With two more deaths reported Thursday, a total of four people have died after taking a supplement containing beni kōji (red fermented rice) made by Kobayashi Pharmaceutical, with about 93 hospitalized.

The Osaka-based company and the health ministry are scrambling to find answers as the cause of the death remains unknown. Kobayashi Pharmaceutical, along with other companies who use beni kōji in their products, are issuing voluntary recalls as public concern grows over the substance.

However, experts say that there are no dangers in the beni kōji itself and that the health hazard was most likely caused by some unknown substance that made its way into batches of the supplement produced during a certain time frame.

The drugmaker held a general shareholders’ meeting on Thursday morning and a health ministry panel of experts began an investigation later in the day.

“Relevant ministries and agencies will continue to work together to do their utmost to ensure food safety, including identifying the substance that caused the health hazard as well as how it ended up in the product,” Chief Cabinet Secretary Yoshimasa Hayashi said Thursday.

Kobayashi Pharmaceutical is set to hold a news conference on the issue on Friday.

What do we know so far?

News of a problem first broke last Friday, when Kobayashi Pharmaceutical issued a voluntary recall of their line of dietary supplements after 13 people reported experiencing kidney problems after taking it, of which six were in a condition severe enough for them to be hospitalized.

The recall was issued on about 300,000 packs of three of their products that contained beni kōji. They were all advertised as supplements that help lower cholesterol, blood pressure and visceral fat.

On Monday, the company announced that the number of hospitalizations had grown to 26, after having confirmed 20 additional cases over the weekend through a hotline they established for the issue.

The following day, the first fatal case was reported when the company disclosed details on an individual who had been taking one of their supplements, Beni Koji Koresute Herupu (roughly translated to Beni Koji Cholesterol Help), for about three years since April 2021 and had died of a kidney disease last month.

A second death linked to the same product was reported on Wednesday, with hospitalizations shooting up to 106.

On Thursday, an additional two deaths were reported by the company, bringing the total number of deaths up to four. Both cases were reported by bereaved family members who say the deceased were taking the beni kōji supplement prior to their death.

An Investigation into a possible link between the deaths and the consumption of the supplements is underway. The company has said it is highly likely that the health problems were caused by an unintended substance contained in the beni kōji produced between July and October last year.

Under instructions from the health ministry, the Osaka Municipal Government ordered Kobayashi Pharmaceutical on Wednesday to recall the three products.

The Consumer Affairs Agency is set to review 7,000 government-reported food products that claim to promote health and to investigate whether any health hazards have been caused by them.

What is beni kōji?

Beni kōji, or red fermented rice, is made by fermenting rice with a reddish-purple mold called monascus purpureus. It has been used as food coloring and is also said to have health benefits, such as lowering cholesterol.

“Beni kōji contains the same substance used in the medicine we (as doctors) most often prescribe to lower cholesterol levels,” explains Rei Shibata, a doctor at Nagoya University Graduate School of Medicine. “That’s why recently it has been used most commonly in health supplements that advertise the benefits of lowering cholesterol.”

Shibata added that since beni kōji itself is a safe substance, the dangerous side effects caused by Kobayashi Pharmaceutical’s products were most likely due to something that was introduced or mixed in during the manufacturing process.

In the past, there have been reports of health hazards caused by products using beni kōji in Europe, with the EU having commissioned in 2019 a regulation for food supplements on maximum levels of citrinin — a substance sometimes found in beni kōji said to produce mycotoxin, which is thought to cause kidney diseases.

However, Kobayashi Pharmaceutical has said that citrinin was not found in their products.

“That’s most likely true since the strain of beni kōji that Kobayashi Pharmaceutical uses do not generate citrinin to begin with — which would mean that there must have been some other ‘factor x’ (substance) that was mixed into the product in the manufacturing process,” Shibata said.

He says the main priority should be pinpointing what the unknown substance is in order to figure out how much of it would need to be ingested to cause kidney disease and how consumers can be treated going forward.

For those concerned about having consumed other beni kōji products, Shibata says the first step is to stay calm and identify whether the consumed product contains substances that have been flagged by Kobayashi Pharmaceutical as being hazardous.

“If you have taken the specific products, it may be necessary to consult your doctor,” especially if you are experiencing symptoms like swelling or irregularity in urination, Shibata said.

“It’s more risky for those taking the supplements since it's something you consume everyday — but nothing to be as concerned about if you’ve only had (the product) once.”