Management
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PROP Nutrition Management Guidelines
First Edition
March 2017, v.1.2
Updated: September 2017
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Nutrition Recommendations
Question
3. For the individual with PROP, do specific nutrient supplementation or other treatment modalities improve outcomes?
Conclusion Statement
Derived from evidence and consensus based clinical practice

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.

Recommendation 3.1

 In well individuals with PROP, provide sufficient oral L-carnitine to maintain plasma free carnitine in the normal range.

Strength of Recommendation:
Insufficient EvidenceConsensusWeakFairStrong
Clinical Action:
ConditionalImperative
Recommendation 3.2

Supplement biotin in newly identified individuals with PROP to rule out multiple carboxylase deficiency and discontinue biotin after the diagnosis of PROP is confirmed.

Strength of Recommendation:
Insufficient EvidenceConsensusWeakFairStrong
Clinical Action:
ConditionalImperative
Recommendation 3.3

Consider, in consultation with the medical team, the use of metronidazole in acutely ill individuals with PROP in order to reduce gut production of short chain fatty acids.

Strength of Recommendation:
Insufficient EvidenceConsensusWeakFairStrong
Clinical Action:
ConditionalImperative
Recommendation 3.4

Consider, in consultation with medical team, the use of carbamylglutamate (carglumic acid) to treat secondary hyperammonemia resulting from the inhibition of N-acetylglutamate synthase (NAGS) by elevated propionic acid.

Strength of Recommendation:
Insufficient EvidenceConsensusWeakFairStrong
Clinical Action:
ConditionalImperative
Recommendation 3.5

Discourage use of supplemental amino acids (e.g. VAL, ILE) in favor of providing additional intact protein in individuals with PROP who have low plasma concentrations of propiogenic amino acids. See Q#1 for evidence and consensus.

Strength of Recommendation:
Insufficient EvidenceConsensusWeakFairStrong
Clinical Action:
ConditionalImperative
Recommendation 3.6

Consider the use of prebiotics to support bowel health in individuals with PROP.

Strength of Recommendation:
Insufficient EvidenceConsensusWeakFairStrong
Clinical Action:
ConditionalImperative
Recommendation 3.7

Consider supplementation of vitamins and other agents that may enhance mitochondrial energy production.

Strength of Recommendation:
Insufficient EvidenceConsensusWeakFairStrong
Clinical Action:
ConditionalImperative
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