Dietary Quercetin Disappoints in Duchenne MD Study, But Surprise Twist Hints at Some Effect

Dietary quercetin, an antioxidant belonging to a group of plant pigments that gives many fruits and vegetables their color, may partly protect muscles in Duchenne muscular dystrophy (DMD), according to a study conducted in mice and published in the scientific journal Plos One.

The results of the study, “Long-Term Quercetin Dietary Enrichment Partially Protects Dystrophic Skeletal Muscle,” while disappointing, did find that treated DMD mice were considerably more active than those in a non-treated group. This twist surprised the researchers, although reasons for this “spontaneous” activity could not pinpointed.

Quercetin, which is a compound with both antioxidant and anti-inflammatory properties, activates a biologic pathway called PGC-1α, which increases muscle function, decreases muscle damage, and increases the abundance of utrophin, a protein similar to dystrophin that is missing in Duchenne MD.

To test whether dietary quercetin might protect muscles in Duchenne MD, researchers led by Dr. Joshua Selsby, with the Department of Animal Science at Iowa State University, treated mdx mouse, a popular model for studying Duchenne MD, with dietary quercetin for 12 months.

They then measured muscle function in the calf muscle and the EDL muscle, situated toward the side and front of the animals’ legs. They compared results to muscle function in untreated mdx mice and in normal mice.

Dietary quercetin was seen to reverse 50% of the loss in specific muscle tension related to the disease, and to partly preserve fatigue resistance in the calf muscle. But it did not protect against injury in the EDL, induced by specific tension and resistance to contraction.

Since some gain of function in the calf muscles was observed, researchers analyzed the muscles under the microscope, but they did not find any improvements in the composition of muscle tissue. Similarly, they did not observe an increase in the PGC-1α pathway activation.

Similar results were also obtained from analysis of the animals’ diaphragm.

“These data suggest that the benefits conferred to dystrophic muscle following 12 months of quercetin enrichment were underwhelming,” the researchers wrote.

However, at the end of the 12-month treatment, mdx mice given dietary quercetin were more active and engaged in more vigorous activity compared to untreated mdx mice. This led the group to suggest that dietary quercetin might aid in muscle protection, as a modest preservation of muscle function and a greater capacity for spontaneous physical activity — in the absence of tissue damage — was clearly seen in the mice.

“[O]ne of the most notable findings in the current study was the quercetin-mediated elevations in spontaneous activity in caged mice,” the team wrote. “It is unclear if quercetin directly impacts behavior such that it serves to stimulate activity via mechanisms beyond the scope of this investigation … or if quercetin supports improved function such that it permits increased spontaneous activity.”

Further and long-term studies are needed to investigate dietary quercetin’s potential in Duchenne MD, the researchers concluded.