Table 1.

Summary of complementary and alternative medicine therapies: clinical trials.

Authors	Therapy	Study design	MS type	n	Duration of intervention	Outcome	Results	Ref.
Bates et al.	Omega-3	RDBPC	Acute–remitting	312	1.2 years	Duration, frequency and severity of relapses	No significant difference (p = 0.07)	[52]
Gallai et al.	Omega-3	Randomized controlled	Relapsing–remitting	20	3 months	Change from baseline in PBMC-secreted cytokine levels	Significant decrease in IL-1β, TNF-α, IL-2 and IFN-γ (p < 0.05 for all)	[47]
Shinto et al.	Omega-3	Open-label	Relapsing–remitting	10	3 months	Change from baseline in PBMC-secreted MMP-9	Significant decrease in PBMC-secreted MMP-9 levels (p < 0.01)	[48]
Yadav et al.	Lipoic acid	RDBPC	Relapsing–remitting	37	14 days	Pharmacokinetics and safety. Correlation between mean LA levels and MMP-9 and sICAM-1, respectively	Significant negative correlation between serum LA and MMP-9 (p = 0.04). Significant dose–response relationship between LA and mean change in serum sICAM-1 levels (p = 0.03)	[70]
Lovera et al.	Ginkgo	RDBPC	Any type	43	12 weeks	California Verbal Learning Test-II; Paced Auditory Serial Addition Test; Controlled Oral Word Association Test; Symbol Digit Modalities Test; Useful Field of View Test; and the color-word interference condition from the Stroop Color and Word Test	Significant improvement in ginkgo group on the color-word interference condition of the Stroop test (p = 0.015). No differences between ginkgo and placebo were found on the other neuropsychological tests. No serious drug-related adverse events	[94]
Weinstock-Guttman et al.	Low-fat diet and fish oil or American Heart Association diet plus olive oil (placebo)	RDBPC	Relapsing–remitting	31	1 year	Physical Components Summary Scale (PCS) of the Short Health Status Questionnaire (SF-36)	Clinical benefits favoring the fish oil group were observed on PCS/SF-36 (p = 0.050) and MHI (p = 0.05) at 6 months. Reduced fatigue was seen on the olive oil diet at 6 months (p = 0.035)	[163]
Nordvik et al.	Dietary advice; fish oils; vitamins	Open-label	Newly diagnosed	16	2.2 years	Relapse rate and EDSS	Significant reduction in mean relapse rate compared with baseline (p < 0.001) and significant reduction in mean EDSS compared with baseline (p < 0.01)	[164]
Swank et al.	Low-fat diet and cod liver oil vs higher-fat diet	Open-label comparison group	Not specified	144	34 years	Mortality, ambulation	Patients who adhered to low-fat diet and fish oil had less mortality and greater ambulation than those who did not follow a low-fat diet	[159]
Wingerchuck et al.	Oral calcitrol (2.5 μg/day target dose)	Open-label	Relapsing–remitting	15	48 weeks	Safety, tolerability	Mild adverse events reported, oral cacitrol was safe and tolerable for up to 1 year in MS patients	[141]
Killestein et al.	THC–CBD	Crossover	Secondary and primary progressive	16	4 weeks	Ashworth VAS spasticity	No significant change in Ashworth No significant change in VAS spasticity	[150]
Wade et al.	THC–CBD	Crossover	Not specified	14	4 weeks	Ashworth VAS spasticity	No significant change in Ashworth VAS spasticity improved (p < 0.05)	[151]
Zajicek et al.	THC–CBD	RDBPC	Any type	395	15 weeks	Ashworth	No significant change in Ashworth	[152]
Wade et al.	THC–CBD	RDBPC	Any type	154	6 weeks	Ashworth VAS spasticity	No significant improvement in Ashworth VAS spasticity improved (p = 0.001)	[153]
Vaney et al.	THC–CBD	Crossover	Not specified	57	2 weeks	Ashworth	No significant improvement in Ashworth	[154]
Collin et al.	THC–CBD	RDBPC	Not specified	184	6 weeks	Ashworth	No significant improvement in Ashworth	[155]

EDSS: Expanded Disability Status Score; LA: Lipoic acid; MHI: Mental Health Inventory; MMP: Matrix metalloproteinase; MS: Multiple sclerosis; PBMC: Peripheral blood mononuclear cell; RDBPC: Randomized double-blind placebo-controlled; sICAM: Soluble intercellular adhesion molecule; THC–CBD: δ-9-tetrahydrocannabinol–cannabidol; VAS: Visual analog scale.