SMA Patients May Benefit from Low-fat Diet, Mouse Study Suggests

Adhering to a low-fat diet may be beneficial for people with spinal muscular atrophy (SMA), a mouse study suggests.

Mice fed on low-fat diets lived longer, and showed reduced liver damage and lower reliance on fat as an energy source, according to preliminary findings. Additional clinical studies are still needed to develop evidence-based nutritional guidelines for SMA patients, the researchers said.

Their study, “Low fat diets increase survival of a mouse model of spinal muscular atrophy,” was published in the journal Annals of Clinical and Translational Neurology.

The extended lifespan of people with SMA from new therapies has helped to reveal the impact of the disease beyond the characteristic motor dysfunction.

Evidence has shown that SMA patients have an increased risk of impaired kidney function and defects in lipid (fat) metabolism — the synthesis and breakdown of fatty molecules largely ingested in foods or synthesized by the liver.

A recent study — by researchers at the University of Ottawa and Ottawa Hospital Research Institute, in Canada, and colleagues — showed that children with SMA were highly prone to develop dyslipidemia (the presence of abnormally high levels of cholesterol and/or triglycerides in the blood) and fatty liver disease (a condition in which the liver becomes inflamed and damaged due to fat accumulation).

These findings highlighted the need to identify co-adjuvant therapies or interventions to manage these additional non-muscular impairments associated with SMA.

Making changes in diet may be a potential approach to manage SMA-associated defects in lipid metabolism because dietary intake is an important contributor to fat liver build-up, and many families report subjective clinical benefits in SMA children while on a low‐fat diet called the “amino acid diet.”

With this is mind, the same Canadian team sought to evaluate the potential benefits of a low-fat diet in a mouse model of intermediate SMA. These mice usually live for about 25 days, and were previously shown to also develop dyslipidemia and features of non-alcoholic fatty liver disease.

The researchers analyzed changes in the survival, lipid metabolism, and liver fat content in these mice, which were fed four different diets from birth: regular, high fat, low fat, or high glucose (sugar)/low fat.

Results showed that both low-fat diets — low fat/low sugar and low fat/high sugar — significantly extended by two-fold the lifespan of the mice (38 days for low fat/sugar, and 39 days for low fat/high sugar), compared with mice fed the regular diet (21 days). The high-fat diet did not prolong mice lifespan (22 days).

Interestingly, these low-fat diets reduced the levels of a liver damage marker but they did not improve the mice’s reduced liver function or change their liver fat accumulation. This suggested that the survival benefits of a low-fat diet were not due to a reduction in liver fat build-up.

Instead, a low-fat diet appeared to reduce the body’s dependence on fat molecules as an energy source, as ketone levels were normalized in these mice. Ketones bodies are the byproducts of the breakdown of fat in the liver so that the body can use fat instead of glucose as energy fuel.

The team noted that these findings suggest that a low-fat diet significantly improves the lifespan of a mouse model of SMA by reducing circulating fat (coming directly from dietary intake) and fat-dependent energy production, likely leading to a shift in energy source.

“Overall, this study suggests that supplementation of non-fatty substrates for energy use is a key beneficial determinant of survival,” the researchers wrote. “Our findings strongly suggest that clinical nutritional guidelines need to be established from evidence‐based research to provide better care for SMA patients.”