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Beetroot and Its Remarkable Health Benefits: A Natural Boost for Body Brain and Heart

by with No Comment Food

Published on: 20 June 2025

Category: Wellness I Functional Foods & Nutraceuticals

Written By: Dewanshee Ingale, BPharm

Reviewed and Fact Checked By:

Samruddhi Jadhav B.Sc-Microbiology,

MSc-Nutrition and Food Science

(Clinical & Holistic Nutritionist)

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Source: Freepik.com

Beta vulgaris, commonly known as beetroot or simply beet, is the nutrient-rich taproot of a plant belonging to the Amaranthaceae family. It is a versatile, fast-growing annual crop, widely cultivated across diverse regions including Asia, the Mediterranean, Europe, Egypt, India, and Ukraine. Known for its adaptability and nutritional value, beetroot is primarily grown for its edible, fleshy taproot, which varies in color, ranging from deep red to golden yellow and even white.

Beetroot is cherished not only for its earthy-sweet flavor but also for its impressive health-promoting properties. Beetroot can be consumed in a variety of forms, raw, roasted, boiled, steamed, pickled, or canned, making it a highly versatile addition to any diet. The leaves of the beet plant, known as beet greens, are also edible and nutrient-dense, rich in fiber, antioxidants, and essential micronutrients.

The vivid red to purple coloration of beetroot is primarily due to betalain pigments, specifically betacyanins, which are chemically distinct from anthocyanins found in many other red or purple vegetables. These betalains, in combination with other bioactive compounds such as polyphenols, vitamins (like folate and vitamin C), and essential minerals (like iron, magnesium, and potassium), are responsible for many of the beet’s therapeutic effects, ranging from antioxidant and anti-inflammatory activity to cardiovascular and cognitive benefits.

Beetroot is increasingly being studied for its health benefits, including its various roles in strengthening cardiovascular health and offering antioxidants, and can also be used as a natural colorant. 

Nutritional Constituents

Beetroot is a nutrient-dense root vegetable, low in calories (43 kcal per 100 g) and rich in essential nutrients. It provides 9.6 g of carbohydrates and 2.8 g of fiber and is an excellent source of folate (27% DV), supporting cell growth and repair. It also offers potassium (325 mg) for blood pressure regulation, along with smaller amounts of magnesium, calcium, phosphorus, and iron. Beetroot contains vitamin C, vitamin B6, and riboflavin, contributing to immune support and energy metabolism. Its standout bioactive compounds include betalains, polyphenols, flavonoids, and glycine betaine, known for their antioxidant, anti-inflammatory, and liver-protective effects. Beetroot is also a great source of dietary nitrates, which contribute to cardiovascular health.

This potent mixture of nutrients and phytochemicals, beetroot, supports cardiovascular health, digestive wellness, and overall vitality.

Health Benefits of Beetroot

Cardiovascular Health

Beetroot promotes cardiovascular health through the synergistic effects of its high dietary nitrate and potassium content. The dietary nitrates in beetroot are converted into nitric oxide in the body, a molecule that helps relax and widen blood vessels, leading to improved blood flow and a reduction in both systolic and diastolic blood pressure. This effect is well-supported by clinical trials, particularly those involving beetroot juice.

At the same time, potassium, another key nutrient in beetroot, contributes by helping to balance sodium levels and reduce tension in blood vessel walls, which offers additional support in maintaining healthy blood pressure. Together, these compounds make beetroot a valuable dietary addition for individuals aiming to prevent or manage hypertension and reduce the risk of heart disease and stroke.

Antioxidant and Anti-Inflammatory Effects

Beetroot is rich in potent antioxidants, primarily due to its high content of betalains, especially betanin, alongside other bioactive compounds that exhibit strong antioxidant and anti-inflammatory properties. A review on the Research of beetroot titled “Beetroot as a Functional Food with Huge Benefits” highlighted that betalains act as effective free radical scavengers and also stimulate the body’s endogenous antioxidant defense systems. Betanin, the most abundant betalain in beetroot, has been shown to neutralize a wide range of reactive oxygen species, including DPPH radicals, hydroxyl radicals, superoxide, and galvinoxyl, and even protect DNA from oxidative damage induced by agents like hydrogen peroxide. This antioxidant activity is believed to be mediated through the Nrf2 signaling pathway, which enhances the expression of protective proteins such as heme oxygenase-1 (HO-1), glutathione (GSH), and paraoxonase-1 (PON1).

Furthermore, betalains have been shown to inhibit the oxidative metabolism of neutrophils in humans, effectively reducing inflammation at the cellular level. They also enhance the activity of antioxidant enzymes such as peroxidase and superoxide dismutase in various tissues.

Anti-Cancer Properties of Beetroot

Beetroot exhibits promising anti-cancer properties, largely attributed to its high content of betalains, especially betanin, along with other bioactive compounds. A growing body of in vitro and in vivo studies indicates that beetroot and its constituents can inhibit cancer development through multiple pathways.

The key compound betanin has demonstrated the ability to inhibit the proliferation of cancer cells and induce apoptosis (programmed cell death) without harming healthy cells. It activates intrinsic apoptosis pathways by triggering the release of cytochrome c from mitochondria into the cytoplasm, leading to caspase-3 activation, disruption of mitochondrial membrane potential, and the generation of reactive oxygen species (ROS), ultimately resulting in cancer cell death. Moreover, beetroot extracts combined with chemotherapy have demonstrated synergistic effects, enhancing cytotoxicity against various cancer cell lines, including pancreatic, prostate, and breast cancers.

Liver and Kidney Protection

Beetroot is rich in antioxidants and bioactive compounds that help protect the liver and kidneys from oxidative stress and toxic damage. Multiple studies in both animals and humans have shown that beetroot juice enhances liver enzyme activity, reduces inflammation, and minimizes tissue injury caused by toxins or drug exposure.

In animal models, long-term beetroot supplementation prevented liver damage induced by hepatotoxins by activating the Nrf2 pathway and boosting the activity of phase I and II detoxification enzymes, thereby enhancing the body’s cellular antioxidant defenses. Human studies also report significant reductions in liver enzymes such as AST and ALT, particularly in patients with non-alcoholic fatty liver disease (NAFLD), indicating improved liver function.

Beetroot also exhibits nephroprotective (kidney-protective) effects. Rodent studies have demonstrated that beetroot extract can reverse drug-induced renal toxicity by lowering inflammation markers, reducing oxidative stress, and improving renal tissue integrity.

Enhanced Physical Performance

Beetroot juice is widely recognized among athletes and fitness enthusiasts for its ability to boost stamina and reduce muscle soreness. Its high nitrate content is converted into nitric oxide in the body, which enhances muscle oxygenation during exercise. This leads to improved stamina, greater energy efficiency, and reduced fatigue, making workouts more effective and less taxing. As a result, beetroot juice has become a popular natural performance enhancer and recovery aid in the world of sports and physical fitness.

Cognitive and Brain Health

The dietary nitrates in beetroot not only benefit cardiovascular health but also play a significant role in supporting brain function. By increasing the production of nitric oxide, beetroot helps enhance cerebral blood flow, which is crucial for maintaining cognitive performance, especially in older adults

Improved brain circulation has been linked to better memory, attention, and processing speed, and may help reduce the risk of dementia and other neurodegenerative conditions. Regular consumption of beetroot may therefore contribute to healthy aging and cognitive vitality.

Other Notable Health Benefits of Beetroot

Digestive Health

Beetroot is a good source of dietary fiber, which supports healthy digestion, promotes regular bowel movements, and fosters the growth of beneficial gut bacteria, contributing to overall gut health.

 Skin Health

The enhanced blood circulation and anti-inflammatory properties associated with beetroot consumption may improve skin tone, reduce inflammation, and promote a clearer, more radiant complexion.

Blood Sugar Regulation

Emerging evidence suggests that beetroot may assist in regulating blood glucose levels due to its low glycemic load and antioxidant profile. While promising, more research is needed to establish its role in diabetes management.

Conclusion

Beetroot stands out as a nutritional powerhouse, offering a rich profile of essential vitamins, minerals, and potent phytochemicals. From improving cardiovascular health and enhancing athletic performance to protecting the liver, kidneys, and brain, beetroot delivers a wide range of science-backed benefits. Its high content of dietary nitrates, betalains, antioxidants, and fiber makes it one of the most valuable root vegetables for preventive and functional nutrition.

At Pharmacally, we recognize beetroot as more than just a superfood; it is a clinically supported functional food with the potential to complement modern therapeutic strategies. Whether you’re managing blood pressure, seeking natural ways to combat oxidative stress, or looking to support overall wellness, incorporating beetroot into your daily diet is a simple, natural, and effective step toward better health.

Reference

Marjan Nikan, Azadeh Manayi, Chapter 3.5 – Beta vulgaris L., Editor(s): Seyed Mohammad Nabavi, Ana Sanches Silva, Nonvitamin and Nonmineral Nutritional Supplements, Academic Press, 2019, Pages 153-158, https://doi.org/10.1016/B978-0-12-812491-8.00021-7.

Ceclu L, Oana-Viorela N (2020) Red Beetroot: Composition and Health Effects – A Review. J Nutri Med Diet Care 6:043. doi.org/10.23937/2572-3278.1510043

Deepali Mudgal et al, Nutritional composition and value added products of beetroot: A review, Journal of Current Research in Food Science 2022; 3(1): 01-09

Clifford T, Howatson G, West DJ, Stevenson EJ. The potential benefits of red beetroot supplementation in health and disease. Nutrients. 2015 Apr 14;7(4):2801-22. Doi: 10.3390/nu7042801. PMID: 25875121; PMCID: PMC4425174.

Baião DDS, Silva DVTD, Paschoalin VMF. Beetroot, a Remarkable Vegetable: Its Nitrate and Phytochemical Contents Can be Adjusted in Novel Formulations to Benefit Health and Support Cardiovascular Disease Therapies. Antioxidants (Basel). 2020 Oct 8;9(10):960. Doi: 10.3390/antiox9100960. PMID: 33049969; PMCID: PMC7600128.

Chen L, Zhu Y, Hu Z, Wu S, Jin C. Beetroot as a functional food with huge health benefits: Antioxidant, antitumor, physical function, and chronic metabolomics activity. Food Sci Nutr. 2021 Sep 9; 9(11):6406-6420. Doi: 10.1002/fsn3.2577. PMID: 34760270; PMCID: PMC8565237.

Carrillo C, Rey R, Hendrickx M, Del Mar Cavia M, Alonso-Torre S. Antioxidant Capacity of Beetroot: Traditional vs Novel Approaches. Plant Foods Hum Nutr. 2017 Sep;72(3):266-273. Doi: 10.1007/s11130-017-0617-2. PMID: 28620796.

Tan ML, Hamid SBS. Beetroot as a Potential Functional Food for Cancer Chemoprevention, a Narrative Review. J Cancer Prev. 2021 Mar 30; 26(1):1-17. Doi: 10.15430/JCP.2021.26.1.1. PMID: 33842401; PMCID: PMC8020175.

Lechner JF, Stoner GD. Red Beetroot and Betalains as Cancer Chemopreventative Agents. Molecules. 2019 Apr 23;24(8):1602. Doi: 10.3390/molecules24081602. PMID: 31018549; PMCID: PMC6515411.

Saber A, Abedimanesh N, Somi MH, Khosroushahi AY, Moradi S. Anticancer properties of red beetroot hydro-alcoholic extract and its main constituent; betanin on colorectal cancer cell lines. BMC Complement Med Ther. 2023 Jul 18; 23(1):246. Doi: 10.1186/s12906-023-04077-7. PMID: 37464362; PMCID: PMC10355081.

Violetta Krajka-Kuźniak, Hanna Szaefer, Ewa Ignatowicz, Beetroot juice protects against N-nitrosodiethylamine-induced liver injury in rats, Food and Chemical Toxicology, Volume 50, Issue 6, 2012, Pages 2027-2033, https://doi.org/10.1016/j.fct.2012.03.062.

Domínguez R, Cuenca E, Maté-Muñoz JL et al, Effects of Beetroot Juice Supplementation on Cardiorespiratory Endurance in Athletes. A Systematic Review. Nutrients. 2017 Jan 6;9(1):43. Doi: 10.3390/nu9010043. PMID: 28067808; PMCID: PMC5295087.

Arazi H, Eghbali E. Possible Effects of Beetroot Supplementation on Physical Performance Through Metabolic, Neuroendocrine, and Antioxidant Mechanisms: A Narrative Review of the Literature. Front Nutr. 2021 May 13;8:660150. Doi: 10.3389/fnut.2021.660150. PMID: 34055855; PMCID: PMC8155490.

Miraftabi H et al, Effects of Beetroot Juice Supplementation on Cognitive Function, Aerobic and Anaerobic Performances of Trained Male Taekwondo Athletes: A Pilot Study. Int J Environ Res Public Health. 2021 Sep 28; 18(19):10202. Doi: 10.3390/ijerph181910202. PMID: 34639501; PMCID: PMC8507686.

Dewanshee
About Author
Ms. Dewanshee Ingale is a pharmacy graduate with a deep passion for medical writing and evidence-based healthcare communication. She brings a sharp scientific perspective to her work, enriched by certifications in WHO’s Research Ethics Online Learning and Artificial Intelligence in Research and Science. At Pharmacally, she combines her academic foundation and research-driven insights to translate complex medical topics into accessible and reliable health information.
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Ibezapolstat: AcurX Pharmaceuticals First-in-Class Mechanism Antibiotic for Clostridioides difficile Infection Shows Promising Results in Phase 2b Trial

by with No Comment Clinical Trails

Published On: 20 June 2025

Category: Clinical Trial I Infectious Disease I

Gut and Gastrointestinal Infections

Written By: Pharmacally Medical News Desk

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Source: Freepik.com

Clostridioides difficile infection (CDI) is among the most challenging hospital-acquired infections globally. C.Difficile, known for its high recurrence rates and significant impact on the gut microbiome. To date, vancomycin has long been a standard treatment; however, it lacks selectivity and often disrupts beneficial gut bacteria, which contributes to relapses.

Ibezapolstat, a first-in-class antibiotic being developed by AcurX Pharmaceuticals, aims to decipher these issues. Unlike traditional broad-spectrum agents, Ibezapolstat specifically targets DNA polymerase IIIC, an enzyme essential for the replication of Gram-positive bacteria like C. difficile, which is absent in beneficial anaerobic flora.

The recently published Phase 2b clinical trial results in The Lancet Microbe mark a crucial step forward in this drug’s journey, offering new hope in reducing recurrence and treating serious hospital-acquired infections like Clostridioides difficile.

The Phase 2b Trial: Design & Goals

AcurX Pharmaceutical recently concluded its phase 2b trial, and the results are published in Lancet Microbes. The trial was conducted across 15 U.S. centers between March 2021 and October 2023. The randomized, double-blind, active-controlled trial enrolled adults aged 18 to 90 with confirmed C. difficile infection. Patients were randomly assigned to receive

  • Ibezapolstat 450 mg orally every 12 hours (n = 18 total; 16 included in the efficacy analysis)
  • Vancomycin 125 mg orally every 6 hours (n = 14)

The primary objective was clinical cure at the end of treatment (EOT), defined as the resolution of diarrhea and no need for further CDI therapy 48 hours post-treatment.

Efficacy: A Match for Vancomycin

In the Phase 2b clinical trial, ibezapolstat demonstrated clinical efficacy that was analogous to vancomycin, which is the current standard of care for Clostridioides difficile infection. Among the patients evaluated in the trial, 94% of patients treated with ibezapolstat achieved complete clinical cure at the end of treatment, while 100% of patients receiving vancomycin met the same endpoint. This slight numerical difference was not statistically significant and met the criteria for non-inferiority, establishing Ibezapolstat as an equally effective treatment option. More compelling, however, were the findings from a pooled analysis of data from both the Phase 2a and 2b trials. In pooled analysis, done from the combined dataset of Phases 2a and 2b, ibezapolstat achieved a clinical cure rate of 96%. Surprisingly, ibezapolstat sustained a cure rate of 100%, meaning no recurrences were observed one month after treatment. This is in contrast to historical data for vancomycin, where recurrence rates range from 26% to as high as 58%. These results position ibezapolstat not only as an equally effective treatment as vancomycin for acute CDI but also as a promising candidate for reducing the risk of relapse, a critical issue in current CDI management.

Microbiome and Bile Acid Profiles

Even if ibezapolstat showed comparable clinical efficacy to vancomycin, ibezapolstat shows significant advantages over vancomycin in terms of protecting gut health, which is an essential factor in preventing recurrent infections. One of the prominent findings from the study was the rapid microbiological clearance of C. difficile, with 94% of patients treated with ibezapolstat showing eradication of the organism by Day 3, compared to 71% in the vancomycin group. But the main differentiation lies in ibezapolstat’s ability to save the beneficial gut microbiota. Unlike vancomycin, which broadly disrupts the intestinal flora, ibezapolstat preserved vital bacterial groups such as the Firmicutes and Actinobacteria phyla known for supporting immune function and maintaining colonization resistance. This preservation of the microbiome might play a role behind why Ibezapolstat showed zero recurrence rates.

Additionally, stool analysis revealed that ibezapolstat favorably altered bile acid profiles, reducing primary bile acids (which promote C. difficile germination) and increasing secondary bile acids (which inhibit it). This bile acid shift further enhances the gut’s natural defense against reinfection.

These microbiome and metabolomic findings highlight ibezapolstat’s potential not just to treat CDI effectively, but to do so in a way that supports long-term gut health and prevents recurrence, something current therapies generally fail to achieve.

Safety & Pharmacokinetics

Ibezapolstat demonstrated a favorable safety profile in the Phase 2b trial. No drug-related serious adverse events, treatment discontinuations, or deaths were reported in either the ibezapolstat or vancomycin treatment groups.

Pharmacokinetic analysis further supported its targeted mechanism of action, with ibezapolstat achieving high concentrations in stool exceeding 1,000 μg/g by days 8 to 10 while showing minimal systemic absorption. This gut-localized exposure is particularly advantageous in treating C. difficile infections, as it maximizes local antimicrobial activity while minimizing the risk of systemic side effects or toxicity.

The Unique Mechanism of Action

Unlike vancomycin, which largely disrupts bacterial cell wall synthesis and also affects a wide range of gut bacteria due to its common mechanism pathway through inhibiting cell wall synthesis, ibezapolstat offers a more targeted line of attack. It selectively inhibits DNA polymerase IIIC (PolC), an enzyme essential for the replication of Gram-positive pathogens like C. difficile but absent in human cells and many beneficial gut bacteria. This precision targeting enables ibezapolstat to kill C. difficile effectively while showing mercy on much of the gut’s healthy microbiota. As a result, it minimizes disruption to colonization resistance, the gut’s natural defense against reinfection. This selective mechanism is increasingly being recognized as the gold standard in modern antimicrobial development, aligning efficacy with microbiome preservation.

The Road to Approval

Ibezapolstat has already received the U.S. FDA Qualified Infectious Disease Product (QIDP) and Fast Track designations, accelerating its development and review timeline. At the same time, the European Medicines Agency (EMA) has recognized AcurX Pharmaceuticals with Small and Medium-sized Enterprise (SME) status, offering additional guidance and regulatory incentives. A global Phase 3 trial is currently in development and is expected to enroll over 600 patients. This pivotal study will compare ibezapolstat directly with vancomycin in a larger and more diverse population to confirm its efficacy and safety on a broader scale. A crucial regulatory meeting with the FDA is scheduled for mid-2025 to finalize the Phase 3 development plan and determine the path toward potential market approval.

Conclusion & Pharmacally Take

Current treatments for CDI have improved outcomes, but eradicating C. Difficile, preventing recurrence, and protecting other gut microbiomes continue to be major hurdles, “but ibezapolstat offers a new hope in this direction. With its narrow-spectrum precision, gut microbiome-sparing effects, and potential to prevent relapse, it addresses the shortcomings of traditional CDI therapies like vancomycin.

If Phase 3 results confirm these findings, ibezapolstat could emerge not just as an alternative but as a preferred first-line therapy for initial and recurrent CDI.

At Pharmacally, we’re closely watching ibezapolstat’s development as a milestone in microbiome-conscious antibiotic therapy. Its success could pave the way for a new era of targeted antimicrobials that treat without extra damage.

References

Taryn A Eubank, Jinhee Jo, M Jahangir Alam, et al, Efficacy, safety, pharmacokinetics, and associated microbiome changes of Ibezapolstat compared with vancomycin in adults with Clostridioides difficile infection: a phase 2b, randomised, double-blind, active-controlled, multicentre study, Lancet Microbe 2025, https://doi.org/10.1016/ j.lanmic.2025.101126

Acurx Announces Publication in Lancet Microbe of Phase 2b Clinical Trial Data for Ibezapolstat in CDI, AcurX pharmaceuticals, 17 June 2025, https://www.acurxpharma.com/news-media/press-releases/detail/111/acurx-announces-publication-in-lancet-microbe-of-phase-2b

Acurx Announces Publication in Lancet Microbe of Phase 2b Clinical Trial Data for Ibezapolstat in CDI, PRNewswire, 17 June 2025, https://www.prnewswire.com/news-releases/acurx-announces-publication-in-lancet-microbe-of-phase-2b-clinical-trial-data-for-ibezapolstat-in-cdi-302483504.html

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Venclexta Falls Short in Late-Stage Trial for Higher-Risk Myelodysplastic Syndrome (MDS): Roche and AbbVie Release Results

by with No Comment Disease & Drugs

Published: June 18, 2025

Category: Clinical Trial | Hematology | Oncology

Written By: Team Pharmacally    

                                                                                        

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Source: Freepik.com

In the latest development surrounding Venclexta (venetoclax), a flagship hematology drug from the Roche and AbbVie alliance, it has failed to attain its primary endpoint in a critical Phase III study for higher-risk myelodysplastic syndrome (MDS), announced by Roche-Abbvie Alliance on June 16 2025. This marks the second major trial setback for AbbVie and Roche with Venclexta. The drug had previously failed to meet its endpoints in the CANOVA study, which evaluated its use in relapsed or refractory multiple myeloma patients who tested positive for a specific biomarker and had undergone at least two prior lines of therapy

Trial Summary

The VERONA trial was a global, Phase III, randomized, double-blind study involving approximately 500 patients diagnosed with newly diagnosed higher-risk myelodysplastic syndrome (MDS). The trial compared venetoclax (400 mg on Days 1–14) in combination with azacitidine (75 mg/m²) versus azacitidine with placebo, administered in 28-day induction cycles. The study’s co-primary endpoints were complete remission (CR) rate and overall survival (OS). Despite earlier encouraging data from Phase 1b studies, the VERONA trial did not meet its primary endpoint. The trial failed to demonstrate a statistically significant improvement in overall survival when venetoclax was added to standard therapy. As of now, key outcome metrics such as the hazard ratio (HR), median OS values, and p-values have not yet been publicly disclosed. More detailed data are anticipated at upcoming scientific meetings or in peer-reviewed publications.

Despite initial promise and prior regulatory recognition, including an FDA Breakthrough Therapy Designation for various other ailments, the combination therapy did not result in a statistically significant improvement in overall survival in higher-risk MDS patients, which was the trial’s primary goal.

About Myelodysplastic Syndrome (MDS)

Myelodysplastic syndrome, also known as myelodysplasia or myelodysplastic neoplasm, is a group of conditions, mostly of cancerous etiology, that affect bone marrow and its ability to produce mature and healthy blood cells like RBCs, platelets, and WBCs. A result of a lack of mature cells in the blood leads to conditions like anemia, frequent bleeding, and infections; in some cases, patients may develop acute myeloid leukemia. Patients with higher-risk MDS face a poorer prognosis, with limited frontline therapeutic options beyond supportive care and hypomethylating agents like azacitidine.

Venclexta is a selective B-cell lymphoma 2 (BCL-2) inhibitor. In some blood cancers, BCL-2 prevents cancer cells from undergoing apoptosis, a natural death or self-destruction process. Venclexta inhibits the BCL-2 protein and works to help restore the process of apoptosis. It was being evaluated to determine whether it could drive deeper remissions and improved survival in this underserved patient population.

Venclexta’s Standing in Other Indications

It’s important to note that despite the VERONA trial setback for MDS, Venclexta (venetoclax) remains FDA-approved and widely used in the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), specifically in adult patients who are unfit for intensive chemotherapy. The drug continues to hold an important place in modern hematology, having generated over $2.6 billion in global sales in 2024, which underscores both its clinical relevance and broad adoption in real-world practice.

Clinical Implications

While the outcome of the VERONA trial is disappointing, it provides meaningful insights for both clinicians and researchers. Even though the Venclexta is already approved for AML, The results underscore the distinct biological complexities between MDS and AML, despite their clinical similarities. As Venclexta was emerges as the hope for MDS patient after its positive phase I result, but failure of phase III study highlight the urgent and continuing need for effective frontline treatment options for patients with higher-risk MDS. On the safety front, no new adverse signals were reported, although a full safety profile will be presented at upcoming medical conferences.

In response to the trial results, Roche and AbbVie released a joint statement, saying, “Although this outcome is not what we hoped for, we remain committed to exploring novel therapeutic strategies in MDS and other hematologic malignancies.”

Conclusion and Pharmacally Perspective

The failure of Venclexta in the VERONA trial represents a disappointing moment in the pursuit of better treatments for higher-risk myelodysplastic syndromes. Yet, in science, not all setbacks are dead ends. This trial underscores the biological complexity of MDS and the ongoing need for innovation in hematologic oncology. For AbbVie and Roche, it offers lessons to refine future therapeutic approaches. For clinicians and patients, it reinforces the importance of rigorous, data-driven advancement.

At Pharmacally, we believe that every clinical trial, whether successful or not, contributes to the greater mission of advancing smarter, safer, and more targeted care. We will continue to monitor developments in this space and report on emerging therapies, translational research, and key regulatory updates that shape the future of blood cancer treatment

Reference

Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Disease Activity In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome (Verona). http://clinicaltrials.gov/study/NCT04401748

Venclexta (venetoclax), Package Insert https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208573s013lbl.pdf

AbbVie Provides Update on VERONA Trial for Newly Diagnosed Higher-Risk Myelodysplastic Syndromes, PRNewswire, https://www.prnewswire.com/news-releases/abbvie-provides-update-on-verona-trial-for-newly-diagnosed-higher-risk-myelodysplastic-syndromes-302481869.html?utm_source=chatgpt.com

Roche, AbbVie say trial of Venclexta in patients with myelodysplastic syndromes falls short, Fierce Pharma, https://www.fiercepharma.com/pharma/roche-abbvie-trial-venclexta-patients-myelodysplastic-syndromes-falls-short

Genentech Provides Update on Phase III Verona Study, Genentech, A member of the Roche Group, https://www.gene.com/media/press-releases/15068/2025-06-16/genentech-provides-update-on-phase-iii-v?utm_source=chatgpt.com

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Bhringraj (Eclipta Alba): A Powerhouse for Hair Health

by with No Comment Wellness

Written By:

Pragati Ekamalli BPharm

Medically Reviewed and Fact-Checked By:

Ayurvedacharya Dr. Gaurav Pathare, BAMS

ChatGPT Image Jun 18, 2025, 12_57_35 PM
Source: Generative AI/openai

Bhringraj, botanically known as Eclipta Alba, is a revered herb in traditional Ayurvedic medicine and is also called the “King of Hair” due to its exceptionally beneficial effects on hair health. Commonly called “false daisy,” bhringraj has small white flowers and blooms in moist environments, especially across India, Thailand, and Brazil. For centuries, bhringraj has played a central role in the Indian Ayurvedic system in hair health due to its nourishing, rejuvenating, and restorative properties. The Sanskrit name Kesharaja directly translates to “Ruler of Hair.”

In this article, we’ll explore Bhringraj’s unmatched benefits for hair, from stimulating growth and reversing hair fall to delaying premature greying and soothing scalp issues. Whether you’re dealing with thinning hair, dandruff, or just want your hair to look its best, Bhringraj offers natural, science-backed solutions.

What makes Bhringraj known as the King of Hair?

Bhringraj is rich in key phytochemicals like flavonoids, alkaloids, and coumestans, along with vitamins and minerals essential for hair vitality. It’s nourishing action works at the follicular level, improving blood circulation to the scalp, encouraging new hair growth, and strengthening existing strands.

Let’s explore the different ways Bhringraj promotes optimal hair health:

Top Ayurvedic Benefits of Bhringraj

Bhringraj Oil for Hair Growth and Scalp Health

Bhringraj oil, derived by boiling its leaves with a carrier oil such as coconut or sesame, is best known for revitalizing hair follicles. Rich in flavonoids, alkaloids, and essential nutrients, it strengthens hair at the roots, prevents breakage, and combats hair fall. The oil’s antifungal and antibacterial actions also make it effective in treating dandruff and scalp irritation.

Usage Tip: Warm the oil slightly before application. Massage gently into the scalp in circular motions for 10–15 minutes. Leave it overnight or for at least 1–2 hours before washing with a mild herbal shampoo. Use two to three times weekly.

Pro Tip: Combine with Amla oil to further enhance hair growth and scalp nourishment.

Bhringraj Powder for Hair Fall and Graying

A homemade DIY hair pack with Bhringraj powder can treat excessive hair fall and early greying. Mix two tablespoons of Bhringraj powder with three tablespoons of coconut oil, yogurt, or aloe Vera gel. Add a tablespoon of honey for extra hydration if needed. It deeply conditions the scalp, nourishes hair roots, reduces split ends and dullness, and revives shine and softness.

Apply the smooth paste to your scalp and hair, leave it on for 30–45 minutes, and then rinse with a mild Ayurvedic shampoo. For natural darkening, blend with indigo powder.

Bhringraj as an Ayurvedic Tonic for Stronger Hair from Within

Apart from its external use, Bhringraj can be consumed (with professional guidance) to nourish hair internally. In Ayurveda, Bhringraj is classified as a “Rasayana” a rejuvenative herb.  It’s detoxifying and rejuvenating effects on the liver linked to skin and hair health in Ayurveda help which improve quality of hair from the inside out.

Supplement Options

  • Bhringraj Capsules: Support scalp circulation and hair growth
  • Bhringraj Tea or Powder: Acts as a Rasayana (rejuvenator) to reduce stress and hormonal imbalances affecting hair

    How to Take

    ¼ teaspoon Bhringraj powder with honey or warm water, once daily on an empty stomach (after consulting an Ayurvedic practitioner)

    4. Scalp Conditions Treated by Bhringraj

    Soothes Itchy, Inflamed Scalp

    Due to bhringraj’s anti-inflammatory and antimicrobial properties, bhringraj oil helps relieve scalp issues like psoriasis, eczema, and dandruff.

    Boosts Scalp Circulation

    Massaging the scalp at the root of the hairs with Bhringraj improves microcirculation, delivering more oxygen and nutrients to hair roots for growth and thickness.

    5. Bhringraj for Premature Graying and Hair Pigmentation

    Bhringraj’s antioxidant activity fights oxidative stress that leads to graying. It also stimulates melanin production, the pigment responsible for hair color

    For natural hair darkening, combine Bhringraj with Indigo powder or Brahmi, use regularly as a hair pack or oil massage, and avoid chemical shampoos and heat-based styling that strip natural oils

    6. Enhances Hair Texture

    Bhringraj revitalize your hair, restoring its natural shine and leaving it soft, silky, and beautifully smooth which prevent Dry and lackluster strands.

Popular Hair Products with Bhringraj

Product

Key Benefits

Bhringraj Oil

Nourishes roots, reduces hair fall, and promotes regrowth

Bhringraj Powder

Used in DIY hair masks, strengthens follicles, and prevents breakage

Bhringraj Shampoo

Gently cleanses scalp, supports long-term hair repair

Bhringraj Capsules

Internal support for scalp circulation and hormonal balance

Safety and Patch Testing

Bhringraj is generally safe for all hair types, but always do a patch test before full application. If you’re trying internal use, consult a certified Ayurvedic doctor for personalized dosage.

Conclusion

Bhringraj is a timeless herbal solution for modern hair concerns. Whether you’re aiming to stop hair fall, encourage regrowth, or bring back your hair’s natural shine, this Ayurvedic hair powerhouse has everything your scalp and strands need to thrive.

Consistent use of Bhringraj, especially in combination with a healthy lifestyle and diet, can lead to visibly stronger, thicker, and more youthful hair.

References

Ayurvedic Health Benefits of Bhringraj, Dr. D.Y.Patil College ofAyurvedic and Research Centre, https://ayurved.dpu.edu.in/blogs/bhringraj-benefits-ayurveda-hair-skin-wellness

Lauren Manaker MS. Health Benefits of Bhringraj https://www.health.com/author/lauren-manaker

Satheesh Naik K, Gurushanthaiah M, Kavimani M, Prabhu K, Lokanadham S. Hepatoprotective Role of Eclipta alba against High Fatty Diet Treated Experimental Models – A Histopathological Study. Maedica (Bucur). 2018 Sep;13(3):217-222. Doi: 10.26574/maedica.2018.13.3.217. PMID: 31490461; PMCID: PMC6290179.

Bhringraj: The Secret Ingredient for Healthy Hair, Cultivators, https://shop.cultivator.in/blogs/blog/bhringraj-the-secret-ingredient-for-healthy-hair?srsltid=AfmBOoqSKHX3RXJJN3IWB8qVXQsQvO4hgwsBrBlGv9L2CVsq0_YqiS5a

10 Benefits Of Bhringraj Oil for Hair Growth + How To Use, Kama Ayurveda, https://www.kamaayurveda.in/blog/bhringraj-oil?srsltid=AfmBOooqacd7jTY6Pmz3ZpZeFmmjYM_ysxok2yhTOXoAm2JkJdXmFYlN

2149158051

After Second Liver Failure Death, Sarepta Therapeutics Halts Global Elevidys Dosing in Non-Ambulatory Duchenne Muscular Dystrophy Patients; Phase III ENVISION Trial Impacted

by with No Comment Disease & Drugs

Medically Written and Reviewed By:

Vikas Londhe, MPharm

2149158051
Source: Freepik.com

On June 15, 2025, Sarepta Therapeutics announced the second death of a teenage male patient linked to acute liver failure (ALF) following its one-time gene therapy drug Elevidys in a non ambulatory Duchenne Muscular Dystrophy (DMD) patient, someone who is no longer able to walk due to this condition. The first fatality occurred in March 2025, when a 16-year-old boy succumbed to liver failure months after his treatment with Elevidys.

Official response

As soon as Sarepta was aware about adverse event, they suspended all commercial shipments of Elevidys to non‑ambulatory patients. Sarepta has completely paused dosing to non-ambulatory patient cohort in ENVISION Phase III trial which is going on in ambulatory and non-ambulatory older patient globally; as they are focusing on designing and enhancing more acceptable immunosuppressant regimen along with Elevidys.

Sarepta summon an independent panel of DMD and liver experts to evaluate alternate therapies like sirolimus in combination with corticosteroids to mitigate liver failure risk.

Alongside, Sarepta is continuously discussing with the FDA and other regulatory bodies their proposed plan for this event.   

Roche, which is partnered with Sarepta and is responsible for Elevidys’ marketing outside the United States, has equally halted dosing and shipments of Elevidys for non‑ambulatory patients globally.

Sarepta has particularly reported that both fatalities were associated with non-ambulatory patients who were no longer able to walk, a subgroup with advanced DMD. Approximately 140 such patients have been treated, and now, with two ALF-related deaths, this is considered to be a serious safety signal.

However ambulatory patients (those still walking) can continue treatment under the current corticosteroid regimen, as company has not amended protocols for them.

Elevidys & liver risk

Elevidys (delandistrogene moxeparvovec) is an innovative gene therapy that uses an Adeno-Associated Virus (AAV) as a delivery system to transport a micro‑dystrophin genetic material into the body via a single IV infusion. AAV-based gene therapies are known to cause acute liver injury, which can lead to liver failure, though fatalities were rare.

The Elevidys’ previous FDA approval already requires corticosteroid administration one day before initiating treatment and continuing for 60 days post-administration, along with close monitoring for liver function, but those measures have not prevented these rare, severe outcomes. Sarepta is now working on an enhanced safety regimen, which may include the addition of the extra immunosuppressant drug sirolimus into the current corticosteroid regimen. This modification of treatment is held up by preclinical data, which demonstrated sirolimus’ effectiveness in suppressing certain liver enzymes, which may help to mitigate this potential safety signal.

Implications for patients and the market

The tragic loss of two non-ambulatory patients highlights the importance of carefully analyzing Elevidys’s further benefits against the serious risks of liver failure in this subgroup. The ENVISION trial will be amended to include stronger immunosuppressant protocols by the addition of sirolimus; however, this change must receive FDA clearance before dosing resumes. While the FDA has agreed to the pause and is reviewing emerging safety data, full restoration of the trial and treatment depends on how effectively Sarepta is mitigating liver risk in non-ambulatory patient populations.

Summary

Sarepta Therapeutics has reported a second death from acute liver failure in a non-ambulatory patient treated with its Duchenne Muscular Dystrophy gene therapy, Elevidys. Both fatalities occurred in patients who were no longer able to walk, prompting Sarepta and its partner Roche to suspend dosing and commercial shipments of Elevidys for this subgroup globally; however, treatment continues for ambulatory patients. For the time being, dosing to the non-ambulatory cohort group in the Phase III ENVISION trial is on hold pending regulatory review of enhanced immunosuppressant protocols, possibly for the addition of sirolimus into the regimen. The company is working with an independent panel of experts to evaluate stronger liver-protection strategies. These developments have deepened inspection of Elevidys’s safety profile, particularly in advanced-stage DMD. At the same time, it is raising questions about gene therapy risks.

References

Sarepta Community Letter: Safety Update regarding Elevidys in non-ambulatory individuals with Duchenne, Sarepta Therapeutics, June 15, 2025, https://www.parentprojectmd.org/wp-content/uploads/2025/06/Elevidys-Community-Letter-6.15.2025.pdf

Highlights of prescribing information, Elevidys, https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-ELEVIDYS_1.pdf

Sarepta Reports Second Death of Patient Using Its Gene Therapy, Bloomberg, https://www.bloomberg.com/news/articles/2025-06-15/sarepta-reports-second-death-of-patient-using-its-gene-therapy

Sarepta reports second case of liver failure death after its gene therapy treatment, Reuters, https://www.reuters.com/business/healthcare-pharmaceuticals/sarepta-reports-second-case-liver-failure-death-after-its-gene-therapy-treatment-2025-06-15/

A safety update on Elevidys, June-2025, Parent Project Muscular Dystrophy, https://www.parentprojectmd.org/a-safety-update-on-elevidys-june-2025/?utm_source=chatgpt.com

Second DMD Patient Dies after Treatment with Sarepta Gene Therapy, https://www.genengnews.com/topics/genome-editing/second-dmd-patient-dies-after-treatment-with-sarepta-gene-therapy/

Sarepta Provides Safety Update for ELEVIDYS and Initiates Steps to Strengthen Safety in Non-Ambulatory Individuals with Duchenne, Sarepta Therapeutics, https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-provides-safety-update-elevidys-and-initiates-steps

freepik__the-style-is-candid-image-photography-with-natural__83723

The Essence of Panchakarma: The Fivefold Path to Healing and Inner Balance

by with No Comment Wellness

Written & Reviewed By:

Ayurvedacharya

Dr. Gaurav Pathare, BAMS

freepik__the-style-is-candid-image-photography-with-natural__83723
Source: Freepik.com

At the heart of Ayurveda lies a simple yet profound guiding principle:

“Swasthasya swasthya rakshanam, aturasya vikara prashamanam cha.”
(Charaka Samhita, Sutrasthana 30.26)


“To maintain the health of the healthy individual and to treat the disease of the sick”

This dual objective defines the true spirit of Ayurvedic medicine. Ayurveda, derived from the Sanskrit words “Ayu” (life) and “Veda” (knowledge), literally means “the knowledge of life science.” It is an eternal healing system practiced since ancient times to promote health, prevent disease, and ensure longevity. First documented in the Atharvaveda, Ayurveda is more than a medical system; it is a complete philosophy of life that harmonizes body, mind, and spirit with the rhythms of nature.

What Is Health According to Ayurveda?

In Ayurveda, health (Aarogya) is not just the absence of disease; it is a state of complete physical, mental, and spiritual harmony. Ayurveda clearly states that only a balanced condition of doshas, dhatus, and malas is Aarogya (Good health or disease-free condition), and their imbalance is the cause of ill health or disease.

 समदोषा: समाग्नी: च समधातुमलक्रीय: |

 प्रसन्न आत्म इंद्रियमना: स्वस्थ्य इति अभिधियते||

“Balanced doshas (biological energies), balanced Agni (digestive/metabolic fire), properly formed and functioning dhatus (body tissues), efficient elimination of malas (waste products), along with a pleasant state of the soul, senses, and mind—as per Ayurveda this is health.”

What is Panchakarma?

virechana

Clockwise: Vaman, Basti, Virechan, Raktamokshan, Nasya,  

Source: Ayurdharmaclinic.com, shattayuayurveda.com

Panchakarma is a cornerstone of Ayurvedic therapy, which is designed to purify the body at the deepest cellular level. It focuses on detoxification (shodhana) and rejuvenation (rasayana), restoring balance to the body, mind, and consciousness.

The term “Panchakarma” comes from the Sanskrit:

  • “Pancha” = Five
  • “Karma” = Actions or therapeutic procedures

Together, it refers to a group of five therapeutic procedures for internal purification of the body, which aimed at cleansing the body, mind, and consciousness. This eliminates accumulated toxins (Ama), regulates Doshas (Vata, Pitta, Kapha), and rejuvenates the body from the inside out.

Objectives of Panchakarma

Panchakarma is not just a physical detoxification; it is a complete reset for your system. Its goals are

Detoxification of the Body: Removes deep toxins from tissues and organs.

Balancing the Doshas: Restores the natural harmony of Vata, Pitta, and Kapha, essential for health

Enhancing Immunity (Ojas): Strengthens the immune system and improves the body’s resistance to illness.

Promoting Longevity: Prevents the accumulation of disease-causing factors and supports graceful aging.

Rejuvenation and Vitality: Renews energy, improves clarity of mind, and promotes overall well-being.

The Five Main Panchakarma Therapies Procedure

Main Dosha Targeted

Purpose

Vaman

Kapha

Emesis therapy (vomiting)

Virechan

Pitta

Purgation therapy

Basti

Vata

Enema therapy

Nasya

Kapha (above shoulder)

Nasal administration of medicines

Raktamokshan

Raktadhatu

Bloodletting therapy

Vaman (Therapeutic Emesis)

Indicated for: Asthma, bronchitis, skin disorders, and obesity

Process: Use of emetic drugs to induce vomiting

Benefits: Clears the respiratory and digestive tract, removes excess Kapha

 

Virechan (Purgation Therapy)

Indicated for: Hyperacidity, skin disorders, liver issues

Process: Herbal laxatives are used to cleanse the intestines

Benefits: Eliminates excess Pitta, improves digestion and metabolism

 

Basti (Enema Therapy)

Indicated for: Arthritis, constipation, neurological disorders

Process: Medicated oil or decoction administered rectally

Benefits: Balances Vata, nourishes tissues, relieves pain

 

Nasya (Nasal Therapy)

Indicated for: Sinusitis, migraine, stress, memory issues

Process: Nasal administration of medicated oils/ghee

Benefits: Clears head channels, enhances brain function

 

Raktamokshan (Bloodletting)

Indicated for: Skin diseases, hypertension, varicose veins

Methods: Siravedha (venesection), Jalaukavacharan (leech therapy)

Benefits: Purifies blood, removes localized toxins

Pre-procedure of Panchakarma

Before undergoing the main Panchakarma therapies like Vaman (emesis), Virechana (purgation), and Basti (enema), preparatory steps are essential to loosen and mobilize the doshas (toxins).

Snehan (Oleation)

Definition: Application of medicated oils internally and/or externally to soften and mobilize toxins.

Method: External application of warm medicated oils through Abhyanga (massage).

Purpose:

Loosens accumulated doshas

Nourishes body tissues

Facilitates easier elimination during main Panchakarma therapy

Swedan (Sudation / Sweating)

Definition: Induction of sweating through steam or heat.

Method: Application of heat using medicated steam, hot bolus, or steam chambers.

Purpose:

Dilates body channels

Promotes sweating to liquefy toxins

Enhances absorption of Snehan

Sthanik Snehan & Swedana (Localized Oleation & Sudation)

 Definition: Application of oil and heat to specific body parts.

Common Use: Especially done before Nasya Karma (nasal therapy) — typically on the face, head, and neck.

Purpose: Prepares the localized area for better absorption and effectiveness of the Nasya therapy.

Post-procedure of Panchakarma

After completion of the main Panchakarma therapies, the body needs gradual restoration to regular diet and lifestyle.

Sansarjan Karma (Dietary Regimen)

Definition: A structured post-Panchakarma diet plan.

Phases of Diet:

Peya – Thin rice gruel

Vilepi – Thick rice gruel

Kritakrita Yusha – Light vegetable soup

Kritakrita Mamsarasa – Light meat soup

Purpose: Gradually rekindles digestive fire (Agni), Prevents digestive shock, Helps sustain the therapeutic effects.

Dhumapana (Medicated Smoke Inhalation)

When: After Vamana (therapeutic emesis).

Purpose:

Clears residual Kapha from the upper respiratory tract

Prevents complications like cough, cold, or heaviness

Kavala (Gargling with Hot Water/Decoction)

When: After Nasya (nasal therapy)

Purpose:

Clears throat and oral cavity.

Removes residual oil or kapha

Maintains hygiene and promotes oral health

Benefits of Panchakarma

Enhances digestion, absorption, and assimilation at all levels (physical, mental, spiritual)

Improves sleep quality and provides deeper, more restful sleep

Detoxifies body and mind, eliminating toxins

Restores balance of Doshas and promotes holistic health

Strengthens the immune system and builds disease resistance

Promotes tissue rejuvenation and supports longevity

Normalizes menstrual cycles and supports hormonal balance

Boosts mental clarity, emotional stability, and overall awareness

Increases physical flexibility and mobility

Counters stress and slows the aging process

Induces deep relaxation and enhances a sense of well-being

Contraindications

Pregnancy

Extreme weakness or emaciation

Certain acute infections or emergencies

Children and elderly (need adapted versions)

Conclusion

Panchakarma is a powerful, time-tested method for detoxification and rejuvenation. Panchakarma empowers the body’s innate ability to heal and renew.  It offers holistic healing by balancing mind, body, and spirit.  Incorporating Panchakarma under expert supervision can lead to optimal health and well-being.

References

Charaka Samhita

Ashtanga Hridaya

Modern Ayurveda textbooks and journals

63715

“UK’s Martha’s Rule: A Mother’s Fight That Sparked a National Reform and a Global Wake-Up Call on Patient Safety”

by with No Comment Health Tidings

Written by: Soniya Hajare, MPharm

Reviewed and Fact-Checked by: Vikas Londhe, MPharm

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Source: Freepik.com

The UK government has recently introduced ‘Martha’s Rule,’ a new policy that allows patients and their families to directly request a rapid second medical opinion when someone’s condition is worsening or when there is disagreement about their care. This rule was created following the tragic death of Martha Mills, a a 13-year-old girl who tragically died of sepsis at King’s College Hospital in August 2021. Despite multiple warning signs—fever, rash, fluctuating vitals, and parents’ repeated concerns—the pediatric liver team failed to transfer her care to intensive support.

Martha’s Rule, implemented in NHS hospitals across England in April 2024, is a patient safety measure aimed at ensuring timely medical intervention when a patient’s condition worsens. It gives patients, their families, caregivers, or healthcare staff the right to request an urgent review by a critical care outreach team if they are worried about a patient’s health or feel their concerns are not being adequately addressed.

Martha’s Rule also serves as a cultural shift in healthcare, aiming to reduce hierarchical barriers, improve open communication, and empower patients and families to take an active role in medical decisions. Early reports from its initial rollout, shared in December 2024, suggest that the policy is already leading to better patient outcomes by preventing avoidable harm and deaths.

Background

In the summer of 2021, 13-year-old Martha Mills suffered a pancreatic injury after a bicycle accident during a family holiday in Wales, due to seriousness of injury she transferred to King’s College Hospital in London, a specialist centre for paediatric pancreatic trauma under the supervision of paediatric hepatology team. Although her health condition showed signs of worsening (high BPEWS score), she remained on a general paediatric ward and tragically succumbed to septic shock on 31 August 2021.

Investigations and Inquests

Following Martha’s death, a detailed internal investigation by King’s College Hospital found five missed opportunities to involve the intensive care unit, despite ICU beds being available at the time. In March 2022, the coroner concluded that Martha would likely have survived if she had been transferred to the intensive care ward earlier when worsening signs started appearing.

The inquest also highlighted systemic issues, such as the continued use of paper-based observation charts, poor communication between departments, and an absence of a well-defined ICU escalation protocol.

In May 2025, the General Medical Council (GMC) conducted a tribunal into the conduct of the senior consultant overseeing Martha’s care. He was found guilty of professional misconduct, including giving inaccurate and outdated information about Martha’s condition during a critical stage of her illness. Despite these findings, the tribunal decided not to impose any formal sanction, citing his long-standing career, previous good record, and the complexity of the situation.

The Five Missed Opportunities

  1. Failure to escalate to high-dependency or ICU beds early enough
  2. Ignoring early sepsis indicators
  3. Communication breakdown and team culture issues
  4. Misdiagnosis of rash on 29 August
  5. Absence of senior consultant reviews during critical deterioration

Implementation

Martha’s mother, Merope Mills, a senior editor at The Guardian, used her platform not just to share her grief but to campaign for change. She didn’t seek blame; she wanted reform. Her stand was simple: families should have a formal right to escalate concerns if they believe something is wrong. This led to the creation and rollout of Martha’s Rule

After the heart-rending and preventable death of 13-year-old Martha Mills, a series of reforms and actions were taken in response to the findings of the investigation and public pressure from her family. The most significant and systemic change was the implementation of ‘Martha’s Rule’ across all NHS hospitals in England. Below is a detailed summary of the key implementations:

Introduction of “Martha’s Rule”

Martha’s Rule is a national policy designed to give patients and families direct access to a second clinical opinion or critical care review when they are concerned that a patient is deteriorating and not being properly heard.

Core Features

24/7 access for patients and families to request a rapid clinical review from a critical care team (separate from the patient’s current care team)

Hospitals must prominently display how and when to escalate concerns, including bedside posters and leaflets

Staff training to encourage listening to families, recognizing that they often detect subtle signs of deterioration early

Strengthening the early warning score systems and escalation pathways already in place, making them more transparent and family-accessible

Rollout of Martha’s Rule

The implementation of Martha’s Rule began as a phased rollout following strong public pressure and policy discussions initiated in late 2023. NHS England, working with patient safety experts and Martha Mills’s family, selected 143 NHS trusts to pilot the scheme in early 2024.

These pilot sites tested how effectively patients and families could escalate a rapid clinical review when they were concerned about a patient’s condition. Following positive evaluations, the NHS committed to nationwide implementation. By April 2025, Martha’s Rule was made mandatory across all acute hospitals in England, with dedicated resources, signage, and staff training provided to ensure uniform compliance.

Impact & Data from Pilot Evaluation

During the initial rollout across 143 NHS hospitals in England (September–October 2024), 573 calls were made by patients, families, carers, and staff concerning suspected deterioration. Of these:

286 calls (50%) led to an urgent clinical review by critical care outreach teams

Around 57 reviews (20%) resulted in a change in treatment; such as administration of antibiotics, oxygen, or other life-saving interventions. However the patient remained on their ward.

14 patients were urgently transferred to intensive care units (ICU) after the escalation, potentially prevention serious complications or death.

By March 2025

A total of over 2,000 escalations had been made under the Rule

More than 300 escalations were followed by documented improvements in care

Over 100 patients were transferred to ICU or its equivalent directly due to their concerns being flagged through Martha’s Rule

Additionally, about 75% of calls originated from family members, highlighting the vital role that caregivers play in recognising deterioration that might otherwise be missed

These figures clearly exemplify both the scale and effectiveness of Martha’s Rule: it is being used with meaningful results, not abused, and is saving lives. NHS England’s national medical director, Prof Sir Stephen Powis, described it as “one of the most significant changes in patient safety in recent years,” and England’s Patient Safety Commissioner, Dr Henrietta Hughes, confirmed it “improving safety and reducing harm”

Conclusion and Pharmacally’s Take

At Pharmacally, we believe that patient safety begins with patient empowerment and Martha’s Rule marks a powerful shift in that direction. Martha’s Rule is arises from the heartbreaking loss of 13-year-old Martha Mills, This reform is more than just a policy, It is a major step toward making sure that patients and families are listened, their concerns are taken seriously, and their role in care decisions is truly respected.

For a long time, when patients or families raised concerns, those warnings often got delayed or overlooked due to complicated hospital systems and strict hierarchies. Martha’s Rule changes that it gives patients and families the power to speak up and be taken seriously, not just with empathy, but with real action.

At Pharmacally, where our core mission is to translate cutting-edge medical insight into safer outcomes, we see Martha’s Rule as a milestone for all who believe that safety is a shared responsibility. It formalizes a patient’s right to speak up and be taken seriously, especially when every minute matters.

We urge our readers, patients, caregivers, clinicians, and health systems to view Martha’s Rule not just as a protocol, but as a cultural reset. A chance to build a health system that listens, learns, and acts faster.  Patient Safety doesn’t start in the ICU it starts at the bedside, with a voice saying, “I think something is wrong.”

Martha’s Rule isn’t just Martha’s legacy. It’s a blueprint for a safer, smarter, more responsive healthcare system. And at Pharmacally, that’s exactly the kind of future we stand for

2020

Stay Healthy This Monsoon: Ayurvedic Lifestyle Tips for Varsha Ritu

by with No Comment Lifestyle

Written and Reviewed By:

Ayurvedacharya Dr. Gaurav Pathare, BAMS

 

2020
Source: Freepik.com

Period: Full Jyeshtha, Ashadha, and partly Shravana (approximately late June to mid-August)

In Ayurveda, the seasonal routine Ritucharya is an essential part of preventive healthcare. Each season affects the body and mind differently and calls for specific lifestyle and dietary adjustments. Varsha Ritu (Rainy Season) is one of the most sensitive periods for health due to the combined effects of heat accumulation from the previous season and the sudden coolness and moisture in the environment.

Seasonal Impact on the Body

Agni (digestive fire) becomes weak due to sudden cold and increased humidity.

Dosha Effects:

Vata becomes aggravated due to cold, dryness, and irregularity in weather.

Pitta increases due to natural acidity and internal heat built up during summer. Symptoms of Pitta may remain hidden initially due to the external coldness.

The body’s overall resistance is weakened, making it prone to infections, indigestion, and joint problems.

Dietary Regimen (Ahara Charya)

What to Eat

 Light, warm, oily, and easily digestible foods

Old grains (1 year aged): Wheat, Jowar, Rice

Pulses: Moong dal, Tur dal, Lentils (in moderation)

Dishes: Moong (yellow split mung beans) Khichdi, Upma (Semolina pudding), Moong Varan-Bhat, Jowar (Sorghum) Bhakri

Fats: Moderate use of ghee and oils

Spices & Digestives

Asafoetida (Hing), Garlic, Ginger, Mint, Black Pepper, Cumin, Coriander, Cinnamon, Onion

Special Items

Buttermilk (with rock salt)

Honey (small quantity)

Amaranth laddus (Rajgira ladoo)

Roasted gram flour (Sattu)

Horse gram (Kulthi flour)

Soups

Hot chicken/mutton soup with garlic, ginger, and asafoetida (in moderation)

Water Intake

Boiled and medicated water using:

Nagarmotha, Cumin, Dry Ginger (Sunthi), Coriander

Avoid chilled water; prefer warm or lukewarm water

Foods to Avoid

Raw and heavy-to-digest foods: Tubers, potatoes, sweet potatoes, peas, lentils, chickpeas

New grains, fermented foods (e.g., pizza, cheese)

Leafy vegetables (due to risk of worms and bloating)

Cold and damp-inducing items: Cucumber, sugarcane juice, ice cream, soft drinks

Excess dairy: Curd at night, yogurt, excess milk with salt

Meat and seafood (especially fried or fermented)

Sweets, fried snacks, and overly oily foods

Lifestyle Guidelines (Vihara Charya)

 Do’s

 Use warm water for bathing and washing

 Apply oil (Abhyanga) and take steam (Swedana) regularly

Practice Basti therapy (medicated enemas) as part of Panchakarma

Ensure proper clothing and bedding to avoid exposure to cold wind

Use aromatics and disinfectants in the home environment

Don’t

Avoid day sleeping, strenuous physical activity, and walking in the rain.

Refrain from cold exposure and excess sexual activity (maximum once a fortnight)

Do not eat without hunger or overeat

Avoid sleeping late, mental stress, and irregular routines

Panchakarma for Rainy Season

In Varsha Ritu, the body is susceptible to Vata aggravation, and the digestive system is weak. Therefore, Panchakarma therapies help maintain balance and remove accumulated Doshas

Snehana (Oleation)—Internal and external application of medicated oils

Swedana (Sudation Therapy)—Fomentation or sweating therapy to open body channels

Basti (Medicated Enema)—Most effective treatment for Vata disorders in this season

Conclusion

The rainy season is a vulnerable time for health in Ayurvedic understanding. Adopting a season-appropriate regimen helps maintain balance, supports immunity, and prevents common seasonal disorders such as indigestion, joint pains, and skin diseases. Through mindful dietary practices, lifestyle adjustments, and therapeutic Panchakarma treatments, one can harmonize with nature and stay healthy during Varsha Ritu.

Reference

Ashtang Hridaya Chapter 3

2148920822

Moderna Launches mNEXSPIKE: New FDA-Approved COVID Vaccine for High-Risk Groups

by with No Comment New Drug Approval

Written By: Dewanshee Ingale, BPharm

2148920822
Source: Freepik.com

In a landmark move, the FDA has granted approval to Moderna’s mNEXSPIKE, marking a new chapter in COVID-19 vaccine evolution. Approved on May 30, 2025, was a historic landmark towards the continuous development and evolution of messenger RNA (mRNA) technology based vaccines. The vaccine is such created that it acts as a next generation booster to improve the COVID-19 protection primarily focusing on the high-risk people. High risk populations include older adults from the age of 65 and above as well as smaller adults from the age of 12-24 with serious medical conditions defined by the Centres’ for Disease Control and Prevention (CDC) and that can increases the worsening of the outcomes if they are infected by virus. With the grand approval, Moderna now expects to provide mNEXSPIKE in addition to its original Spikevax® vaccine during this upcoming 2025-2026 respiratory virus season.          

Present data and background

COVID-19 still serves as a major public health risk in the world. In 2024, the virus took more than 47,000 lives in America, which translates to a death every 11 minutes. Older adults usually experience very severe sickness, hospitalization, and death as compared to other groups. CDC surveillance data from October 2023 to April 2024 show that this older age group represented 70% of adult hospitalizations. Adults aged 65 and older comprised approximately 70% of all COVID-19-related hospitalizations among adults in the U.S. Among the adults who died in the hospital due to COVID-19, 80% were aged 65 and above.

The high prevalence of certain medical conditions further compounds this vulnerability. For example, obesity may increase the risk of severe COVID-19 outcomes by 1.4 times, diabetes by 1.8 times, and chronic lung diseases by as much as 3.2 times. These conditions significantly raise the likelihood of serious health complications. This data underscores the urgent need for effective and targeted vaccination strategies such as Moderna’s next-generation mNEXSPIKE vaccine to protect those most at risk, especially as the COVID-19 virus continues to evolve.

mNEXSPIKE is built upon Moderna’s mRNA-1273 (Spikevax) platform, but with an updated design, which primarily focusing on the key regions of the SARS-CoV-2 spike protein instead of targeting the whole structure. This invention, when combined with a lower dose (10 µg vs. Spikevax’s 50 µg), aims to improve efficiency while reducing reactogenicity. The development of mNEXSPIKE was guided by real-time data and advancements in prognostic analytics, reflecting Moderna’s commitment to continuous innovation and optimization.

A Novel Approach

Moderna’s mNEXSPIKE characterizes an important step ahead in COVID-19 vaccine. It is created on the basic foundation of mRNA technology but is designed in such a way that it is more efficient and can address present and future challenges as compared to previously present COVID-19 vaccines. mNEXSPIKE offers an enhanced mRNA technique that targets the specific region of the SARS-CoV-2 spike protein. This enables the human’s immune system to react strongly while it delivers a significantly low dose at 10 micrograms, which is one-fifth of the dose of Moderna’s original Spikevax vaccine.

The lowered-dose formulation is not only responsible for reducing the side effects but also for rationalizing manufacturing and distribution. mNEXSPIKE can be stored at regular refrigerator temperatures (2-8°C) for 90 days, overcoming the logistical difficulties of the prior existing mRNA vaccines and enabling use in a wide geographic area, particularly in areas where the facility of cold storage does not exist.

Individuals who have already received the COVID-19 vaccine are advised to use this vaccine as a booster vaccine to protect adults 65 years and above or 12-64 years old with other comorbidities. Clinical trials have established that this new vaccine offers more protection or equivalent protection in comparison to the previously existing vaccine. A stronger immune response is elicited against both the Omicron subvariants and the original virus strain.

With a designed antigen, reduced doses, and improved storage stability, mNEXSPIKE bears a very clever strategy for pandemic protection. This leads to increased efficiency, adaptability, and patient friendliness for those who are at risk. 

Clinical trials and approval

Rigorous clinical trial data support the FDA approval of Moderna’s mNEXSPIKE COVID-19 vaccine, which represents efficacy and safety in different populations. The efficacy and safety of mNEXSPIKE were evaluated in a randomized, active-controlled NextCOVE clinical trial (NCT05815498) that was conducted in the United States, the United Kingdom, and Canada. The conducted large-scale evaluation included 11,417 individuals who were aged 12 years and above, with a median follow-up of 8.8 months.

The study population was distinct, with an average age of 56 years (range: 12-96 years). Demographically, the trial included

8.7% adolescents (12-17 years)

62.6% of adults (18-64 years)

28.7% older adults (65+ years)

The NextCOVE trial enrolled participants who were evenly divided between the mNEXSPIKE group (n = 5,706) and the comparator vaccine group (n = 5,711). Nearly all participants had received at least one prior COVID-19 vaccine dose, with an average interval of 9.8 months since their most recent vaccination. Notably, 74.3% of participants showed evidence of prior SARS-CoV-2 infection at baseline.

The mNEXSPIKE vaccine used in the study was a bivalent formulation, delivering a 10 microgram total dose comprising 5 µg targeting the original SARS-CoV-2 (Wuhan strain) and 5 µg targeting the Omicron variant. This represents a substantial dose reduction compared to the 50 µg dosage of the comparator vaccine. Participants received a single 0.2 mL intramuscular injection, administered at least three months after their previous COVID-19 vaccine dose.

Results

The primary endpoint of the NextCOVE Phase 3 trial (NCT05815498) was to evaluate the efficacy of Moderna’s mNEXSPIKE (mRNA-1283) vaccine in preventing symptomatic COVID-19, starting 14 days after a single booster dose, compared to the existing Spikevax (mRNA-1273) vaccine. The study enrolled over 11,400 participants aged 12 years and older, with nearly all having received at least one prior COVID-19 vaccination. The results demonstrated that mNEXSPIKE met the criteria for non-inferiority to Spikevax and showed a relative vaccine efficacy (rVE) of 9.3% in preventing symptomatic COVID-19 across all adults. Notably, in adults aged 65 and older, mNEXSPIKE showed an even higher rVE of 13.5%, indicating stronger protection in this high-risk group. The vaccine was also well tolerated, with a safety and reactogenicity profile comparable to or slightly improved over Spikevax, despite using a significantly lower dose of just 10 µg (versus 50 µg for Spikevax).

Safety profile

Moderna’s mNEXSPIKE has established a favorable safety profile across all age groups, with most side effects being mild to moderate and transient. Commonly reported adverse reactions included pain at the injection site, fatigue, headache, muscle pain, joint pain, chills, and nausea or vomiting, with slightly lower frequencies observed in adults aged 65 and older.

A key safety consideration is the rare risk of myocarditis and pericarditis, particularly in males aged 12–24 years, typically occurring within one week of vaccination. The estimated rates are approximately 8 cases per million doses in recipients under 64 years and 25 per million in males aged 12–25.

The vaccine is contraindicated in individuals with a history of severe allergic reactions (e.g., anaphylaxis) to any mNEXSPIKE component or prior Moderna COVID-19 vaccine dose. Syncope may also occur post-vaccination, as seen with other injectables.

Overall, the safety profile of mNEXSPIKE is consistent with other mRNA vaccines, and combined with its 9.3% higher relative vaccine efficacy, especially in older adults, it is a strong candidate for protecting high-risk populations during the ongoing COVID-19 threat.

Impact and future viewpoint

The sanction of Moderna’s mNEXSPIKE COVID-19 vaccine demonstrates an important invention in the pandemic protection, particularly for high risk groups like elderly people and those who have comorbidities. mNEXSPIKE offers an improved efficiency at a reduced dose and storage requirements, and is expected to increase the accessibility of vaccines and uptake, usually in areas with limited cold storage requirements. The vaccine’s improved safety and effectiveness characteristics are likely to reduce the total number of hospitalizations and deaths caused the COVID-19 which has taken thousands of lives in the U.S. over a year.

Looking at the future, mNEXSPIKE has undoubtedly set an entirely new standard for the upcoming next-generation vaccines, showcasing the potential for design and innovation that can protect the vulnerable population better. The approval also depicts the transformation toward personalized and adaptable vaccine planning strategies, which are of utmost importance due to the continuous evolution of the virus.

Overall, the newly created booster vaccine, Moderna’s mNEXSPIKE, is not only capable of strengthening the present pandemic preparedness but also lays the way for future innovation in mRNA vaccine technology and protection of public health.

References

mNEXSPIKE FDA Approval History https://www.drugs.com/history/mnexspike.html

Introducing mNEXSPIKE: Moderna’s New COVID-19 Vaccine https://www.modernatx.com/media-center/all-media/blogs/introducing-mnexspike-modernas-new-covid-19-vaccine

Moderna Receives U.S. FDA Approval for COVID-19 Vaccine mNEXSPIKE https://investors.modernatx.com/news/news-details/2025/Moderna-Receives-U-S–FDA-Approval-for-COVID-19-Vaccine-mNEXSPIKE/default.aspx

FDA approves Moderna’s new COVID-19 vaccine https://www.cidrap.umn.edu/covid-19/fda-approves-modernas-new-covid-19-vaccine

FDA Package Insert – MNEXSPIKE  https://www.fda.gov/media/186738/download

Spyros Chalkias, Antionette Pragalos, Adebayo Akinsola, et al, Safety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain and N-Terminal Domain mRNA Vaccine, The Journal of Infectious Diseases, Volume 231, Issue 4, 15 April 2025, Pages e754–e763, https://doi.org/10.1093/infdis/jiaf022

A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19 (NextCOVE), moderna clinical trials, https://trials.modernatx.com/study/?id=mRNA-1283-P301&Latitude=27.6648274&Longitude=-81.5157535&LocationName=Florida,%20USA&MileRadius=100

The article is reviewed  and fact-checked by the editorial team of Pharmacally.com

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The Hidden Pain Pathway: Paracetamol (Acetaminophen) Metabolite AM404 Blocks Peripheral Sodium Channels – A New Mechanism Uncovered

by with No Comment Research

Medically Written and Reviewed By: Vikas Londhe, M.Pharm, Pharmacology

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Source: Freepik.com

For over a century, paracetamol (acetaminophen) has been one of the world’s most widely used analgesics and antipyretics. Despite its widespread use, its exact mechanism of action has remained unclear. It was long believed to work mainly by blocking certain enzymes called cyclooxygenases (COX), especially COX-2. These enzymes are responsible for producing prostaglandins, which are chemicals that promote pain, inflammation, and fever. By reducing prostaglandin production, paracetamol helps lower pain and fever without significantly reducing inflammation like other NSAIDs. However, it is believed that paracetamol is only effective in mild inflammations, like after tooth extraction, and it is not effective in severe inflammation that arises from rheumatoid arthritis and acute gout.

Another pathway involves the TRPV1 receptor, short for Transient Receptor Potential Vanilloid 1, which plays a role in sensing heat and pain. Some research suggests that an active metabolite of paracetamol, the fatty acid amide N-arachidonoylphenolamine (AM404), may activate TRPV1 in a way that leads to pain relief by desensitizing these pain-sensing receptors.

However, new research conducted at Hebrew University of Jerusalem and the findings are published in The Proceedings of the National Academy of Sciences (PNAS) has uncovered a previously unknown mechanism of paracetamol. The new research proposed that paracetamol acts directly at peripheral nerve endings. Its metabolite AM404 can block sodium channels in the nerves, which are essential for sending pain signals to the brain. This discovery adds a new dimension to our understanding of how paracetamol relieves pain: not just through the inhibition of certain enzymes and receptors, but also by directly inhibiting the body’s ability to send pain signals to the brain.

The Breakthrough Study

A team led by Professors Alexander Binshtok and Avi Priel from the Hebrew University of Jerusalem published these game-changing findings in the prestigious PNAS, titled “The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels”

The key findings of the Research Includes

Local production of AM404: After oral intake of paracetamol, the body converts it to p-aminophenol in the liver, which is subsequently transformed into AM404 by fatty acid amide hydrolase (FAAH) in primary sensory neurons, essentially at the nerve endings where pain signals originate.

Inhibition of nociceptive sodium channels: AM404 directly blocks voltage-gated sodium channels Na_V1.7 and Na_V1.8, both crucial for generating action potentials in pain-sensing neurons. The blockade occurs via the local anesthetic binding site.

Peripheral analgesia: Through this localized mechanism, AM404 prevents pain signals at their source, producing potent relief in both regular and inflammatory pain models in rodents.

Researchers found that AM404, a metabolite formed from paracetamol in the body, accumulates in peripheral sensory neurons where it directly inhibits voltage-gated sodium channels Na_V1.7 and Na_V1.8. These channels are critical for the initiation and conduction of pain signals at the site of injury or inflammation. By blocking these sodium channels, AM404 effectively diminishes nociceptive signal transmission at its source, preventing pain before it even reaches the spinal cord. This peripheral action represents a fundamental shift in our understanding of how paracetamol works. It positioned paracetamol not only as a central analgesic but also as a locally acting modulator of neuronal excitability.

Results

AM404 significantly reduced sodium current amplitude in isolated dorsal root ganglion (DRG) neurons in a dose-dependent manner. The greatest effect was observed on tetrodotoxin-resistant (TTX-R) sodium currents, which are characteristic of Nav1.8, a key player in chronic and inflammatory pain. AM404 had minimal effect on potassium and calcium currents, indicating a selective action on sodium channels.

In pharmacological profiling, AM404 showed the strongest inhibition of Nav1.7 and Nav1.8, both of which are highly expressed in nociceptive (pain-sensing) neurons. Other Nav subtypes, such as Nav1.5 (cardiac) and Nav1.6 (CNS), were minimally affected, suggesting a favorable safety profile by avoiding cardiac or CNS toxicity.

In formalin-induced inflammatory pain models, peripheral injection of AM404 significantly reduced both early (neurogenic) and late (inflammatory) phases of pain behaviors (licking, flinching). In the hot plate and tail flick thermal assays, AM404 increased latency to pain response, indicating effective thermal analgesia. Systemic or central (intrathecal) administration of AM404 had less prominent effects, highlighting that peripheral action is essential for its analgesic activity.

Computational docking predicted that AM404 binds to a hydrophobic fenestration site within the channel’s domain IV S6 segment, a region known to influence channel gating and drug binding.

Implications

This research challenges the traditional view of paracetamol as a centrally acting analgesic. It highlights that peripheral mechanisms, particularly in the context of inflammatory pain, are also crucial to its analgesic action. A key finding is the active pharmacological role of AM404, a metabolite of paracetamol, which is not just a metabolic byproduct but a potent modulator contributing to its pain-relieving effects. This adds to the recognition of the importance of drug metabolites in determining therapeutic efficacy. Moreover, the study strengthens the therapeutic relevance of targeting sodium channel subtype Na_V 1.7, positioning AM404 as a promising lead compound or molecular scaffold for the development of new, non-opioid analgesics.

Broader Impact: Beyond Paracetamol

This study opens exciting new avenues in the field of pain research. It triggers a re-evaluation of some metabolites that have been silent since their discovery and are also traditionally overlooked, but may possess key pharmacological actions, suggesting that other commonly used drugs could harbor unexplored therapeutic potential through their metabolites.

Additionally, the findings strengthen the scientific rationale for targeting peripheral sodium channels, particularly in managing chronic and inflammatory pain conditions. AM404, a paracetamol metabolite, exerts analgesic effects without causing sedation or respiratory depression, positioning it as a promising foundation for developing safer, non-addictive alternatives to opioids.

Conclusion

The discovery that AM404 blocks peripheral NaV channels redefines how we understand one of the worlds’s most commonly used analgesics. By uncovering this hidden peripheral pain pathway, researchers at the Hebrew University of Jerusalem have significantly advanced the field of analgesic pharmacology. This work not only deepens our molecular understanding of paracetamol but also opens up new possibilities for developing better pain medicines and emphasizing the vital role of peripheral targets in pain relief.

References

Y Maatuf, Y. Kushnir, A.Nemirovski, et al, The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels, Proc. Natl. Acad. Sci. U.S.A. 122 (23) e2413811122, https://doi.org/10.1073/pnas.2413811122

Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth. 2008 Oct; 18(10):915-21. Doi: 10.1111/j.1460-9592.2008.02764.x. PMID: 18811827

Israeli study finds acetaminophen drug works by first blocking pain in nerves, The Times of Israel, https://www.timesofisrael.com/israeli-study-finds-acetaminophen-drug-works-by-first-blocking-pain-in-nerves/

New discovery: Tylenol stops pain at the nerves, before it hits the brain, ScienceDaily, https://www.sciencedaily.com/releases/2025/06/250610074247.htm#:~:text=Summary%3A,channels%20in%20pain%2Dsensing%20nerves.

Mallet C, Desmeules J, Pegahi R, Eschalier A. An Updated Review on the Metabolite (AM404)-Mediated Central Mechanism of Action of Paracetamol (Acetaminophen): Experimental Evidence and Potential Clinical Impact. J Pain Res. 2023 Mar 29;16:1081-1094. Doi: 10.2147/JPR.S393809. PMID: 37016715; PMCID: PMC10066900.

Sharma CV, Long JH, Shah S, Rahman J, Perrett D, Ayoub SS, Mehta V, First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid. J Pain Res. 2017; 10:2703-2709 https://doi.org/10.2147/JPR.S143500