folic acid to prevent birth defects. Folic acid insufficiency can play a role in childhood
development problems, depression, immune function, and is a risk factor for cardiovascular
disease.
If HIGH
Consider supplementing with folic acid. Stop alcohol. If homocysteine is elevated, consider
using 5-methyltetrahydrofolate.
Elevations of homocysteine, methylmalonate and formiminoglutamate are the most sensitive

markers and indicators for megaloblastic anemia
Vitamins C and E and coenzyme Q10 are grouped together because they are all involved in
antioxidant protection. The special role of antioxidant vitamins is to protect your cells from
damage. Without them, your rate of aging and risk of chronic disease are increased.
p-Hydroxyphenyllactate
p-Hydroxyphenyllactate is a metabolite of the amino acid Tyrosine. It is a sensitive marker

for the depletion of methyl- p-hydroxyphenyllactate which is an important cell growth inhibiting
agent. Due to its pro-oxidative character high levels are associated with carcinogenesis.
If HIGH
Consider supplementing with Vitamin C. Vitamin C is easily lost from the body and must be
replaced frequently. Most experts agree that the average healthy person needs a minimum of
100-150 mg of vitamin C per day to stay healthy.

8-Hydroxy-2-deoxyguanosine
8-Hydroxy-2-deoxyguanosine is marker for oxidative damage to DNA. Causes of increased

levels of 8-Hydroxy-2-deoxyguanosine may be due to stress, smoking, chronic inflammation,
diabetes, air pollution, high polyunsaturated fat intake, irradiation, thermal injury, heavy metal
and pesticide toxic exposure.
If HIGH
Consider supplementing with Vitamin C, E, lipoic acid and NAC. Also consider using green tea,
grapes and berries. Although an increase consumption of alcohol will have a detrimental
impact on this marker, an occasional glass of red wine may be of value due to its high level of
flavonoids.
High levels of p-Hydroxyphenyllactate, 8-Hydroxy-2-deoxyguanosine, Glucarate, and

Quinolinate are associated with increased oxidative stress. Significant elevations in one or
more of these compounds could indicate a strong need for other antioxidants as well.
2-Hydroxphenylacetic Acid
Metabolite of phenylalanine
If HIGH
Excessive phenylalanine (dietary or PKU) or tyrosine; OR reduced oxygenation (e.g., iron
deficiency anemia, pulmonary disorder); OR low tetrahydrobiopterin (BH4), which may result in
low neurotransmitters and/or nitric oxide
CONSIDER
Amino Acid Analysis is recommended to rule out excessive phenylalanine &/or tyrosine.
Correct oxygenation if relevant.
Supplement vitamin C (increases BH4 levels in body).
5-MTHF (from folic acid) may help nitric oxide production when BH4 is low
4-Hydroxphenylpyruvic Acid
(Metabolite of tyrosine, precursor of homogentisic acid)

If HIGH
Impaired metabolism to homogentisic acid due to cofactor insufficiencies (copper, vitamin C,
O2); OR possible low iron (if homogentisic acid is markedly elevated);
Supplement vitamin C or Cu, improve oxygenation
(e.g., correct anemia, pulmonary problems, cardiac insufficiency, etc.)

Homogentisic acid
IF HIGH
Impaired metabolism due to cofactor insufficiency (iron, vitamin C, O2); OR alkaptonuria (rare)
CONSIDER
Supplement iron (if low), vitamin C, improve oxygenation
Consider NAC to protect enzyme
a-Ketoadipic Acid (AKAA)
(Made from tryptophan and lysine via alpha-aminoadipic acid, also a byproduct of yeast;
precursor of glutaric acid)
If HIGH
May be secondary to high glutaric acid (check glutaric level); OR impaired metabolism due to
cofactor insufficiencies OR toxic metals (As, Hg, Sb, Cd); OR may be secondary to yeast or
fungal infection (derives from alphaaminoadipic acid)see yeast markers.
CONSIDER
Supplement cofactors (vitamins B1, B2, B3, B5, Mg, cysteine, or lipoic acid); remove toxic
metals (As, Hg, Sb, Cd)
Antifungals, anti-yeast diet, probiotics, if relevant Alpha-ketoadipic Acid (AKAA)
Glutaric Acid
Metabolite of lysine and tryptophan.

If HIGH
Possible low FAD (riboflavin) (cofactor for alternative metabolism of one of glutaric acids
precursors); OR inborn error of metabolism; may be associated with CETP genetic
polymorphism.
CONSIDER
Supplement vitamin B2, consider mitochondrial support nutrients (e.g. CoQ10)

Orotic Acid
(Metabolite of aspartic acid.

If HIGH
Possible liver damage (e.g., from alcohol), urea cycle dysfunction, ammonia excess OR;
barbiturates; OR impaired metabolism due to cofactor insufficiencies (vitamins B3, B6, folate,
Mg, glutamine, glycine, serine); OR use of allopurinol or chemotherapy
CONSIDER
Supplement vitamins B3, B6, folic acid, Mg, glutamine, glycine, serine
Consider alpha-ketoglutarate and arginine for ammonia excess, support liver
Pyroglutamic Acid
Intermediate in the recycling of glutathione)

If HIGH
Impaired recycling to glutathione due to cofactor insufficiencies (Mg, cysteine, glycine, glutamic
acid); consistent with deficient GSH
Supplement Mg, N-acetylcysteine (NAC), possible glycine, L-glutamine, &/or GSH
If LOW
Low glutathione (insufficient precursors, toxicity, or oxidant stress)
CONSIDER
Supplement NAC, possible Mg, glycine, L-glutamine, &/or GSH
Identify and correct toxicity
Adipic Acid
(Formed from omega oxidation of fats when beta oxidation is impaired)

If HIGH
Impaired mitochondrial beta oxidation of fats; may be secondary to insufficient carnitine, B2, or
acetyl CoA, or to insulin excess; OR may be secondary to ketosis.
Consider supplementing with L-carnitine or acetyl-L-carnitine, riboflavin, acetyl CoA precursors
(cysteine, B5, Mg)

b-OH-b-Methyglutaric Acid (HMG)
(Formed
from acetyl CoA, precursor of cholesterol and CoQ10)
If HIGH
Citric acid cycle impairment (anaerobic glycolysis); OR
carbohydrate unavailability (e.g., high-protein diet, fasting, diabetes); OR inhibited utilization of HMG
(e.g., from high cholesterol diet, yeast overgrowth, glucocorticoid excess, statins)
CONSIDER
Identify and correct specific underlying imbalance (e.g., remove yeast overgrowth, reduce dietary
cholesterol, remove blocks in citric acid cycle)
b-OH-Butyric (BHBA)
(Ketone formed from acetyl CoA)

If HIGH
Ketosis from carbohydrate unavailability (e.g., fasting, diabetes, strenuous exercise, ketogenic
diet)
CONSIDER
See comments above for HMG)
Credit is contributed to the following labs for their advancement in the field of functional
medicine:
Metametrix Clinical Laboratory
3425 Corporate Way
Duluth, GA 30096
800-221-4640
www.metametrix.com
Genova Diagnostics
63 Zillicoa Street
Asheville, NC 28801
800-522-4762
www.gdx.net


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Functional Medicine Universitys

Functional Diagnostic Medicine

Limits of Liability & Disclaimer of Warranty

Functional Medicine Training Program Page1 of 18

ORGANIC ACIDS SIMPLIFIED ........................................................................... 4

Functional Medicine Training Program Page2 of 18

Diagram by MetaMetrix- www.metametrix.com

Functional Medicine Training Program Page3 of 18

Oxidative phosphorylation is a metabolic pathway that uses energy released by the

Adenosine-5'-triphosphate (ATP) has been coined the "molecular currency" of intracellular

Organic Acids Simplified

Functional Medicine Training Program Page4 of 18

The figure below illustrates a well-functioning metabolic pathway. Molecule A is converted to

Adapted from Metametrix interpretation guide for Organic Acids- metametrix.com

Adapted from Metametrix interpretation guide for Organic Acids- metametrix.com

Functional Medicine Training Program Page5 of 18

Adapted from Metametrix interpretation guide for Organic Acids- metametrix.com

Functional Medicine Training Program Page6 of 18

Functional Medicine Training Program Page7 of 18

Acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its

Functional Medicine Training Program Page8 of 18

-Hydroxybutyrate is a metabolic marker of blood sugar utilization and insulin function.

Functional Medicine Training Program Page9 of 18

Functional Medicine Training Program Page10 of 18

Hydroxymethylglutarate (HMG) is a metabolic precursor of cholesterol used by your cells to

Functional Medicine Training Program Page11 of 18

Xanthurenate is a functional marker of B6 (Pyridoxine) and is a metabolite of the amino acid

-Hydroxyisovalerate is a sensitive indicator of biotin deficiency and is a metabolite of the

Functional Medicine Training Program Page12 of 18

Functional Medicine Training Program Page13 of 18

Formiminoglutamate (FIGLU) is a functional marker of insufficiency of folic acid and is a

Elevations of homocysteine, methylmalonate and formiminoglutamate are the most sensitive

p-Hydroxyphenyllactate is a metabolite of the amino acid Tyrosine. It is a sensitive marker

Functional Medicine Training Program Page14 of 18

8-Hydroxy-2-deoxyguanosine is marker for oxidative damage to DNA. Causes of increased

High levels of p-Hydroxyphenyllactate, 8-Hydroxy-2-deoxyguanosine, Glucarate, and

(Metabolite of tyrosine, precursor of homogentisic acid)

Functional Medicine Training Program Page15 of 18

a-Ketoadipic Acid (AKAA)

Metabolite of lysine and tryptophan.

Functional Medicine Training Program Page16 of 18

(Metabolite of aspartic acid.

Intermediate in the recycling of glutathione)

(Formed from omega oxidation of fats when beta oxidation is impaired)

Functional Medicine Training Program Page17 of 18

(Ketone formed from acetyl CoA)

Functional Medicine Training Program Page18 of 18

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