X-Message-Number: 32230
Date: Thu, 17 Dec 2009 21:23:56 -0800 (PST)
Subject: evidence based OTC treatment of Alzheimer's disease V

[Rosmarinic acid is an effective peroxynitrite scavenger, and is found in a 
number of spices, including lemon balm, marjorum, oregano, peppermint, rosemary,
sage, and thyme. In addition to the lemon balm trial, two different varieties 
of sage (spanish:salvia lavandulaefolia & common:salvia officinalis) have been 
successful at reversing symptoms of Alzheimer's disease in two human clinical 
trials conducted in New Zealand, and Iran respectively . Rosmarinic acid also 
extended lifespan in an animal model of ALS in Japan.]

[Spanish sage appears to be beneficial.]

Pharmacol Biochem Behav. 2003 Jun;75(3):651-9.

Salvia for dementia therapy: review of pharmacological activity and pilot 
tolerability clinical trial.

Perry NS, Bollen C, Perry EK, Ballard C. Department of Pharmacology and 
Toxicology, University of Otago, Dunedin, New Zealand.

    S. lavandulaefolia Vahl. (Spanish sage) extracts and constituents have 
    demonstrated anticholinesterase, antioxidant, anti-inflammatory, oestrogenic
    and CNS depressant (sedative) effects all of which are currently relevant 
    to the treatment of Alzheimer's disease (AD). The essential oil inhibits the
    enzyme acetylcholinesterase (AChE) from human brain tissue and bovine 
    erythrocyte and individual monoterpenoid constituents inhibit AChE with 
    varying degrees of potency. In vivo AChE inhibition of select brain 
    (striatal and hippocampal over cortical) AChE was obtained following oral 
    administration of the essential oil to rats. In a study in healthy 
    volunteers essential oil administration produced significant effects on 
    cognition. In a pilot open-label study involving oral administration of the 
    essential oil to patients with AD, a significant increase in diastolic and 
    systolic blood pressure was observed in two patients, however this may have 
    been due primarily to preexisting hypertension and there were no 
    abnormalities in other vital signs or blood samples during the trial period.
    Although an open label trial is not free from practice effects or 
    rater-caregiver expectations, statistically significant differences between 
    baseline and 6 weeks treatment were a reduction in neuropsychiatric symptoms
    and an improvement in attention.
PMID: 12895683

[An extract of common sage was successful at reversing Alzheimer's disease to an
extent similar to that of lemon balm.]

J Clin Pharm Ther. 2003 Feb;28(1):53-9.

Salvia officinalis extract in the treatment of patients with mild to moderate 
Alzheimer's disease: a double blind, randomized and placebo-controlled trial.

Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. 
Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences and 
Institute of Medicinal Plants, Iranian Academic Centre for Education, Culture 
and Research, Tehran, Iran.

    BACKGROUND: Alzheimer's disease is characterized by a slow, progressive 
    decline in cognitive function and behaviour. Acetylcholine esterase 
    inhibitors are the only agents approved by the Food and Drug Administration 
    for the treatment of Alzheimer's disease. All other agents prescribed for 
    the treatment of Alzheimer's disease are used on an off-label basis. Current
    research into new drugs is focused on agents that will prevent, slow down 
    and/or halt the progress of the disease process. Salvia officinalis has been
    used in herbal medicine for many centuries. It has been suggested, on the 
    basis of traditional medicine, its in vitro cholinergic binding properties 
    and modulation of mood and cognitive performance in humans, that Salvia 
    officinalis might potentially provide a novel natural treatment for 
    Alzheimer's disease. The objective of this study was to assess the efficacy 
    and safety of Salvia officinalis extract using a fixed dose (60 drops/day), 
    in patients with mild to moderate Alzheimer's disease, over a 4-month 
    period. METHODS: This was a 4-month, parallel group, placebo-controlled 
    trial undertaken in three centres in Tehran, Iran. Patients with mild to 
    moderate Alzheimer's disease aged between 65 and 80 years (n = 42, 18 women)
    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 randomized to placebo or fixed dose of S. officinalis extract. 
    Over the 16 weeks, the main efficacy measures were the change in the 
    ADAS-cog and CDR-Sum of Boxes scores compared with baseline. In addition, 
    side-effects were systematically recorded throughout the study using a 
    checklist. RESULTS: At 4 months, S. officinalis extract produced a 
    significant better outcome on cognitive functions than placebo (ADAS-cog: F 
    = 4.77, d.f. = 1, P = 0.03) (CDR-SB: F = 10.84, d.f. = 1, P < 0.003). There 
    were no significant differences in the two groups in terms of observed 
    side-effects except agitation that appears to be more frequent in the 
    placebo group (P = 0.09). CONCLUSIONS: The results of this study indicate 
    the efficacy of S. officinalis extract in the management of mild to moderate
    Alzheimer's disease. Moreover, S. officinalis may well reduce agitation of 
    patients but this needs to be confirmed.
PMID: 12605619

[Rosmarinic acid extends lifespan in an animal model of amyotrophic lateral 

J Neurosci Res. 2009 Oct 1. [Epub ahead of print]

Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of
familial amyotrophic lateral sclerosis.

Shimojo Y, Kosaka K, Noda Y, Shimizu T, Shirasawa T. Beauty Care Product 
Developing Team, Research and Development Center, Nagase & Co., Ltd.,Hyogo, 

    Amyotrophic lateral sclerosis (ALS) is a late-onset progressive 
    neurodegenerative disease affecting motor neurons. About 2% of patients with
    the disease are associated with mutations in the gene encoding Cu/Zn 
    superoxide dismutase (SOD1). The purpose of this study is to assess the 
    effect of rosemary extract and its major constituents, rosmarinic acid (RA) 
    and carnosic acid (CA), in human SOD1 G93A transgenic mice, which are 
    well-established mouse models for ALS. The present study demonstrates that 
    intraperitoneal administration of rosemary extract or RA from the 
    presymptomatic stage significantly delayed motor dysfunction in paw grip 
    endurance tests, attenuated the degeneration of motor neurons, and extended 
    the life span of ALS model mice. In addition, RA administration 
    significantly improved the clinical score and suppressed body weight loss 
    compared with a vehicle-treated group. In conclusion, this study provides 
    the first report that rosemary extract and, especially, RA have preventive 
    effects in the mouse model of ALS. (c) 2009 Wiley-Liss, Inc.
PMID: 19798750

[Colostrum extract was slightly beneficial.]

Med Sci Monit. 2002 Oct;8(10):PI93-6.

Colostrinin proline-rich polypeptide complex from ovine colostrum--a long-term 
study of its efficacy in Alzheimer's disease.

Leszek J, Inglot AD, Janusz M, Byczkiewicz F, Kiejna A, Georgiades J, Lisowski 
J. Department of Psychiatry, Medical University of Wroclaw, Wroclaw, Poland.

    BACKGROUND: Colostrinin, a proline-rich polypeptide complex (PRP) isolated 
    from ovine colostrum, with immunoregulatory and procognitive properties, has
    shown positive effects in the treatment of Alzheimer's disease (AD). The 
    aim of the present study was to evaluate the effects of long-term 
    Colostrinin treatment of AD patients. MATERIAL/METHODS: The patients were 
    taking Colostrinin tablets (containing 100 mg of PRP complex) every other 
    day for three weeks, followed by a 2-week hiatus to avoid the development of
    hyporeactivity. This mode of application, '3+2 weeks,' was used 
    consistently throughout the trial. The efficacy of treatment was assessed by
    the MMSE scale, and each patient was evaluated at 4-month intervals. 33 
    patients were treated for 16 months. However, 13 patients from this group 
    had already been treated with Colostrinin for 12 months during 
    placebo-controlled studies, and thus participated in the trial for a total 
    of 28 months. RESULTS: The results we obtained showed that Colostrinin 
    induced slight but statistically significant improvement or stabilization of
    the health status of the patients in the trial. The adverse reactions 
    observed, if any, were remarkably mild, including anxiety, logorrhea, and 
    insomnia, and subsided spontaneously within a short period of time (3-4 
    days). CONCLUSIONS: Colostrinin is a very promising preparation which can be
    used to retard the development of AD.
PMID: 12388930

Arch Immunol Ther Exp (Warsz). 1999;47(6):377-85.

Colostrinin: a proline-rich polypeptide (PRP) complex isolated from ovine 
colostrum for treatment of Alzheimer's disease. A double-blind, 
placebo-controlled study.

Leszek J, Inglot AD, Janusz M, Lisowski J, Krukowska K, Georgiades JA. The 
Psychiatric Unit, University Medical School, Wroclaw, Poland.

    A proline-rich polypeptide (PRP) complex, subsequently called Colostrinin, 
    was isolated from ovine colostrum. The complex showed immunomodulatory 
    properties in mice, rats, and chickens, inducing maturation and 
    differentiation of thymocytes. It was recently found that Colostrinin is a 
    cytokine-like factor that acts as an inducer of interferon gamma (IFN-gamma)
    and other cytokines in human peripheral blood and cord blood leukocyte 
    cultures and has psycho-immuno-enhancing activity in volunteers. These 
    observations prompted us to study the effect of Colostrinin on patients with
    Alzheimer's disease (AD). Forty six AD patients were divided into 3 groups 
    and randomly assigned to receive orally either Colostrinin (100 microg per 
    tablet, every second day), commercially available bioorganic selenium (100 
    microg selenium per tablet, every second day) or placebo tablets. One cycle 
    of the treatment lasted 3 weeks and was separated from the next cycle by a 2
    week hiatus. Each patient received 10 cycles of treatment during the year 
    of the clinical trial. Outcomes were assessed by psychiatrists blinded to 
    the treatment assignment. Eight of the 15 AD patients treated with 
    Colostrinin improved and in the 7 others the disease had stabilized. In 
    contrast, none of the 31 patients from the selenium or placebo groups with 
    similar mild or moderate AD improved. The administration of selenium 
    promoted stabilization in 13 of the 15 patients, whereas in the placebo 
    group only 8 of the 16 patients were stabilized at the 12 month trials 
    end-evaluation. Colostrinin was found to be a remarkably safe drug. Mild and
    transient effects were anxiety, stimulation, insomnia, and tiredness. The 
    results obtained showed that oral administration of Colostrinin improves the
    outcome of AD patients with mild to moderate dementia. The results are very
    encouraging and deserve further research.
PMID: 10608295

[Thiamin is slightly beneficial.]

J Geriatr Psychiatry Neurol. 1993 Oct-Dec;6(4):222-9.
Preliminary findings of high-dose thiamine in dementia of Alzheimer's type.

Meador K, Loring D, Nichols M, Zamrini E, Rivner M, Posas H, Thompson E, Moore 
E. Department of Neurology, Medical College of Georgia, Augusta 30912-3200.

    Thiamine is important not only in the metabolism of acetylcholine but also 
    in its release from the presynaptic neuron. Pathologic, clinical, and 
    biochemical data suggest that thiamine deficiency is detrimental to the 
    cholinergic system and that thiamine-dependent enzymes may be altered in 
    Alzheimer's disease. Two previous studies reported contradictory results in 
    patients with dementia of Alzheimer's type treated with 3 g/day of thiamine.
    In the present study, we examined the effects of 3 to 8 g/day thiamine 
    administered orally. Our results suggest that thiamine at these 
    pharmacologic dosages may have a mild beneficial effect in dementia of 
    Alzheimer's type. The mechanism of the observed effect is unknown, but the 
    findings warrant further investigation, not only for their therapeutic 
    implications but for their possible etiologic clues. In addition, the 
    results suggest long-term carry-over effects that should be considered in 
    the design of future studies.
PMID: 8251051

Arch Neurol. 1991 Jan;48(1):81-3.
A trial of thiamine in Alzheimer's disease.

Nolan KA, Black RS, Sheu KF, Langberg J, Blass JP. Altschul Laboratory for 
Dementia Research, Cornell University Medical College, Burke Rehabilitation 
Center, White Plains, NY 10605.

    Because a previous short-term study demonstrated a statistically 
    significant, but not clinically important, improvement in cognitive test 
    scores during thiamine treatment in patients with dementia of the 
    Alzheimer's type, a 12-month, double-blind, parallel-group study was 
    conducted to examine whether long-term administration of thiamine at 3 g/d 
    might slow the progression of dementia of the Alzheimer's type. Fifteen 
    subjects were enrolled and 10 completed the 1-year study. Data are available
    for two additional subjects through the first 9 months of study. No 
    significant differences were found between the placebo and thiamine groups 
    at any point during the study. In both groups, overall means for the 
    Mini-Mental State Examination, verbal learning, and naming scores decreased 
    significantly over the 12-month study period. These results do not support 
    the hypothesis that long-term administration of thiamine at 3 g/d might slow
    the progression of dementia of the Alzheimer's type.
PMID: 1986730

Arch Neurol. 1988 Aug;45(8):833-5.
Thiamine and Alzheimer's disease. A pilot study.

Blass JP, Gleason P, Brush D, DiPonte P, Thaler H. Will Rogers Institute, White 
Plains, NY.

    As a test of the significance of previously described biochemical 
    abnormalities in thiamine-dependent enzymes in brains and other tissues in 
    patients with Alzheimer's disease, a double-blind, placebo-controlled, 
    crossover, outpatient pilot study compared the effects of 3 g/d of oral 
    thiamine hydrochloride for three months with those of a niacinamide placebo.
    Eleven moderately impaired patients with "probable Alzheimer's disease" by 
    the National Institute of Neurological and Communicative Disorders and 
    Stroke-Alzheimer's Disease and Related Disorders Association criteria 
    completed the study. All patients were well nourished and had no stigmata of
    dietary thiamine deficiency. Their initial mean +/- SEM Mini-Mental State 
    Examination score was 14.2 +/- 1.4, and the mean age was 72 years. Global 
    cognitive rating by the Mini-Mental State Examination was higher during 
    three months with 3 g/d of oral thiamine hydrochloride than with niacinamide
    placebo. Behavioral ratings, however, did not differ significantly, nor did
    clinical state when it was judged subjectively.
PMID: 2969232

[Guess the number of human clinical trials using fruit and vegetable juices. The
answer is appended at the end of this file.]

Am J Med. 2006 Sep;119(9):751-9.
Fruit and vegetable juices and Alzheimer's disease: the Kame Project.

Dai Q, Borenstein AR, Wu Y, Jackson JC, Larson EB. Department of Medicine, 
Division of General Internal Medicine and Public Health, Vanderbilt Center for 
Health Services Research, Vanderbilt-Ingram Cancer Center, Vanderbilt School of 
Medicine, Nashville, Tenn, USA.

    BACKGROUND: Growing evidence suggests that oxidative damage caused by the 
    beta-amyloid peptide in the pathogenesis of Alzheimer's disease may be 
    hydrogen peroxide mediated. Many polyphenols, the most abundant dietary 
    antioxidants, possess stronger neuroprotection against hydrogen peroxide 
    than antioxidant vitamins. METHODS: We tested whether consumption of fruit 
    and vegetable juices, containing a high concentration of polyphenols, 
    decreases the risk of incident probable Alzheimer's disease in the Kame 
    Project cohort, a population-based prospective study of 1836 Japanese 
    Americans in King County, Washington, who were dementia-free at baseline 
    (1992-1994) and were followed through 2001. RESULTS: After adjustment for 
    potential confounders, the hazard ratio for probable Alzheimer's disease was
    0.24 (95% confidence interval [CI], 0.09-0.61) comparing subjects who drank
    juices at least 3 times per week with those who drank less often than once 
    per week with a hazard ratio of 0.84 (95% CI, 0.31-2.29) for those drinking 
    juices 1 to 2 times per week (P for trend < .01). This inverse association 
    tended to be more pronounced among those with an apolipoprotein Eepsilon-4 
    allele and those who were not physically active. Conversely, no association 
    was observed for dietary intake of vitamins E, C, or beta-carotene or tea 
    consumption. CONCLUSIONS: Fruit and vegetable juices may play an important 
    role in delaying the onset of Alzheimer's disease, particularly among those 
    who are at high risk for the disease. These results may lead to a new avenue
    of inquiry in the prevention of Alzheimer's disease.
PMID: 16945610
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[Guess what contains peroxynitrite scavengers?]

J Neurosci. 2008 Jun 18;28(25):6388-92.

Grape-derived polyphenolics prevent Abeta oligomerization and attenuate 
cognitive deterioration in a mouse model of Alzheimer's disease.

Wang J, Ho L, Zhao W, Ono K, Rosensweig C, Chen L, Humala N, Teplow DB, 
Pasinetti GM. Department of Psychiatry, Mount Sinai School of Medicine, New 
York, New York 10029, USA.

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by 
    progressive impairments in memory and cognition. Extracellular accumulation 
    of soluble high-molecular-weight (HMW) Abeta oligomers has been proposed to 
    be largely responsible for AD dementia and memory deficits in the Tg2576 
    mice, a model of AD. In this study, we found that a naturally derived grape 
    seed polyphenolic extract can significantly inhibit amyloid beta-protein 
    aggregation into high-molecular-weight oligomers in vitro. When orally 
    administered to Tg2576 mice, this polyphenolic preparation significantly 
    attenuates AD-type cognitive deterioration coincidentally with reduced HMW 
    soluble oligomeric Abeta in the brain. Our study suggests that grape 
    seed-derived polyphenolics may be useful agents to prevent or treat AD.
PMID: 18562609
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