OMX Organic Metabolomics / Diagnostic Solutions

Advanced Organic Acids and Amino Acids Profile

Metabolomics, also called comprehensive metabolic profiling, evaluates patterns of metabolites related to core biological systems, offering insight into biochemical dysfunctions that may be of concern.

Organic acids and other small molecules are intermediate compounds that can define the efficient flow of pathways and substrates such as amino acids to reveal the level of inputs, which together establish the functional status of key areas of health.

Metabolites are impacted by many factors and can change in response to diet, nutrient status, toxin exposures, exercise, physiologic demands, genetics, gut microbiome alterations, or disease stage.

Metabolic analysis can help to evaluate the function of key pathways to better target support.

OMX Provides Insight Into the Following Areas of Health:

- Metabolic and macronutrient processing

- Nutritional and vitamin status

- Level and flow of amino acid

- Detoxification

- Mood issues

- Gut concerns

- Overall well-being

1-Methylhistidine

Optimal range: 88 - 394.4 nmol/mg Creatinine

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.

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1-Methylhistidine (Plasma)

Optimal range: 0 - 16 nmol/ML

1-methylhistidine is derived from the dipeptide anserine (which consists of the amino acids 1-methylhistidine and beta-alanine). Anserine and its derivatives are associated with the consumption of poultry and fish. Both 1-methylhistidine and 3-methylhistidine have been proposed as markers of meat intake. Note that confusion exists in the literature regarding the numbering of atoms in the imidazole ring of histidine – 1 versus 3 – and thus, there is caution with interpretation and clinical significance of these two markers.

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2-,3-, and 4-Methylhippuric acid

Optimal range: 0 - 0.6 nmol/mg Creatinine

2-Methylhippuric Acid (2MHA), 3-Methylhippuric Acid (3MHA), 4-Methylhippuric Acid (4MHA) -- These are metabolites of xylenes, solvents found in paints, lacquers, cleaning agents, pesticides, and gasoline. Exposure to xylenes generates methylhippuric acid isomers.

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2-Methylhippuric Acid

Optimal range: 0 - 2.1 nmol/mg Creatinine

2-Methylsuccinic Acid

Optimal range: 3.7 - 36 nmol/mg Creatinine

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.

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3,4-Dihydroxyhydrocinnamic Acid

Optimal range: 0 - 4.4 nmol/mg Creatinine

- 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

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3,5-Dihydroxybenzoic Acid

Optimal range: 0 - 521.8 nmol/mg Creatinine

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.

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3-Methylhistidine (Plasma)

Optimal range: 0 - 26.9 nmol/ML

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.

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3-Phenylpropionylglycine

Optimal range: 0 - 0.5 nmol/mg Creatinine

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.

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4-Hydroxybenzoic Acid

Optimal range: 1.4 - 15.7 nmol/mg Creatinine

(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.

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4-Hydroxyphenylacetic Acid

Optimal range: 43.1 - 528.1 nmol/mg Creatinine

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.

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4-Hydroxyphenylpyruvic Acid

Optimal range: 0 - 355.9 nmol/mg Creatinine

AKA: 4-Hydroxyphenylpyruvate, 4-HPPA

4-hydroxyphenylpyruvic acid is an intermediate in the breakdown of phenylalanine.

4-hydroxyphenylpyruvic acid is converted to homogentisate; a blockage at this step results in increased homogentisate, which can be diagnostic of alkaptonuria.

If the pathway is not blocked, 4-HPPA ends up in the Krebs cycle converted into fumaric acid.

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5-Hydroxyindoleacetic Acid

Optimal range: 0 - 23.3 nmol/mg Creatinine

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.

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8-Hydroxy-2'-deoxyguanosine

Optimal range: 0 - 6.4 nmol/mg Creatinine

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.

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a-Hydroxybutyric Acid

Optimal range: 15.4 - 95.6 nmol/mg Creatinine

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).

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a-Keto-b-methylvaleric Acid

Optimal range: 0 - 83.5 nmol/mg Creatinine

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.

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a-Ketobutyric Acid

Optimal range: 0 - 12.6 nmol/mg Creatinine

- 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.

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a-Ketoglutaric Acid

Optimal range: 0 - 169.6 nmol/mg Creatinine

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.

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a-Ketoisocaproic Acid

Optimal range: 0 - 20.4 nmol/mg Creatinine

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.

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a-Ketoisovaleric Acid

Optimal range: 0 - 6.1 nmol/mg Creatinine

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

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a-­Aminoadipic Acid (Plasma)

Optimal range: 0 - 4.8 nmol/ML

- An intermediate metabolite of lysine metabolism, produced primarily under oxidative stress (metal-catalyzed oxidation).

- In adolescents, α-aminoadipic acid was associated with adipogenesis and insulin resistance.

- Higher plasma α-aminoadipic acid was associated with a 4-fold risk of future diabetes and identified risk up to 12 years before the onset of overt disease.

- BCAAs, cystine, α-aminoadipic acid, phenylalanine, and leucine + lysine were significantly increased in obesity, T2D, and with worsening health.

Alpha-aminoadipic acid (also known as 2-aminoadipic acid) is an intermediary biomarker of lysine and tryptophan metabolism. The further metabolism of alpha-aminoadipic acid to alpha-ketoadipic acid requires vitamin B6.

Plasma alpha-aminoadipic acid is strongly associated with the risk of developing diabetes as seen in an assessment of the Framingham Heart Study data. Circulating levels were found to be elevated for many years prior to the onset of diabetes. Preclinical data shows it may also play a role in oxidation and atherosclerotic plaque formation.

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Adipic Acid

Optimal range: 4.3 - 55.6 nmol/mg Creatinine

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

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Alanine

Optimal range: 65.4 - 572.6 nmol/mg Creatinine

Alanine (Plasma)

Optimal range: 271.5 - 730 nmol/ML

- In a review of 46 studies higher plasma alanine was a potential predictor of insulin resistance and diabetes.

- In a review of baseline urine markers and conventional metabolic assessments, with a 5-year follow up, elevated baseline urine alanine was found to correlate with elevated levels of A1C (effect size >.8) and insulin resistance, independent of weight.

- Plasma alanine and asparagine were reduced in B6 deficiencies in animal studies.

- Plasma alanine and glutamic acid both positively correlated with depression.

- Branched-chain amino acids (BCAA) are the primary nitrogen source for glutamine and alanine synthesis; BCAA are associated with metabolic disease.

- Blood alanine was lower in IBD compared to controls.

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Aldosterone

Optimal range: 0 - 2.1 mcg/g Creat.

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.

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Anserine (Plasma)

Optimal range: 0 - 18.4 nmol/ML

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.

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Anthranilic Acid

Optimal range: 0 - 11.9 nmol/mg Creatinine

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.

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Arabinitol

Optimal range: 0 - 9 nmol/mg Creatinine

- 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.

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Arginine (Plasma)

Optimal range: 36.9 - 112.2 nmol/ML

Arginosuccinic Acid

Optimal range: 0 - 49.7 nmol/mg Creatinine

Arginosuccinic Acid (Plasma)

Optimal range: 0 - 14.2 nmol/ML

Asparagine (Plasma)

Optimal range: 15.6 - 62.7 nmol/ML

Asparagine is a non-essential protein amino acid that is present in many fruits and vegetables including asparagus, from which it gets its name. Other dietary sources include meat, potatoes, eggs, nuts, and dairy. It can also be formed from aspartic acid and glutamine using the enzyme asparagine synthetase.

In addition to being a structural component of many proteins, asparagine is also useful to the urea cycle. It acts as a nontoxic carrier of residual ammonia to be eliminated from the body. Asparagine is rapidly converted to aspartic acid by the enzyme asparaginase. Interestingly, L-asparaginase has been successfully used as a chemotherapeutic agent for decades.

It causes extracellular depletion of asparagine which seems to play a critical role in cellular adaptations to glutamine and apoptosis.

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Aspartic Acid (Plasma)

Optimal range: 5.4 - 21.5 nmol/ML

Aspartic acid is a nonessential amino acid that plays roles in many important metabolic processes, such as energy production (citric acid cycle), hormone metabolism, CNS activation, and the urea cycle. It is found in many protein sources such as oysters, meats, seeds, avocado, asparagus, and beets. It is also an ingredient in artificial sweeteners.

Aspartic acid is a precursor to many amino acids and other molecules like asparagine, arginine, isoleucine, lysine, methionine, isoleucine, threonine, nucleotides, NAD, and pantothenate. Aspartate, like glutamine, can also be considered a neuroexcitatory neurotransmitter since it activates the N-methyl-D-aspartate receptor in the brain.

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b-Hydroxybutyric Acid

Optimal range: 3.2 - 116.4 nmol/mg Creatinine

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.

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b-Hydroxyisovaleric Acid

Optimal range: 0 - 102.8 nmol/mg Creatinine

b-­Hydroxyisovaleric Acid [aka 3-Hydroxyisovaleric Acid (3-HIA)] is formed from the metabolism of the branched-chain amino acid leucine. Methylcrotonyl-CoA carboxylase catalyzes an essential step in this pathway and is biotin dependent. Reduced activity of this enzyme leads to an alternate pathway of metabolism resulting in 3-hydroxyisovaleric acid.

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b-­Alanine (Plasma)

Optimal range: 0 - 0.7 nmol/ML

β-alanine is a breakdown product of carnosine and anserine, which are dipeptides from meat consumption. Although β-alanine’s properties are limited, its relationship to carnosine makes it important. Both have antioxidant properties. Carnosine is critical for pH buffering in skeletal muscle during exercise, but its formation can be limited by enzymatic factors.

For this reason, supplementation with β-alanine is sometimes used to enhance carnitine and therefore improve athletic performance. In addition to diet and supplementation, β-alanine can also be endogenously produced. This occurs via degradation of uracil in the liver but it can also be made by intestinal bacteria such as E. coli.

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Benzoic Acid

Optimal range: 0 - 621.4 nmol/mg Creatinine

Benzoylform

Optimal range: 0 - 3.6 nmol/mg Creatinine

Branched Chain Alpha-Keto Organic Acids

Optimal range: 2.2 - 91.9 nmol/mg Creatinine

- 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.

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Carnosine

Optimal range: 3.9 - 70 nmol/mg Creatinine

Carnosine (Plasma)

Optimal range: 0 - 2.7 nmol/ML

Carnosine (beta-alanyl-L-histidine) is a urinary biomarker which comes from the consumption of beef, pork, and to a lesser extent, poultry.

It is a dipeptide consisting of the amino acids histidine and beta-alanine and is concentrated in skeletal and heart muscle, brain, and kidneys. Carnosine has antioxidant properties, antiglycation effects, enhanced calcium sensitivity, and pH buffering activity during highintensity exercise.

It also has neuroprotective properties and may play an important role in Alzheimer’s disease and other neurodegenerative diseases.

Carnosine is also protective against secondary diabetic renal complications.

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cis-Aconitic Acid

Optimal range: 126.3 - 668.9 nmol/mg Creatinine

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

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Citric Acid

Optimal range: 203 - 3208.6 nmol/mg Creatinine

- 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.

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Citrulline (Plasma)

Optimal range: 13.8 - 59.7 nmol/ML

Cortisol

Optimal range: 0 - 82 nmol/mg Creatinine

Cortisone

Optimal range: 0 - 250 mcg/g Creat.

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).

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Creatinine

Optimal range: 29.3 - 296.8 nmol/mg Creatinine

Cystathionine (Plasma)

Optimal range: 0 - 0.3 nmol/ML

Cystathionine is an intermediate dipeptide within the process of transsulfuration. Transsulfuration is the main route for irreversible homocysteine disposal, glutathione production, and energy. The initial step involves the enzyme cystathionine β-synthase enzyme (CBS). This reaction requires nutrient cofactors such as vitamin B6 and iron. Cystathionine is then converted to cysteine, and eventually goes on to either make glutathione or feed the Kreb’s cycle. Currently, there is no known source or physiologic function for cystathionine other than serving as a transsulfuration intermediate. Some literature suggests that cystathionine may exert protection against endoplasmic reticulum stress-induced tissue damage and cell death, but studies are sparse.

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Cystine (Plasma)

Optimal range: 13.4 - 51.9 nmol/ML

Cystine is rate limiting for glutathione production. Cystine is the oxidized form of cysteine.

Cystine is formed from the oxidation of cysteine, or from the degradation of glutathione oxidation products. It is two cysteines linked together with a disulfide bond.

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D-Lactic Acid

Optimal range: 0.6 - 29.9 nmol/mg Creatinine

- 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.

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Equol

Optimal range: 0 - 15.4 nmol/mg Creatinine

- 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.

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Ethanolamine (Plasma)

Optimal range: 0 - 16.9 nmol/ML

Ethanolamine is an intermediary metabolite in the serine-to-choline sequence. It can be used to synthesize phosphatidylethanolamine (PE), a very important membrane phospholipid. Ethanolamine is not only a precursor, but also a breakdown product of PE. Ethanolamine is abundant in both intestinal and bacterial cell membranes. It plays a significant role in the renewal and proliferation of intestinal cells and intestinal inflammation. Also, since ethanolamine plays a structural role in skeletal muscle cell membranes, some evidence suggests it may be a marker of skeletal muscle turnover.

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Ethylmalonic Acid

Optimal range: 9.9 - 65.6 nmol/mg Creatinine

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.

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Formiminoglutamic Acid

Optimal range: 0 - 2.7 nmol/mg Creatinine

Formiminoglutamic Acid (FIGlu) is an intermediary organic acid in the conversion of the amino acid histidine to glutamic acid. This enzymatic conversion requires tetrahydrofolic acid.

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Fructose

Optimal range: 0.1 - 9.2 nmol/mg Creatinine

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.

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Fumaric Acid

Optimal range: 0 - 16.1 nmol/mg Creatinine

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

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g-Aminobutyric Acid (Plasma)

Optimal range: 0 - 1.5 nmol/ML

Gamma-aminobutyric acid (GABA) is an amino acid that functions as an inhibitory neurotransmitter. It serves one-third of brain neurons and is involved in depression and mania.

Although there are some dietary supplement and food sources for GABA (cruciferous vegetables, spinach, tomatoes, beans, and rice), the primary source may be endogenous prodution. Nervous tissue, the gut microbiome, the liver, pancreas, and endothelial cells are important sources for production.

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Glucaric Acid

Optimal range: 0 - 31.5 nmol/mg Creatinine

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.

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Glucose

Optimal range: 0 - 15.2 mg/dL

- 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.

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Glutamic Acid (Plasma)

Optimal range: 38.3 - 251.2 nmol/ML

Glutamine (Plasma)

Optimal range: 352.4 - 1017.1 nmol/ML

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.

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Glutamine / Glutamate Ratio (Plasma)

Optimal range: 2.1 - 21.7 nmol/ML

- 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).

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Glutaric Acid

Optimal range: 0 - 8.5 nmol/mg Creatinine

Glutaric Acid (Glutarate) is endogenously produced in the catabolism of lysine and tryptophan.

- Increased Glutaric acid is associated with secondary carnitine deficiency.

- Glutaryl-CoA (from lysine or tryptophan) normally enters the Krebs cycle via transition to acetyl-CoA.

    » Glutaryl-CoA dehydrogenase (GCDH) + glutaryl-CoA + B2 → acetyl-CoA.

    » If GCDH is blocked, glutaryl-CoA + carnitine → elevated glutaric acid.

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Glycine (Plasma)

Optimal range: 154.2 - 582.7 nmol/ML

Glycylproline (Plasma)

Optimal range: 0 - 2.6 nmol/ML

- Patients with pressure sores had significantly increased glycylproline, finding positive predictive value for pressure sores of 70%.

- In an older (1964) review of bone markers of patients with bone disease, researchers found glycylproline only in patients with severe active rickets.

- Urine glycylproline and hydroxylysine patients with pressure sores, compared to controls.

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Hexanoylglycine

Optimal range: 0.7 - 9.6 nmol/mg Creatinine

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

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Hippuric Acid

Optimal range: 198.7 - 3104.6 nmol/mg Creatinine

Histidine (Plasma)

Optimal range: 61.2 - 104.7 nmol/ML

Histidine is involved in one-carbon units for conversion of formiminoglutamic acid (FIGLU) to glutamic acid.

- High plasma histidine has been associated with increased plasma glutamic acid, alanine and glutamine, and decreased branched-chain amino acids.

- Elevated urine histidine means it is not available for hemoglobin production. Hemoglobin is 10% histidine.

- High levels have been associated with progression of type 2 diabetes after gestational diabetes (= a type of diabetes that can develop during pregnancy in women who don't already have diabetes.)

- Decreased plasma histidine was associated with increased risk of ulcerative colitis relapse; a higher serum CRP in Crohn’s disease; chronic kidney disease; increased inflammation; and atopic dermatitis.

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Homocitrulline (Plasma)

Optimal range: 0 - 3.4 nmol/ML

Homocystine (Plasma)

Optimal range: 0 - 2.2 nmol/ML

Homocystine is a common amino acid in your blood. You get it mostly from eating meat. High levels of it are linked to early development of heart disease.

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Homogentisic Acid

Optimal range: 0 - 153.7 nmol/mg Creatinine

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

Elevated in the genetic disease homogentisic aciduria (alkaptonuria).

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Homovanillic Acid

Optimal range: 0 - 42.1 nmol/mg Creatinine

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.

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Hydroxykynurenine

Optimal range: 0 - 18 nmol/mg Creatinine

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

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Hydroxyproline

Optimal range: 0 - 25.3 nmol/mg Creatinine

- 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.

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Hydroxyproline (Plasma)

Optimal range: 0 - 30.6 nmol/ML

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.

- Plasma hydroxylproline may be reduced with fatigue (caused by deprivation of rest and sleep; a physical stress condition) or oxidative stress.

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Indoleacetic Acid

Optimal range: 3 - 55.5 nmol/mg Creatinine

Isocitric Acid

Optimal range: 137.1 - 794.9 nmol/mg Creatinine

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. 

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Isoleucine/allo-Isoleucine (Plasma)

Optimal range: 35.5 - 112.4 nmol/ML

Branched Chain Amino Acids (Isoleucine, Leucine, Valine) are the three branched chain amino acids (BCAAs). Branched chain amino acids (BCAA) are essential amino acids and must be obtained from the diet (mainly meat, grains, and dairy).

Branched-Chain Amino Acids (BCAAs) are required for protein synthesis and are metabolized outside hepatic tissues, unlike most other essential amino acids. They are converted to branched-chain keto acids which require B-complex vitamins. BCAAs have been associated with obesity, weight loss, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). 

BCAA’s are nitrogen donors, facilitate glucose uptake by liver and skeletal muscle, and enhance glycogen synthesis.

- BMI was positively associated with urine 2-hydroxyisobutyrate, isoleucine, valine, tryptophan, and tyrosine.

- Elevated urine levels were associated with higher colorectal cancer.

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KT Ratio (Plasma)

Optimal range: 0.018 - 0.101 Ratio

KT Ratio stands for Kynurenine/Tryptophan Ratio (KTR).

What is Tryptophan?

Tryptophan is involved in serotonin production and is the least abundant amino acid.

What is Kynurenine?

Kynurenine is primary breakdown product of tryptophan.

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Kynurenic Acid

Optimal range: 7.8 - 54 nmol/mg Creatinine

Kynurenic Acid is product of the metabolism of L-Tryptophan and appears in urine in Vitamin B6 deficiencies. Your body needs vitamin B6 (pyridoxine) to utilize amino acids derived from dietary protein.

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Kynurenine (Plasma)

Optimal range: 0 - 4.4 nmol/ML

Kynurenine is the primary breakdown product of tryptophan.

- Kynurenine blood levels have been found higher in type 2 diabetes, obesity, CVD, ADHD in children, HOMA-IR.

- Higher kynurenine increases Treg cell differentiation via the AhR (aryl hydrocarbon receptor) pathway.

- Blood levels were lower in acute ischemic stroke patients, older age, adults with ADHD.

- Upregulation of other tryptophan breakdown enzymes KMO (Kynurenine monooxygenase) and KYNU (Kynureninase) may decrease kynurenine.

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Lactic Acid

Optimal range: 12.2 - 458.2 nmol/mg Creatinine

- 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.

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Leucine (Plasma)

Optimal range: 57.1 - 187.5 nmol/ML

Branched Chain Amino Acids (Isoleucine, Leucine, Valine) are the three branched chain amino acids (BCAAs). Branched chain amino acids (BCAA) are essential amino acids and must be obtained from the diet (mainly meat, grains, and dairy).

- Activator of mTOR

- 3-hydroxymethylglutaric acid (HMG) is an “off-product” intermediate in leucine degradation

- Has an anabolic effect on cell signaling and protein synthesis; an activator of the mammalian target of rapamycin (mTOR).

- Elevated urine levels have been associated with higher colorectal cancer rates and a possible biomarker of rheumatoid arthritis (along with phenylalanine).

- Leucine supplementation has been shown to increase plasma ammonia concentrations.

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Lysine (Plasma)

Optimal range: 210.6 - 498.2 nmol/ML

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.

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Malic Acid

Optimal range: 1 - 27.1 nmol/mg Creatinine

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.

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Mandelic Acid

Optimal range: 0 - 16.9 nmol/mg Creatinine

Methionine (Plasma)

Optimal range: 12.1 - 38.5 nmol/ML

Methionine is an essential amino acid that plays an important role in the methylation cycle. Methionine is obtained from dietary intake or through homocysteine remethylation. Methionine’s dietary sources include eggs, fish, meats, Brazil nuts, and other plant seeds. Methionine is converted to the body’s main methyl donor, S-adenosylmethionine (SAM). This conversion requires the enzyme methionine adenosyltransferase (MAT).

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Methylmalonic Acid

Optimal range: 0 - 24.9 nmol/mg Creatinine

Methylmalonic Acid (MMA) is formed from propionylCoA via methylmalonyl-CoA. Major dietary sources of propionyl-CoA include valine, isoleucine, methionine, threonine, and odd chain fatty acids. MethylmalonylCoA is converted to succinyl-CoA to feed the Citric Acid Cycle via the enzyme methylmalonyl-CoA mutase. This enzyme is very vitamin B2 dependent. In B12 deficiency, methylmalonyl-CoA is hydrolyzed to methylmalonic acid.

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Microalbumin

Optimal range: 0 - 130.4 nmol/mg Creatinine

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.

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Ornithine

Optimal range: 0 - 63 nmol/mg Creatinine

Ornithine (Plasma)

Optimal range: 39 - 132.1 nmol/ML

Orotic Acid

Optimal range: 1.2 - 13.1 nmol/mg Creatinine

Oxalic Acid

Optimal range: 144.9 - 1749.5 nmol/mg Creatinine

pH

Optimal range: 5.5 - 7.7 Units

Phenylacetic Acid

Optimal range: 0 - 8.7 nmol/mg Creatinine

Produced from bacterial degradation of unabsorbed phenylalanine.

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Phenylalanine (Plasma)

Optimal range: 31.7 - 71 nmol/ML

Final products include: DOPA, dopamine, norepinephrine, epinephrine, thyroid hormones, melanin, in TCA cycle, or 4-hydroxyphenylacetic acid.

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Phosphate

Optimal range: 11.2 - 192.4 nmol/mg Creatinine

Phosphoethanolamine (Plasma)

Optimal range: 0 - 6.3 nmol/ML

Phosphoethanolamine is an intermediate in the serine-to-choline sequence. It is both a precursor and byproduct of phospholipid biosynthesis and breakdown. As a precursor to the phospholipid phosphatidylethanolamine, phosphoethanolamine plays a key role in myelination. Elevated phosphoethanolamine reflects brain phospholipid turnover, an indicator of neural membrane synthesis and signal transduction. Research into neurologic conditions like Alzheimer’s disease and Huntington’s disease suggests that depletions of both phosphoethanolamine and ethanolamine accompany neuronal death. Phosphoethanolamine is also important in cartilage structure and function, especially in bone and teeth.

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Picolinic Acid

Optimal range: 0 - 4 nmol/mg Creatinine

Other names: Picolinate

From the breakdown of hydroxykynurenine via ACMS decarboxylase

- Decreased picolinic acid and increased quinolinic acid blood levels noted in suicidal subjects.

- A tryptophan metabolite produced through non-enzymatic conversion.

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Pimelic Acid

Optimal range: 1.5 - 24.8 nmol/mg Creatinine

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.

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Proline (Plasma)

Optimal range: 117.2 - 411.9 nmol/ML

Proline is a nonessential amino acid. It contains a secondary α-imino group and is sometimes called an α-imino acid. Proline, and its metabolite hydroxyproline, constitute a third of the total amino acids found in collagen. Lysine, proline, hydroxyproline, and vitamin C are all important in the synthesis of collagen for skin, bones, tendons, and cartilage. Proline is abundant in meat, bone meal, poultry, salmon, wheat, barley, and corn. In addition to dietary sources, proline can be synthesized from glutamate/glutamine, arginine, and ornithine. It can also be synthesized within enterocytes from degradation of small peptides.

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Pyridoxic Acid

Optimal range: 0 - 98.3 nmol/mg Creatinine

- Pyridoxic acid (4-Pyridoxate) is a catabolic product of vitamin B6 that is excreted in the urine. Pyridoxic acid represents > 90% of vitamin B6 species excreted in the urine, and 40-60% of dietary vitamin B6 intake. Urine 4-pyridoxic acid correlated with plasma PLP and RBC PLP.

- 4-Pyridoxic acid level varies according to vitamin B6 intake and responds within 1–2 weeks to vitamin B6 depletion and repletion. Very low levels (<dl on the report) may indicate B6 need, and very high levels may identify excess intake.

- Increased xanthurenic acid after a tryptophan load may occur in vitamin B6-deficient individuals.

- In a mathematical model without a tryptophan load, xanthurenic acid and kynurenine increased at a more pronounced deficiency. Kynurenic acid may be more sensitive but may also result in a slight decrease.

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Pyroglutamic Acid

Optimal range: 75.8 - 543.8 nmol/mg Creatinine

Pyroglutamic acid (5-oxoproline) is produced and utilized in the gamma-glutamyl cycle. This cycle is needed to assist in the production and recycling of glutathione (GSH), a powerful antioxidant.

Glutathione is a tripeptide, consisting of glutamate, cysteine, and glycine. Using the gamma-glutamyl cycle, GSH is divided into cysteinyl glycine and a gammaglutamyl molecule which attaches to another amino acid for transport across a membrane or into a cell. Gammaglutamyl transferase then splits off that attached amino acid, and the glutamate becomes pyroglutamic acid (5-oxoproline).

Cysteinyl glycine is also broken down and transported into the cell as cysteine and glycine. The entire GSH molecule needs to be reformed intracellularly from pyroglutamic acid by recombining cysteine, glycine, and glutamic acid using GSH synthetase.

This enzymatic reformation requires cofactors such as ATP and magnesium.

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Pyruvic Acid

Optimal range: 0 - 67.4 nmol/mg Creatinine

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.

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Quercetin

Optimal range: 0 - 14.9 nmol/mg Creatinine

Research has noted antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer's, antiarthritic, cardiovascular, and wound-healing effects.

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Quinolinic Acid

Optimal range: 29.4 - 178.5 nmol/mg Creatinine

Kynurenic acid and Quinolinic acid are tryptophan metabolites formed through the kynurenine pathway. Tryptophan is the amino acid precursor to serotonin; its major route for catabolism is the kynurenine pathway. Important products of the kynurenine pathway include xanthurenic acid and kynurenic acid, which can further metabolize into quinolinic acid. The historical importance of this pathway has mainly been as a source of the coenzyme NAD+, which is important for all redox reactions in the mitochondria.

However, it is now understood that kynurenic and quinolinic acid have physiologic implications. This alternate pathway is upregulated in response to inflammation and stress, which can lead to deficient serotonin production. Kynurenic acid has shown some neuroprotective properties in the brain, since it can stimulate NMDA receptors. However, its importance on the periphery is still not fully elucidated. Some studies outline antiinflammatory, analgesic, antiatherogenic, antioxidative, and hepatoprotective properties to peripheral kynurenic acid.

The correlation to levels of urinary excretion needs further study. Quinolinic acid, in and of itself, can be inflammatory and neurotoxic.

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Sarcosine (Plasma)

Optimal range: 0 - 10.4 nmol/ML

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.

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Sebacic Acid

Optimal range: 1.5 - 21 nmol/mg Creatinine

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.

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Serine (Plasma)

Optimal range: 54.2 - 207.4 nmol/ML

- 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.

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Suberic Acid

Optimal range: 0.7 - 9.3 nmol/mg Creatinine

- 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.

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Suberylglycine

Optimal range: 0 - 0.4 nmol/mg Creatinine

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.

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Succinic Acid

Optimal range: 12.3 - 260.4 nmol/mg Creatinine

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

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Sulfocysteine (Plasma)

Optimal range: 0 - 1.4 nmol/ML

Sulfocysteine is the product of sulfite-dependent cleavage of cystine. In the pathway, cysteine becomes sulfite, which converts to sulfate via sulfite oxidase + Mo. If the pathway is blocked, sulfocysteine builds up.

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Tartaric Acid

Optimal range: 9.9 - 408.4 nmol/mg Creatinine

- Tartaric acid is a compound found in plant foods. It has been identified as a biomarker of grape intake, though it has also been identified in other foods. Tartaric acid levels peak at 4–8 hours after intake. Levels in foods vary significantly between types of foods and within individual foods.

- Tartaric acid cannot be processed by humans and is either excreted or utilized by gut bacteria as a carbon source. Some bacteria have genes for tartaric metabolizing enzymes, so levels can be impacted by gut microbiome. The process starts once tartaric acid is released (i.e., grapes are crushed or are invaded by pathogens), making it susceptible to catabolic enzymes from microorganisms, which may reduce it to oxaloacetate, glyceric acid, and pyruvic acid.

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Taurine (Plasma)

Optimal range: 25.9 - 107.2 nmol/ML

Taurine differs from other amino acids because a sulfur group replaces the carboxyl group of what would be the nonessential amino acid, β-alanine. It takes part in biochemical reactions and is not fully incorporated into proteins. In most tissues, it remains a free amino acid.

Taurine’s highest concentration is in muscle, platelets, and the central nervous system. Taurine is mainly obtained via dietary sources (dairy, shellfish, turkey, energy drinks), but can also come from sulfur amino acid metabolism (methionine and cysteine).

It has been proposed that taurine acts as an antioxidant, intracellular osmolyte, membrane stabilizer, and a neurotransmitter.

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Threonine (Plasma)

Optimal range: 51.4 - 184.9 nmol/ML

Total Branched Chain Amino Acids (Plasma)

Optimal range: 211.9 - 577.3 nmol/ML

- BCAAs are key nitrogen donors in the form of glutamic acid, glutamine, and alanine.

- Elevated total BCAAs have been associated with obesity, weight loss, insulin resistance, and NAFLD.

- Elevated plasma BCAAs were associated with an increased risk of hypertension, cardiovascular disease.

- BCAAs are higher in a “Western” diet. Check B6 need.

- Lower levels seen in liver cirrhosis and urea cycle disorders.

- Decreased amino acids are seen with decreased protein and calorie intake; increased tissue uptake, and body losses (urine, sweat, etc.).

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Tryptophan (Plasma)

Optimal range: 36.9 - 87.1 nmol/ML

Three pathways:

- Kynurenine Pathway (primary pathway) – leading to niacin production

- Serotonin/Melatonin

- Indoles

Tryptophan is involved in serotonin production via vitamin B6-dependent pathways resulting in the intermediate 5-hydroxytryptophan (5-HTP).

5-HTP is often used as a supplement for serotonin formation instead of tryptophan, which can be quickly metabolized in other pathways. Serotonin is further metabolized to melatonin via methylation. Because of these downstream conversions, therapeutic administration of 5-HTP has been shown to be effective for depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.

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Tyrosine (Plasma)

Optimal range: 27.8 - 84.5 nmol/ML

- 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.

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Valine (Plasma)

Optimal range: 109.3 - 283 nmol/ML

Valine is a branched-chain amino acid (BCAA).

BCAA’s are nitrogen donors, facilitate glucose uptake by liver and skeletal muscle, and enhance glycogen synthesis.

Branched-Chain Amino Acids (BCAAs) are required for protein synthesis and are metabolized outside hepatic tissues, unlike most other essential amino acids. They are converted to branched-chain keto acids which require B-complex vitamins. BCAAs have been associated with obesity, weight loss, insulin resistance, and nonalcoholic fatty liver disease (NAFLD).

- BMI was positively associated with urine 2-hydroxyisobutyrate, isoleucine, valine, tryptophan, and tyrosine.

- Plasma valine, lysine, and tyrosine positively associated with gestational diabetes mellitus (= a type of diabetes that can develop during pregnancy in women who don't already have diabetes.) and insulin activity.

- Elevated urine levels have been associated in higher colorectal cancer.

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Vannilylmandelic Acid

Optimal range: 5.3 - 36.1 nmol/mg Creatinine

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

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Xanthurenic Acid

Optimal range: 0.6 - 10.2 nmol/mg Creatinine

Xanthurenic acid is produced as part of the kynurenine pathway of tryptophan catabolism, along with kynurenic and quinolinic acid.

From the breakdown of hydroxykynurenine via kynurenine aminotransferases (KAT) +B6

- Elevated xanthurenic acid has been noted with B6 deficiency.

- Elevated levels have been noted as more significant in oral contraceptive users in studies using a tryptophan load.

- In a mathematical model without a tryptophan load, a moderate vitamin B6 deficiency resulted in a slight increase in xanthurenic acid and a slight decrease in kynurenic acid and anthranilate.

- Without a tryptophan load, urine kynurenine and xanthurenic acid both increase in a pronounced B6 deficiency.

- Animal studies found a low urinary excretion ratio of xanthurenic acid/ kynurenic acid as a possible marker of niacin need, proposing that levels may increase with repletion.

- Niacin (vitamin B3) is a product of tryptophan degradation. In alcoholic pellagra patients, the tryptophanniacin pathway is inhibited after the 3-hydroxyanthranilate oxidase step, which can result in increased kynurenic acid, and decreased xanthurenic acid and quinolinic acid.

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