Table 1.
Clinical and review studies.
| Study | Main results | References |
|---|---|---|
| Systematic review | Overall incidence rate of MS was 3.6/100,000 person-years | (116) |
| Higher latitude was associated with higher MS incidence | ||
| Latitude gradient was attenuated after 1980, increase in ratio of female-to-male in MS incidence in lower latitudes | ||
| Review and meta-regression analysis | Universal increase in prevalence and incidence of MS over time | (115) |
| A general increase in incidence of MS in females | ||
| Latitude gradient of incidence of MS is apparent for Australia and New Zealand | ||
| Medical hypothesis | Low incidence of MS near the equator may be due to UV light induced suppressor cells to melanocyte antigens | (25) |
| Ecological study | Strong association between MS prevalence and annual UVB | (114) |
| Female and male prevalence rates were correlated with annual UVB | ||
| The effect of UVB on prevalence rates differed by sex | ||
| Review and meta-regression analyses | Statistically significant positive association between MS prevalence and latitude globally | (10) |
| The latitude-dependent incidence of MS, possibly due to UV radiation/vitamin D | ||
| Case-control study | Lower nocturnal serum melatonin levels in MS patients with major depression (MD) compared to patients without MD | (28) |
| Negative correlation between Beck Depression Scale (BDS) scores and serum melatonin levels | ||
| Case-control study | No significant difference between saliva melatonin levels of MS patients vs. healthy subjects; however, when taking the effect of age, a significant difference was found | (29) |
| Case-control study | Decreased levels of 6-sulphatoxy-melatonin (6-SMT) in MS patients | (30) |
| IFN-β treatment increased 6-SMT in patients with improved fatigue | ||
| Case report | 4-years of melatonin therapy improved primary progressive MS | (32) |
| Systematic review | The evidence for vitamin D as a treatment for MS is inconclusive | (38) |
| Larger studies are warranted to assess the effect of vitamin D on clinical outcomes in patients with MS | ||
| Randomized placebo-controlled trial | Low-dose vitamin D therapy had no significant effect on the EDSS score or relapse rate of MS patient. | (39) |
| A larger multicenter study of vitamin D in RRMS is warranted to assess the efficacy of this intervention | ||
| Prospective cohort study | Higher vitamin D levels associated with a reduced hazard of relapse | (40) |
| Each 10 nmol/l increase in vitamin D resulting in up to a 12% reduction in risk of relapse | ||
| Raising 25-OH-D levels by 50 nmol/l could cause relapse | ||
| Randomized, double blind study | Melatonin secretion is negatively correlated with alterations in serum vitamin D in IFN-β treated MS patients | (43) |
| Melatonin should be considered as a potential mediator of vitamin D neuro-immunomodulatory effects in MS patients |