[Ronhutton]

I have recently increased my curcumin with piperine to 3,000mg per day.
That sounds a lot, but the following report says,

"
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
(12,000mg)

The number of useful functions with few side effects is impressive, but do take it with piperine, (bioperine), or it is not well absorbed
Ron


http://www.lmreview.com/articles/alz...ic.html#Aref70
Current Research on Promising Nutraceuticals

1. Curcumin

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.

[mrsD]

Curcu-gel.

I was taking regular herb, with fish oil (to enhance absorption), until I found this one.

The claims are quite good for it. And its antioxidant value is listed at 13,000 ORACs.

http://www.epic4health.com/cuul500mgena.html

I am using it for other reasons, and so far have been able to discontinue my SAMe. (arthritis).

As a result, BCM-95® is six-to seven times more bioavailable than ordinary 95% extract. Just one 400 mg dose of this new bioavailability-enhanced turmeric extract is equivalent to taking 2,772 mg of standard “95%” curcumin extract or 2,548 mg of plant-bound curcumin extract with piperine. In the Life Extension human trial, BCM-95® delivered 6.93 times more curcumin to the bloodstream than the ordinary standalone curcumin product and 6.37 times more curcumin to the bloodstream than the plant-bound curcumin extract with piperine.22

http://www.lef.org/magazine/mag2007/...urcumin_01.htm

I agree curcumin is looking very good for many things that affect us as we age.
It also shows effects at decreasing endothelial inflammation, a very important blood vessel
protection.

[lou_lou]

http://neurotalk.psychcentral.com/thread66912.html

[Ronhutton]

Another very recent article,
Ron

http://www.associatedcontent.com/art..._of.html?cat=5

Spice of Life: The Medicinal Value of Tumeric for Parkinson's Disease
January 05, 2009 by Stephen Moon Stephen Moon Published Content: 26 Total Views: 1,534
What if an addition to the regular recipes served in your home could make a dramatic change in the state of your health? What if the addition of turmeric to your monthly menu planning might gradually lead you to better health? Would you be willing to adjust your pallet to include some dishes that could improve, even restore your health? What if...because thus far it has been impossible to create a bio-synthetic form of curcumin.

Curcumin is the primary bioactive active ingredient of tumeric. Commonly used as a seasoning, in South Asian and Middle Eastern cooking, as a tea in Japan, as an inexpensive saffron substitute, as a colorant for some mustards, turmeric is the important ingredient in most curry powders. That's where the yellow comes from, the polyphenolic compounds. Research over the last 50 years has demonstrated that it is the curcumin which provided the range of medicinal properties.

I have read that fewer than 1% of Parkinson's patients use turmeric, the spice used in Indian cooking, as a treatment for the symptoms of the disease. It's a strong antioxidant that may slow or reverse the progression of Parkinson's Disease. Many patients taking it do not notice any change in their symptoms or progression when first taking it, which could be the reason the usage rate is so low. Patients with arthritis may notice more rapid effects.

In the US and UK 280 out of 100,000 patients get Parkinson' disease, In India the rate is only 14 per 100,000. The US and UK are at the high end of the scale while India appears to be at the low end of the prevalence scale.

Besides its antioxidant powers, it is an anti-inflammatory. Curcumin chelates heavy metals and removes them from the body. It is thought to strengthen the blood/brain barrier although more research is necessary and in progress.
A recently published study on 12-14-08, by the prestigous John Hopkins Medical Institutions may result in increase patient usage. News Max reported that "Nerve-like cells in the brain make a mutant form of a protein that causes brain cells to die. The researchers found that when curcumin was applied to brain cells only 19% died as compared to 50% of the cells that were untreated."

Curcumin is safe having undergone six human trials with doses up to 8 grams per day. It has been approved by the FDA as a safe food. Although curcumin has poor oral bioavailability because its metabolites may not have the same bio-activity, that is balanced by at least ten different neuroprotective actions. There has been mention of some interaction with NSADS - non-steroidal anti-inflamatory drugs, which indicates that a discussion with your physician may be necessary before using tumeric on a regular basis

Curcumin is also an anticarcinogenic, it is proving to be effective against a variety of cancers. Colorectal cancer trials appear to indicate that oral supplementation may be effective. Its anti-tumeral effects against melanoma cells have already been seen. Cell culture and animal data show that dietary Curcumin can be used to treat age-related neurodegenerative diseases like Parkinson's, Alzheimer's and stroke. There are currently ongoing clinical trials.

In Ayurvedic medicine, turmeric is often used as an antibacterial. It is thought to have fluoride and is considered an essential for dental health. There are supplements available if cooking with tumeric is not an option.

A beneficial side effect of Curcumin is its effectiveness as an anti-inflammatory and painkiller in the treatment of arthritis. It acts like a cox I or cox II painkiller similar to aspirin or Vioxx but is safer. It is also discussed as possibly being of significant benefit for diabetes and AIDS.

The earliest uses of turmeric were probably as a coloring agent. Turmeric has been used in India for at least 4000 years in the Vedic culture. Marco Polo mentioned it in 1280 in his travel notes of China. Although most commonly grown in Southeast Asia, Peru is the third largest producer of turmeric. You will find it as a common ingredient in Caribbean cooking and is imported from Haiti and Jamaica.

Do not confuse turmeric the rhizome with tumeric root, another name for Golden Seal. Golden Seal is also known for its medicinal properties but cannot be used for sustained periods of time.
Turmeric is a member of the ginger family and is often used with ginger root in teas and curries. Although most turmeric is used in the powered form for cooking, it can be sliced or chopped in the same way that ginger is often used. Its flavor has been described as earthy, a combination of ginger and pepper, musky, slightly bitter and pungent

Turmeric is known by a several names and is also known by its misspelling tumeric. Its botanical name is curcuma longa actually a derivation of the arabic word for saffron. In Sanscrit it was shati, in India it is haldi while in Thai it is kumin. In other Southeast Asian areas it is known as kunyit. Recipes can be searched by any of these names. It is also known as saffron des Indes, Gelbwurz, kharkoum, fa nwin, wong geung fun, kaha, munjal, kamin and Yellow Ginger.

A final note about turmeric: when using it in cooking, remember its origin as a dye. Whether you use the bright yellow powder from India or the brownish version from China, this yellow-orange rhizome can stain most everything with which it comes into contact. Select your cooking vessels carefully. Good Health.