Alcove

Science, culture, complexity

Tag: Ministry of AYUSH

  • CSIR touts dubious ‘Ayurveda’ product for diabetes

    At 6 am on September 13, the CSIR handle on X.com published the following post about an “anti-diabetic medicine” called either “Daiba 250” or “Diabe 250”, developed at the CSIR-Indian Institute of Integrative Medicine (IIIM):

    Its “key features”, according to the CSIR, are that it created more than 250 jobs and that Prime Minister Narendra Modi “mentioned the startup” to which it has been licensed in his podcast ‘Mann ki Baat’. What of the clinical credentials of Diabe-250, however?

    Diabe-250 is being marketed on India-based online pharmacies like Tata 1mg as an “Ayurvedic” over-the-counter tablet “for diabetes support/healthy sugar levels”. The listing also claims Diabe-250 is backed by a US patent granted to an Innoveda Biological Solutions Pvt. Ltd. Contrary to the CSIR post calling Diabe-250 “medicine”, some listings also carry the disclaimer that it’s “a dietary nutritional supplement, not for medicinal use”.

    (“Ayurveda” is within double-quotes throughout this post because, like most products like Diabe-250 in the market that are also licensed by the Ministry of AYUSH, there’s no evidence that they’re actually Ayurvedic. They may be, they may not be — and until there’s credible proof, the Ayurvedic identity is just another claim.)

    Second, while e-commerce and brand pages use the spellings “Diabe 250” or “Diabe-250” (without or without the hyphen), the CSIR’s social media posts refer to it as “Daiba 250”. The latter also describe it as an anti-diabetic developed/produced with the CSIR-IIIM in the context of incubation and licensing. These communications don’t constitute clinical evidence but they might be the clearest public basis to link the “Daiba” or “Diabe” spellings with the CSIR.

    Multiple product pages also credit Innoveda Biological Solutions Pvt. Ltd. as a marketer and manufacturer. Corporate registry aggregators corroborate the firm’s existence; its CIN is U24239DL2008PTC178821). Similarly, the claim that Diabe-250 is backed by a US patent can be traced most directly to US8163312B2 for “Herbal formulation for prevention and treatment of diabetes and associated complications”. Its inventor is listed as a G. Geetha Krishnan and Innoveda Biological Solutions (P) Ltd. is listed as the current assignee.

    The patent text describes combinations of Indian herbs for diabetes and some complications. Of course no patent is proof of efficacy for any specific branded product or dose.

    The ingredients in Diabe-250 vary by retailer and there’s no consistent, quantitative per-tablet composition on public pages. This said, multiple listings name the following ingredients:

    • “Vidanga” (Embelia ribes)
    • “Gorakh buti” (Aerva lanata)
    • “Raj patha” (Cyclea peltata)
    • “Vairi” or “salacia” (often Salacia oblonga), and
    • “Lajalu” (Biophytum sensitivum)

    The brand page also asserts a “unique combination of 16 herbs” and describes additional “Ayurveda” staples such as berberine source, turmeric, and jamun. However, there doesn’t appear to be a full label image or a quantitative breakdown of the composition of Diabe-250.

    Retail and brand pages also claim Diabe-250 “helps maintain healthy sugar levels”, “improves lipid profile/reduces cholesterol”, and “reduces diabetic complications”, sometimes also including non-glycaemic effects such as “better sleep” and “regular bowel movement”. Several pages also include the caveat that it’s a “dietary nutritional supplement” and that it’s “not for medicinal use”. However, none of these source cite a peer-reviewed clinical trial of Diabe-250 itself.

    In fact, there appear to be no peer-reviewed, product-specific clinical trials of Diabe-250 or Daiba-250 in humans; there are also no clinical trial registry records that were specific to this brand. If such a trial exists and its results were published in a peer-reviewed journal, it hasn’t been cited on the sellers’ or brand pages or in accessible databases.

    Some ingredient classes in Diabe-250 are interesting even if they don’t validate Diabe-250 as a finished product. For instance, Salacia spp., especially S. reticulata, S. oblonga, and S. chinensis have been known to be α-glucosidase inhibitors. In vitro studies and chemistry reviews have also described Salacia spp. can be potent inhibitors of maltase, sucrase, and isomaltase.

    In one triple-blind, randomised crossover trial in 2023, biscuits fortified with S. reticulata extract reduced HbA1c levels by around 0.25% (2.7 mmol/mol) over three months versus the placebo, with an acceptable safety profile.In post-prandial studies involving healthy volunteers and type 2 diabetes, several randomised crossover designs had lower post-meal glucose and insulin area under the curve when Salacia extract was co-ingested along with carbohydrate.

    Similarly, berberine-based neutraceuticals (such as those including Berberis aristata) have shown glycaemic improvements in the clinical literature (at large, not specific to Diabe-250) in people with type 2 diabetes. However, these effects were often reported in combination with other compounds and which researchers also indicated depended strongly on formulation and dose.

    Finally, a 2022 systematic review of “Ayurvedic” medicines in people with type 2 diabetes reported heterogeneous evidence, including some promising signals, but also emphasised methodological limitations and the need for randomised controlled trials of higher quality.

    Right now, if Diabe-250 works as advertised, there’s no scientific proof in the public domain, especially in the form of product-specific clinical trials that define its composition, dosage, and endpoints.

    In India, Ayurvedic drugs come under the Drugs & Cosmetics Rules 1945. Labelling provisions under Section 161 require details such as the manufacturer’s address, batch, and manufacturing and expiry dates while practice guides also note the product license number on the label for “Ayurvedic” drugs. However, several retail pages for Diabe-250 display it as a “dietary nutritional supplement” and add that it’s “not for medicinal use”, implying that it’s being marketed with supplement-style claims rather than as an Ayurvedic “medicine” in the narrow regulatory sense — which runs against the claim in the CSIR post on X.com. Public pages also didn’t display an AYUSH license number for Diabe-250. I haven’t checked a physical pack.

    A well-known study in JAMA in 2008, of “Ayurvedic” products purchased over the internet, found that around 20% of them contained lead, mercury or arsenic, and public-health advisories and case reports that have appeared since have echoed these concerns. This isn’t a claim about Diabe-250 specifically but a category-level risk of “Ayurvedic” products that are available to buy online and which are compounded by the unclear composition of Diabe-250. The inconsistent naming also opens the door to counterfeit products that are also more likely to be contaminated.

    Materials published by the Indian and state governments, including the Ministry of AYUSH, have framed “Ayurveda” as complementary to allopathic medicine. For example, if a person with diabetes chooses to try “Ayurvedic” support, the standard advice is to not discontinue prescribed therapy and to monitor one’s glucose, especially if the individual is using α-glucosidase-like agents that alter the post-prandial response.

    In sum, Diabe-250 is a multi-herb “Ayurvedic” tablet marketed by Innoveda for glycaemic support and has often been promoted with a related US patent owned by the company. However, patents are not clinical trials and patent offices don’t clinically evaluate drugs described in patent applications. That information can only come from clinical trials, especially when a drug is being touted as “science-led”, as the CSIR has vis-à-vis Diabe-250. But there are no published clinical trials of the product. And while there’s some evidence for some of its constituents, particularly Salacia, to reduce postprandial glucose and to effect small changes in the HbA1c levels over a few months, there’s no product-specific proof.

  • On the Nature feature about the Sarafs, a rare disease, and time

    Heidi Ledford has a tragic and powerful story published yesterday in Nature, about a team of scientists at the CSIR-Institute of Genomics and Integrative Biology racing to develop a CRISPR treatment for Uditi Saraf, a young girl whose brain was losing neurons due to a very rare, very aggressive genetic condition called FENIB. The story’s power comes from what it reveals about several facets of developing new treatments, looking for a cure for a rare disease, the importance of state support as well as control, the fact of the existence of neglected diseases, the demands made of clinical researchers, self-sufficiency in laboratory research infrastructure, and of course the cost of treatment. Most of all, it is a critical study of time. Uditi passed away four months after one of the researchers working on a CRISPR-based treatment for her told her parents they’d be ready with a solution for her in six. But even before her passing, there was time, there was no time, there was hurry, and there were risks.

    Uditi’s disease was caused by a mutation that converts a single DNA base from a ‘G’ to an ‘A’. A variation on CRISPR genome editing, called base editing, could theoretically correct exactly this kind of mutation (see ‘Precision gene repair’). … But Rajeev and Sonam saw an opportunity for hope: perhaps such a therapy could slow down the progression of Uditi’s disease, buying time for scientists to develop another treatment that could repair the damage that had been done. The Sarafs were on board.

    …

    There were a lot of unknowns in the base-editing project. And in addition to the work on stem cells in the lab, the team would need to do further experiments to determine which base-editing systems would work best, where and how to deliver its components into the body, and whether the process generated any unwanted changes to the DNA sequence. They would need to do experiments in mice to test the safety and efficacy of the treatment. They also needed to get Ghosh’s facility approved by India’s regulators for producing the base-editing components.

    Then there was the pandemic:

    In December 2019, the Sarafs moved back to India. … Then the COVID-19 pandemic struck, and in January 2021, Uditi was hospitalized with severe COVID-19. She spent 20 days in the hospital and her health was never the same, says Sonam. Communication became increasingly difficult for Uditi and she began to pace the house incessantly, rarely even going to sleep. The Sarafs decided to speed up the base-editing project by funding a second team in India.

    Developing treatments take time. Uditi’s story was a one-off, a singular disease that few researchers on the planet were working on, so developing an experimental alternative based on cutting-edge medical technology was a reasonable option. And yet:

    Meanwhile, Devinsky had petitioned a US foundation to devise a different experimental treatment called antisense therapy for Uditi. … The treatments didn’t work. And the experience taught Rajeev and Sonam how long it could take to get approval to try an experimental therapy in the United States. They decided Uditi’s base-editing therapy should also be manufactured and administered in India.

    Uditi didn’t live long enough to receive treatment that could have slowed FENIB’s progression — hopefully long enough for researchers to come up with a better and more long-lasting solution. Now, after her death, the thinking and effort that motivated the quest to find her a cure is in the future tense.

    It will take years to establish the techniques needed to create rapid, on-demand, bespoke CRISPR therapies. Most people with these conditions don’t have that kind of time. … Rajeev has urged Chakraborty to finish the team’s studies in mice, so that the next person with FENIB will not have to wait as long for a potential treatment. … “We are not really trying as aggressively as we did earlier,” he says.

    When the health of a loved one is rapidly deteriorating, the clock of life resets — from the familiar 24-hour rhythms of daily life to days that start and end to the beats of more morbid milestones: a doctor’s visit, a diagnostic test result, the effects of a drug kicking in, the chance discovery of a new symptom, an unexpected moment of joy, the unbearable agony of helplessness. The passage of time becomes distorted, sometimes slow, sometimes too fast. People do what they can when they can. They will take all their chances. Which means the chances they encounter on their way matters. Technological literacy and personal wealth expand this menu of options. The Sarafs knew about CRISPR, had a vague idea of how it worked, and could afford it, so they pursued it. They came really close; their efforts may even prove decisive in pushing a cure for FENIB past the finish line. For those who don’t know about CRISPR-based therapies and/or don’t have the means to pay for it, the gap between hope and cure is likely to be more vast, and more dispiriting. And one chapter of the Sarafs’ journey briefly threatened to pull them to this path — and relentlessly threatens to waylay many families’ laborious pursuits to save the lives of their loved one:

    The Sarafs studied what they could find online and tried the interventions available to them: Indian ayurvedic treatments, a ketogenic diet, special schools, seeing a slew of physicians and trying out various medicines.

    Ledford’s narrative doesn’t get into who these physicians were, but let’s set them and the special schools aside. Just this morning, I read a report by Rema Nagarajan in The Times of India that a company called Natelco in Bengaluru has been selling human milk even though its license was cancelled two years ago. The FSSAI cancelled Natelco’s license in 2021; a few months later, Natelco obtained a license from the Ministry of AYUSH claiming it was selling “Aryuevdic proprietary medicine”. When the Breastfeeding Promotion Network of India complained to the ministry, the ministry cancelled its license in August 2022. Then, a month later, the Karnataka high court granted an interim stay on this cancellation but said the respondents — AYUSH representatives in Karnataka, in the Karnataka licensing authority or from the ministry — could have it vacated. They didn’t bother. In June 2023, the ministry filed objections but nothing more. It finally moved to vacate the stay only in March this year.

    Natelco’s case is just one example. There are hundreds of companies whose charade the Ministry of AYUSH facilitates by allowing specious claims ranging from “Ayurvedic toothpaste” to calling human breast milk “Ayurvedic medicine”. This is not Ayurveda: very few of us know what Ayurveda is or looks like; even Ayurveda itself doesn’t belong in modern medicine. But together with the FSSAI, the food regulation body notorious for dragging its feet when the time comes to punish errant manufacturers, and a toothless advertisement monitoring regime, the Indian food and beverages market has provided a hospitable work environment for quacks and their businesses. And inevitably, their quackery spills over into the path of an unsuspecting yet desperate father or mother looking for something, anything, that will help their child. When faced with trenchant criticism, many of these business adopt the line that their products are not unsafe. But they are terribly unsafe: they steal time to do nothing with it, taking it away from a therapy or a drug that could have done a lot. Such cynical alternatives shouldn’t be present anywhere on any family’s path, yet the national government itself gives them a license to be.

  • Government by Supreme Court

    On February 27, a bench of the Supreme Court upbraided Patanjali Ayurved and its chairman Acharya Balkrishna for continuing to disparage systems of medicine other than Ayurveda (technically, what it calls Ayurveda) and claiming its products offer “permanent relief” from “blood pressure, diabetes, arthritis, asthma and obesity” in its advertisements, despite having assured the court in November 2023 that it won’t do so. The Indian Medical Association had filed the case in August 2022 alleging that Patanjali Ayurved had flouted the Drugs and Magic Remedies (Objectionable Advertisements) Act 1954 and its Rules.

    It’s a straightforward case with an understandable outcome, but it isn’t unsurprising. That Patanjali Ayurved so openly violated the Act and the Rules – but also good sense, as Pushpa Mitra Bhargava pointed out in an excoriating essay in 2016 – forced the IMA to approach the court, and for some time now the courts have been the last democratic institutions in India interested in upholding the law (and even then it’s iffy). The ‘backstop’ the courts have offered against advertisements in particular running away with bullshit has been particularly useful because the laws are not so much outdated as unable to respond to the new ways in which advertisers are twisting words, taking advantage of grey areas, and, generally, “telling a lie in a way that it appears to be the truth,” in Bhargava’s words.

    More importantly, advertisement regulation in India is weak. As Kaushik Moitra and Shreya Sircar wrote in 2022 (emphasis added):

    Advertisers must address complaints regarding deviations from the ASCI Code. If such complaints are not remedied, ASCI may take coercive steps to regulate the (allegedly) offending advertisement. Illustratively, ASCI may recommend that broadcasters not air the offending advertisement and may also publish instances of non-compliance by advertisers on its website. ASCI may also report infractions to the Ministry of Information and Broadcasting.

    Additionally, – and uniquely for a self-regulatory organisation in India – ASCI has been recognised as a self-regulator under the Cable Television Networks (Amendment) Rules, 2021. ASCI promulgations are advisory and can neither supplant nor supersede the law. Moreover, ASCI cannot compel compliance. However, any action brought against an advertiser for breach of ASCI promulgations will proceed on the basis that ASCIs position has statutory endorsement.

    It’s ultimately up to some government agency to take action and to advertisers to check themselves. In 2010, ASCI had flagged more than “50 campaigns by ayurvedic and homeopathic drug makers offering a cure for COVID-19 in April alone” to the government. The charge was grounded not in the 1954 Act but in a Ministry of AYUSH order earlier that month prohibiting the advertisement of AYUSH-related claims about curing COVID-19.

    In fact, between April 2014 and July 2024, a portal of the Department of Consumer Affairs said it had logged more than 1,400 misleading advertisements pertaining to AYUSH products and services. Similarly, the Pharmacovigilance Centres for Ayurveda, Siddha, Unani and Homeopathy Drugs reported 18,812 “objectionable advertisements” between 2018 and 2021. In 2022, the ASCI also reported 1,229 misleading AYUSH-related advertisements between 2017 and 2019. Yet the same ministry is unconcerned when Patanjali Ayurved offers unsubstantiated (possibly intentionally ambiguous) “permanent relief” from a variety of conditions. In fact, “unconcerned” is inaccurate. On February 19, 2021, the then Union health minister Harsh Vardhan endorsed a ‘drug’ developed by Patanjali Ayurved, called Coronil, and which the minister, Balkrishna (the chairman), and Baba Ramdev claimed was the “first evidence-based medicine for coronavirus”. It wasn’t; it was an untested quack-remedy backed by spurious claims that the WHO had certified it.

    Such circumstances force those who are concerned about the effects of these advertisements to approach the courts for relief, and it is heartening that the courts among all institutions retain some sense. Yet this is also a tragedy: if the regulations that the government has put in place are followed and enforced properly by regulatory agencies, people wouldn’t have to approach courts for every remedy. Courts are already burdened with a large number of cases; equally, judges – while being equipped to examine the propriety of processes and adherence to the law and Constitutional principles – are not subject experts.

    In the Patanjali Ayurved case, of course, the company was advancing clearly pseudoscientific claims backed by non-existent data, and its defence was easy to dismiss. What would happen when, say, the government approves a poorly tested vaccine with a known risk of injury in the event of a self-determined emergency; a civil society group files a petition asking for the approval to be rolled back; and the government contends that the group is spreading vaccine hesitancy? The court shouldn’t be expected to be able to examine the results of clinical trials, yet it may have to. In fact, contemporary environmental governance offers a real example of such a problem in action.

    Unlike a specialised expert tribunal, Constitutional courts don’t possess the necessary skill and expertise to examine the technical and scientific correctness of any project. Judges are trained to examine and adjudicate on the legality and propriety of the decision-making process.

    Environmental lawyer Ritwick Dutta wrote this in The Hindu following the Joshimath disaster, when the Union government halted work on the Helang-Marwari bypass. This work had received a green signal from the Supreme Court in 2022 to proceed, raising “questions about the validity of the apex court’s decision” (not that the Union government was opposed to the project).

    The separation of powers is a division of labour, rendered more critical than other such divisions by the need to keep the greatest powers of the land in check. Yet it has often been flouted, such as the Supreme Court’s decision to set up the Central Empowered Committee, which stands in between the Standing Committee of the National Board for Wildlife and the Union Cabinet when approvals for non-forest use of sanctuaries and national parks are at stake. If this committee disagrees with a decision of the Standing Committee, the committee can forward it to the Supreme Court with its own opinion for the apex court to take the final call – a clear violation of the separation of powers.

    However, not everyone would have thought so at the time many such measures were instituted. The environment ministry created the committee in 2002 following a Supreme Court direction in T.N. Godavarman, “for the purposes of monitoring and ensuring compliance of the orders of the … Supreme Court covering the subject matter of environment, forest and wildlife, and related issues arising out of the said orders and to suggest measures and recommendations generally to the State, as well as Central Government, for more effective implementation of the [Environment (Protection)] Act and other orders of the Court” (source).

    Since then, however, and in keeping with Dutta’s assessment, the Supreme Court has adjudicated on the “technical and scientific correct” of various projects. That the environment ministry has parallelly and persistently weakened safeguards to protect the country’s natural resources to favour ‘ease of business’ has only allowed the court to intervene further. But at the same time, because the politically instituted mechanisms to protect the lives and livelihoods of people and the well-being of flora and fauna living near sites of resource extraction exist more and more only in theory, researchers, activists, and others have also welcomed the court’s interventions to nix deleterious project proposals. (In September 2023, in fact, the environment minister replaced the Supreme Court’s committee with a new one of the same name, populated fully with members that report to the ministry.)

    Simplistically, those in charge are making bad decisions and those not supposed to be in charge are making good decisions.