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Role of Dietary Intervention in Ameliorating Disability

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The Role of Dietary Intervention in Ameliorating Disability Experienced by Multiple Sclerosis Patients

Mark M. Makar

Hypothesis: Diet modification can significantly improve disability and quality of life in multiple sclerosis patients.

Abstract (word count: 213)

Hypothesis: Diet modification can significantly improve disability and quality of life in multiple sclerosis patients.

Methods: The PubMed database was searched on January 18, 2017 to identify studies relevant to this review. The database search combined terms from three themes: 1) multiple sclerosis patients 2) diet and 3) diet modification. This search yielded 118 articles for screening, with no duplicates. With abstract screening and inclusion criteria, 10 articles were included in this final review.

Results: Modifying the diet of multiple sclerosis patients can greatly reduce fatigue and moderately help decrease symptoms experienced during this disease. Replacing animal based protein and saturated fatty acids from the diet, with plant-based alternatives that are high in starch showed noticeable improvement in symptoms experienced by multiple sclerosis patients. The plant based diet showed a decrease in inflammatory cells, damage of the blood brain barrier, demyelination, as well as axonal and oligodendrocyte injury.

Conclusions: A variety of dietary modifications have been demonstrated to effectively improve quality of life and reduce disability in patients suffering from multiple sclerosis. More studies are needed to assess the efficacy of dietary intervention with respect to reducing episodes of disability experienced by multiple sclerosis patients and including diet modification into the current disease modifying therapies available.

Key Words: multiple sclerosis, diet modification, review

Ultramini Abstract: A search of the PubMed database yielded 10 articles for review. A variety of randomized controlled trials, cohort studies, case studies, cross sectional studies, and surveys regarding multiple sclerosis patients and diet modification to exclude animal protein from the diet and include only a plant based diet, can help to ameliorate disability.

Introduction

Multiple Sclerosis has an ongoing prevalence of 33% globally, with its incidence growing in North America and Europe (Evans C et al., 2013). Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. It is the number one cause of non-traumatic neurodegenerative disability in the young adult population, and is twice as common in women as men (Browne, P et al., 2014). The etiology of multiple sclerosis is still unknown; however, it is believed to have autoimmune origins. Patients tend to experience multiple sclerosis differently; the most common presenting symptoms include sensory (40%), motor (39%), fatigue (30%), and visual (30%), and urinary incontinence (17%) along with less common symptoms presenting as pain and cognitive decline (Evans C et al., 2013). The wide array of symptoms experienced in multiple sclerosis has sprung forth an influx of scholarly research on beneficial disease- modifying therapies (DMTs) and alternative non-traditional methods for treating multiple sclerosis.

Many governments across the world subsidize the current platform therapies for multiple sclerosis across the world including interferon-beta and/ or glatiramer acetate (Browne, P et al., 2014). There is a considerable degree of variance between different levels of income groups in society with regards to accessibility of government-funded therapies for multiple sclerosis (Browne, P et al., 2014). Availability of government funded DMTs were accessible to 96% of high-income countries, 45% of lower to middle income countries, and none in the low-income countries (Browne, P et al., 2014). These surprising statistics have led to new research development, which focus on new treatment methods for multiple sclerosis that cannot only be efficacious, but also be economically accessible for all levels of socioeconomic statuses across the world. There is much speculation regarding cost effectiveness of current treatment regiments for multiple sclerosis with interferon-beta and/ or glatiramer acetate. There is a common consensus that the current platform therapies are not cost effective for the long-term therapy of multiple sclerosis (Bogglid, M et al., 2009).

Given the pathology of multiple sclerosis, it is believed that dietary factors play a key role in autoimmune degradation and can induce myelin breakdown in the central nervous system by molecular mimicry (Ashtari, F et al., 2015). Multiple sclerosis prevalence is believed to be high in regions furthest away from the equator, however recent research has found that these regions of the world also consume a greater amount of saturated fat and animal protein such as dairy (Swank, R et al., 1990). Diets high in animal protein saturated fatty acids tend to worsen progression of multiple sclerosis and increase relapse of symptoms (Hadgkiss, E et al., 2015).It has been proposed that dietary interventions such as low fat, plant-based diet may decrease autoimmune inflammation in the central nervous system and help maintain the protective integrity of the blood brain barrier (Riccio, P et al., 2016). Dietary modifications are thought to be both a cost effective and efficacious treatment option for mitigating symptoms experienced by multiple sclerosis patients such as loss of motor and or sensory function, as well as fatigue (Yadav, V et al., 2016).

This paper aims to provide a practical overview of recent scholarly literature in order to answer the research question: Does diet modification significantly decrease the level of disability and improve the quality of life in patients suffering from multiple sclerosis? The review will be guided under the hypothesis: diet modification can significantly improve disability and quality of life in patients suffering with multiple sclerosis.

Methods

Articles about multiple sclerosis and diet modification were searched on January 19, 2017 using the databases Pub Med and Google Scholar. The database search combined terms from three themes: 1) multiple sclerosis patients (relapsing remitting multiple sclerosis OR primary progressive multiple sclerosis OR multiple sclerosis OR central nervous system demyelination OR autoimmune encephalomyopathy OR demyelinating disease 2) diet (food OR animal protein OR vegan diet OR plant based diet) and 3) diet modification (meal plan OR starch based diet).

When searching for articles, screening settings were set to be within 10 years, English language, full text articles, review, meta-analysis, randomized control trials, and clinical trials. Boolean operators used were OR and AND; OR was used to extract specific terms from the three main themes. AND was used to connect the three themes used in this review. This search yielded 118 articles for screening, with no duplicates. With abstract screening and inclusion criteria, 10 articles were included in this final review.

Inclusion Criteria

All the articles used in this systemic review had to meet the following criteria: 1) English 2) patients with multiple sclerosis for at least 6 months 3) diet modification/ assesment or pharmacological treatment as intervention. The term "multiple sclerosis" was defined as patients showing symptoms for at least 6 months and "diet modification" was defined as any change in daily food intake.

Exclusion Criteria

Articles were excluded from the review if they were published prior to 2007 and/or were not written in the English language and/or if patients had any type of prior chronic disease other than multiple sclerosis.

Results

Randomized Controlled Studies

In a randomized controlled study by Vijayshree Yadav et al, 61 patients with relapsing remitting multiple sclerosis were monitored for a one-year period. The participants were randomly allocated into two groups: Diet group and control group. The diet group was placed on a strict starch plant based diet (potatoes, corn, beans, bread, sweet potato and rice), while the control group was allowed to continue with their usual diet (meat, eggs, dairy products, fish) throughout the study. Each participant was surveyed once every three months or the duration of the study during which disability, and fatigue levels were recorded (by the expanded disability status scale, EDSS and fatigue severity scale, FSS/ modified fatigue impact scale, MFIS respectively). Serum lipid levels and brain MRI were also recorded at the end of the twelve months. The results observed demonstrated a significant reduction (p< 0.0011) in fatigue in the diet group. Figure 1 shows a summary of fatigue improvement throughout the duration of the study. These findings suggest that intervention with a plant-based diet does indeed help reduce fatigue in multiple sclerosis patients.

Macintosh HD:Users:markmakar:Desktop:Screen Shot 2017-02-06 at 11.49.19 AM.png

Figure 1: Graph of Fatigue Scores as Measured by FSS score (A) and MFIS score (B) over a 12 Month Time Span

In a similar randomized control trial by Anja Mahler et al, 18 patients with relapsing remitting multiple sclerosis were randomly divided into two groups. The intervention group was started on 600 mg green tea catechin capsule per day and the control group received a placebo capsule for 12 weeks. A 4-week period was allotted during crossover to assure a sufficient wash out period. The results observed determined there was a significant increase in efficiency of muscle work from 20 (SD= 3) in the placebo group to 25 (SD= 6) in the intervention group (p>0.004). This finding suggests that intervention with plant based green tea extract helps to decrease muscle fatigue in multiple sclerosis patients.

Cohort and Cross Sectional Studies:

Emily Hadgkiss et al surveyed 2087 patients with multiple sclerosis globally. The comprehensive online survey inquired about dietary habits, quality of life, disability, and relapse rate. Dietary habits were assessed using the Diet Habits Questionnaire (DHQ), baseline quality of life was calculated using the Multiple Sclerosis Quality of Life scale (MSQOL-54), and disability was calculated by using the Expanded Disability Status Scale (EDSS). Results of this study demonstrated that patients who reported higher intake of fruits and vegetables and low intake of fats had significantly higher physical health scores (PHC) ranging from 54 to 68 (p<0.001), while their mental health composite scores (MHC) ranged from 61 to 75 (p<0.001), both subsets of the MSQOL-54. Figure 2 and Figure 3 shows a brief summary of these results.

Macintosh HD:Users:markmakar:Desktop:Screen Shot 2017-02-07 at 2.56.52 PM.png

Figure 2: Mean Physical Health Composite by Dietary Factors   

Macintosh HD:Users:markmakar:Desktop:Screen Shot 2017-02-07 at 2.57.45 PM.pngFigure 3: Mean Mental Health Composite by Dietary Factors

Another significant finding in this study showed that patients who consumed meat and dairy had much poorer disability scores 624 (p<0.001) as compared to those participants who's diet consisted of more fruits and vegetables 356 (p<0.001). This trend can be observed in Table 1. The frequency ofmultiple sclerosis disease activity was also significantly increased in meat and dairy consumers, 309% and 271% respectively (p<0.001) as compared to 190% in fruit and vegetable consumers (p<0.001). A healthier diet with fruits and vegetables only slightly improved relapsing rates, with only a 1.2% decrease over the twelve month span (95% CI 0.981- 0.995, P<0.001). These findings suggest that reducing and increasing fruit and vegetable intake and meat and dairy consumption from patients diets, may improve physical and mental health and reduce frequency and disability disability in multiple sclerosis patients.

Macintosh HD:Users:markmakar:Desktop:Screen Shot 2017-02-07 at 9.06.09 PM.pngTable 1: Level of disability and disease activity by dietary subgroups

Soodeh Jahromi et al surveyed the diets of 75 women with multiple sclerosis from Iran. Dietary patterns were assessed using a 168-item food frequency questionnaire (FFQ). This study found patients who's diet consisted mainly of animal fat (high in animal fats, potato, other meat products, sugars, hydrogenated fats and low in whole grains, spices, and poultry without skin) had higher incidence of multiple sclerosis (OR = 1.99; CI: 1.63-2.94; P = 0.04), and patients who had a vegetable based diet (high in green leafy vegetables, hydrogenated fats, tomato, yellow vegetables, fruit juices, onion, and other vegetables) had lower incidence of multiple sclerosis. (OR = 0.42; 95% CI = 0.19-0.90; P = 0.026). These findings suggest an inverse relationship between high amount of hydrogenated fats, green leafy vegetables, fruit juices, and other vegetables and risk of multiple sclerosis.

A longitudinal retrospective analysis was conducted by Weinstock-Guttman et al, where lipid levels of 492 multiple sclerosis patients were assessed for one a year time period. The study deduced that increasing LDL (p<0.006) levels significantly correlated with a worse EDSS. A similar trend was also found with higher cholesterol levels (p<0.008) and accelerating disease progression in patients with multiple sclerosis. There was, however, no significant correlation between high HDL levels (p= 0.79) and disease progression. These findings suggest that increased serum cholesterol and LDL levels were associated with a worse EDSS and increased incidence of brain lesions seen on MRI of multiple sclerosis patients

Geeta Ramsaransing et al investigated the levels of 23 dietary nutrients in 80 patients with multiple sclerosis: 27 with benign course multiple sclerosis, 32 with secondary progressive multiple sclerosis, and 21 with primary progressive multiple sclerosis. The secondary progressive group demonstrated significant decreases in magnesium intake (p<0.009) and calcium intake (p<0.03), while the benign course group and primary progressive group showed no changes in magnesium or calcium intake. These findings suggest that. This study also found that multiple sclerosis patients had subpar intake of folic acid (p<0.002), copper (p<0.01), and magnesium (p<0.002) compared to the daily-recommended allowance. These findings suggest that adequate dietary intake of folic acid, magnesium, and copper may potentially be factors in diminishing multiple sclerosis disease progression.

In a cohort study by Mike Bogglid et al, 5583 multiple sclerosis patients in the UK were monitored from May 2002 to April 2005 in an effort to establish the long term cost effectiveness of current platform therapy (interferon-beta and/ or glatiramer acetate) for multiple sclerosis. Following the duration of the study, 49% of patients that were on platform therapy were found to have experienced progressive deterioration in EDSS 2.68 at baseline, 2.90 after one year, and 3.24 after two years (p<0.001). These findings suggest that the current disease modifying therapies for multiple sclerosis are not effective when used for long-term treatment.

Case Control Studies

In a comparable study to Soodeh Jahromi et al's work, a cross sectional analysis by Tatjana Pekmezomiv et al was conducted to investigate possible dietary trends in patients living with multiple sclerosis. The dietary habits of 110 multiple sclerosis patients were compared to 110 healthy controls. Results showed that meat intake such as chicken (OR=2.0, p=0.045), lamb (OR=2.1, p=0.013), and beef (OR=1.7, p=0.043) was significantly higher in multiple sclerosis patients as compared to healthy controls. Furthermore, the study found that multiple sclerosis patients consumed significantly higher levels of ice cream (OR=0.18, p=0.031) and butter (OR=1.7, p=0.056) in comparison to controls. Table 2 shows a brief summary of these results. These findings suggest that there is a significant association between dietary intake of meat products such as chicken, lamb, and beef, as well as ice cream and butter to the disease in question. This may suggest that removal or reduction of said food items may be beneficial in decreasing the incidence of multiple sclerosis.

Table 2: Consumption frequency of different food groups and food items in MS patients and controls

Macintosh HD:Users:markmakar:Desktop:Screen Shot 2017-02-12 at 5.01.54 PM.png

Fereshteh asharti et al conducted a case control study in order to evaluate cow's milk allergy (CMA) in multiple sclerosis patients versus healthy individuals. The authors compared 48 multiple sclerosis patients with 48 healthy controls. After 16 weeks there were no differences in the frequency of CMA between the two groups. Contrary from the results of Emily Hadgkiss et al's study, the study done by Vahid Shaygannejad et al, found that there was a higher frequency of dairy products consumed by healthy control individuals (67%, p=0.01) compared to multiple sclerosis patients. These findings suggest that there is no reliable association between milk consumption and risk of multiple sclerosis development.

Discussion

This review attempted to answer the question: Does diet modification significantly decrease the level of disability and improve the quality of life in patients suffering from multiple sclerosis? The general shared consensus of articles included in this review support the proposed hypothesis of diet modification can, indeed, significantly improve disability and quality of life in multiple sclerosis patients (Hadgkiss E et al., 2015; Jahromi S et al., 2012; Shaygannejad V et al., 2016; Yadav V et al., 2016; Ramsaransing G et al., 2009; Jahroomi S., 2012; Pekmezovic T et al., 2012). However, one article concluded that consumption of animal protein in the form of milk did not increase the risk of developing multiple sclerosis (Shaygannejad V et al., 2016). However, these findings should not be generalized to the general population as the sample size used was too small and did not represent a true spectrum of multiple sclerosis prevalence across the world. The remaining articles reviewed corroborated that removal of both animal based protein and saturated fatty acids from the diet, and their replacement, high starch, plant-based alternatives, provided improved disability and fatigue in patients suffering from this disease (Pekmezovic T et al., 2012; Yadav V et al., 2016). The plant based, high starch diet (potato and rice) was found not only be an efficacious treatment option for mitigating symptoms experienced by multiple sclerosis patients but is also economically accessible for all levels of society across the world. It is also evident that most clinicians involved in the articles reviewed, found enough evidence in their research to warrant providing advice to patients with multiple sclerosis about the importance of healthy diet modification in regards to their condition (Hadgkiss E et al., 2015; Jahromi S et al., 2012; Yadav V et al., 2016; Ramsaransing G et al., 2009;).

Many of the articles reviewed used a survey platform to assess the diets of multiple sclerosis patients; this may have had some effect on the results due to the nature of the retrospective study design used, making way for possible recall bias, hence potential misreporting of dietary intake (Pekmezovic T et al., 2012; Hadgkiss, E et al., 2015;). As well, since many of the articles used a food frequency survey approach, it may have limited the interventions possible with regards to experimenting with different types of foods that may have improved or worsened multiple sclerosis outcomes. A common limitation in this review is that none of the articles inquired about portion sizes of their meals, just food items (Hadgkiss E et al., 2015; Jahromi S et al., 2012; Yadav V et al., 2016; Ramsaransing G et al., 2009; Jahroomi S., 2012;). Across all articles reviewed, mean age of the study population was between 30- 47 years; therefore the results of this review may not be true for younger or more elderly patients. Many of the researchers in this review found it difficult to recruit many subjects due to health concerns regarding a low protein diet (Hadgkiss E et al., 2015; Jahromi S et al., 2012; Yadav V et al., 2016; Ramsaransing G et al., 2009; Jahroomi S., 2012). It is possible that the results observed with regards to studying the diets of multiple sclerosis patients may have been due to associations with other confounding variables. It is also important to note that given the disabling nature of multiple sclerosis as a disease state, many of the patients may be relying on a caregiver or family member for their meals, which may influence their dietary intake.

Limitations encountered in this review include only utilizing articles written within the past 10 years, articles collected from only two databases (PubMed and Google Scholar), and articles were only included only if they were published in the English language.

Future research may consider standardizing meal portion sizes during experimentation as various parts of the world have varying standard portion sizes. Future studies should also consider accounting for possible supplementation use in the participants such as vitamin and mineral intake. This would help diminish possible confounding variable. Future research may also utilizing experimental analysis encompassing a larger age range. All together, these factors would help encompass a much broader spectrum of patients living with multiple sclerosis.

Conclusion

In conclusion, diet modification has been shown to be a viable option not only for effectively improving quality of life, and reducing disability in patients suffering from multiple sclerosis, but also in lowering the risk of developing the disease. Evidence showed that removal of both animal based protein and saturated fatty acids from the diet, and replacing them with plant-based alternatives which are high in starch showed noticeable improvement in muscle weakens and fatigue levels. Unfortunately we do not have sufficient research that definitively demonstrates that diet modification can be used alone without traditional medication to prevent and/ or treat multiple sclerosis. Additional studies are needed to assess the efficacy of dietary intervention with respect to reducing episodes of disability experienced by multiple sclerosis patients and including diet modification into the current disease modifying therapies available.

References

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Appendix

First Author

Population

Year of Publication

Study Design

Outcome

Ashtari, F.

48 patients with Multiple Sclerosis and 48 healthy patients as control group, mean age 30.7

March 18, 2013

Case control Study

Serum IgE levels against cow's milk antigen was taken from both groups. Results were very similar between both groups and showed no statistical significance (30.7 ± 6.9 vs. 30.9 ± 6.3 respectively, P value = 0.83)

Boggild, M.

5583 patients with multiple sclerosis monitored from May 2002 to April 2005 from neurology clinics across the UK

August 5, 2009

Prospective Cohort Study

Patients received Interferon Beta treatment to determine long term cost effectiveness. Results showed worse disability progression than in the untreated group (deviation score of 113%; increase in mean disability status scale 0.28)

Hadgkiss, E.

2087 patients with multiple sclerosis, mean age 45.5 participated in a comprehensive online survey

March 17, 2014

Cross Sectional Study

Participants reporting more healthy habits in relation to their intake of fruit and vegetables and fat were significantly more likely to have better health related quality of life (HRQOL). Subjects reporting no meat consumption or dairy consumption had significantly higher physical health composite (PHC) and mental health composite (MHC) scores (P < 0.001), when compared to meat and dairy consumers.

Jahroomi, S.

75 women with multiple sclerosis from Iran, mean age 32.9

January 15, 2012

Cross Sectional Study

Subjects who ate a diet that consist of high animal fat, meat, and hydrogenated fats , were related to a higher risk of relapsing remitting multiple sclerosis (OR = 0.42; 95% CI = 0.19-0.90;

P = 0.026). Subjects who's diet consisted mainly of vegetable based foods and no meat products were related to a lower risk of relapsing remitting multiple sclerosis (OR = 1.99; CI: 1.63-2.94; P = 0.04)

Mähler, A.

18 patients with multiple sclerosis

January 14, 2015

Randomized Control Trial, Placebo controlled Double blind Crossover study

Subjects received 600 mg/d of plant based green tea catechins and a placebo over 12 weeks. Green tea catechins given to multiple sclerosis patients for 12 weeks improved muscle metabolism during moderate exercise.

Pekmezovic, T.

110 patients with multiple sclerosis from Serbia from 2001 to 2006

December 7, 2012

Case Control Study

Consumption of beef or butter was significantly related to multiple sclerosis OR=2.0, p=0.017 and OR=1.9, p=0.027, respectively

Ramsaransing, G.

80 patients with multiple sclerosis were enrolled: 27 with a benign course, 32 with secondary progressive MS, and 21 with primary progressive MS.

August 10, 2009

Prospective Cohort Study

There was 20% decreased intake of magnesium (p = 0.009) and a 15% increased intake of calcium (p = 0.03) in secondary progressive Multiple sclerosis patients, when compared to patients with either benign or primary progressive MS

Shaygannejad, V.

536 multiple sclerosis patients from Iran, mean age 34.37

June 8, 2016

Case Control Study

The frequency of dairy consumption in the control group was significantly higher than in MS patients. However,

no relation between processed milk and risk of MS development (case = 56.6%, control = 67.5%, P = 0.01)

Weinstock-Guttman, B.

492 patients with multiple sclerosis, mean age 47.1

October 4, 2011

Single-center, retrospective, longitudinal cohort study

Increased LDL (p = 0.006)

and total cholesterol levels (p = 0.001)

are associated with increased disability progression in MS.

Yadav, V.

61 patients with relapsing-remitting multiple sclerosis (RRMS), mean age 40.9. One year long study

July 1, 2016

Randomized Control Trial

MRI outcomes between the starch only diet group and control group showed no difference in brain volumes after the study. Fatigue, however, was greatly reduced in the starch only diet group. Diet group also experienced a reduced BMI by an average of 0.18 kg/m2 per month


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