Succinate

Urine
check icon Optimal Result: 0 - 20.99 ug/mg creatinine.

Succinate (or succinic acid) is an important metabolite that is involved in several chemical processes in the body. Succinic acid is a key intermediate of both the Kreb’s cycle and the electron transport chain that generates adenosine triphosphate (ATP), the currency for most of the body’s energy transactions.

Succinate is produced from bacterial degradation of unabsorbed glutamine and is a metabolite of alpha-ketogluturate, as well as methionine, valine & leucine; precursor of fumaric acid; also formed from bacterial action on glutamine.

What does it mean if your Succinate result is too high?

Elevated levels of succinate may occur when there are nutritional enzyme inhibitions of the breakdown pathways, inherited low-activity enzymes are present, if there are high levels of precursors (succinyl-CoA, alpha-ketoglutarate), or if there are higher levels of its downstream products (fumarate).

High levels of succinate may also occur if there is complex II electron transport chain (ETC) inhibition. A loss of gastrointestinal barrier function (leaky gut) can increase circulating levels of bacterial proteins (lipopolysaccharides), which may also inhibit these enzymes.

Chronically increased succinate levels may increase oxidative stress and dysregulate the immune system. Dicarboxylic acids (cis-aconitate, isocitrate, succinate, malate, suberate, and adipate) may be excreted in high amounts due to increased mobilization of fatty acids, beta-oxidation defects (increased adipate and suberate), increased gut permeability or fasting.

1. Consider supporting the conversion of succinate into fumarate with vitamins B2, B3, copper, iron, zinc, CoQ10, resveratrol, and antioxidants. Melatonin may help upregulate enzyme activity.

2. Adult-onset complex II ETC inherited defects are rare and may present with cardiac problems or muscle weakness, incoordination, and possibly seizures.

- Complex II (succinate dehydrogenase)

- Elevated lactate

- Some will also have elevated succinate, fumarate

- Consider supporting ETC function with additional vitamins B2, B3, B5, B12, E, selenium, taurine and melatonin.

3. Obesity or diabetes can decrease alpha-ketoglutarate but increase succinate.

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What does it mean if your Succinate result is too low?

Low levels of succinate can occur if there are low levels of precursors (succinyl-CoA, alpha-ketoglutarate), if there are nutritional enzyme inhibitions, or if a low-activity enzyme variant is inherited. The succinate precursor succinyl-CoA can be synthesized in the liver from dietary fats via the omega-oxidation pathway, or from dietary proteins. Inhibition of the omega-oxidation pathway may result in low succinate levels.

- Consider supporting succinate synthesis from alpha-ketoglutarate with vitamins B1, B2, calcium, and lipoic acid.

- The succinate precursor succinyl-CoA may also be derived from branch-chain amino acids or fatty acids. Support this pathway in patients on “keto”, high protein, or low carbohydrate diets. Consider supporting alternate pathways with vitamins B1, B2, B3, B6, B12, biotin, r-lipoic acid, iron (if deficient), magnesium, and molybdenum. If the liver omega-oxidation pathway is inhibited (B3 or zinc deficiency) then levels of adipate, suberate, ethylmalonate, and methylsuccinate may be low.

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