Table 3.

Inclusion and exclusion criteria of reviewed studies.

Study	Age	MS Diagnosis	EDSS Score	Serum 25(OH)D Level	Other Inclusion Criteria	Exclusion Criteria
[19]	18–50 years	MS	≤4.5	n/a	n/a	Inability to walk 500 m or more; conditions or medication affecting bone health; pregnancy, lactating during the past 6 months; menopause; unwillingness to use contraception
[21]	15–60 years	RRMS	≤6	>40 ng/mL	RRMS for 1–12 years, no relapse for at least one month; continue current medications	SPMS and PPMS; other conditions; use of vitamin D supplements; pregnancy
[12]	≥18 years	RRMS	<7	<75 nmol/L or (<30 ng/mL)	IFN-β therapy or those who continue to suffer from FLS beyond 4 months of treatment with IFN-β	Abnormalities of vitamin D related hormonal system; use of medications that influence vitamin D metabolism; conditions of increased susceptibility to hypercalcemia; pregnancy
[14]	18–55 years	RRMS	<5	<85 nmol/L or (<34 ng/mL)	IFN-β therapy for at least 1month and no neutralizing antibodies; contraception; at least one relapse during the year prior the study and/or MRI activity defined as presence of Gd-enhancing lesions on brain MRI	Serum calcium > 2.6 mmol/L; other conditions; pregnancy; use of other immunomodulatory therapy than INFB-1β; allergy to cholecalciferol or peanuts; alcohol or drug abuse
[16]	18–55 years	RRMS	<4	n/a	No relapse 30 days before inclusion; negative β-HCG test for women; calcium < 11 mg/dL	Pregnancy; lactation; other disease; receiving > 4000 IU of vitamin D, corticosteroids treatment in the previous 30 days; aspartate or alanine transaminase > 3xnormal values, ALP > 2.5xnormal values
[15]	18–50 years	RRMS	<4.5	n/a	n/a	Disease or medication affecting bone health; menopause; pregnancy; lactation; nephrolithiasis
[18]	18–55 years	RRMS	<4	<85 ng/mL	No relapse 30 days prior to study day; negative β-HCG test for women; calcium < 11 mg/dL; no relapse during the study	Pregnancy; lactation; other diseases; receiving >4000 IU of vitamin D, corticosteroids therapy in the previous 30 days; AST > 3xnormal values, ALP > 2.5xnormal values
[17]	18–50 years	RRMS	≤4	n/a	No relapse within 30 days prior to study day; first clinical event occurring within 5 years prior to screening; have had at least one relapse, or one or more Gd-enhancing or new T2 MRI lesions within the 12 months; receiving IFNβ-1a > 90 days and <12 months	Pregnancy or lactation; other diseases; use of corticosteroids or adrenocorticotrophic hormone within 30 days prior to SD1 abnormalities of vitamin D-related hormonal system; use of medications that influence vitamin D metabolism; taking N400 IU (N10 μg) of vitamin D supplement daily
[13]	18–55 years	RRMS	n/a	20–50 ng/mL	No relapse within 30 days; serum creatinine >1.5 mg/dL	Daily intake of vitamin D > 1000 IU or change of immunomodulatory therapy within the past 3 months, systemic glucocorticoid therapy; pregnancy, other condition
[20]	18–55 years	RRMS	≤5.0	<85 nmol/L	IFNB-1b use for at least 1month; no neutralising antibodies to IFNβ, as measured by the indirect myxovirus A (MxA) test, using appropriate contraceptive methods.	Pregnancy; serum calcium >2.6 mmol/L; primary hyperparathyroidism; alcohol or drug abuse; use of immunomodulatory therapy other than IFNB-1b; known allergy to cholecalciferol or peanuts; therapy with digitalis, calcitonin, vitamin D3 analogues or vitamin D; any condition predisposing to hypercalcaemia; significant hypertension (blood pressure < 180/110 mm Hg); hyperthyroidism or hypothyroidism in the year before the study began; a history of kidney stones in the previous 5 years; cardiac insufficiency or significant cardiac dysrhythmia; unstable ischaemic heart disease; depression; and inability to perform serial MRI scans.

MS, multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; EDSS, expanded disability status scale; FLS, flue like symptoms; HCG, Human chorionic gonadotropin; ALP, Alkaline phosphatase; AST, Aspartate transaminase; SPMS, secondary progressive multiple sclerosis; PPMS, primary progressive multiple sclerosis, SD1; study day 1; IFNβ, Interferon-β.