Association Between Improved Serum Fatty Acid Profiles and Cognitive Function During a Dietary Intervention Trial in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Cognitive impairment is a common multiple sclerosis (MS)-related symptom that impacts quality of life (QOL). Diet interventions are shown to be beneficial in managing QOL, and the intake of essential fatty acids is linked with improved cognitive function. However, the effect of diets on serum fatty acid profiles and cognitive function is unknown. METHODS: A previous randomized, parallel-arm trial recruited participants with relapsing-remitting MS (N = 77). Study visits included 4 time points: run-in, baseline, 12 weeks, and 24 weeks. During the run-in phase, participants followed their usual diet and were then randomly assigned to either a modified paleolithic (Wahls) or a low saturated fat (Swank) diet at baseline. Assessments at study visits included cognitive function assessed by Symbol Digit Modalities Test-Oral (SDMT-O) and Perceived Deficits Questionnaire (PDQ), and serum fatty acids, including eicosapentaenoic (EPA), docosahexaenoic (DHA), and arachidonic (ARA) acids. RESULTS: Both groups had significant improvements in all serum fatty acids (P < .01), except for ARA, as well as SDMT-O at 24-weeks (P < .05), total PDQ at 12 and 24 weeks (P < .01) compared with baseline values. The 12-week changes in ω-3 (EPA + DHA) index and EPA serum fatty acids were associated with SDMT-O changes (P ≤ .05); however, the changes in fatty acid levels did not mediate the effect of the diets on SDMT-O or PDQ (P > .05). CONCLUSIONS: Both diets led to improvements in serum fatty acid profiles and cognitive function, with associations between the 12-week ω-3 (EPA + DHA) index and EPA changes with SDMT-O.

The effect of dietary interventions on inflammatory biomarkers among people with multiple sclerosis: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system, characterized by demyelination and neurodegeneration, which has a profound impact on the quality of life. Dysregulated inflammatory processes are a major driver of MS progression, with many areas of research being dedicated to modulating inflammation in people with MS. Several dietary patterns have been associated with improvements in inflammatory biomarkers; although, the findings have been inconsistent. Thus, this study aims to evaluate the effects of dietary interventions on inflammatory markers in adults with MS. METHODS: Electronic databases, including PubMed/MEDLINE, Web of Science, Scopus, and Cochrane/Central, will be searched. Screening, selection, and extraction of data, along with quality assessment of included studies, will be done by two separate reviewers, and any potential conflicts will be settled through discussion. Two reviewers will independently assess the risk of bias in included studies using the Cochrane Risk of Bias Tool. If plausible, the results will be synthesized and pooled for meta-analysis. The overall quality of evidence of each study will be evaluated using the NutriGRADE tool, which is a modification to the Grading Recommendations Assessment, Development, and Evaluation (GRADE) developed specifically for nutrition research. DISCUSSION: Studies have demonstrated conflicting results regarding the effects of dietary interventions on serum levels of inflammatory biomarkers among people with MS. Thus, it is expected that the planned systematic review and meta-analysis will yield robust evidence on the effects of diet on inflammatory profile in the setting of MS.

Effects of a Remote Multimodal Intervention Involving Diet, Walking Program, and Breathing Exercise on Quality of Life Among Newly Diagnosed People with Multiple Sclerosis: A Quasi-Experimental Non-Inferiority Pilot Study.

Background: Interventions involving diet, physical activity, and breathing exercises are shown to be beneficial in managing both fatigue and quality of life (QoL) related to MS; however, the impact of such interventions among people newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS) who decline disease-modifying therapies (DMTs) is unknown. Methods: A 12-month prospective quasi-experimental non-inferiority trial recruited people newly diagnosed with CIS or RRMS who voluntarily declined DMTs (health behavior group; HB, n = 29) or followed standard of care (SOC, n = 15). Participants in the HB group were remotely coached on the study diet, moderate-intensity walking, and breathing exercises. All participants completed questionnaires validated to assess MS symptoms, including perceived mental and physical QoL (MSQOL54); fatigue (Fatigue Severity Scale, FSS; and Modified Fatigue Impact Scale, MFIS); mood (Hospital Anxiety and Depression Scale, HADS); and cognitive function (Perceived Deficits Questionnaire, PDQ). Results: During the 12 months, the HB group experienced improvement in scores for mental QoL (MSQOL54 - Mental, 0.24, 95% CI 0.01, 0.47; p = 0.04), fatigue (Total MFIS, -7.26, 95% CI -13.3,-1.18; p = 0.02), and perceived cognitive function (Total PDQ, PDQ-Attention, PDQ-Promemory, and PDQ-Planning, p ≤ 0.03 for all). A between-group difference was observed only for PDQ-Planning (p = 0.048). Non-inferiority analysis revealed that the 12-month changes in means for the HB group were not worse than those for the SOC group with respect to fatigue (FSS, p = 0.02), mood (HDS-Anxiety, p = 0.02; HADS-Depression, p < 0.0001), physical QoL (MSQOL54 - Physical, p = 0.02), or cognitive dysfunction (Total PDQ, p = 0.01). Conclusion: The multimodal lifestyle intervention for individuals newly diagnosed with CIS or RRMS, who voluntarily decline DMTs, did not yield patient-reported outcomes worse than those observed in the SOC group regarding perceived mental quality of life, mood, fatigue, and cognitive function. Trial Registration: clinicaltrials.gov identifier: NCT04009005.

Association of type 2 diabetes mellitus with dementia-related and non-dementia-related mortality among postmenopausal women: A secondary competing risks analysis of the women's health initiative.

INTRODUCTION: Alzheimer's disease (AD) and AD-related dementias (ADRD) are leading causes of death among older adults in the United States. Efforts to understand risk factors for prevention are needed. METHODS: Participants (n = 146,166) enrolled in the Women's Health Initiative without AD at baseline were included. Diabetes status was ascertained from self-reported questionnaires and deaths attributed to AD/ADRD from hospital, autopsy, and death records. Competing risk regression models were used to estimate the cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the prospective association of type 2 diabetes mellitus (T2DM) with AD/ADRD and non-AD/ADRD mortality. RESULTS: There were 29,393 treated T2DM cases and 8628 AD/ADRD deaths during 21.6 (14.0-23.5) median (IQR) years of follow-up. Fully adjusted HRs (95% CIs) of the association with T2DM were 2.94 (2.76-3.12) for AD/ADRD and 2.65 (2.60-2.71) for the competing risk of non-AD/ADRD mortality. DISCUSSION: T2DM is associated with AD/ADRD and non-AD/ADRD mortality. HIGHLIGHTS: Type 2 diabetes mellitus is more strongly associated with Alzheimer's disease (AD)/AD and related dementias (ADRD) mortality compared to the competing risk of non-AD/ADRD mortality among postmenopausal women. This relationship was consistent for AD and ADRD, respectively. This association is strongest among participants without obesity or hypertension and with younger age at baseline, higher diet quality, higher physical activity, higher alcohol consumption, and older age at the time of diagnosis of type 2 diabetes mellitus.

Diet-induced changes in functional disability are mediated by fatigue in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES randomized parallel-arm trial.

Background: People with multiple sclerosis (MS) often report dietary modifications; however, evidence on functional outcomes remains sparse. Objective: Evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets on functional disability among people with relapsing-remitting MS. Methods: Baseline-referenced MS functional composite (MSFC) scores were calculated from nine-hole peg-test (NHPT), timed 25-foot walk, and oral symbol digit modalities test (SDMT-O) collected at four study visits: (a) run-in, (b) baseline, (c) 12 weeks, and (d) 24 weeks. Participants were observed at run-in and then randomized at baseline to either the Swank (n = 44) or Wahls (n = 43) diets. Results: Among the Swank group, MSFC scores significantly increased from -0.13 ± 0.14 at baseline to 0.10 ± 0.11 at 12 weeks (p = 0.04) and 0.14 ± 0.11 at 24 weeks (p = 0.02). Among the Wahls group, no change in MSFC scores was observed at 12 weeks from 0.10 ± 0.11 at baseline but increased to 0.28 ± 0.13 at 24 weeks (p = 0.002). In both groups, NHPT and SDMT-O z-scores increased at 24 weeks. Changes in MSFC and NHPT were mediated by fatigue. Discussion: Both diets reduced functional disability as mediated by fatigue. Trial Registration: Clinicaltrials.gov Identifier: NCT02914964.

Evaluation of a web-based program for the adoption of wellness behaviors to self-manage fatigue and improve quality of life among people with multiple sclerosis: A randomized waitlist-control trial.

BACKGROUND: Wellness is a promising area of research in multiple sclerosis (MS); however, considerable questions remain regarding the efficacy of behavioral interventions to improve wellness and which delivery methods yield favorable results. OBJECTIVE: To evaluate the efficacy of a wellness intervention consisting of diet, stress reduction techniques, sleep hygiene, and exercise, delivered via a 7-week web-based program with no tailored intervention support (e.g., counseling or resources) from the study team, on quality of life (QoL) and fatigue among people with MS. METHODS: Individuals (n = 100) with self-reported physician's diagnosis of relapsing-remitting MS or clinically isolated syndrome were recruited to enroll in this randomized waitlist-control trial consisting of three timepoints at 0, 12, and 24 weeks. Participants were randomized to begin the intervention at baseline (INT; n = 51) or to a waitlist to begin the intervention after the 12-week timepoint (WLC; n = 49), and both groups were followed for 24 weeks. RESULTS: At 12-weeks, 95 participants (46 INT and 49 WLC) completed the primary endpoint and 86 (42 INT and 44 WLC) completed the 24-week follow-up. Compared to baseline, the INT group had a significant increase in physical QoL (5.43 ± 1.85; P = 0.003) at 12-weeks which was maintained at 24-weeks. Physical QoL values in the WLC group did not significantly increase between weeks 12 and 24 (3.24 ± 2.03; P = 0.11); however, physical QoL values significantly improved compared to week 0 values (4.00 ± 1.87; P = 0.033). Neither group had significant changes in mental QoL. The INT group had a mean baseline to 12-week change of ­5.06 ± 1.79 (P = 0.005) for MFIS and -0.68 ± 0.21 (P = 0.002) for FSS, both of which were maintained at 24-weeks. The 12- to 24-week changes for the WLC group were -4.50 ± 1.81 (P = 0.013) for MFIS and -0.44 ± 0.17 (P = 0.011) for FSS. At 12-weeks, the INT group had significantly greater reductions in fatigue compared to the WLC (P = 0.009 for both MFIS and FSS). There were no between-group mean differences for physical or mental QoL, but a significantly higher proportion of participants had clinically significant improvement in physical QoL in the INT group (50%) compared to the WLC group (22.5%) at 12-weeks (P = 0.006). The 12-week intervention effect was similar during the active intervention phase (i.e., baseline to 12 weeks for INT and 12 to 24 weeks for WLC) in each group. Course completion rates significantly differed between groups with 47.9% of the INT group and 18.8% of the WLC group completing the course (P = 0.01). CONCLUSION: A wellness intervention delivered via a web-based program, without tailored support, resulted in significant improvements in fatigue compared to control. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05057676.

Association of serum homocysteine, folate, and vitamin B12 and mood following the Swank and Wahls elimination dietary interventions in relapsing-remitting multiple sclerosis: Secondary analysis of the WAVES trial.

BACKGROUND: Depression and anxiety are common psychiatric comorbidities among people with multiple sclerosis (MS). Emerging data suggest abnormal serum homocysteine, vitamin B12, and folate levels in people with MS, which are related to a range of neurological disorders, including mood and mental illnesses. Evidence suggests that dietary interventions could affect mood disorders via several pathways. This study aimed to evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets, along with a supplement regimen, on mood as assessed by Hospital Anxiety and Depression Scale (HADS), and Mental Health Inventory (MHI). The secondary objective was to identify changes in serum levels of homocysteine, folate, and vitamin B12 and the association and mediation effects between their changes and HADS and MHI scores and their subscales among people with relapsing-remitting MS (RRMS). METHODS: In a previously conducted randomized parallel-arm trial, participants with RRMS (n = 77) were randomly allocated to either the Swank or Wahls diets at baseline and followed for 24 weeks. Blood was drawn at four study visits spaced 12 weeks apart: (1) run-in, (2) baseline, (3) 12 weeks, and (4) 24 weeks. Serum vitamin B12, folate, and homocysteine were analyzed. HADS and MHI questionnaires were also completed by participants at the four study visits to assess symptoms of depression and anxiety, behavioral control and positive affect respectively. RESULTS: Significant improvement in severity of depression (HADS-D) and anxiety (HADS-A) symptoms, MHI total, and MHI subscores were seen at 12 and 24 weeks in each diet group. Further, a significant within-group reduction in serum homocysteine and a significant increase in serum vitamin B12 level were observed in both groups at 12 and 24 weeks compared to corresponding baseline values (p ≤ 0.05 for all). All participants exceeded the analytical maximum threshold for folate of 20 nmol/L at 12 and 24 weeks. Changes in serum levels of homocysteine and vitamin B12 were not associated with and did not mediate changes in HADS depression, anxiety, MHI total and four subscales scores (p > 0.05). CONCLUSION: Participants on both Swank and Wahls dietary interventions, including folate and vitamin B12 supplements, showed significant improvement in mood. However, the favorable effects of both diets on mood were not associated with or mediated by the effect of the diets on serum levels of homocysteine, folate, and vitamin B12 (p > 0.05).

Comparison of the Ketogenic Ratio of Macronutrients With the Low-Carbohydrate Diet Score and Their Association With Risk of Type 2 Diabetes in Postmenopausal Women: A Secondary Analysis of the Women's Health Initiative.

BACKGROUND: Previous attempts to identify low-carbohydrate diets (LCDs) in epidemiological studies relied on the LCD Score, which is unable to identify ketogenic dieters. Ketogenic ratios of macronutrients are clinical equations proposed to predict ketogenic diets; however, their utility in epidemiological studies is unknown. OBJECTIVE: To determine the number of participants consuming a ketogenic diet, compare ketogenic ratios to the LCD Score, and evaluate their association with type 2 diabetes mellitus (T2DM). DESIGN: Secondary analysis of the Women's Health Initiative with 17.9 ± 6.03 years of follow-up. Baseline food frequency questionnaires were used to calculate the ketogenic ratio as follows: (0.9 × grams fat + 0.46 × grams protein) / (0.1 × grams fat + 0.58 × grams protein + grams net carbohydrate), a value ≥1.5 is the minimum threshold for a ketogenic diet. PARTICIPANTS/SETTING: One hundred twenty-five nine hundred eighty-two postmenopausal women without diabetes (aged 50 to 79 years) enrolled in the multicenter Women's Health Initiative observational study and clinical trials were included. MAIN OUTCOME MEASURES: Risk of self-reported incident T2DM. STATISTICAL ANALYSES PERFORMED: Cox proportional hazards models, adjusted for age, race, ethnicity, education, income, health insurance, relationship status, geographic region, Women's Health Initiative study component, female hormone use, smoking status, alcohol use, recreational physical activity, total energy intake, diet quality, body mass index, hyperlipidemia, and hypertension, were used to compare hazard ratios and 95% CIs for T2DM among quintiles of the ketogenic ratio. RESULTS: A total of 18,775 incident cases of T2DM occurred. The median ketogenic ratio was 0.35 (interquartile range 0.28 to 0.42) and 15 individuals (0.01%) exceeded the threshold for a ketogenic diet. Higher ketogenic ratio quintiles were associated with increased risk of T2DM in a dose-dependent manner. Comparing extreme quintiles of the ketogenic ratio, the hazard ratio for diabetes was 1.24 (95% CI 1.18 to 1.31; Ptrend < 0.001) in fully adjusted models. Similarly, comparing extreme quintiles, the hazard ratio for diabetes was 1.36 (95% CI 1.29 to 1.43; Ptrend < 0.001) for the LCD Score and 1.13 (95% CI 1.07 to 1.19; Ptrend < 0.001) for the simplified ketogenic ratio in fully adjusted models. CONCLUSIONS: Increasing ketogenic ratio values are associated with increased risk of T2DM and align well with LCD Scores; however, too few participants consumed a ketogenic diet to determine its association with T2DM.

Facilitators of and Barriers to Adherence to Dietary Interventions Perceived by Women With Multiple Sclerosis and Their Support Persons.

BACKGROUND: People with multiple sclerosis (MS) frequently report implementing dietary strategies as part of their personal wellness programs; however, little is known about the perceived themes of healthy behavior change in people with MS. METHODS: Semistructured one-on-one interviews were conducted with 20 women with MS enrolled in 2 different restrictive dietary intervention studies and their 18 self-identified support persons consisting of partners and adult children. Interviews were transcribed, coded, categorized, and then grouped into summative themes. The frequency of issues being mentioned as facilitators of or barriers to diet adherence was evaluated to identify possible differences in perceived experiences between women with MS and their support persons during the studies. RESULTS: Five qualitative themes were identified: (1) personal motivation, (2) diet components, (3) time, (4) support, and (5) resource access. Major facilitators of dietary adherence were positive support from support persons and study staff, access to resources, symptom improvement, and personal motivation. Major barriers included the novelty of the study diet, lack of cooking skills, no change in or worsening of symptoms, lack of diet knowledge, and food preferences and temptations. Symptom severity was more frequently reported as a barrier to study diet adherence among participants with secondary progressive MS. CONCLUSIONS: Methods to enhance personal motivation and ensure positive support from support persons and study staff may improve study diet adherence. Due to the unique challenges faced by people with MS, future studies should tailor interventions to their unique MS cohort to increase diet adherence.

The Wahls Behavior Change Model for Complex Chronic Diseases: A Clinician's Guide.

Behavior change models are used to understand and intervene on health-related behaviors and outcomes. However, there is a gap in the literature regarding how to create and maintain behavior change in patients with complex chronic diseases such as Multiple Sclerosis (MS). To address this gap, the Wahls Behavior ChangeTM Model (WBCM) (The trademark applies to subsequent mention of the model.) was developed based on existing behavior change theory, empirical evidence, and extensive clinical experience caring for patients with complex chronic diseases. A patient-centered, comprehensive, and multimodal approach, this model provides a framework for understanding and implementing lifestyle behavior change. The overall goals of this paper are to: (1) review existing behavior change theories; (2) introduce the WBCM, including the model's 11 Principles for behavior change in patients with complex chronic diseases; and (3) share how providers can be trained to implement the WBCM. The WBCM can potentially improve short- and longer-term function and quality of life outcomes for people with complex chronic diseases.

Dietary Approaches to Treating Multiple Sclerosis-Related Symptoms.

Although there is no dietary pattern than has been proven to be effective for reducing the number of relapses or enhancing lesions in patients with multiple sclerosis (MS), several pilot studies have demonstrated the efficacy of dietary plans to reduce MS-related symptoms. Low saturated fat (Swank), low fat vegan (McDougall), modified Paleolithic (Wahls), gluten free, Mediterranean, intermittent fasting, calorie restriction, and intermittent calorie restriction (fasting mimicking diet) all have been associated with reduction of MS-related symptoms such as reduced fatigue, improved mood, and improved quality of life. Mediterranean diet has proven effectiveness for prevention and reduction of comorbid disease severity.

Association of multiple sclerosis with risk of mortality among a nationally representative sample of adults in the United States.

Background: Multiple sclerosis (MS) has been associated with increased mortality ratios, but few studies have investigated the independent association of MS with mortality. Objective: To examine the prospective association of MS with risk of mortality in a nationally representative sample of U.S. adults. Methods: This prospective study included 23,053 adults aged 45-79 years who participated in the National Health Interview Survey in 2002 and 2008. Physician-diagnosed MS was reported by participants during household interviews. These participants were linked to death records from survey date through December 31, 2015. Results: Among the 23,053 participants included in this study, 120 reported a physician's diagnosis of MS, with a higher prevalence in females (0.85%) than in males (0.31%). During on average 9.4 years (maximum 13.8 years) of observation, 4208 deaths occurred. After adjustment for age, sex, race/ethnicity, socioeconomic factors, lifestyle factors, and BMI, participants with MS had an 80% higher risk of mortality (HR 1.80; 95% CI, 1.11-2.92), compared with those without MS. The association remained significant (HR 1.75; 95% CI, 1.07-2.87) after further adjustment for baseline diabetes, cardiovascular disease, chronic lung disease, and cancer. Conclusion: In this nationally representative sample of U.S. adults, MS was associated with an increased risk of mortality.

Association between improved metabolic risk factors and perceived fatigue during dietary intervention trial in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES trial.

Background: Preliminary dietary intervention trials with the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets have shown favorable effects on fatigue among people with multiple sclerosis (MS); however, their impact on metabolic health is unknown. Objective: To evaluate the impact of the Swank and Wahls diets on markers of metabolic health and to determine the association and mediation effect between changes in metabolic health and perceived fatigue among people with relapsing-remitting MS (RRMS). Methods: As part of a randomized parallel-arm trial, vital signs, blood metabolic biomarkers, and the fatigue scale for motor and cognitive functions (FSMC) were collected from participants with relapsing-remitting MS (n = 77) at four study visits spaced 12 weeks apart: (1) run-in, (2) baseline, (3) 12-weeks, and (4) 24-weeks. Participants followed their usual diet at run-in, then were randomized at baseline to either the Swank or Wahls diets and followed for 24 weeks. Results: Both groups had significant reductions in weight, body mass index (BMI), total cholesterol, and low-density lipoprotein (LDL) at 12- and 24-weeks compared to respective baseline values (p ≤ 0.04 for all). The Swank group also had a significant reduction in high-density lipoprotein (HDL) at 12- and 24-weeks (p = 0.0001 and p = 0.02, respectively), while the Wahls group had significant reductions in diastolic blood pressure (DBP). In addition, both groups had significant reductions in FSMC total perceived fatigue and the motor and cognitive fatigue subscales at 12- and 24-weeks (p ≤ 0.01 for all); however, change in the cognitive subscale was not significant at 12-weeks in the Swank group (p = 0.06). Furthermore, the favorable effects, of both diets, on markers of metabolic health were not associated with and did not mediate the effect of the diets on perceived fatigue (p > 0.05 for all). Conclusion: Both diets lead to significant reductions in perceived fatigue, weight, BMI, total cholesterol, and LDL, but the significant reductions in perceived fatigue were independent of changes in markers of metabolic health.

Change in Micronutrient Intake among People with Relapsing-Remitting Multiple Sclerosis Adapting the Swank and Wahls Diets: An Analysis of Weighed Food Records.

The low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets have shown promise for MS symptoms; however, due to their restriction of specific foods, inadequate intake of micronutrients is concerning. Therefore, as part of a randomized trial, weighed food records were collected on three consecutive days and were used to evaluate the intake of micronutrients among people with relapsing remitting MS adapting these diets. After randomization to either the Swank or Wahls diets, diet education and support was provided by registered dietitians at baseline and throughout the first 12 weeks of the intervention. Usual intake of each micronutrient was estimated and then evaluated with the EAR-cut point method. At 12 weeks, the Swank group had significant reductions in the proportion with inadequate intake from food for vitamins C, D, and E, while the Wahls group had significant reductions for magnesium and vitamins A, C, D, and E. However, the proportion with inadequate intake significantly increased for calcium, thiamin, and vitamin B12 in the Wahls group and for vitamin A in the Swank group. Inclusion of intake from supplements reduced the proportion with inadequate intake for all micronutrients except calcium among the Wahls group but increased the proportion with excessive intake for vitamin D and niacin among both groups and magnesium among the Swank group. Both diets, especially when including intake from supplements, are associated with reduced inadequate intake compared to the normal diet of people with relapsing remitting MS.

Impact of the Swank and Wahls elimination dietary interventions on fatigue and quality of life in relapsing-remitting multiple sclerosis: The WAVES randomized parallel-arm clinical trial.

OBJECTIVE: To compare the effect of the modified Paleolithic elimination (Wahls) and low-saturated fat (Swank) diets in relapsing-remitting MS (RRMS). METHODS: Individuals (n = 87) with RRMS were randomized to the Swank or Wahls diets in a parallel group clinical trial consisting of four timepoints: 1) run-in, 2) baseline, 3) 12-weeks, and 4) 24-weeks. RESULTS: 77 participants completed 12 weeks and 72 completed 24 weeks. The 12-week change from baseline in fatigue was -0.94 ± 0.18 (FSS) and -9.87 ± 1.93 (MFIS; both p < 0.0001) for Swank, and -0.71 ± 0.24 (FSS; p = 0.004) and -14.41 ± 2.22 (MFIS; p ≤ 0.0001) for Wahls. Physical MSQoL scores improved by 6.04 ± 2.18 (p = 0.006) for Swank and by 14.5 ± 2.63 (p < 0.0001) for Wahls. Mental MSQoL scores improved by 11.3 ± at 2.79 (p < 0.0001) for Wahls while the Swank did not change (3.85 ± 2.63; p = 0.14). Neither group showed significant changes in 6-minute walking distance at 12 weeks. All outcomes were maintained or further improved at 24 weeks. CONCLUSIONS: Both diets were associated with clinically meaningful within-group reductions in fatigue and improvements in QoL.Trial Registration: Clinicaltrials.gov Identifier: NCT02914964.

A Modified MCT-Based Ketogenic Diet Increases Plasma ß-Hydroxybutyrate but Has Less Effect on Fatigue and Quality of Life in People with Multiple Sclerosis Compared to a Modified Paleolithic Diet: A Waitlist-Controlled, Randomized Pilot Study.

OBJECTIVE: To investigate the feasibility of a modified MCT-based ketogenic diet and its impact on plasma ß-hydroxybutyrate and MS outcomes compared to a modified Paleolithic diet and usual diet in people with Multiple Sclerosis (MS). METHODS: Fifteen individuals with MS were randomized to 3 groups: 1) modified Paleolithic diet (Paleo; n = 6); 2) medium-chain triglyceride (MCT)-based ketogenic diet that included coconut as a fat source (Keto; n = 5); or 3) usual diet (Control; n = 4). Participants had blood drawn every 4 weeks to monitor nutritional ketosis. Participants completed 4-day weighed food records, measures of disability, fatigue, quality of life (QoL), cognitive function, and physical function at baseline and 12-weeks. RESULTS: Macronutrient intake significantly shifted toward a ratio indicative of a ketogenic diet in the Keto group at 12 weeks. Similarly, plasma ß-hydroxybutyrate indicated nutritional ketosis in the Keto group, whereas neither macronutrient intake nor plasma ß-hydroxybutyrate indicated nutritional ketosis in the Paleo and Control groups. The Paleo group had significant within group reductions in fatigue scores and maintained cognitive function scores compared to the Control group. The Keto group had significant reductions in fasting glucose and insulin compared to baseline values; however, no clinical outcomes significantly changed. CONCLUSIONS: Participants consuming the MCT-based ketogenic diet achieved nutritional ketosis; however, it was not associated with significant clinical improvement in this study whereas the modified Paleolithic diet was associated with significant clinical improvements. Larger randomized controlled trials are needed to determine the safety and efficacy of the modified Paleolithic and MCT-based ketogenic diets on MS.

Eating Pattern and Nutritional Risks among People with Multiple Sclerosis Following a Modified Paleolithic Diet.

Preliminary studies suggest that a modified Paleolithic diet may benefit symptoms of fatigue in progressive multiple sclerosis (MS). However, this diet restricts the consumption of eggs, dairy, and gluten-containing grains, which may increase the risk of micronutrient deficiencies. Therefore, we evaluated the nutritional safety of this diet among people with progressive MS. Three nonconsecutive 24-h dietary recalls were collected from (n = 19) progressive MS participants in the final months of a diet intervention study and analyzed using Nutrition Data System for Research (NDSR) software. Food group intake was calculated, and intake of micronutrients was evaluated and compared to individual recommendations using Nutrient Adequacy Ratios (NARs). Blood was drawn at baseline and the end of the study to evaluate biomarker changes. Mean intake of fruits and vegetables exceeded nine servings/day and most participants excluded food groups. The intake of all micronutrients from food were above 100% NAR except for vitamin D (29.6 ± 34.6%), choline (73.2 ± 27.2%), and calcium (60.3 ± 22.8%), and one participant (1/19) exceeded the Tolerable Upper Limit (UL) for zinc, one (1/19) for vitamin A, and 37% (7/19) exceeded the chronic disease risk reduction (CDRR) for sodium. When intake from supplements was included in the analysis, several individuals exceeded ULs for magnesium (5/19), zinc (2/19), sodium (7/19), and vitamins A (2/19), D (9/19), C (1/19), B6 (3/19), and niacin (10/19). Serum values of vitamins D, B12, K1, K2, and folate significantly increased compared to respective baseline values, while homocysteine and magnesium values were significantly lower at 12 months. Calcium and vitamin A serum levels did not change. This modified Paleolithic diet is associated with minimal nutritional risks. However, excessive intake from supplements may be of concern.

Reversed phase UPLC/APCI-MS determination of Vitamin K1 and menaquinone-4 in human plasma: Application to a clinical study.

A rapid and sensitive liquid chromatographic-tandem mass spectrometric method was developed and validated to simultaneously quantitate vitamin K1 (PK) and vitamin K2 (MK-4) concentrations in human plasma to evaluate nutritional interventions. Charcoal-stripped human plasma was used for standard and calibration preparation with vitamin E-d6 as the internal standard. Patient plasma samples were extracted using n-hexane and analytes separated using an ACE -PFP C18 column (50 × 2.1 mm, 3 µ) equipped with standard C18 guard. The mobile phase consisted of 0.1 % formic acid in water and 0.1 % formic acid in methanol at a flow rate of 0.5 mL/min. Analyte quantification was achieved by using MS/MS with a positive atmospheric pressure chemical ionization in multiple reaction monitoring (MRM) mode. The lower limit of quantification was 0.01 ng/mL for both PK and MK-4. The assay was linear over the concentration range from 0.01-50 ng/mL for all analytes with a determination coefficient (r2) of 0.998 or better. The intra-and inter-day accuracy and precision were within the acceptable limits per FDA guidance. The validated method was successfully applied to a clinical study for quantification of PK and MK-4 in human plasma to assess nutritional status and dietary interventions in patients with neurodegenerative diseases. Baseline plasma concentrations of PK and MK-4 ranged from 0.23 to 1.81 ng/mL and 0.33-0.57 ng/mL, respectively.

Nutrient Composition Comparison between a Modified Paleolithic Diet for Multiple Sclerosis and the Recommended Healthy U.S.-Style Eating Pattern.

Multiple sclerosis (MS) is a demyelinating disease that attacks the central nervous system. Evidence-based dietary guidelines do not exist for MS; the default advice is to follow the Dietary Guidelines for Americans (DGA). A modified Paleolithic Wahls Elimination (WahlsElim) diet promoted for MS excludes grains and dairy and encourages 9+ cups fruits and vegetables (F/V) and saturated fat for cooking. This study evaluated the nutritional adequacy of seven-day menus and modeled them with varying amounts of F/V for comparison with the DGA Healthy US-Style Eating Pattern (HEP) for ages 31⁻50 years. WahlsElim menus had low added sugar and glycemic index. Nutritional adequacy of the menus and modeled versions were similar to HEP for 17 vitamins and minerals (mean adequacy ratio ≥92%). Nutrient shortfalls for the modeled diet with 60% F/V were identical to HEP for vitamin D, iron (females), magnesium (marginally males), choline and potassium; this modeled diet was also low in dietary fiber and calcium but met vitamin E requirements while HEP did not. WahlsElim-prescribed supplements corrected vitamin D and magnesium shortfalls; careful selection of foods are needed to meet requirements of other shortfall nutrients and reduce saturated fat and sodium. Doctors should monitor nutritional status, supplement doses, and possible contraindications to high vitamin K intake in individuals following the WahlsElim diet.