A new weight loss supplement or a repeat of a sordid history?

A “breakthrough” weight management product was released this week, promising that clinical evidence has shown it reduces cravings, hunger and food intake by as much as 25%. The company says its innovative chromium picolinate supplement “is based on the powerful results of a randomized, double-blind, placebo-controlled study” conducted by key researchers at the Pennington Biomedical Research Center, “the largest academically-based nutrition research center in the world.”

Consumers trying to do everything right to ensure that they’re taking supplements that have been proven safe and effective, may have let their guard down upon hearing that this new diet pill had been tested in a randomized, double-blind, placebo-controlled study and at a prestigious university research center. Even the websites and product literature appeared impressive and trustworthy, citing studies and even describing the FDA and scientific community as seeming to be in agreement about its use.

This proved to be an especially glaring example of how easy it is to make science and medical claims appear to say something entirely different from what the research and scientists actually concluded. It’s no wonder so many consumers believe the evidence behind supplements is sounder than it is. It’s also an important cautionary tale for us.

This story highlights how important it is to go to original sources and to look closely, not just at what words are really saying, but to also look for what isn’t being said.

First, the latest press release

The latest Nutrition 21, Inc. press release describes its chromium picolinate supplement, sold under the Iceland Health brand and given the name Appetite Control Formula. This product is not new, but a new name for its chromium picolinate product known as Chromax. Nutrition 21 makes the chromium picolinate sold throughout the country. Since last year, the company has been working to rebrand all of its supplement products under the Iceland Health brand.

Going to the Iceland Health website to buy the product — valued at $149.85 for two bottles — finds no clinical research listed and not even an address for the company. The website features a Certified Holistic Health Counselor (a certification for an alternative modality of holistic wellness and longevity through ‘food energetics’) saying “study after study has shown the ingredients…can reduce hunger levels and cravings for fat foods.”

The press release quotes Nutrition 21’s vice president saying that chromium picolinate has now been shown effective for reducing cravings, hunger and appetite and that it “can be an effective and cost-efficient tool within the framework of a sensible weight loss program to help people achieve a sustainable quality of life improvement.”

Any idea what is “quality of life improvement?” They didn’t define it, either. Even though the press release title announced a “breakthrough weight management product,” nowhere in the press release did it actually say that the product has any effect on weight!

Nor is this claim new. A nearly identical press release had been issued last year, on September 23, 2008. But the claims themselves, go back more than a decade.

Nutrition 21 website

Careful shoppers may go to the company’s website, Nutrition 21.com, to check out the science. They won’t find any science to support these claims.

The homepage lists its chromium picolinate and omega-3 supplements that promise to improve health and ‘quality of life.’ Its flagship product is Chromax, which it says “promotes healthy blood sugar, fights food cravings and supports cardiovascular health.” Its other chromium picolinate products include an Advanced Memory Formula, which claims to maintain brain health and improve memory; and several Diabetes Essentials formulas, which claim to promote healthy blood sugars and correct low chromium levels that it says have been linked to cardiovascular disease in diabetics. Chromax, it says, is also “often found as a key ingredient in weight loss and sports nutrition supplements.”

The public is told that there are more than 35 published clinical trials of chromium involving over 2,300 patients that “support the ingredient’s safety and efficacy,” and that the company holds patents covering chromium picolinate use for: “reducing hyperglycemia and stabilizing blood glucose, increasing lean body mass and reducing body fat, and for maintaining healthy cholesterol levels; [and] relieving symptoms of depression and premenstrual syndrome (PMS).”

According to its 2005 Securities And Exchange Commission (SEC) filing, the company had 37 U.S. patents and 12 pending patents, with chromium picolinate its primary product. It has been a key funder of chromium research, $2.7 million in 2005 alone. As we’ve learned, claims made in patents don’t mean they are grounded in science.

Only two weight studies mentioned on the website — and they have quite a history

Combing the company’s website finds no clinical trial on weight loss, appetite or food cravings, or any study conducted at Pennington Biomedical Research Center. The website’s Research Summary page for weight products references only two studies as being “key, representative studies in this area.” But, as we know, just because a study has been done doesn’t mean it was well-designed to be a fair test, or that its results supported the claims.

Both of these studies had been led by the same author, Gilbert R. Kaats, Ph.D., and published in the same journal, Current Therapeutics Research, ten and twelve years ago. The second paper was merely a follow-up to the first one. While Nutrition 21 doesn’t share any information about these papers on its website, this research has a scandalous history. Nutrition 21 had been slammed by the Federal Trade Commission for making unsubstantiated claims, after its finding that the scientific evidence didn’t support the company’s weight claims.

FTC crackdown. Chromium picolinate was “the miracle of the 1990s” and at that time, at least 9 million American consumers were spending $100 million a year for chromium picolinate products, according to the FTC. The FTC charged Nutrition 21, the sole supplier of chromium picolinate in the U.S., and companies selling chromium picolinate products, for making unsupported claims about weight loss and other health benefits.

In the settlement released on November 7, 1996, the FTC ruled that there was no scientific substantiation for the company’s claims that chromium picolinate can result in weight loss, reduce body fat and build muscle, increase metabolism, control appetite, reduce cravings for sugar, lower cholesterol, regulate blood sugar levels; increase energy and/or stamina; and treat and prevent diabetes. The FTC also ruled that the company had failed to substantiate its claims that 90% of American adults didn’t get enough chromium in their diets to support normal insulin function and therefore are at risk for obesity, heart disease and diabetes; that its benefits are proven by scientific studies; and that the testimonials used in their ads reflected typical experiences.

As part of this FTC settlement, and final order, issued on July 11, 1997, Nutrition 21 was prohibited from making any of these claims for chromium picolinate in the future, unless they have competent and reliable scientific evidence to support them. The company was ordered to present to the FTC for their inspection all advertisements and promotional materials and all tests, reports, studies, surveys, demonstrations or other evidence about any representation, including any consumer complaints. “The settlements would further prohibit the respondents from misrepresenting the results of any test, study, or research.”

The common source. The lead author of the only two papers used to support chromium picolinate for weight was Gilbert Kaats, a psychology professor who is currently President and CEO of Integrative Health Technologies, Inc. From 1989 to 2006, he was the owner and director of Health and Medical Research Center in San Antonio, Texas.

In 2002, he and his company came under fire when the Texas Attorney General filed a complaint in the District Court of Dallas County against him and his company, along with defendants with Mark Nutritionals, Inc., for violating the Texas Deceptive Trade Practices-Consumer Protection Act and the Texas Food, Drug and Cosmetic Act, Texas Health and Safety Code. Since 1999, they had been manufacturing, distributing, advertising and selling chromium picolinate weight loss products called Body Shaper and Body Solutions Evening Weight Loss Formula across the country.

You may remember their radio and television spots which claimed, often through testimonials, that you could lose weight, burn fat and build muscle while you slept, all without dieting, and even while pigging out. The Court found that their advertising and promotional materials were representing the formula as having been clinically proven, but “in truth and in fact, Evening Formula is not clinically proven…and constitutes a deceptive practice, and the making of false advertisements , in violation of §17.46(a) and (b) of the DTPA.”

These two studies were recently reviewed as part of a careful meta-analysis of randomized, double-blind, placebo-controlled clinical trials of chromium picolinate’s effect on body weight done by Dr. Edzard Ernst, M.D., Ph.D., and colleagues at the Universities of Exeter and Plymouth. Following the scientific process for evaluating fair test used by the Cochrane Collaborative, they found 31 potentially relevant trials, but after excluding the duplicate publications and those that weren’t randomized, double-blind, controlled trials reporting body weight, they were left with only ten trials with an average duration of 11 weeks, reporting on a total of 473 people. Dr. Ernst and colleagues found a small pooled effect on weight compared to a placebo, but it was primarily accounted for in those two trials by Kaats (which reported a 1 kg difference between those on supplements versus placebo). Not only had about one-third of the participants dropped out, but the studies hadn’t controlled for diet or exercise. The clinical relevance of the effect is debatable, Dr. Ernst and colleagues concluded, because of the study’s poor scientific robustness. “Therefore, we feel that this finding has to be interpreted with caution.” To date, the most carefully conducted studies on chromium have shown no benefits for weight loss.

Safety and effectiveness claims

Consumers searching the Nutrition 21 website looking for research to support any of its product claims find only a Research Overview page. Let’s look at what it says and compare it to the original source.

To support the safety of chromium picolinate, the company references an unpublished paper from the Council for Responsible Nutrition which cites animal and test tube studies and says “there are safety studies and reviews dating back to at least 1975 that support the safety of chromium picolinate.” The Council for Responsible Nutrition — the trade organization for manufacturers and suppliers of dietary supplements — recently made news for its view that randomized controlled clinical trials on humans is scientific dogma and unnecessary for making health claims.

Nutrition 21 states on its website:

Most recently, in conjunction with allowing a qualified health claim for chromium picolinate in reducing the risk of insulin resistance, and therefore possibly reducing the risk of type 2 diabetes, the FDA stated: “FDA concludes at this time, under the preliminary requirements of 21 CFR 101.14(b)(3)(ii), that the use of chromium picolinate in dietary supplements as described in the qualified health claims discussed in section IV [of this document] is safe and lawful under the applicable provisions of the Act.”

Therefore, there appears to now be a consensus within the relevant scientific community regarding the safety of Cr(Pic)3 for use as a nutritional or dietary supplement in humans.

With these statements, how many readers came away thinking that the FDA had approved the health claims for chromium picolinate? How many think that the FDA and scientists concur that chromium picolinate is a useful nutritional supplement? How many felt reassured that it had been found to be safe and could reduce their risks for insulin resistance and type 2 diabetes?

Millions thought so.

The original FDA document, “Qualified Health Claims: Letter of Enforcement Discretion — Chromium Picolinate and Insulin Resistance,” wasn’t provided by the company, but easily found online. It turns out that the FDA quote used by Nutrition 21 was pulled from an introductory overview examining if chromium could even be called a dietary supplement, which meant chromium had to be a component in food first, and found at levels to be safe and lawful under applicable food safety provisions of the Act.

But the FDA had cautioned that “information is lacking on the long-term effect of chronic chromium picolinate consumption and on individual patterns (i.e., how much and how long) of chromium picolinate dietary supplement use (IOM, 2001 and 2005).” The IOM had stated there is a need for more research on the safety of high-dose supplements and the National Toxicology Program is still conducting studies* to determine the potential toxicity and/or carcinogenicity of prolonged usage.

This FDA document went on to review at length (8,000 words) the hundreds of studies and research evidence behind each of the company’s health claims for chromium picolinate. The FDA’s conclusions on the Strength of the Scientific Evidence for each of the company’s claims stated:

Claim 1: Chromium picolinate may reduce the risk of insulin resistance.

[In the lengthier review section, the FDA found only one small study (Cefalu et al, 1999) purporting to show a benefit using insulin resistance as a surrogate endpoint for type 2 diabetes. “This study was of moderate methodological quality. This study did not show a statistically significant beneficial effect of chromium chloride supplementation on measures of insulin resistance.”]

FDA finds that there is very limited credible evidence for a qualified health claim specifically for chromium picolinate and a reduced risk of insulin resistance, and therefore possibly a reduced risk of type 2 diabetes. However, the reported findings of Cefalu et al., 1999 have not been replicated…there is very little data from which to conclude whether such a relationship actually exists. Based on the review of the strength of the total body of publicly available scientific evidence, FDA ranks this evidence as the lowest level for a qualified health claim. For the reasons given above, FDA concludes that the existence of a relationship between chromium picolinate and reduced risk of either insulin resistance or type 2 diabetes is highly uncertain.

Claim 2: Chromium picolinate may reduce the risk of cardiovascular disease when caused by insulin resistance.

[T]here was no scientific evidence to support the proposed claim nor was there scientific evidence to demonstrate that an increased risk of cardiovascular disease due to insulin resistance is reduced with the consumption of chromium picolinate. Based on the review of the scientific evidence, FDA concludes that there is no credible scientific evidence to support the proposed claim.

Claim 3: Chromium picolinate may reduce the risk of abnormally elevated blood sugar levels.

[T]here were five studies that evaluated the effect of chromium picolinate supplementation on measures of blood sugar levels. None of these studies showed a statistically significant beneficial effect of chromium picolinate on FBS and/or OGTT. Based on the review of the strength of the total body of publicly available scientific evidence, FDA concludes that there is no credible scientific evidence for the proposed claim.

Claim 4: Chromium picolinate may reduce the risk of cardiovascular disease when caused by abnormally elevated blood sugar levels.

[T]here is no scientific evidence to support the proposed claim nor is there scientific evidence to demonstrate that an increased risk of cardiovascular disease due to abnormally elevated blood sugar levels is reduced with the consumption of chromium picolinate. Based on the review of the total body of publicly available scientific evidence, FDA concludes that there is no credible evidence for the proposed claim.

Claim 5: Chromium picolinate may reduce the risk of type 2 diabetes.

[T]here were no studies that evaluated the effect of chromium picolinate on the incidence of type 2 diabetes…. Moreover, there are five studies that did not show a benefit for another surrogate endpoint of type 2 diabetes, blood glucose levels…. Based on the review of the strength of the total body of publicly available scientific evidence, FDA ranks this evidence as the lowest level for a qualified health claim.

Claim 6: Chromium picolinate may reduce the risk of cardiovascular disease when caused by type 2 diabetes.

[T]here is no scientific evidence to support the proposed claim nor is there scientific evidence to demonstrate that an increased risk of cardiovascular disease due to type 2 diabetes is reduced with the consumption of chromium picolinate. Based on the review of the total body of publicly available scientific evidence, FDA concludes that there is no credible evidence for the proposed claim.

Claim 7: Chromium picolinate may reduce the risk of retinopathy when caused by abnormally high blood sugar levels.

[T]here is no scientific evidence to support the proposed claim nor is there evidence to demonstrate that an increased risk of retinopathy due to high blood sugar levels is reduced with the consumption of chromium picolinate. Based on the review of the total body of publicly available scientific evidence, FDA concludes that there is no credible evidence to support the proposed claim.

Claim 8: Chromium picolinate may reduce the risk of kidney disease when caused by abnormally high blood sugar levels.

[T]here is no scientific evidence to support the proposed claim nor is there evidence to demonstrate that an increased risk of kidney disease due to abnormally high blood sugar levels is reduced with the consumption of chromium picolinate. Based on the review of the total body of publicly available scientific evidence, FDA concludes that there is no credible evidence to support the proposed claim.

The FDA also considered the company’s request to use disclaimers so that it could still make claims that didn’t have credible evidence. The FDA stated:

We considered but rejected use of a disclaimer or qualifying language to accompany the proposed claims for which there was no credible evidence to support the claim. We concluded that neither a disclaimer nor qualifying language would suffice to prevent consumer deception here, where there is no credible evidence to support any of these claims. Adding a disclaimer or incorporating qualifying language that effectively characterizes the claim as baseless is not a viable regulatory alternative because neither the disclaimer nor the qualifying language can rectify the false message conveyed by the unsubstantiated claim.

Finally, the FDA concluded:

Based on FDA's consideration of the scientific evidence, information submitted with your petition, and other pertinent scientific evidence and information, FDA concludes that there is no credible evidence to support qualified health claims for chromium picolinate and reduced risk of: cardiovascular disease when caused by insulin resistance, abnormally elevated blood sugar levels, cardiovascular disease when caused by abnormally elevated blood sugar levels, cardiovascular disease when caused by type 2 diabetes, retinopathy when caused by abnormally high blood sugar levels, or kidney disease when caused by abnormally high blood sugar levels. Thus, FDA is denying these claims.

Missing balance

Nowhere on the Nutrition 21 website will the public find this information from the FDA or any of these studies. The company’s SEC filing seemed to leave similar misimpressions of the FDA ruling, stating:

On August 25, 2005, the U.S. Food & Drug Administration (FDA), through its Qualified Health Claim (QHC) process, acknowledged there is limited but credible evidence to suggest that chromium picolinate may reduce the risk of insulin resistance, and therefore may possibly reduce the risk of type 2 diabetes. The FDA ruling is the first QHC related to diabetes, and it is for chromium picolinate and not other forms of chromium…

The Company's products did not require FDA safety approval because they were marketed as dietary supplements prior to October 1994…To enhance its market applications, the Company elected to seek FDA approval for health claims. On August 25, 2005, the FDA issued a favorable response, recognizing chromium picolinate as a safe nutritional supplement that may reduce the risk of insulin resistance and possibly type 2 diabetes. The FDA declined to permit other qualified health claims that were proposed by the Company. The FDA concluded:

"One small study suggests that chromium picolinate may reduce the risk of insulin resistance, and therefore possibly may reduce the risk of type 2 diabetes. FDA concludes, however, that the existence of such a relationship between chromium picolinate and either insulin resistance or type 2 diabetes is highly uncertain."

Chromium was covered in depth here, along with other evidential reviews. We learned that chromium is so prevalent in food that if we’re eating at all, we’re getting the trace amounts the body needs, and actual deficiencies are extraordinarily rare (four cases from nearly half a century ago in hospital patients before chromium was understood). We also learned in what foods and beverages this trace element is found — it’s richest in processed foods and baked goods, sweets, coffee, cocoa, beer and wine. None of the claims that taking more in supplements offer any health benefits have been shown to be valid, even after decades on the market.

According to researchers with the Linus Pauling Institute at Oregon State University, for instance, 15 randomized clinical trials found chromium had no effect on glucose or insulin concentrations in nondiabetics or nondeficient people; 12 randomized, placebo-controlled studies found no effect on lean body mass or body fat (even using the most sensitive and accurate measuring methods — dual energy x-ray absorbtiometry or DEXA and hydrodensitometry or underwater weighing); and ten recent randomized, double-blind, placebo-controlled trials found no clinically relevant weight loss.

Yet, taking unnecessary supplements may come with risks. There have been reports in the medical literature of serious adverse reactions to chromium supplements even taken for just two weeks and in healthy young people. People have suffered kidney failure and impaired liver function and liver necrosis from 600 mcg/day taken for just six weeks and after 1-2 grams/day taken over four months. A formerly healthy 33-year old woman, for example, suffered renal failure, liver problems, anemia and thrombocytopenia that required blood transfusions and dialysis and her symptoms finally resolved a year later.

What we don’t hear in marketing claims can often be the most important stuff.

And what about that new clinical evidence for weight management that the company claimed in this week’s press release to have found?

The latest chromium picolinate weight trial

This was actually not a new clinical trial, but had been done in May, 2007 and published last October in Diabetes Technology & Therapeutics, a journal published by Mary Ann Liebert, Inc. This trial (ClinicalTrials.gov #NCT00477854) was led by Stephen D. Anton, Ph.D., at Pennington Biomedical Research Center. A total of 536 potential participants were screened and eventually 56 overweight, healthy women were randomized to receive a placebo or 1,000 mcg. chromium picolinate/day. To participate in this study, women (18-50 years of age) had to have no chronic diseases, to have a BMI between 25-40, to have regular menstrual cycles, to report carbohydrate food cravings (a sign that they are dieters or restrained eaters), be nonsmokers, and not be taking any diet or psych medications.

At randomization, however, the supplement group differed significantly from the placebo group — for example, they were about 2.5 years younger (average age 32 years) and were restrained eaters, consuming about 318 kcal fewer calories and 15% less fat per day. Not surprisingly, they also scored as being hungrier before each meal on food craving and eating inventory scales. Diet and exercise levels were not monitored or controlled during the trial. Only 40 women completed the 8 week trial (19 in the placebo arm, 21 in the supplement)

The women were weighed at the clinic, as well as had Dual energy X-ray absorptiometry (DEXA) whole body scans, and glucose and insulin levels drawn. At the end of the 8 week trial, there was no difference between the groups in fasting blood sugars and “fasting insulin and homeostatic model assessment of insulin sensitivity (HOMA-S) levels did not change significantly in either group,” the authors concluded. The study also found no statistical difference in body weight change.

At 8 weeks, the placebo group reported being hungrier before a test dinner (4.5 hours after a test lunch) than the supplement group, but the supplement group reported higher hunger ratings immediately after lunch, both consistent with restrained eaters being less in touch with their hunger and satiety. “There were no differences by condition in change in hunger levels over time.” And concerning food “cravings,” the authors concluded: “CrPic did not decrease cravings for carbohydrates and sweets to a greater extent than placebo; thus, it is unclear whether CrPic has a specific effect upon any particular food craving (e.g., fats vs. carbohydrates/sweets).”

Besides the weaknesses in the study design, this study was clearly null and fails to support any claims that chromium picolinate affects appetite or weight in people.

In a second study published with this same paper, the authors injected chromium picolinate directly into the brains of 8 rats, which resulted in a “small but statistically significant decrease in their food intake, but only at the highest dosage, but it had no effect on food intake at lower doses.” There was no control group. The authors concluded this indicated that chromium picolinate “may function by a central mechanism.” We really don’t need to drive the truck through that one, do we?

Please be careful out there

Hopefully, this illustration has helped to show the importance of thinking critically whenever we hear about a new product promising to offer health benefits. We can’t let our guard down just because something is said to have been scientifically proven.

Credible, sound science is not determined by how many studies are said to support it (good science isn’t about tallying studies, but about the quality of studies that are fair tests and actually testing the claim), by how many scientists or degreed professionals are said to support it (good science isn’t about consensus, but the quality of the science and building a body of independently replicated research), or how prestigious or credible-looking the source (woo has invaded the country’s top academic and medical institutions).

It’s helpful to remember that supplements are not regulated — they don’t have to be approved by the government, to be registered with the FDA or undergo safety evaluations before they can be sold. The FDA can no longer legally act to take a fraudulent product off the market until the FDA proves it to be unsafe and to pose “a significant and unreasonable risk” and then, only after a product is on the market. It’s up to consumers to educate and protect themselves and to let the FDA know if they’ve suffered adverse reactions so that it can act to help protect others. [More information the regulations, how to avoid false claims, and contact information for reporting side effects, here.]

Please be careful out there.

© 2009 Sandy Szwarc

* The NTP’s 2005 Executive Summary Chromium Picolinate referenced by the FDA said:

A beneficiary of the Dietary Supplement Health and Education Act of 1994, chromium picolinate can be sold legally without evidence of safety or efficacy… The synthetic process for metal picolinates was patented by the U.S. Department of Agriculture and leased to Nutrition 21. Nutrition 21 holds the exclusive U.S. license on the patent rights to chromium picolinate and sells it to the public through distributors.

According to the NTP, there had been no studies investigating chromium picolinate and cancer risk in human and no carcinogenicity studies have been published in animals. One unpublished study had reported negative short-term toxicity but that study had been found to have ambiguous methodology and the experiment was not properly controlled.

On February 27-28, 2008, the NTP released its draft technical report on the toxicology and carcinogenesis in rats and mice. Regardless of the dose, chromium picolinate had no effect on the animals’ weights after 2 years, and the NTP found no clear evidence of gene mutations, but did find equivocal evidence of carcinogenic activity in male rats (based on an increase in preputial gland adenomas).