Abstract
Background:
Fatigue can be a disabling MS symptom with no effective treatment options.
Objectives:
Determine whether a low-fat diet improves fatigue in people with MS (PwMS).
Methods:
We conducted a 16-week randomized controlled trial (RCT) and allocated PwMS to a low-fat diet (active, total daily fat calories not exceeding 20%) or wait-list (control) group. Subjects underwent two weeks of baseline diet data collection [24-hour diet recalls (24HDR)], followed by randomization. The active group received two weeks of nutrition counseling and underwent a 12-week low-fat diet intervention. One set of three 24HDRs at baseline and week 16 were collected. We administered a food frequency questionnaire (FFQ) and Modified Fatigue Impact Scale (MFIS) every 4 weeks. The control group continued their pre-study diet and received diet training at the study completion.
Results:
We recruited 39 PwMS [20 – active; 19 – control]. The active group decreased their daily caloric intake by 11% (95% CI: −18.5%, −3.0%) and the mean MFIS by 4.0 (95% CI −12.0, 4.0) compared to the control (intent to treat). Sensitivity analysis strengthened the association with a mean MFIS difference of −13.9 (95% CI: −20.7, −7.2)
Conclusions:
We demonstrated a significant reduction in fatigue with a low-fat dietary intervention in PwMS.
Keywords: Multiple sclerosis, fatigue, low-fat diet, actigraphy, randomized controlled trial, clinical trial
Introduction
Fatigue is one of the most common and disabling multiple sclerosis (MS) symptoms, but has no effective treatment options.(1) A recent randomized, double-blind, placebo-controlled crossover trial of the comparative effectiveness of commonly prescribed treatments for fatigue, including amantadine, modafinil, and methylphenidate, found no significant differences in mean modified fatigue impact scale (MFIS) score between these treatments and placebo.(2)
A dietary intervention to improve fatigue in people with MS (PwMS) is highly desirable given the low risk of adverse events and the potential to improve other parameters of a person’s health, such as body mass index (BMI) and metabolic profile. Diets such as Paleolithic, ketogenic, Mediterranean, and intermittent fasting have been tried in MS with variable effects on fatigue (3–11). Low-fat diets studied in PwMS include one popularized by Dr. Roy Swank with a saturated fat intake of less than 20 grams/day and another by Dr. John McDougall with a total fat intake of less than 10% of daily calorie intake.(10, 12, 13) Low-fat diets, while not as clearly defined, have been studied for weight loss and effect on cardiovascular outcomes.(14–16) The 2015 Dietary Guidelines for adults recommended 20-35% of calories to be obtained from fat sources. In the National Health and Nutrition Examination Survey data from the What We Eat in America Survey 2017, women over 20 years of age consumed an average of 37.5% of calories from fats while men consumed 36.6%.(17)
Our previous work using the very low-fat plant-based diet showed a significant benefit on fatigue in PwMS and found a possible association between weight loss and fatigue.(10) However, this dietary approach was limited by many participants finding it too restrictive. We, therefore, designed this study to explore whether a less restrictive, low-fat diet could decrease fatigue in PwMS and be well-tolerated.
Materials and Methods
We conducted a 16-week, single-center, two-arm, open-label, randomized controlled trial (RCT) to determine whether a 12-week low-fat diet intervention affected fatigue levels in PwMS. Oregon Health & Science University (OHSU) IRB (IRB# 16600, Clinical Trials NCT03322982) approved the study. We obtained written consent and randomized subjects to the low-fat diet (active) or wait-list (control) group. Our primary outcome was fatigue measured by MFIS. Other study outcomes included assessments of cognitive function, mobility, body composition, serum markers of metabolism such as lipids and hemoglobin A1C, diet adherence, safety, and tolerability.
Participants
OHSU MS Center was the primary recruitment site with additional referrals from local MS clinics and the National MS Society (NMSS) advertisements. We included people 18-70 years with physician-confirmed MS diagnosis (any subtype), Expanded Disability Status Scale (EDSS) <7.5 and MFIS ≥ 38. (18–21) We excluded subjects with: significant depression (Beck Depression Inventory Score (BDI) >28) (22); diabetes or other significant medical problems leading to fatigue; pregnant or breastfeeding; clinically significant MS exacerbation or those receiving intravenous steroids within 30 days of the screening visit; a dietary fat content <30% [Food Frequency Questionnaire (FFQ)](23) at the screening visit or those using fish or flax seed oil supplementation within 30 days of the screening visit.
Procedures
Subjects followed their usual MS care throughout the study and were advised not to change their level of physical activity or medications unless medically necessary.
Study diet:
A low-fat diet (fat total daily calories =< 20%) with saturated fat < 7% of daily caloric intake and rest of caloric breakdown consisting of 20% protein and 60% carbohydrate (primarily complex). While predominantly plant-based, the diet allowed lean animal protein sources, except red meat, and prohibited dairy products (supplemental text).
Baseline visit:
All subjects underwent the following measures: 1) Fatigue [MFIS, Fatigue Severity Scale (FSS)(24)]; 2) physical activity [rapid physical activity (RAPA) (25); 3) cognition [the symbol digit modality test (SDMT)](26); 4) disability [EDSS, 9-hole peg test (9HPT)(27), 6-minute timed walk (6MWT)(28) and timed 25-foot walk (T25FW)]; and 5) body composition [dual-energy X-ray absorptiometry (DEXA)(29), BMI]. Fasting blood was drawn to assess complete blood counts with differential (CBC), complete metabolic panel (CMP), lipid profile, and hemoglobin A1c.
Data collection 1 (week 0-2):
Following the baseline visit, subjects wore an Actigraphy accelerometer for one week (ActiGraph wGT3X-BT)](30) to measure physical activity and underwent three random 24-hour diet recalls (24HDR)(31) with a registered dietitian for a 2-week period. The 24HDR includes the participants’ food intake during the previous 24 hours on two weekdays and one weekend day.
Nutrition counseling (week 2-4):
Subjects underwent randomization upon completion of 24HDRs. The active group received diet training between weeks 2-4. The control group received identical diet training at week 16. Registered dietitians conducted the nutrition counseling sessions virtually and in person with two-three, one-hour meetings. Participants received hard-copy and online diet training materials, including a 167-page cookbook and training manual.
Intervention period (week 4-16):
Active group followed the study diet for 12 weeks. All subjects completed MFIS, FSS, and FFQ every 4 weeks. Study dietitian monitored the active group at least once weekly for diet adherence and adverse events. Research coordinators emailed monthly surveys to the control group and checked for adverse events.
Week 16 visit (Study end):
Outcomes identical to the baseline visit were measured at this visit. All subjects underwent three additional 24HDRs and wore an Actigraphy monitor for one week.
Primary Outcome
Modified Fatigue Impact Scale (MFIS)(32):
It is a 21-item questionnaire that assesses overall self-reported fatigue (supplemental text).
Secondary Outcomes included:
Fatigue (FSS), diet composition (24HDR), and diet adherence (FFQ). Other outcomes included EDSS, BDI, 6MWT, T25FW, height, weight, and BMI from DEXA, RAPA, SDMT, 9HPT, serum glucose, and lipid biomarkers, and mean weekly sleep from actigraphy (supplemental text).
Statistical Analysis
We planned a sample size of 27 in each arm to give 80% power to detect a difference of 7.0 on the MFIS with a pooled standard deviation of 9.0. Assuming a 20% dropout rate, we planned to enroll 34 subjects per arm, bringing the target enrollment to 68 subjects. Subjects were randomly assigned 1:1 to the active or control groups using the REDCap randomization module using a block size of 6 to ensure approximately equal numbers in each group. Continuous variables were summarized using mean and standard deviation (±SD) and categorical variables with frequency (N) and relative frequency (%). We used the mean of the screening and baseline visits as the baseline MFIS value for the nine subjects who had both a screening and baseline visit. The principal statistical analysis used linear mixed models, with a random effect for the subject to account for the within-subject correlation, in an intent-to-treat (ITT) framework to determine the effect of a low-fat diet on MFIS, FSS, adherence to diet from 24HFR and FFQ, and other outcomes of interest. The model included an interaction term of time*group to estimate changes (WG) and between-group (BG) changes. If there was a significant difference in covariates at baseline between the two groups, those covariates were added to the final model. We report the mean change in WG, BG, and corresponding 95% confidence intervals (CI) between baseline and week 16 of the mixed models.
To assess model diagnostics, we examined quantile-quantile (QQ) plots comparing the observed probability quantiles of the model residuals against expected quantiles at each time point to assess normality. Potential outliers were identified with a visual inspection of the residual plots, and outliers assessed on a subject-level basis. We visually examined the homogeneity of the error variance using plots of model residuals against the predicted responses. We calculated Spearman correlation coefficients on the fat intake (FFQ) and fatigue (MFIS) change scores (week 16 – baseline) and compared active with control, and both groups combined.
We evaluated the study diet’s safety and tolerability by examining lab values if exceeded two times the upper limits of normal including CBC and CMP. Data from two active subjects was not included in the safety analysis due to lack of fasting values. Per-protocol analysis included only those subjects who adhered to the diet and excluded two subjects who changed their diet significantly in the control group despite study instructions. Sensitivity analysis excluded five subjects (three controls, two active) as outliers based on visual inspection of the residual plots of the MFIS. All analyses were performed using STATA, Release 16, College Station, TX.(33)
Results
Between Spring 2018 and Summer 2021, we enrolled and randomized 39 PwMS out of the 68 planned for enrollment (Fig. 1). Target enrollment failure resulted from the COVID-19 pandemic and inadequate funding. The two groups were similar in the demographic, physiologic and body composition measures including weight [mean (+/− SD) 87 kilos (±20)] and BMI [mean (+/− SD) 31 kg/m2 (±7)] (Table 1). Mean subject age was 50 (±12) years with 82% being female (N=32) and 92% having relapsing-remitting MS (RRMS) (N=36). Eighty% of the subjects were on disease-modifying therapies (DMT) (N=31). Eight active and three control group participants were on fatigue medications (example Amantadine, methylphenidate, modafinil).
Figure 1:
Consort Diagram
Table 1:
Baseline Demographics and disease characteristics
| Characteristic | Active (N=20) | Control (N=19) | Total (N=39) |
|---|---|---|---|
| Age, mean (SD), years | 52.2 (10.4) | 47.16 (12.7) | 49.74 (11.7) |
| Time since onset, mean (SD), yearsa | 16.42 (7.0) | 17.72 (11.4) | 17.05 (9.3) |
| Time since dx, mean (SD), years | 13.00 (7.7) | 12.21 (9.9) | 12.62 (8.7) |
| Race, n (%) | |||
| Black or African American | 1 (5.0) | 1 (5.3) | 2 (5.1) |
| White | 16 (80.0) | 17 (89.5) | 33 (84.6) |
| Multiracial | 3 (15.0) | 1 (5.3) | 4 (10.3) |
| Female, n (%) | 16 (80.0) | 16 (84.2) | 32 (82.1) |
| Disease subtype, n (%) | |||
| RRMS | 18 (90.0) | 18 (94.7) | 36 (92.3) |
| SPMS | 1 (5.0) | 0 (0.0) | 1 (2.6) |
| PPMS | 1 (5.0) | 1 (5.3) | 2 (5.1) |
| MFIS Total, mean (SD) | 51.50 (8.9) | 55.79 (11.7) | 53.59 (10.4) |
| MFIS Physical, mean (SD) | 25.53 (5.2) | 24.37 (6.5) | 24.96 (5.8) |
| MFIS Cognitive, mean (SD) | 21.25 (6.9) | 26.82 (5.8) | 23.96 (6.9) |
| MFIS Psychosocial, mean (SD) | 4.73 (1.5) | 4.60 (1.8) | 4.67 (1.6) |
| FSS, mean (SD)a | 5.60 (0.7) | 5.41 (1.0) | 5.51 (0.9) |
| Systolic BP, mean (SD), mm/Hga | 127.37 (12.0) | 129.72 (14.7) | 128.51 (13.2) |
| Diastolic BP, mean (SD), mm/Hga | 75.47 (10.2) | 73.33 (12.5) | 74.43 (11.3) |
| Height, mean (SD), meters | 1.68 (0.1) | 1.67 (0.1) | 1.68 (0.1) |
| Weight, mean (SD), kga | 87.94 (18.2) | 86.68 (22.0) | 87.31 (19.9) |
| BMI, mean (SD), kg/m2 a | 31.25 (7.2) | 30.82 (7.0) | 31.04 (7.0) |
| Total Cholesterol, mean (SD), mg/dL | 182.1 (35.1) | 201.4 (45.2) | 191.5 (41.0) |
| LDL Cholesterol, mean (SD), mg/dL | 104.0 (33.4) | 122.2 (40.0) | 112.8 (37.4) |
| HDL Cholesterol, mean (SD), mg/dL | 58.7 (11.2) | 56.9 (14.6) | 57.8 (12.8) |
| Triglycerides, mean (SD), mg/dL | 98.0 (33.1) | 111.5 (59.4) | 104.6 (47.6) |
| EDSS Score, mean (SD) | 4.15 (1.31) | 3.38 (1.4) | 3.78 (1.4) |
| BDI Score, mean (SD) | 10.60 (5.9) | 13.05 (7.6) | 11.79 (6.8) |
| Percent caloric intake from: mean (SD)a, b | |||
| Fat | 39.10 (9.4) | 35.67 (6.5) | 37.34 (8.1) |
| Protein | 15.53 (3.6) | 15.40 (3.7) | 15.46 (3.6) |
| Carbohydrate | 44.04 (8.8) | 45.70 (7.8) | 44.89 (8.3) |
| 9HPT, mean (SD), secondsa | 22.33 (4.3) | 23.99 (9.9) | 23.18 (7.6) |
| SDMT, mean (SD) | 48.72 (11.9) | 47.68 (10.7) | 48.19 (11.2) |
| Disease Modifying Therapies, n (%) | |||
| None | 6 (30.0) | 2 (10.5) | 8 (20.5) |
| Platform Therapies | 3 (15.0) | 4 (21.1) | 7 (18.0) |
| Interferon | 2 (66.7) | 2 (50.0) | 4 (57.1) |
| Glatiramer | 1 (33.3) | 2 (50.0) | 3 (42.9) |
| Oral Therapy | 6 (30.0) | 8 (42.1) | 14 (35.9) |
| Anti CD 20 Therapy | 4 (20.0) | 4 (21.1) | 8 (20.5) |
| Tysabri | 1 (5.0) | 1 (5.3) | 2 (5.1) |
| Medication Use, n (%) | |||
| Antidepressantsa | 9 (47.3) | 12 (63.2) | 21 (55.3) |
| Fatiguea | 8 (42.1) | 3 (15.8) | 11 (29.0) |
| Thyroida | 2 (10.5) | 3 (15.8) | 5 (13.2) |
| Statinsa | 6 (31.6) | 0 (0.0) | 6 (15.8) |
| RAPA Scorea, mean (SD) | 3.74 (0.8) | 4.21 (0.8) | 3.97 (0.8) |
SD: standard deviation; MS: Multiple Sclerosis; RRMS: Relapsing-Remitting MS; SPMS: Secondary Progressive MS; PPMS: Progressive primary MS; MFIS: Modified Fatigue Impact Scale; FSS: Fatigue Severity Scale; BP: Blood Pressure; BMI: Body Mass Index; EDSS: Expanded Disability Status Scale; BDI: Beck Depression Inventory; 9HPT: 9-Hole Peg Test; SDMT: Symbol Digit Modalities Test; RAPA: Rapid Assessment of Physical Activity
2 missing systolic & diastolic BP, 1 missing weight, BMI, 1 missing FSS, 2 missing time since onset, 2 missing percent caloric intake, 2 missing 9HPT, 1 missing medication for antidepressants, fatigue, thyroid, statins, 1 missing physical activity
24-hour diet recall
Diet composition – 24HDR
24HDR showed no between-group changes in average total caloric intake (active: −348 kcal and control: −333 kcal, p= 0.95). Active group showed mean percentage decrease in fat calories (10%) compared to an increase in the control group (0.5%) [% BG decrease: 10.6 (95% CI: −18.2, −3.0%; p=0.006)]. Active group showed increase in the carbohydrate calories [(+9.0) mean %) whereas control group showed decrease (−0.1) [BG increase: 9.1% (95% CI 1.0, 17.2; p=0.03)]. Total fiber intake increased in the active group by 3 grams and decreased by 5 grams in the control group [BG change = 8.2 grams (95% CI 2.0 - 14.5 grams; p=0.01)]. The protein calories were unchanged in the two groups (Table 5A). The per-protocol analysis showed decrease in total daily fat calories by 10 points (39% to 29%) and increase in daily carbohydrate calories by 9 points (43% to 54%) in the active group.
Table 5A:
24-hour food recall, mean (SE)a (ITT analysis)
| Active (N=18) | Control (N=19) | BG change (95% CI)b | |||||
|---|---|---|---|---|---|---|---|
|
| |||||||
| Baseline | Week 16 | WG Changea | Baseline | Week 16 | WG Changea | ||
| Total Grams | 3391.5 (197.6) | 3350.1 (197.6) | −41.5 | 3690.5 (196.0) | 3456.2 (201.3) | −234.3* | 192.9 (−134.0, 519.8) |
| Energy (kcal) | 2086.5 (157.6) | 1738.7 (157.6) | −347.8* | 2326.6 (154.5) | 1993.5 (164.6) | −333.1* | −14.7 (−453.5, 424.2) |
| Total Fat (g) | 95.9 (7.3) | 60.4 (7.3) | −35.6** | 93.5 (7.1) | 82.8 (7.7) | −10.7 | −24.9 (−51.9, 2.1) |
| Total Carb (g) | 233.4 (25.3) | 237.4 (25.3) | 4.0 | 275.8 (24.8) | 240.3 (26.5) | −35.4 | 39.4 (−33.3, 112.2) |
| Total Protein (g) | 77.1 (5.6) | 70.3 (5.6) | −6.8 | 87.8 (5.5) | 73.4 (5.9) | −14.4* | 7.6 (−8.8, 23.9) |
| Total Saturated Fatty Acids (g) | 32.6 (3.2) | 18.9 (3.2) | −13.8** | 28.7 (3.1) | 30.3 (3.4) | 1.6 | −15.4* (−27.9, −2.9) |
| Total Monounsaturated Fatty Acids (g) | 34.1 (2.8) | 21.0 (2.8) | −13.1** | 34.7 (2.7) | 27.6 (3.0) | −7.1* | −6.0 (−15.5, 3.6) |
| Total Dietary Fiber (g) | 22.6 (2.5) | 26.0 (2.5) | 3.4 | 25.2 (2.4) | 20.4 (2.6) | −4.9* | 8.2* (2.0, 14.5) |
| % Calories from fat | 39.2 (2.0) | 29.1 (2.0) | −10.0** | 35.7 (1.9) | 36.2 (2.1) | 0.5 | −10.6**(−18.2, −3.0) |
| % Calories from Carb | 44.0 (2.2) | 53.0 (2.2) | 9.0* | 45.7 (2.1) | 45.6 (2.3) | −0.1 | 9.1* (1.0, 17.2) |
| % Calories from Protein | 15.5 (0.9) | 16.6 (0.9) | 1.1 | 15.4 (0.9) | 15.9 (1.0) | 0.5 | 0.6 (−2.6, 3.9) |
SE: Standard Error; WG: Within Group; WG change (week 16 – baseline);
BG: Between-Group; BG change (active WG change – control WG change);
p<0.05;
p<0.01
Diet Adherence - FFQ
The mean fat calorie intake at baseline was 39% in the active group that decreased to 33% at week 4 and 24% at week 8 and then remained stable at 24% until the study end. Forty-five % (9/20) of active group subjects achieved <25 % calories from fat compared to 5.3% (1/19) in the control group. Five out of twenty (25%) active group subjects achieved <20% calories from fat compared to 1 out of 19 (5.3%) control group. The mean fat calorie intake decreased by 15% in the active group versus a 1% decrease in the control group [BG change = −14 (95% CI: −20.1, −7.1 %; p<0.001)], suggesting good adherence to the study diet (Fig. 2). (Table 4A).
Figure 2:
Change in % Calories from fat (FFQ) in ITT & per-protocol analyses
Table 4A:
FFQ, mean (SE)a (ITT analysis)
| Active (N=20) | Control (N=19) | BG change (95% CI)b | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||||||
| Baseline | Week 4 | Week 8 | Week 12 | Week 16 | WG Changea | Baseline | Week 4 | Week 8 | Week 12 | Week 16 | WG Changea | ||
| Total Caloric Intake | 1835.1 (130.6) | 1492.0 (136.5) | 1139.8 (139.6) | 1147.9 (139.6) | 1127.8 (139.6) | −707.3** | 1895.8 (134.0) | 1517.7 (140.2) | 1389.6 (139.9) | 1380.2 (140.2) | 1321.9 (143.3) | −573.9** | −133.4 (−556.9, 290.1) |
| % Cal from fat | 38.7 (1.8) | 33.2 (1.9) | 23.7 (2.0) | 23.5 (2.0) | 23.9 (2.0) | −14.9** | 39.4 (1.9) | 36.6 (2.0) | 38.6 (2.0) | 37.7 (2.0) | 38.1 (2.0) | −1.3 | −13.6** (−20.1, −7.1) |
| Total Fat (g) | 80.4 (6.4) | 56.7 (6.7) | 30.7 (6.9) | 30.5 (6.9) | 31.56 (6.9) | −48.9** | 85.2 (6.6) | 63.8 (6.9) | 58.7 (6.9) | 58.7 (7.1) | 59.3 (7.1) | −25.9** | −23.0* (−44.9, −1.0) |
| Saturated Fat (g) | 27.8 (2.2) | 17.4 (2.3) | 7.2 (2.4) | 7.5 (2.4) | 7.8 (2.4) | −20.1** | 26.2 (2.3) | 20.5 (2.4) | 19.5 (2.4) | 16.5 (2.5) | 18.2 (2.5) | −8.1** | −12.0** (−20.0, −4.0) |
| Trans fat (g) | 2.3 (0.2) | 1.4 (0.3) | 0.7 (0.3) | 0.9 (0.3) | 0.8 (0.3) | −1.5** | 2.2 (0.3) | 1.9 (0.3) | 1.8 (0.3) | 1.6 (0.3) | 2.0 (0.3) | −0.2 | −1.3** (−2.1, −0.5) |
| Sodium | 3393.9 (271.2) | 2787.6 (281.7) | 2439.0 (286.9) | 2570.8 (286.9) | 2262.2 (286.9) | −1131.7** | 3475.6 (278.3) | 2842.3 (288.9) | 2701.7 (288.3) | 2660.1 (294.2) | 2548.1 (294.2) | −927.4** | −204.2 (−978.4, 570.0) |
| Total Fiber | 20.9 (1.8) | 22.7 (1.8) | 22.3 (1.9) | 21.9 (1.9) | 21.4 (1.9) | 0.5 | 21.6 (1.8) | 17.5 (1.9) | 15.1 (1.9) | 15.5 (1.9) | 15.2 (1.9) | −6.3** | 6.9** (1.9, 11.9) |
| Insoluble Fiber | 14.3 (1.3) | 15.8 (1.3) | 15.2 (1.3) | 15.2 (1.3) | 14.8 (1.3) | 0.5 | 14.5 (1.3) | 11.6 (1.4) | 10.2 (1.4) | 10.0 (1.4) | 10.2 (1.4) | −4 2** | 4.7** (1.2, 8.3) |
| Soluble Fiber | 6.6 (0.6) | 7.3 (0.6) | 7.3 (0.6) | 6.7 (0.6) | 6.8 (0.6) | 0.2 | 7.0 (0.6) | 5.9 (0.6) | 5.0 (0.6) | 5.4 (0.7) | 5.1 (0.7) | −1.9** | 2.2* (0.4, 3.9) |
| Veg servings | 2.6 (0.5) | 3.7 (0.5) | 3.8 (0.5) | 3.8 (0.5) | 3.5 (0.5) | 0.9 | 3.1 (0.5) | 2.9 (0.5) | 3.1 (0.5) | 2.8 (0.5) | 3.0 (0.5) | −0.1 | 1.0 (−0.4, 2.3) |
| Fruit servings | 1.3 (0.4) | 2.1 (0.4) | 2.5 (0.4) | 2.1 (0.4) | 2.1 (0.4) | 0.9* | 0.9 (0.4) | 1.6 (0.4) | 1.1 (0.4) | 1.7 (0.4) | 0.8 (0.4) | −0.1 | 0.9 (−0.1, 1.9) |
SE: Standard Error; WG: Within Group; WG change (week 16 – baseline);
BG: Between-Group; BG change (active WG change – control WG change);
p<0.05;
p<0.01
MFIS
The mean (+/− SD) baseline MFIS score was 54 (±10) across both groups. ITT analysis showed mean total MFIS score reduction in the active group [14 points (p<0.01)] and the control group [10 points (p<0.01)] [BG mean decrease (active–control) - 4 points (95% CI −12, 4; p=0.32)] (Table 2A). The per-protocol analysis strengthened this finding with a mean BG decrease of 8 points (95% CI: −16, −0.4; p=0.04) (Table 2B and Fig. 3) and sensitivity analysis further strengthened this BG decrease by 14 points (95% CI: −21, −7; p<0.01).
Table 2A:
Fatigue outcomes (MFIS & FSS), mean (SE)a (ITT analysis)
| Active (N=20) | Control (N=19) | BG change (95% CI)b | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||||||
| Baseline | Week 4 | Week 8 | Week 12 | Week 16 | WG Changea | Baseline | Week 4 | Week 8 | Week 12 | Week 16 | WG Changea | ||
| MFIS Total | 51.5 (3.0) | 52.0 (3.2) | 41.4 (3.2) | 39.2 (3.2) | 37.5 (3.2) | −14.0** | 55.8 (3.1) | 52.3 (3.2) | 52.0 (3.4) | 53.1 (3.3) | 45.7 (3.3) | −10.1** | −4.0 (−12.0, 4.0) |
| MFIS Physical | 25.5 (1.5) | 25.9 (1.6) | 20.5 (1.6) | 19.8 (1.6) | 18.5 (1.6) | −7.0** | 24.4 (1.6) | 24.4 (1.6) | 23.0 (1.7) | 23.8 (1.6) | 20.6 (1.6) | −3.8** | −3.2 (−7.2, 0.8) |
| MFIS Cognitive | 21.3 (1.7) | 21.3 (1.8) | 17.3 (1.8) | 16.1 (1.8) | 15.7 (1.8) | −5.6** | 26.8 (1.7) | 23.2 (1.8) | 24.7 (1.9) | 24.8 (1.8) | 21.1 (1.8) | −5.8** | 0.2 (−3.9, 4.3) |
| MFIS Psychosocial | 4.7 (0.4) | 4.9 (0.4) | 3.7 (0.4) | 3.4 (0.4) | 3.3 (0.4) | −1.5** | 4.6 (0.4) | 4.7 (0.4) | 4.3 (0.4) | 4.6 (0.4) | 4.1 (0.4) | −0.5 | −1.0 (−2.0, 0.1) |
| FSS (9 item) | 5.5 (0.3) | 5.5 (0.3) | 5.0 (0.3) | 4.7 (0.3) | 4.7 (0.3) | −0.8** | 5.4 (0.3) | 5.5 (0.3) | 5.4 (0.3) | 5.3 (0.3) | 5.0 (0.3) | −0.4 | −0.4 (−1.2, 0.4) |
SE: Standard Error; WG: Within Group; WG change (week 16 – baseline);
BG: Between-Group; BG change (active WG change – control WG change);
p<0.05;
p<0.01
Table 2B:
Fatigue outcomes (MFIS & FSS), mean (SE)a (per-protocol analysis)
| Active (N=20) | Control (N=17) | BG change (95% CI)b | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||||||
| Baseline | Week 4 | Week 8 | Week 12 | Week 16 | WG Changea | Baseline | Week 4 | Week 8 | Week 12 | Week 16 | WG Changea | ||
| MFIS Total | 51.5 (2.9) | 52.1 (3.0) | 41.4 (3.1) | 39.2 (3.1) | 37.5 (3.0) | −14.0** | 55.9 (3.1) | 53.5 (3.2) | 54.4 (3.4) | 55.7 (3.37) | 50.0 (3.3) | −5.9* | −8.1* (−15.7, −0.4) |
| MFIS Physical | 25.5 (1.5) | 25.9 (1.5) | 20.5 (1.6) | 19.8 (1.6) | 18.6 (1.5) | −7.0** | 24.2 (1.6) | 25.0 (1.6) | 24.0 (1.7) | 25.2 (1.7) | 22.6 (1.7) | −1.5 | −5.4* (−9.2, −1.6) |
| MFIS Cognitive | 21.3 (1.6) | 21.3 (1.7) | 17.3 (1.7) | 16.1 (1.7) | 15.7 (1.7) | −5.5** | 27.1 (1.8) | 23.7 (1.8) | 25.7 (1.9) | 25.7 (1.9) | 22.87 (1.9) | −4.3** | −1.3 (−5.2, 2.7) |
| MFIS Psychosocial | 4.7 (0.4) | 5.0 (0.4) | 3.7 (0.4) | 3.4 (0.4) | 3.3 (0.4) | −1.5** | 4.7 (0.4) | 4.8 (0.4) | 4.7 (0.4) | 4.8 (0.4) | 4.6 (0.4) | −0.1 | −1.3* (−2.4, −0.3) |
| FSS (9 item) | 5.5 (0.3) | 5.5 (0.3) | 5.0 (0.3) | 4.7 (0.3) | 4.7 (0.3) | −0.8** | 5.4 (0.3) | 5.3 (0.3) | 5.4 (0.3) | 5.5 (0.3) | 5.2 (0.23) | −0.1 | −0.7 (−1.4, 0.1) |
SE: Standard Error; WG: Within Group; WG change (week 16 – baseline);
BG: Between-Group; BG change (active WG change – control WG change);
p<0.05;
p<0.01
Figure 3:
Change in Total MFIS in ITT & per-protocol analyses
FSS
The mean baseline FSS score was 6 (±1). Per the ITT analysis, active group reduced the mean FSS scores by 0.8 points (p<0.01) versus 0.4 points in the control [mean between-BG (active–control) decrease = 0.4 points (95% CI: −1.2, 0.4; p=0.30)] (Table 2A). This association strengthened on the per-protocol analysis, with a BG mean decrease of 0.7 points (95% CI: −1.4, 0.1; p=0.08) (Table 2B) and sensitivity analysis showed a significant mean BG mean decrease of 1.2 points (95% CI: −1.9, −0.5; p=0.001) (Table 2).
Physical Activity
Mean RAPA score increased 0.3 points in the active group but decreased by 0.6 (p<0.01) in the control group [mean increase of 0.9 (95% CI 0.4, 1.5; p=0.002)] (Table 3A).
Table 3A:
Other outcomes, mean (SE)a (ITT analysis)
| Active (N=20) | Control (N=19) | BG change (95% CI)b | |||||
|---|---|---|---|---|---|---|---|
|
| |||||||
| Baseline | Week 16 | WG Changea | Baseline | Week 16 | WG Changea | ||
| EDSS | 4.2 (0.3) | 4.2 (0.3) | 0.0 | 3.4 (0.3) | 3.4 (0.3) | 0.0 | −0.0 (−0.4, 0.3) |
| BDI | 10.6 (1.7) | 11.3 (1.8) | 0.7 | 13.1 (1.7) | 11.8 (1.8) | −1.3 | 2.0 (−2.8, 6.8) |
| 9HPT (seconds) | 22.1 (1.9) | 21.6 (2.0) | −0.5 | 24.0 (2.0) | 25.4 (2.0) | 1.4 | −1.9 (−4.7, 0.9) |
| SDMT | 49.2 (2.3) | 48.4 (2.3) | −0.8 | 47.7 (2.3) | 50.0 (2.4) | 2.4 | −3.2 (−6.8, 0.4) |
| 25-foot walk (seconds)c | 7.9 (2.4) | 8.3 (2.4) | 0.5 | 8.0 (2.6) | 8.3 (2.6) | 0.3 | 0.1 (−1.1, 1.3) |
| 6-min walk (meters)c | 336.2 (25.4) | 341.4 (25.6) | 5.3 | 389.7 (26.5) | 383.7 (27.0) | −5.9 | 11.2 (−23.8, 46.2) |
| Physical Activity (RAPA)c | 3.7 (0.2) | 4.0 (0.2) | 0.3 | 4.2 (0.2) | 3.6 (−0.6) | −0.6** | 0.9** (0.4, 1.5) |
| Sleep (minutes) (from actigraphy)c | 458.6 (15.0) | 447.7 (16.7) | −10.8 | 417.2 (16.0) | 430.9 (16.3) | 13.7 | −24.5 (−63.3, 14.3) |
| Fat tissue (%) | 43.9 (2.0) | 42.0 (2.0) | −1.9** | 42.7 (2.1) | 42.0 (2.1) | −0.7 | −1.3 (−3.0, 0.5) |
| Fat mass | 38167.7 (3847.3) | 36053.0 (4138.4) | −2114.8 | 41466.5 (3888.7) | 35437.4 (4174.8) | −6029.1 | 3914.3 (−6096.5, 13925.1) |
| Lean mass | 46376.5 (2261.0) | 46201.4 (2289.5) | −175.2 | 47028.6 (2314.2) | 44920.6 (2341.6) | −2108.1** | 1932.9 (−282.6, 4148.5) |
| Weight (kg) | 87.7 (4.2) | 85.3 (4.3) | −2.4 | 86.7 (4.3) | 83.7 (4.4) | −3.0* | 0.6 (−3.0, 4.3) |
| BMIc | 31.2 (1.5) | 30.4 (1.5) | −0.8 | 30.8 (1.5) | 29.7 (1.5) | −1.1* | 0.3 (−1.0, 1.6) |
| HbA1c | 5.4 (0.1) | 5.3 (0.1) | −0.1* | 5.5 (0.1) | 5.4 (0.1) | −0.1 | −0.0 (−0.2, 0.1) |
| Total Cholesterol | 182.1 (8.4) | 169.2 (8.6) | −12.9** | 201.4 (8.7) | 208.6 (9.0) | 7.1 | −20.0** (−34.3, −5.8) |
| LDL Cholesterol | 103.9 (7.5) | 91.7 (7.7) | −12.2** | 122.2 (7.7) | 128.7 (8.0) | 6.4 | −18.6** (−30.5, −6.8) |
| HDL Cholesterol | 58.7 (2.9) | 55.5 (3.0) | −3.2 | 57.0 (3.0) | 57.6 (3.1) | 0.6 | −3.8 (−9.9, 2.2) |
| Triglycerides | 98.0 (10.4) | 109.7 (10.8) | 11.7 | 111.5 (10.7) | 110.5 (11.3) | −1.0 | 12.7 (−10.2, 35.6) |
LDL: low-density lipoprotein; HDL: High Density Lipoprotein
SE: Standard Error; WG: Within Group; WG change (week 16 – baseline);
BG: Between-Group; BG change (active WG change – control WG change);
p<0.05;
p<0.01
missing baseline data in active group: 3 missing for 25-foot walk, 6-min walk, actigraphy, 2 missing 9HPT and SDMT, 1 missing DEXA, RAPA; missing baseline data in control group: 2 missing 25-foot walk, 6-min walk, 1 missing actigraphy.
BDI, EDSS, 9HPT, T25W, 6MWT and Actigraphy inactivity duration
The two groups showed no changes in mean BDI, EDSS, 9HPT, T25W, 6MWT, and Actigraphy inactivity duration (Table 3A).
DEXA Body Composition
Both study groups showed weight loss, with mean weight loss of 2.4 (active) and 3.0 (control) kg (p<0.05) respectively. Per-protocol analysis attenuated control group weight loss to 1.4 kg that further attenuated to 0.9 kg on the sensitivity analysis while the active group weight loss remained unchanged. The active group showed greater within-group change in fat mass than the lean mass (2.4 kg vs 0.18 kg) (Table 3A).
Serum Lipids and Glucose
The mean total cholesterol decreased in the active group (−12.9 mg / dL), compared to the control (+ 7.1 mg/dL) [BG difference - 20.0 mg/dL (95% CI: −34.3 mg/dL, −5.8 mg/dL; p=0.006)]. Mean LDL cholesterol decreased in the active group (−12.2 mg/dL) compared to the control (+6.4 mg/dL) [BG difference - 18.6 mg/dL (95% CI: −30.5 mg/dL, −6.8 mg/dL; p=0.002). HDL cholesterol and mean HbA1c were unchanged (Table 3A).
Fat calories and Fatigue correlation
We observed no correlation between change (week 16 – baseline) in MFIS scores and FFQ fat calories (Table 6).
Table 6:
Spearman correlation coefficients on MFIS and FFQ fat components change scorea
| Active + Control | Active | Control | ||||
|---|---|---|---|---|---|---|
|
| ||||||
| ITT (N=33) | per-protocol (N=31) | ITT (N=17) | per-protocol (N=17) | ITT (N=16) | per-protocol (N=14) | |
| % Calories from fat | −0.07 (p=0.72) | 0.10 (p=0.59) | −0.27 (p=0.30) | −0.27 (p=0.30) | −0.33 (p=0.21) | 0.00 (p=1.00) |
| Total fat | −0.0008 (p=0.99) | −0.05 (p=0.78) | −0.22 (p=0.39) | −0.22 (p=0.39) | −0.03 (p=0.92) | −0.25 (p=0.39) |
| Saturated fat | 0.03 (p=0.86) | −0.001 (p=0.99) | −0.31 (p=0.23) | −0.31 (p=0.23) | 0.02 (p=0.95) | −0.13 (p=0.66) |
change score calculated as week 16 - baseline
Safety and tolerability of the diet
We saw no laboratory safety concerns with the CMP and CBC (Supplemental Table 1). Two active group subjects reported an increase in preexisting MS symptoms. One subject reported trigeminal neuralgia at week 16 that resolved with medical management and the second subject reported an increase in fatigue between weeks 4 and 16.
Discussion
In this 16-week RCT of a low-fat diet in PwMS, we demonstrate a significant improvement in fatigue with the study diet using per-protocol and sensitivity analyses. We observed good diet adherence as seen with the significant reduction in the active group’s daily fat and fat calories intake during the study, whereas the control group showed none.
Several diets have shown benefits in symptoms in PwMS (3–9, 12, 13, 34), but many are restrictive, leading to poor adherence or tolerability due to deficiencies. Our prior one-year-long RCT that used a very low-fat plant-based diet in PwMS found significant fatigue improvement and mediational analysis suggested weight loss as a likely reason for this improvement.(10) The two groups in the current study showed no significant weight changes, but active group showed significant decrease in dietary fat intake. While we observed decrease in both the fatigue scores and total and saturated fat calories between baseline and week 16, further analysis showed no significant correlation between these two. These findings suggest that more complex metabolic mechanisms play a role in the MS fatigue pathophysiology than fat reduction alone.
Our study subjects while predominantly female and RRMS, included all MS subtypes and were on DMT. With a mean disease duration of 17 years, majority were fully ambulatory without aid but had moderate-severe disability in at least one functional domain, making the results very generalizable. (Table 1). According to the NMSS, four times as many women have MS as men. This distinction is important for diet interventions, as MS affects body composition differently in men and women. Men with MS have significantly less whole-body lean mass and higher fat mass than their BMI-matched non-MS counterparts.(35) Our study population is similar to a study conducted by Wahls et al. in 2021 in RRMS, that compared a low-saturated fat (Swank) diet with a modified Paleolithic elimination (Wahls) for fatigue treatment in MS. (34) Our study differs from another study in progressive MS that used a diet-based multimodal intervention for MS-related fatigue where the majority of participants had secondary progressive MS, and had a higher mean EDSS of 6.2 and 67% were not on DMT.(36) To understand if the study diet alone can impact fatigue, we intentionally advised our subjects to not change their physical activity during the study.
Our study had several limitations. First, this was a small, open-label, pilot study where COVID-19 pandemic and inadequate funding limited the ability to meet the enrollment target, leading to inadequate power to detect impact on fatigue in the ITT analysis. Second, both active and control groups reduced total calorie intake. We speculate that this may be attributed to access to nutrition counseling and awareness of food intake in the diet in both groups. Third, the active group did not achieve the study defined diet adherence target of decreasing total daily fat calories to 20% of total caloric intake. However, the active group total daily fat percentage decreased from baseline of 40% to 30% at week 16, depicting a 25% reduction. Recent results from the Women’s Health Initiative study that examined cardiovascular outcomes in normotensive women counseled to follow a low-fat diet demonstrated an average decrease from baseline of fat ~41% of calories to 25.3%, in line with the results of our intervention.(37, 38) Thus, we believe that despite being unable to achieve the study defined target fat percentage, the daily fat intake reduction is clinically meaningful and is consistent with the US 2020 dietary guidelines that can gain broader acceptance.(39) Fourth, we did not capture data on the participants’ socioeconomic status and education, and our study population was predominantly female, which could affect the generalizability of these findings. Lastly, a higher percentage of active group subjects (N = 8, 42.1%) were on fatigue medications compared to the control group (N=3, 15.8%) (p=0.07). However, since fatigue medications were not added during the study or near enrollment, we do not believe this imbalance affected the study results.
In conclusion, this 16-week pilot study of a diet intervention that included a significant reduction in saturated fat and increased carbohydrates and fiber calories appears to improve fatigue in PwMS. Despite not achieving the study’s target enrollment, we show that this dietary approach may help fatigue in PwMS even for those on maximal therapeutic options. While this diet primarily focused on fat calorie reduction, the biological mechanisms underlying the fatigue improvement are likely more complex. As the next step we plan to analyze collected data for the gut microbiome and untargeted metabolomics in these subjects. Additionally, a larger multicenter study to validate findings across a more heterogeneous patient population and to increase external validity is being planned.
Supplementary Material
Table 3B:
Other outcomes, mean (SE)a (per-protocol analysis)
| Active (N=20) | Control (N=17) | BG change (95% CI)b | |||||
|---|---|---|---|---|---|---|---|
|
| |||||||
| Baseline | Week 16 | WG Changea | Baseline | Week 16 | WG Changea | ||
| EDSS | 4.2 (0.3) | 4.2 (0.3) | 0.0 | 3.4 (0.3) | 3.4 (0.3) | 0.0 | 0.0 (−0.4, 0.40) |
| BDI | 10.6 (1.7) | 11.3 (1.8) | 0.7 | 12.8 (1.8) | 12.2 (1.9) | −0.7 | 1.4 (−3.6, 6.4) |
| 9HPT (seconds) | 22.1 (1.9) | 21.6 (1.9) | −0.5 | 23.6 (2.0) | 24.3 (2.0) | 0.8 | −1.3 (−3.7, 1.2) |
| SDMT | 49.2 (2.3) | 48.3 (2.3) | −0.8 | 48.1 (2.5) | 49.5 (2.5) | 1.4 | −2.2 (−5.7, 1.3) |
| 25 foot walk (seconds)c | 7.9 (2.5) | 8.3 (2.5) | 0.5 | 8.3 (2.8) | 8.8 (2.9) | 0.5 | 0.0 (−1.2, 1.3) |
| 6-min walk (m)c | 336.3 (25.9) | 341.3 (26.1) | 5.0 | 394.4 (28.6) | 381.0 (29.3) | −13.4 | 18.4 (−15.0, 51.8) |
| Physical activity (RAPA)c | 3.7 (0.2) | 4.0 (0.2) | 0.3 | 4.2 (0.2) | 3.6 (0.2) | 0.6** | 0.9** (0.3, 1.5) |
| Sleep (minutes) (actigraphy)c | 458.6 (15.2) | 447.7 (17.0) | −10.9 | 417.5 (16.8) | 429.9 (17.1) | 12.4 | −23.3 (−63.3, 16.8) |
| Fat tissue (%) | 43.9 (2.0) | 42.0 (2.1) | −1.9** | 42.1 (2.2) | 42.1 (2.2) | 0.0 | −1.9* (−3.5, −0.4) |
| Fat mass | 38154.3 (2971.3) | 35286.4 (2982.5) | −2867.9** | 37114.1 (3220.5) | 36585.7 (3233.7) | −528.4 | −2339.5** (−3977.0, −702.1) |
| Lean mass | 46372.3 (2192.8) | 46199.7 (2201.5) | −172.6 | 45967.1 (2376.7) | 44669.8 (2386.9) | −1297.3** | 1124.7 (−114.6, 2364.0) |
| Weight (Kg) | 87.7 (4.0) | 85.2 (4.0) | −2.4** | 84.8 (4.4) | 83.4 (4.4) | −1.4** | −1.1 (−3.3, 1.1) |
| BMIc | 31.2 (1.4) | 30.4 (1.4) | −0.9** | 30.2 (1.6) | 29.7 (1.6) | −0.5 | −0.3 (−1.1, 0.4) |
| HbA1c | 5.4 (0.1) | 5.3 (0.1) | −0.1* | 5.5 (0.1) | 5.4 (0.1) | −0.1 | 0.0 (−0.2, 0.2) |
| Total Cholesterol | 182.1 (8.1) | 169.2 (8.3) | −12.9* | 207.3 (8.7) | 215.8 (9.2) | 8.5 | −21.5** (−36.7, −6.3) |
| LDL Cholesterol | 103.9 (7.2) | 91.7 (7.4) | −12.2** | 127.1 (7.8) | 135.2 (8.1) | 8.0 | −20.2** (−32.8, −7.7) |
| HDL Cholesterol | 58.7 (3.0) | 55.5 (4.0) | −3.2 | 57.4 (3.2) | 58.2 (3.4) | 0.8 | −4.0 (−10.5, 2.4) |
| Triglycerides | 98.0 (11.0) | 109.7 (11.0) | 11.7 | 114.1 (11.5) | 111.5 (12.2) | −2.6 | 14.3 (−9.5, 38.1) |
LDL: Low density lipoprotein; HDL: High Density Lipoprotein
SE: Standard Error; WG: Within Group; WG change (week 16 – baseline);
BG: Between-Group; BG change (active WG change – control WG change);
p<0.05;
p<0.01
missing baseline data in active group: 3 missing for 25 foot walk, 6-min walk, actigraphy, 2 missing 9HPT and SDMT, 1 missing DEXA, RAPA; missing baseline data in control group: 2 missing 25-foot walk, 6-min walk, 1 missing actigraphy.
Table 4B:
FFQ, Mean (SE)a (per-protocol analysis)
| Active (N=20) | Control (N=17) | BG change (95% CI)b | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||||||
| Baseline | Week 4 | Week 8 | Week 12 | Week 16 | WG Changea | Baseline | Week 4 | Week 8 | Week 12 | Week 16 | WG Changea | ||
| Total Caloric Intake | 1835.1 (129.1) | 1491.3 (134.8) | 1138.9 (137.7) | 1147.0 (137.7) | 1126.9 (137.7) | −708.2** | 1825.5 (140.0) | 1605.8 (147.0) | 1411.5 (146.7) | 1417.5 (147.0) | 1370.8 (150.5) | −454.7** | −253.5 (−672.8, 165.8) |
| % Cal from fat | 38.7 (1.9) | 33.2 (2.0) | 23.7 (2.0) | 23.5 (2.0) | 23.9 (2.0) | −14.9** | 40.4 (2.0) | 36.3 (2.1) | 39.3 (2.1) | 37.7 (2.1) | 38.0 (2.2) | −2.3 | −12.6** (−19.4, −5.7) |
| Total Fat (g) | 80.4 (6.4) | 56.7 (6.7) | 30.7 (6.9) | 30.5 (6.9) | 31.6 (6.9) | −48.9** | 84.7 (7.0) | 67.3 (7.4) | 60.2 (7.4) | 60.6 (7.6) | 61.3 (7.6) | −23.4** | −25.5* (−48.2, −2.7) |
| Saturated Fat (g) | 27.8 (2.2) | 17.4 (2.3) | 7.2 (2.4) | 7.5 (2.4) | 7.8 (2.4) | −20.1** | 25.8 (2.4) | 21.8 (2.6) | 20.1 (2.5) | 17.0 (2.6) | 19.0 (2.6) | −6.8* | −13.2** (−21.4, −5.1) |
| Trans fat (g) | 2.3 (0.3) | 1.4 (0.3) | 0.7 (0.3) | 0.9 (0.3) | 0.8 (0.3) | −1.5** | 2.1 (0.3) | 2.0 (0.3) | 1.9 (0.3) | 1.7 (0.3) | 2.2 (0.3) | 0.1 | −1.6** (−2.4, −0.8) |
| Sodium | 3393.9 (271.4) | 2787.0 (281.7) | 2438.1 (286.8) | 2570.0 (286.8) | 2261.4 (286.8) | −1132.5** | 3408.0 (294.4) | 2923.4 (306.8) | 2724.4 (306.2) | 2668.6 (313.2) | 2570.4 (313.2) | −837.7** | −294.9 (−1086.1, 496.4) |
| Total Fiber | 20.9 (1.8) | 22.7 (1.8) | 22.3 (1.9) | 21.9 (1.9) | 21.4 (1.9) | 0.5 | 21.4 (1.9) | 18.1 (2.0) | 14.8 (2.0) | 15.6 (2.1) | 15.4 (2.1) | −6.0** | 6.5* (1.3, 11.8) |
| Insoluble Fiber | 14.3 (1.3) | 15.8 (1.3) | 15.2 (1.4) | 15.2 (1.4) | 14.8 (1.4) | 0.5 | 14.4 (1.4) | 11.9 (1.5) | 10.0 (1.5) | 10.2 (1.5) | 10.4 (1.5) | −4.0** | 4.5* (0.8, 8.3) |
| Soluble Fiber | 6.6 (0.6) | 7.3 (0.6) | 7.3 (0.6) | 6.7 (0.6) | 6.8 (0.6) | 0.2 | 6.8 (0.67) | 6.1 (0.7) | 4.9 (0.7) | 5.4 (0.7) | 5.0 (0.7) | −1.8** | 2.1* (0.2, 3.9) |
| Veg servings | 2.6 (0.5) | 3.7 (0.5) | 3.8 (0.5) | 3.8 (0.5) | 3.5 (0.5) | 0.9 | 3.1 (0.5) | 2.8 (0.5) | 2.9 (0.5) | 2.7 (0.6) | 2.6 (0.6) | −0.6 | 1.4* (0.0, 2.8) |
| Fruit servings | 1.3 (0.4) | 2.1 (0.4) | 2.5 (0.4) | 2.1 (0.4) | 2.1 (0.4) | 0.9* | 0.9 (0.8) | 1.7 (0.4) | 1.1 (0.4) | 1.7 (0.5) | 0.9 (0.5) | 0.0 | 0.8 (−0.2, 1.9) |
SE: Standard Error; WG: Within Group; WG change (week 16 – baseline);
BG: Between-Group; BG change (active WG change – control WG change);
p<0.05;
p<0.01
Table 5B:
24-hour food recall, mean (SE)a (per-protocol analysis)
| Active (N=18) | Control (N=17) | BG change (95% CI)b | |||||
|---|---|---|---|---|---|---|---|
|
| |||||||
| Baseline | Week 16 | WG Changea | Baseline | Week 16 | WG Changea | ||
| Total Grams | 3391.7 (198.0) | 3350.8 (198.0) | −40.9 | 3598.7 (207.5) | 3375.0 (214.2) | −223.7 | 182.9 (−165.8, 531.4) |
| Energy (kcal) | 2087.2 (156.0) | 1738.5 (156.0) | −348.7* | 2216.1 (162.0) | 2010.6 (173.1) | −205.5 | −143.2 (−569.9, 283.5) |
| Total Fat (g) | 95.9 (7.4) | 60.4 (7.4) | −35.5** | 91.3 (7.7) | 81.0 (8.4) | −10.2 | −25.3 (−54.0, 3.4) |
| Total Carb (g) | 233.2 (24.5) | 237.5 (24.5) | 4.3 | 255.4 (25.4) | 246.3 (27.1) | −9.1 | 13.4 (−51.7, 78.5) |
| Total Protein (g) | 77.1 (5.5) | 70.3 (5.5) | −6.8 | 83.2 (5.7) | 72.1 (6.1) | −11.1 | 4.3 (−12.4, 21.0) |
| Total Saturated Fatty Acids (g) | 32.6 (3.1) | 18.9 (3.1) | −13.8** | 27.7 (3.2) | 28.7 (3.6) | 1.1 | −14.8* (−27.7, −2.0) |
| Total Monounsaturated Fatty Acids (g) | 34.1 (2.9) | 21.0 (2.9) | −13.1** | 34.2 (2.9) | 26.9 (3.2) | −7.3 | −5.8 (−16.0, 4.4) |
| Total Dietary Fiber (g) | 22.6 (2.5) | 26.0 (2.5) | 3.4 | 24.6 (2.6) | 19.9 (2.8) | −4.7 | 8.1* (1.5, 14.7) |
| % Calories from fat | 39.2 (2.0) | 29.1 (2.0) | −10.1** | 36.3 (2.1) | 36.0 (2.3) | −0.2 | −9.8* (−17.8, −1.9) |
| % Calories from Carb | 43.9 (2.2) | 53.0 (2.2) | 9.0** | 44.9 (2.2) | 46.2 (2.4) | 1.3 | 7.7 (−0.3, 15.8) |
| % Calories from Protein | 15.5 (0.9) | 16.6 (0.9) | 1.1 | 15.3 (0.9) | 15.9 (1.0) | −0.2 | 1.3 (−1.8, 4.4) |
SE: Standard Error; WG: Within Group; WG change (week 16 – baseline);
BG: Between-Group; BG change (active WG change – control WG change);
p<0.05;
p<0.01
Funding:
NMSS: CA 1073-A-4; NIH: UL1 RR024140; Tykeson Family Term Professorship in Wellness Research.
Footnotes
Disclosure: None.
Data Availability Statement:
Data supporting study findings are available within the article and upon request.
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Supplementary Materials
Data Availability Statement
Data supporting study findings are available within the article and upon request.