CurcuVIVA

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CurcuVIVA

AOR CODE: AOR04257

A Maintenance Dose for Mild Pain and Inflammation


  • Moderate-dose optimized curcumin from turmeric

  • Free from rapid breakdown by the body

  • Remains in the bloodstream for up to 24 hours

  • Supports the joints, digestion, liver health, and more


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Use this product for: Heart Health Osteoarthritis

Details

CurcuVIVA™ provides an 80 mg maintenance dose of Longvida Optimized Curcumin for those with osteoarthritis, joint pain, chronic pain and more. Longvida Curcumin was specially formulated to provide a solution to the curcumin conundrum of low bioavailability, poor absorption and rapid breakdown. Although bioavailability and absorption help determine effectiveness, the key lies within its ability to remain free. This free state of curcumin is achieved due to the formula’s ability to avoid being rapidly broken down within the body. Because free curcumin retains its “unbroken” form, it is then taken up through the lymph system into the bloodstream where it is stable, concentrated, and retains maximum effectiveness for up to 24 hours. 

Curcumin not only provides relief from joint pain and arthritis, but has many other benefits. It supports digestion, liver and gallbladder health, carries antibacterial, antifungal and antiviral effects, and even promotes healthy cholesterol levels and cardiovascular health. 

Label Info

Discussion

CurcuVIVA is a highly absorbable curcumin formula that is free from rapid excretion. It is traditionally used in herbal medicine as an anti-inflammatory to help relieve mild joint pain. It is also used to aid in digestion, protect the liver and assist in the healing of minor wounds.

Product Variation

Product Code NPN Size
AOR04257 80034713 60 VEGI-CAPS

Supplements Facts

Serving Size: 1 Capsule Amount
Longvida® Optimized Curcumin* (from Curcuma longa root 25-30:1) 80 mg

*LONGVIDA® is a registered trademark of Verdure Sciences Inc. International, patent pending.

Non-medical ingredients:

ascorbyl palmitate, soy lecithin, maltodextrin, microcrystalline cellulose, silicon dioxide, stearic acid, sodium stearyl fumarate. Capsule: hypromellose.

Guarantees

AOR™ guarantees that all ingredients have been declared on the label. Contains no wheat, gluten, nuts, peanuts, sesame seeds, sulphites, mustard, dairy, eggs, fish, shellfish or any animal byproduct.

Adult Dosage

Take 1 capsule per day with/without food, or as directed by a qualified health care practitioner.

Cautions

Consult a health care practitioner prior to use if you are pregnant, taking antiplatelet medications or blood thinners, have stomach ulcers, excess stomach acid, gallstones, or a bile duct obstruction. Consult a health care practitioner if symptoms persist or worsen.

Source

Longvida® Optimized Curcumin (from Curcuma longa/turmeric root)

Main Application

Antioxidant

Maintenance

Mild pain & inflammation

Auto-immunity

Cognitive support

Cellular growth & differentiation

Lipid metabolism

Gastrointestinal health

Disclaimer

The information and product descriptions appearing on this website are for information purposes only, and are not intended to provide or replace medical advice to individuals from a qualified health care professional. Consult with your physician if you have any health concerns, and before initiating any new diet, exercise, supplement, or other lifestyle changes.

Research

Background

Free Yourself, with Free-Form Curcumin

Turmeric, Curcumin & Bioavailability – What’s All The Hype About?

Curcumin is well known for its anti-inflammatory and pain relieving properties, which are well supported by clinical studies. These studies have shown that curcumin is highly effective for improving joint mobility and for reducing stiffness, swelling and pain. However, until recently, very high doses of curcumin (over 8 g per day) have been required to achieve these results due to weak turmeric extracts that provide only 2% curcumin, and to the poor bioavailability of curcumin. Studies suggest that you need to take more than 8g of a regular 95% curcumin extract, which is somewhere between 10 and 20 capsules, before it becomes detectable in your blood! Taking this many capsules per day just to achieve an effective dose is highly inconvenient and costly! Furthermore, many products on the market are highly misleading, and may not be effective at all! Being aware of what is actually in each product and taking advantage of the latest advances in nutraceutical technology can help to ensure that you are getting the best possible curcumin supplement, and therefore the most effective relief from pain and inflammation.

Optimized Curcumin – Discover The Benefits

AOR’s Optimized Curcumin products are based on proven Solid Lipid Particle™ (SLP) technology and have the following advantages:

The only curcumin shown to be free from rapid breakdown within the body and remain in its free form within the blood stream for up to 24 hours! Other so-called bioavailable curcumins result in various metabolites in the blood that have been broken down (ie. glucuronides) and are no longer active or effective, making their improved bioavailability useless.

Clinically tested bioavailability in human subjects, notably in diseased patients, with results published in the prestigious Journal of Agricultural and Food Chemistry (Gota et al., 2010).

A 100-fold increase in bioavailability compared to regular curcumin. No other curcumin on the market has been proven to have this kind of bioavailability. Other so-called bioavailable curcumin products have maximum bioavailability improvements of 30-fold or less.

A recent human study (DiSilvestro et al., 2012) shows that a low dose of 1 capsule of 80 mg Optimized Curcumin reduces blood levels of beta-amyloid in healthy people in just 1 month!

Vegan formula

Optimized Curcumin consists of Solid Lipid Particles™ (SLP). This process involves a unique combination of highly purified lipids that coat the curcumin particles, which are also significantly reduced to 1 millionth of a millimeter in size. This combination is organized in such a way as to increase bioavailability and absorption, and remarkably avoid being rapidly broken down within the body. This unique formulation allows for each solid lipid curcumin particle to be taken up through the lymph system, as opposed to being absorbed directly into the circulation and broken down by the liver, therefore avoiding “first pass metabolism” or glucuronidation. The liver is the major organ responsible for metabolizing or breaking down substances. When something is ingested, it is either glucuronidated or sulphated by the liver. This process involves adding a glucuronide or sulphate group to the substance, making it extremely soluble. It is then carried to our kidneys and bowel and is ready for excretion. When curcumin is able to avoid this rapid breakdown, it retains its activity as free form curcumin. When it cannot, it is excreted out of the body rapidly, which is unfortunately the case with all other curcumins on the market. Finally, the tiny particle size and the lipid coating allows the curcumin to be taken up into the body’s cells quickly and put to use. This means that it delivers all of the health benefits of curcumin, including pain relief, reduced inflammation, antioxidant properties and other effects much faster and more effectively than any other curcumin product. Do you want to free yourself, with free form curcumin?

Try our Optimized Curcumin products today and start feeling the benefits of a true high-potency, free form curcumin supplement.

 

CurcuVIVA provides an 80 mg maintenance dose of Optimized Curcumin. Optimized Curcumin was specially formulated to provide a solution to the curcumin conundrum of low bioavailability, poor absorption and rapid breakdown. Although bioavailability and absorption help determine effectiveness, the key lies within its ability to remain free. This free state of curcumin is achieved due to the formula’s ability to avoid being rapidly broken down within the body. Because free curcumin retains its “unbroken” form, it is then taken up through the blood stream where it is stable, concentrated, and retains maximum effectiveness for up to 24 hours, making it the most effective, absorbable curcumin available.

CurcuVIVA provides an excellent maintenance dosage for mild pain, inflammation, and supports joint function. Curcumin also supports digestion, liver and gallbladder health. Curcumin also has antibacterial, antifungal and antiviral effects, and supports healthy cholesterol levels and cardiovascular health.

 

CurcuVIVA provides an excellent dose for those with mild pain and inflammation and to support healthy joints. It is also a perfect maintenance dose for those who have previously used Curcumin Active or CurcuMIND for severe pain and inflammation and want to maintain their results and their health.

 

Research

Curcumin is currently being heavily studied for use as an adjunct to conventional cancer treatments. Unfortunately, most of the studies have noted minimal results despite promising in vitro and animal studies. Researchers have recognized that the cause for the poor results is curcumin’s poor bioavailability.

Bioavailability

Gota and colleagues did a safety and bioavailability study on healthy volunteers and patients with non-responsive bone cancer. Subjects were given doses between 400 and 1,200 mg of curcumin in solid lipid particle form (equivalent to 1 to 3 capsules of CurcuVIVA). All doses showed significant absorption into the bloodstream over 8 hours with no adverse events. This is especially significant since previous studies giving 8,000-12,000 mg of pure regular curcumin barely showed any blood levels or clinical improvements.  In addition, the 1,200 mg dose produced blood levels of curcumin necessary to reduce isoprostanes, TNF-α, and amyloid-β, which are markers for diseases like cancer and Alzheimer’s disease.

Amyloid-β Reductions

There is also significant interest in its ability to reduce amyloid-β plaque, which is thought to be a causative factor of Alzheimer’s disease. In vitro and animal studies have shown that curcumin can significantly reduce levels of amyloid-β and preserve Alzheimer model animal memory. Finally, a recent human study has shown that just 80 mg of curcumin can reduce amyloid-β in humans. The curcumin that was finally able to do so was Longvida® curcumin SLP, and in just one month.

Longvida® Curcumin in Humans

A human trial on curcumin showed statistically significant effects on clinical endpoints in a healthy population. The fact that such a low dose (80 mg) was needed to achieve effects in only 30 days is an interesting and unique finding as well, and adds to the substantial amount of pharmacokinetic and pharmacodynamic data compiled on Longvida®. The results of the study suggest that curcumin can produce beneficial effects in people who are without immediate disease states. The study was conducted on 38 healthy middle aged people between the age of 40 and 60 who were either given a dose of 80 mg/day of Longvida® curcumin extract for four weeks or were a part of the 19 person placebo group. The study is particularly interesting because the relatively small dose of curcumin, from Longvida® which was used, exerted a variety of health promoting effects leading researchers to presume that a significant amount of the curcumin was absorbed, although not tested directly.

Blood sample readings collected from test subjects to assess nitric oxide and sICAM molecules which are relevant to assessing cardiovascular risk and related to blood pressure and atherosclerosis, were notably affected by the curcumin. Both readings corresponded to a decreased risk of cardiovascular disease. The study also indicated that curcumin may have a positive effect on liver health maintenance as was noted from the reduction of indicators used to mark liver injury. Participants had lowered levels of triglycerides which relates to other research demonstrating that cholesterol could potentially be lowered in relatively healthy persons given higher dosages of the substance, thus benefiting those with or at risk of having cardiovascular disease.

Interestingly, other markers of inflammation and free radicals/toxic species that cause inflammation and damage to cells were also significantly lowered. Both direct and indirect antioxidant actions of curcumin were evident in the subjects; these findings are consistent with in vitro and animal studies used to measure increases in curcumin induced antioxidant enzyme activity.

 

Market Trends

Numerous supplements on the market contain the curcumin extract of turmeric or just straight turmeric extract. However, many of these are poorly absorbed and offer little value in terms of therapeutic benefit due to their poor bioavailability.

New Technology – Better Products!

Over the last ten years a great deal of research has been done to develop formulations that improve the bioavailability of curcumin. The goal has been to deliver more of the active molecules to the body in a much lower daily dose; as few as one to three capsules per day. There have been a number of technologies developed, but the one that has provided the most compelling evidence is nano-technology.

 

AOR Advantage

Longvida® curcumin was introduced to Canada exclusively by AOR in 2011. CurcuVIVA’s advanced technology allows it to be absorbed very rapidly by the body, meaning that it is an excellent choice for rapid pain relief. Furthermore, with an effective dose of just one capsule per day CurcuVIVA is more convenient and more economical than most other curcumin supplements out there!

AOR’s CurcuVIVATM is based on this proven technology and has the following advantages:

Clinically tested with results published in 2010 in the prestigious Journal of Agricultural and Food Chemistry. In the study, patients with cancer of the bone experienced few to no adverse effects and good tolerability of the equivalent of up to 15 capsules of CurcuVIVA.

A 100-fold increase in bioavailability compared to regular curcumin

Patented by the University of California

Published study showing positive effects in reducing beta-amyloid levels in humans at 80 mg in just one month

CurcuVIVA TM consists of solid lipid particles (SLP) which are tiny nano-sized (1 billionth of a meter) particles that have a protected layer that provides a phenomenal increase in stability, potency and effectiveness. Unlike regular curcumin that is easily broken down by stomach acids, Curcumin Fast Relief particles are resistant to acid breakdown. Even more important is the fact that these tiny particles are absorbed very rapidly. This means that they deliver all of the health benefits of curcumin, including pain relief, reduced inflammation, antioxidant properties and other effects much faster than any other curcumin product.

Try CurcuVIVA TM today and start feeling the benefits of a real high-potency, high-bioavailability curcumin supplement.

 

References

Begum et al. Curcumin Structure-Function, Bioavailability, and Efficacy in Models of Neuroinflammation and Alzheimer’s Disease. J Pharmacol Exp Ther. 2008 Jul;326(1):196-208.

Dadhaniya P, Patel C, Muchhara J, Bhadja N, Mathuria N, Vachhani K, Soni MG. Chronic safety of Longvida. Food Chem Toxicol. 2011 May 6.

Disilvestro RA, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012 Sep 26;11:79.

Frautschy, SA. Bioavailability, brain concentrations, activity and dose-response of Longvida® SLCP. 38th Annual Meeting of the Society of Neuroscience , Washington DC, November 15, 2008.

Frautschy, SA et al. Omega 3 DHA and a bioavailable curcumin formulation synergize for Alzheimer prevention. 39th Annual Meeting of the Society of Neuroscience , Chicago, IL October 2009.

Frautschy, SA et al. Efficacy of Longvida® in relation to systemic availability in the brain. 39th Annual Meeting of the Society of Neuroscience , Chicago, IL October 2009.

Gota et al. afety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Ag Food Chem 2010 58(4): 2095-2099.

Ray B, Lahiri DK. Neuroinflammation in Alzheimer’s disease: different molecular targets and potential therapeutic agents including curcumin. Curr Opin Pharmacol. 2009 Aug;9(4):434-44.

 

Abstract

Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population.

J Psychopharmacol. 2014 Oct 2.

Cox KH, Pipingas A, Scholey AB.

Curcumin possesses many properties which may prevent or ameliorate pathological processes underlying age-related cognitive decline, dementia or mood disorders. These benefits in preclinical studies have not been established in humans. This randomized, double-blind, placebo-controlled trial examined the acute (1 and 3 h after a single dose), chronic (4 weeks) and acute-on-chronic (1 and 3 h after single dose following chronic treatment) effects of solid lipid curcumin formulation (400 mg as Longvida®) on cognitive function, mood and blood biomarkers in 60 healthy adults aged 60-85. One hour after administration curcumin significantly improved performance on sustained attention and working memory tasks, compared with placebo. Working memory and mood (general fatigue and change in state calmness, contentedness and fatigue induced by psychological stress) were significantly better following chronic treatment. A significant acute-on-chronic treatment effect on alertness and contentedness was also observed. Curcumin was associated with significantly reduced total and LDL cholesterol and had no effect on hematological safety measures. To our knowledge this is the first study to examine the effects of curcumin on cognition and mood in a healthy older population or to examine any acute behavioral effects in humans. Results highlight the need for further investigation of the potential psychological and cognitive benefits of curcumin in an older population.

 

Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice.

J Biol Chem. 2013 Feb 8;288(6):4056-65.

Ma QL, Zuo X, Yang F, Ubeda OJ, Gant DJ, Alaverdyan M, Teng E, Hu S, Chen PP, Maiti P, Teter B, Cole GM, Frautschy SA.

The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected.

 

Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people.

Nutr J. 2012 Sep 26;11:79.

Disilvestro RA, Joseph E, Zhao S, Bomser J.

BACKGROUND: Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures.

METHODS: The present study was conducted in healthy middle aged people (40-60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion.

RESULTS: Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities.

CONCLUSION: Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.

A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis.

Phytother Res. 2012 Nov;26(11):1719-25.

Chandran B, Goel A.

Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions.

 

Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers.

J Agric Food Chem. 2010 Feb 24;58(4):2095-9

Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG.

Curcumin is the lipid-soluble antioxidant compound obtained from the rhizome of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and inflammatory pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, the clinical literature lacks conclusive evidence supporting its use as a therapeutic agent due to its low bioavailability in humans. The purpose of this study was to quantify plasma levels of free curcumin after dosing of a solid lipid curcumin particle (SLCP) formulation versus unformulated curcumin in healthy volunteers and to determine its tolerability and dose-plasma concentration relationship in late-stage osteosarcoma patients. Doses of 2, 3, and 4 g of SLCP were evaluated in 11 patients with osteosarcoma. Plasma curcumin levels were measured using a validated high-performance liquid chromatography method. The limit of detection of the assay was 1 ng/mL of curcumin. In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of SLCP was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected. In both healthy individuals and osteosarcoma patients, high interindividual variability in pharmacokinetics and nonlinear dose dependency was observed, suggesting potentially complex absorption kinetics. Overall, good tolerability was noted in both healthy and osteosarcoma groups.

 

Curcumin Structure-Function, Bioavailability, and Efficacy in Models of Neuroinflammation and Alzheimer’s Disease.

J Pharmacol Exp Ther. 2008 Jul;326(1):196-208.

Begum et al.

Curcumin can reduce inflammation and neurodegeneration, but its chemical instability and metabolism raise concerns, including whether the more stable metabolite tetrahydrocurcumin (TC) may mediate efficacy. We examined the antioxidant, anti-inflammatory, or anti-amyloidogenic effects of dietary curcumin and TC, either administered chronically to aged Tg2576 APPsw mice or acutely to lipopolysaccharide (LPS)-injected wild-type mice. Despite dramatically higher drug plasma levels after TC compared with curcumin gavage, resulting brain levels of parent compounds were similar, correlating with reduction in LPS-stimulated inducible nitric-oxide synthase, nitrotyrosine, F2 isoprostanes, and carbonyls. In both the acute (LPS) and chronic inflammation (Tg2576), TC and curcumin similarly reduced interleukin-1β. Despite these similarities, only curcumin was effective in reducing amyloid plaque burden, insoluble β-amyloid peptide (Aβ), and carbonyls. TC had no impact on plaques or insoluble Aβ, but both reduced Tris-buffered saline-soluble Aβ and phospho-c-Jun NH2-terminal kinase (JNK). Curcumin but not TC prevented Aβ aggregation. The TC metabolite was detected in brain and plasma from mice chronically fed the parent compound. These data indicate that the dienone bridge present in curcumin, but not in TC, is necessary to reduce plaque deposition and protein oxidation in an Alzheimer’s model. Nevertheless, TC did reduce neuroinflammation and soluble Aβ, effects that may be attributable to limiting JNK-mediated transcription. Because of its favorable safety profile and the involvement of misfolded proteins, oxidative damage, and inflammation in multiple chronic degenerative diseases, these data relating curcumin dosing to the blood and tissue levels required for efficacy should help translation efforts from multiple successful preclinical models.

 

Omega 3 DHA and a bioavailable curcumin formulation synergize for Alzheimer prevention.

39th Annual Meeting of the Society of Neuroscience , Chicago, IL October 2009.

Frautschy, SA et al.

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce risk for Alzheimer’s disease (AD) and may work for prevention but significant side-effect concerns have motivated a search for safer alternatives for chronic use. One alternative, the omega-3 fatty acid DHA, appears promising based on both epidemiology and APP transgenic model work. Successful use of a second alternative, curcumin, an NSAID/ antioxidant used in traditional Indian and Asian medicines, has been hampered by extremely poor bioavailability. Here we report that a more bioavailable lipidated formulation of curcumin can be combined in a cocktail with the omega 3 fatty acid DHA to provide effective interventions in multiple animal models for AD. The curcumin cocktail improves cognitive function, pathology, signal transduction and synaptic deficits in multiple animal models for Alzheimer’s disease including APP Tg mice, 3xAD-Tg mice and htau Tg mice. Interventions have been synergistically effective in preventing cognitive deficits in Morris Water Maze and Y Maze as well as Aβ oligomer-induced insulin/neurotrophic factor inactivation, tau kinase activation and fyn/Tiam1/rac/PAK pathway defects related to synaptic deficits in vivo and in vitro. Further, while DHA alone is very effective in vitro and with early interventions in vivo, effective late stage cocktail interventions in AD model mice with significant pre-existing pathology, neuron loss and cognitive deficits are clearly dependent on the inclusion of the bioavailable lipidated curcumin. The added efficacy with curcumin may reflect a synergistic emulation of NSAID efficacy in suppressing arachidonic acid metabolites and direct binding of β-pleated amyloid structure. Unlike animal models that have pre-pathology cognitive deficits, clinical decline in minimal cognitive impairment and Alzheimer’s disease follows an extensive pro-dromal buildup of both beta amyloid and tau pathology. “Late stages” in transgenic models with extensive pathology better reflects the pathological status of humans at initial stages of clinically relevant cognitive decline. Therefore, success at “late stages” in AD models may be a better predictor of success in clinical trials aimed at prevention and early stage intervention.

 

Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions.

Anticancer Res. 2001 Jul-Aug;21(4B):2895-900.

Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY.

Curcumin (diferuloylmethane), a yellow substance from the root of the plant Curcuma longa Linn., has been demonstrated to inhibit carcinogenesis of murine skin, stomach, intestine and liver. However, the toxicology, pharmacokinetics and biologically effective dose of curcumin in humans have not been reported. This prospective phase-I study evaluated these issues of curcumin in patients with one of the following five high-risk conditions: 1) recently resected urinary bladder cancer; 2) arsenic Bowen’s disease of the skin; 3) uterine cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5) intestinal metaplasia of the stomach. Curcumin was taken orally for 3 months. Biopsy of the lesion sites was done immediately before and 3 months after starting curcumin treament. The starting dose was 500 mg/day. If no toxicity > or = grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration of curcumin in serum and urine was determined by high pressure liquid chromatography (HPLC). A total of 25 patients were enrolled in this study. There was no treatment-related toxicity up to 8,000 mg/day. Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients. The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of crucumin and gradually declined within 12 hours. The average peak serum concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were 0.51 /- 0.11 microM, 0.63 /- 0.06 microM and 1.77 /- 1.87 microM, respectively. Urinary excretion of curcumin was undetectable. One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment. In contrast, histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out of 6 patients of intestinal metaplasia of the stomach, I out of 4 patients with CIN and 2 out of 6 patients with Bowen’s disease. In conclusion, this study demonstrated that curcumin is not toxic to humans up to 8,000 mg/day when taken by mouth for 3 months. Our results also suggest a biologic effect of curcumin in the chemoprevention of cancer.

 

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