Giloy (Tinospora cordifolia), widely promoted as an immunity booster during COVID-19, has been linked to cases of drug-induced liver injury — ranging from mild enzyme elevation to acute liver failure — in several Indian case series. If you’ve been taking giloy or other herbal supplements and notice jaundice, dark urine, or unusual fatigue, get liver function tests done promptly.

For evaluation of suspected herbal or drug-induced liver injury, consult Dr. Chetan Kalal, DM Hepatologist at Gleneagles Hospital, Mumbai.

The Indian government has embarked on a no-holds-barred giloy promotion spree in the last two years, through the AYUSH and health ministries.
According to doctors, giloy is forbidden for people who suffer from autoimmune disorders, and can lead to death if it is consumed in sufficiently large quantities.
But no government agency has warned that people with autoimmune disorders should avoid giloy – a reckless position exacerbated by uncritical media coverage.

New Delhi: The Ministry of AYUSH published a statement on February 16, 2022, on giloy – a plant that features in many Ayurvedic recipes. The ministry, and the Indian government by extension, has widely publicised this herb as an “immunity booster” during the COVID-19 pandemic. “Certain sections of the media have falsely linked … giloy/guduchi with liver damage,” the ministry statement read. “The Ministry of AYUSH reiterates that giloy/guduchi (Tinospora cordifolia) is safe and as per available data, guduchi does not produce any toxic effect.” Curiously, there have been no recent media reports criticising giloy. The most proximate event The Wire Science could find was a list of questions The Wire Science had sent to the Ministry of AYUSH, seeking its response to a study that had criticised the willy-nilly consumption of giloy as an “immunity booster”. Nonetheless, several media outlets reported the statement, many verbatim. Some people consume the herb raw. Others prefer Ayurvedic ‘preparations’ in the form of capsules, powders or juices. Whenever giloy has propped up in a negative context in the past, the AYUSH ministry has been quick to issue a statement defending it. The first such release appeared on July 7, 2021. It was responding to a scientific study published in the Journal of Clinical and Experimental Hepatology on July 2. The study revealed that the mindless consumption of giloy was contributing to liver toxicity, specifically drug-induced liver injury (DILI). The study’s findings were based on detailed case studies of six people who had consumed giloy and developed DILI. According to the study paper: “Tinospora cordifolia (giloy) consumption seems to induce an autoimmune-like hepatitis or unmask an underlying autoimmune chronic liver disease, which may support its immune stimulant mechanism. However, the same mechanism can cause significant liver toxicity, and we recommend that caution be exercised in the use of this herb, especially in those predisposed to autoimmune disorders.” The government’s immediate reaction was to completely dismiss the study. In its statement, the AYUSH ministry said: “The authors of the study have not analysed the contents of the herb that was consumed by the patients… In fact, there are many studies that point out that identifying the herb not correctly could lead to wrong results. A similar looking herb Tinospora crispa might have a negative effect on the liver.” That is, the government wanted to know if the authors knew whether the six people had consumed Tinospora cordifolia or Tinospora crispa. The latter is poisonous. The ministry suggested the researchers consult an expert in botany. It’s a known fact that the two plants are impossible to tell apart with the naked eye. Even Ayurveda experts can’t do so. And both are available in the market, often labelled ‘giloy’.

More than six months after the study was published, The Wire Science spoke to Dr Aabha Nagral, one of the study’s authors and a senior hepatologist

. She said that of the six patients, four had consumed the raw herb: “Our follow-up research has proved that the four consumed Tinospora cordifolia only,” she said. Dr Nagral also said she and her colleagues will soon be publishing a paper that demonstrates this fact: that the patients in question didn’t consume a known poisonous substance, yet suffered liver toxicity. “The two others had taken giloy as part of a concoction of immunity-boosting products from two popular companies,” she added. “So legally, those companies couldn’t have mixed the poisonous form.” Update, November 14, 2022, 10:24 am: Abha Nagral’s findings, which she had shared with The Wire Science in February 2022, were published by the Journal of Clinical and Experimental Hepatology on November 6. A botanical analysis plus other studies confirmed that all their study subjects who had suffered serious liver injuries had indeed consumed Tinospora cordifolia and not Tinospora crispa. A Hyderabad-based hepatologist also said he has encountered many such patients in the last two years. “Forget about these researchers – do I tell a patient who comes to me with DILI symptoms to bring the herb on the next visit? Even if she does, how am I supposed to distinguish between the two forms?” he asked. He didn’t wish to be named because he feared reprisal by the Ayurveda industry. “We are trolled on social media. We are served legal notices just for speaking our minds. It is too much trauma to take,” according to him. Indeed, it wasn’t just the ministry that went after Dr Nagral and her colleagues. The journal’s editor also received numerous letters from Ayurveda medical colleges and companies manufacturing supposedly Ayurvedic drugs. These included the Patanjali group; the JSS Medical College, Mysore; the State Ayurvedic College, Lucknow; and the All India Institute of Ayurveda, Delhi. They all case doubt on the research paper on various pretexts. The most common argument was “giloy has traditionally proven safe”. The Ayurveda proponents also claimed that a thyroid drug or a fungal infection could have caused the toxicity. The journal published all these responses. At the same time, many hepatologists reported to the same journal that they were seeing patients with DILI after they had consumed giloy. Also read: Face It: The Indian Government Is Peddling Pseudoscience Sandeep Kumar, 32, is a resident of Simariya village in Ambedkarnagar district, Uttar Pradesh. His family of eight consumed giloy as kaadha

during the second wave of India’s COVID-19 outbreak. His father, aged 58, took it everyday, first thing in the morning. He was diabetic and had high blood pressure.

“We had read in a newspaper that giloy was good at preventing coronavirus infections,” Kumar told The Wire Science. “Our neighbours also took it.”

Two months later, his father developed jaundice and was admitted to King George’s Medical University (KGMU), Lucknow, and soon after died there. Doctors told Kumar that his father died due to excessive consumption of giloy. Kumar is still in a fix about how no one else in the family suffered any adverse events, whereas his father died. The answer is clear: a certain section of the population cannot consume giloy, raw or packaged, doctors said. “This herb is a strict no-no for those who suffer from any autoimmune disorders, like hypothyroidism or type-2 diabetes,” Dr A.K. Patwa, a doctor at KGMU, told The Wire Science. Sandeep’s father was suffering from the latter. Autoimmune disorders are those in which the body’s immune system attacks an organ in a way that compromises the organ’s ability to function normally. Dr Nagral’s study pointed to the same contraindications. (Note: Recent research has suggested that type-2 diabetes could be an autoimmune disease. Hypothyroidism is not an autoimmune disorder but is often caused by one.) Yet the Indian government has embarked on a no-holds-barred giloy promotion spree in the last two years, with the participation of every official from the AYUSH ministry to the health ministry. The national COVID-19 taskforce chairman Vinod K. Paul has asked people on more than one occasion to consume kaadha and giloy. In September 2021, the ministry launched a “campaign to distribute prophylactic medicines” against COVID-19. A statement at the time read:

“The kit of Ayurveda prophylactic medicines for COVID-19 contains Sanshamani Vati, which is also known as Guduchi or Giloy Ghan Vati and Ashwagandha Ghan Vati. The kit and the guidelines have been prepared by the Central Council for Research in Ayurvedic Medicines (CCRAS).”

But no government agency has warned that people with autoimmune disorders should avoid giloy – a reckless position exacerbated by uncritical media coverage and advertisements in newspapers and magazines. Kumar himself is regretful. “My father was very mindful of not consuming anything that would worsen his diabetes,” he said. “We never imagined giloy was harmful to a diabetic.”

According to Dr Pavan Hanchanale, a hepatologist in Jupiter Hospital, Pune, “Giloy enhances the immune response, but it hurts the liver in some people. Thus they end up with autoimmune liver diseases.” Even as the Indian government and some Ayurveda proponents vehemently contested the conclusions of Dr Nagral’s paper, three scientists from the US, all part of the US DILI network, investigated the paper themselves. They concluded that there was a meaningful temporal (i.e. time-related) relationship between exposure to giloy and the patients’ clinical picture. That is, they found that the giloy-based drugs could likely have induced autoimmune hepatitis in the six patients. The condition couldn’t have emerged in a vacuum. They also advised systematic investigations if such cases continue to appear. The Indian government hasn’t conducted any such follow-up, however. This also means the side-effects of consuming giloy could be hidden from the AYUSH ministry’s pharmacovigilance network. All the hepatologists to whom The Wire Science spoke said the incidence of DILI cases had increased during the country’s COVID-19 epidemic, especially during each wave. And as each wave waned, so did the DILI cases.

Dr Hanchancle, in Pune, said he had seen two or three people with giloy-induced illnesses every month. “Earlier, I used to see one such patient in a couple of months.”

“COVID-19 has exposed a large population to herbal drugs. Earlier also, people used to consume, but not in such high quantities,” Kishore Patwardhan, a professor of Ayurveda at Banaras Hindu University (BHU), Varanasi, told The Wire Science. “So if the incidence of adverse effects was, for example, one in one million, that would be hardly noticed. Now, with consumption going up, we see more people coming in with adverse effects.” Also read: The Modi Government’s Pseudoscience Drive Is More Than an Attack on Science The study by Dr Nagral and her colleagues was the first of its kind in the country, to link DILI with giloy. And it wasn’t the last. The biggest study to date on this front was a multi-centre study undertaken at 13 hospitals in nine cities. It was published in January 2022 in the Journal of the American Association for the Study of Liver Diseases. Its authors presented no less than case studies of 43 patients with acute hepatitis, acute worsening of chronic liver disease and liver failure, all thanks to giloy. Of the 43 patients, four died. Two had to undergo liver transplants. The rest recovered. “Some patients recover just by giving up giloy,” according to the Hyderabad-based hepatologist. “But some suffer from persistent liver injury. They have to remain on drugs for two to three years.” The paper also said giloy could “unmask” autoimmune hepatitis in people who had a silent form of the disease.

Dr Chetan Kalal, of Mumbai’s H.N. Reliance Hospital and one of the trial investigators, anticipates rebuttals from pro-Ayurveda groups. “Yes, liver diseases can occur due to alcohol, liver-specific viruses, other viruses, post-COVID effects and existing autoimmune disorders,” he said.

“But we ruled out all these and related aetiologies one by one. We conducted other necessary investigations, too. We were left with one cause and that was a drug-induced factor,” Dr Kalal said.

Ayurveda and side-effects

All these hepatologists emphasised one point: that they were not against giloy per se, but against the impression that Ayurvedic products couldn’t have side effects. They can. They all agreed that people should consume giloy only on the prescription of a registered practitioner, and not self-medicate. The practitioner should also clearly state the dose. This is also important to ensure that if a person suffers debilitating side-effects, the practitioner can be held accountable. Next, they asked that the government regulate the sale of certain Ayurvedic products. The government is already aware that a poisonous simile of giloy exists, that it is hard to distinguish from real giloy and that it is available in the market. The AYUSH ministry had published a statement in October last year that covered a part of these grounds: “It is observed that different species of Tinospora are available and only Tinospora cordifolia should be used in therapeutics, whereas similar looking species like Tinospora crispa may manifest adverse effects. Thus, it is reiterated that guduchi is a safe and effective Ayurveda medicine, however it is advisable to use it in consultation with a qualified, registered AYUSH physician.”

But the experts said it must step up the awareness. Some hepatologists also told The Wire Science of patients who had grown giloy in their gardens or backyards for their consumption, without having to visit a pharmacy. This complicates regulation.

Finally, they asked the Indian government to specify that giloy is contraindicated for some people, that it set out these categories in detail and, again, spread awareness. “Some tuberculosis drugs cause liver toxicity, but they aren’t banned. Doctors prescribe them carefully,” Dr Kalal said. Excess paracetamol can also damage the liver but nobody criticises the drug. “Why can’t it happen with giloy?” he asked. In a prospective study, researchers with the Indian Network of DILI documented 1,288 cases of DILI from 2013 to 2018. The injury in 46% of cases had occurred due to tuberculosis drugs. The second biggest cause was complementary and alternative medicines (CAMs), to the tune of 14% (see chart below). CAMs include Ayurveda and homeopathy. However, Dr Kalal said that in his experience CAMs have been responsible for DILI half the time.

Common causes of DILI in India

Denial Apart from the government and people with a commercial stake in Ayurveda, there is a third group that responds with denial to diagnoses that pin the blame on herbal products: the patients themselves. Often their first response is: ‘If the entire family is fine except me, this couldn’t have been the drug.’

“Even some of my colleagues in other departments were not ready to accept until the multi-centre study got published,” Dr Patwa, of KGMU, said.

The Wire Science sent an email to Rajesh Kotecha, the secretary of the AYUSH ministry, on February 16 with a detailed questionnaire. It went unanswered. But the ministry issued its press release defending giloy a few hours later. In early 2021, before the Nagral et al study was published, Kotecha denied giloy’s ill-effects to The Ken. “Currently, there are no standards for sub-therapeutic dosage consumption

of over-the-counter drugs. We are working with the Food Standards and Safety Authority of India to fix these.” A year later, these guidelines are yet to materialise. Kerala-based hepatologist Dr Cyriac Abby Phillips wrote a letter to Prime Minister Narendra Modi on February 7 this year in which he cited many giloy-related studies and requested the leader’s office to take necessary steps in the interest of public health. The letter didn’t elicit a response. In June last year, Dr Phillips had spoken in an interview about the danger of consuming large quantities of giloy. Earlier this month, he received a notice from the Kerala State Medical Council for Indian Systems of Medicine threatening punishment. He is reportedly drafting a reply. Finally, in a flipped reflection of the government’s and many patients’ denial, some Ayurveda exponents said follow-up investigations are important.

For example, Patwardhan, the Ayurveda professor at BHU, said, “Science develops by working on all such events,” and agreed with other doctors that the government ought to regulate the dosage of giloy and increase awareness on the side-effects of Ayurvedic products.