Folic acid supplementation in postmenopausal women with hot flushes: phase III randomised double-blind placebo-controlled trial

Objective To assess whether folic acid supplementation ameliorates hot flushes. Design Double-blind, placebo-controlled randomised trial. Setting Nine hospitals in England. Population Postmenopausal women experiencing ≥50 hot flushes weekly. Methods Women (n = 164) were randomly assigned in a 1:1 ratio to receive folic acid 5 mg tablet or placebo daily for 12 weeks. Participants recorded frequency and severity of hot flushes in a Sloan Diary daily and completed Greene Climacteric and Utian Quality of Life (UQoL) Scales at 4-week intervals. Main outcome measures The change in daily Hot Flush Score at week 12 from randomisation based on Sloan Diary Composite Score B calculation. Results Data of 143 (87%) women were available for the primary outcome. The mean change (SD) in Hot Flush Score at week 12 was −6.98 (10.30) and −4.57 (9.46) for folic acid and placebo group, respectively. The difference between groups in the mean change was −2.41 (95% CI −5.68 to 0.87) (P = 0.149) and in the adjusted mean change −2.61 (95% CI −5.72 to 0.49) (P = 0.098). Analysis of secondary outcomes indicated an increased benefit in the folic acid group regarding changes in total and emotional UQoL scores at week 8 when compared with placebo. The difference in the mean change from baseline was 5.22 (95% CI 1.16–9.28) and 1.88 (95% CI 0.23–3.52) for total and emotional score, respectively. Conclusions The study was not able to demonstrate that folic acid had a statistically significant greater benefit in reducing Hot Flush Score over 12 weeks in postmenopausal women when compared with placebo. Tweetable abstract Folic acid may ameliorate hot flushes in postmenopausal women but confirmation is required from a larger study

Folate Augmentation of Treatment – Evaluation for Depression (FolATED): protocol of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Clinical depression is common, debilitating and treatable; one in four people experience it during their lives. The majority of sufferers are treated in primary care and only half respond well to active treatment. Evidence suggests that folate may be a useful adjunct to antidepressant treatment: 1) patients with depression often have a functional folate deficiency; 2) the severity of such deficiency, indicated by elevated homocysteine, correlates with depression severity, 3) low folate is associated with poor antidepressant response, and 4) folate is required for the synthesis of neurotransmitters implicated in the pathogenesis and treatment of depression.</p> <p>Methods/Design</p> <p>The primary objective of this trial is to estimate the effect of folate augmentation in new or continuing treatment of depressive disorder in primary and secondary care. Secondary objectives are to evaluate the cost-effectiveness of folate augmentation of antidepressant treatment, investigate how the response to antidepressant treatment depends on genetic polymorphisms relevant to folate metabolism and antidepressant response, and explore whether baseline folate status can predict response to antidepressant treatment.</p> <p>Seven hundred and thirty patients will be recruited from North East Wales, North West Wales and Swansea. Patients with moderate to severe depression will be referred to the trial by their GP or Psychiatrist. If patients consent they will be assessed for eligibility and baseline measures will be undertaken.</p> <p>Blood samples will be taken to exclude patients with folate and B12 deficiency. Some of the blood taken will be used to measure homocysteine levels and for genetic analysis (with additional consent). Eligible participants will be randomised to receive 5 mg of folic acid or placebo. Patients with B12 deficiency or folate deficiency will be given appropriate treatment and will be monitored in the 'comprehensive cohort study'. Assessments will be at screening, randomisation and 3 subsequent follow-ups.</p> <p>Discussion</p> <p>If folic acid is shown to improve the efficacy of antidepressants, then it will provide a safe, simple and cheap way of improving the treatment of depression in primary and secondary care.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN37558856</p

Language disorders subsequent to left cerebellar lesions: A case for bilateral cerebellar involvement in language?

Background: Crossed cerebello-cerebral diaschisis, reflecting a functional depression of supratentorial language areas due to reduced input via cerebello-cortical pathways, may represent the neuropathological mechanism responsible for language deficits associated with cerebellar pathology. Although it has been proposed that language is lateralized to the right cerebellar hemisphere, recent clinical and neuroimaging studies suggest that the cerebellum may bilaterally influence the regulation of language, with the left cerebellar hemisphere also contributing to the mediation of language via ipsilateral cerebello-cortical pathways. Aims: The aim of the study was to determine the effect of left primary cerebellar lesions on general as well as higher-level language function. Methods and Procedures: Linguistic profiles of a group of ten individuals with left primary cerebellar lesions were compared with those of a group of non-neurologically impaired controls matched for age, gender and level of education. Outcomes and Results: The findings confirmed that higher-level language deficits may result from left primary cerebellar lesions possibly as a consequence of ipsilateral cerebral diaschisis. Conclusions: The results challenge the notion of a right lateralized cerebellum and support a role for the left as well as the right cerebellar hemisphere in the regulation of language function. Copyright (c) 2007 S. Karger AG, Basel