Beyond limiting the dietary intake of the propiogenic amino acids in the management of PROP, there are supplements, medications and interventions that are used to decrease propionate production, increase its excretion or limit its ability to interfere with various cellular or biochemical processes.

L-carnitine is used in both acute and chronic management of PROP to increase propionate excretion as propionyl carnitine. Doses, ranging from 25-100 mg/kg/d (PO) in chronic management and 100-300 mg/kg/d (IV) in acute management, have been associated with improved outcomes, although excessive L-carnitine is associated with fishy odor and GI symptoms.

Metronidazole is frequently prescribed in acute and chronic management to reduce gut propionate production and, when given, is usually prescribed for 1-2 weeks, followed by rest or use of alternative antibiotics. Laxatives have been shown to increase fecal transit time and reduce propionate in individuals with PROP but the use of some centrally-acting laxatives may be contraindicated. The use of probiotics and prebiotics has not been well investigated in PROP; however prebiotics, particularly FOS and GOS which lower pH and depress propionic acid-producing bacteria, appear to be safe.

Biotin is a cofactor for the enzyme propionyl CoA carboxylase (PCC), but beyond giving 5-20 mg/d during the diagnostic phase when ruling out multiple carboxylase deficiency, biotin has not been shown to increase PCC activity or decrease propionate concentration.

There is no strong evidence that supplementing with individual amino acids improves outcome in PROP.

Elevated propionate can inhibit N-acetyl glutamate synthatase (NAGS) leading to hyperammonemia in acutely ill individuals. Medical management traditionally has included the nitrogen-scavenging medications sodium phenylbutyrate or acetate and sodium benzoate. Carbaglutamate specifically enhances NAGS and appears to be effective in reducing ammonia in patients with PROP.

Elevated propionate has also been shown to cause secondary mitochondrial dysfunction. Supplements to enhance mitochondrial function, minimize reactive oxidation species, and supply Kreb cycle intermediates (anaplerosis) are often discussed as a management strategy. CoQ10, D,L-hydroxybutarate, riboflavin, thiamin, vitamin E, N-acetyl cysteine, malate and citrate have been tried; however, they were not provided in a controlled fashion and there is only minimal evidence to support or refute their benefit. Until further research is conducted, supplementation should not exceed established tolerable upper intake levels. Of these, CoQ10 is the most frequently prescribed and there is limited evidence that it may improve cardiomyopathy associated with PROP.