Chronic Fatigue Syndrome Abstracts 1

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Improved management of primary chronic fatigue syndrome with the supplement French oak wood extract (Robuvit(R)): a pilot, registry evaluation.
            (Belcaro et al., 2014) Download
AIM: The aim of this supplement study was to evaluate French oak wood extract (Robuvit(R), Horphag Research Ltd) used as a supplement in association with a defined management plan for chronic fatigue syndrome (CFS) in healthy subjects with CFS, a condition that has, so far, no specific treatment or management standards. METHODS: Robuvit(R) is a new proprietary and exclusive extract of oak wood with important antoxidant actions. The dosage of the supplementation was 200 mg/day for at least 6 months. The CFS questionnaire and the Brief Mood Introspection Scale (BMIS) questionnaire were used to evaluate mood variations associated with CFS patients. The CFS form includes an analogue scale to record the variations of single symptoms with a score range of 0-10. At inclusion into the registry study, at least 5 symptoms were present. All subjects (age range 35-44; BMI range 24-26) with CFS were tested for oxidative stress: 61 out of 91 subjects had an increased value of oxidative stress. The BMIS scale evaluating mood changes in time was also used. The evaluation was repeated at 3 and 6 months. RESULTS: Out of 91 eligible subjects with CFS, 48 subjects (31 with increased oxidative stress) were accepted as part of the supplement registry study using Robuvit; 43 (30 with increased oxidative stress) were accepted as controls using only the management plan. In the Robuvit(R) group there were 3 drop outs; also 3 controls were lost. Oxidative stress was increased in 64.58% of subjects that used Robuvit and in 69.7% of controls. The average values of oxidative stress were expressed for the whole group. The average follow up was 199.3;9.2 days in the Robuvit group and 202.2;5.5 in the control group with a minimum of 6 months. Considering variations in oxidative stress, there was no significant average change in controls, but a significant decrease from the initial values was observed in Robuvit subjects after 3 and 6 months. The CFS questionnaire variations in score indicated that there was a significant improvement for most symptoms after 3 and 6 months in the Robuvit group. Positive variations were also present in controls, indicating the positive effect of an increased attention to CFS. The improvement in signs/symptoms was significantly more valuable in subjects using the oak wood extract considering the main 8 symptoms and the accessory symptoms. Considering the BMIS variations, the totals for positive and negative items were significantly more favourable for Robuvit subjects. Overall mood evaluation in the oak wood extract group improved from an inclusion average of -6.93;2.1 to +4.32;2.6 at 6 months; in contrast it changed from -6.5;2.5 to -3.4;1.5 in controls. No side effects were observed during the supplementation with Robuvit. The compliance was optimal with 93% of the capsules correctly used. CONCLUSION: This promising pilot supplement registry study indicates a new opportunity of management for these difficult and often neglected patients. Correlation between oxidative stress and CFS have to be better explored.

Absorption, metabolism, and effects at transcriptome level of a standardized French oak wood extract, Robuvit, in healthy volunteers: pilot study.
            (Natella et al., 2014) Download
The consumption of wine and spirits, traditionally aged in oak barrels, exposes humans to roburin ingestion. These molecules belong to a class of ellagitannins (ETs), and their only known source is oak wood. Very little is currently known about roburin bioavailability and biological activity. We reported for the first time human absorption of roburins from a French oak wood (Quercus robur) water extract (Robuvit) by measuring the increase of total phenols (from 0.63 +/- 0.06 to 1.26 +/- 0.18 mug GAE equiv/mL plasma) and the appearance of roburin metabolites (three different glucoronidate urolithins and ellagic acid), in plasma, after 5 days of supplementation. Robuvit supplementation induced also the increase of plasma antioxidant capacity from 1.8 +/- 0.05 to 1.9 +/- 0.01 nmol Trolox equiv/mL plasma. Moreover, utilizing a combined ex vivo cell culture approach, we assessed the effect of Q. robur metabolites (present in human serum after supplementation) on gene expression modulation, utilizing an Affymetrix array matrix, in endothelial, neuronal, and keratinocyte cell lines. The functional analysis reveals that Robuvit metabolites affect ribosome, cell cycle, and spliceosome pathways.

Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome
            (Forsyth et al., 1999) Download
BACKGROUND: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology, consisting of prolonged, debilitating fatigue, and a multitude of symptoms including neurocognitive dysfunction, flu-like symptoms, myalgia, weakness, arthralgia, low-grade fever, sore throat, headache, sleep disturbances, and swelling and tenderness of lymph nodes. No effective treatment for CFS is known. OBJECTIVE: The purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide (NADH) i.e., ENADA the stabilized oral absorbable form, in a randomized, double-blind, placebo-controlled crossover study in patients with CFS. Nicotinamide adenine dinucleotide is known to trigger energy production through ATP generation which may form the basis of its potential effects. METHODS: Twenty-six eligible patients who fulfilled the Center for Disease Control and Prevention criteria for CFS completed the study. Medical history, physical examination, laboratory studies, and questionnaire were obtained at baseline, 4, 8, and 12 weeks. Subjects were randomly assigned to receive either 10 mg of NADH or placebo for a 4-week period. Following a 4-week washout period, subjects were crossed to the alternate regimen for a final 4-week period. RESULTS: No severe adverse effects were observed related to the study drug. Within this cohort of 26 patients, 8 of 26 (31%) responded favorably to NADH in contrast to 2 of 26 (8%) to placebo. Based upon these encouraging results we have decided to conduct an open-label study in a larger cohort of patients. CONCLUSION: Collectively, the results of this pilot study indicate that NADH may be a valuable adjunctive therapy in the management of the chronic fatigue syndrome and suggest that further clinical trials be performed to establish its efficacy in this clinically perplexing disorder.

Clinical activity of folinic acid in patients with chronic fatigue syndrome
            (Lundell et al., 2006) Download
A high incidence of severe B-cell immunodeficiency and chronic reactivated Epstein-Barr virus (EBV) infection in patients with chronic fatigue syndrome (CFS) is reported herein. Of the 58 patients evaluated, 100% had evidence of prior EBV exposure and 72% had evidence for reactivated EBV infection. Notably, 94% of CFS patients had B-cell immunodeficiency with a marked depletion of their CD19+IgM+ mature B-lymphocyte population. A remarkable 81% of CFS patients experienced subjective improvement of their symptoms after treatment with folinic acid (CAS 58-05-9, leucovorin). The findings provide unprecedented evidence that CFS frequently is a folinic acid responsive clinical entity accompanied by B-cell immunodeficiency and inappropriate antibody responses to EBV.

 

 


 

References

Belcaro, G, et al. (2014), ‘Improved management of primary chronic fatigue syndrome with the supplement French oak wood extract (Robuvit(R)): a pilot, registry evaluation.’, Panminerva Med, 56 (1), 63-72. PubMedID: 24231834
Forsyth, L. M., et al. (1999), ‘Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome’, Ann Allergy Asthma Immunol, 82 (2), 185-91. PubMedID: 10071523
Lundell, K., et al. (2006), ‘Clinical activity of folinic acid in patients with chronic fatigue syndrome’, Arzneimittelforschung, 56 (6), 399-404. PubMedID: 16889122
Natella, F, et al. (2014), ‘Absorption, metabolism, and effects at transcriptome level of a standardized French oak wood extract, Robuvit, in healthy volunteers: pilot study.’, J Agric Food Chem, 62 (2), 443-53. PubMedID: 24354337

©

Improved management of primary chronic fatigue syndrome with the supplement French oak wood extract (Robuvit(R)): a pilot, registry evaluation.
            (Belcaro et al., 2014) Download
AIM: The aim of this supplement study was to evaluate French oak wood extract (Robuvit(R), Horphag Research Ltd) used as a supplement in association with a defined management plan for chronic fatigue syndrome (CFS) in healthy subjects with CFS, a condition that has, so far, no specific treatment or management standards. METHODS: Robuvit(R) is a new proprietary and exclusive extract of oak wood with important antoxidant actions. The dosage of the supplementation was 200 mg/day for at least 6 months. The CFS questionnaire and the Brief Mood Introspection Scale (BMIS) questionnaire were used to evaluate mood variations associated with CFS patients. The CFS form includes an analogue scale to record the variations of single symptoms with a score range of 0-10. At inclusion into the registry study, at least 5 symptoms were present. All subjects (age range 35-44; BMI range 24-26) with CFS were tested for oxidative stress: 61 out of 91 subjects had an increased value of oxidative stress. The BMIS scale evaluating mood changes in time was also used. The evaluation was repeated at 3 and 6 months. RESULTS: Out of 91 eligible subjects with CFS, 48 subjects (31 with increased oxidative stress) were accepted as part of the supplement registry study using Robuvit; 43 (30 with increased oxidative stress) were accepted as controls using only the management plan. In the Robuvit(R) group there were 3 drop outs; also 3 controls were lost. Oxidative stress was increased in 64.58% of subjects that used Robuvit and in 69.7% of controls. The average values of oxidative stress were expressed for the whole group. The average follow up was 199.3;9.2 days in the Robuvit group and 202.2;5.5 in the control group with a minimum of 6 months. Considering variations in oxidative stress, there was no significant average change in controls, but a significant decrease from the initial values was observed in Robuvit subjects after 3 and 6 months. The CFS questionnaire variations in score indicated that there was a significant improvement for most symptoms after 3 and 6 months in the Robuvit group. Positive variations were also present in controls, indicating the positive effect of an increased attention to CFS. The improvement in signs/symptoms was significantly more valuable in subjects using the oak wood extract considering the main 8 symptoms and the accessory symptoms. Considering the BMIS variations, the totals for positive and negative items were significantly more favourable for Robuvit subjects. Overall mood evaluation in the oak wood extract group improved from an inclusion average of -6.93;2.1 to +4.32;2.6 at 6 months; in contrast it changed from -6.5;2.5 to -3.4;1.5 in controls. No side effects were observed during the supplementation with Robuvit. The compliance was optimal with 93% of the capsules correctly used. CONCLUSION: This promising pilot supplement registry study indicates a new opportunity of management for these difficult and often neglected patients. Correlation between oxidative stress and CFS have to be better explored.

Absorption, metabolism, and effects at transcriptome level of a standardized French oak wood extract, Robuvit, in healthy volunteers: pilot study.
            (Natella et al., 2014) Download
The consumption of wine and spirits, traditionally aged in oak barrels, exposes humans to roburin ingestion. These molecules belong to a class of ellagitannins (ETs), and their only known source is oak wood. Very little is currently known about roburin bioavailability and biological activity. We reported for the first time human absorption of roburins from a French oak wood (Quercus robur) water extract (Robuvit) by measuring the increase of total phenols (from 0.63 +/- 0.06 to 1.26 +/- 0.18 mug GAE equiv/mL plasma) and the appearance of roburin metabolites (three different glucoronidate urolithins and ellagic acid), in plasma, after 5 days of supplementation. Robuvit supplementation induced also the increase of plasma antioxidant capacity from 1.8 +/- 0.05 to 1.9 +/- 0.01 nmol Trolox equiv/mL plasma. Moreover, utilizing a combined ex vivo cell culture approach, we assessed the effect of Q. robur metabolites (present in human serum after supplementation) on gene expression modulation, utilizing an Affymetrix array matrix, in endothelial, neuronal, and keratinocyte cell lines. The functional analysis reveals that Robuvit metabolites affect ribosome, cell cycle, and spliceosome pathways.

Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome
            (Forsyth et al., 1999) Download
BACKGROUND: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology, consisting of prolonged, debilitating fatigue, and a multitude of symptoms including neurocognitive dysfunction, flu-like symptoms, myalgia, weakness, arthralgia, low-grade fever, sore throat, headache, sleep disturbances, and swelling and tenderness of lymph nodes. No effective treatment for CFS is known. OBJECTIVE: The purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide (NADH) i.e., ENADA the stabilized oral absorbable form, in a randomized, double-blind, placebo-controlled crossover study in patients with CFS. Nicotinamide adenine dinucleotide is known to trigger energy production through ATP generation which may form the basis of its potential effects. METHODS: Twenty-six eligible patients who fulfilled the Center for Disease Control and Prevention criteria for CFS completed the study. Medical history, physical examination, laboratory studies, and questionnaire were obtained at baseline, 4, 8, and 12 weeks. Subjects were randomly assigned to receive either 10 mg of NADH or placebo for a 4-week period. Following a 4-week washout period, subjects were crossed to the alternate regimen for a final 4-week period. RESULTS: No severe adverse effects were observed related to the study drug. Within this cohort of 26 patients, 8 of 26 (31%) responded favorably to NADH in contrast to 2 of 26 (8%) to placebo. Based upon these encouraging results we have decided to conduct an open-label study in a larger cohort of patients. CONCLUSION: Collectively, the results of this pilot study indicate that NADH may be a valuable adjunctive therapy in the management of the chronic fatigue syndrome and suggest that further clinical trials be performed to establish its efficacy in this clinically perplexing disorder.

Clinical activity of folinic acid in patients with chronic fatigue syndrome
            (Lundell et al., 2006) Download
A high incidence of severe B-cell immunodeficiency and chronic reactivated Epstein-Barr virus (EBV) infection in patients with chronic fatigue syndrome (CFS) is reported herein. Of the 58 patients evaluated, 100% had evidence of prior EBV exposure and 72% had evidence for reactivated EBV infection. Notably, 94% of CFS patients had B-cell immunodeficiency with a marked depletion of their CD19+IgM+ mature B-lymphocyte population. A remarkable 81% of CFS patients experienced subjective improvement of their symptoms after treatment with folinic acid (CAS 58-05-9, leucovorin). The findings provide unprecedented evidence that CFS frequently is a folinic acid responsive clinical entity accompanied by B-cell immunodeficiency and inappropriate antibody responses to EBV.

 

 


 

References

Belcaro, G, et al. (2014), ‘Improved management of primary chronic fatigue syndrome with the supplement French oak wood extract (Robuvit(R)): a pilot, registry evaluation.’, Panminerva Med, 56 (1), 63-72. PubMedID: 24231834
Forsyth, L. M., et al. (1999), ‘Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome’, Ann Allergy Asthma Immunol, 82 (2), 185-91. PubMedID: 10071523
Lundell, K., et al. (2006), ‘Clinical activity of folinic acid in patients with chronic fatigue syndrome’, Arzneimittelforschung, 56 (6), 399-404. PubMedID: 16889122
Natella, F, et al. (2014), ‘Absorption, metabolism, and effects at transcriptome level of a standardized French oak wood extract, Robuvit, in healthy volunteers: pilot study.’, J Agric Food Chem, 62 (2), 443-53. PubMedID: 24354337