Multiple Sclerosis Articles 8

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A multimodal intervention for patients with secondary progressive multiple sclerosis: feasibility and effect on fatigue.
            (Bisht et al., 2014)  Download
BACKGROUND:  Multiple sclerosis is an autoimmune disease influenced by environmental factors. OBJECTIVES:  The feasibility of a multimodal intervention and its effect on perceived fatigue in patients with secondary progressive multiple sclerosis were assessed. DESIGN/SETTING:  This was a single-arm, open-label intervention study in an outpatient setting. INTERVENTIONS:  A multimodal intervention including a modified paleolithic diet with supplements, stretching, strengthening exercises with electrical stimulation of trunk and lower limb muscles, meditation, and massage was used. OUTCOME MEASURES:  Adherence to each component of the intervention was calculated using daily logs. Side-effects were assessed from a monthly questionnaire and blood analyses. Fatigue was assessed using the Fatigue Severity Scale (FSS). Data were collected at baseline and months 1, 2, 3, 6, 9, and 12. RESULTS:  Ten (10) of 13 subjects who were enrolled in a 2-week run-in phase were eligible to continue in the 12-month main study. Of those 10 subjects, 8 completed the study and 6 subjects fully adhered to the study intervention for 12 months. Over a 12-month period, average adherence to diet exceeded 90% of days, and to exercise/muscle stimulation exceeded 75% of days. Nutritional supplements intake varied among and within subjects. Group daily average duration of meditation was 13.3 minutes and of massage was 7.2 minutes. No adverse side-effects were reported. Group average FSS scores decreased from 5.7 at baseline to 3.32 (p=0.0008) at 12 months. CONCLUSIONS:  In this small, uncontrolled pilot study, there was a significant improvement in fatigue in those who completed the study. Given the small sample size and completer rate, further evaluation of this multimodal therapy is warranted.

Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: a pilot study.
            (Irish et al., 2017)  Download
Background/objective:  A Paleolithic diet may improve fatigue and quality of life in progressive multiple sclerosis (MS) patients, but past research has evaluated the effects of this dietary intervention in combination with other treatments such as exercise. Thus, the purpose of this pilot study was to evaluate a modified Paleolithic dietary intervention (MPDI) in the treatment of fatigue and other symptoms in relapsing-remitting MS (RRMS). Methods:  We measured the effects of a MPDI in 17 individuals with RRMS. Of 34 subjects randomly assigned to control (maintain usual diet) and intervention (MPDI) groups, nine subjects (one man) completed the control group and eight subjects (one man) completed the MPDI. Results:  Significant improvements were seen in Fatigue Severity Scale score and also in Multiple Sclerosis Quality of Life-54 and time to complete (dominant hand) 9-Hole Peg Test from baseline in MPDI subjects compared to controls. Increased vitamin K serum levels were also observed in MPDI subjects postprotocol compared to controls. Conclusion:  A Paleolithic diet may be useful in the treatment and management of MS, by reducing perceived fatigue, increasing mental and physical quality of life, increasing exercise capacity, and improving hand and leg function. By increasing vitamin K serum levels, the MPDI may also reduce inflammation.

Levocarnitine administration in multiple sclerosis patients with immunosuppressive therapy-induced fatigue.
            (Lebrun et al., 2006)  Download
Nutritional factors and comedications are among the postulated causes of fatigue, a highly prevalent symptom in the multiple sclerosis (MS) population, with serious impact on patients' quality of life. Deficiency of carnitine may play a role by reducing energy production through fatty acid oxidation and numerous MS therapies can induce fatigue syndrome. The aim of this prospective open-labelled study was to collect and study serum carnitine levels in MS patients with and without disease-modifying treatment-induced fatigue syndrome. We investigated whether restoration of the carnitine pool might improve treatment-induced fatigue in MS patients. In our study, there was no statistical difference in fatigue frequency between treated and untreated patients (P=0.5). Matched to age, gender and treatments, carnitine levels were lower for MS treated patients compared to untreated MS patients (P <0.05) or controls (P <0.001). Consecutive patients with low plasma carnitine levels who experienced fatigue were substituted. Treatment consisted of oral levocarnitine, 3-6 g daily. All patients achieved normal plasma carnitine levels. For 63% of patients treated with immunosuppressive or immunomodulatory therapies, oral levocarnitine adjunction decreased fatigue intensity, especially in patients treated with cyclophosphamide and interferon beta.

A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis.
            (Lee et al., 2017)  Download
OBJECTIVE:  The objective of this study was to examine whether participation in a 12-month multimodal intervention would improve mood and cognitive function in adults with progressive multiple sclerosis (MS). METHODS:  In this one-arm, open-label feasibility trial, participants were prescribed a home-based multimodal intervention, including (1) a modified Paleolithic diet; (2) an exercise program (stretching and strengthening of the trunk and lower limb muscles); (3) neuromuscular electrical stimulation (EStim) of trunk and lower limb muscles; and (4) stress management (meditation and self-massage). Individuals completed measures of mood (Beck Anxiety and Depression Inventories) and cognitive (Cognitive Stability Index, Cognitive Screening Test, Delis-Kaplan Executive Function System) and executive function (Wechsler Adult Intelligence Scale) at baseline and 3, 6, 9, and 12 months after the start of the intervention. Dosage of the multimodal intervention was assessed at 3, 6, 9, and 12 months. RESULTS:  The more individuals participated in the intervention activities, the greater improvements they had from baseline to 12 months on self-report measures of anxiety (Beck Anxiety Inventory [BAI]; ps = 0.001 to 0.02), depression (Beck Depression Inventory [BDI]; ps = <0.0001 to 0.09), cognitive function (Cognitive Stability Index [CSI/T], Delis-Kaplan Executive Function System [DKEFS]; ps = 0.001 to 0.06), and executive function (Wechsler Adult Intelligence Scale [WAIS]; ps = <0.0001 to 0.09). Mood and cognitive improvements were more closely related to a higher intake of the modified Paleolithic diet than to exercise and stress management dosage. Anxiety and depression changes were evident after just a few months, whereas changes in cognitive function were generally not observed until later in the intervention period. Mood and cognitive function changes from baseline to 12 months were significantly associated with fatigue improvements (ps = <0.0001 to 0.03). CONCLUSIONS:  A modified Paleolithic diet, exercise, EStim, and stress management intervention like this one has the potential to improve the mood and cognitive symptoms that can lead to considerable suffering in people with MS, potentially improving quality of life and function for people with progressive MS.

Neuromuscular electrical stimulation and dietary interventions to reduce oxidative stress in a secondary progressive multiple sclerosis patient leads to marked gains in function: a case report.
            (Reese et al., 2009)  Download
Neuromuscular electrical stimulation has been used to aid musculoskeletal recovery. Excessive oxidative stress and excitoxicity are implicated in secondary progressive multiple sclerosis. A 52-year-old white female with SPMS had been scooter- and cane-dependent for 4 years. She requested and received a trial of neuromuscular electrical stimulation. Two months after initiating NMES the patient adopted several nutritional interventions to lower oxidative stress and excito-toxicity. During the first 2 months of neuromuscular electrical stimulation, the therapist observed modest gait improvements. Following the addition of nutritional interventions, more rapids gains in strength and endurance, including muscle groups not receiving neuromuscular electrical stimulation were observed by both the therapist and the patient. After 8 months of neuromuscular electrical stimulation (6 months of nutritional intervention) the patient's function had improved sufficiently that she no longer used a scooter or cane and rode her bicycle routinely 8 miles, including hills.

Erythrocyte membrane fatty acids in multiple sclerosis patients and hot-nature dietary intervention with co-supplemented hemp-seed and evening-primrose oils.
            (Rezapour-Firouzi et al., 2013a)  Download
The risk of developing multiple sclerosis (MS) is associated with increased dietary intake of saturated fatty acids. For many years it has been suspected that this disease might be associated with an imbalance between unsaturated and saturated fatty acids. We determined erythrocyte membrane fatty acids levels in Hot nature dietary intervention with co-supplemented hemp seed and evening primrose oils in multiple sclerosis patients. To determine the erythrocyte membrane fatty acids levels and correlate it with expanded disability status scale (EDSS) at baseline after 6 months intervention in MS patients by gas chromatography, in this double blind, randomized trial, 100 RRMS patients with EDSS<6 were allocated into three groups: "Group A" that received co-supplemented hemp seed and evening primrose oils with advised Hot nature diet. "Group B" received olive oil and "Group C" received the co-supplemented oils. The results showed that the mean follow-up was 180 ± 2.9SD days (N=65, 23 M and 42 F aged 34.25 ± 8.07 years with disease duration of 6.80 ± 4.33 years). There was no significant difference in the study parameters at baseline. After 6 months, EDSS, Immunological parameters and the erythrocyte cell membrane with regard to specific fatty acids showed improvement in the group A and C, whereas there was worsening condition for the group B after the intervention. We concluded that Hot-nature dietary intervention with co-supplemented hemp seed and evening primrose oils caused an increase PUFAs in MS patients and improvement in the erythrocyte membrane fatty acids composition. This could be an indication of restored plasma stores, and a reflection of disease severity reduction.

Immunomodulatory and therapeutic effects of Hot-nature diet and co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients.
            (Rezapour-Firouzi et al., 2013b)  Download
BACKGROUND:  Multiple sclerosis (MS) is the most chronic and inflammatory disorder. Because of limited efficacy and adverse side effects, identifying novel therapeutic and protective agents is important. This study was aimed to assess the potential therapeutic effects of hemp seed and evening primrose oils as well as Hot-nature dietary intervention on RRMS patients. METHODS AND MATERIALS:  In this double blind, randomized trial, 100 MS patients with EDSS<6 were allocated into 3 groups: "Group A" who received co-supplemented hemp seed and evening primrose oils with advised Hot-nature diet, "Group B" who received olive oil, "Group C" who received the co-supplemented oils. Mizadj, clinically EDSS and relapse rate as well as immunological factors (IL-4, IFN-γ and IL-17) were assessed at baseline and after 6 months. RESULTS:  Mean follow-up was 180±2.9 SD days (N=65, 23 M and 42 F aged 34.25±8.07 years with disease duration 6.80±4.33 years). There was no significant difference in studies parameters at baseline. After 6 months, significant improvements in Mizadj, EDSS and relapse rate were found in the groups A and C, while the group B showed a border significant decrease in relapse rate. Immunological parameters showed improvement in groups A and C, whereas there was worsening condition for group B after the intervention. CONCLUSION:  The co-supplemented hemp seed and evening primrose oils with Hot-nature diet have beneficial effects in improving of clinical score in RRMS patients which were confirmed by immunological findings.

Activity of liver enzymes in multiple sclerosis patients with Hot-nature diet and co-supplemented hemp seed, evening primrose oils intervention.
            (Rezapour-Firouzi et al., 2014)  Download
BACKGROUND:  It is unknown whether diets with a high dietary total antioxidant capacity (TAC) can modify oxidative stress, low-grade inflammation, or liver dysfunction, all of which are risk factors for multiple sclerosis disease. This study assesses alanine amino-transferase (ALT), aspartate-aminotransferase (AST) and gamma-glutamyl transferase (GGT) activities in MS patients treated with co-supplemented hemp seed and evening primrose oils as well as Hot-nature diet and the therapeutic potential this intervention. METHODS AND MATERIALS:  In this double blind, randomized trial, 100 MS patients with EDSS<6 were allocated into 3 groups: "group A", who received co-supplemented hemp seed and evening primrose oils with advised Hot-nature diet; "group B",who received olive oil; and "group C", who received the co-supplemented oils. Clinically, EDSS as well as serum level of liver enzymes (GGT, AST, and ALT) were assessed at baseline and after 6 months. RESULTS:  Mean follow-up was 180±2.9 SD days (N=65, 23 M and 42 F aged 34.25±8.07 years with disease duration of 6.80±4.33 years). There was no significant difference in the study parameters at baseline. Serum levels of liver enzymes (GGT, AST, and ALT) were serially monitored. Intervention was associated with liver function alteration in three groups. Significance decreased in EDSS score and the levels of liver enzymes were found in groups A and C, whereas elevated serum liver enzymes and EDSS score were observed in group B after the intervention. CONCLUSION:  Selecting foods according to their Total antioxidant capacity such as co-supplemented hemp seed and evening primrose oils with Hot-nature diet affects antioxidant intake and can have beneficial effects on improving EDSS score and activity of liver enzymes in RRMS patients.

Alteration of delta-6-desaturase (FADS2), secretory phospholipase-A2 (sPLA2) enzymes by Hot-nature diet with co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients.
            (Rezapour-Firouzi et al., 2015)  Download
BACKGROUND:  The effect of nutrition and dietary supplements as environmental factors has been suggested as possible factors affecting both disease risk and progression in on the course of multiple sclerosis with complex genetic-risk profiles. This study was aimed to assess regulation of surface-membrane enzymes such as Delta-6-desaturase (FADS2), secretory Phospholipase A2(sPLA2) by hemp seed and evening primrose oils as well as Hot-natured dietary intervention in relapsing remitting multiple sclerosis (RRMS) patients. METHODS AND MATERIALS:  In this double blind, randomized trial, 100 RRMS patients with Extended disability status score (EDSS)<6 were allocated into 3 groups: "Group A" who received co-supplemented hemp seed and evening primrose oils along with advised Hot nature diet; "Group B", who received olive oil; "Group C", who received the co-supplemented oils. Clinically EDSS and functional score as well as biochemical parameters [blood cells polyunsaturated fatty acid (PUFA), FADS2, sPLA2] were assessed at baseline and after 6 months. RESULTS:  Mean follow-up was 180±2.9SD days (N=65, 23 M and 42 F aged 34.25±8.07 years with disease duration 6.80±4.33 years). There was no significant difference in studies parameters at baseline. After 6 months, significant improvements in EDSS and functional score were found in the groups A and C while EDSS and pyramidal score showed significant increase in group B. Alteration of biochemical parameters showed improvement in groups A and C whereas there was worsening condition for group B after the intervention. CONCLUSION:  The co-supplemented hemp seed and evening primrose oils with Hot nature diet can have beneficial effects in improving clinical symptoms and signs in RRMS patients which were confirmed by regulation of surface-membrane enzymes.


 

The Wahls Protocol.
            (Scherger, 2017)  Download
This is an important book. Terry Wahls, MD, is a clinical professor of medicine at the University of Iowa. In her 40s she developed disabling multiple sclerosis (MS). Despite the latest medical treatments, her disease progressed. She undertook painstaking research into what nutritional and other lifestyle factors might help her with the disease. By adopting an anti-inflammatory Paleo-styled diet, she was able to reverse her autoimmune disease and return to normal function. Since then she has reached out to help others suffering from MS and other autoimmune conditions in a variety of clinical trials. She conducts a clinic at the University of Iowa, has an interactive website,1 and lectures widely. She has met with considerable success helping others, and this book is a culmination of her work to date.

High doses of biotin in chronic progressive multiple sclerosis: a pilot study.
            (Sedel et al., 2015a)   Download
BACKGROUND:  No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. OBJECTIVES:  The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. STUDY DESIGN:  Uncontrolled, non-blinded proof of concept study METHODS:  23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. RESULTS:  In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. CONCLUSIONS:  These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going.


 

Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.
            (Sedel et al., 2015b)   Download
Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production.

Dietary approaches to treat MS-related fatigue: comparing the modified Paleolithic (Wahls Elimination) and low saturated fat (Swank) diets on perceived fatigue in persons with relapsing-remitting multiple sclerosis: study protocol for a randomized controlled trial.
            (Wahls et al., 2018)  Download
BACKGROUND:  Fatigue is one of the most disabling symptoms of multiple sclerosis (MS) and contributes to diminishing quality of life. Although currently available interventions have had limited success in relieving MS-related fatigue, clinically significant reductions in perceived fatigue severity have been reported in a multimodal intervention pilot study that included a Paleolithic diet in addition to stress reduction, exercise, and electrical muscle stimulation. An optimal dietary approach to reducing MS-related fatigue has not been identified. To establish the specific effects of diet on MS symptoms, this study focuses on diet only instead of the previously tested multimodal intervention by comparing the effectiveness of two dietary patterns for the treatment of MS-related fatigue. The purpose of this study is to determine the impact of a modified Paleolithic and low saturated fat diet on perceived fatigue (primary outcome), cognitive and motor symptoms, and quality of life in persons with relapsing-remitting multiple sclerosis (RRMS). METHODS/DESIGN:  This 36-week randomized clinical trial consists of three 12-week periods during which assessments of perceived fatigue, quality of life, motor and cognitive function, physical activity and sleep, diet quality, and social support for eating will be collected. The three 12-week periods will consist of the following: 1. OBSERVATION:  Participants continue eating their usual diet. 2. INTERVENTION:  Participants will be randomized to a modified Paleolithic or low saturated fat diet for the intervention period. Participants will receive support from a registered dietitian (RD) through in-person coaching, telephone calls, and emails. 3. FOLLOW-UP:  Participants will continue the study diet for an additional 12 weeks with minimal RD support to assess the ability of the participants to sustain the study diet on their own. DISCUSSION:  Because fatigue is one of the most common and disabling symptoms of MS, effective management and reduction of MS-related fatigue has the potential to increase quality of life in this population. The results of this study will add to the evidence base for providing dietary recommendations to treat MS-related fatigue and other symptoms associated with this disease. TRIAL REGISTRATION:  ClinicalTrials.gov, NCT02914964 . Registered on 24 August 2016.

 


References

Bisht, B, et al. (2014), ‘A multimodal intervention for patients with secondary progressive multiple sclerosis: feasibility and effect on fatigue.’, J Altern Complement Med, 20 (5), 347-55. PubMed: 24476345
Irish, AK, et al. (2017), ‘Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: a pilot study.’, Degener Neurol Neuromuscul Dis, 7 1-18. PubMed: 30050374
Lebrun, C, et al. (2006), ‘Levocarnitine administration in multiple sclerosis patients with immunosuppressive therapy-induced fatigue.’, Mult Scler, 12 (3), 321-24. PubMed: 16764345
Lee, JE, et al. (2017), ‘A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis.’, J Am Coll Nutr, 36 (3), 150-68. PubMed: 28394724
Reese, D, et al. (2009), ‘Neuromuscular electrical stimulation and dietary interventions to reduce oxidative stress in a secondary progressive multiple sclerosis patient leads to marked gains in function: a case report.’, Cases J, 2 7601. PubMed: 19918474
Rezapour-Firouzi, S, et al. (2013a), ‘Erythrocyte membrane fatty acids in multiple sclerosis patients and hot-nature dietary intervention with co-supplemented hemp-seed and evening-primrose oils.’, Afr J Tradit Complement Altern Med, 10 (6), 519-27. PubMed: 24311880
Rezapour-Firouzi, S, et al. (2013b), ‘Immunomodulatory and therapeutic effects of Hot-nature diet and co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients.’, Complement Ther Med, 21 (5), 473-80. PubMed: 24050582
Rezapour-Firouzi, S, et al. (2014), ‘Activity of liver enzymes in multiple sclerosis patients with Hot-nature diet and co-supplemented hemp seed, evening primrose oils intervention.’, Complement Ther Med, 22 (6), 986-93. PubMed: 25453518
Rezapour-Firouzi, S, et al. (2015), ‘Alteration of delta-6-desaturase (FADS2), secretory phospholipase-A2 (sPLA2) enzymes by Hot-nature diet with co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients.’, Complement Ther Med, 23 (5), 652-57. PubMed: 26365444
Scherger, JE (2017), ‘The Wahls Protocol.’, Fam Med, 49 (2), 149-50. PubMed: 28218946
Sedel, F, et al. (2015a), ‘High doses of biotin in chronic progressive multiple sclerosis: a pilot study.’, Mult Scler Relat Disord, 4 (2), 159-69. PubMed: 25787192
Sedel, F, et al. (2015b), ‘Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.’, Neuropharmacology, PubMed: 26327679
Wahls, T, et al. (2018), ‘Dietary approaches to treat MS-related fatigue: comparing the modified Paleolithic (Wahls Elimination) and low saturated fat (Swank) diets on perceived fatigue in persons with relapsing-remitting multiple sclerosis: study protocol for a randomized controlled trial.’, Trials, 19 (1), 309. PubMed: 29866196