Diet as medicine in mitochondrial diseases?

Researchers from the University of Helsinki, Finland, found that diet could have a strong impact on the progression of mitochondrial disease.

In the study, published in EMBO Molecular Medicine, low-carbohydrate diet aggravated muscle damage in patients with a mitochondrial muscle disease called “progressive external ophthalmoplegia” (PEO). However, damage was not permanent. The patients recovered quickly and short-term muscle damage eventually resulted in a modest improvement of muscle strength in the long run.– More research is still needed before diet change is used as a tool in therapeutic strategy, emphasises Professor Anu Suomalainen, senior author of the publication.

Mitochondrial diseases are a group of disorders that result from defects in mitochondria, specialized cellular compartments that convert nutrition into chemical energy the cell can use. In PEO, the muscles of the eyes are affected, leading to limitations in eye movement and drooping eyelids. In addition, patients often suffer from weakness of muscles in the arms or legs, particularly during exercise.

– Since mitochondria turn the food we eat into energy, we expected that diet should have an impact on disease progression, Professor Suomalainen says. After promising results from mouse experiments, she and her colleagues set out to test this notion in a small pilot trial comprising five PEO patients and ten control subjects

All participants were switched to a high-fat, low-carbohydrate “modified Atkins” diet. Contrary to the researchers’ expectations, the primary reaction of the patients to the diet was detrimental. They suffered from progressive muscle pain and showed signs of muscle damage so that the trial was prematurely discontinued after a maximum of 11 days on the diet. However, the patients recovered quickly and 2.5 years later, they had actually gained in muscle strength as compared to pre-diet state. Apparently, the short-term muscle damage induced by diet had a modest beneficial impact in the long run.

A thorough examination of the patients allowed the researchers to explain this devious route to improvement. They showed that modified Atkins diet selectively kills muscle fibers that were already damaged through disease-related mitochondrial dysfunction. Whereas most body cells can use a broad range of biomolecules as fuel, pre-damaged fibers apparently depend on carbohydrates.

– If carbohydrates are not provided in the diet the fibers die, explaining the short-term adverse reactions of the patients. This could stimulate muscle regeneration:  healthy satellite cells - muscle stem cells - are activated; they divide and eventually fuse with existing muscle fibers, supplying them with healthy mitochondria, the scientists speculate.

The results point to the potential of using dietary change as a therapeutic strategy, although in a carefully controlled clinical setting. – In fact, caution is required. Low-carbohydrate diet can lead to long-term improvement but can also cause muscle damage, Suominen points out.

This observation also casts light on the alleged safety of low-carbohydrate diets as a means of weight loss. For some people with subclinical mitochondrial diseases, it may have adverse side effects on muscles.

For more information, please contact:
Professor Anu Suomalainen-Wartiovaara
Tel. +358 9 471 71965, +40 5936386, email:
Molecular Neurology Research Program, University of Helsinki

Reference: Ahola S, Auranen M, Isohanni P, Niemisalo S, Urho N, Buzkova J, Velagapudi V, Lundbom N, Hakkarainen A, Muurinen T, Piirilä P, Pietiläinen KH, Suomalainen A.Modified Atkins diet induces subacute selective ragged-red-fiber-lysis in mitochondrial myopathy patients. EMBO Molecular Medicine 19th September, 2016 doi: 10.15252/emmm.201606592