Currently browsing posts about: GRAS

Last week, the FDA essentially took tara flour out of the food supply.

Today, the U.S. Food and Drug Administration (FDA) posted on its website its determination that tara flour in human food does not meet the Generally Recognized As Safe (or GRAS) standard and is an unapproved food additive. The FDA’s assessment of the ingredient is detailed in a memo added to the agency’s public inventory.

The FDA explained what this is about.

In 2022, Daily Harvest used tara flour in a leek and lentil crumble product which was associated with roughly 400 adverse event reports. The firm took prompt action to voluntarily recall the product and conduct their own root cause analysis, during which they identified tara flour as a possible contributor to the illnesses. To date, the FDA has found no evidence that tara flour caused the outbreak; however, it did prompt the agency to evaluate the regulatory status of this food ingredient.

Daily Harvest makes frozen vegan meals for home delivery.  One of these meals contained tara flour.  Of 26,000 such meals sent out, 400 caused eaters to become desperately sick, some needing hospitalization, some needing surgery (I’ve met some of them).

In my posts, I speculated about why tara flour could cause such severe reactions.

Bill Marler, the food safety lawyer representing a great many of the victims, pushed the FDA to get tara flour out of the food supply before anyone else got sick.  His December 2023 letter reviews what is known about this situation to date.  The FDA paid attention!

Now, two years later, the FDA is doing what it can to prevent tara flour from getting into the food supply.  Good.

Here’s what I’ve had to say about this:

• The Daily Harvest mystery—a cause at last?
• The Daily Harvest recall mystery: update
• Tara flour: a quick review of the research
• What’s up with the Daily Harvest recall?

Here’s what Food Safety News has to say.  It notes more cases than are reported by the FDA, many of them represented by food-safety attorney Bill Marler.

Daily Harvest seems to have survived this tragedy, is still in business, and right on top of currents trends.  Its latest:

Daily Harvest’s January Jumpstart program features GLP-1-focused meal plans:  Daily Harvest’s debut of its GLP-1 Companion Food Collection as part of its quick-to-prep January Jumpstart plan includes “meals made with only real foods that are calorie-conscious while delivering ample vitamins and minerals,” Carolina Schneider, MS, RD, Daily Harvest’s nutrition advisor, told FoodNavigator-USA…. Read more

Thanks to Bill Marler for keeping us all up to date on the Daily Harvest saga.  He keeps up with the literature and writes, Is the Tara mystery closer to being solved?

My most recent post on this mystery was almost a year ago.

To review: Daily Harvest is a company that makes and ships preprepared vegan frozen meals, one of which, French Lentil + Leek Crumbles, has been recalled after several hundred people who ate it developed serious problems with their livers and gall bladders.

This was no trivial incident.  The FDA reported “As of 10/18/2022, there were 393 adverse illness reports in 39 states with 133 hospitalization and 0 deaths.”  But it could not detrmine the specific cause or route of contamination.

My post had breaking news:

The ingredient that caused the illnesses among people who consumed Daily Harvest’s French Lentil + Leek Crumbles has been identified, sort of.  As suspected, it’s the tara flour.  But what’s the toxin in the tara flour?  That, we still don’t know.

Now we have a new study: Is Baikiain in Tara Flour a Causative Agent for the Adverse Events Associated with the Recalled Frozen French Lentil & Leek Crumbles Food Product? A Working Hypothesis. 

In summary, the results of these initial studies support a working hypothesis that the adverse events reported by individuals consuming the Daily Harvest Crumbles product originate from the tara flour ingredient and are due, at least in part, to high levels of nonprotein amino acids (e.g., baikiain). It is further hypothesized that in vivo metabolism of metabolically unstable baikiain results in a toxic metabolite(s) that depletes glutathione and/or is an irreversible enzyme inhibitor (for L-pipecolate oxidase), resulting in adverse events which are dependent on the dose consumed and potentially exacerbated for individuals that have specific genetic predispositions.

Baikiain, which I had never heard of, is an analog of the amino acid proline.  In bacteria, it catalyzes proline destruction.  If it does this in humans, it also might account for the liver toxicity experienced by people who ate the Daily Harvest frozen meals containing tara.

The authors of the tara flour study identified baikiain in the flour.  They gave baikiain to mice, who did not fare well with it.

The hypothesis here is that some people are more susceptible to the toxic effects of baikiain than others.  The French Lentil + Leek Crumbles were sent to 26,000 customers, of which 400 or so got sick, more than 100 of them badly enough to have to be hospitalized; some required surgery.

The lesson here is that food ingredients need better testing.   Whoever makes tara must consider it GRAS (generally recognized as safe) for human consumption.

As Tom Neltner writes,

Tara flour is yet another example of how FDA’s GRAS program is broken—putting the health of Americans at unnecessary risk. FDA should use its big food reboot to fix the program so that we can have confidence in the safety of our food. The agency should also work with members of Congress who have introduced bills intended to fix GRAS and to have FDA reevaluate old food safety decisions in light of new science.

Amen to that.

Last week I did a post on the FDA’s reorganization.   I should have made one other point: the long-standing inadequacy of FDA funding.  For decades, Congress has assigned tasks to the FDA but provided inadequate funding to do those tasks adequately (hence 1% of imported foods are inspected).  Congress also assigns the funding for specific purposes.

Yes, FDA ought to be doing more, but it is not up to the agency to decide how to deploy its funds.

One more point: For long-standing historical reasons, FDA funding comes from congressional Agriculture committees, even though it is an agency of the Public Health Service.  That is one reason why USDA’s food safety programs are funded at so much higher a level than FDA’s.

With that said, the FDA has come out with some recent initiatives of interest.

I.  Front-of-Package labels.  The FDA is proposing to research a front-of-package symbol: “an easy-to-understand, standardized system that is 1) mandatory, 2) nutrient-specific, 3) includes calories, and is 4) interpretive with respect to the levels of added sugars, sodium, and saturated fat per serving.”

It is doing this in response to a petition from the Center for Science in the Public Interest.

The comments that have come in so far are here.

It is examining the use of front-of-pack symbols in other countries.

It also plans to conduct research on consumer understanding of multiple designs.  Here are the prototype packages on which the designs will be tested.

None of these is likely to be as effective as the ones used in other countries.

Here is one of the better options, in my opinion.

To file comments, go here.  It’s important to do this because the Consumer Brand Association (formerly the Grocery Manufacturers Association) and other industry groups are unlikely to accept any labeling scheme that might discourage you from buying a product.

II.  Qualified health claim: cocoa flavanols.  The FDA has approved a qualified health claim for cocoa flavanols and reduced risk of cardiovascular disease.

This was in response to a petition from the Swiss chocolate company, Barry Callebaut.

Here’s what the FDA will allow.  Yes, this is absurd (look at what the FDA has to go through to get to this), but companies must think statements like this will sell their products.

• “Cocoa flavanols in high flavanol cocoa powder may reduce the risk of cardiovascular disease, although FDA has concluded that there is very limited scientific evidence for this claim.”
• “Cocoa flavanols in high flavanol cocoa powder may reduce the risk of cardiovascular disease. FDA has concluded that there is very limited scientific evidence for this claim.”
• “Very limited scientific evidence suggests that consuming cocoa flavanols in high flavanol cocoa powder, which contains at least 4% of naturally conserved cocoa flavanols, may reduce the risk of cardiovascular disease.”
• “Very limited scientific evidence suggests that consuming cocoa flavanols in high flavanol cocoa powder, which contains at least 4% of naturally conserved cocoa flavanols, may reduce the risk of cardiovascular disease. This product contains at least 4% of naturally conserved cocoa flavanols. See nutrition information for_____ and other nutrients.”

III.  GRAS panels.  The FDA has issued final guidance on best practices for panels deciding which ingredients can be Generally Recognized as Safe.

This lays out the guidelines for

• Identifying GRAS panel members who have appropriate and balanced expertise.
• Steps to reduce the risk of bias, or the appearance of bias, that may affect the credibility of the GRAS panel’s report, including assessing potential GRAS panel members for conflict of interest and the appearance of conflict of interest.
• Limiting the data and information provided to a GRAS panel to publicly available information.

A lot of this is headache-inducing.  FDA rulemaking takes forever.  Can’t wait to see how all this turns out.

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The watchdog Environmental Working Group has analyzed the approval process for new food chemicals.  Its disturbing conclusions:

Nearly 99 percent of all food chemicals introduced since 2000 were greenlighted for use by the food and chemical industry,…not by the Food and Drug Administration, the agency responsible for ensuring food is safe.

That’s because food and chemical companies exploited a loophole in the law allowing them to decide which chemicals are safe to consume, contrary to what Congress intended when it enacted food chemical laws in 1958….for 756 of 766 new food chemicals added to the food supply since [2000], or 98.7 percent, these companies have exploited a loophole for substances that are “generally recognized as safe,” or GRAS. The loophole lets them – not the FDA – decide a substance is safe.

The data:

Do we care?  I think we should.

EWG deserves thanks for keeping an eye on this issue.

NutraIngredients.com had an intriguing (to me, at least) article about the latest complaints about FDA’s lack of action on GRAS ingredients—those Generally Recognized As Safe.

A recent paper claims FDA is in the dark as to how many new ingredients have come onto the market via the GRAS process. Only limited progress has been made in the decade since a Congressional report first raised the issue and directed the Agency to make changes, the authors found.”

The article referred to a this paper, Ten years post-GAO assessment, FDA remains uninformed of potentially harmful GRAS substances in foods.

The starting point for this paper is a study done by the Government Accountability Office (GAO) ten years ago: FDA Should Strengthen Its Oversight of Food Ingredients Determined to be Generally Recognized as Safe (GRAS)

The new paper argues that ten years later, the FDA has done little to address the GAO’s concerns.

Since 2010, FDA has addressed only a few of the criticisms regarding its process for establishing a food substance as GRAS. …most critically, FDA has chosen to remain uninformed about food substances self-determined as GRAS by manufacturers…FDA cannot fulfill its statutory obligation for ensuring the chemical safety of the U.S. food supply if it does not know which substances, in which quantities, have been added to foods.

This took me right back to a blog post I did in 2016: The FDA’s unfortunate ruling on GRAS regulations.

The FDA has announced its Final Rule on Substances Generally Recognized as Safe (GRAS).

The FDA explains:

Unlike food additives, GRAS substances are not subject to FDA pre-market approval; however, they must meet the same safety standards as approved food additives…The GRAS criteria require that the safe use of ingredients in human and animal food be widely recognized by the appropriate qualified experts.

Uh oh.  “Appropriate qualified experts?”  Like those selected by the companies themselves?  The FDA has failed the public on this one.

Consumers Union (CU) says

FDA missed a major opportunity to clean up the food system… Companies will still be able to introduce novel substances into food in secret, without having to show they are safe.  The agency also failed to fix the rampant conflicts of interest that affect the review process for ingredients. That is unacceptable and deeply disappointing [CU should know.  It filed comments on the FDA’s proposed GRAS rules in 2011].

Senator Ed Markey (Dem-MA) says

FDA’s Final Rule On Food Safety Process Is A Missed Opportunity…The health and well-being of the American people depend on a meaningful food safety regulatory policy, not a self-graded take home exam that industry doesn’t even have to hand in…I plan to explore whether a legislative remedy is needed to ensure the safety of our food supply [Sen. Markey sent FDA a letter in April asking if the agency needs statutory authority to ensure the safety of GRAS substances and encouraging the FDA to issue guidance on how to prevent conflicts of interest for outside experts evaluating GRAS substances.

The backstory

The FDA’s final GRAS rule is the result of a settlement agreement following a 2014 lawsuit filed by the Center for Food Safety. The basic issue: GRAS substances are not subject to FDA premarket approvals required for food additives.  Manufacturers are allowed to decide for themselves whether their additives are GRAS without informing the FDA. The new rules confirm this self-managed GRAS notification procedure.

I wrote about this issue in an editorial for JAMA Internal Medicine in 2013 when I commented on a study by Tom Neltner and his colleagues on the blatant conflicts of interest in FDA approval of GRAS substances.

Their study examined conflicts of interest among scientific experts serving on panels deciding whether food additives–substances that preserve, flavor, blend, and thicken food—should be deemed generally recognized as safe (GRAS) and exempt from Food and Drug Administration (FDA) premarket approval requirements.  Their findings are alarming. An astonishing 100 percent of the members of 290 expert panels included in their review worked directly or indirectly for the companies that manufactured the additive in question.  Even more alarming, the experts on these panels form a tight professional cadre.  Although 850 people served on the panels, 10 experts served on 27 panels or more, and one of these ten participated in three-quarters of the panels.

My editorial reviewed the lengthy history of FDA’s dithering about the GRAS process.  None of this would matter if all food additives were safe.  But some are not.  I also pointed out:

The problems created by conflicts of interest for the FDA go well beyond those related to food additives and GRAS exemptions.  A recent analysis of requests for waivers by people serving on FDA advisory committees views conflicts of interest as a severe threat to scientific integrity.  As Neltner et al. argue, the lack of independent review in GRAS determinations raises serious questions about the public health implications of unregulated additives in the food supply, particularly the additives that the FDA does not even know about. It also raises questions about conflicts of interest in other regulatory matters.

The FDA’s decision is a loss for public health.

It constitutes yet another reason not to eat products with long lists of additive ingredients.

Addition, August 16

The Environmental Working Group also issued a statement.

EWG is disappointed the FDA has decided to once again ignore its legal obligation to ensure the safety of our nation’s food supply…The so-called “GRAS loophole” – originally intended to only allow known ingredients proven safe to skip regulatory approval – has swallowed the law, permitting novel chemicals to be added to food without government oversight.

Yesterday, Emily Main of Rodale Press sent me this question:

Have you ever heard of this new “sweetness enhancer” that just got approved by the FDA? It’s called Sweetmyx and is made by a company called Senomyx, and is apparently licensed by Pepsi for exclusive use.  All I can really find out about it is that it enhances the sweet flavor of other sugars, so soda companies can use less sugar in their regular products…Do you have any insight about it?

Nope.  Never heard of it..  All I could find out was that Pepsi had an exclusive deal to use it, according to a Bloomberg report.

Sweetmyx, a new ingredient by Senomyx Inc. (SNMX), received approval for foods and beverages, clearing the way for PepsiCo Inc. (PEP) to use it to make lower-sugar beverages taste sweeter.

The Flavor and Extract Manufacturers Association’s expert panel has determined that Sweetmyx is generally recognized as safe as an ingredient, San Diego-based Senomyx said today in a statement. PepsiCo has the exclusive right to use the product, a so-called flavor modifier, in many nonalcoholic drinks under a 2010 agreement.

While I was trying to discover what Sweetmyx is, exactly, this notice came in from the FDA: 

On March 11, 2014, Senomyx, Inc. issued a public statement suggesting that its food ingredient Sweetmyx (also known as S617) was generally recognized as safe (GRAS). The statement appeared to suggest that the U.S. Food and Drug Administration (FDA) had made the GRAS determination. In fact, the agency had not made this determination nor had it been notified by Senomyx regarding a GRAS determination for this food ingredient. The company’s statement has been corrected and now notes that a third party organization made the determination.

A company can make an independent GRAS determination without notifying the FDA. However, the agency does have a voluntary GRAS notification program whereby a company can inform the FDA of the company’s determination. The FDA maintains an inventory of such GRAS Notices on its website, allowing the public to confirm whether FDA has filed and responded to a GRAS notice.

When making a GRAS self-determination, companies should not state or imply that the FDA has made a GRAS determination on their food ingredients.

For more information on the GRAS notification process, please see: Generally Recognized as Safe (GRAS).

Recall from one of my previous posts the shocking gap in FDA regulatory authority over GRAS determinations.

• Manufacturers get to decide whether food additives are safe or not.
• Manufacturers get to decide whether to bother to tell the FDA the additives are in the food supply, and even if they do.
• Manufacturers get to decide who sits on the panels that review the evidence for safety.
  

In the case of Sweetmyx, the company’s consultant says it’s safe so why bother to see if the FDA agrees.

My questions:

• Pepsi: don’t you want FDA approval before putting this stuff in your drinks?
• Chemists: what is Sweetmyx anyway?
• FDA: don’t you think you ought to take a look at this thing?
• Congress: how about insisting that the FDA establish a better system for dealing with food additives

Hey, I can dream.

Additions, March 14:

A reader reminds me that the Center for Food Safety filed a lawsuit to get the FDA to do a better job on GRAS determinations (more information is here).

Another reader points out that Coca-Cola also was flirting with Senomyx a few years ago but evidently gave up the idea.

And another notes that Senomyx’s financial report makes it clear that the company knows it has regulatory issues: “Senomyx may be asked to complete additional studies to evaluate and/or monitor the safety of new flavor ingredients in order to maintain applicable regulatory approvals and/or obtain regulatory approvals outside of the United States.”

The FDA has just announced a proposal to withdraw GRAS (Generally Recognized As Safe) status for trans-fat.

My first reaction: Isn’t trans-fat already out of the food supply?  Hasn’t this been one of the food industry’s greatest public health achievements?

Once the FDA started to require trans-fat to be listed on food labels, food companies quickly stopped using partially hydrogenated oils (the source of trans-fat) and found healthier substitutes.  That’s why most food labels list zero grams trans-fat.

But the FDA allows food labels to say zero trans-fat if its amount is below 0.5 gram per serving.

Some manufacturers are still using a little.  This new initiative will encourage them to get rid of those last little bits.

Contrary to the New York Times headline, this is not exactly a ban on trans-fat.  If trans-fat is no longer GRAS, manufacturers can still file a food additive petition to continue using partially hydrogenated oils.

The Federal Register notice asks for input for the next 60 days.

I say congratulations to all:

• To food companies who worked hard to find ways to substitute healthier fats for trans-fats.
• To the FDA for finally taking care of the trans-fat 0.5-gram loophole.
• To Center for Science in the Public Interest for bringing health problems with trans-fat to public attention.
• To all of the researchers who did the science linking trans-fat to higher LDL-cholesterol levels and to heart disease risk.
• To the New York City health department for banning trans-fats from use in city restaurants.

Americans will be healthier as a result of all of your efforts.

Resources

At the moment, the FDA has not yet posted its Federal Register notice on the GRAS status of trans-fat. When it does, the notice should be available here.

CSPI’s home page on trans fat

The FDA trans-fat home page

FDA consumer materials

• Talking About Trans Fat: What You Need to Know
• What are the different types of fat that a food can contain? How are they different?
• Trans Fat Now Listed With Saturated Fat and Cholesterol (Including Examples of Nutrition Labels)

FDA guidance for industry

• Guidance for Industry: Trans Fatty Acids in Nutrition Labeling, Nutrient Content Claims, Health Claims; Small Entity Compliance Guide
• Federal Register – 2003 Food Labeling rule on trans-fat (68 FR 41434)
• Health Claim Notification for Saturated Fat, Cholesterol, and Trans Fat, and Reduced Risk of Heart Disease

Research

• FDA Health and Diet Survey – 2004 Supplement – Fats and Carbs – A Snapshot of Consumer Knowledge from a Recent FDA Survey
• Trans Fat Basics (CDC)
• Updated Estimate of Trans Fat intake by the U.S. population, 2012