On dietary and nutritional therapies for ME/CFS

ME/CFS in case you don't already know refers to Myalgic Encephalomyelitis / Chronic Fatigue Syndrome and, according to the findings reported by Nadia Campagnolo and colleagues [1], is in need of quite a bit more scientific investigation when it comes to the application of dietary changes and nutritional supplements to potentially alter the course of the condition(s).

Surveying the peer-reviewed literature "from 1994 to May 2016" the authors looked for peer-reviewed studies where "CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing)." They found 17 studies that included 14 different interventions. Unfortunately they concluded that: "Many studies did not show therapeutic benefit on CFS/ME" alongside the observation that the methodological quality of the research in this areas 'could do better'.

But it was not all research doom-and-gloom as some approaches seemed to show promise: "Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10." Without wishing to toot my blogging trumpet, some of these approaches have been discussed before on this blog (Coenzyme Q10 and NADH supplementation for Chronic Fatigue Syndrome? and Coenzyme Q10 and NADH supplementation for Chronic Fatigue Syndrome continued) and beyond that, the target organ of something like the use of probiotics for CFS has made an appearance more than once too (see here for example). I might also add that just outside of the search dates used by Campagnolo et al was the suggestion that issues with a staple foodstuff - cows milk - might be over-represented in cases of CFS (see here) and that a milk-free diet could be useful [2] for some at least. By saying all that, I'm not giving any medical or clinical advice...

As science starts to move further away from the the biopsychosocial (BPS) model of CFS/ME (see here) and starts looking at genetics, biology and somatic disease processes with regards to the various presentations included under the banner of ME/CFS (see here) I foresee some interesting developments further down the line. Granted, dietary and nutritional approaches to CFS/ME are probably not considered 'mainstream' in terms of management strategies but that does not mean they aren't important or at least important in the context of a diagnosis of ME/CFS seemingly being protective of nothing. Central to any future studies in this or any related area is the idea that there may be lots going on under the 'plural' diagnostic umbrella of ME/CFS (see here). Indeed, something that even the PACE trial is starting to take on board [3].

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[1] Campagnolo N. et al. Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. J Hum Nutr Diet. 2017 Jan 22.

[2] Rowe PC. et al. Cow's milk protein intolerance in adolescents and young adults with chronic fatigue syndrome. Acta Paediatr. 2016 Sep;105(9):e412-8.

[3] Williams TE. et al. Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial. Psychol Med. 2017 Jan 23:1-12.

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Campagnolo N, Johnston S, Collatz A, Staines D, & Marshall-Gradisnik S (2017). Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association PMID: 28111818

Coenzyme Q10 and NADH supplementation for Chronic Fatigue Syndrome continued

In a previous post on this blog I briefly discussed the research paper from Jesus Castro-Marrero and colleagues [1] suggesting that "oral CoQ10 [Coenzyme Q10] (200 mg/day) plus NADH [nicotinamide adenine dinucleotide (NADH)] (20 mg/day) supplementation" might be something useful for some people diagnosed with Chronic Fatigue Syndrome (CFS).

Enter then a new paper from Castro-Marrero and colleagues [2] (open-access available here) building on the original findings by suggesting that "CoQ10 plus NADH supplementation for 8 weeks is safe and potentially effective in reducing max HR [maximum heart rate] during a cycle ergometer test and also on fatigue in CFS." The max HR by the way, is a measure of cardiovascular function as part of exercise performance. A cycle ergometer test is all about testing parameters such as max HR using a stationary bicycle.

"A proof-of-concept, 8-week, randomized, double-blind, placebo-controlled trial was conducted" whereby either CoQ10 plus NADH was given (n=39) or a placebo (n=34) over the study period. Baseline and end of study max HR was tested alongside self-reported changes to "fatigue, pain and sleep problems" based on scoring using the Fatigue Impact Scale (FIS) among other things.

Based on an intention-to-treat (ITT) analytical strategy, authors reported that: "statistically significant differences were observed in CoQ10 + NADH group during the study, with a reduction in max HR after 8 weeks of treatment compared with baseline max HR." That being said, when comparing max HR from baseline to 8 weeks between the groups (CoQ10+NADH vs placebo), no statistically significant group differences were noted despite a trend towards greater max HR reduction in the experimental group. Insofar as other biological parameters also measured over the course of the study period ("VO2, VCO2, maximal workload, respiratory quotient and arm systolic and diastolic blood pressure") no significant differences were noted between baseline and end of study.

Fatigue scores showed a similar trend in terms of intra- and inter-group comparisons. So, for the CoQ10+NADH group, comparisons between baseline, week 4 and week 8 scores suggested significant reductions in total FIS scores. When it came to comparisons with the placebo group however, no significant differences were reported (indeed, the placebo group also showed a reduction in FIS total scores at least between baseline and week 4). The authors suggest that a lack of study power might have contributed to the lack of significant effects when comparing the experimental and placebo groups.

These are interesting results and from an intra-group perspective (comparing across different testing occasions) suggest that there may be more to see from this preparation on this patient group. Bearing in mind the emphasis on actually looking at physiological parameters such as max HR and as the authors note: "the use of strict inclusion criteria based on 1994 CDC case definition ensures that the participants were appropriately selected and without confounding comorbidities" further research is indicated to further assess such claims and determine specific biological mechanisms pertinent to any effect.

Music: Ike & Tina Turner - River Deep Mountain High.

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[1] Castro-Marrero J. et al. Does oral Coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in Chronic Fatigue Syndrome? Antioxid Redox Signal. 2014 Nov 11.

[2] Castro-Marrero J. et al. Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - A randomized, controlled, double-blind trial. Clin Nutr. 2015 Jul 17. pii: S0261-5614(15)00189-2.

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Castro-Marrero J, Sáez-Francàs N, Segundo MJ, Calvo N, Faro M, Aliste L, Fernández de Sevilla T, & Alegre J (2015). Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - A randomized, controlled, double-blind trial. Clinical nutrition (Edinburgh, Scotland) PMID: 26212172

Coenzyme Q10 and NADH supplementation for Chronic Fatigue Syndrome?

A quick post today to direct your attention to the paper by Jesus Castro-Marrero and colleagues [1] reporting results which seemed to suggest that under double-blind, placebo-controlled conditions "oral CoQ10 [Coenzyme Q10] (200 mg/day) plus NADH [nicotinamide adenine dinucleotide (NAD) + hydrogen (H)] (20 mg/day) supplementation" might have some positive effects for cases of Chronic Fatigue Syndrome (CFS). The NIH entry for the trial can be found here.

I volunteer as tribute! 

Reporting on both fatigue-related and "biochemical parameters in 73 Spanish CFS patients", researchers found that the NADH / CoQ10 preparation (ReConnect) was superior to a phosphoserine/serine plus vitamin C placebo based on fatigue scores derived from the Fatigue Impact Scale (FIS) [2]. Further, that "a recovery of the biochemical parameters was also reported. NAD+/NADH (p< 0.001), CoQ10 (p< 0.05), ATP (p< 0.05) and citrate synthase (p< 0.05) were significantly higher and lipoperoxides (p< 0.05) were significantly lower in blood mononuclear cells (BMCs) of the treated group."

Obviously there is quite a bit more to do in this area but these results are perhaps not so surprising given other more open-trial data as per the paper from Garth Nicholson and colleagues [3]. I'm also minded to refer you back to some other research discussed in this area with regards to mitochondria and CFS (see here) and mention of the paper by Maes and colleagues [4] which concluded: "lowered levels of CoQ10 play a role in the pathophysiology of ME/CFS and that symptoms, such as fatigue, and autonomic and neurocognitive symptoms may be caused by CoQ10 depletion."

"Larger sample trials are warranted to confirm these findings." I couldn't have said it better myself.

Music: The Skatalites and Guns of Navarone based around a story by one of my favourite novelists.

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[1] Castro-Marrero J. et al. Does oral Coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in Chronic Fatigue Syndrome? Antioxid Redox Signal. 2014 Nov 11.

[2] Frith J. & Newton J. Fatigue Impact Scale. Occup Med (Lond). 2010 Mar;60(2):159.

[3] Nicholson G. et al. Lipid Replacement Therapy with a Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Fatigue in Intractable Chronic Fatiguing Illnesses and Chronic Lyme Disease Patients. International Journal of Clinical Medicine. 2012; 3: 163-170.

[4] Maes M. et al. Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett. 2009;30(4):470-6.

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Castro-Marrero J, Cordero MD, Segundo MJ, Saez-Francas N, Calvo N, Román-Malo L, Aliste L, Fernandez de Sevilla T, & Alegre-Martin J (2014). Does oral Coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in Chronic Fatigue Syndrome? Antioxidants & redox signaling PMID: 25386668