Several deaths linked to Kobayashi Pharmaceutical Co.’s tainted health supplements have many experts questioning the integrity of research papers cited when marketing these products.

Not only has the scandal rattled public confidence, but concerns and eyebrows are also being raised over industry transparency.

A majority of articles purporting supplement efficacy were written by the employees of the food and drug companies selling them.

This was first made possible in 2015 under then-Prime Minister Shinzo Abe’s growth strategy when “foods with function claims” (FCC) labeling was introduced.

Kobayashi Pharmaceutical’s “benikoji” red yeast supplement touted to lower cholesterol falls under this category, as do products claiming to reduce body fat.

To obtain this label, all companies need to do is file scientific articles with the Consumer Affairs Agency that are supposed to prove an item’s effectiveness.

The government does not screen the products.

A University of Kyoto team has also published its own report about the dubious integrity of these internally produced articles.

The February report stated 70 percent of 32 research papers on FCC food and supplements singled out positive effects. Some of the papers emphasized subjects' reduced body fat, but then made no mention of changes in their weight and waist sizes.

Furthermore, 18 of the 32 articles were carried by the same medical journal. Of these 18, all but one had potential errors, according to the team.

Satoshi Tanaka, a professor of pharmacology at Kyoto Pharmaceutical University who is well-versed in clinical trials, also cast doubt on research papers run by the medical journal.

He said several articles printed in the August 2023 edition alone lacked adequate descriptions of test subjects or statistical analysis despite it being a required procedure.

“Those articles contained statements that would not have made it into the publication if a peer review had been properly conducted,” he said.

The Asahi Shimbun also found a similar trend when it studied the content of scientific articles that food and supplement makers submitted to the agency as the basis for their health claims.

Of roughly 8,000 registered products, the Asahi could access lists of references associated with 7,389 items.

The investigation showed that 3,942 articles, or 53 percent, were published by this specific journal.

In general, a research paper only makes it to print after multiple rounds of revisions corresponding to feedback from reviewers.

While specifics may vary depending on the publication, it is not uncommon for submitted articles to take a few years before they are officially published.

The medical journal in question states publicly that it will publish an article two to three months after its submission.

University of Tokyo pharmacology and toxicology professor emeritus Hideaki Karaki expressed concern about this journal’s practice.

“The publisher is trying to accommodate the needs of makers of functional foods that want to see relevant articles published sooner,” he said. “Such a relationship between a medical journal and businesses is not what the Consumer Affairs Agency anticipated would happen.”

In an interview with the Asahi, the publisher of the medical journal said it will “seriously take” the criticism that it is carrying articles with potential legal baggage.

The publisher added that it has added more reviewers and is overhauling the journal’s submission guidelines.

A WIDESPREAD PRACTICE

Kobayashi Pharmaceutical cited an article run by this journal when it notified the Consumer Affairs Agency of the sale of the cholesterol-reducing supplement.

The paper was also written by an employee of the Osaka drug maker.

The company is not alone in doing this, however. Scientists have also flagged what appears to be a widespread practice of businesses citing papers authored by in-house researchers for the sake of marketing.

“If a researcher employed by a company produces a paper on their products, it raises the question of a conflict of interest and could undermine impartiality,” Karaki said. “The assessment should be made even more rigorously than normal in those cases. It is concerning that it has not happened.”

Japanese medical experts raised the issue in The Lancet, an authoritative British medical journal. The May critique targeted the “insufficient transparency of the research papers” associated with the government’s foods with function claims systems.

“There is an inherent problem with the government setup since to try to show the health effects of food is an incorrect approach in the first place,” said Akihiko Ozaki, one of the authors of the The Lancet article and a doctor at Jyoban Hospital in Fukushima Prefecture.

The Asahi’s study of the medical journal that published the paper on benikoji also indicated that most of the publication’s research papers were written by researchers employed by food and supplement makers.

The Asahi examined 1,672 articles that have been available since 2001 on the journal’s website and employers whose authors were identified.

Of these papers, 1,065, or 64 percent, were written by in-house researchers.

The ratio surges to 74 percent when it comes to articles published from 2015 when FCC labeling was implemented.

“Our basic stance is that authors ought to produce papers responsibly,” Yutaka Arai, chief of the Consumer Affairs Agency, told a news conference in June in response to criticism of the dubious quality of certain research papers.

Following the incident surrounding Kobayashi Pharmaceutical, the agency set up a panel to discuss reforming the system.

Multiple consumer groups blamed the system for allowing makers to market their products simply by filing research papers with the agency.

However, a review of the system was not considered.

As least one consumer group issued a written opinion to the agency calling for a sweeping overhaul of the system, including its abolition as an option.

The agency instead settled on adding a step to have medicine and pharmacology experts provide input when new ingredients are listed by makers claiming health benefits.

Kobayashi Pharmaceutical has since recalled all products containing the ingredient, will no longer process or use it and is covering the medical bills of affected customers.

(This article was written by Ryoma Komiyama and Ryosuke Nonaka.)