X-Message-Number: 32230
Date: Thu, 17 Dec 2009 21:23:56 -0800 (PST)
From:
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
sclerosis.]
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,
Japan.
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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266591/pdf/nihms37963.pdf
[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
Free text>
http://www.jneurosci.org/cgi/reprint/28/25/6388
ZERO.
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