Consuming red meat, which is rich in sialic acid N-glycolylneuraminic acid (Neu5Gc), may exacerbate disease severity in people with Duchenne muscular dystrophy (DMD), according to a new study published in The American Journal of Pathology.
This finding suggests that eliminating red meat from the diet may improve disease pathology and delay the progression of DMD.
Humans cannot synthesize Neu5Gc due to a mutation in the cytidine-5′-monophospho-(CMP)–N-acetylneuraminic acid hydroxylase (CMAH) gene, which is responsible for its synthesis. However, almost all humans consume a diet containing Neu5Gc. This Neu5Gc can be taken up by cells and incorporated in cell membranes. This can lead to the immune system generating anti-Neu5Gc serum antibodies and is thought to worsen inflammation-driven diseases like cancer.
Read more about DMD etiology
The first aim of the present study was to assess whether patients with DMD had anti-Neu5Gc antibodies in their serum and whether their levels were comparable to that of people of the same age without the disease.
“Patients with Duchenne muscular dystrophy (DMD) had a threefold increase in overall anti-Neu5Gc antibody titer compared with age-matched controls”, wrote Paul T. Martin, PhD, and the co-authors of the study.
Then to further elucidate the effect of these antibodies in DMD, the researchers used an mdx mouse (a widely used animal model to study DMD) in which the Cmah gene was also inactivated. The inactivation of this gene in mice is known to modulate the severity of a number of diseases including DMD in this animal model. The researchers then induced the mice to develop anti–Neu5Gc-glycan antibodies like humans.
They found that the animals had increased muscle fibrosis and expression of inflammatory markers in the heart as well as decreased survival. This could be through a mechanism where the anti-Neu5Gc antibodies amplify muscle inflammation that is already present in DMD, they said. This inflammation could increase Neu5Gc uptake in muscles, “generating a vicious cycle”.
Disease severity might, therefore, be exacerbated by the ingestion of Neu5Gc-rich foods such as red meat in DMD patients, the researchers concluded.
Martin PT, Kawanishi K, Ashbrook A, et al. Serum antibodies to N-glycolylneuraminic acid are elevated in Duchenne muscular dystrophy and correlate with increased disease pathology in Cmah-/-mdx mice. Am J Pathol. 2021;191(8):1474-1486. doi:10.1016/j.ajpath.2021.04.015