Preliminary results from a feasibility study suggest a potential role for flavonoid enriched cocoa to treat fatigue, one of the most challenging symptoms of multiple sclerosis
In their JNNP paper, Coe et al report the preliminary results of a feasibility trial on flavonoid enriched cocoa for the treatment of multiple sclerosis (MS) related fatigue, showing promising results that encourage the conduction of a phase III clinical trial to confirm the results of possible clinical effects on MS related fatigue.1
As described in the paper, fatigue is the most common symptom reported by individuals affected by MS, affecting the majority of patients. It is often present even when neurological disability is low and in the early stages of the disease, but impacts significantly the quality of life in MS patients, diminishing independence in everyday activities. Fatigue symptoms are described by patients as tiredness, generalised weakness or lack of energy. MS related fatigue still represents a challenge in the treatment and management of individuals with MS because its mechanisms are multifactorial. Hence it is not surprising that previous studies resulted in some inconsistencies.
Fatigue symptoms have generally been attributed to several pathways with a common mechanism: an activity dependent conduction impairment. The different pathways that can contribute to generation of this impairment are directly related to the disease (ie, cytokines or nitric oxide production determined by inflammatory activity). The main factors are represented by reduced brain connectivity due to loss of axons, oligodendrocytes and synapses that consequently determine altered hypothalamic and autonomic pathways. According to several authors, however, the main contributors to fatigue could be secondary mechanism, depending on the presence of depression, sleep disturbances, comorbid disorders and psychosocial factors. Finally, several disease modifying treatments have been reported to be associated with fatigue.
The impact of fatigue does not seem to correlate with lesion load, rather it appears to relate to the site of the lesions, mainly prefrontal, temporal and thalamic. Apart from physical exercise, amantadine, modafinil and 3,4 amynopiridine are among the most used drugs for the treatment of fatigue.3 All of these treatments have potential side effects that limit their use to a certain extent. According to previous reviews on symptomatic therapy of MS, amantadine was reported to be associated with nausea, headache, anxiety and palpitation although not seriously. For modafinil, insomnia and gastrointestinal complaints where the main limiting factors. Treatment with 3,4 amynopiridine was reported to cause insomnia and nausea, but also increased paraesthesiae, and rarely seizures and hepatotoxicity.2 The most important limiting factor is however the limited evidence of their effectiveness in obtaining durable relief of fatigue.
Epidemiological studies have shown that diets rich in flavonoids are directly related to increased longevity and a decreased incidence of cardiovascular disease.4 The effects of flavonoid have been reported to determine anti-inflammatory effects and to exert antioxidant and free radical scavenging properties in vitro, as well as positively modifying the microbiota.5
Finally, several studies have explored he effects of epicathenin containing dark chocolate on mitochondrial activity, with intriguing results.6 Although the study of Coe et al is an exploratory trial, it adds further interesting suggestions to the possible positive effects of flavonoid intake on the management of fatigue in patients with MS. A well designed, randomised, controlled, long term study with clinically meaningful endpoints is needed to clarify the potential benefits of flavonoid enriched chocolate to treat MS related fatigue.
Coe S , Cossington J , Collett J , et al . A randomised double-blind placebo-controlled feasibility trial of flavonoid-rich cocoa for fatigue in people with relapsing and remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2019. doi:10.1136/jnnp-2018-31949