Fumarate (together with Succinate and Malate) is used in the body’s metabolic pathway that generates cellular energy – the Citric Acid Cycle. This cycle critically supports organ maintenance and neurological function. Fumarate is also a product of the urea cycle. Much like vitamin D, fumaric acid is formed by the body, in the skin, during exposure to sunlight.
Low levels of Fumarate can indicate a general amino acid insufficiency.
Nutritional Considerations:
Low levels of fumarate have been correlated with lower levels of: Tyrosine and/or Phenylalanine, B6, B2, Arginine, Essential Amino Acids and CoQ10.
Clinical Observation:
Use of malic acid supplements (such as magnesium malate) often can help short term as the underlying cause of the low result is clinically determined.
Possible Interfering Factors:
Diet low in protein or insufficient in essential amino acid balance. Use of acid blockers that decrease assimilation/breakdown of ingested protein.
Clinical Considerations:
Some individuals with low level of fumarate may have an increased exacerbation of psoriasis. Low levels may correlate with increased fatigue and sense of low energy to perform daily functions. May wish to look at confirmatory tests for possible low iron status, such as ferritin, TIBC, Total Iron, Transferrin. Can be symptomatic of poor conversion of phenylalanine to tyrosine or altered urea cycle metabolism.
Important Clinical Note:
Since Phenylalanine and Tyrosine feed into the CAC pathway via fumarate, supplementation with these two amino acids may be particularly indicated for individuals with lower mood, since the catecholamine pathway (dopamine, epinephrine, norepinephrine) is also fueled by these amino acids.
- Check levels and intake of amino acids that flow into the Krebs cycle: tyrosine and phenylalanine.
- Evaluate B-complex status.
- In chronic kidney disease in those with type 2 diabetes, urinary fumaric acid and malic acid predicted progression of disease.
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Excess urea cycle function can generate high levels of fumarate, because fumaric acid is one of the urea cycle products.
Higher levels of these compounds in urine indicate inefficiencies in energy production.
Possible causes:
- Impaired metabolism due to low B3
- May be secondary to high pyruvate or lactate
- Yeast overgrowth
Additional investigations:
- Vitamin and Mineral Analysis
- Comprehensive Urine Elements Analysis
- Adrenal Hormone Profile
- Complete Digestive Stool Analysis
Treatment considerations:
- Consider B3 supplementation, unless secondary to high pyruvate or lactate
- Rule out/address yeast overgrowth
If α-ketoglutarate is elevated along with succinate, malate, and fumarate, you may need additional CoQ10, a nutrient that enables the body to use oxygen to generate large amounts of energy.
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1-Methylhistidine, 2-Methylhippuric Acid, 2-Methylsuccinic Acid, 3,4-Dihydroxyhydrocinnamic Acid, 3,5-Dihydroxybenzoic Acid, 3-Methylhistidine, 3-Phenylpropionylglycine, 4-Hydroxybenzoic Acid, 4-Hydroxyphenylacetic Acid, 4-Hydroxyphenylpyruvic Acid, 5-Hydroxyindoleacetic Acid, 8-Hydroxy-2'-deoxyguanosine, a-Hydroxybutyric Acid, a-Ketoglutaric Acid, a-Ketoisovaleric Acid, a-Aminoadipic Acid, a-Keto-b-methylvaleric Acid, a-Ketoglutaric Acid, a-Ketoisocaproic Acid, Adipic Acid, Alanine, Anserine, Anthranilic Acid, Arabinitol, Arginine, Arginosuccinic Acid, Asparagine, Aspartic Acid, b-Hydroxybutyric Acid, b-Alanine, b-Hydroxyisovaleric Acid, Benzoic Acid, Benzoylform, Branched Chain Alpha-Keto Organic Acids, Carnosine, cis-Aconitic Acid, Citric Acid, Citrulline, Cortisol, Creatinine, Cystathionine, Cystine, Equol, Ethanolamine, Ethylmalonic Acid, Formiminoglutamic Acid, Fructose, Fumaric Acid, g-Aminobutyric Acid, Glucaric Acid, Glucose, Glutamic Acid, Glutamine, Glutamine / Glutamate Ratio, Glutaric Acid, Glycine, Glycylproline, Hexanoylglycine, Hippuric Acid, Histidine, Homocitrulline, Homocystine, Homogentisic Acid, Homovanillic Acid, Hydroxykynurenine, Hydroxyproline, Indoleacetic Acid, Isocitric Acid, Isoleucine/allo-Isoleucine, KT Ratio, Kynurenic Acid, Kynurenine, Lactic Acid, Leucine, Lysine, Malic Acid, Mandelic Acid, Methionine, Methylmalonic Acid, Microalbumin, Ornithine, Orotic Acid, Oxalic Acid, Phenylacetic Acid, Phenylalanine, Phosphate, Phosphoethanolamine, Picolinic Acid, Pimelic Acid, Proline, Pyridoxic Acid, Pyroglutamic Acid, Pyruvic Acid, Quercetin, Quinolinic Acid, Sarcosine, Serine, Suberic Acid, Suberylglycine, Succinic Acid, Sulfocysteine, Tartaric Acid, Taurine, Threonine, Total Branched Chain Amino Acids, Tryptophan, Tyrosine, Valine, Vannilylmandelic Acid, Xanthurenic Acid
