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A study of dietary modification: Perceptions and attitudes of patients with multiple sclerosis
Multiple Sclerosis and Related Disorders, July 2016, Pages 54 - 57
Modifiable risk factors for multiple sclerosis (MS), including obesity and the gut microbiome, have been studied and have been found to be potentially relevant. Given this, there is a growing interest in diet modification as a means of impacting MS risk and disease course.
The aim of this study was to determine the current behaviors, level of interest, and relevant factors surrounding modification of diet in MS patients.
A total of 601 MS patients were mailed a dietary modification survey containing questions regarding subject demographics, disease course, and diet-related questions.
Of the 199 survey responders, 17% admitted to currently attempting a diet for their MS and 91.5% were interested in diet modification as a means of benefiting their disease. Willingness to attempt diet therapy was not affected by demographic features or an individual’s disease course. Over 85% of these patients were willing to attempt diet therapy for 3 months or longer.
The majority of survey responders expressed interest in diet modification in attempts to improve or treat their MS. Our data demonstrate the feasibility of patient recruitment for future studies assessing therapeutic intervention by way of diet modification for MS disease.
- A feasible number of MS patients are interested in diet therapy for their disease.
- Disease and demographic factors do not appear to predict willingness to modify diet.
- A feasible proportion of patients are willing to attempt diet therapy for >3 months.
Keywords: Multiple sclerosis, Diet, Autoimmune, Obesity.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that is characterized by accrual of multifocal demyelinating lesions in the brain and spinal cord driven by an underlying, dysregulated immune response. The cause of MS is multifactorial, with recognized contributions from both genes and environmental exposures (Belbasis et al., 2015). Proposed environmental risk factors include vitamin D deficiency (Munger et al., 2006), exposure to smoking (Handel et al., 2011), Epstein Barr virus infection (Handel et al., 2010), and indigenous geography and migration patterns (Gale and Martyn, 1995, Hernan et al, 1999, and Wallin et al, 2004). In addition to these environmental risk factors, obesity in adolescence appears to be associated with an increased risk of MS (Hedstrom et al, 2012 and Langer-Gould et al, 2013). The underlying pathobiologic mechanism that accounts for the association between obesity and risk of multiple sclerosis is not known; however, it may potentially relate to the fact that obesity both increases the risk of vitamin D deficiency (Brenton et al., 2014) and is associated with the development of a chronic, serological pro-inflammatory state (Wisse, 2004 and Sanna et al, 2003).
In line with the potential effects of obesity upon risk for MS, major attention has been given to the role that an individual's gut microbiome plays in the development of autoimmune disease. As gut-associated lymphoid tissue comprises the body's largest mass of lymphoid tissue, the bacterial milieu within the gastrointestinal tract likely has a substantial influence on an individual's immune response. To this end, small case-control studies have demonstrated differences in the gut flora between patients with MS and those without MS (Miyake et al., 2015). It stands to reason that dietary intake, thereby, has a direct influence upon gut flora and ultimately upon the expression of an individual's immune system.
Diet modification and its impact upon MS has been posited to have a potential effect on disease risk and clinical course. One of the greatest obstacles in any dietary study is ensuring and measuring subject compliance with a diet in order to assess long-term benefit upon MS disease course. Several studies have attempted to determine the impact of various diet modifications (Socha et al, 2014, Millar et al, 1973, Farez et al, 2015, Baarnhielm et al, 2014, and Hoare et al, 2015); however, these studies are small, relatively short-term, and often rely on the patient's dietary recall. Despite a large proportion of MS patients reporting utilization of dietary strategies (Yadav et al., Baldauf-Wagner), studies aimed at rigorously defining impact of diet upon MS are few. A Cochrane meta-analysis assessed the impact of diet interventions upon MS and concluded that supportive evidence is insufficient, primarily due to a lack of randomized controlled trials within this field (Farinotti et al., 2012).
Conceptually, a subject's willingness and ability to adhere to diet therapy can be a challenging obstacle. While there have been several studies looking at diet modification in the MS population, we are unaware of any studies that directly address patient-focused perceptions and/or barriers to diet-based research within the MS community. Therefore, we performed a cross-sectional survey study of our MS patient population to determine the prevalence of MS patients currently attempting a diet, patient willingness to initiate and adhere to dietary modification in hopes of benefiting their disease, and factors that influence a patient's willingness to modify their diet.
This cross-sectional, survey-based cohort study was approved by the University of Virginia's Institutional Review Board. A total of 601 MS patients (including all MS subtypes), seen at the University of Virginia's J.Q. Miller Multiple Sclerosis Clinic, were mailed a 4-page survey packet with a return self-addressed, stamped envelope in April 2015. One page of this packet was dedicated to a diet survey and contained questions regarding subject demographics (gender, body mass index (BMI), current age, age-at-diagnosis), disease course (MS subtype, disease duration, number of disease modifying therapies (DMT) attempted), and diet-related questions (patient-perceived obesity, current diet, willingness to try a diet for MS and time willing to adhere to that diet). The first 3 pages of the questionnaire contained the 12 Item MS Walking Scale (MSWS-12) and the Modified Fatigue Impact Scale (MFIS), prepared as part of a separate study of item response theory for these two outcome measures. Given that obesity was hypothesized to have an impact on willingness to attempt diet modification, clinic-recorded BMI from the patient's last clinic visit was obtained for all returned surveys so that it could be compared to the patient-reported value.
Subjects who answered “yes” for interest in attempting dietary therapy for MS were then asked to select any or all diet types from a list of popular diets that they would be willing to attempt: high carbohydrate, paleo, vegan, vegetarian, low carbohydrate/high fat, and/or low salt diets. They were also asked to estimate how long they would be willing to adhere to diet therapy for the purposes of a diet-based study in MS. To be included in the survey mailing list, a patient had to have a neurologist-confirmed diagnosed of MS (Polman et al., 2011). Patients were automatically excluded from the study if they did not fully complete the questionnaire.
Data was compiled on all dietary surveys completed and received by October, 2015. Additionally, a chart review was conducted on all 402 subjects who were mailed a survey and did not respond. Data obtained on this non-responder population included gender, MS subtype, BMI, age-at-diagnosis, current age, disease duration, and number of DMTs attempted. Non-responders who had not been seen at our institution within the past 2 years of this chart review were excluded from the non-responder data analysis.
Statistical analysis was completed using SAS 9.2 software. Demographic factors were analyzed collectively for the entire responder pool. Following primary analysis, subjects were divided into two groups: those that would and those that would not change their diet in attempts to impact their MS disease course. Demographic traits were then compared between these two groups using T-test and chi-square as appropriate for continuous and ordinal variables. Similarly, demographic traits between the responder and non-responder cohorts were compared using the same statistical methods. A two-sided p-value of <0.05 was defined as statistically significant.
From 601 mailed surveys, 199 subjects (33%) returned a fully-completed survey questionnaire. Of survey responders, there was a predominance of female sex (70%). Patients exhibited a mean disease duration of 12 years and a median duration of 9 years (range: <1 year to 54 years). MS subtype proportion in our study appeared representative of the expected clinical prevalence: relapsing-remitting MS (RRMS): 71.4%; progressive relapsing MS (PRMS): 7.5%; primary progressive MS (PPMS): 8.5%; secondary progressive MS (SPMS): 12.6%. The average, self-reported body mass index (BMI) of our collective responders was 28.3 (median: 26.6; range: 14.8 to 54.9).
Overall, 34 (17%) responders reported they were currently attempting a diet for their MS and 182 subjects (91.5%) were interested in diet modification as a means of benefiting their MS disease. Though the number of patients unwilling to attempt diet modification for MS was small, two cohorts were analyzed comparatively based upon willingness (or unwillingness) to alter diet in attempts to impact their underlying MS. Demographic factors (Table 1) were not significantly different between these two cohorts. A subject's willingness to attempt dietary therapy was not affected by the patient's gender, disease duration, BMI (self-reported and actual), self-perceived obesity, current diet, or number of DMTs attempted in the past. Willingness to attempt diet therapy may be more likely in younger MS subjects, as both age and age-at-diagnosis exhibited a trend toward significance (p=0.07 and p=0.06 respectively). Comparison among all four individual MS subtypes demonstrated a non-significant (p=0.08), but trending difference in a subject's willingness to attempt diet therapy; however, when directly comparing relapsing remitting versus pooled progressive (including primary and secondary) MS subjects, a significant difference was found with progressive MS subjects being significantly more likely to pursue dietary therapy (RRMS: 90% versus PPMS/SPMS: 100%; p=0.03). There was no significant difference between patient-reported BMI and actual BMI values (as obtained and recorded by a medical professional), though the mean self-reported values were consistently lower than the actual BMI values.
Clinical Characteristics of Subjects Based on Willingness to Attempt Diet Modification.
|Would change diet||Would not change diet||p-Value|
|Number of patients||182 (91.5%)||17 (8.5%)|
|Current age mean (Range)||50 years (21–80)||56.2 years (19–78)||0.07|
|Mean age at diagnosis (Range)||38.1 years (16–70)||43.9 years (18–73)||0.06|
|Relapsing remitting MS||128 (70.3%)||14 (82.4%)|
|Progressive relapsing MS||12 (6.6%)||3 (17.6%)|
|Primary progressive MS||17 (9.3%)||0 (0%)|
|Secondary progressive MS||25 (13.8%)||0 (0%)|
|Patient-reported BMI, Mean (Range)||28.5 (16.4–54.9)||26.1 (14.8–41.5)||0.17|
|True BMI, Mean (Range)||29.0 (16.9–53.4)||27.3 (18.5–43.4)||0.33|
|Underweight (BMI<18.5)||3 (1.6%)||2 (11.8%)|
|Normal weight (BMI 18.5–24.99)||66 (36.3%)||6 (35.3%)|
|Overweight (BMI 25–29.99)||44 (24.2%)||5 (29.4%)|
|Obese (BMI>30)||69 (37.9%)||4 (23.5%)|
|Disease duration||11.9 years (0.5–54)||12.2 years (1–40)||0.61|
|Medications attempted||2 (0–7)||1.5 (0–6)||0.15|
|Current diet||32 (17.6%)||2 (11.8%)||0.54|
|Duration willing to attempt diet|
|<1 month||3 (1.5%)|
|1–2 months||23 (12.5%)|
|3–4 months||29 (16%)|
|5–6 months||31 (17%)|
|>6 months||96 (53%)|
Over half of patients willing to attempt diet therapy (53%) were also willing to do so for a duration of greater than 6 months. The majority of patients were willing to attempt diet therapy for at least 1 month (98.5%). The subjects willing to attempt diet therapy were then given specific diet choices from a list of commonly acknowledged diets. From this list, the subject was asked to choose any (or all) diets that they would personally consider attempting. Of all diets listed, the number of patients who reported interest by diet type was: paleo diet – 107 (58.8%), high carbohydrate diet – 97 (53.3%), low salt diet – 94 (51.6%), modified Atkins diet – 83 (45.6%) diet, vegetarian diet – 61 (33.5%), vegan diet – 34 (18.7%) (Fig. 1).
Diet Modification Type Most Desired by Multiple Sclerosis Patients.
Data assessment of subjects that did not respond to the survey (“non-responders”) included a total of 324 subjects meeting study inclusion/exclusion criteria. Non-responders were excluded from analysis as follows: 8 subjects were deceased, 34 subjects had a change of address prior to the mailing, and 36 subjects had not been seen in our clinic for over 2 years. Demographic factors of the remaining 324 non-responders were compared against the total cohort of survey responders. Non-responder characteristics were not statistically different from the responder cohort–including mean age-at-diagnosis (37.4 years; range 8–63), current age (48.7 years; range 14–81), actual BMI (29.5; range 14.3–56.1), and number of DMTs attempted (2 medications; 0–7).
In this cross-sectional, survey-based study, we examined the attitudes of MS patients toward diet modification and found that the majority of surveyed patients indicated interest in diet therapy as a means of potentially impacting their disease course. Given that the majority of patients expressed interest in diet modification, our comparator group (no interest in diet change) was subsequently small. When compared to each other, there were no demographic factors that predicted a patient's willingness to modify their diet; however, given the small size of the comparator group, the study was insufficiently powered to reliably assess significant differences between these factors. It is notable that a few of these demographic characteristics (including current age, age-at-diagnosis, and MS subtype) had p-values approaching significance, suggesting that these factors are potentially meaningful and may prove to be of significance in a study of larger sample size.
The concern of adherence to a strict diet therapy is a valid concern when conceptualizing a clinical diet-based therapy study. In the population surveyed, over 85% were willing to adhere to diet therapy for 3 months or longer for the purpose of determining if a particular diet impacted disease course. A small percentage (1.5%) was only willing to attempt diet therapy for less than one month. These numbers would suggest that a safety and tolerability pilot study assessing a three month diet intervention would be feasible within the MS population. Though the indicated duration of patient compliance in our study may not directly translate to patient adherence in a formal study environment, our data do indicate a strong willingness to pursue long-term diet therapy in attempts of providing disease benefit.
Despite the distinct lack of rigorous data on the benefits of individual dietary therapies in MS, subjects are most interested in pursuing a paleo diet. Though no current data exists on the benefits of a paleo diet for multiple sclerosis, this diet has been promoted in popular press and social media as beneficial for autoimmune disease. Other popular diets included a high carbohydrate diet, low salt diet, and modified Atkins diet. Higher sodium intake has been associated with increased clinical symptoms and new T2-hyperintense and/or gadolinium enhancing lesions on MRI (Farez et al., 2015), though a recent study on salt intake in pediatric-onset MS suggests no effect on disease risk (McDonald et al., 2015). Though no data exists on high amounts of carbohydrate intake in MS, there are a few studies regarding the impact of high fat on MS (Baarnhielm et al, 2014, Hoare et al, 2015, and Kim et al, 2012). In a single animal model study, a high fat diet was associated with a more severe expression of experimental allergic encephalomyelitis (EAE) (Timmermans et al., 2014); however, studies in human subjects have failed to show this. In fact, one study demonstrated an inverse association between increased polyunsaturated fatty acids and risk of CNS demyelination (Hoare et al., 2015). In line with this study, a higher fatty fish intake has also been associated with a lower risk of MS disease in human subjects (Baarnhielm et al., 2014). Collectively, these studies could indicate a dichotomous role of dietary fat intake upon MS disease risk, with potential beneficial effects conferred from unsaturated fatty acids and maladaptive effects from high amounts of saturated fats.
This study has some limitations, including the limited response rate to the survey; however, the demographics of our survey responders represent an expected distribution from a typical MS population sample – with the exception of our study population exhibiting an older average age. While it may be a typical demographic, our study could exhibit a selection bias towards those subjects who elected to complete and return the survey, as this population may represent a more proactive group that would be more inclined to undergo dietary change. It is unlikely that our data exhibits a pro-diet bias as a result of survey contents, given that the diet questionnaire was only a subset of a larger, multi-purpose survey. Additionally, a comparison of non-responder and responder data proved to be similar in regards to patient and disease characteristics. Another concern, is the overall small number of patients in our sample who reported being unwilling to attempt diet therapy (the comparator group). Given the small number of patients unwilling to attempt diet therapy for MS, the comparison between those who are willing may be limited. It is possible that the demographic factors hypothesized to impact willingness to attempt diet therapy are, in fact, significant predictors; however, given the small size of the comparative cohort, this relationship was not able to be demonstrated.
This study demonstrates the feasibility of patient recruitment for future studies assessing dietary therapy in attempts to determine impact upon MS disease course. Our data suggest that pilot studies for a particular diet should be targeted at a 3 to 6 month timeframe for the purposes of assessing safety and tolerability within the MS population. Our study did show a trend towards significance for younger patient willingness to pursue a diet change, suggesting that future diet studies in MS targeting younger MS subjects as the primary study group will increase the ease of recruitment. Though 100% of our PPMS and SPMS population indicated interest in diet therapy, a high level of interest was also seen amongst the relapsing group (90%), indicating that future diet studies may focus recruitment on any or all disease subtypes.
Once safety and tolerability are demonstrated, larger-scale, longitudinal data would then be needed to assess a diet's impact upon disease outcome measures – which may include (but are not limited to) quality of life, fatigue scores, weight change, annualized relapse rate, physical disability progression, cognition, and radiographic progression. Though clinical dietary studies in MS may face several logistic obstacles, encouragingly, our study supports a feasible proportion of the MS patient population with interest in engaging in diet-based clinical research to determine the effects of modification of diet upon MS disease.
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Department of Neurology, University of Virginia, USA
⁎ Correspondence to: Department of Neurology, University of Virginia, PO Box 800394, Charlottesville, VA 22908, USA.
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