most important feature of an ingredi- ent-usually as a component o f con- ventional food or dietary supplement. "Efficacy means the abllity of an lngre- dlent to produce beneficiary effect. In this context, the proven efficacy may be considered as competent and reli- able scientific evldence for substantra- tlon of cla~m(s)."

For the consumer experience, which is important for continued use, efficacy has everything t o do with their percep- tion that they are indeed gettlng a ben- efit, Kamarei explained. "For a number of ingredients, they elther do or don't experience a difference in how they feel. If they take a joint health produa, for example, every day for four months and don't feel better, they will stop buy- mg and using that product. So proved efficacy for the manufacturer deciding h l c h ingredients to Include in a prod- uct, the body of science may be more compelling, but for the consumer, it is often their personal experience that determines efficacy."

Clinical Proof Straight to the point, an ingredient's efficacy needs to be determined by scl- enttfic research, said Victor Ferrari, CEO of Horphag Research (USA) In New Jersey, suppller of PycnogenolG3. "The ultimate efficacy has to be shown in human clinical trials. The tlme for test- tube experiments, such as ORAC and other arbitrary fiqures, 1s runninq out. The ~ o t i s u m ~ r deserves a clear message of wnal beliefis a nurrcnt will orovidc."

And the overriding focus of an effica- cy study is that it must direaly evaluate the desired effect, Matulka exptained. "If the Ingredient is an antioxidant pro- vlded to help support oxidative status of the consumer, then the endpoint evaluated must be oxidative status in the cells of the consumer that mn- sumed the Ingredient (some endpoints that may be appropnate for evaluating oxidatlve status in clinical trials include examination of blood serum levels of antioxidant enzymes, such as glu- tathione peroxidase or the lipid peroxl- dation marker malondialdehyde, or evaluating urinary isoprostane levels).

"A theoretical, test-tube determina- tion of ORAC value may not be suffi- cient," he added. "Substantiating effica- cy for broad or general statements (e.g., 'helps malntain colon function') 1s much more difficult than a concise, clearly defined effect (e.g., 'helps maintain nat- ural flow through the colon'). Regardless of the product type, proving the efficacy of ingredients utilizing parameters for

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which there are no validated methods available is more difficult than for end- points that have clearly defined, well- researched and validated protocols for specific endpoints."

Those endpoints must have meaning to the consumer. Califomla-based InterHealth Nutraceutlcals' CEO Paul Dijkstra said the company invests heavl- ly in clinlol research to ensure it pro- vides ingredients that can substantiate meaningful product clalms. "Product clalms should be backed by well- designed clinical studies so as to not mislead consumers of any expected benefits," he said. "From a supplier's perspwtive, finding better ingred~ents or better forms of existing ingredients will help support many health issues Americans face, such as blood sugar, j o~n t and weight problems "

Cold Standards In terms of ingredtent efficacy, the stud- ies necessary to prove that an ingredi- ent does what is stated on the package vary as greatly as the different types of ingredients themselves

"Stating that an Ingredient has a hlgh antioxidant capacity is relatively easy to prove by utilinng the oxygen radical absorbance capacity (ORAC) assay,'' said Burdock Group's Matulka. "However, stating that an lngred~ent helps maintam or increases antioxidant status in the consumer is more difficult, as it requires at least one clinical trial (there has been some discussion of requinng two clinical trials, but nothing definitive has been stated by regulators)."

The "gold standard" of clinical trials is the double-blind, placebocontrolled, crossover trial. FDA has stressed that the totality of the evidence, including evaluating criteria, such as quality, quantity [number of various types of studies and sample slzes), relevance of exposure, and conslstency and replica- tion of the findings, is necessary to determine if a claim is truthful and not misleading, Matulka explained. A clinl- cal trial must be able to cause a stabsti- cally significant change in a specific bio- logic endpoint (that the regulatory agency agrees to be representative of the desired biological outcome), and that effect must be d~rectly related to the consumption of the ingredient.

"When it comes to efficacy, you really need to look at the preponderance of evidence produced over a perlod of time-not just a single study. That's dii- ficult for some in our Westem, allopath- ic world to understand and accept,"

said Bob Green, president of New Jersey-based Nutratech, Inc. "Too often they want to apply Western clinical designs to nutr~tional research, seebng only double-blind, placebo-controlled clinical research studies. But natural ingredients affect multiple systems and functions in the body. In our category- weight management-for example, there are so many different pathways to weight loss that you simply can't apply the single magic bullet theory It doesn't always give the complete picture of an ingredient's efficacy.

"Suentlsts and researchers are always telling me,there are many valid markers of highquality research, which are often dictated by the nature of the research ~tself," Green added. He explained that a single, double-blind, placebo-con- trolled study, no matter how state-of- the-art, can never represent the be-all and end-all in evaluating an ingredient's efficacy. That's why it E necessary to look at the body of research, which usu- ally includes many different study designs (from double-blind, placebo- controlled clinical studies to epidemto- logical studies to meta-analysls reviews t o animal research to m-vitro studles, etc.)-and the collective direction of that research to determine the true markers of Ingredient efficacy.

Horphag's Ferrari pointed out that food supplements are by definition not intended to cure daeases, but are a powerful alternative to promote overall health and wellness. "We are in the wellness industry, contrary to the phar- maceutical industry which clearly targets illness," he said. "To this effect, clinical trials are more targeted to people who want to make a qualified choice with regard to prevention, wellness and bet- ter llfe performance."

Problem Solving Suppliers face a myriad of obstacles- ingredient to ingredient-from agricul- tural, costs, pmvidlng conslstency and reliabillo/, to marketing.

"In the last three years, the natural product Industry has witnessed several challenges, a prlmary one being the supply situation of natural extracts," said Sablnsa's Kamarei. "These plafits and herbs, which were once seen as an abundance, were negatively impacted either by changes in climate, which caused harvests to fail, or by poor agri- cultural practices Yet, there are other reasons, some not widely known of, such as exploitation b y the farmers themselves for a penny more. Hoarding and even looting of supplces to gain a

Nutrition Industry Executive 29

occurs. Ultimatdy, it leaves our diaary suppkment industry with- out the vw ate+ntial exhats that consumers ham tskn for many ywm."

A g a d example &.this is sumurnin, according to Ramwei, who said the ingredient was introdbced and pio- neered in this industrv bv Dr.

1 Muhmmed M a j d &d Sabinsa fwT# its Cwcumin C3 Complex@) aS a rich antiosidant and no-& as an anri-inflam- mataty ingredient. 'To pay tn'bm to how succeaful Sabimk Curcumin C3 Complex has become, lust took at the knadc-offs, clafming that this bio-avail-

I I ability or that oil fradon are betterthan S;lbinsd"srlainal urrwmln, which has

7 1 , been the goid standard for many pars and the p;edominant material sudied at universities around the world."

Yet for Sabitm to sustain $ curcumin mrrrket was no easy tssk; in the last two years alone, prl- nearly aipled, Kamaret adcled. "Ow customer6 who bought etaewhem bewuse we couldn't supply paid upwards of $300 lun per

I klo, bile we went to p a t &art to I I keep our priw below $200 per kg,

I which we felt was the right move in ' 1 order to ke* the curcurflin busine* 1 alive. Our own cultivation &forts in India

could not keep up wkh demand created by the growing body of science, and the prices we were paying for turmeric skgocketed,"

1 ffimarei said Sabinm pumued a

I mursr: that ensured the welfare of the farmers and the W N ~ V ~ of this ingredient in the marketplace teddy.

customem was litmired, Sabinsa made sum that the reseanh centers and universities around the world received their share bf mrcumin for their cling cals. Sabinna kept the research alive on cum~rnin.~

Another example of an ingredient challenae IC3marei oo:nted to is

I mleus;?nt~dutedby Sabinsa tn the I mid-90s as an ingredient far ban body

ma8s porsLean@), it had major break- I thro%ks in the sperts nuaHon market I and further intu high-end wet& man-

r\gemmt systems. This ingredient,

1, derived from a simple pi& from

11 India, would ga on to win major

1 awards far Sabinm and ultimately changed how future wjghi mnage-

I m w t ingredients were launched in the nutraceutical industry, Kmarei *aid

"forshan, the patent4 and brand- ed coieur, ingredient from Sabinsa.

SO NUtMm l&L&y M C U W I

becanre a $100 million band, I'ierally overnight, which cawed severe short- aws worldwide. CultiMtion programs were put into place irnmd~atelfi but we were able to only meet 20 p""t of the demand; the rest were left to sourcing fmm whvever we muld get material," said Kamareli. "That led t6

"Providing a safe,

efficacious product to

consumers in the quickest

amount of time at the lowest

cost is a major challenge, while also supplying

novelty and functional attributes."

quality i w e s by other suppliers who wanted +o m a h a quick buck ignaring bwic GMPs and, unfortunately, led to ingredient spiking. It seems that short- *= brings out the m t in certain sqpliers, wh~oh we considar a ohal- Imse for th~xmntfre industry."

These examples strowcase not only tR.e present chakngm, but also the on- going &ratad% that the natuml product industty is facing, bmarei added. "There is no right answer; nor a %laxion

that \Nit1 cam: up overnight. It is a deep and thomugh undermnd~ng of the issues by customers and cornurnen alike that will help enwm stability in an unstabke market. Now, while competi- tion is certainly heakhy, the less &ical sueoliars will hawe a hnler time SUN~V- I '&i'mder GMP rer(lriremenlx as their wbrcement has become more robust."

Providing a safe, &caciowa product ta cowmars iil the quickest amunt .Bf time at the low& cBsr is a majw &a[- Imp, B u r h k s Mawllca a p e d , while alsa supptying novelty and functional awbutes.

"Consumrus continually look for innovation, and ingredient suppliers must check to make sure an ihgredim is appropriately mgulated for its pro- p o d use," Marulka said. *Fw exam- ple, m a r y extract is approved for we as a flavor Etypically used at a law mncentk8on in f w d ) , but is n4t nec: essar~ly approved for use as a preserve- tiwave. &I& w u I d mod l~kely require much higher concentrations of the extract, The s a w ef an ingredient 1s dependent on the intended use, and efficacy mu& be prwen pdor to mak- ing a daim on the food package that mntains the ingredient"

Highly d e ~ ~ on c w t arrd func- tionality is the rnaktability of an ingre- dient, noted InterHealth's Dijkcha. "We have seen rnw funaimal beverage produca, such BS miem and rrwit juice' along with dairy pradusts, snackban and cereals become more popular in the marktplace in the East dew years,'' hesald. "The effect a functional iwredi- ent can have on the taste psofile of a product is an important considerafton when developing new praduct form&- tions. S e l d n g irrgrediinrs that are %eless. ordortess ad cobrlass in sdu- tion w:ll nave line or no impact on the overall organoleptics of a finishod prod- ua. This can also heiu reduce the I a m m t of wgar or ahc ia l flavws needed to tsnwre a aonsumer-friendly W e profile. This makes TO mom*ac- t'm to the consumerand helps wt down @n manufa.Wring costs as well w the retail pet* of the finished product."

It is important to con&4ei stabflity when folmulatin$ wit+ n u m ~ t t c a i s , said D i jha , a&ig that stability data confirmingthe bgredient hw retained its stmctural integrity for the life of the product k needed to ensure efficacy. interHealth takapsmral s tep to help enwre thatthe finished prod- u m containing its ingfedients contain fhe appropriate nutriiionel profilaand

(Coqti~ued on,pge 34)

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