March 20, 2013
Mary Poos, Ph.D., Acting Director
Office of Nutritional Products, Labeling, and Dietary Supplements
Center for Food Safety and Applied Nutrition
U.S. Food and Drug Administration
CPK-1 Bldg. Room 4C-095
5100 Paint Branch Parkway
College Park, MD 20740
Dear Dr. Poos:

Senomyx Inc. is a company that develops taste modifiers that may enable food
manufacturers to reduce levels of such ingredients as salt, sugar, artificial sweeteners, and
monosodium glutamate (MSG). 1 The company has self-affirmed (through FEMA, the Flavor
and Extract Manufacturers Association) that two sweetness enhancers—4-amino-5,6dimethylthieno[2,3-d]pyrimidin-2(1H)-one and 4-amino-5,6-dimethylthieno[2,3d]pyrimidin-2(1H)-one hydrochloride (FEMA No. 4669; JECFA No. 2117; CAS Nos. 12174618-7 and 1033366-59-4); and 3-[(4-amino-2,2-dioxido-1H-2,1,3-benzothiadiazin-5yl)oxy]-2,2-dimethyl-N-propylpropanamide (FEMA No. 4701; JECFA No. 2082; CAS No.
1093200-92-0)—are Generally Recognized As Safe (GRAS). We understand that one or
both of those products are currently being used by food manufacturers. We are writing to
ask the FDA to advise the food industry that “sweetness enhancers” and similar taste
modifiers should be listed individually by name in ingredient statements.
It appears that Senomyx is advising customers that its flavor modifiers may be labeled as
“artificial flavoring” on food labels. According to an article in The New York Times, “Unlike
artificial sweeteners, Senomyx’s chemical compounds will not be listed separately on
ingredient labels. Instead they will be lumped into a broad category—‘artificial flavors’—
already found on most packaged food labels. ‘We're helping companies clean up their
labels,’ said Senomyx's chief executive, Kent Snyder.’” 2

http://www.senomyx.com/flavor_programs/appTech.htm.
Warner M. Food companies test flavorings that can mimic sugar, salt or MSG. The New York Times. April 6,
2005.

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FDA regulations stipulate that artificial flavors actually impart flavor of their own to food:
“The term artificial flavor or artificial flavoring means any substance, the function of which
is to impart flavor…” [boldface emphasis added; italics in the original] (21 CFR
101.22(a)(1)) However, Senomyx has emphasized that its products do not impart flavor:
•

•

Gwen Rosenberg, vice president, investor relations, Synomyx, said: “Nobody else we
know of has a sucrose enhancer [S6973] that does not have any taste on its own, it
just boosts the taste of the sugar that is there.” 3

Employees of Senomyx (and one from Coca-Cola Co.) stated in a scientific paper:
“SE-2 did not taste sweet…and it was not bitter…. the [positive allosteric
modulators] reported in this study are not agonists and do not taste sweet on their
own…” 4 (SE-2 is a synthetic molecule made by Senomyx.)

Furthermore, Senomyx likens its products to flavor enhancers, such as MSG, inosine
monophosphate (IMP), and guanosine monophosphate (GMP). A scientific paper coauthored by employees of Senomyx and another company states:
These molecules work as sweet taste ‘enhancers,’ which possess no taste of their
own but potentiate the sweet taste of sugars. Examples of taste enhancers can be
found in umami taste, which is known for its unique characteristic of synergism.
Purinic ribonucleotides such as inosine-5’-monophosphate (IMP) and guanosine-5’monophosphate (GMP) can strongly potentiate the umami taste intensity of
glutamate and are rare examples of naturally occurring GPCR PAMs. In taste tests,
200 uM IMP, which does not elicit any umami taste by itself, can increase human
umami taste sensitivity to glutamate by 15-fold. 5

The FDA requires MSG (and related protein hydrolysates) to be declared by name on
product labels.
•
•

“Any monosodium glutamate used as an ingredient in food shall be declared by its
common or usual name ‘monosodium glutamate.’" (21 CFR 101.22 (h)(5))

“Because protein hydrolysates function in foods as both flavorings and flavor
enhancers, no protein hydrolysate used in food for its effects on flavor may be
declared simply as ‘flavor,’ ’natural flavor,’ or ‘flavoring.’ The ingredient shall be
declared by its specific common or usual name as provided in 102.22 of this
chapter.” (21 CFR 101.22 (h)(7))

In addition, sweetness enhancers accentuate the sweet taste of sugar, but industry
contends that sweetness is not a flavor. Hence, companies do not lump artificial or natural
Watson E. New fructose enhancers promise “significant amplification” of sweet taste in HFCS. Food
Navigator-USA.com. Sept. 6, 2011.
4 Servant G, Tachdjian C, Tang X-Q, et al. Positive allosteric modulators of the human sweet taste receptor
enhance sweet taste. PNAS. 2010;107:4746-51.
5 Zhang F, Klebansky B, Fine RM, et al. Molecular mechanism of the sweet taste enhancers. PNAS.
2010;107:4752-57.
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non-caloric sweeteners under the term “artificial flavorings,” and labels may state “no
artificial flavorings” on artificially sweetened foods. Sweetness enhancers should not be
permitted to be considered artificial flavorings for purposes of labeling.
Importantly, we believe that consumers would like to know when their taste buds are
being influenced or manipulated by novel ingredients, even ones beneficial to health.

For all of those reasons, FDA should require that Senomyx’s taste modifiers be labeled by
name on food labels and not included in the generic term “artificial flavorings.” We ask the
FDA to notify Senomyx and all other companies that manufacture, distribute, or use taste
modifiers of that labeling requirement.
Thank you for considering our views.
Sincerely,

Michael F. Jacobson, Ph.D.
Executive Director

Lisa Lefferts, MSPH
Senior Scientist
cc: Mike Landa, Jessica Leighton