{"id":10763,"date":"2022-01-05T08:42:50","date_gmt":"2022-01-05T13:42:50","guid":{"rendered":"http:\/\/blogs.edf.org\/health\/?p=10763"},"modified":"2025-07-08T14:58:32","modified_gmt":"2025-07-08T19:58:32","slug":"broken-gras-its-time-for-fda-to-wake-up-and-protect-consumers-from-dubious-ingredients","status":"publish","type":"post","link":"https:\/\/blogs.edf.org\/health\/2022\/01\/05\/broken-gras-its-time-for-fda-to-wake-up-and-protect-consumers-from-dubious-ingredients\/","title":{"rendered":"Broken GRAS: It\u2019s time for FDA to wake up and protect consumers from dubious ingredients"},"content":{"rendered":"

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

This blog is the third in our <\/em>Broken GRAS series<\/em><\/a> where we explore how the Food and Drug Administration\u2019s Generally Recognized as Safe (GRAS) voluntary notification system for novel chemicals added to food works in practice and why it is broken. <\/em><\/p>\n

In this blog, we examine another voluntary GRAS notice submitted to the FDA, this one for <\/em>Venetron<\/em><\/a>, an extract of Apocynum venetum leaves. It is marketed for sleep improvement and anti-stress and used as a dietary supplement and food ingredient. <\/em>Documents<\/em><\/a> obtained through a Freedom of Information Act (FOIA) request reveal that FDA scientists raised safety concerns about Venetron. Under the broken GRAS system, however, the company that manufactures the ingredient was able to withdraw its notification and continue to market the chemical as GRAS, despite the questions raised by the agency.<\/em><\/p>\n

____<\/p>\n

Japanese company Tokiwa Phytochemical (Tokiwa) voluntarily notified<\/a> the Food and Drug Administration (FDA) in August 2014 that it had determined its extract of Apocynum venetum<\/em> leaves was Generally Recognized as Safe (GRAS). The extract, called Venetron, would be an \u201cingredient in food\u201d at levels up to 100 mg per day, the company said in the notice (GRN 530<\/a>). Tokiwa indicated that Venetron could be incorporated into \u201chealth food product[s], such as tablet[s] or capsule[s],\u201d but did not identify specific foods to which the substance might be added.<\/p>\n

In support of its GRAS determination, the company presented results of preclinical and clinical investigations that examined the safety of the extract in mice and healthy adult male volunteers. They also reported data on the effectiveness of Venetron to treat individuals with mild depression. It convened a panel of three experts \u2012 Drs. Veronika Butterweck (Univ. of Applied Sciences and Arts, Northwestern Switzerland), Sansei Nishibe (Health Sciences Univ. of Hokkaido), and Kuo-Hsiung Lee (Univ. North Carolina at Chapel Hill) \u2012 to review the studies, as well as a \u201chistory of human intake\u201d of Rafuma [another name for A. venetum<\/em>] leaf extract and its use as a dietary supplement in Japan and as a drug in China to treat insomnia, kidney disease, hypertension and heart palpitations.<\/p>\n

Tokiwa said the panel \u201cunanimously concluded that VENETRON\u2122, when used in foods in general at levels providing a daily total intake of 100mg\/person\/day, is safe,\u201d and that the GRAS determination was based on \u201cscientific procedures supported by a history of safe use.\u201d<\/p>\n

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

Tokiwa described Venetron as a brown powder \u201cextracted from A[pocynum] venetum<\/em> leaves and contains not less than 4% of hyperoside<\/a> and isoquercitrin<\/a>,\u201d chemicals that are members of a larger class of plant polyphenols called flavones. The extracted product can then be incorporated into health food \u201cfor anti-stress, anti-depression and sleep improvement,\u201d the company said.<\/p>\n

FDA had (many) questions<\/strong><\/p>\n

After receiving the GRAS notification, FDA scientists asked the company whether the extract was intended to be used in food or as dietary supplement. If the former, the FDA asked Tokiwa to indicate which types of food Venetron would be used in. A few days later, the company confirmed that the extract was \u201cintended to be used as a dietary supplement.\u201d In response, the FDA said Tokiwa should contact the agency\u2019s dietary supplement program and concluded that it \u201cintended to stop evaluation of your GRAS notice.\u201d<\/p>\n

However, a few days later the company reached out to FDA again saying that the extract \u201cis intended to be used in conventional food, such as beverage, jelly, as well as supplement. Therefore, we hope you will continue the evaluation of our notice.\u201d<\/p>\n

As the company requested, FDA scientists continued their review of the safety assessment, outlining a number of concerns. The FDA said Tokiwa\u2019s notice:<\/p>\n