OMX Organic Metabolomics / Diagnostic Solutions

It is a component of the dietary peptide anserine. Anserine is beta-alanyl-1-methyl-L-histidine, and it is known to come from chicken, turkey, duck, rabbit, tuna and salmon.

Methylsuccinic acid is a normal metabolite found in human fluids. Increased urinary levels of methylsuccinic acid (together with ethylmalonic acid) are the main biochemical measurable features in ethylmalonic encephalopathy, a rare metabolic disorder with an autosomal recessive mode of inheritance that is clinically characterized by neuromotor delay, hyperlactic acidemia, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. The underlying biochemical defect involves isoleucine catabolism. 

Moreover, methylsuccinic acid is found to be associated with ethylmalonic encephalopathy, isovaleric acidemia, and medium-chain acyl-CoA dehydrogenase deficiency, which are also inborn errors of metabolism.

Note: These tests are used to check for rare metabolic disorders, usually in infants. There is no apparent reason nor benefit to checking ethylmalonic and methylsuccinic acid levels in adults who aren’t suspected to have rare genetic disorders.

- 3,4-dihydroxyphenylpropionic acid is found in red beetroot, common beet, olives, and correlated with coffee intake.

- One of the most abundant phenolates, formed by microbial transformation of dietary polyphenols and endogenous metabolites such as dopamine, phenylalanine, tyrosine, and tryptophan. 3,4-dihydroxyphenylpropionic acid is highly correlated with homovanillic acid (HVA).

- 3,4-dihydroxyphenylpropionic acid has antioxidant properties and significantly inhibited the secretion of pro-inflammatory cytokines

3,5-Dihydroxybenzoic acid was highly correlated with intake of whole-grain bread and breakfast cereals, and a primary metabolite of alkylresorcinols, a biomarker for whole-grain intake.

Alkylresorcinols are a naturally occurring type of phenolic lipid found in high concentrations in the outer layer and bran of cereal grain, primarily wheat and rye.

3-Methylhistidine is an amino acid which is excreted in human urine.

The measurement of 3-methylhistidine provides an index of the rate of muscle protein breakdown. 3-Methylhistidine is a biomarker for meat consumption, especially chicken. It is also a biomarker for the consumption of soy products.

Phenylpropionylglycine is an acyl glycine. Acyl glycines are normally minor metabolites of fatty acids. However, the excretion of certain acyl glycines is increased in several inborn errors of metabolism. In certain cases the measurement of these metabolites in body fluids can be used to diagnose disorders associated with mitochondrial fatty acid beta-oxidation. Acyl glycines are produced through the action of glycine N-acyltransferase, which is an enzyme that catalyzes the chemical reaction: acyl-CoA + glycine < -- > CoA + N-acylglycine.

(p-Hydroxybenzoate or 4-HB)

- One of the most abundant phenolates formed by the microbiota. It is a product of microbial transformation of dietary polyphenols and endogenous metabolites such as dopamine, phenylalanine, tyrosine, and tryptophan.

- It is found in red huckleberry, coriander, blueberry, Swiss chard, carrots, olive, and sour cherries.

- Coenzyme Q10 is synthesized in multiple steps from the precursor 4-hydroxybenzoic acid. CoQ10 is composed of a benzoquinone ring.

- 4-hydroxybenzoic acid increased on a low FODMAP diet and is positively associated with Firmicutes, Verrucomicrobia, and A. muciniphilia, and negatively with Actinobacteria.

- 4-hydroxybenzoic acid is the common metabolite of all parabens, structurally related benzoic acid (without the OH group) and has potential endocrine activity.

4-Hydroxyphenylacetate is a tyrosine metabolic product of certain Clostridia bacteria. Elevated levels are associated with Clostridia overgrowth, small intestinal bowel overgrowth (SIBO), or small bowel disease. May also indicate celiac disease.

For individuals with normal, healthy intestinal function, the compound p-Hydroxyphenylacetate should not appear as more than background concentrations in urine.

Measurement of 4-hydroxyphenylacetic acid excretion in urine is useful in screening for diseases of the small intestine associated with bacterial overgrowth.

5-Hydroxyindoleacetic acid (5HIAA) is a breakdown product of serotonin that is excreted in the urine. Serotonin is a hormone found at high levels in many body tissues. Serotonin and 5HIAA are produced in excess amounts by carcinoid tumors, and levels of these substances may be measured in the urine to test for carcinoid tumors.

8-hydroxy-2-deoxyguanosine measures the oxidative impact to DNA. 8-hydroxy-2-deoxyguanosine levels will be high if your total antioxidant protection is inadequate.

a-hydroxybutyric acid (2-hydroxybuturic acid [2-HB]) is a marker that relates to oxidative stress.

a-hydroxybutyric acid is an organic acid produced from a-ketobutyrate via the enzymes lactate dehydrogenase (LDH) or a-hydroxybutyrate dehydrogenase (HBDH).

- Alpha-ketobutyric acid results from the breakdown of threonine or methionine during glutathione production.

- Specifically, cystathionine is metabolized to alpha-ketobutyric acid and cysteine.

- a- ketobutyric acid enters the mitochondrial matrix and get converted to propionyl-CoA by the branched chain keto-acid dehydrogenase complex (BCKDHC) and enters the Krebs cycle at succinyl-CoA.

- Evaluate lactate and the branched chain keto acids

- Evaluate alpha-hydroxybutyric acid

- Associated Nutrients: Vitamin B3

- a -Ketobutyric acid is produced from cystine, along with hydrogen sulfide (H2S) as a by-product.

- a- Ketobutyric acid is reversibly converted to a- hydroxybutyric acid.

Alpha-Ketoisovalerate (together with Alpha-Ketoisocaproate and Alpha-Keto-Beta-methylvalerate) requires Vitamins B1, B2, B3, B5 and lipoic acid to be metabolized.

a-Keto-b-Methylvaleric Acid is a B-Complex Vitamin Marker. Vitamins are compounds that your body needs to be healthy. Vitamins are “essential” for proper function, which means that they are not made inside your body and must be consumed in the diet.

A metabolites of isoleucine.

Alpha-Ketoglutarate is an organic acid that is important for the proper metabolism of all essential amino acids. It is formed in the Krebs cycle, the energy-producing process that occurs in most body cells.

2-Ketoisocaproic Acid is a B-Complex Vitamin Marker (Leucine catabolism).

2-Ketoisocaproic Acid is an abnormal metabolite that arises from the incomplete breakdown of branched-chain amino acids.

Adipic Acid, together with Suberate and Ethylmalonate are all functional markers for deficiency of carnitine.

Aldosterone is a mineralcoritcoid and a hormone. It allows the transport of sodium across the cell membrane. Aldosterone is important in blood pressure regulation and also for the volume of blood found in the blood vessels.

Anserine is part of a group of Beta-Amino Acids and Derivatives. Anserine is beta-alanyl-1-methyl-L-histidine, and it is known to come from chicken, turkey, duck, rabbit, tuna and salmon.

Other names: Anthranilate

- Several clinical studies have reported increased excretion of anthranilic acid and other metabolites in bladder cancer patients.

- Anthranilic acid was one of nine markers that positively correlated with proteinuria.

- Anthranilic acid comes from the kynurenine pathway, which is B6 dependent; Anthranilic acid activity may be reduced during vitamin B6 restriction.

- In a mathematical model without a tryptophan load, a moderate B6 deficiency resulted in slight decreases in kynurenic and anthranilic acids.

- Patients with acute intermittent porphyria had significantly increased urinary excretion of kynurenine and anthranilic acid.

- Evaluate for consumption of foods and pharmaceuticals that contain arabinitol.

- Because a common substrate for the production of arabinitol in the body is glucose, reduced intake of dietary sugars is a key therapeutic area for elevated arabinitol.

- Urinary arabinitol has been noted as a marker for invasive candidiasis or infection by Candida fungal species, though other genera are capable of production.

- Microbiome analysis is a reasonable next step if high levels of arabinitol are found in the urine. Treatment of an imbalanced microbiome can help reduce the overgrowth of pathogenic species that have been found to produce arabinitol.

b-hydroxybutyrate is one of the ketone bodies. 

The term ketone body describes any of 3 molecules: acetoacetate, b-hydroxybutyrate, or acetone. Acetoacetate is produced by acetyl-CoA metabolism, b-hydroxybutyrate is the result of acetoacetate reduction, and acetone is produced by the spontaneous decarboxylation of acetoacetate.

Ketone bodies are fundamental for metabolic homeostasis during periods of prolonged starvation. The brain cannot use fatty acids for energy production and usually depends on glucose to meet its metabolic needs. In cases of fasting or starvation, ketone bodies become a major fuel for brain cells, sparing amino acids from being catabolized to gluconeogenesis precursors to be used to supply the brain with energy. After prolonged  starvation, ketone bodies can provide as much as two thirds of the brain's energy needs.

Ketone bodies are strong organic acids that fully dissociate in blood. When ketone body production becomes uncontrollable, the buffering systems are saturated, and blood pH drops; this is a condition known as ketoacidosis.

The two common clinical scenarios for ketoacidosis are diabetic ketoacidosis and alcoholic ketoacidosis.

- Each of the BCAAs is catabolized by a dehydrogenase enzyme forming branched-chain keto acids (BDKA), or 2-oxo acids. The dehydrogenase enzyme is heavily dependent on B-complex vitamins, the lack of which may decrease pathway function, possibly leading to an elevation of the BCKA.

- Early research found a vitamin B1 (thiamin)-responsive form of maple syrup urine disease (MSUD).

- Higher urinary BCKA was found to decrease with B-complex vitamins supplementation.

- Evaluate intake of B-complex, primarily thiamin (B1).

- Evaluate dietary intake or supplementation with branched-chain amino acids.

Cis-Aconitic Acid is involved in both energy production and removal of toxic ammonia.

- Diet has a significant impact on citric acid levels:

    » Increased acid load due to diets high in animal-based proteins, carbonated drinks, and in severe carbohydrate restriction can lead to mild metabolic acidosis, hypercalciuria, and reduced citric-acid excretion.

    » Plant-based diets are associated with increased citric acid. Alkalinization of urine through consumption of citrus foods, alkaline mineral water, fruits and vegetables, or citrate supplements (such as mag-citrate) increase citric acid levels.

- Low urine citric acid has been associated with insulin resistance, metabolic acidosis, bonedensity, hypokalemia, the development of kidney stones, kidney disease, and chronic kidney disease, and immune-mediated inflammatory diseases, including rheumatoid arthritis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, Crohn’s disease, and ulcerative colitis.

Cortisone is the inactive form of cortisol. Cortisone shows minimal biological activity per se, reflecting negligible affinity for the glucocorticoid and aldosterone receptors. The kidney, colon and saliva gland have lots of activity for changing cortisol to cortisone (active to inactive) to keep cortisol off the aldosterone receptor. Cortisone is converted back in the liver, fat, etc. (inactive to active).

- Only elevated is of concern. D-lactic acid is generally produced in minimal quantities by human cells. It comes from three sources,

    1. from human methylglyoxal (MGO) pathway (assumed to be the sole source of blood D-lactate in healthy people),

    2. production by gut bacteria (mostly in patients with short bowel syndrome (SBS)), and

    3. ingestion of preformed D-lactate.

- The source of D-lactic acid is dependent on the situation. MGO is a precursor of glycation of proteins and DNA, resulting in advanced glycation end products (AGEs), which is associated with increased oxidative stress. MGO is predominantly detoxified by the glyoxalase system (requires glutathione), with the majority going to D-lactate.

- Equol is a bacterial-derived metabolite with estrogenic and antioxidant activity. Reductase enzymes secreted by the gut microbiota convert daidzein into equol. Daidzein is an isoflavone from soy, tofu, soy milk, tempeh, miso.

- The ability to produce equol varies among individuals because only people who possess the intestinal bacteria capable of producing equol are regarded as equol producers. Vegetarians reported significantly higher rates of equol production.

- Spot-urine equol levels have been found to correlate strongly with serum concentrations.

- Women with PMS had a significantly higher risk of being an equol nonproducer. Intake of daidzein from soy has been associated with reductions of estrogen-dependent and aging-associated disorders. Isoflavonoid-rich herbal supplement (included daidzein) improved intima-media thickness of carotid arteries (CIMT) and inhibited growth of existing atherosclerotic plaques of postmenopausal women.

Ethylmalonate, together with Adipate and Suberate, gives information about your ability to process fatty acids.

Note: These tests are used to check for rare metabolic disorders, usually in infants. There is no apparent reason nor benefit to checking ethylmalonic and methylsuccinic acid levels in adults who aren’t suspected to have rare genetic disorders.

Emerging research seems to show a relationship between the rise in metabolic diseases and the increased consumption of fructose—particularly consumption of non-natural sources of fructose found in sugar-sweetened beverages and other processed foods.

Elevated fructose levels should be further investigated. Dietary fructose intake should be determined, modified if excessive, and monitored for metabolic changes.

Fumarate (together with Succinate and Malate) is used in the body’s metabolic pathway that generates cellular energy – the Citric Acid Cycle.

AKA: Glucarate / D-Glucaric Acid

- Urinary glucaric acid has been used as an indicator of induced hepatic drug metabolization and elevated with exposure to xenobiotics.

- Levels may indirectly represent P-450 activity or an end-product of the glucuronidation pathway.

- Calcium-D-glucarate is the calcium salt of D-Glucarate.

- Dietary glucaric acid and supplementation with calcium-D-glucarate may suppress cell proliferation and inflammation, induce apoptosis, and have anticancer properties. Glucaric acid from dietary plants may act as a nontoxic β-glucuronidase inhibitor. Glucaric acid is normally in equilibrium with D-glucaro-1,4- lactone, and an increase in dietary glucaric acid increased D-glucaro-1,4- lactone, which suppresses blood and tissue beta-glucuronidase activity. Vegetarians may have higher levels.

- It has been found increased with increased PCBs, toxins, and medications.

- Glucose identifies processing of overall diet. Small amounts of glucose may be found in the urine of healthy individuals.

- Researchers found that those with a high waist-to-hip ratio (WHR), but no history of diabetes, had significantly lower urine glucose excretion.

- Metabolism of glucose – glycolysis – is heavily dependent on magnesium.

Glutamic acid (or Glutamate) is a major mediator of excitatory signals in the brain and is involved in most aspects of normal brain function including cognition, memory and learning.

Glutamine is the most abundant amino acid in the blood and is an important source of energy for many tissues in the body. It is derived from the amino acids histidine and glutamic acid.

- Glutamic acid has been associated with higher BMI, blood pressure, and insulin resistance, while glutamine levels were inversely associated.

- A high plasma glutamine-to-glutamic acid ratio was associated with lower risk of diabetes in the Framingham Heart Study (n=1015).

- Higher glutamine-to-glutamic acid ratio was associated with a better cardiometabolic-risk profile over 10 years in the PRIMED study (n=1879).

Urinary hexanoylglycine is a specific marker for the diagnosis of Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. 

Homogentisic acid is a breakdown product of 4-Hydroxyphenylpyruvic Acid (4-HPPA). 

Elevated in the genetic disease homogentisic aciduria (alkaptonuria).

Homovanillate (aka Homovanillic Acid) is a dopamine metabolite.

Homovanillate and Vanilmandelate are breakdown products from neurotransmitters involved in hormone and nerve impulse transmission, called catecholamines.

3-Hydroxykynurenine is a metabolic intermediate of the kynurenine pathway that elicits neurotoxic effects.

- Hydroxyproline is the key factor in stabilizing collagens.

- Hydroxyproline is abundant in meat and low in plant-based foods. Meat intake increases levels of proline and hydroxyproline.

- Increased hydroxyproline has been found in collagen catabolism (bone resorption, increased reactive oxygen species [ROS]), tissue degradation, muscle damage, or other conditions such as Paget's disease or Alzheimer's disease.

- Proline and hydroxyproline both negatively correlated with a higher likelihood of anxiety, depression, and psychoses.

Citric acid, cis-aconitic acid, and isocitric acid are the first three metabolites in the Krebs Citric Acid energy production cycle, which operates in the mitochondria of your cells. 

- Lactic acid is produced endogenously under anaerobic conditions.

- Main route of lactic acid disposal is conversion to pyruvic acid or excretion via urine.

- Higher urine lactic acid levels have been associated with diabetes, fasting glucose, HOMAIR, IBD, chronic kidney disease, Fanconi syndrome, and age-related macular degeneration.

    » Both L- and D-lactic acids were elevated in diabetes

- Nutrient deficiencies of B1, CoQ10, and/or lipoic acid, have been associated with elevated lactic acid levels in both urine and blood.

- Limited research noting a higher decline of T4 was associated with a low lactic acid, alanine and glycine.

Lysine catabolism leads to collagen and carnitine production.

- Higher plasma valine, lysine, and tyrosine were independently and positively associated with gestational diabetes mellitus and insulin activity.

- Increased urinary lysine was associated with a lower risk of chronic kidney disease (0.73 [0.50-0.90].

- Low lysine has been associated with increased anxiety in human and animal studies.

- Lysine and arginine supplementation were found to reduce anxiety and basal salivary cortisol levels in adults.

- Lower plasma lysine and glutamine levels, and higher glutamic acid, were significantly associated with ADHD.

Malic Acid is involved in the citric acid cycle (aka. Krebs cycle). The citric acid cycle is a series of reactions that occur in the mitochondrion to generate chemical energy that fuels the metabolism.

Albumin is not normally found in urine. Temporary dysfunction of the filtration barrier can occur under certain conditions, including fever, dehydration, a urinary tract infection (UTI), and after vigorous exercise, allowing small amounts of albumin through the barrier.

Recommendations for follow-up include three measurements one month apart. Although microalbuminuria does have relatively benign causes, its presence in urine should be further evaluated for serious and chronic conditions.

Many factors affect levels, including gender, race, blood pressure, time of day, exercise, dehydration, smoking, hypertension, diabetes, muscle mass, and amount of food, water, and salt intake, producing up to a 40% daily variation.

Endothelial dysfunction is likely to be involved in the initiation and development of microalbuminuria, initially reversible but becoming fixed with increasing vascular structural changes.

Produced from bacterial degradation of unabsorbed phenylalanine.

Pimelic acids are excreted in elevated amounts in urine in disorders of mitochondrial beta-oxidation and disorders of peroxisomal beta-oxidation, for which they are of significant diagnostic value.

Pimelic acid originating from fatty acid synthesis pathway is a bona fide precursor of biotin in B. subtilis.

Pyruvic Acid feeds into the citric acid cycle & converts into acetyl CoA. Pyruvate is formed from carbohydrate via glucose or glycogen & secondarily from fats (glycerol) & glycogenic amino acids.

Sarcosine is also known as N-methylglycine. It is an intermediate and byproduct in the glycine synthesis and degradation. Sarcosine is metabolized to glycine by the enzyme sarcosine dehydrogenase, while glycine-N-methyl transferase generates sarcosine from glycine.

Increased urinary products of the omega fatty acid metabolism pathway may be due to carnitine deficiency, fasting, or increased intake of triglycerides from coconut oil, or some infant formulas.

- Plasma serine was found higher in depression, and psychoses including schizophrenia.

- Methionine supplementation significantly increased plasma serine.

- Serine is involved in cysteine and methionine metabolism.

- Blood serine was lower in patients with hypertension.

- Blood serine was lower in patients with greater liver fat fractions, higher alanine transaminase (ALT) and triglyceride, in patients with fatty liver disease.

- Suberic acid is present in the urine of people with fatty acid oxidation disorders.

- A metabolic breakdown product derived from oleic acid.

- Elevated levels of this unsaturated dicarboxylic acid are found in individuals with medium-chain acyl-CoA dehydrogenase deficiency (MCAD).

- Elevated in Schizophrenics

- People with metabolic syndrome or diabetes had significantly elevated adipic acid, suberic acid, lactic acid, and fumaric acid.

- Ketosis is sometimes accompanied by excessive excretion of adipic and suberic acid.

Suberylglycine is an acyl glycine. Acyl glycines are normally minor metabolites of fatty acids. However, the excretion of certain acyl glycines is increased in several inborn errors of metabolism. In certain cases the measurement of these metabolites in body fluids can be used to diagnose disorders associated with mitochondrial fatty acid beta-oxidation.

Succinate (or succinic acid) is an important metabolite that is involved in several chemical processes in the body.

- A higher protein intake or supplementation results in increased levels.

- Low protein intake or inflammation can lead to lower levels.

- Nutrient cofactors of tyrosine pathways include BH4, non-heme iron, vitamins B6 and B3, copper, niacin, vitamin C, magnesium, and SAMe.

- Elevated tyrosine is associated with a higher risk of type 2 diabetes and gestational diabetes and a higher body mass index.

- Tyrosine-supplementation effects on cognition vary – unfavorable effects were noted on working-memory performance in older adults.

- Higher tyrosine was related to better cognitive skills in younger adults.

- Urine and blood tyrosine were noted to be lower in depression.

Metabolite of epinephrine and norepinephrine. Often elevated due to stress induced catecholamine output or lead toxicity.