PomegranatePowerful Protection for

Aging Arteries—and Much More

ByTiesha D.Johnson, BSN, RN

Every year, more than a million Americans are struck down by a heart attackor stroke. For many, sudden death will be their first—and last—symptom ofundetected vascular disease. Those lucky enough to survive often face invasiveprocedures like angioplasty and coronary bypass surgery, followed by a lifetimeof curtailed physical activity and costly heart medications.

If you trust your vascular health to mainstream doctors, you may be gam-bling with your life. Although cardiovascular disease remains the nation's num-ber-one killer, American medicine prioritizes heart disease treatment rather thanpreverition. Sadly, it has become far more profitable to treat heart disease thanto prevent it.

Fortunately, natural strategies that can help avert life-threatening heartattacks and strokes are readily available today. One of the most promisingheart-protective agents to emerge in recent years is pomegranate. Packed withunique antioxidants that guard the body's endothelial cells against free-radicalassault, pomegranate has been shown to prevent—and even reverse—cardiovascular disease.

Research also shows that pomegranate can stop the progression of deadlyprostate cancer. And scientists are now exploring pomegranate's potential inaverting ailments ranging from diabetes to Alzheimer's disease, as well as its rolein supporting skin, joint, dental, and liver health.

In this article, we examine the growing volume of research that attests topomegranate's myriad health-promoting properties—particularly its role insafeguarding the delicate endothelial cells that line blood vessels and are socritical to preserving optimal vascular fiinction in aging adults. > > >

May 2007 LIFE EXTENSION 55

POMEGRANATE:POWERFUL SUPPORT FOR

CARDIOVASCULAR H E A L m

Approximately 71 millionAmericans suffer from cardiovasculardiseases such as hypertension (highblood pressure), coronary artery dis-ease, a history of stroke, or peripheralvascular disease (impaired blood flowto the extremities). Atherosclerosis—adisease of the blood vessels, charac-terized by inflammation, vascularendothelial cell dysfunction, andimpaired nitric oxide production—isa major component of cardiovascu-lar disease.

In hoth laboratory and clinicalstudies, pomegranate shows greatpromise in averting the numerouspathological changes associated withcardiovascular disease. Scientistsbelieve pomegranate works throughseveral mechanisms to fight cardio-vascular disease by:

• reducing oxidative stress• supporting the synthesis and

activity of nitric oxide• inhibiting the oxidation of

potentially harmful LDL(low-density lipoprotein).

56 LIFE EXTENSION May 2007

Reducing oxidative stress andinflammatory damage in blood ves-sels is a well-documented way tolower the risk of cardiovascular dis-ease, both known and undetected.'Mounting evidence suggests thatcompounds in pomegranate knownas pimicalagins are cardioprotectiveby virtue of their powerful antioxi-dant and anti-inflammatory effects.

In one study, for example, pome-granate juice outperformed numer-ous otiier potent antioxidants—grapejuice, blueberry juice, red wine, vita-min C, and vitamin E, among others^in "quenching" the damaging effectsof free radicals on cell membranes.-While all the antioxidant nutrientstested effectively prevented theovergrowth of undesirable musclecells in blood vessel walls—a factorcontributing to elevated blood pres-sure—pomegranate juice was by farthe most effective of all.

Supporting the action of nitricoxide is another way to protect thecardiovascular system. Nitric oxideexerts many essential antioxidantand anti-inflammatory effects in thebody, including scavenging certainreactive oxygen species, preventing

LDL oxidation, deterring the adhe-sion and aggregation of blood cellsand platelets along the endothelialcell lining, and inhibiting the prolif-eration of vascular smooth musclecells.' Together, these effects helpretard the progression of atheroscle-rosis. When scientists tested pome-granate against other antioxidants,they found that it helped enhancethe biological actions of nitricoxide, thus conferring significantcardioprotection.

Preventing dangerous LDL oxida-tion is also crucial to protecting theblood vessels ofthe heart. OxidizedLDL can severely damage cardio-vascular health by injuring cells thatline the coronary arteries, leading toinflammation and narrowing thatcan precipitate a heart attack. LDLoxidation also reduces the activity ofenzymes that produce nitric oxidein those blood vessels, thus prevent-ing them from responding normallyto changing demands for biood flow.When scientists treated human cor-onary artery cells with pomegran-ate juice, they discovered a dramaticcorrection in levels of nitric oxideproduction.' This correction is likelyto be beneficial in preventing com-plications of blood vessel disease,including heart attacks.

Just as water flowing rapidlydown a canyon gradually erodes thecanyon walls and stirs up residues,hlood flowing under high pressure ordisturbed by narrowed arteries candamage blood vessel walls, increas-ing oxidative damage and worsen-ing atherosclerosis.'' A recent Italianstudy found that pomegranate juiceconcentrate reduced oxidant-relatedcellular ciianges in blood vessel cellsexposed to high shear stresses, suchas those produced by disturbed blood

flow.̂ The juice also increased nitricoxide production, further protectingthe cells. After demonstrating theseeffects in cell cultures, the scientistsadministered pomegranate juice tomice with elevated cholesterol levels,and found that they could markedlyimpede the progression of atheroscle-rosis. These exciting findings suggestthat the dangerous effects inducedhy perturbed shear stress can bereversed by chronic administrationof pomegranate juice.

POMEGRANATE MAYREVERSE ATHEROSCLEROSIS

Human studies of pomegranatejuice have demonstrated even moredramatic effects, showing that pome-granate may actually reverse athero-sclerosis. Israeli scientists studiedpatients with narrowing of theircarotid arteries as a result of athero-sclerosis." The carotid arteries in theneck are responsible for more than80% of blood flow to the brain, andnarrowing of these major vessels is amajor risk factor for stroke. Amongpatients given daily pomegranatejuice supplements (providing 78 mgof punicalagins) for one year, ath-erosclerotic lesions in the commoncarotid artery decreased by 35% insize, while actually growing by 9%in a control group. Thus, pomegran-ate reversed existing atherosclerosis,which continued to worsen in thosewho did not consume pomegran-ate. Blood analysis showed that totalantioxidant activity increased 130%in the pomegranate juice group,compared to before-treatment val-ues. Finally, the participants' systolicblood pressure fell by an impressive21% after one year of pomegranatejuice supplementation.

The same Israeli scientists showedthat this blood pressure reductionfrom drinking as little as 2 ouncesof pomegranate juice daily (provid-ing 78 mg of punicalagins) was dueto decreased activity of angiotensinconverting enzyme (ACE).'' This isa tremendotisly important finding,since drugs tbat inhibit ACE activityare commonly used to treat hyper-tension. Further, the study raises the

possibility that pomegranate juicemay help patients avoid having totake such drugs.

A study from the California-based Preventive Medicine ResearchInstitute examined the effects ofpomegranate juice in human patientswith established coronary heartdisease." Forty-five patients withcoronary heart disease and cardiacischemia (insufficient biood flow tothe heart muscle) were randomlyassigned to drink 8 ounces of pome-granate juice or a placebo beveragedaily. At the onset and conclusionof the three-month study, scientistsmeasured the participants' blood flowto the heart muscle, both at rest andduring stress. Before administrationof pomegranate juice, both groupsshowed the same amount of stress-induced ischemia. At the end of threemonths, however, the pomegranategroup demonstrated a significantimprovement in stress-related isch-emia, indicating more optimal bloodflow to the heart muscle. By con-trast, stress-related ischemia wors-ened in the placebo group. Becausetbese effects could not be attributedto cbanges in the patients' weight,blood sugar, or cardiac medications,it appears that daily consumption ofpomegranate juice alone improvedstress-induced ischemia in thesepatients.

Its effects in supporting healthyblood pressure, ensuring optimalblood flow, and preventing andreversing atherosclerosis make pome-granate an essential nutrient in everyheart health program.

POMEGRANATE COUNTERSDIABETES AND

METABOLIC SYNDROME

In addition to its diverse cardio-protective effects, pomegranate mayhave profound benefit for people withdiabetes and the pre-diabetic condi-tion known as metabolic syndrome.

To start with, pomegranate com-ponents appear to lower bloodsugar levels immediately followinga meal, according to research fromAustralia.'° Scientists there whostudied obese rats with type II

.granace:\\7u// Yon Need to Knox

Pomegranate offers abundant benefitsfor the cardiovascular system bypreventing damage to arterial walls,promoting healthy blood pressure levels,improving blood flow to the heart, andpreventing or reversing atherosclerosis.Pomegranate may benefit people withdiabetes and those at risk for thedisease. Pomegranate helps lowerafter-meal blood sugar levels and pro-tects the cardiovascular system fromdiabetes-induced damage.Pomegranate shows promise in killingprostate cancer cells, whether the ceilsare hormone-sensitive or not. Pome-granate also helped halt the progres-sion of prostate cancer in men who hadundergone surgery or radiation for thedisease.

Pomegranate may fight the degenera-tion of joint tissue that leads to painfulosteoarthritis, and may protect thebrain against oxidative stress-inducedchanges that can lead to Alzheimer's.Pomegranate extracts—alone orin combination with the herb gotukola—help kill the bacteria that con-tribute to dental plaque, while helpingto heal gum disease. Pomegranate alsoappears to protect the health of theskin and liver.

' The health benefits of pomegranate canbe conveniently obtained through theuse of low-cost, concentrated juicesand extracts.

diabetes found that oral administra-tion of pomegranate extract mark-edly lowered the animals' bloodsugar levels after a meal, while hav-ing minimal effect on the hloodsugar levels of animals that had noteaten. This exciting finding suggeststhat pomegranate extracts block thebreakdown of sucrose (table sugar)in the intestine by inhibiting alpha-glucosidase, an enzyme that breaksdown sugars. This action could helpprevent sugars from being absorbed,thus lessening the abrupt after-mealspike in blood sugar that is so dam-aging to diabetics.

Diabetes is associated withnumerous detrimental changes thatimpair the function of heart tis-sue. These include increased levelsof non-functional fibrous tissuesand increased accumulation of tri-glycerides within the heart muscleitself. Australian researchers recentlyfound that diabetic rats that weregiven pomegranate extract for sixweeks greatly reduced the amountof non-functioning fibrous tissue intheir hearts," while long-term pome-granate supplementation helpedimprove abnormal cardiac lipidmetabolism.'̂

Diabetes is associated withincreased oxidative stress and thedevelopment of atherosclerosis.Pomegranate's antioxidant powerand ability to fight atherosclerosisled Israeli researchers to examinethe effects of pomegranate juiceon inflammatory cells in diabeticrats.'^They compared the antioxi-dant effects of pomegranate juice to(hose of white grape juice on macro-phages, the immune cells that stimu-late inflammation in arterial walls asthe result of oxidative stress, lust 10days of pomegranate juice consump-tion greatly decreased macrophageoxidant levels and increased cellularantioxidant levels, while the animalsfed white grape juice demonstratedexactly the opposite effects.

The Israeli researchers then pro-ceeded to examine the effects ofpomegranate juice on the blood andmacrophages of human diabetics.'^The subjects received 50 milliliters(1.69 fluid ounces) of pomegranate

juice daily (providing 78 mg of puni-calagins) for three months, and theirhlood and macrophage status wascompared to that of healthy controls.Not surprisingly, the diabetics hadmuch higher measures of tissue oxi-dative damage compared to controls.However, dramatic improvementwas found at the three-month markin the pomegranate-treated group,which recorded a 56% reduction inserum lipid peroxides, an indica-tor of damaging lipid peroxidation.Similarly powerful effects were seenon oxidant levels in the patients'macrophages—pomegranate helpedreduce cellular oxygen radicals by71%, wbiie mcr̂ (25///g cellular antiox-idants by 141%! Perhaps of greatestimportance to preventing atheroscle-rosis and heart disease, pomegran-ate-supplemented subjects had a39% reduction in their macrophages'uptake of oxidized LDL—the deadlyfat-protein compound that triggersvascular disease.

Iranian researchers took the nextlogical step, evaluating the effectsof pomegranate juice on the mix ofblood fats and cholesterol in diaheticpatients.'• Twenty-two diabetics withelevated blood lipids consumed40 grams (1.41 fluid ounces) perday of concentrated pomegranatejuice for eight weeks, when bloodlipid levels were measured again.Total cholesterol and LDL levelsdecreased substantially, demonstrat-ing that pomegranate juice markedlyreduces cardiac risk factors in dia-betic patients.

Pomegranate thus offers an arrayof protective benefits for people withdiabetes, from preventing aberrantlybigh blood sugar levels to protect-ing the heart against the potentiallydevastating cardiovascular conse-quences of diabetes.

POMEGRANATE MAYPREVENT AND SLOWPROSTATE CANCER

Prostate cancer is the most com-mon malignancy and second lead-ing cause of cancer death amongAmerican men."' Scientists arerapidly learning that the growth of

prostate cancer can be preventedby proper dietary supplementation,especially with antioxidant and anti-inflammatory agents.'' '•' Several ofthe pure chemical compounds foundin pomegranate—including ellagicacid and luteolin—work togethersynergistically to inhibit cancer cell

Results of a recent laboratorystudy underscore the dramaticprotective effects of antioxidants inpomegranate.-' When human pros-tate cancer cells were exposed topomegranate fruit extract, they imme-diately began to produce substancestliat led to their own death. Thisprocess of programmed cell death,called apoptosis. is vital to the body'snormal regulation of potentially can-cerous tissue. In another experiment,oral administration of pomegranatefruit extract greatly inhibited tumorgrowth in mice.'' This correlatedwith a dramatic decline in bloodlevels of prostate-specific antigen(PSA), which doctors use to monitorprostate cancer progression. This ledthe study authors to conclude thatpomegranate juice may be useful inpreventing prostate cancer, as well asin slowing the progression of existingprostate cancer.---'

An even more detailed study of theeffects of various pomegranate com-ponents was conducted by Germaninvestigators, who were interested infinding ways to slow or reverse pros-tate cancer growth.-' The German sci -entists studied several different typesof prostate cancer, including boththose that are dependent on andro-

58 LIFE EXTENSION May 2007

gens (male hormones) and those thatare not. Rates of growth and repro-duction were slashed in all prostatecancer cell types tested, regardless ofwhether the pomegranate extractwas derived from the seeds, juice, oroiis ofthe fruit.

Moreover, the researchers deter-mined that the pomegranate extractsworked via several mechanismssimultaneously to slow cancer cellgrowth—in sharp contrast to chemo-therapy drugs, which work throughonly a single mechanism. Over time,cancer cells can develop resistanceto chemotherapy (that is, failure torespond to a previously effectiveagent), leading some scientists topropose that anti-cancer agents thatwork hy multiple mechanisms mayoffer greater treatment efficacy.

Finally, the German investigatorswere able to show that the cell-killingand growth-inhibiting effects ofthepomegranate extracts were limitedto cancerous cells—normal prostatecells were much less significantlyaffected.̂ -' If these findings hold truein men with prostate cancer, pome-granate may help kill cancerous cellswhile leaving healthy tissues intact.

Convincing data from humanclinical trials now support pomegran-ate extract's ability to fight prostatecancer. Doctors at UCLA investi-gated whether pomegranate couldslow the rate of cancer progressionin men who had undergone surgeryor radiation treatment for prostatecancer.-"The subjects drank8 ouncesof pomegranate juice daily (provid-

ing 280-375 mg of punicalagins),and their PSA doubling times werecompared before and after treat-ment. A short PSA doubling timeindicates rapid growth of residualprostate cancer, white a longer dou-bling time signifies slower tumorgrowth. Daily intake of pomegranatejuice increased mean PSA doublingtime from 15 months at baseline to54 months in 80% of the men post-treatment—a nearly fourfold jump.Even more remarkable, when bloodserum from these men was obtainedafter treatment and applied directlyto prostate cancer cells in culture,cell growth rates plummeted andcell death rates soared. The cells alsoincreased their ability to withstandoxidative stress.

In sum, these important findingssuggest that pomegranate may helpprevent the occurrence of prostatecancer, while slowing the growth andspread of existing prostate cancers.

PROMISING NEWAPPLICATIONS FOR

POMEGRANATE

Preliminary research findingssuggest that, in addition to itspotentially lifesaving benefits forheart, diabetes, and cancer patients,pomegranate may confer a mul-titude of other health-promotingeffects in the body, from alleviatingthe pain and discomfort of arthritisto supporting optimal brain, dental,skin, and liver health.

PREVENTINGOSTEOARTHRITIS

Inflammation destroys joint-cushioning cartilage, inflicting tre-mendous pain and disability on theestimated 21 million Americanswho suffer from osteoarthritis. Byseverely curtaining physical activity,osteoarthritis can initiate a viciouscycle in which its sufferers becomeever more sedentary (and often over-weight), triggering additional healthproblems."

Pomegranate's ability to breakthe cycle of infiammation and tis-sue damage-" spurred scientists at

Case Western University to explorewhether it could protect joint carti-lage from infiammation in patientswith osteoarthritis.^^ In an in-vitroexperiment, they first treated car-tilage from osteoarthritis patientswith pomegranate fruit extract, andthen stimulated the tissue withinterleukin-l beta, a potent infiam-matory mediator. The scientiststhen measured the extent of car-tilage destruction and productionof infiammatory molecules in thetissue samples.

Pretreatment with pomegranatefruit extract inhibited enzymes thatbreak down cartilage, and sharplyreduced the volume of inflam-matory products released from thetissue. The researchers concludedthat pomegranate fruit extract "mayinhibit cartilage degradation in osteo-arthritis and may also be a usefulnutritive supplement for maintain-ing joint integrity and function."

AVERTING ALZHEIMER'S

In 2006, scientists at California'sLoma Linda University reportedgroundbreaking research on apotential role for pomegranate juicein averting Alzheimer's disease.^"

The researchers knew that antiox-idant polyphenois from other fruitsand vegetables have protected braincells in various animal models," andthat pomegranate juice itself hadbeen shown to limit brain damagein mice that suffered experimentallyinduced strokes.^^ Since oxidation isthought to produce the Alzheimer'sprotein known as amyloid beta, theLoma Linda team decided to testtheir hunch that pomegranate juicecould put a stop to amyloid-betaaccumulation. They also exploredthe more radical notion that pome-granate juice alone would havea detectable effect on cognitiveabihties, using a "water maze task"that tests animals' ability to accu-rately and quickly make their wayout of a water-filled labyrinth.

The researchers' intuition wasrewarded, as mice with Alzheimer's-like disease that were given pome-granate juice from 6 to 13 months

May 2007 LIFE EXTENSION 59

of age accumulated about 50% lessamyloid beta than control mice.The juice-treated animals out-performed control animals, exitingthe water maze 35% faster than thecontrol group.'"Theauthors declaredtheir study to be "the first to showbeneficial effects (both behavioraland neuropathological) of pome-granate juice in an animal model ofAlzheimer's disease."

PRESERVING DENTALHEALTH

Emerging research suggests thatpomegranate holds promise in pro-moting optimal dental health.

A recent study indicates thatpomegranate fights dental plaque,the yellowish buildup of micro-organisms on the teeth that canlead to cavities and gum disease.Scientists found that pomegranateextract helped kill microorganismsisolated from the dental plaque ofhealthy adults. Additionally, rins-ing the mouth for one minute with a

mouthwash containing pomegran-ate effectively reduced the amountof microorganisms cultured fromdental plaque.*'

Thai researchers studying gumdisease discovered that pomegran-ate extracts, when combined withextracts of another traditional herbcalled gotu kola [Centella asiatica),enhance gum healing followingdental scaling and root planing(deep cleaning between the gumsand the teeth down to the roots.)'^Such procedures are commonlydone to restore the vital connectionbetween the gums and tooth roots,in the absence of which bacterialinfection, decay, and tooth loss mayoccur. By simply implanting tinychips impregnated with pomegran-ate and gotu kola extracts into thegap between the gum and tooth root,the scientists were able to reducethe size of the gap and increasegum and tooth attachment.'^A laterstudy by the same group'^ showedthat treated patients also had lessgum bleeding and considerably

DOSING STRATEGIES TO OBTAIN OPTIMAL BENEFITS FROM POMEGRANATE

Given the wide array of health benefits associated with pomegranate juice and extracts, thequestion is not whetherto supplement with pomegranate, but rather how much offers optimalbenefits.

Choosing the ideal dose of pomegranate poses a challenge, as different preparationsmay contain vastly different amounts of important constituents such as polyphenols—powerful anfioxidants that underlie many of the benefits of plant-derived therapies. Many of theclinical studies examining pomegranate's effects in relation to certain disease states (such ascardiovascular disease and prostate cancer) utilized juices and extracts that were notstandardized for their polyphenol constituents—making it difficult to ascertain the mostefficacious pomegranate formulation and dosage.

Life Extension conducted an extensive review of the scientific literature in order toidentify the most beneficial phytochemicals in pomegranate juices and extracts, and the dosagesrequired for maximum efficacy. Punicalagins were identified as the most clinically importantpomegranate phytochemicals. Punicalagins are highly bioavaiiable and possess antioxidantactivity that greatly exceeds that of many plant-derived antioxidants.^^'^Mn the most significantclinical studies to date, a dally dose of 78 mg of punicalagins yielded such remarkable benefitsas reversing atherosclerosis, reducing high blood pressure, and preventing the adverse cardio-vascular consequences of diabetes.'^-^^ Moreover, an important clinical study demonstrated that280-375 mg of punicalagins per day halted the progression of prostate cancer in men who hadfailed conventional therapy.^^ Life Extension thus recommends 78 mg of punicalagins per day forcardiovascular protection, and 280-375 mg of punicalagins daily to promote prostate health.

To provide consumers with the maximum possible health benefit. Life Extension hasidentified several pomegranate products—including pomegranate juice concentrate andencapsulated pomegranate extract—that are standardized to provide an abundant source ofpunicalagins.

lower levels of interleukin-1 betaand interleukin-6, two inflamma-tory cytokines linked to cardiovas-cular disease."*-̂ '

Maintaining optimal dentalhealth is not only important for pre-serving the appearance and functionof the teeth, but also for protect-ing against cardiovascular disease.Scientists now know that the chronicinfiammation from periodontal dis-ease is closely tied to the worseningof cardiovascular diseases. '"'•'

PROTECTING SKIN HEALTH

New evidence suggests thatpomegranate extracts may protectskin against two important factorsthat degrade its health and appear-ance over time: accumulating dam-age infiicted by ultraviolet light, anda decreased ability to regenerateor heal.

Excessive exposure to ultravio-let B {UVB) radiation has numer-ous adverse health effects on skin,including redness, hyperpigmen-tation, immune suppression, andphotoaging. Research shows thatpomegranate extracts protecthuman skin cells against UVB-induced changes by modulating thebiochemical pathways that can pro-voke cancer and infiammation.^"

Pomegranate also protectsagainst ultraviolet A (UVA) radia-tion, or the damaging, long-waverays that penetrate deeply into theskin to promote wrinkles and bothbenign and malignant tumors. Thisis an important finding, as many

60 LIFE EXTENSION May 2007

commercially available sunscreensoffer only limited UVA protection.When human skin cells were incu-bated with pomegranate extracts,they were better able to withstandUVA-induced damage. Scientistsbelieve that pomegranate modulatescellular pathways to confer protec-tion against ultraviolet rays.""

As skin ages, it often becomesthinner and slower to heal. A prom-ising new study demonstrates thatpomegranate extracts may helpavert age-related changes in theskin." Investigators applied vari-ous pomegranate constituents toskin cells derived from the epider-mis (outermost layer) and dermis(layer underneath the epidermis).Pomegranate seed oil extract pro-moted regeneration and thicken-ing of the skin's epidermis, while anextract of the peel promoted repairofthe dermis. Pomegranate extractsmay thus help promote healing andregeneration of skin tissues."'

ENSURING LIVER HEALTH

As one of the body's most meta-bolically active organs, the liver isresponsible for breaking down andrendering harmless a multitude ofchemicals, toxins, drugs, and hor-mones. Performing this daily taskrequires a prodigious amount of anti-oxidants, and new findings suggestthat pomegranate is a rich source ofliver-protective antioxidants.

In the laboratory, pomegran-ate extract effectively quenched avariety of dangerous reactive oxy-gen species, including superoxide.hydrogen peroxide, and hydroxylradicals. When mice were givenpomegranate before exposure toan oxidative stressor that normallycauses liver toxicity, they were sig-nificantly protected and maintainedhigh levels of crucial liver antioxi-dants. Pomegranate extract helpedprotect the animals against patho-logical changes that accompanyliver damage, such as degeneration,fatty changes, and necrosis (tissuedeath) ."̂ Pomegranate extract thusconfers everyday benefits for liverhealth.

CONCLUSION

Pomegranate is one of nature'srichest sources of antioxidants.Accumulating research offersample evidence that routine sup-plementation with pomegranatejuice or extract may protect andeven improve cardiovascular func-tion. Pomegranate also appears tocounter the deleterious effects ofdiabetes and metabolic syndrome,and may even help to prevent andarrest the development of certaincancers. Exciting new researchfindings suggest that pomegranatelikewise fights the infiammatoryprocesses involved in Alzheimer'sdisease, osteoarthritis, and gum dis-ease, while protecting the health ofthe skin and the liver.

Utilizing concentrated, low-costpomegranate juice or standard-ized pomegranate extract capsulesoffers consumers a way to reap thebroad-spectrum health benefits ofthis exotic fruit, while avoiding theexcessive sugar calories and highcost associated with commercialpomegranate juice products. •

REFKRBNCEvS

1. Xu S. Touyz RM. Reactive ox>'gen speciesand vascular remodelling in hypertension:slill alive. CaiijV/miiol 2006 Sep;22(l I ):947-51.

2. Ignarro IJ. Byrns RE, Sumi D, de NF, NapnliC. Pomegranate juice protects nitric oxideagainst oxidative destruction and enhancesthe biological actions of nitric oxidivNitric Oxide. 2mf>Se\x\5[2y>y.\'\\)2.

3. Ignarro U, Napoli C. Novel features of nitricoxide, endothelial nitric oxide synthase. andatherosclerosis. CiirrAlheroscler lief).2004]ul;e(4):281-7.

POMEGRANATE CHALLENGED IN MEDIA

The mainstream media is quick to leverage the latest information in the hopes ofcreating excitement. Regrettabiy, given the media's penchant for covering medical andscientific issues in a distortive. misleading way, this makes for poor science reporting,

A recent example is a case report published in 2006 and highlighted by many mainstreampublications, which suggested a link between pomegranate juice and a case ofrhabdomyolysis (a serious illness characterized by muscle breakdown) in a 48-year-old mantaking a prescription drug (the statin drug rosuvastatin, or Crestor®) to lower cholesterol."

Unfortunately, the mainstream media failed to report a number of important facts in this case:

1. The patient's creatine phosphokinase (CPK) level (which measures muscle enzyme leveland is typically elevated in rhabdomyolysis) was 659 U/L at baseline, which is alreadyextremely elevated;

2. This patient was taking a wide variety of other medications at the time of illness,medications that could have interacted in such a way as to cause problems;

3. There was no discussion of the fact that although both grapefruit and pomegranatejuice are known to inhibit a specific drug metabolism pathway (CYP3A4); rosuvastatinis not known to be metabolized by this pathway.

Given the impressive, scientifically documented health benefits of pomegranate in a widevariety of applications (e.g., cardiovascular system, prostate, and breast health), the greattragedy is that individuals who may derive tremendous benefit from pomegranate may nottake this simple, natural product because of concern about having a potentially dangerousdrug interaction—a misconception engendered by irresponsible reporting.

A recently published study helps to place in better context pomegranate's potential tocause significant interactions with medications. This study evaluated the relative impactof several fruit juices on the CYP3A system, a well-known liver pathway responsible formetabolizing many prescription medications. This study showed that the inhibitory potentialof pomegranate juice on human CYP3A was significantly less than that of grapefruit juice, inthe order of: grapefruit > black mulberry > wild grape > pomegranate > black raspberry."

The mainstream media has a responsibility to accurately report the facts and not causeconsumers to overreact to fear-mongering, misleading reports.

May 2007 LIFE EXTENSION 61

4. de Nigris F, Williams-Ignarro S, Botti C, etal. Pomegranate juice reduces oxidizedlow-density lipoprotein downregulation ofendotheiiai nitric oxide symhase in humancoronary endothelial cells.Nitric Oxide. 2006 Nov;!5(3):259-63.

5. de Nigris F, Williams-Ignarro S, Sica V, et al.Effects of a pomegranate fruit extract richin punicalagin on oxidation-sensitive genesand eNOS activity at sites of perturbed shearstress and atherogenesis.Cardiovasc Res. 2007 Ian l5:73(2):4I4-23.

6. de Nigris F, WHliams-lgnarro S. LermanLO. et al. Beneficial effects of pomegranatejuice on oxidation-sensitive genes andendothplial nitric oxide synthase activityat sites of perturbed shear stress. Proc NailAcadSci USA. 2005 Mar29:102(13):4896-901.

7. Aviram M, Rosenblat M, Gaitini D, etal. Pomegranate juice consumption for3 years by paiients with carotid arter\'stenosis reduces common carotid intima-media thickness, blood pressure and LDLoxidation. Clin Nutr. 2004 Jun:23(3);423-33.

8. Aviram M. Dornfeld L. Pomegranate juiceconsumption inhibits serum angiotensinconverting enzynie activity and reducessystolic blood pressure. Atherosclerosis.2001 Sep: 158(1): 195-8.

9. Sumner MD, EUiott-Eller M, Weidner G, et al.Effects of pomegranate juice consumptionon myocardial perfusion in patients withcoronary heart disease.AmJ Cardiol. 2005 Sep 15;96(6):8]0-4.

10. U Y, Wen S, Kota BH et al. Punica granatumflower extract, a potent alpha-glucosidaseInhibitor, improves postprandialhyperglycemia in Zucker diabetic fatty rats.]Ethnopharrtiacol 2005 |un 3;99(2}:239-44.

11. Huang TH, Yang Q, Harada M, et al.Pomegranate flower extract diminishescardiac fibrosis in Zutker diabetic fatty rats:modulation of cardiac endothelin-l andnuclear factor-kappaB pathways./ Cardiovasc Pharmacol.2005Det:46(6):856-62.

12. Huang TH. Peng G, Kota BR et al.Pomegranate flower improves cardiac lipidmetabolism in a diabetic rat model: role oflowering circulating lipids.Br]Pharmacol. 2003 Iul;I45(6):767-74.

13. Rozenberg 0, Howell A, Aviram M.Pomegranate juice sugar fraction reducesmacrophage oxidative state, whereas whitegrape juice sugar fraction increases it.Atherosclerosis. 2006 Sep;188(l):6B-76.

14. Rosenblat M, HayekT. Aviram M. Anti-oxidative effects of pomegranate juice (Pi)consumption by diabetic patients on serumand on macrophages. Atherosclerosis.2006Aug:187(2):363-71.

15. Esmaillzadeh A. Tahbaz E Gaieni I, avi-MajdH, Azadbakht L. Concentrated pomegranatejuice improves lipid profiles in diabeticpatients with hyperlipidemia.J Med Food. 2004;7(3):305-8.

16. Arlen PM, Dahut WL. Gulley )LImmunotherapy for prostate cancer: what'sthe future? Hematol Oncol Clin North Am.2006Aug:20(4):965-83.

17. Adhami VM, Mukhtar H. Polyphenols fromgreen tea and pomegranate for preventionof prostate cancer. Free Radic Res.2006Oct;40(10):1095-104.

18. Ghan |M. Feraco A, Shuman M, Hernandez-Diaz S. The epidemiology of prostatecancer—with a focus on nonsteroidal anti-inflammatory drugs. Hematol Oncol ClinNorth Am. 2006 Aug',20{4):757-S0d.

19. Krysiak R, Okopien B, Szkrobka W, HermanZS. Prostate cancer chemoprevention.PrzeglLek. 2005;62(9):929-33.

20. Lansky EP Harrison G, Froom R JiangWG. Pomegranate (Punica granatum)pure chemicals show possible synergisticinliibition of human PG-3 prostate cancercell invasion across Matrigel.Invest New Drugs. 2005 Mar;23(2)il2]-2.

21. Lansky ER Hang W. Mo H, et al. Possiblesynergistic prostate cancer suppressionby anatomically discrete pomegranatefractions. Invest New Drugs.2005Jan;23(l):ll-20.

22. Seeram NR Adams LS. Henning SM. et al.In vitro antiproliferative, apoptotic andantioxidant activities of punicalagin, ellagicacid and a total pomegranate tannin extractare enhanced in combination with otberpolyphenois as found in pomegranate juice.

J Nutr Biochem. 2005 |un:16(6):360-7.23. MalikA.AfaqF,SarfarazS. et

al. Pomegranate fruit juice forchemoprevention and chemotherapy ofprostate cancer. Proc Natl Acad Sci USA.2005 Oct ll;102(41):I4813-8.

24. Malik A, Mukhtar H. Prostate cancerprevention through pomegranate fruit.Cell Cycle. 2006Feb;5(4):371-3.

25. Albrecht M, liangW, Kumi-Diaka ), et al.Pomegranate e?ctracts potently suppressproliferation, xenograft growth, andinvasion of human prostate cancer cells.J Med Food. 2004;7(3):274-83.

26. Pantuck AI, Leppert IT. Zomorodian N, etal. Phase II study of pomegranate juice formen with rising prostate-specific antigenfollowing surger>' or radiation for prostatecancer. Clin Cancer Res.2006Iull;12(I3):4018-26.

27. Piechota G, Maikiewicz 1, Karwat ID. Obesityas a cause and result of disability.PrzeglEpidemiol. 2005;59ll):l55-6\.

28. Afaq E Malik A, Syed D, et al. Pomegranatefruit extract modulates IJV-B-mediatedphosphcrylation of mitogen-activatedprotein kinases and activation of nuclearfactor kappa B in normal human epidermalkeratinocytes paragraph sign.Photachem Photobiol. 2005 |an:8Ul):38-45.

29. Ahmed S. Wang N, Hafeez BB, CheruvuVK, Haqqi TM. Punica granatum L. extractinhibits IL-lbeta-induced expression ofmatrix metalloproteinases by inhibiting theactivation of MAP kinases and NE-kappaBin human chondrocytes in vitro.JNutr. 2005 Sep;135(9):2096-102.

30. Hartman RE, Shah A, Eagan AM, et al.Pomegranate juice decreases amyloid loadand Improves behavior in a mouse model ofAlzheimer s disease.AfeMTO&io; DJs. 2006 Dec;24(3):506-15.

31. Dai Q. Borenstein AR, Wu Y. Jackson IC.Larson EB. Fruit and vegetable juices andAlzheimer s disease: the Kame Project.<4myMfrf. 2006Sep;119(9):751-9.

32. Loren Dl. Seeram NH SchulmanRN, Holtzman DM. Maternal dietarysupplementation with pomegranate juiceis neuroprotective in an animal model ofneonatal hv'poxic-ischemic brain injury.Pediatr Res. 2005 Jun;57(6):858-64.

33. Menezes SM, Cordeiro LN, Viana GS. Punicagranatum (pomegranate) extract is activeagainst dental plaque.JHerb Pharmacother. 200fi:6[2):79-92.

34. Sastravaha G, Yotnueiignit R Booncong RSangtberapitikul H Adjunctive periodontaltreatment with Centella asiatica and Punicagranatum extracts. A preliminary study./ Int Acad Periodontol.2003Oct:5(4):106-15.

35. Sastravaha G, Gassmann G,Sangtherapitikul R Grimm WD. Adjunctiveperiodontal treatment with Gentella asiaticaand Punica granatum extracts in supportiveperiodotital therapy. / Int Acad Periodontol.2005Jul:7(3):70-9.

36. Dellegrottaglie S, Sanz I, RajagopalanS. Molecular determinants of vascularcalcification: a bench to bedside view.Cwrr Mo/M«/. 2006 Aug;6(5):515-24.

37. Terrell AM, Grisostomo PR, Wairiuko GM, etal. lak/STAT/SOCS signaling circuits andassociated cytokine mediatedinflammation and hypertrophy inthe hean. Shock. 2006Sep;26(3):226-34.

38. Dumitrescu AL. Influence of periodontaldisease on cardiovascular diseases.Rom/Intern Med. 2005:43[ 1 -2):9-21.

39. Mattila K], Pussinen PI, Paju S. Dentalinfections and cardiovascular diseases: areview. / Periodontol. 2005Nov;76(llSuppl):2085-8.

40. Syed DN, Malik A. Hadi N, Sarfaraz S, Afaq F,Mukhtar H. Photochemopreventlve effect ofpomegranate fruit extract on LIVA-mediatedactivation of cellular pathways in normalhuman epidermal keratinocytes,Photochem Photobiol. 2006Mar-Apr;82(2):398-405.

41. Aslam MN, Lansky ERVarani I. Pomegranateas a cosmeceutical source: pomegranatefractions promote proliferation andprocoUagen synthesis and inhibit matrixmetalloproteinase-i production in humanskin cells. / Ethnopharmacol.2006 Feb 20;]03(3):311-8.

42. Kaur G, labbar Z, Athar M, Alam MS. Punicagranatum (pomegranate] flower extractpossesses potent antioxidant activity andabrogates Fe-NTA induced hepatotoxicityin mice. Food Chem Toxicol.2006Jul:44(7):984-93.

43. Sorokin AV. Duncan B. Panetta R, ThompsonPD. Rhabdomyclysis associated withpomegranate juice consumption.Am J Cardiol. 2006 Sep l:98(5):705-6.

44. Kim H, Yoon Y), Shon |H, Cha U, Shin |G,Liu KH. Inhibitory effects af fruit juices onGYP3A activity, Drug Metab Dispos.2006 Apr;34(4):521-3,

45. Cerda B, IJorach R, Ceron II, Espin JC,Tomas-Barberan PA. Evaluation ofthebioavailabiJity and metabolism in the rat ofpunicalagin, an antioxidant polyphenol frompomegranate juice. Eur JNutr.2003|an;42{l):18-28.

46. Gil Ml, Tomas-Barberan FA, Hess-Pierce B,Holcroft DM. Kader AA. Antioxidantactivity of pomegranate juice and itsrelationship with phenolic compositionand processing. //igriV Food Chem.2000Oct:48(10):4581-9.

62 LIFE EXTENSION May 2007