Effect of B Vitamins and Lowering Homocysteine on Cognitive Impairment in Patients With Previous Stroke or Transient Ischemic Attack

Abstract

Background and Purpose-High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack ≥6 months previously. Methods-A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score <24 on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up. Results-A total of 3089 participants (38%) voluntarily undertook the MMSE >6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE ≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L; P<0.001) but no change from baseline in the mean MMSE score (−0.22 points versus −0.25 points; difference, 0.03; 95% confidence interval, −0.13 to 0.19; P=0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47%; risk ratio, 1.01; 95% confidence interval, 0.69-1.48; P=0.976), cognitive decline (9.1% versus 10.3%; risk ratio, 0.89; 0.67-1.18; P=0.414), or cognitive impairment or decline (11.0% versus 11.3%; risk ratio, 0.98; 0.75-1.27; P=0.855). Conclusions-Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.

Exploratory study of sublimed sulfur, in cognitively normal subjects and in Alzheimer’s dementia (AD) subjects: implications for Sulfur targeting Hydrogen sulfide (H2S)/Homocysteine (Hcy) and beta-galactosidase (GALAC)/Autophagy Signaling in AD

“…Our preliminary study of SS in AD is consistent with pivotal roles of Hcy and vitamin B12 and folate as AD risk factors [19,[40][41][42]. A recent meta-analysis of 67 studies [42] using the stata 12.0 statistical software conclude that AD patients distinguish from age-adjusted matched control in having higher levels of Hcy, and lower levels of age-dependent vitamin B12 and folate.…”

“…Nevertheless, our preliminary findings on Sulmedol on lowering Hcy levels in normal subjects, and in improving the neurobehavioral symptoms in moderateadvanced AD stage, raise the relevance of Sulmedol in targeting Hcy/ H 2 S link in development of novel AD therapeutics. Intervention trials using B-vitamin supplementation, however, have produced somewhat inconsistent findings on cognitive function [18][19][20][21][22]. In reviewing the plethora of many cross-sectional and prospective studies, increased levels of plasma total homocysteine are related to the severity of cognitive impairment and AD and vascular dementia.…”

“…The threshold cut-off value of Hcy level for AD risk is set at 10.0 μmol/L. Studies on effects of folate and Vitamin B group have shown mixed and somewhat inconsistent effects in rescuing cognitive deficits in hyper-homocysteinemia [19][20][21]. A systematic review found that 6/7 randomized controlled trials of subjects who were followed for 2-5 years, reported cognitive benefits with high Hcy or low folate levels at baseline [22].…”

İkinci trimester homosistein, B12 vitamini ve folat düzeylerinin olumsuz obstetrik sonuçlarla ilişkisi: Klinik çalışma

“…In response to multivitamin treatment, levels of homocysteine decline within 2-6 weeks in over 90% of the patients. Dietary modifications may also affect homocysteine levels in the blood (29)(30).…”

Cognitive Impairments in Vitamin B12 and Folic Acid Deficiencies and Hyperhomocysteinemia

“…Такая диссоциация, по мнению авторов, обусловлена тем, что механизмы повышения риска сердечно-сосудистых заболеваний при гипергомоцистеинемии реализуются вне зависи-мости от содержания в крови маркеров воспаления. Следует отметить, что результаты исследования не по-зволили установить влияние проводимой терапии на риск развития когнитивного снижения в последую-щем [23]. В связи с этим можно рассматривать приме-нение витаминов группы В в качестве средства преду-преждения ишемического инсульта и сосудистой деменции у пациентов с гипергомоцистеинемией, ве-роятно, в комбинации с другими препаратами.…”