{"id":10729,"date":"2021-12-21T11:29:25","date_gmt":"2021-12-21T16:29:25","guid":{"rendered":"http:\/\/blogs.edf.org\/health\/?p=10729"},"modified":"2025-05-08T14:11:21","modified_gmt":"2025-05-08T19:11:21","slug":"broken-gras-scientists-safety-concerns-are-hampered-by-fdas-inactions-on-food-chemicals","status":"publish","type":"post","link":"https:\/\/blogs.edf.org\/health\/2021\/12\/21\/broken-gras-scientists-safety-concerns-are-hampered-by-fdas-inactions-on-food-chemicals\/","title":{"rendered":"Broken GRAS: Scientists\u2019 safety concerns are hampered by FDA\u2019s inactions on food chemicals"},"content":{"rendered":"

Maricel Maffini, consultant,<\/em> and Tom Neltner<\/em><\/a>, Chemicals Policy Director <\/em><\/p>\n

A federal district court this fall <\/em>ruled<\/em><\/a> that the Food and Drug Administration (FDA) has the authority to allow food companies to make Generally Recognized as Safe (GRAS) safety determinations for novel chemicals added to food without notifying the agency. The decision followed a lawsuit by EDF and others, in which we challenged this practice. The court agreed, in part, with FDA that an uptick in companies voluntarily choosing to send notices to the agency since the 2016 rule went in effect was a sign that the program was working.\u00a0 We disagree with the court\u2019s conclusion but opted not to appeal. <\/em><\/p>\n

This blog is the second in our Broken GRAS series where we explore how the voluntary notification system works in practice and why it is broken. The <\/em>first<\/em><\/a> dealt with a synthetic chemical called apoaequorin and marketed as Prevagen, a chemical found in jellyfish and used in protein shakes. The company claims the substance helps memory, but FDA has repeatedly raised serious questions about its safety. Despite the agency\u2019s concerns the company continues to sell the product as GRAS.\u00a0 <\/em><\/p>\n

In this blog, we examine another voluntary GRAS notice, this one for GABA, a neurotransmitter naturally produced in the brain and known to slow down certain nervous system activities. It is marketed as a food ingredient despite FDA’s serious concerns with the notice that prompted the company to withdraw it. The agency does not make such information publicly available. We were able to learn of FDA\u2019s concerns through a Freedom of Information Act (FOIA). <\/em><\/p>\n

____<\/p>\n

Companies have the option to voluntarily notify FDA when they determine that a use of a new chemical or a new use of an existing chemical is Generally Recognized as Safe, or GRAS. When they do notify FDA, agency scientists then review the data and supporting information and can ask additional questions. In most of the cases, FDA agrees with the company\u2019s determination and publishes a \u201cno questions<\/a>\u201d letter. In roughly 20% of cases, however, companies ask the agency to stop the process after receiving the scientists\u2019 questions. FDA then stops its review and announces a \u201ccease to evaluate\u201d status in the GRAS notification inventory<\/a>, and that\u2019s the end of it. There is no public record of as to why the company withdrew the notice. In some cases, a brief summary is included in the agency\u2019s response to the cease to evaluate letter published in its website. The company is free to market and sell the substance if it still believes the chemical\u2019s use is GRAS.<\/p>\n

This happened with gamma<\/em> aminobutyric acid (GABA). As you will see, the GABA case is a prime example of the 1) importance of FDA\u2019s scientific review of safety data, and 2) profound implications for health risks when the agency takes no action in response to safety concerns raised by its own experts. A product with the safety concerns we describe below warrants closer examination, regardless of its current market share. Where serious health effects are found, it is important for FDA to act quickly before a specialty product like this one becomes more popular, and its health risks amplified.<\/p>\n

What is GABA?<\/strong><\/p>\n

GABA is a neurotransmitter we all have in our bodies. Its primary function is to modulate communications between nerve cells and reduce neuronal activity. The GABA we make helps us fall asleep, reduces mental and physical stress, lowers anxiety, and creates calmness. It is made in the brain from glutamate, an amino acid commonly found in foods like cheese, meats, fish, eggs, tomatoes, walnuts, and broccoli.<\/p>\n

Many companies currently manufacture and sell GABA as a dietary supplement and promote it as a sleep-aid. However, it appears that FDA has only reviewed the safety of this use once. That review was in response to a 2016 new dietary ingredient notification<\/a> \u2013 the method FDA employs to evaluate ingredients in dietary supplements not in use before 1994. Minnesota-based Green Rose LLC told FDA that its product, Take5, contains GABA and the amino acid L-theanine. FDA objected<\/a> to the notification because it \u201cconsists of one page that is essentially a cover letter,\u201d and did not include basic information like the conditions of use, safety data, and description of the supplement.<\/p>\n

FDA review of GABA uses as food ingredient \u2013 Take 1\u00a0 <\/strong><\/p>\n

Japanese company Pharma Foods International (Pharma Foods) submitted the first GABA GRAS safety determination to FDA (GRN 257<\/a>) in July 2008. The company said GABA would be used as a food ingredient (as opposed to a dietary supplement) added to a \u201cvariety of food products including beverages and beverage bases, chewing gum, ready-to-drink coffee and tea products, and candy at concentrations ranging from 0.04 to 4% in various food types.\u201d Pharma Foods hired the consulting firm Cantox, now known as Intertek,[1]<\/a> to assist with the notification.<\/p>\n

The notification<\/a> states that an expert panel convened by the consulting firm produced a consensus statement concerning the \u201cGRAS status of GABA for use as a food ingredient.\u201d The panel consisted of three university professors, Joseph F. Borzelleca, Ph.D. (Virginia Commonwealth University, School of Medicine), William J. Waddell, M.D. (University of Louisville School of Medicine) and Stephen L. Taylor, Ph.D. (University of Nebraska).<\/p>\n

According to the notice submitted to FDA, the expert panel, \u201cindependently and collectively, critically evaluated a comprehensive package of scientific information and data\u201d compiled by Cantox. FDA scientists, however, pointed out a series of issues, including:<\/p>\n