Clinically Proven for Weight Loss?

There is a new weight loss ingredient on the scene and its evidence base is shaky at best.

By Douglas Kalman

Have you heard about the joke that was clinically proven to be funny? In fact, in the New Joke Application process, the group submitting the joke supplied two sets of what they thought were supportive data along with testimonials of joke professionals who also thought the joke had merit. For some reason, however, the “authorities” did not feel the joke had enough supportive data. But the comedian chose to tell it anyway. Thus, it appears the process of due diligence may not have been properly followed.

Let’s examine this scenario from a dietary supplement and research perspective. Perhaps there is a way to meander through the New Dietary Ingredient (NDI) process and compile substantiation for safety and perhaps even efficacy of a product. In some cases, even though companies do not have enough supportive data they decide to market the ingredient anyway.

We all know that if you want to market an ingredient to the public and said ingredient was not previously sold in the U.S. prior to October 15, 1994, then a dossier of either animal and human safety data and/or proof of historical use as a food must be presented to the FDA/CFSAN. Many companies believe (wrongly?), however, that if there is evidence that the ingredient has been consumed in regions outside the U.S., then they have proof of its common use. It is important to note, however, that aspects of the NDI definition do indicate that the item should be one consumed here within U.S. borders.

Speaking of NDIs, there is a new weight loss ingredient on the nutraceuticals scene. The promotion behind this new product seems to suggest it is the new “hoodia” of the weight loss market, and indeed could be more effective. Advertisements even go as far as to state that the product is not full of puffery, but rather hard science. It is the “hard science” part of this ingredient’s promotion, however, that warrants further scrutiny.

Examining the Hard Science

If you were to read the word “treatment” in the title of a study paper, would you assume that a disease state was being investigated? Excluding discussions herein of whether or not animal safety studies have utility as related to efficacy-outcome oriented research (in humans), let’s assume that the product of interest was found to be of acceptable safety margin when used in human doses. This means that the animal studies found the ingredient to be non-carcinogenic, to have a high-LD50 and was not organotoxic. In addition, the human studies also found the product did not affect blood pressure, heart rate or markers of safety as denoted by specific blood tests (liver, kidney, etc.). From the compilation of animal and brief human studies, we can also assume that the product is non-toxic, though further more invasive safety data is necessary.

On August 25, 2004, an NDI submission was sent to FDA. As part of the submission, data from two non-peer reviewed studies were utilized as substantiation for the safety of the ingredient. But let’s concentrate on the efficacy (does it aid in weight loss?).

The first study enrolled 50 (poorly described) subjects who had a BMI greater than 26. The subjects were separated into two groups and studied in an eight-week weight loss trial. The term poorly described is used because to state that subjects had a BMI higher than 26 and not to describe the range of subjects is loose. In other words, a BMI between 25 and 29.9 is considered overweight, while a BMI of 30 to 34.9 is considered obese. BMI’s greater than 35 are also obese and are denoted by a staging system. Thus, it is conceivable that there could have been subjects in this study with a BMI between 26 and 50. The subjects in this study do not appear to be equal or balanced, thus we have a huge confounding variable to deal with (and weakness in the design).

The study paper also indicates the study subjects were told not to diet and to do a total of 60 minutes of walking per day (compliance checks anyone?). As far as efficacy goes, the author of this study surmised that this cactus ingredient is an appetite suppressant. The only problem with this conclusion is if subjects were told not to change their diet and were not housed in a metabolic ward and did not undergo any meal challenges or observation of actual intake, then how could the product be denoted as an appetite suppressant? It was also noted in the results of the study that some of the side effects observed were likely due to the gelatin capsules used and not the actual ingredient, since people in India tend to eat a more vegetarian diet. Because this study contains so many fundamental design flaws, it should not be considered part of the ingredient’s substantiation for weight loss. To date, this study has not been published in any moderate or high impact factor scientific journal, it has only been presented in abstract/poster form.

A second study on this product was conducted in the U.S. at a geriatric research center (geriatric = older adults, not necessarily the target population for a weight loss study). According to the NDI, 26 overweight (again, not well described) subjects were enrolled in study, which lasted for a period of one month. No inclusion or exclusion criteria were noted, and there was no mention of which Institutional/Ethical Review Board (IRB/ERB) reviewed the study parameters. Furthermore, there was no mention of the diet or lifestyle of the subjects within this report.

For some reason, the researchers chose to enroll in an unbalanced fashion. In other words, for every one person on placebo, two or three would be enrolled to receive the active product (the researchers had 19 subjects on active treatment and seven on placebo—a 3:1 ratio). From a statistical analytical standpoint, enrolling subjects in such a way weakens the study. Some people incorrectly assume the more people that are in the active group, the better the chance for positive results. But, in fact, unbalanced studies like this one are weak because the “power” is only as strong as the smallest group.

The researchers reported that 60% of those taking the active product lost six pounds in a month. But no real statistical analyses were noted in any report I have seen from this study. Thus, I believe the claim that 60% of the active subjects losing six pounds should be considered spurious and of no scientific merit. Examining this from a different perspective, 60% of 19 is 11 people; however, since no data about the alleged placebo group was shared, how do we know if all seven subjects on placebo did not also lose the same amount of weight?

Perhaps not surprisingly, this product did not pass the NDI process because FDA felt there was not enough substantiation. FDA also noted discrepancies in the reports regarding the extraction process. Despite these developments, however, the product is still being sold on the market.

True, well-designed, randomized, double-blind, placebo-controlled clinical trials enrolling participants that represent the target market for the product are needed for product substantiation. In the area of weight loss, this means incorporating standardized dietary and exercise controls along with psychometric measures and mechanism of action endpoints. These parameters are necessary in order to be able to make weight loss claims. Hopefully the group who submitted the NDI described in this column will pursue more solid substantiation in the future, so manufacturers can truly feel comfortable using it in weight loss formulations. Furthermore, perhaps the company should re-file with FDA so it can market the product legally.NW