Cocoa May Curb Fatigue in Multiple Sclerosis

Damian McNamara

March 12, 2019

Consuming cocoa may offer a feasible and effective dietary approach to the common problem of fatigue in patients with relapsing-remitting multiple sclerosis (RRMS), new research suggests.

Results of a small, double-blind feasibility study show that after 6 weeks, RRMS patients who drank high-flavonoid cocoa experienced improvement in fatigue and walking speed compared with their counterparts who consumed a low-flavonoid version of the beverage.

Those in the high-flavonoid group also experienced a self-reported reduction in pain symptoms.

"Our study establishes that the use of dietary interventions is feasible and may offer possible long-term benefits to support fatigue management, by improving fatigue and walking endurance," the investigators, led by Shelly Coe, RNutr, Oxford Brookes Centre for Nutrition and Health, Oxford, England, write.

The study was published online March 4 in the Journal of Neurology, Neurosurgery & Psychiatry.

Common, Difficult to Treat

Fatigue and fatigability — the speed at which mental and physical fatigue set in — is common in MS, affecting an estimated 90% of patients. In addition, it is difficult to treat and has a significant, negative impact on quality of life.

Previous research has evaluated medication and other strategies to reduce MS-related fatigue. To date, exercise shows the greatest success. Even so, results with exercise can be limited and "other approaches or combination therapies need to be investigated," the investigators note.

Dark chocolate containing 70% to 85% cocoa solids is well known for its high antioxidant and flavonoid content. Research in patients with chronic fatigue syndrome suggests dark chocolate consumption can improve fatigue as well as sleep quality in this population.

However, there has been limited research into dietary approaches for symptom management in MS, the investigators note.

To determine whether flavonoids may offer an effective dietary intervention in MS, researchers conducted a small 6-week feasibility study that included 40 adults with RRMS and fatigue (30 men, 10 women).

Of these, 19 were randomized to receive a packet of high-flavonoid cocoa powder that was added to a mug of heated rice milk each morning after overnight fasting. The control group followed the same protocol but used low-flavonoid cocoa.

Participants were instructed to wait 30 minutes before taking any prescribed medication or eating or drinking anything else, but otherwise adhered to their usual diet.

Study participants had experienced no MS relapses or sudden symptom changes in the 3 months before the study, rated their fatigue as greater than 4 out of 7 on the Fatigue Severity Scale, and were either treatment naïve or taking first-line disease-modifying therapies.

Reduced Pain

Patients received text message reminders to rate their fatigue on a 1-10 scale three times a day. In addition, at baseline and at 6 weeks, participants walked a track in a university corridor while researchers tracked time and distance to assess fatigability.

At baseline and at 3 and 6 weeks, participants also reported their physical fatigue for the previous week using the Quality of Life in Neurological Disorders (Neuro-QOL) short form questionnaire.

Cognitive fatigue was assessed with the Adult Memory and Information Processing Battery (AMIPB).

Participants also completed questionnaires addressing physical activity, quality of life, anxiety, and depression. In addition, they wore an accelerometer to monitor physical activity. Blood markers of inflammation were also measured.

After 6 weeks there was a small improvement in fatigue in 11 of those drinking high-flavonoid cocoa vs eight of those drinking the low-flavonoid version as measured by the Neuro-QOL (effect size [ES], 0.04; 95% confidence interval [CI], –0.40 - 0.48) and a moderate effect on fatigability as measured by the 6-minute walk test (ES, 0.45; 95% CI, 0.18 - 1.07).

Although self-reported, pain symptoms also improved more in the high-flavonoid group.

Improvement on the AMIPB cognitive performance measure was defined as clinically meaningful if it was a one standard deviation change in 11.5 seconds.

However, based on these criteria, only one person improved in the intervention group and no one in the control group, so the investigators did not calculate a relative risk for this outcome.

Going the Distance

The strongest relative risk, 1.80, favored the responders in the intervention group in terms of distance walked during the 6-minute test. Those in the high-flavonoid cocoa group showed a larger increase in how many meters they could walk at 6 weeks versus baseline — 34 additional meters compared with 11 additional meters in the control group.

Adverse events reported in the study did not cause any safety concerns and were similar between groups, the researchers note.

Coe said the high-dose powder contained approximately 18 grams of flavonoid-rich cocoa. However, he added, a relatively small dose of flavonoid-rich pure cocoa daily may help fatigue and other symptoms in MS.

"Our study establishes that the use of dietary interventions is feasible and may offer possible long-term benefits to support fatigue management, by improving fatigue and walking endurance," the researchers note.

They also call for further investigation to support their findings, including studies looking at a longer follow-up, cost effectiveness, and use in combination with exercise, disease modifying therapies, and/or physiotherapy.

"The use of dietary approaches to reduce fatigue and associated factors in people with MS may be an easy, safe, and cost-effective way to have an impact on quality of life and independence, allowing people to feel more in control of their condition. A full evaluation, including wider geography, longer follow up and cost effectiveness is now indicated," the investigators conclude.

Promising Findings

In an accompanying editorial, Paolo Ragonese, MD, PhD, Department of Experimental, Biomedicine and Clinical Neurosciences, University of Palermo, Italy, notes that the study findings are promising and warrant a phase 3 clinical trial to confirm the results.

Although it 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," he writes.

He also endorsed further investigation.

"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," he writes.

A Multiple Sclerosis Society grant funded the study. Coe and Ragonese report no relevant financial relationships.

J Neurol Neurosurg Psychiatry. Published online March 4, 2019. Abstract, Editorial

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