The “dietary supplement” industry manufactures and sells more than vitamins, fish oil, and Echinacea. Way more. And some of its products could literally be your worst nightmare.

U.S. Marshals, acting on a request from the U.S. Food and Drug Administration, earlier this month seized almost 90,000 bottles of a dangerous herbal product whose brand name is RelaKzpro. Sold by Dordoniz Natural Products of South Beloit, Illinois, it is labeled as containing kratom, a witches’ brew of potent psychotropic chemicals that are derived from leaves of the Mitragyna speciosa tree, which is prized in Asia for its mind-altering effects.

Kratom serves as a reminder that “natural” is not synonymous with “safe”: Some of the deadliest toxins known, such as alpha-amanitin from the “death cap” mushroom Amanita phalloides and ricin from the castor bean, are “natural” compounds found in plants.

Here is how one user described kratom’s effects:

Very quickly, anxiety and feelings of profound ‘wrongness’ set in. … I was getting closed eye visuals of people who seemed to be covered in mold or fungi and ‘hearing’ a kind of toothless mumbling that disturbed me immensely. It sounded like the noise a severely mentally challenged person might make, and my head was full of thoughts of ordinary people subjected to ruinous torture and experimentation.

This is the kind of psychotic ideation that can cause people to jump out windows or attack other people they falsely perceive as a threat. And yet kratom has been available online, and it’s legal except in four states.

Recommended by Forbes
Northwestern MutualVoice: Why Women Should Care About The Retirement Savings Gap

We Worry About Trace Amounts Of BPA While Playing Russian Roulette With Dietary…
Northwestern MutualVoice: Why Women Should Care About The Retirement Savings Gap

FDA Yanks Meridia — And Finds It In A Supplement
Death By Dietary Supplement
Massive Drug Recalls are a Wake-Up Call for Vitamin and Supplement Industry
MOST POPULAR Photos: Canada’s 25 Best Employers 2016
TRENDING ON TWITTER 9 Things That Make Good Employees Quit
MOST POPULAR Photos: The Richest Person In Every State
Herbal and dietary supplements are seen for sale in a shop May 26, 2010 in New York City. A U.S. government probe into herbal and dietary supplements found that some contain contaminants and use false marketing claims. (Photo by Mario Tama/Getty Images)

M. speciosa is indigenous to Thailand but it’s banned there, so why, one might ask, is this morphine-like recreational drug considered a supplement and legal here? They are some of the mysteries spawned by the bizarre federal Dietary Supplements Health and Education Act of 1994 (DSHEA), which exempts drugs from regulation if they are called “supplements.”

So what is this stuff?

Kratom is not a single chemical substance; it contains dozens of chemicals called alkaloids—nitrogen-containing chemicals that are found in plants and many of which are known poisons.

A single drug can sometimes have multiple effects, often from interacting with enzymes or receptors that it was never intended to affect–so called off-target toxicity. Antidepressants are notorious for having multiple psychological and physiological effects. A far more common example is caffeine, which produces both neuro-stimulatory and diuretic effects by interacting with different receptors.

But when dozens of chemical compounds, many of which have never been studied (or even identified), are involved, you might expect to see multiple off-target effects. This is almost unavoidable and is certainly the case with kratom.

Mitragynine, the major psychotropic alkaloid in kratom, binds to myriad receptors which mediate all sorts of physiological effects. Below is a table with a partial list of some of the known receptor targets of the drug, and some of the functions of those receptors.

miller table

A concoction that affects so many critical bodily functions simultaneously and unpredictably is exactly what one wants to avoid in a pharmaceutical. That’s a problem for many herbal supplements, which are seldom pure or standardized and may have a wide range of side effects. The fact that a drug binds to multiple receptors does not guarantee that it will elicit a physiological response, but it certainly increases the likelihood–a common red flag when any new drug is being developed.

According to FDA’s associate commissioner for regulatory affairs Melinda Plaisier, the agency has “identified kratom as a botanical substance that could pose a risk to public health and have the potential for abuse,” and she promised that “FDA will continue to exercise our full authority under law to take action on these new dietary ingredients, especially if they ignore the notification requirements, as part of our commitment to protecting the health of the American people.”

We find somewhat puzzling Ms. Plaisier’s emphasis on the New Dietary Ingredient Notification requirements because it seems quite obvious that products such as kratom are by definition an “imminent hazard,” according to the FDA’s own regulations:

Within the meaning of the Federal Food, Drug, and Cosmetic Act an imminent hazard to the public health is considered to exist when the evidence is sufficient to show that a product or practice, posing a significant threat of danger to health, creates a public health situation (1) that should be corrected immediately to prevent injury and (2) that should not be permitted to continue while a hearing or other formal proceeding is being held. The imminent hazard may be declared at any point in the chain of events which may ultimately result in harm to the public health. The occurrence of the final anticipated injury is not essential to establish that an imminent hazard of such occurrence exists.

There is no doubt that many herbal supplements pose “a significant threat of danger to health.” In a study published last October in the New England Journal of Medicine, “ER [Emergency Room] Visits for Adverse Events Related to Dietary Supplements,” researchers from the CDC and the FDA analyzed representative surveillance data from 63 hospital Emergency Rooms over a 10-year period (2004-2013). Their statistical analysis projected about 23,000 ER visits annually resulting from ingestion of supplements, about one-tenth of which led to hospitalization. And this is surely the tip of the iceberg.

According to the authors, “Such visits commonly involve cardiovascular manifestations from weight-loss or energy products among young adults and swallowing problems, often associated with micronutrients, among older adults.” But DSHEA prohibits federal authorities from requiring evidence that herbal remedies are safe or effective, or even that the dosage information on the label is correct. Since 1994, these products have not been subject to the same regulatory requirements as prescription drugs—or in fact to any meaningful regulation at all.

Although the law prohibits supplements from being marketed for the treatment or prevention of disease, this restriction is widely ignored, as any viewer of TV ads can attest. The marketers of these products evade the mandate simply by playing word games: Instead of claiming that a product treats, controls or cures a condition (which would subject it to onerous regulation as a “drug”), they simply substitute the term “supports,” as in “supports the immune system or supports heart (or brain or prostate) health.” If they add a pro forma disclaimer—“This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease”–it seems they can sell pretty much anything.

The estimated number of supplement products exploded from 4,000 in 1994 to more than 55,000 in 2012 (the most recent year for which data are publicly available). Approximately half of all adults in the United States report having used at least one dietary supplement in the past month. In 2007, sales of herbal or complementary nutritional products reached $14.8 billion, one-third of the out-of-pocket expenditures for prescription drugs. And sales are unquestionably much higher today.

Henry I. Miller and Josh Bloom

The “dietary supplement” industry manufactures and sells more than vitamins, fish oil, and Echinacea.  Way more.  And some of its products could literally be your worst nightmare.

U.S. Marshals, acting on a request from the U.S. Food and Drug Administration, earlier this month seized almost 90,000 bottles of a dangerous herbal product whose brand name is RelaKzpro. Sold by Dordoniz Natural Products of South Beloit, Illinois, it is labeled as containing kratom, a witches’ brew of potent psychotropic chemicals that are derived from leaves of the Mitragyna speciosa tree, which is prized in Asia for its mind-altering effects.

Kratom serves as a reminder that “natural” is not synonymous with “safe”: Some of the deadliest toxins known, such as alpha-amanitin from the “death cap” mushroom Amanita phalloides and ricin from the castor bean, are “natural” compounds found in plants.

Here is how one user described kratom’s effects:

Very quickly, anxiety and feelings of profound ‘wrongness’ set in. … I was getting closed eye visuals of people who seemed to be covered in mold or fungi and ‘hearing’ a kind of toothless mumbling that disturbed me immensely. It sounded like the noise a severely mentally challenged person might make, and my head was full of thoughts of ordinary people subjected to ruinous torture and experimentation.

This is the kind of psychotic ideation that can cause people to jump out windows or attack other people they falsely perceive as a threat. And yet kratom has been available online, and it’s legal except in four states.

Herbal and dietary supplements are seen for sale in a shop May 26, 2010 in New York City. A U.S. government probe into herbal and dietary supplements found that some contain contaminants and use false marketing claims. (Photo by Mario Tama/Getty Images)

M. speciosa is indigenous to Thailand but it’s banned there, so why, one might ask, is this morphine-like recreational drug considered a supplement and legal here? They are some of the mysteries spawned by the bizarre federal Dietary Supplements Health and Education Act of 1994 (DSHEA), which exempts drugs from regulation if they are called “supplements.”

So what is this stuff?

Kratom is not a single chemical substance; it contains dozens of chemicals called alkaloids—nitrogen-containing chemicals that are found in plants and many of which are known poisons.

A single drug can sometimes have multiple effects, often from interacting with enzymes or receptors that it was never intended to affect–so called off-target toxicity. Antidepressants are notorious for having multiple psychological and physiological effects. A far more common example is caffeine, which produces both neuro-stimulatory and diuretic effects by interacting with different receptors.

But when dozens of chemical compounds, many of which have never been studied (or even identified), are involved, you might expect to see multiple off-target effects. This is almost unavoidable and is certainly the case with kratom.

Mitragynine, the major psychotropic alkaloid in kratom, binds to myriad receptors which mediate all sorts of physiological effects. Below is a table with a partial list of some of the known receptor targets of the drug, and some of the functions of those receptors.

miller table

A concoction that affects so many critical bodily functions simultaneously and unpredictably is exactly what one wants to avoid in a pharmaceutical. That’s a problem for many herbal supplements, which are seldom pure or standardized and may have a wide range of side effects. The fact that a drug binds to multiple receptors does not guarantee that it will elicit a physiological response, but it certainly increases the likelihood–a common red flag when any new drug is being developed.

According to FDA’s associate commissioner for regulatory affairs Melinda Plaisier, the agency has “identified kratom as a botanical substance that could pose a risk to public health and have the potential for abuse,” and she promised that “FDA will continue to exercise our full authority under law to take action on these new dietary ingredients, especially if they ignore the notification requirements, as part of our commitment to protecting the health of the American people.”

We find somewhat puzzling Ms. Plaisier’s emphasis on the New Dietary Ingredient Notification requirements because it seems quite obvious that products such as kratom are by definition an “imminent hazard,” according to the FDA’s own regulations:

Within the meaning of the Federal Food, Drug, and Cosmetic Act an imminent hazard to the public health is considered to exist when the evidence is sufficient to show that a product or practice, posing a significant threat of danger to health, creates a public health situation (1) that should be corrected immediately to prevent injury and (2) that should not be permitted to continue while a hearing or other formal proceeding is being held. The imminent hazard may be declared at any point in the chain of events which may ultimately result in harm to the public health. The occurrence of the final anticipated injury is not essential to establish that an imminent hazard of such occurrence exists.

There is no doubt that many herbal supplements pose “a significant threat of danger to health.” In a study published last October in the New England Journal of Medicine, “ER [Emergency Room] Visits for Adverse Events Related to Dietary Supplements,” researchers from the CDC and the FDA analyzed representative surveillance data from 63 hospital Emergency Rooms over a 10-year period (2004-2013). Their statistical analysis projected about 23,000 ER visits annually resulting from ingestion of supplements, about one-tenth of which led to hospitalization. And this is surely the tip of the iceberg.

According to the authors, “Such visits commonly involve cardiovascular manifestations from weight-loss or energy products among young adults and swallowing problems, often associated with micronutrients, among older adults.” But DSHEA prohibits federal authorities from requiring evidence that herbal remedies are safe or effective, or even that the dosage information on the label is correct. Since 1994, these products have not been subject to the same regulatory requirements as prescription drugs—or in fact to any meaningful regulation at all.

Although the law prohibits supplements from being marketed for the treatment or prevention of disease, this restriction is widely ignored, as any viewer of TV ads can attest. The marketers of these products evade the mandate simply by playing word games: Instead of claiming that a product treats, controls or cures a condition (which would subject it to onerous regulation as a “drug”), they simply substitute the term “supports,” as in “supports the immune system or supports heart (or brain or prostate) health.” If they add a pro forma disclaimer—“This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease”–it seems they can sell pretty much anything.

The estimated number of supplement products exploded from 4,000 in 1994 to more than 55,000 in 2012 (the most recent year for which data are publicly available). Approximately half of all adults in the United States report having used at least one dietary supplement in the past month. In 2007, sales of herbal or complementary nutritional products reached $14.8 billion, one-third of the out-of-pocket expenditures for prescription drugs. And sales are unquestionably much higher today.