As brand marketers, you know it is imperative to select suppliers' ingredients that can be traced to origin, and proven safe and effective. The latter is where a supplier builds a credible (and hopefully impenetrable) portfolio of research. Yes, human clinicals (published and performed by a credible research partner) comprise the gold standard. But suppliers cannot just jump into pilot studies on people.
In our case, once we become interested in the long-term merits of a natural-origin ingredient, our team gets to work. Here is the process.
1.) The very first thing we are interested in is the history of use through modern times—to get an ethnopharmacological or ethnobotanical picture. This creates a roadmap of where to begin. Tongkat Ali root, for example, has been used in Malaysia for generations by men seeking more virility, both sexually and physically. Much work has been performed by the University of Malaya and MIT to study the components of the root extract (identified as glycosaponins, eurycomanone and eurypeptides; the latter two are so named by the herb's Latin binomial, Eurycoma longifolia).
2.) Unique phytocomponents are examined in depth to discern if they may be active or inert. Previous literature and published research is consulted to see what phytochemical researchers may have already revealed.
In the case of LJ100®, the University of Malaya and MIT had identified and isolated a bioactive peptide fraction (a 4300 dalton glycopeptide with 36 amino acids chain) that is responsible for its effects in improving testosterone levels, increasing muscle size and strength, and activating androgen biosynthesis. These findings led to a patent issued jointly to the Government of Malaysia and the Massachusetts Institute of Technology (United States Patent #7,132,117) for the method in creating a sophisticated extraction technology to yield the root's most concentrated components.
3.) Somewhat similar to the beginnings of pharmaceutical investigation prior to human clinical trials (which are much more intensive, involving several phases per trial for drugs), we also conduct extensive pre-clinical studies. These involve in vitro (test tube or cell culture) and in vivo animal experiments using wide-ranging doses of the ingredient to obtain preliminary efficacy, mechanism of action, toxicity (safety), and pharmacokinetic information.
4.) Proving safety for human (and animal) consumption is absolutely critical. This is usually begun using laboratory animals in controlled settings. In the case of LJ100®, oral toxicity studies on Wistar rats determined the LD50 of Tongkat Ali root extract (LJ100®) as 2,000 mg/kg body weight (acute) and the NOAEL (no observed adverse effect level) as greater than 1,000 mg/kg body weight (28 –day sub-acute feeding).
5.) Responsible ingredient manufacturers also should have an LD50. LD stands for "Lethal Dose." LD50 is the amount of a material, given all at once, which causes the death of 50 percent of a group of test animals. The LD50 is one way to measure the short-term poisoning potential ( or acute toxicity) of a material.
This is critical to move onto human studies; animal studies call for much lower doses to begin to ascertain both mechanism of action and then efficacy. For example, if only 1,000 mg of a substance or one of its active components is found to be lethal for laboratory animals, we know for certain that perhaps only 20 mg may exert beneficial properties in the next phases of animal experimentation.
6.) When laboratory animal studies begin to yield information about how a substance works and at what doses, we may then proceed with human pilot studies to unveil impact as well as tolerance. A pilot study is a small scale preliminary investigation conducted in order to evaluate feasibility, dosage, time, cost, adverse events, and effect size (statistical variability) in an attempt to predict an appropriate sample size and improve upon the study design prior to performance of a full-scale.
Nowadays, human clinicals need to be published in a proper journal. Otherwise, it does not meet the FDA standard and cannot count as a research. In addition, a minimum of two Phase II studies are needed for companies to make any health claims. Phase II typically enrolls a minimum of 60 individuals and needs to be double-blind and placebo-controlled in order to be recognized by the FDA, FTC,and the industry as a good study.
7.) Typically, before conducting a phase II human clinical, we must first obtain approval from an ethical committee..In certain cases, we even register our human clinical trial protocol on clinicaltrials.gov. These larger studies are also your human safety studies that are required by FDA, Health Canada, and other regulatory agencies to register the product. Without a minimum of two Phase II human clinicals, you also run into problems with the FTC. Brand marketers cannot substantiate the health benefits and claims that are necessary in their marketing efforts.
Today there is a fine line between nutraceuticals and pharmaceuticals. Some of our ingredients have some human studies with several dosage amounts against placebo. These are designed to see how little and/or how quickly the ingredient would perform most optimally. It also provides us and our brand marketers with dosage options to use for specific targeted health benefit or for formulas containing other ingredients.
8.) When working with any supplier and honing in on an exciting ingredient to use, ensure that the supplier has invested in all stages of research, and that the most important are not "borrowed." For example, no two same species-originated ingredients will act or perform the same. First, the differentiating point is where it is grown and its climate and harvesting. The second consideration is the increasing number of proprietary methodologies to extract and process the raw material. Therefore, human studies on these ingredients will yield their own distinctive results upon which responsible and accurate label claims can be built.