Dietary supplements: Scary substances manufactured under scary conditions

If there’s a law that I view as a horrible, horrible, law, it’s the Dietary Supplement Health Education Act of 1994 (DSHEA of 1994). It is a law that blog bud and former ScienceBlogs blogger Dr. Peter Lipson has rightly called a travesty of a mockery of a sham, and, quite frankly, I think he has been too easy on it. Clearly, if there is a single instance of a massive triumph of the forces of quackery in the U.S. that I could point to, the DSHEA of 1994 would be it. This particular misbegotten law in essence opened the floodgates for the sale of dubious supplements and turned a relatively small industry into a huge industry.

The way that the DSHEA accomplished that was to make a distinction between food and medicine. While on its surface this would appear to be a reasonable distinction, given that it doesn’t make sense from a policy or scientific standpoint to hold food to the standards as rigorous as the standards to which drugs are held, as implemented by the DSHEA this distinction has the pernicious effect of allowing manufacturers to label all sorts of botanicals, many of which possess pharmacological activity, as “supplements,” and supplements, being defined as food and not medicine, do not require prior approval by the FDA before marketing. In other words, supplement manufacturers basically work on the honors system when it comes to deciding what they will market as a supplement, and the FDA can’t do anything about a harmful supplement until after it has been on the market and caused harm. The only real practical restriction on them is that they can’t make specific health claims for their supplements in terms of their being able to treat or diagnose any disease or medical problem. Allowed are vague “structure-function” claims. These include suitably vague claims that I’ve seen or heard in ads such as “boosts the immune system,” “protects prostate health” (whatever that means), “strengthens your liver,” or “aids in digestion.”

If the dietary supplements on the market were, in fact, food or real nutritional supplements, this might not be such a problem. I like to quote Quackwatch when explaining the problem because it’s about as concise an explanation of what is wrong as I have ever found:

DSHEA worsened this situation by increasing the amount of misinformation that can be directly transmitted to prospective customers. It also expanded the types of products that could be marketed as “supplements.” The most logical definition of “dietary supplement” would be something that supplies one or more essential nutrients missing from the diet. DSHEA went far beyond this to include vitamins; minerals; herbs or other botanicals; amino acids; other dietary substances to supplement the diet by increasing dietary intake; and any concentrate, metabolite, constituent, extract, or combination of any such ingredients. Although many such products (particularly herbs) are marketed for their alleged preventive or therapeutic effects, the 1994 law has made it difficult or impossible for the FDA to regulate them as drugs. Since its passage, even hormones, such as DHEA and melatonin, are being hawked as supplements.

The ban on advertising supplements as having the ability to treat or diagnose specific diseases is widely flouted, as well. For example, manufacturers themselves often try to inoculate themselves with what Peter Lipson has so brilliantly referred to as the “Quack Miranda Warning,” while implying all sorts of health benefits that are not supported by science. As I mentioned only a couple of weeks ago, there are also companies who make sure that their literature strictly complies with the DSHEA ban on making specific health claims but then wink at proxies who sell their products as a cure-all, making claims up to and including that the product can cure cancer or AIDS, claiming plausible deniability regarding their actions. Meanwhile, any time any attempt is made to tighten up regulations on dietary supplements, legislators who have been bought and paid for by the supplement industry, like Utah Senator Orrin Hatch or Indiana Representative Dan Burton, pounce, doing their best to kill or water down any legislation that strengthens the FDA’s hand in removing potentially dangerous supplements. Indeed, some legislators go beyond defense and go on offense, trying to widen the scope of the health claims that can be made for supplements, as long as a single study can be found to support the claim.

Yet, despite these problems, the supplement industry assures the government and its customers that its products are safe and effective, that they are manufactured according to the most rigorous standards. We’ve discussed the issues of efficacy before, discussing how there is little or no evidence that supplements prevent cancer, for example, and that there is no evidence that they prolong life. Over the weekend, Chicago Tribune reporter Trine Tsouderos published a damning report that indicates that many supplements are not safe either, because of criminally shoddy manufacturing standards.

Tsouderos’ article, Dietary supplements: Manufacturing troubles widespread, FDA inspections show, is an indictment of the entire supplement industry. It also shows that, due to lack of resources, the FDA is clearly not up to the task of exercising even the minimal level of oversight required by the DSHEA. In the last four years, according to Tsouderos, the FDA has found major violations of manufacturing rules in nearly half of the 450 companies it has inspected:

The inspection reports portray an industry struggling to meet basic manufacturing standards, from verifying the identity of the ingredients that go into its products to inspecting finished batches of supplements.

Some firms don’t even have recipes, known as master manufacturing records, for their products.

Others make their supplements in unsanitary factories. New Jersey-based Quality Formulation Laboratories produced protein powder mixes and other supplements in a facility infested with rodents, rodent feces and urine, according to government records. FDA inspectors found a rodent apparently cut in half next to a scoop, according to a 2008 inspection report.

“It’s downright scary,” said Daniel Fabricant, head of the FDA’s Division of Dietary Supplement Programs. “At least half of industry is failing on its face.”

As a result of these inspections, one in four supplement manufacturers has received a warning letter, which is considered significant, and:

So far this year, FDA inspectors have found violations of good manufacturing practices during two-thirds of the 204 inspections they have conducted in nearly 200 supplement firms’ facilities, agency officials said. Seventy of these inspections resulted in the agency’s most serious rating.

Personally, I find it rather ironic that one of the key arguments that the supplement manufacturing industry always makes whenever attempts are made to tighten regulations governing supplements is that supplements are “food, not medicine.” Yet, the most important aspects of food preparation and manufacturing are aspects where the supplement industry fails almost completely: Sanitary conditions and knowing that the ingredients for their “food” product are pure. In fact, in many cases, supplement companies don’t even have real recipes for their products, which makes me wonder exactly how it is they make their products. A pinch of this and a pinch of that? Remember, for example, how CanCell was made on a hot plate in Jim Sheridan’s kitchen, and how Sheridan was described as having “no tolerance for complying with rigid manufacturing procedures that the FDA demanded.”

The excuses of the supplement industry, as reported by Tsouderos, are pathetic, as well. Hilariously, a flak for the Natural Products Association, in a classic bit of massive understatement, referred to the inspection numbers as “unfortunate,” while other representatives of various trade organizations for the supplement industry whine that the industry hasn’t had enough time, even though the more recent rules, which should have been in effect all along, were only finalized in 2007. Yes, that’s right. Five years apparently isn’t enough for the industry to get more than half of its members into compliance with basic food manufacturing standards.

Lest you think that this issue doesn’t have potentially horrific consequences, consider the story of John Adams and 200 people who were poisoned by a supplement:

In 2008 more than 200 people — including a 4-year-old — were poisoned by selenium after taking liquid multivitamin dietary supplements that were sold in health stores and by chiropractors, according to a medical paper published on the mass poisoning. The products, called Total Body Formula and Total Body Mega Formula, contained an average of 40,800 micrograms of selenium per serving instead of 200, according to the paper.

John Adams, of Chipley, Fla., was one of the victims. His silver hair — which had earned him the nickname “Silvertop” at work — began falling out in clumps. His fingernails and toenails became discolored, peeled off, regrew and peeled off again. He had a hard time remembering how to do his job as a telephone repairman. He became so weak it was hard to get in and out of his work truck, and eventually he was forced to retire.

Adams and his wife, who also experienced problems, sued along with dozens of others. This year, the couple received a settlement. Adams, now 65, said he is still weak on his left side, has ruined fingernails and toenails that do not grow and struggles with memory problems.

So what was the excuse given by Total Body Essential Nutrition, the distributor of the supplements that caused the mass poisoning? A lawyer for the company blamed a contractor for incorrectly interpreting the formula, incorrectly formulating it, or both. I kid you not. Amusingly (from a schadenfreude standpoint, not from the standpoint of any injury to any person), it’s not just Total Body Essential Nutrition who’s produced a dangerous batch of supplements and tried to blame it on a contractor’s screw-up. In fact, two years ago Gary Null, conspiracy theorist and quack supreme, suffered a similar fate to that of John Adams, but he was poisoned by one of his own products. Specifically, what happened was that Null overdosed on vitamin D consuming Gary Null’s Ultimate Power Meals. As a result, he suffered from “excruciating fatigue along with bodily pain,” and “began to suffer from extreme cracks and bleeding from within his feet.” The reason? There was 1,000 times as much vitamin D in his power meal than what the label listed. That meant that instead of ingesting 2,000 IU of Vitamin D daily, Null was ingesting 2 million IU. The usual recommended daily intake is 600 IU per day.

One thing that came to mind as I read this article is a simple question: Why did it take the FDA until 2008 to begin to enforce in a serious way manufacturing standards in the supplement industry? After all, even with the DSHEA, the FDA always had the power to do this, just as it’s always had the power to enforce rules and regulations governing the manufacture and production of food and food products. Take a look at the Dietary Supplement Current Good Manufacturing Practices (CGMPs), as finalized in 2007. There’s nothing radical there. There’s nothing even controversial there when examined from a food manufacturing point of view. The requirements include that manufacturers:

  • Employ qualified employees and supervisors;
  • Design and construct their physical plant in a manner to protect dietary ingredients and dietary supplements from becoming adulterated during manufacturing, packaging, labeling and holding;
  • Use equipment and utensils that are of appropriate design, construction, and workmanship for the intended use;
  • Establish and use master manufacturing and batch production records;
  • Establish procedures for quality control operations;
  • Hold and distribute dietary supplements and materials used to manufacture dietary supplements under appropriate conditions of temperature, humidity, light, and sanitation so that the quality of the dietary supplement is not affected;
  • Keep a written record of each product complaint related to CGMPs; and
  • Retain records for 1 year past the shelf life date, if shelf life dating is used, or 2 years beyond the date of distribution of the last batch of dietary supplements associated with those records.

These are some very basic standards that one would expect to be in force for any food manufacturing facility. Certainly they’re far less stringent than what is required for pharmaceutical manufacturing. Yet, the supplement industry is still, four years after the standards have gone into effect and five years after it knew the final form they would likely take, apparently unable or unwilling to comply with some very basic good manufacturing processes that a typical cannery would be expected to follow. Note that, until recently, the actual ingredients weren’t really that big an issue; the FDA only wanted to make sure that what the manufacturer lists as being in the supplement and what is actually in the supplement match. Regarding what is actually in the supplement, the FDA appeared to be more or less agnostic. Indeed, it took some fairly egregious examples to get the FDA to act, such as the attempt to label an industrial chelator as a dietary supplement by chemist-turned-antivaccinationist.

Yet, still the supplement industry resists, as described by Tsouderos:

Bradford Williams, manager of the FDA Division of Dietary Supplement Programs, expressed exasperation while addressing an audience at SupplySide West, a large dietary supplement conference in Las Vegas in October.

“It doesn’t seem that the firms are getting it,” Williams said. “How do I reach this industry? Do I have to use nuclear bombers to do it?”

And:

Fabricant said the FDA’s rules are basic and often cover practices — like ensuring the finished product matches specifications — that should have been in place long ago. Warning letters typically are sent after firms fail to fix problems identified in earlier inspections, he said.

Exactly.

Ironically, before becoming director of the FDA’s Division of Dietary Supplement Programs, Daniel Fabricant, PhD was vice president of the Natural Products Association, the largest trade group in the U.S. representing supplement manufacturers and distributors. One wonders if it is the knowledge he acquired serving in that capacity that now informs his actions as the main honcho spearheading the FDA’s renewed drive to bring supplement manufacturing processes into line with at least the same sorts of basic rules that factories making bread, cookies, crackers, cake, soups, pasta, potato chips, and soda, in fact, of pretty much every sort of food, have had to follow for decades.

Although it is heartening to see an actual effort seeking, if not to require scientific evidence of efficacy for supplements, at least to hold supplement manufacturers to good manufacturing guidelines that make sure that whatever manufacturers list as being in their products is actually in their products, it is sad that it took so long for the FDA to undertake. It is also a perilous time for the FDA, because the supplement industry is powerful, with lots of influential friends in Congress. It has already succeeded in getting the FDA to issue a “clarification” of new rules regarding New Dietary Ingredients (NDI) proposed for supplements, and its friends in Congress have successfully beat back pretty much every attempt to strengthen the DSHEA. So while I cheer the new effort since 2008 to make sure that supplements are at least manufactured according to food industry standard practices, I fear that any victory will be short-lived.