Novel TurmericCompound

Delivers Much MoreCurcumin to the Blood

By Dale Kiefer

Life Extension readers have long been aware ot the vast arrayof health benefits conferred by the curry spice turmeric, which isthe source of curcumin. Scientific researchers around the worldare investigating applications for curcumin that include fightingcancer, arthritis, diabetes, cardiovascular disease, osteoporosis,and reversing the pathological processes underlying Alzheimer'sdisease, among other conditions.'"^-'

Curcumin has long been known to have poor bioavailability,requiring high doses to achieve desired hlood levels. A novelcurcumin absorption system has been developed that delivers upto seven times more pharmacologically bioactive curcumin to theblood compared with commercial curcumin products.

This revolutionary development will radically change the extentto which people may obtain additional health benefits from thisrevered herb. > > >

October 2007 LIFE EXTENSION

A wealth of data shows thatcurcumin and its related chemicals(collectively known as curcuminoids)help to prevent and fight a widerange of diseases—from cancer tocardiovascular disease—through avariety of mechanisms.'^"'^ Theseinclude powerful anti-inflammatory,antioxidant, chemopreventive (can-cer-preventive), and antineoplastic(cancer-fighting) properties.

Perhaps one of curcumin's mostimportant activities in the humanbody is its ability to inhibit acti-vation of the transcription factor,nuclear factor-kappa B (NF-kB),^''a potent inducer of chronic infiam-mation. NF-kB is a protein that actsas a sort of switch, turning on inflam-mation by activating genes involvedin the production of infiammatorycompounds. As NF-kB activationhas been implicated in all the stagesof carcinogenesis, this transcriptionfactor is a potential target in cancerchemoprevention and is the subjectof intensive research.

The Curcumin Revolution:Greatly Enhanced Bioavailability

Despite its impressive array ofbenefits, the effectiveness of oralsupplementation with curcuminhas been limited by poor absorp-tion into the bloodstream throughthe digestive tract. In the past, afew formulators worked aroundthis problem by adding a derivativeof black pepper, piperine, whichenhanced the absorption of ingre-dients such as curcumin.^'' Scientistshave long sought a more bioavailableform of curcumin to provide evengreater pharmaceutical potencies tomaximize curcumin's efficacy.

Life Extension has reviewednumerous curcumin products thatshowed varying degrees of enhancedabsorption. Oae published clinicalstudy caught our attention. In it, anovel manufacturing technologywas able to dramatically increaseblood plasma curcumin to levelsnot previously seen through supple-mentation. While only 50-60% ofpure curcumin administered toanimals is typically absorbed, this

Absorption Comparison of Different Formulations of Curcumin

350-

• Super Bio-Curcumin*(BCM-95*)• Plant-Bound Curcumin with Piperine• Curcumin Standalone Extract

3 4 5 6Time (hours)

new technology increased theabsorption of curcumin to a remark-able 96%.-' This impressive rise inbioavailability was achieved withoutthe addition of piperine.

Impressed with these data andseeking to verify these findings. LifeExtension then ran an objectivecomparison trial on human vol-unteers to determine if this novelcurcumin could really deliversignificantly greater concentrationsof curcumin to the bloodstream andfor a longer sustained time period.'^The findings from Life Extension'sindependent study basicallymirrored those in the first study. Asa result, we identified a curcuminformula that provides better bio-availability than was ever thoughtpossible. Known as BCM-95®, this

"next generation" formulation is farmore readily absorbed than othercurrently or previously available cur-cumin products. In fact, both studiesdelivered close to seven times morecurcumin than was previously avail-able from a standard supplement.

Life Extension's study of thisnew formulation was designed todocument the "pharmacokinet-ics," or absorption, circulation, andmetabolism of curcumin and cur-cuminoids in human subjects. Thestudy compared BCM-95® with

two other curcumin products: aplant-bound curcumin formulationwith piperine and a purified 95%curcumin standalone extract (whichis what most supplement compa-nies sell today). Eleven volunteerswere recruited. They were dividedinto three groups. Subjects receivedBCM-95''\ plant-bound curcuminextract with piperine, or ordinarycurcumin extract. Blood was drawnat baseline and again six times overthe following eight hours. After a two-week washout period, suhjects wereswitched (crossed over) to an alter-nate formulation; BCM-95® subjectswere given ordinary "control" cur-cumin, while subjects originally giveneither of the two "control" curcuminformulations were given BCM-95®.

New Formulation IncreasesBlood Levels More, Sooner, Longer

Subjects' plasma samples weresubsequently assayed to deter-mine curcumin concentrations.The results clearly showed thatBCM-95® was rapidly absorbedfrom the digestive system, allowingmore of turmeric's powerful disease-fighting chemicals to circulatethroughout the bloodstream, whiledelivering the full punch of curcum-in's properties as never before. In

30 LIFE EXTENSION October 2007

fact, curcumin reached a peak withinone hour in the bloodstreams ofsubjects who took BCM-gS*'. Aftera brief dip at about two hours' post-dose, curcumin reached a second,still higher peak again at 4.5 hours,and then gradually declined. By eighthours' post-dose, curcumin was stilldetectable in stibjects' blood.̂ ^

In contrast, ordinary standalonecurcumin took two hours to reachpeak concentration, and thenrapidly declined. By 4.5 hours' post-dose, when BCM-95* curcumin wasjust hitting its stride, curcumiii fromthis control formulation had virtuallydisappeared from subjects' blood-streams. Even at its peak, this controlcurcumin formulation reached onlyabout half the concentration of cur-cumin from BCM-BS"*. Likewise, theBCM-95* showed superior absorp-tion compared with the plant-boundcurcumin with piperine formula.Thus, BCM-95* not only deliversmore curcumin to the bloodstream,sooner, but it sticks around nearlytwice as long, too. This is an extremelyimportant advantage, which shouldresult in greatly enhanced benefits.

How did the inventors of thispatent-pending curcumin achievethis breakthrough? Rather thanfocusing on further purification ofcurcumin and curcuminoids derivedfrom turmeric (usually marketed as

"95% curcumin/curcuminoids"), theformulators went back to the "roots,"so to speak, reincorporating manyof the components of raw turmericroot—which are normally removedduring the extraction process—andgreatly enhancing the bioavail-ability of active constituents in theprocess. In essence, this revolution-ary reformulation relies on theinherent synergy of the turmericrhizome's natural components todramatically enhance bioavailability.

As a result, BCM-95* is six-toseven times more bioavailable thanordinary 95% extract. Just one 400mg dose of this new bioavailability-enhanced turmeric extract is equiva-lent to taking 2,772 mg of standard

"95%" curcumin extract or 2,548 mgof plant-bound curcumin extractwith piperine. In the Life Extension

s^ 250-

2 200-

100-

Absorption of Super Bio-Curcumin'" in RatsCompared with Conventional Curcumin '̂

CurcuminStandalone Extract

Super Bio-CurcumJn'''{BCM-951

Chart 1, Bioavailability in rats fed with BCM-95*is 7.8 times higher than conventional curcumin.

3500-

3000-

2500-

2000-

1500

1000-

500-

Absorption of Super Bio-Curcumin" in HumansCompared with Conventional

CurcuminStandalone Extract

Super Bio-Curcumin''(BCM-95*)

Chart 2. Super Bio-Curcumin* (BCM-95*) showed 6.9 times greater bioavailability(absorption and sustalnability over 8 hours) in humans compared with conventionalcurcumin (as measured by the area under the curve [AUC] in a plot of blood levels

against time, that is, the total amount of curcumin absorbed by the body over 8 hours).

Absorption of Super Bio-Curcumin' in HumansCompared with Plant-Bound Curcumin with Piperine"

Chart 3. Super Bio-Curcumin* (BCM-95®) showed 6.3 times greater bioavaiiability(absorption and sustainability over 8 hours) in humans compared to plant-bound

curcumin with piperine (as measured by the area under the curve [AUC] in a plot of blood levelsagainst time, that is, the total amount of curcumin absorbed by the body over 8 hours).

human trial, BCM-95® delivered 6.93times more curcumin to the blood-stream than the ordinary standalonecurcumin product and 6.37 timesmore curcumin to the bloodstreamthan the plant-bound curcuminextract with piperine.^

Life Extension's results confirmedthe findings shown previously forBCM-95®.

Curcumin's Many Benefits

Curcumin's benefits are so diversethat they affect virtually every organsystem in the body. It's no accidentthat the National Institutes of Healthhas funded numerous studies inves-tigating curcumin, which includediverse applications such as treat-ment of cystic fibrosis, the feasibil-ity of controlling the autoimmunedisease, scleroderma, and variouscancer chemoprevention trials.-^Meanwhile, pharmaceutical compa-nies around the world are activelyworking to derive patentable mol-ecules based on curcumin, whichthey hope to market, at great profit,as anticancer treatments.^^

Among other activities, curcuminhas demonstrated antibacterial,antifungal, antiviral, anti-inflamma-tory and antioxidant capabilities.'^It's even showing great promisein the fight against the most com-

mon genetic disorder in Caucasians,cystic fibrosis.'"^ To this list, addpowerful anticancer protection,cardiovascular protection, andprotection against neurodegenera-tive disorders, such as Alzheimer'sand Parkinson's diseases.^'^'^^"^^Additionally, curcumin shows prom-ise as a potential treatment for multi-ple sclerosis,^ and may protect againstcataracts'" as well as reverse some ofthe damage associated with the highhlood sugar levels that character-ize diabetes.-'' Curcumin also showsgreat promise as a treatment for skindisorders such as psoriasis, and inthe treatment of wounds. '̂̂ ^

Poioerful Cancer Protection

Scientists usually go out oftheir way to avoid hyperbole whendescribing the subjects of their inqui-ries, hut curcumin's amazing proper-ties evidently tempt even the moststaid researcher to throw caution tothe wind. "Curcumin appears to pos-sess all the desirable features of a desk-designed, multipurpose drug," wroteone research team, recently.'' Otherinvestigators focused on promisinganticancer activity. "Curcumin... hasemerged as one of the most power-ful chemopreventive and anticanceragents," wrote Indian researchers lastyear. "Its biological effects range from

antioxidant [andl anti-inflammatoryto inhibition of angiogenesis, and[it] is also shown to possess specificantitumoral activity."-" Althoughanticancer drugs weaken tlie immunesystem, curcumin actually enhancesit, '̂ "-^' acting as an "immunore-storer."̂ "* It's little wonder, then, thatcancer prevention and treatment hasemerged as one of the most avidlyresearched aspects of curcumin'spotential benefits.

Writing in Cancer Letters,American scientists noted recently,"Pre-clinical studies in a variety of can-cer cell lines including breast, cervi-cal, colon, gastric, hepatic, leukemia,oral epithelial, ovarian, pancreatic,and prostate have consistently shownthat curcumin possesses anticanceractivity in vitro and in pre-clinicalanimal models."" Other investigatorswrote: "Carcinogenesis encompassesthree closely associated stages: ini-tiation, progression, and promotion.[Curcumin] has been shown lo pos-sess anti-inflammatory, antioxidant,and antitumor properties. |It| hasalso been shown to be beneficial inall three stages of carcinogenesis.""

Specific Anticancer MechanismDiscovered

In mid-2007, scientists at theUniversity of Alabama at Birminghampublished a report in the journalCancer Research, detailing at leastone of perhaps many mechanismsby which curcumin functions as ananticancer agent. The investigatorsgrew prostate cancer cells in the lab-oratory, and exposed them to varyingconcentrations of curcumin. The cur-cumin reduced the cells" productionof a protein known as MDM2, whichis associated with the formation ofmalignant tumors. Simultaneously,curcumin prompted the cells toproduce another protein associatedwith the promotion of programmedcell death (apoptosis).^' Like NF-kB,an inducer of inflammation, MDM2has been suggested as a novel targetfor human cancer therapy.

To test curcumin's effects in alive model, the scientists graftedhuman prostate cancer cells onto

32 LIFE EXTENSION October 2007

special mice, which subsequentlydeveloped tumors. The mice werethen fed either curcumin or aplacebo, five days a week, for fourweeks. Afterwards, curcumin-fedmice were further divided into threetest groups. One group continuedto receive curcumin alone, whileanother received curcumin plus thecancer chemotherapy drug, gem-citabine. The final group receivedcurcumin plus radiation treatment.

"Curcumin inhibited growth ofI human-to-mouse prostate cancergrafts! oud enhanced the antitumoreffects of gemcitabine and radiation.In these tumors, curcumin reducedthe expression of MDM2." wrote theresearchers. This suppression, or"down-regulation" of MDM2 expres-sion was declared to be a newlydiscovered mechanism by whichcurcumin exerts its anticancer activ-ity. MDM2 down-regulation hycurcumin" may be essential for its che-mopreventive and chemotherapeiiticeffects," the scientists concluded.-'

It's interesting to note thatepidemiological studies show theincidence of prostate cancer amongmen in India to he among the low-est in the world. One recent studyestimated that the annual prostatecancer incidence rate in India rangesfrom 5.0 to 9.1 per 100,000/year.In contrast, among whites in theUnited States, the incidence rate is110.4 per 100,000/year—more tbanten times higher compared with

men from India. The rate for AfricanAmericans is even higher."*'' Perhapsnot coincidentally, Indian men'sconsistent intake of turmeric, in theform or curry, is among the highestin the world. The average intake ofturmeric in the Indian populationis 2-2.5 g/day, providing 60-200 mgcurcumin.

Pancreatic Cancer

Curcumin has also been shownto enhance the efficacy of thechemotherapy agent, gemcitabine,in the treatment of pancreaticcancer. Although it is currently thehest treatment for this aggressivecancer, gemcitabine often loses itseffectiveness as cancer cells developresistance to the drug. Scientistsfrom the University of Texas M.D.Anderson Cancer Center showedrecently that curcumin preventstbe development of this resistance,in both cultured pancreatic cancercells and in living animal modelsof the disease. "Overall, our resultssuggest that curcumin potentiatesthe antitumor effects of gemcitabinein pancreatic cancer by suppressingproliferation, angiogenesis, NF-kB.and NF-kB-regutated gene products,"concluded the scientists."^

Colon and Breast Cancers

Curcumin's efficacy against coloncancer has received great atten-tion, primarily because curcumin'sbioavailability has been less of anissue, given that the colon is exposedto curcumin as it passes throughthe digestive tract^^ Its excellenttolerability and safety have beendemonstrated in five Phase 1 clinicaltrials in colon cancer, and Phase II tri-als are currently enrolling patients.̂ ""British investigators showed recentlythat curcumin interferes with theproliferation of various types of coloncancer, and tliat it enhances the effi-cacy of an existing chemotherapeuticagent, oxaliplatin.^"

Curcumin's potential role in thefight against breast cancer is nothingshort of remarkable. Italian research-ers reported recently that curcumin

< * •

Novel CurcuminP\)rmulation:What You Need to Know

One of today's most promising naturaldisease-tighting agents is curcumin.Derived from the curry spice furmeric.curcumin has been used tor millennia totarget disease and promote good health.Most commercially availablepreparations of curcumin have very poorbioavailability, impairing their ability toconfer life-sustaining properties.Scientists have recently discovered anovel curcumin preparation withexceptional bioavailability. In a humanstudy, this advanced curcuminpreparation—termed BCM-95®—delivered up to seven times morecurcumin to the bloodstream thana standard curcumin product. Thisincreased bioavailability should greatlyenhance curcumin's benefits.Curcumin promotes health by diversemechanisms. Scientists havedocumented curcumin's anti-inflammatory, antioxidant, anti-microbial,neuroprotective, cancer-fighting,and immune-enhancing abilities.Studies suggest that curcumin may helpprevent or fight prostate, pancreatic,breast, and colon cancers.Curcumin may help protect the brainagainst the devastating consequencesof stroke and exposure to toxic heavymetals.

Individuals who consume more curcumin-rich curry are less likely to experiencecognitive decline, suggesting curcumincould help protect the nervous systemagainst aging. In laboratory and animalmodels, curcumin shows promise inpreventing the pathological changesseen in the brains of Alzheimer'sdisease sufferers.

is effective against a common varietyof breast cancer cells and a mutantline of cells that has developedresistance to common chemother-apy drugs. "Through analyses of theeffects on cell proliferation, cyclingand death, we have observed thatthe antitumor activity of curcumin...is at least equal in the [multi-drug-resistant breast cancer) cell line com-pared to the [ordinary breast cancercell linej," wrote researchers.'" Thisefficacy also held true for a type ofmulti-drug-resistant leukemia cell.

The Italians' research indicatesthat curcumin seems capable ofadapting its anticancer activityaccording to need. "Remarkably,"wrote the scientists, "Icurcuminand one of its derivatives] appearedto modify their molecular effectsaccording to the diverse gene expres-sion patterns existing in the [multi-drug-resistant and ordinary breastcancer cell line]. Clearly, the struc-ture and properties of curcumin canform the basis for the developmentof antitumor compounds..."**^

PoioerjulNervous System Protection

Among curcumin's many benefits,protection from neurological dam-age ranks high on many research-ers' lists. "Curcumin has at least 10known neuroprotective actions andmany of these might be realized in[living subjects}..." wrote Americanscientists recently, in Advances inExperimental Medicine and Biology.

"Dietary curcumin is a strong

candidate," they added, "for use inthe prevention or treatment of majordisabling age-related neurodegen-erative diseases like Alzheimer's,Parkinson's, and stroke.""'

These scientists are not alonein their assessment of curcumin'spotential for protection againstdreaded diseases such as Alzheimer's.Numerous researchers are investigat-ing curcumin's protective activitiesin the brain. For example, Chinesescientists reported in early 2007 thatcurcumin protects the brains of lab-oratory animais from a type of injurythat often follows stroke. Known asischemia/reperfusion injury, thisdamage to brain tissue is believed tooccur due to stroke-related deficitsin the blood-brain barrier. A singleinjection of curcumin dramaticallyreduced ischemia-reperfusion dam-age, neurological deficits, and death,among animals with experimentallyinduced stroke.^^

As another example, SouthAfrican investigators wondered ifcurcumin could protect rats' brainsfrom lead poisoning.One way leaddamages brain tissue is by induc-ing lipid per oxidation.^" Brain tissueis largely composed of lipids, so it'sespecially vulnerable to this typeof damage. By adding curcumin totest animals' diets, lead toxicity wassignificantly reduced, possibly byraising concentrations of the anti-oxidant giutathione.^' Previously,Indian researchers reported thatcurcumin raised concentrationsof glutathione and two potentantioxidant enzymes, superoxide

dismutase and catalase, in the brainsof lead-poisoned rats, significantlyattenuating lead-induced damage.''^Other researchers report thatcurcumin may cheiate, or bind to,toxic heavy metals, such as lead andcadmium, greatly reducing their tox-icity to neurological tissues."

Furthermore, scientists havereported that curcumin protectsbrain tissue against oxidative stressby promoting production of a pro-tective enzyme, heme oxygenase-l(HO-1). "In the [central nervous sys-tem[," wrote the researchers, "HO-1has been reported to operate as afundamental defensive mechanismfor neurons exposed to an oxidantchallenge."'"' Traumatic injury to thehrain also results in oxidative stress,often affecting cognition and "syn-aptic plasticity," which is believed toplay a crucial role in healthy learn-ing and memory. In animal experi-ments, US researchers showed,

"Supplementation of curcumin inthe diet dramatically reduced oxi-dative damage and... counteractedthe cognitive impairment caused byItraumatic brain injury]."^^

Cognitive Decline and Dementia

Even in the absence of injury ortoxicity, loss of cognitive functionis a hallmark of aging. Memory lossis believed to begin by age 50, and,by age 80, it's predicted that nearlyhalf of all individuals will advance tosome form of dementia.'*

Wondering if curcumin mightprotect aging brains from cognitivedecline, Asian scientists conductedan epidemiological study of curryconsumption and cognitive func-tion among the elderly. They foundthat men and women who con-sumed turmeric-laced curry "occa-sionally," "often," or "very often,"had significantly better scores on astandardized test of mental statusthan subjects who "never or rarely"consumed curry. The investiga-tors described these findings as

"tentative evidence of bettercognitive performance from curryconsumption in nondementedelderly Asians..."-^

Alzheimer's Disease Protection

Curcumin may offer protectionagainst the most common causeof dementia: Alzheimer's disease.Alzheimer's disease is characterizedby the accumulation of a malformedprotein, amyloid-beta. Ordinarily,immune cells known as maciophagesidentify these defective proteins,engulf them, and destroy them. Butfor reasons that are not entirely clear,macrophages fail to perform this cru-cial function in Alzheimer's disease."tlsing animal models of Alzheimer's,scientists have shown that curcumincan enhance clearance of amyloid-beta, while reducing fibrils, whichare also associated with Alzheimer'spatbology. Curcumin's ability to crossthe blood-brain barrier and directlybind to plaques may be important inits anti-amyloid activity/'"

Los Angeles-based researcherstested the anti-amyloid activity ofhuman macrophages taken fromAlzheimer's disease patients. Afterincubation with curcumin in thelaboratory, uptake of amyloid-betaby macrophages from half of thepatients significantly increased.The researchers concluded that thismodification of the innate immunesystem by curcumin, "might be a safe

approach to immune clearance of[abnormal amyloid-beta accumula-tion] in Alzheimer's disease brain."^^These data appear to indicate thatcurcumin is protective against thedevelopment of Alzheimer's disease,and that it may even help reverse thedisease process, once begun.

Safety and Dosing

Given that turmeric is a foodthat has been safely consumed formillennia, curcumin would appear tobe the perfect dietary supplement.'In fact, "Curcumin has an outstand-ing safety profile and a number of[multifunctionall actions..." wroteUS researchers recently."' Phase I clin-ical trials, using massive doses of cur-cumin (tip to 8 g/day for four months)in human volunteers, "did not resultin discernible toxicities..."''

Of course, not everyone findscurry palatable, especially on a rou-tine basis. But virtually anyone canswallow a simple daily supplement.Most commercial products provide300-500 mg per pill, standardizedto 95% curcumin. Reported adversereactions have been limited to mildgastrointestinal distress, whichmay be minimized by consumingcurcumin with food.'*

Conclusion

In this overview, we've seen thatcurcumin has served mankind forthousands of years, and we've notedsome of the potent benefits scientistscontinue to discover. The advent ofa revolutionary delivery systempromises to make these benefitsavailable to anyone willing to takethe proactive step of supplement-ing the diet with just one or twocapsules of enhanced-bioavailablecurcumin eacii day. |

If you have any questions aboutthe scientific content of thisarticle, please call one of our

Health Advisors at 1 -800-226-2370.

Note: BCM-95® is a registeredtrademark of Dolcas-Biotech, LLC.

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