Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial
ABSTRACT Homocysteine is a risk factor for Alzheimer's disease. In the first report on the VITACOG trial, we showed that homocysteine-lowering treatment with B vitamins slows the rate of brain atrophy in mild cognitive impairment (MCI). Here we report the effect of B vitamins on cognitive and clinical decline (secondary outcomes) in the same study.
This was a double-blind, single-centre study, which included participants with MCI, aged ≥ 70 y, randomly assigned to receive a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B(12) and 20 mg vitamin B(6) (133 participants) or placebo (133 participants) for 2 y. Changes in cognitive or clinical function were analysed by generalized linear models or mixed-effects models.
The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilized executive function (CLOX) relative to placebo (P = 0.015). There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3 µmol/L) in global cognition (Mini Mental State Examination, P < 0.001), episodic memory (Hopkins Verbal Learning Test-delayed recall, P = 0.001) and semantic memory (category fluency, P = 0.037). Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score (P = 0.02) and IQCODE score (P = 0.01).
In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine. Further trials are needed to see if this treatment will slow or prevent conversion from MCI to dementia.
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ABSTRACT: Long-term estrogen replacement therapy with estrogen has benefits for many postmenopausal women. However, some women prefer non-steroidal substitution with herbal preparations. The effectivity against vasomotor symptoms has been evidenced for the extracts of pine bark, of linseed and of Lepidium meyenii (Maca), whereas there is controversy about the effectiveness of genistein-rich soy extract. The extracts of cruciferous vegetables such as Broccoli and of linseed induce changes in the metabolism of estrogens, and antioxidants may reverse altered epigenetic DNA methylation, possibly reducing the risk of breast cancer or its recurrence. Indirect evidence from the literature and from clinical trials supports that a nutriceutical composed of plant extracts, low-dose vitamins and minerals may improve the quality of life by delaying certain age-related diseases. On the basis of epidemiologic studies, physiopathological considerations and controlled prospectieve trials, it is suggested that transdermal substitution therapy with estradiol together with nutriceutical food supplementation may increase the number of quality-adjusted life years of postmenopausal women, but complementary, large-scale, prospective trials are still needed.Climacteric 02/2015; DOI:10.3109/13697137.2014.985646 · 2.24 Impact Factor
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ABSTRACT: Each year approximately 2400 pregnancies develop folic acid-preventable spina bifida and anencephaly in Europe. Currently, 70% of all affected pregnancies are terminated after prenatal diagnosis. The prevalence of neural tube defects (NTDs) has been significantly lowered in more than 70 countries worldwide by applying fortification with folic acid. Periconceptional supplementation of folic acid also reduces the risk of congenital heart diseases, preterm birth, low birth weight, and health problems associated with child mortality and morbidity. All European governments failed to issue folic acid fortification of centrally processed and widely eaten foods in order to prevent NTDs and other unwanted birth outcomes. The estimated average dietary intake of folate in Germany is 200 μg dietary folate equivalents (DFE)/day. More than half of German women of reproductive age do not consume sufficient dietary folate to achieve optimal serum or red blood cell folate concentrations (>18 or 1000 nmol/L, respectively) necessary to prevent spina bifida and anencephaly. To date, targeted supplementation is recommended in Europe, but this approach failed to reduce the rate of NTDs during the last 10 years. Public health centers for prenatal care and fortification with folic acid in Europe are urgently needed. Only such an action will sufficiently improve folate status, prevent at least 50% of the NTD cases, reduce child mortality and morbidity, and alleviate other health problems associated with low folate such as anemia.Journal of Perinatal Medicine 03/2015; DOI:10.1515/jpm-2014-0346 · 1.43 Impact Factor
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ABSTRACT: Objective: Vitamin B12 deficiency is common in older adults, and may increase the risk of cognitive impairment. The distribution of vitamin B12 insufficiency in younger age groups is less studied. This study aims to assess the prevalence of vitamin B12 deficiency (<156 ρmol/L) and subclinical low-normal levels (156-250 ρmol/L) in a large, random sample of the Australian population across the adult life span. Methods: We examined serum vitamin B12 levels in a random sample of 1085 men and 1125 women aged 20-97 years between 1994 and 2006; in the Barwon statistical division, a regional area in southeastern Australia that is representative of the socioeconomic status of the Australian population. Results: The age-standardized prevalence of vitamin B12 deficiency in this cohort of men and women was 3.6%. Subclinical low-normal vitamin B12 levels (156-250 ρmol/L) were found in 26%. Serum vitamin B12 levels declined with age among men (P < 0.001) and were lower in men than women (P < 0.001). Vitamin B12 levels were higher among supplements users (8.0% of the cohort). Conclusions: Vitamin B12 levels decline with age, and have been associated with neurodegenerative diseases and cognitive decline. Early intervention by diet education or supplement use to address this age-associated decline in vitamin levels may be an effective strategy to prevent cognitive decline in a significant segment of the population. Such intervention may need to start in mid-life (from 50-years of age) before the onset of age-related decline in vitamin B12 levels.