X-Message-Number: 32229 Date: Thu, 17 Dec 2009 21:21:21 -0800 (PST) From: Subject: evidence based OTC treatment of Alzheimer's disease IV [A combination of pyridoxine (B6) 5 mg, folic acid 1 mg, and other vitamins and iron s a dud.] Clin Ther. 2007 Oct;29(10):2204-14. Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients. Sun Y, Lu CJ, Chien KL, Chen ST, Chen RC. Department of Neurology, En Chu Kong Hospital, San-shia, Taipei, Taiwan. BACKGROUND: Elevated serum homocysteine levels have been associated with the development of Alzheimer's dementia (AD). The combined use of a mecobalamin capsule preparation, which contains vitamin B12 0.5 mg with an active methyl base, and an over-the-counter nutritional supplement that contains folic acid 1 mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering vitamin regimen. OBJECTIVE: The aim of this study was to determine whether oral multivitamin supplementation containing vitamins B6 and B12 and folic acid would improve cognitive function and reduce serum homocysteine levels in patients with mild to moderate AD. METHODS: This randomized, double-blind, placebocontrolled trial was conducted at En Chu Kong Hospital, Taipei, Taiwan. Male and female patients aged >50 years with mild to moderate AD and normal folic acid and vitamin B12 concentrations were enrolled. All patients received treatment with an acetylcholinesterase inhibitor and were randomized to receive add-on mecobalamin (B12) 500 mg + multivitamin supplement, or placebos, PO QD for 26 weeks. The multivitamin contained pyridoxine (B6) 5 mg, folic acid 1 mg, and other vitamins and iron. Serum homocysteine level was measured and cognitive tests were conducted at baseline and after 26 weeks. The primary efficacy outcome was change in cognition, measured as the change in score from baseline to week 26 on the Alzheimer's Disease Assessment Scale 11-item Cognition subscale. Secondary efficacy outcomes included changes in function in performance of activities of daily living (ADLs) and concentrations of homocysteine, B12, and folic acid. Tolerability was assessed by comparing the 2 study groups with respect to physical examination findings, including changes in vital signs, laboratory test abnormalities, concomitant medication use, and compliance of study medication was assessed using an interview with the patient's caregiver, as well as the monitoring of adverse events (AEs) throughout the study. RESULTS: Eighty-nine patients (45 men, 44 women; all Taiwanese; mean [SD] age, 75 [7.3] years) were enrolled and randomized. Overall, there were no significant differences in cognition or ADL function scores between the 2 groups. At week 26, the mean (SD) between-group difference in serum homocysteine concentration versus placebo was -2.25 (2.85) micromol/L (P = 0.008), and the mean serum concentrations of vitamin B12 and folic acid were significantly higher (but within normal range) in the multivitamin group compared with placebo (., +536.9 [694.4] pg/mL [P < 0.001] and +13.84 ng/mL [11.17] [P = 0.012] at 26 weeks, respectively). The 2 most common AEs were muscle pain (11.1% and 6.8%) and insomnia (8.9% and 9.1%) in the multivitamin and placebo groups, respectively. CONCLUSIONS: In this population of patients with mild to moderate AD in Taiwan, a multivitamin supplement containing vitamins B(6) and B(12) and folic acid for 26 weeks decreased homocysteine concentrations. No statistically significant beneficial effects on cognition or ADL function were found between multivitamin and placebo at 26 weeks. PMID: 18042476 [Lipoic acid may be slightly beneficial.] J Neural Transm Suppl. 2007;(72):189-93. Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis. Hager K, Kenklies M, McAfoose J, Engel J, Munch G. Department of Medical Rehabilitation and Geriatrics, Henriettenstiftung, Hannover, Germany. Oxidative stress and neuronal energy depletion are characteristic biochemical hallmarks of Alzheimer's disease (AD). It is therefore conceivable that pro-energetic and antioxidant drugs such as alpha-lipoic acid might delay the onset or slow down the progression of the disease. In a previous study, 600mg alpha-lipoic acid was given daily to nine patients with AD (receiving a standard treatment with choline-esterase inhibitors) in an open-label study over an observation period of 12 months. The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (the mini mental state exam, MMSE and the Alzheimer's disease assessment score cognitive subscale, ADAScog). In this report, we have extended the analysis to 43 patients over an observation period of up to 48 months. In patients with mild dementia (ADAScog < 15), the disease progressed extremely slowly (ADAScog: +1.2 points/year, MMSE: -0.6 points/year), in patients with moderate dementia at approximately twice the rate. However, the progression appears dramatically lower than data reported for untreated patients or patients on choline-esterase inhibitors in the second year of long-term studies. Despite the fact that this study was not double-blinded, placebo-controlled and randomized, our data suggest that treatment with alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD. However, a state-of-the-art phase II trial is needed urgently. PMID: 17982894 [Conflicting results with NADH. Only stabilizated NADH was effective.] Drugs Exp Clin Res. 2004;30(1):27-33. Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. Demarin V, Podobnik SS, Storga-Tomic D, Kay G. Department of Neurology, Sestre Milosrdnice University Hospital, Zagreb, Croatia. This study was designed to evaluate the effect of stabilized oral reduced nicotinamide adenine dinucleotide (NADH) on cognitive functioning in patients with Alzheimer's disease (AD). NADH is a coenzyme that plays a key role in cellular energy production and stimulates dopamine production. In previous trials NADH has been shown to improve cognitive functioning in patients with Parkinson's disease, depression and AD. The present trial was a randomized, placebo-controlled, matched-pairs, double-blind, 6-month clinical study. Patients with probable AD (n = 26) were randomized to receive either stabilized oral NADH (10 mg/day) or placebo. Twelve pairs of subjects were matched for age and baseline total score on the Mattis Dementia Rating Scale (MDRS) and the Mini Mental State Examination. After 6 months of treatment, subjects treated with NADH showed no evidence of progressive cognitive deterioration and had significantly higher total scores on the MDRS compared with subjects treated with placebo (p < 0.05). Analysis of MDRS subscales revealed significantly better performance by NADH subjects on measures of verbal fluency (p = 0.019), visual-constructional ability (p = 0.038) and a trend (p = 0.08) to better performance on a measure of abstract verbal reasoning. There were no differences between groups in measures of attention, memory, or in clinician ratings of dementia severity (Clinical Dementia Rating). Consistent with earlier studies, the present findings support NADH as a treatment for AD. PMID: 15134388 J Neural Transm. 2000;107(12):1475-81. No evidence for cognitive improvement from oral nicotinamide adenine dinucleotide (NADH) in dementia. Rainer M, Kraxberger E, Haushofer M, Mucke HA, Jellinger KA. Memory-Clinic and Psychiatric Department, Donauspital, Sozialmedizinisches Zentrum Ost, Wein, Austria. Reduced nicotinamide adenine dinucleotide (NADH) is advertised as an over-the-counter product or dietary supplement to treat Alzheimer's disease. We performed a 3-month open-label study with oral 10 mg/day NADH with 25 patients with mild to moderate dementia of the Alzheimer, vascular, and fronto-temporal types in addition to their current cholinomimetic drug medication. In 19 patients who completed the study, we found no evidence for any cognitive effect as defined by established psychometric tests. We conclude that NADH is unlikely to achieve cognitive improvements in an extent reported earlier, and present theoretical arguments against an effectiveness of this compound in dementia disorders. PMID: 11459000 [An extract of lemon balm (melissa officinalis) extract was highly beneficial in a small trial in Iran. While the placebo patients continued to deteriorate, the lemon balm patients continuously improved throughout the trial. The results of this trial have been largely ignored in the USA, which may be significant error since the results exceed those of prescription drugs, which typically only slow the decline, or help to temporarity stabilize patients.] J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):863-6. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran. OBJECTIVE: To assess the efficacy and safety of Melissa officinalis extract using a fixed dose (60 drops/day) in patients with mild to moderate Alzheimer's disease. DESIGN: A four month, parallel group, placebo controlled trial undertaken in three centres in Tehran, Iran. METHODS: Patients with mild to moderate Alzheimer's disease aged between 65 and 80 years (n = 42; 18 women, 24 men) with a score of >or= 12 on the cognitive subscale of Alzheimer's disease assessment scale (ADAS-cog) and <or= 2 on the clinical dementia rating (CDR) were randomised to placebo or fixed dose of Melissa officinalis extract. The main efficacy measures were the change in the ADAS-cog and CDR-SB scores compared with baseline. Side effects were systematically recorded. RESULTS: At four months, Melissa officinalis extract produced a significantly better outcome on cognitive function than placebo (ADAS-cog: df = 1, F = 6.93, p = 0.01; CDR: df = 1, F = 16.87, p < 0.0001). There were no significant differences in the two groups in terms of observed side effects except agitation, which was more common in the placebo group (p = 0.03). CONCLUSIONS: Melissa officinalis extract is of value in the management of mild to moderate Alzheimer's disease and has a positive effect on agitation in such patients. PMID: 12810768 Fre text: > http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1738567/?tool=pubmed Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=32229