Patients with maple syrup urine disease (MSUD) have lower levels of docosahexaenoic acid (DHA), resulting from inadequate dietary intake and change in n-3 polyunsaturated fatty acid (PUFA) metabolism, according to a study.
“[T]his study provides evidence of DHA deficiency in patients with MSUD, along with changes in long-chain (LC) PUFA profiles,” the investigators said. “Although insufficient dietary intake may contribute to reduced DHA status, our findings indicate that additional mechanisms beyond intake alone may be involved and require further investigation.”
Sixteen MSUD patients and 22 unaffected siblings sharing a similar household and environmental background were included in this single-centre, cross-sectional study. The investigators recorded the participants’ dietary intake and analysed their plasma fatty acid profiles.
In dietary assessments, intakes of total fat and cholesterol (p<0.001 for both) and n-3 PUFAs (p=0.036) were significantly lower in MSUD patients, with alpha-linoleic acid (ALA) intake as the only individual LC-PUFA significantly reduced (p=0.048). [Eur J Clin Nutr 2026;80:895-903]
In plasma analysis, DHA levels were also substantially reduced in MSUD patients despite similar intakes of dietary DHA (p<0.001), whereas arachidonic acid (AA) and mead acid (MA) were greatly increased (p<0.001 for both).
Plasma DHA concentrations displayed a moderately positive association with dietary ALA intake (r, 0.516; p=0.041), but in regression analysis neither dietary ALA intake (B, 0.005; p=0.584) nor the dietary n-6/n-3 PURA ratio (B, ‒0.552; p=0.706) was independently predictive of plasma DHA levels.
Furthermore, plasma DHA levels in patients with MSUD positively correlated with dietary leucine intake (r, 0.635; p=0.008) and plasma isoleucine concentrations (r, 0.524; p=0.037).
DHA deficiency
“Research on LC-PUFA status in inherited metabolic diseases requiring a protein-restricted diet has predominantly focused on phenylketonuria (PKU),” the investigators said.
“These studies have included all age groups, such as breastfed infants, children, adolescents, and adults, and have measured PUFA levels in plasma and/or erythrocyte membranes,” they added. [J Inherit Metab Dis 2007;30:326-332; J Inherit Metab Dis 2002;25:56-64]
Findings on specific FAs, such as AA, LA, and ALA, varied across studies, but observations on DHA deficiency among individuals with PKU were consistent. [J Inherit Metab Dis 2007;30:326-332; J Inherit Metab Dis 2002;25:56-64; J Inherit Metab Dis 1998;21:373-381]
DHA deficiency was initially thought to be driven by insufficient dietary intake of DHA due to the avoidance of animal-derived foods, but recent studies found no direct association between dietary intake and DHA status. [Acta Biochim Pol 2018;65:303-308]
“Some also reported higher erythrocyte DHA concentrations in individuals with better metabolic control and lower plasma phenylalanine levels, suggesting that factors beyond intake, such as impaired endogenous synthesis or disrupted FA metabolism, may also contribute,” the investigators said. [Prostaglandins Leukot Ess Fat Acids 2016;109:52-57]
In intervention studies on the effects of LC-PUFA supplementation, results showed that DHA deficiency can be corrected in infancy and later in life. [J Nutr Biochem 2000;11:543-547; Mol Genet Metab 2013;109:121-124]
A few studies observed improvements in visual evoked potentials after DHA supplementation, but others saw no significant effects on neurocognitive or visual outcomes. [Nutrients 2019;11:1537; J Nutr Biochem 2000;11:543-547]
“Reflecting the accumulated evidence, recent PKU guidelines underscore the importance of individualized nutritional strategies for LC-PUFA supplementation and specifically recommend that women with PKU who are planning a pregnancy or are pregnant should receive DHA supplementation to support optimal foetal development,” the investigators said. [Mol Genet Metab 2025;145:109125]
“MSUD is an inherited metabolic disorder requiring protein restriction, often limiting intake of animal-derived foods,” they said.