Potential of modified Mediterranean diet to improve quality of life and fatigue severity in multiple sclerosis patients: a single-center randomized controlled trial

Figures & data

Table 1. The main composition of modified Mediterranean (mMeD) and traditional Iranian (control) diets

Major nutrients	mMeD	Control†
	% of calories	% of calories
Protein	17^1*	13
Carbohydrate	51^1	58
Fat	32^1	29
	% of total fat
Saturated	21^1	32
Monounsaturated	56^1	33
Polyunsaturated	15^1	14
ω6: ω3 Fatty Acids	2.1–3:1^2	3.8:1
Cholesterol mg/Cal	0.16^1	0.12
Fiber g/Cal	0.03^3	0.005
Sodium mg/Cal	1.3^1,3	1.6
Serving sizes and frequencies‡	mMeD	Control†
Olive oils	Main added lipid	Max one serves daily
Vegetables	6 serves daily	1.5 serves daily
Fruits	3 serves daily	3 serves daily
Breads and cereals	8 serves daily	10 serves daily
Legumes	3–4 serves weekly	4 serves weekly
Nuts	3–4 serves weekly	2 serves weekly
Fish/Seafood	5–6 servings weekly	2 servings monthly
Eggs	3 servings weekly	3 servings weekly
Poultry	4 servings weekly	4 servings weekly
Dairy foods	2 serves daily	1 serves daily
Red meat	4 servings monthly	5 servings monthly
Sweets	3 servings weekly	6 servings weekly
Red wine	Not recommended	Not exists

*Reference Number:

1. Bédard A, Riverin M, Dodin S, Corneau L, Lemieux S. Sex differences in the impact of the Mediterranean diet on cardiovascular risk profile. British Journal of Nutrition. 2012 Oct;108(8):1428–34.

2. Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the Western diet: health implications for the 21st century. The American journal of clinical nutrition. 2005 Feb 1;81(2):341–54.

3. Kafatos A, Verhagen H, Moschandreas J, Apostolaki I, Van Westerop JJ. Mediterranean diet of Crete: foods and nutrient content. Journal of the American Dietetic Association. 2000 Dec 1;100(12):1487–93.

† Values were calculated based on average usual intakes of the participants in Traditional Iranian Diet.

‡modified Mediterranean Diet; adopted from 1999 Greek Dietary Guidelines (1999): Ministry of health and welfare, supreme scientific health council: Dietary guidelines for adults in Greece.Arch. Hell. Med. 1999, 16, 516–524. Serving sizes specified as: 25 g bread, 100 g potato, 50–60 g cooked pasta, 100 g vegetables, 80 g apple, 60 g banana, 100 g orange, 200 g melon, 30 g grapes, 1 cup milk or yogurt, 1 egg, 60 g meat, 100 g cooked dry beans.

Figure 1. Flow diagram representing study plan

Table 2. Baseline characteristics of subjects in mMeD and control groups

Group continuous variables		mMeD (n = 68) M ± SD	Control (n = 79) M ± SD	P-value^1
Age (y)		38.6 ± 8.6	40.0 ± 9.6	0.309
Weight (kg)		71.2 ± 10.1	68.5 ± 10.5	0.556
Height (cm)		165.4 ± 7.0	163.0 ± 6.8	0.473
BMI (kg/m^2)		26.1 ± 4.1	25.9 ± 4.5	0.757
Percent body fat (%)		33.3 ± 7.5	32.8 ± 8.2	0.623
Duration of the disease (y)		8.1 ± 5.7	9.3 ± 6.9	0.395
EDSS		1.7 ± 0.7	2.0 ± 0.9	0.059
Categorical variables		mMeD (n = 68) n (%)	Control (n = 79) n (%)	P value^2
Gender	Male (17%)	11 (16.2)	14 (17.7)	0.830
	Female (83%)	57 (83.8)	65 (82.3)
Education	Illiterate	3 (4.4)	3 (3.8)	0.332
	Elementary	7 (10.3)	5 (6.3)
	Junior school	7 (10.3)	9 (11.4)
	Diploma	29 (42.6)	46 (58.2)
	University	22 (32.4)	16 (20.3)
Family history	Yes	10 (14.7)	12 (15.2)	0.999
	No	58 (85.3)	67 (84.8)
BMI classification	Normal	28 (41.2)	34 (43.0)	0.948
	Underweight	2 (2.9)	3 (3.8)
	Overweight	18 (26.5)	22 (27.8)
	Obese	20 (29.4)	20 (25.3)

Abbreviations: mMeD, modified Mediterranean Diet; BMI, Body Mass Index; yr, year; SD, Standard Deviation; EDSS, Extended Disability Status Scale; %, within group percent; control, Traditional Iranian Diet.

¹obtained from independent t-test, EXCEPT for Duration of the disease, BMI, and EDSS, that was analyzed by Man-Whitney U test; P < 0.05 considered significant.

²determined with Chi Square, EXCEPT for gender, and Family history, that was analyzed by Fisher’s Exact test, P < 0.05 considered significant.

Table 3. The comparison of some diet-related factors in in patients with relapsing-remitting multiple sclerosis that received either modified Mediterranean Diet (mMeD) or Traditional Iranian Diet (control) group

Dietary factors	Group	Baseline	End of trial	P value^1	Δ^2	P-value^3
Energy (kJoule/day)	mMeD	11173.8 ± 1960.7	9178.1 ± 1327.5	<0.001*	−1995.2 ± 1255.6	<0.001*
	Control	10776.72 ± 1828.3	10831.4 ± 1755.2	0.828	54.60 ± 2223.8
Oleic fat (mg/day)	mMeD	17506.0 ± 1273.3	17546.9 ± 845.3	0.838	40.8 ± 1637.6	0.631
	Control	17351.5 ± 1219.8	17280.4 ± 1224.0	0.730	−71.1 ± 1823.3
Linoleic fat (mg/day)	mMeD	11304.6 ± 1817.8	12862.8 ± 785.5	<0.001*	1558.1 ± 1691.9	<0.001*
	Control	11517.1 ± 2021.5	11651.3 ± 1798.2	0.640	134.1 ± 2539.1
Linolenic fat (mg/day)	mMeD	187.4 ± 72.2	214.7 ± 60.2	0.026*	27.3 ± 98.6	0.030*
	Control	186.7 ± 69.2	182.1 ± 66.8	0.642	−4.6 ± 89.0
DHA Omega 3 (mg/day)	mMeD	64.8 ± 122.6	181.2 ± 144.3	<0.001*	116.4 ± 138.7	<0.001*
	Control	66.5 ± 114.3	57.9 ± 103.4	0.600	−8.5 ± 16.3
EPA Omega 3 (mg/day)	mMeD	20.0 ± 35.2	53.2 ± 41.0	<0.001*	33.2 ± 38.7	<0.001*
	Control	20.4 ± 32.7	18.0 ± 30.6	0.604	−2.4 ± 41.4
Dietary Fiber (g/day)	mMeD	19.1 ± 4.6	21.0 ± 2.9	0.003*	1.9 ± 5.0	0.121
	Control	19.7 ± 4.5	19.7 ± 4.8	0.957	−0.04 ± 6.4
Sodium (mg/day)	mMeD	4333.4 ± 2087.8	2182.7 ± 1238.2	<0.001*	−2150.7 ± 1774.1	<0.001*
	Control	3995.2 ± 2111.0	4121.0 ± 2120.9	0.685	125.8 ± 2748.5
Potassium (mg/day)	mMeD	2692.7 ± 530.8	3102.2 ± 402.3	<0.001*	409.4 ± 621.1	<0.001*
	Control	2753.9 ± 538.5	2733.0 ± 539.5	0.801	−20.9 ± 735.5
Calcium (mg/day)	mMeD	1088.3 ± 286.5	1241.1 ± 144.0	0.001*	152.8 ± 377.1	0.013*
	Control	1102.0 ± 243.0	1099.8 ± 246.1	0.955	−2.2 ± 346.2
Magnesium (mg/day)	mMeD	253.4 ± 50.5	292.7 ± 36.8	<0.001*	39.2 ± 58.9	<0.001*
	Control	259.0 ± 51.0	257.0 ± 52.2	0.810	−1.9 ± 70.9
Zinc (mg/day)	mMeD	9.0 ± 1.1	9.0 ± 0.9	0.992	0.0 ± 1.5	0.881
	Control	8.9 ± 1.0	8.9 ± 1.1	0.750	−0.05 ± 1.6
Selenium (mg/day)	mMeD	0.11 ± 0.02	0.09 ± 0.01	<0.001*	0.02 ± 0.02	<0.001*
	Control	0.11 ± 0.02	0.11 ± 0.02	0.600	0.00 ± 0.03
Beta Carotene (μg/day)	mMeD	710.7 ± 895.8	1746.2 ± 973.6	<0.001*	1035.5 ± 1084.4	<0.001*
	Control	856.2 ± 962.3	801.8 ± 924.4	0.697	−54.3 ± 1236.6
Alpha tocopherol (mg/day)	mMeD	6.1 ± 1.6	6.9 ± 0.6	<0.001*	0.76 ± 1.7	0.002*
	Control	6.5 ± 1.7	6.5 ± 1.8	0.786	0.07 ± 2.4
Vitamin C (mg/day)	mMeD	94.4 ± 53.2	141.5 ± 37.3	<0.001*	47.0 ± 58.7	<0.001*
	Control	104.4 ± 54.6	101.9 ± 54.3	0.755	−2.5 ± 71.4

Data has been presented as mean ± SD.

¹obtained from paired t test.

²mean changes between end of trial & baseline values.

³obtained from Mann-Whitney U test, and <0.05 considered as significant.

Table 4. Health-related quality of life components and Visual Analogue Fatigue Scale (VAFS) at baseline, 3-month after, and end of intervention (6-month) in patients with relapsing-remitting multiple sclerosis that received either modified Mediterranean Diet (mMeD) or Traditional Iranian Diet (control) group

Related variables	Group	Baseline	3-month after	End of trial	P value^1	Δ^2	P-value^3
Physical function	mMeD	55.8 ± 17.9	61.4 ± 17.5	69.9 ± 14.1	<0.001*	14.1 ± 6.8	<0.001*
	Control	58.9 ± 17.2	59.1 ± 17.1	58.6 ± 17.2	0.692	−0.3 ± 5.1
Health perceptions	mMeD	49.2 ± 15.8	55.4 ± 14.6	59.8 ± 11.1	<0.001*	10.6 ± 9.6	<0.001*
	Control	41.7 ± 11.7	42.0 ± 11.2	42.5 ± 12.1	0.084	0.8 ± 4.0
Energy/fatigue	mMeD	51.0 ± 16.3	59.9 ± 7.9	63.9 ± 3.6	<0.001*	12.8 ± 14.5	<0.001*
	Control	47.2 ± 15.2	48.1 ± 15.7	47.4 ± 14.9	0.841	0.1 ± 3.3
Role limitations-physical	mMeD	47.7 ± 13.3	56.9 ± 8.0	57.4 ± 7.8	<0.001*	9.6 ± 10.9	<0.001*
	Control	55.9 ± 13.6	56.3 ± 13.7	55.4 ± 14.4	0.747	−0.5 ± 4.6
Pain	mMeD	64.5 ± 15.3	70.5 ± 13.6	73.2 ± 11.9	<0.001*	8.7 ± 8.8	<0.001*
	Control	60.5 ± 15.3	60.8 ± 14.8	60.6 ± 15.2	0.875	0.1 ± 4.5
Sexual function	mMeD	44.5 ± 9.7	50.6 ± 7.1	51.0 ± 6.9	<0.001*	6.4 ± 7.7	<0.001*
	Control	47.7 ± 12.1	47.5 ± 12.2	48.7 ± 12.5	0.641	1.0 ± 5.0
Social function	mMeD	66.7 ± 5.4	65.7 ± 0.8	65.2 ± 0.6	<0.001*	−1.4 ± 5.3	0.005*
	Control	59.9 ± 9.0	60.0 ± 8.9	59.2 ± 9.7	0.056	−0.7 ± 5.6
Health distress	mMeD	57.6 ± 15.4	68.9 ± 8.1	73.3 ± 2.9	<0.001*	15.7 ± 4.9	<0.001*
	Control	65.1 ± 11.8	64.8 ± 11.8	66.0 ± 12.5	0.481	0.9 ± 4.6
Overall quality of life	mMeD	59.7 ± 6.9	63.2 ± 5.0	65.5 ± 4.6	<0.001*	5.8 ± 8.5	<0.001*
	Control	54.7 ± 12.3	52.7 ± 12.8	56.0 ± 12.8	0.170	1.3 ± 5.4
Emotional well-being	mMeD	64.9 ± 11.7	71.9 ± 7.3	75.2 ± 3.8	<0.001*	10.3 ± 9.8	<0.001*
	Control	62.5 ± 11.8	62.8 ± 12.1	61.5 ± 11.7	0.780	−0.9 ± 4.0
Role limitations-emotional	mMeD	64.3 ± 14.6	54.3 ± 13.1	48.1 ± 6.5	<0.001*	−16.1 ± 12.8	<0.001*
	Control	59.0 ± 13.2	58.4 ± 13.0	59.6 ± 12.7	0.019*	0.6 ± 4.6
Cognitive function	mMeD	41.8 ± 7.9	45.4 ± 5.0	48.4 ± 3.7	0.276	6.6 ± 9.7	<0.001*
	Control	42.3 ± 8.2	42.3 ± 8.2	42.3 ± 9.7	0.805	−0.05 ± 4.9
Satisfaction with sexual function	mMeD	55.1 ± 13.3	54.0 ± 9.3	54.0 ± 9.3	0.017*	−1.1 ± 12.5	0.712
	Control	50.3 ± 11.8	50.6 ± 11.4	49.7 ± 12.5	0.859	−0.6 ± 4.0
Change in health	mMeD	47.8 ± 22.3	58.1 ± 18.5	58.1 ± 18.5	0.026*	10.3 ± 13.1	<0.001*
	Control	46.2 ± 20.0	45.5 ± 19.9	46.5 ± 21.0	0.496	0.3 ± 6.3
PHCS	mMeD	55.6 ± 12.0	61.2 ± 10.0	64.6 ± 7.8	<0.001*	9.0 ± 6.6	<0.001*
	Control	60.8 ± 13.7	60.2 ± 13.8	62.4 ± 14.3	0.430	1.6 ± 6.6
MHCS	mMeD	59.6 ± 6.2	61.7 ± 1.7	62.7 ± 1.4	0.079	3.0 ± 6.9	<0.001*
	Control	57.9 ± 6.9	58.0 ± 6.9	58.5 ± 7.7	0.765	0.6 ± 2.9
VAFS	mMeD	5.1 ± 2.2	5.0 ± 1.0	5.4 ± 0.5	0.214	0.2 ± 2.0	0.184
	Control	4.9 ± 1.9	4.8 ± 1.9	5.0 ± 1.9	0.051	0.1 ± 0.8

Abbreviations: PHCS, Physical Health Composite Score; MHCS, Mental Health Composite Score; VAFS, Visual Analog Fatigue Scale;

Data has been presented as mean ± SD.

¹obtained from MANCOVA test; adjusted for age, gender, education level, family history, and duration of MS.

²mean changes between end of trial and baseline values.

³obtained from Mann-Whitney U test, and <0.05 considered as significant.

Figure 2. Changes for fatigue severity during 6-month follow-up, A, Intervention; B, Control; FSS, Fatigue Severity Scale. Results obtained from MANCOVA; adjusted for age, gender, education, family history, and duration of MS)