Company executives may feel a scientific study gives a misleading view of their food product.

KANSAS CITY — Company executives may feel a scientific study gives a misleading view of their food product. Researchers may feel the study contains information about an ingredient that needs a further explanation or even a correction. A response may seem necessary, but consider the investment.

“It takes about 20 papers to correct a negative,” said Roger Clemens, Ph.D., an advisory council member for FMC Corp., Philadelphia. “A tremendous amount of work and money and time goes into correcting something that’s negative in the social media or even in a scientific publication.”

Industry efforts have defended such ingredients as high-fructose corn syrup, caramel color and aspartame. Now, FMC Corp., which made $3.28 billion in sales in fiscal year 2015, is sticking up for carrageenan, seeking ways to convince consumers and food companies that the red seaweed is safe when used as a food ingredient. Published work already has appeared in a scientific journal and a consumer web site.

“In the case of carrageenan, there is a century-long history of anecdotal evidence supporting carrageenan safety, as well as decades of research performed by the most respected research groups in the field, and we have commissioned much of that research,” said Amy O’Shea, health and nutritional global marketing director for FMC Corp. “Our customers know that in a wide variety of applications carrageenan is the ideal stabilizer and the only one that performs efficiently without altering things like taste or color.”

Yet in 2014 WhiteWave Foods Co., Broomfield, Colo., announced plans to remove carrageenan from its Silk and Horizon Organic products because of consumer concern.

“Once a consumer group has made up its mind, or even a company has made up its mind, it’s not going to change,” said Dr. Clemens, who is also an adjunct professor of pharmaceutical sciences and associate director of the regulatory science program at the University of Southern California’s School of Pharmacy. “You realize those (changes) are linked to sales. They are linked to consumerism. They are linked to perception. When you look at those linkages, a company is not going to change. They are not going to say, ‘Oh, my gosh. I made a mistake.’”

Reasons to respond

Companies still should consider different ways to respond to studies, said Kantha Shelke, Ph.D., principal of Corvus Blue, L.L.C., a food science and research firm based in Chicago.

“It is something about lies, damned lies and scientific studies that can sometimes take a life of their own to perpetuate the misinformation (at a) faster pace than the truth can take hold,” she said. “The result today can range from mildly negative and disparaging to brutally hard on the business and even perceived integrity of the affected company.

“It is really important for companies to take charge of their business and to address the issue on hand and underlying reason for the discrepancy(ies) to help the media and the public-at-large understand that the scientific study is not necessarily a true reflection of their portfolio of products or processes.”

Recent financial results show why FMC Corp. has reason to defend its ingredients. Fourth-quarter revenue in fiscal year 2015 for FMC Health and Nutrition was $172 million, 10% lower compared to the fourth quarter of the previous year, driven by lower carrageenan and alginate sales along with the impact of a weaker euro.

FMC Corp. has funded research for a paper that appeared on-line Nov. 23, 2015, in Food and Chemical Toxicology. Myra L. Weiner, Ph.D., a board certified toxicologist and president of TOXpertise, L.L.C., Princeton, N.J., authored the study. She has published studies on carrageenan that date to the late 1980s and worked for 29 years at FMC Corp.

Dr. Weiner said some carrageenan studies used bad or tumor-derived cells. Others used poligeenan, or degraded carrageenan, which is possibly carcinogenic in humans. The Food and Drug Administration only permits food grade carrageenan in food. Carrageenan suppliers provide certificates of analysis, Dr. Weiner said. Other studies had animals such as rodents consume carrageenan in ways that humans would not consume carrageenan.

Dr. Weiner’s paper called for better methods for studying food additives in general.

“Interpretation of new studies on food additives should consider the interaction of food additives with the vehicle components and the appropriateness of the animal or cell model and dose-response,” the paper said.

Dr. Clemens wrote an article that appeared on the WebMD web site and was more targeted toward consumers. Besides providing evidence on the safety of carrageenan, he explained how the ingredient gives a smooth mouthfeel in food and keeps chocolate from separating from the milk in chocolate milk.

Dr. Shelke said companies in general should consider writing a letter to the editor of the journal that originally published a study shedding a negative image on their product. A company could write a follow-up press release citing the study and how the company’s portfolio does not come under the scientific finding. Trade publications, company web sites and social media outlets are other options.

“If the implications of the scientific study touch upon regulatory aspects of the company’s product, then a note to the F.D.A., U.S.D.A. or the relevant governing body would be a sensible way to address everyone that matters,” Dr. Shelke said.

She urged caution about whether to point out how a study might be flawed.

“It would be more productive to explain the differences between the conditions of the study and the company’s line of work than to throw stones and cast the study as misleading or flawed,” Dr. Shelke said. “A simple ‘here’s what the study found’ plus ‘here’s why these do not apply to our products’ is usually more effective in changing the reader’s mind than an outwardly defensive or offensive approach.  The forum for this should be wherever the initial report was published and wherever audiences that matter can be reached.”

Views on carrageenan

The F.D.A. already supports the use of carrageenan as a food ingredient. A Joint F.A.O./W.H.O. Expert Committee on Food Additives (JECFA) supported carrageenan on July 2, 2014, when it gave conclusions and summaries on the safety of nine food additives.

“The committee concluded that the use of carrageenan in infant formula or formula for special medical purposes at concentrations up to 1,000 mg per liter is not of concern,” the report said.

The Center for Science in the Public Interest, Washington, recommends “caution” in the intake of carrageenan, noting that food grade carrageenan does not cause cancer in animals but it does contain small amounts of degraded carrageenan, or poligeenan, that is possibly carcinogenic in humans.

“While any possible cancer risk would be quite small, some people may wish to err on the side of caution and avoid carrageenan,” the C.S.P.I. said.

In comparison, the C.S.P.I. also recommends “caution” in the intake of monk fruit extract, a natural sweetener.

“This product has not been well tested in animals,” the C.S.P.I. said. “It is derived from a fruit that has been consumed in China for at least several hundred years and used as an herbal medicine for the past several decades. So it may well be safe although any chronic adverse effects might easily have escaped detection.”

The Cornucopia Institute, Cornucopia, Wis., has voiced problems with carrageenan. In a March 2013 report The Cornucopia Institute said animal studies have shown food grade carrageenan causes gastrointestinal inflammation and higher rates of intestinal lesions, ulcerations and even malignant tumors. The report also featured specific people giving examples of how they believed carrageenan had been responsible for their digestion problems, ranging from stomach cramps to diarrhea to vomiting.

In a letter dated March 15, 2013, and sent to the Food and Drug Administration, the Cornucopia Institute stated that a trade group for carrageenan manufacturers had found samples of food-grade carrageenan that contained higher than 5% degraded carrageenan.

More than a year after the Cornucopia letter, the WhiteWave Foods Co. announced plans to remove carrageenan from its Silk and Horizon Organic products. A Facebook posting on Aug. 21, 2014, for Silk said, “Even though it is safe, our consumers have told us they want products without it.”

Blogger Vani Hari, also known as “The Food Babe,” applauded the move and urged her readers to avoid all products industrywide that include carrageenan on the ingredient list.

FMC Corp. will continue to defend carrageenan.

“We respond promptly and carefully to traditional science, trade and consumer media regarding carrageenan safety,” Ms. O’Shea said. “In social media, we engage in an honest and transparent way to educate consumers or correct misinformation.

“We answer to food regulatory agencies around the world, and we respond quickly to questions and initiate conversations about the quality of carrageenan science whenever it is appropriate.”

|||READ MORE: Singling out HFCS|||

A study found no evidence that commercial cola beverages sweetened with either sucrose or HFCS have significantly different effects on hunger, satiety or short-term energy intakes.

Singling out HFCS

Scientific studies may lead to consumers having doubts about, or showing interest in, an ingredient. Examining the studies more closely may lead to different reactions on the safety or the effectiveness of an ingredient. The dose and the setting should be considered. A preliminary study still may need to be peer-reviewed.

A study appearing in the April 2004 issue of The American Journal of Clinical Nutrition contributed to people associating high-fructose corn syrup with a national obesity epidemic, but the researchers never suggested sugar should replace HFCS in foods or beverages. The researchers found HFCS in 1970 represented less than 1% of all caloric sweeteners available for consumption in the United States. By 2000, the percentage had risen to 42%.

“We propose that the introduction of HFCS and the increased intake of soft drinks and other sweetened beverages have led to increases in total caloric and fructose consumption that are important contributors to the epidemic of obesity,” they said.

The study provided a hypothesis that replacing caloric sweeteners, which would include both HFCS and sugar, with non-caloric sweeteners in soft drinks and juice drinks would help reduce the prevalence of obesity.

Since the study came out, the Corn Refiners Association, Washington, has spent more than a decade defending HFCS and arguing against the idea of blaming one ingredient for an obesity epidemic. The Corn Refiners Association and the American Beverage Association helped to fund a study that appeared in The American Journal of Clinical Nutrition in 2007. The study involved 37 people who drank cola sweetened with sucrose or HFCS.

“There was no evidence that commercial cola beverages sweetened with either sucrose or HFCS have significantly different effects on hunger, satiety or short-term energy intakes,” the researchers concluded.

|||READ MORE: Consider the dose|||

The F.D.A. said it has no reason to believe there is any immediate or short-term danger presented by 4-MEI at the levels expected in food from the use of caramel coloring.

Consider the dose

The state of California in 2011 placed 4-methylimidazole (4-MEI) on its Proposition 65 list of substances that may cause cancer. The ruling meant that businesses must provide a warning if they manufacture or sell products in California that cause exposure to significant amounts of 4-MEI, which is found in Class III and Class IV caramel color used in soft drinks.

The California ruling may call into question what “significant amounts” are.

Findings from the National Toxicology Program, Research Triangle Park, N.C., in January 2007 were the basis of the California ruling. The National Toxicology Program gave rats 625 parts per million (p.p.m.) to 2,500 p.p.m. of 4-MEI in their feed. Mice received 312 p.p.m. to 1,250 p.p.m. of 4-MEI in their feed. Researchers concluded 4-MEI caused lung cancer in mice and that 4-MEI may have been associated with female rats developing leukemia.

The results failed to sway the U.S. Food and Drug Administration.

“These N.T.P. studies were conducted in rodents at levels of 4-MEI that far exceed current estimates of human exposure to 4-MEI from the consumption of Class III and Class IV caramel coloring in food products such as colas,” the F.D.A. said and added, “Based on the available information, F.D.A. has no reason to believe that there is any immediate or short-term danger presented by 4-MEI at the levels expected in food from the use of caramel coloring.”

|||READ MORE: Consider the setting|||

The F.D.A. continues to state azodicarbonamide may be used in dough conditioners at a level of less than 45 parts per million.

Consider the setting

Blogger Vani Hari, also known as “The Food Babe,” in February 2014 began a petition to get the Subway restaurant chain to remove azodicarbonamide (ADA), a dough conditioner, from its bread. She pointed out that ADA is used to make yoga mats and that the World Health Organization has linked ADA to respiratory issues, allergies and asthma.

The W.H.O., however, did not examine the use of ADA in food in a Concise International Chemical Assessment Document released in 1999. Instead, it detailed the issue of ADA and human health in the working environment, such as places where ADA was used in the manufacture of products.

“On the basis that azodicarbonamide is a human asthmagen and that the concentrations required to induce asthma in a non-sensitive individual are unknown, it is concluded that there is a risk to human health under present occupational exposure conditions,” the W.H.O. said in the 1999 report.

The F.D.A. continues to state ADA may be used in dough conditioners at a level of less than 45 parts per million.

A study appearing in the Sept. 4, 2011, issue of the Journal of Agricultural Food Chemistry did address ADA’s use in food. Researchers from the University of Hebei in China found ADA partially degrades in the heat of processing to form trace amounts of semicarbazide, which shows carcinogenicity and has been shown to cause tumors. The researchers found semicarbazide in flour treated with ADA.

|||READ MORE: Be wary of preliminary studies|||

Fifth Quarter contains 40% more protein, calcium and electrolytes than conventional milk.

Be wary of preliminary studies

Peer review and publication may lend credence to studies.

A news release from the University of Maryland’s Maryland Technology Enterprise Institute stated, “This press release refers to study results that are preliminary and have not been subjected to the peer review scientific process.” The release relates to Fifth Quarter Fresh, a high-protein chocolate milk, and cognitive and motor function. Fifth Quarter contains 40% more protein, calcium and electrolytes than conventional milk.

A study involved 474 football players from 7 high schools in Maryland during the 2014 season. Fifth Quarter Fresh helped the players improve their cognitive and motor function, even after experiencing concussions, according to the release.

The Maryland Industrial Partnerships program, which jointly funds commercial development projects that team Maryland companies with University of Maryland faculty, was involved in the study., which evaluates health care journalism, advertising, marketing, public relations and other messages that may influence consumers, said it found flaws in the news release. said the news release did not say if the study measured intake of other milk or included a placebo control, did not say if the study had been peer-reviewed or published, and did not disclose any relationship between the research and the manufacturers and distributors of Fifth Quarter Fresh.

|||READ MORE: Design issues arise in carrageenan studies|||

Carrageenan, when used as an ingredient, may keep chocolate from separating from the milk in chocolate milk.

Design issues arise in carrageenan studies

Myra L. Weiner, Ph.D., a board certified toxicologist, has published studies on carrageenan that date to the late 1980s. She worked for 29 years at FMC Corp., Philadelphia, and now serves as president of TOXpertise, L.L.C., Princeton, N.J.

Over the decades Dr. Weiner has noticed flaws and misleading information in carrageenan studies. She provided details on study flaws, along with guidance on better ways to conduct studies, in a paper entitled “Parameters and pitfalls in the conduct of food additive research, Carrageenan as a case study.” It appeared on-line Nov. 23, 2015 in Food and Chemical Toxicology. FMC Corp. provided funding.

Here are some ways that carrageenan studies may go astray, according to Dr. Weiner’s paper:

Bad cells: Cell-based models have been used in carrageenan studies, but tumor-derived cell lines may differ from normal tissues. Many in vitro studies of carrageenan have used the NCM460 cell line. As early as 2007, INCELL, the provider of NCM460 cells, reported the cell line might be tumorigenic. At least 12 in vitro studies used the NCM460 cell lines between 2007 and 2015.

“Just from a scientific point of view, it makes sense to look at those studies again in light of the change of the cells,” Dr. Weiner said. “That may change the conclusion, but that is really up to the journal and the authors of those papers (to re-evaluate the studies).”

Poligeenan vs. carrageenan: Poligeenan also has been called degraded carrageenan. Poligeenan has different molecular weights, physical/chemical properties and toxicological properties than carrageenan, but some studies have confused the two.

“It has been an issue for a while and has created misconception in social media and in the literature, and that’s because some researchers may be using poligeenan, or the old term was degraded carrageenan, but called it carrageenan,” Dr. Weiner said. “If you read the description, you have to dig down to what is actually said in a paper, and if you read the description of their test material, you will see that it was possibly the degraded form, which is a different toxicity and has different properties.”

Regulatory agencies such as the Food and Drug Administration and the World Health Organization only permit food grade carrageenan in food. Carrageenan suppliers provide certificates of analysis.

Consumption of carrageenan: It is important to have animal study designs mimic the use being evaluated. Carrageenan remains bound to protein in diet, milk, infant formula and liquid nutritional supplements. In animal studies, it will bind to protein in rodent chow.

In some animal studies, however, carrageenan was added to drinking water and thus did not bind to protein. These studies do not model humans’ exposure to foods and beverages with carrageenan.

Other studies have found carrageenan caused swelling or inflammation when injected into rats’ paws.

“If you inject it, yes, you will get a response,” Dr. Weiner said.

However, eating carrageenan will not cause swelling/inflammation, she said.