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Curcumin

Overview
http://www.lmreview.com/articles/alzheimers_epidemic.html

Curcumin is the most active of the three curcuminoids found in the yellow-orange Indian curry spice, turmeric (Curcuma longa); the other two are demethoxycurcumin and bis-demethoxycurcumin.

In vitro research has shown curcumin to be a pleiotropic anti-amyloid, antioxidant, anti-inflammatory and immune-modulating treatment for AD.26

Anti-amyloid: By directly binding small Abeta species, curcumin blocks Abeta
aggregation and fibril formation in vitro and in vivo. Adding curcumin to pre-aggregated oligomers results in the appearance of intense monomeric bands, indicating de-aggregation.27

Anti-oxidant: A number of in vitro studies, including research presented at the American Physiological Society's 2004 annual conference in Washington, D.C., have confirmed that curcumin strongly induces expression of the gene hemeoxygenase-1 (HO-1) in astrocytes from the hippocampal region of the brain. HO induction, by generating the vasoactive molecule carbon monoxide and the powerful antioxidant bilirubin, is a protective system against brain oxidative injury. Curcumin also exerts potent antioxidant activity against NO-related radical generation.27,28

Anti-inflammatory: Most inflammatory stimuli activate 1 of 3 independent MAPK pathways, which lead to activation of the p44/42 MAPK (also called ERK1/ERK2), JNK, or the p38 MAPK pathway, respectively. Curcumin inhibits all three pathways directly or indirectly.29,27

Metal chelation: A consistent observation in AD is a dysregulation of metal ions [(Fe(2+), Cu(2+) and Zn(2+)] homeostasis and consequential induction of oxidative stress, associated with Abeta aggregation and amyloid plaque formation. In addition, Abeta has been shown to spontaneously self-aggregate in the presence of divalent metals (Fe2+, Cu2+, Zn2+) into neurotoxic amyloid fibrils in the neocortex. Metal chelation is known to reduce both oxidative stress and amyloid plaque formation. Curcumin has well characterized chelating actions and readily binds both Cu2+ and Fe2+.30,27

Immune modulation: Over the last two decades, curcumin has been shown to be a potent immunomodulatory agent that can regulate the activation of T cells, B cells, macrophages, neutrophils, natural killer cells, and dendritic cells. Curcumin can also downregulate the expression of various pro-inflammatory cytokines including TNF, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, most likely through inactivation of the transcription factor NF-kappaB. Interestingly, however, at low doses, curcumin also enhances antibody responses.31,32

Curcumin in Animal Models of AD
In numerous animal models of AD, curcumin has been shown to cross the blood-brain barrier and reduce senile plaques and cerebrovascular amyloid angiopathy.33
Systemic treatment of mice with curcumin for 7 days clears existing plaques, indicating a potent disaggregation effect. Curcumin also causes significant reversal of structural changes in dystrophic dendrites, including abnormal curvature and dystrophy size. Together, these data suggest that curcumin reverses existing Abeta pathology and associated neurotoxicity in a mouse model of AD.34

Animal studies have demonstrated that curcumin not only clears Abeta from the brain, but reduces AD-related inflammation in brain tissue. Curcumin's brain antioxidant effects have been well-documented in animal models of cerebral ischemia and brain trauma. Not only has plaque buildup been reduced in curcumin-fed rats, but they also outperformed rats on control diets when carrying out maze-based memory tests.27

In AD, several mediators in the inflammation cascade contribute both to neurodegeneration and the production and accumulation of Abeta peptide. Animal studies have shown that curcumin antagonizes many steps in the inflammatory cascade, including AP-1 transcription, activation of NF-kappaB, iNOS and JNK.27

IL-1, an index of neuroinflammation, is also thought to contribute to AD pathogenesis and is elevated in animal models of AD. IL-1 is effectively reduced in curcumin-fed mice compared to controls. The stress-activated (phosphorylated) c-Jun N-terminal kinase (pJNK), also elevated in animal models of AD, is significantly reduced by curcumin as well, and the degree of soluble Abeta reduction is proportional to that of pJNK reduction.27 (JNK is a tau kinase hypothesized to mediate end stage neurodegeneration in AD models.)  

The consensus of researchers conducting animal studies has been unanimous: curcumin's extremely low incidence of side effects, combined with its ability to reduce Abeta burden, and anti-inflammatory and anti-oxidant actions, indicate significant therapeutic potential in combating AD in humans.35,36,37

"The prospect of finding a safe and effective new approach to both prevention and treatment of Alzheimer's disease is tremendously exciting," noted Gregory Cole, MD, a professor of medicine and neurology at the David Geffen School of Medicine at UCLA, in a news release after UCLA research showed curcumin not only inhibits Abeta aggregation and dissolves amyloid fibrils, but does so more effectively than ibuprofen and naproxen. Previous studies had shown that people taking these NSAIDs have a decreased risk of developing Alzheimer's disease.38,34

Curcumin in Human Research
Epidemiological studies have noted very low levels of AD and other dementias in elderly Indian populations whose typical diet is liberally spiced with turmeric. In fact, studies have found that AD affects just 1% of people over the age of 65 living in some Indian villages.39

Similar findings have been noted in other populations. In a recent population-based study of 1,010 elderly non-demented Asians, those who consumed curry ‘‘occasionally’’ and ‘‘often or very often’’ scored significantly better on the Mini-Mental State Examination (MMSE), an established measure of cognitive function, than did those who ‘‘never or rarely’’ consumed curry.40

Bisdemethoxycurcumin restores innate immunity & Abeta clearance in AD patients
Phagocytosis of Abeta by macrophages is excellent in normal subjects but deficient in most AD patients. Increased proinflammatory cytokine levels and activated microglia and macrophages in AD patients may be compensatory for defective clearance of Abeta. Consequently, therapeutic interventions that increase phagocytosis of Abeta might decrease brain inflammation as well as reduce inflammation-induced neurodegeneration.

A secondary curcuminoid in Curcuma longa, bisdemethoxycurcumin, has been shown to improve innate immune system activity in AD patients, increasing Abeta clearance from the brain. In healthy individuals, Abeta presentation stimulates upregulation of genes that increase transcription of beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase (MGAT3) and other genes, including Toll-like receptors. These increase macrophage transport of Abeta into endosomes and lysosomes; in AD patients, however, an increase in Abeta generally down-regulates these genes, resulting in defective phagocytosis. Using blood samples from AD patients, Drs. Milan Fiala and John Cashman have shown that bisdemethoxycurcumin enhances transcription of MGAT3 and Toll-like receptors, restoring macrophage activity to normal levels and enhancing Abeta phagocytosis.41,42

Curcumin extremely safe and well tolerated
At least three different Phase I clinical trials have indicated that curcumin is extremely safe and well tolerated when taken in doses as high as 12 g/day. These results were further confirmed in a dose-escalation trial to determine curcumin’s maximum tolerated dose and safety in which a standardized powder extract of curcumin was administered to 24 healthy volunteers in single doses ranging from 500 to 12,000 mg. Only minimal, non-dose-related toxicity was seen and only in seven subjects (30%).43

Bioavailability enhanced by piperine, the active phytochemical in black pepper
It has been noted that curcumin is extremely rapidly metabolized via glucuronidation in the liver and intestinal wall, which some believe may limit its therapeutic usefulness. Piperine, a known inhibitor of glucuronidation, has been shown to significantly enhance curcumin’s bioavailability in studies involving both rats and healthy human volunteers. In rat studies, administration of curcumin alone at a dose of 2 g/kg, resulted in only moderate serum concentrations over 4 hours. Concomitant administration with piperine (20 mg/kg) increased the serum concentration of curcumin for 1-2 hours post drug, significantly increased the time to maximum concentration, and significantly decreased elimination half-life and clearance, increasing bioavailability by 154%. In humans, administration of curcumin alone produced undetectable or trace amounts in serum; however, concomitant administration with piperine (20 mg/kg) resulted in much higher concentrations and increased bioavailability by a remarkable 2000%.44

Interestingly, black pepper is a common ingredient, along with curcumin, in curry spice blends, which may contribute to the beneficial effects of turmeric consumption seen in epidemiological studies in India and other areas where curries are standard fare.

Diabetes and Obesity


How Young can It Be Given?
This answer was given on the DSTNI Listserve.  It is not an official answer though.
"In some parts of India, turmeric and coconut milk were among the first foods fed to babies. Turmeric was also rubbed on their foreheads. Here is a link where doctors don't recommend spices prior to 8 mo. of age.

http://www.babycenter.in/baby/startingsolids/spicesinbabyfoodexpert/babies were given turmeric.

I have seen another link to herbal supplements from a Dr. in India where he didn't advise his supplement which didn't include turmeric/curcumin prior to 18 mo. of age.

I would be especially careful with dosage if your child is below 18 mo. of age"

Research
  • See attachments at bottom of page.

Brands


Longvida
Website: http://longvida.com/index.php
Aproximately 250mgs Curcumin per 1000mgs Longvida.

Cost:  http://www.riverbendds.org/index.htm?page=longvidadose.html

"The lipid part of Longvida consists of soy lecithin with high phosphatidylcholine content, stearic acid, and vitamin C palmitate." 
Blake Ebersole  bebersole@vs-corp.com

Lecithin
Lecithin is known for helping to prevent arteriosclerosis, protecting against cardiovascular disease, improving brain function, facilitating repair of the liver and promoting energy. Lecithin is a fat emulsifier. It enables fats such as cholesterol to be dispersed in water and removed from the body. It also protects vital organs and
arteries from fatty buildup.  Most commercial lecithin is derived from soy. The best food source of lecithin is egg yolks. Part of the controversy surrounding eggs and cholesterol revolves around the lecithin content of the egg
yolk. Since egg yolks are an excellent source of lecithin they are considered beneficial in reducing cholesterol only if the cooking method preserves the lecithin content. Cooking at high temperatures denatures or destroys the lecithin. This means that any form of cooking that results in runny yolks preserves the lecithin and makes the egg beneficial in reducing cholesterol. Egg yolks cooked solid do not have the same benefit.
http://www.masoncountynews.com/news/article/23539


Available directly from Blake Ebersole or through International Nutrition  http://www.nutrivene.com/view_item.php?ProductID=331&



Enhansa
http://www.leesilsby.com/enhansamain.php

 Enhanced Absorption  Curcumin
 Supplement

 Available as: 150mg.  capsules, 600mg.  capsules, powder


enhansa

Enhansa vs. Standard Curcumin    Dosing Protocol    Testimonials





Concerns
Some people are concerned about possible interactions between Curcumin and other supplements, especially as it has been reported that Curcumin has blood thinning properties.  Here is one post from Einstein Syndrome on this topic:
Okay guys, I figured I had better jump in here before anyone else gets freaked out about GB/NSAID/Curcumin :).
I asked Sally Frautschy about the blood thinning aspects of Curcumin and any interactions with it and here is her response. I posted this a few weeks ago, but maybe nobody saw it ;). There really is not much to worry about.
--------------------------------------
CURCUMIN IS NOT  LIKELY TO PROVE TO BE A BLOOD THINNER.  The in vitro data
arguing that curcumin can be a blood thinnner has not panned out in vivo. It
had the opposite effects in our patient study.     IN terms of the blood
thinning properties of curcumin, there is no data in vivo to support that
curcumin acts that way, nothing at all like aspirin.    It is highly
unlikely since it doesn't impact COX-1 directly.  However, EPA from fish has
"blood thinning"  (as demonstrated by restriction of platelet aggregation)
properties  and DHA may impact that to a lesser extent.  .   I suggest that
when on these supplements to get a clotting tests after 3 months on the
supplement, in case there is an unforeseen interaction of DHA/EPA and
curcumin.  If there is easy bruising when one bumps themselves, make sure to
go get clotting tested.   My guess is that  if one is on a high dose of DHA,
then this would lower the dose of NSAID one needs (curcumin or whatever),
but again , we don't know the perfect combination because NIH and pharma
will not fund the proper number experiments needed to do to answer these
important questions.
INTERACTIONS:  Don't know about interactions of curcumin with ginkgo biloba.
In my mind I would be more concerned with  the interactions  gingko bilboa
with cholinesterase inhibitors  or FDA-approved drugs.   In terms of
interaction of curcumin with other things, it is likely to interact with any
NSAID being used (ibuprofen, steroids, ) so don't take curcumin when on any
other NSAID (eg. perhaps baby aspirin).
----------------------------------------
Hope this clears things up :)!
Qadoshyah
Book - Down Syndrome: What You CAN Do
www.gotdownsyndrome.net/Book/whatyoucandobook.html
Buy it from ~ http://stores.lulu.com/gotdownsyndrome

Curcumin inhibits PST...the enzyme that processes phenols. Without PST you can have a phenol overload and one of the main symptoms of too many phenols is hyperactivity etc. etc. All listed below under PST deficiency. Dr. Feingold with his famous diet for ADHD figured this out many many years ago.

Curcumin is a potent inhibitor of phenol sulfotransferase
http://www.ncbi.nlm.nih.gov/pubmed/12745871

http://www.wrongdiagnosis.com/p/phenol_sulfotransferase_deficiency/intro.htm

Symptoms of Phenol sulfotransferase deficiency
The list of signs and symptoms mentioned in various sources for Phenol sulfotransferase deficiency includes the 18 symptoms listed below:

 a.. Red face
 b.. Red ears
 c.. Dark circles under eyes
 d.. Hyperactivity
 e.. Aggressive behavior
 f.. Head-banging
 g.. Self-injury behavior
 h.. Inappropriate laughter
 i.. Insomnia
 j.. Chronic fatigue in adults
 k.. Headache
 l.. Diarrhea
 m.. Tiredness
 n.. Lethargy
 o.. Excessive thirst
 p.. Night sweats
 q.. Odorous bed clothes
 r.. Autistic behavior
 

See the page on Sulfation Deficits for tips on how to counteract the possible negative side effects of Curcumin. 
 
Ċ
Paul Doney,
14 Sep 2009, 00:59
Ċ
Paul Doney,
14 Sep 2009, 00:59
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