Impact on Isoleucine and Valine Supplementation When Decreasing Use of Medical Food in the Nutritional Management of Methylmalonic Acidemia

Abstract

Background: Methylmalonic acidemia (MMA) is an autosomal recessive disorder treated with precursor-free medical food while limiting natural protein. This retrospective chart review was to determine if there was a relationship between medical food, valine (VAL) and/or isoleucine (ILE) supplementation, total protein intake, and plasma amino acid profiles. Methods: A chart review, of patients aged 31 days or older with MMA treated with dietary intervention and supplementation of VAL and/or ILE and followed at the Children’s Hospital Colorado Inherited Metabolic Diseases Clinic. Dietary prescriptions and plasma amino acid concentrations were obtained at multiple time points. Results: Baseline mean total protein intake for five patients was 198% of Recommended Dietary Allowance (RDA) with 107% natural protein and 91% medical food. Following intervention, total protein intake (p = 0.0357), protein from medical food (p = 0.0142), and leucine (LEU) from medical food (p = 0.0276) were lower, with no significant change in natural protein intake (p = 0.2036). At baseline, 80% of patients received VAL supplementation and 100% received ILE supplementation. After intervention, only one of the cohort remained on supplementation. There was no statistically significant difference in plasma propiogenic amino acid concentrations. Conclusions: Decreased intake of LEU from medical food allowed for discontinuation of amino acid supplementation, while meeting the RDA for protein.

Long term follow-up of the dietary intake in propionic acidemia

“…Although HAZ (−1.078 ± 0.957) of our four patients was not different than previous reports [ 3 , 5 ] and may be better [ 16 ], it did not reflect an ideal linear growth outcome. PA still does not have an ideal growth outcome, and those patients are liable to growth retardation and short stature due to many contributing factors [ 9 ], including, but not limited to excessive natural protein restriction, acute decompensation episodes, metabolic acidosis and food aversion [ 16 ].…”

“…The high leucine intake along with restriction in Val., and Ile., in our patients, contributed to high Leu/Val and Leu/Ile ratios in the diet with a median of 3.03: 1 and 3.4: 1, respectively. This observation is not new and has been described in previous reports [ 5 , 11 ] in methylmalonic aciduria (MMA), a disease that has the same nutritional management as PA [ 1 ]. Although leucine is an important amino acid that plays a role in protein synthesis in muscle and glucose regulation [ 23 ], concerns are emerging regarding the potential long term effects of high leucine intake in PA patients [ 5 , 6 , 10 , 11 ] as high leu diet seems not to be without adverse effects [ 10 , 24 ].…”

“…It was found to induce hyperammonemia in adult males when the intake was at 550 mg/kg/day [ 21 ], but the cut-off of leucine intake that can induce hyperammonaemia in children has not been described, thus we can not assign a safe upper level of intake. This effect can be detrimental in populations vulnerable to hyperammonemia like PA patients especially that most of the published studies, including ours, reported a high intake of leucine [ 5 , 11 ].…”

“…Yet, to meet the Recommended Daily Allowance (RDA) for protein, PA patients had to be supplemented with large amounts of medical formulas free of the “offending” AAs. Through a better understanding of the disease pathophysiology over time, and in recognizing that patients are mainly at risk when they are in catabolic stress, and that severe protein restriction can lead to decrease in the tolerance of the propiogenic AAs amount in diet, it became clear that PA patients can do better by limiting use of medical formulas and allowing more natural protein intake during periods of medical and biochemical stability; strong restriction in natural protein intake would be only necessary during illness, “sick day” [ [2] , [3] , [4] , [5] , [6] ].…”

Transcriptome and carotenoid profiling of different varieties of Coffea arabica provides insights into fruit color formation

“…The KEGG pathway enrichment analysis revealed a number of enriched pathways ( Table S2 ) which may explain the basis for the influence of fruit coloration on quality and nutritional value. For instance, fructose and mannose metabolism; vitamin B6 metabolism, together with valine, leucine and isoleucine degradation have been documented to regulate nutritional composition of many fruits ( Bernstein et al, 2020 ). From the KEGG pathway, two pathways known to regulate fruit coloration were detected: carotenoid biosynthesis and phenylpropanoid/flavonoid/anthocyanin biosynthesis ( Table S2 ) of which the former was more prominent than the latter.…”