2| Insulin Resistance and Glycated Hemoglobin Level: Principal Contributors to the Pathologic Spectrum of Nonalcoholic Fatty Liver Disease 4| Safety and Efficacy of Liv.52 DS in the Management of Nonalcoholic Fatty Liver Disease 6| Liv.52 Drops in the Management of Loss of Appetite in Children 10 | An Interview With Dr Smita Datta 12 | An Interview With Dr Sunil K Sharma Himalaya Livline Vol 6 • No. 5 • Sep–Dec 2023 Answer the End-to-End Quiz and WIN PRIZES! Scan to read the e-version of Himalaya Livline A Publication of Himalaya Wellness Company World Diabetes Day Special
World Diabetes Day (WDD) is observed every year on November 14, the birthdate of Sir Frederick Banting, the scientist who codiscovered insulin with Dr Charles Best. In 1991, the International Diabetes Federation and the World Health Organization decided to designate this day to create awareness about the escalating health threats posed by diabetes. The theme for WDD 2021 to 2023 is Access to Diabetes Care. WDD is the world’s largest diabetes awareness campaign that reaches more than 1 billion people in more than 160 countries. The campaign focuses on issues pertaining to diabetes and aims to promote the importance of taking coordinated and concerted actions to tackle diabetes as a critical global issue. WORLD Diabetes Day
Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 | 1 Editorial CONTENTS Research Update 2 Patient Education 13 Health News 9 Research at Himalaya 4 Doctors’ Feedback 17 Herb Facts 8 Expert Comments 10 The Liver and the Body 15 Dear Doctor, A marked increase in the consumption of a calorie-dense diet and sedentary lifestyle has radically affected the metabolic health status of people of all age groups. The chronic metabolic diseases— nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM)—have been proven to coexist and act in conjunction, resulting in adverse health outcomes. This issue of Himalaya Livline, a World Diabetes Day special, brings to you a collection of articles revolving around this theme. The presence of NAFLD is known to increase the incidence and complications of DM; an interesting article about the effect of insulin resistance and glycated hemoglobin level on the pathogenesis and progression of NAFLD is covered in the Research Update section. In addition, Dr Smita Datta’s expertise on DM-mediated nonalcoholic steatohepatitis and Dr Sunil K Sharma’s insights on loss of appetite are covered in the Expert Comments section. The Research at Himalaya section features an excerpt of the clinical study that demonstrates the safety and efficacy of Liv.52 DS Tablets in the management of NAFLD. A fact column about DM, important lifestyle-related tips for managing DM, and more such engaging content have been included in this issue. We hope you find this issue informative. Happy reading! — Editor Editor: Dr Jayashree B Keshav Editorial Team: Shruthi VB, Shruthi VK, Harika GS, Shruthi M, Priyakshi M, Keerthini D, Harshitha C Layout Artists: Dayananda RS, Santosh G, Monesh NP Copyright © 2023 Himalaya Wellness Company All content in this journal/publication is the property of Himalaya Wellness Company and is protected by Indian and international copyright laws. Any other use, including the reproduction, modification, distribution, transmission, republication, display, or performance, of the content in this journal/publication, without written permission from the owner, is strictly prohibited. For permission to reproduce articles/information published in this journal/publication, please write to publications@himalayawellness.com SUBSCRIPTION If you would like to subscribe to Himalaya Livline, please fill an online form. You can access this form through https://tinyurl.com/LivlineSubscriptionForm OR Please share your views and suggestions about Himalaya Livline through an online form. You can access this form through https://tinyurl.com/LivlineFeedbackForm OR FEEDBACK
2 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 research update Insulin Resistance and Glycated Hemoglobin Level: Principal Contributors to the Pathologic Spectrum of Nonalcoholic Fatty Liver Disease Nonalcoholic fatty liver disease (NAFLD), a major global epidemiologic concern, has gained attention as the hepatic manifestation of metabolic syndrome. The linear link between the metabolic syndrome (partly through glucose intolerance) and hepatic steatosis, fibrosis, and cirrhosis also suggests a close connection between glycemic levels and NAFLD.1,2 Several studies have confirmed that NAFLD elicits a cascade of events that involve impairment of insulin sensitivity and glucose homeostasis and elevation in the levels of liver enzymes (alanine transaminase and g-glutamyl transpeptidase) that predict the onset of type 2 diabetes mellitus.3 While this pathophysiologic interplay is well-documented, studies evaluating the effects of impaired glucose homeostasis on the pathogenesis and progression of NAFLD are underway. Insulin Resistance and Lipotoxicity The pathogenesis of fatty liver can be triggered by increased free fatty acid levels, increased de novo lipogenesis, decreased free fatty acid oxidation, and decreased hepatic triglyceride secretion.4 In addition to promoting glucose uptake by the skeletal muscle, liver, and adipose tissue, insulin suppresses hepatic glucose production. Insulin plays a crucial role in lipid metabolism by promoting fatty acid esterification, storing fatty acids in the form of lipid droplets, and inhibiting lipolysis. Hyperinsulinemia, a response to systemic insulin resistance (IR) by the body, leads to an increase in hepatic de novo lipogenesis.4 IR plays a key role in lipolysis that occurs in the adipose tissue, leading to superfluous free fatty acid trafficking and the development of lipotoxicity. Lipotoxicity impairs insulin signaling, induces oxidative damage, and promotes inflammation and fibrosis. Lipotoxicity is considered as the driving factor in the pathogenic progression of NAFLD.4 Increased intrahepatic lipid accumulation results in triglyceride secretion in the form of very low-density lipoproteins. The accumulating lipids are transported to the adipose tissue, thus, reducing the ability of the adipocytes to store lipids. This series of events that lead to lipotoxicity is found to be associated with the progression from simple steatosis to nonalcoholic steatohepatitis, liver fibrosis, and hepatocellular carcinoma in patients with NAFLD.4 The Role of Elevated Glycated Hemoglobin in NAFLD Glycated hemoglobin (HbA1c) has a unique capacity to reflect the average glucose concentration over the previous 8 to 12 weeks. Substantial evidence from a recent study confirms that diabetic, nondiabetic, obese, and lean individuals with HbA1c > 5.7% are 4 times more prone to developing fatty liver disease.3,5 Insulin Resistance Blood vessel Pancreas Cells do not respond e ciently Insulin
Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 | 3 Summary • The linear link between metabolic syndrome and hepatic steatosis, fibrosis, and cirrhosis suggests a close connection between glycemic levels and NAFLD. • NAFLD elicits a cascade of events that involves impairment of insulin sensitivity and glucose homeostasis and elevation in the levels of liver enzymes. • The pathogenesis of fatty liver can be triggered by increased levels of free fatty acids, de novo lipogenesis, decreased free fatty acid oxidation, and hepatic triglyceride secretion. • Hyperinsulinemia, a response to systemic IR by the body, leads to an increase in hepatic de novo lipogenesis. • Lipotoxicity impairs insulin signaling, induces oxidative damage, and promotes inflammation and fibrosis. The following are a few ways the pathogenesis of NAFLD is associated with elevated levels of HbA1c: Glucose permeability HbA1c is influenced by the lifespan and glucose permeability of erythrocytes. Thus, transmembrane glucose gradient (rather than the rate of glucose transport) correlates with the HbA1c level. Therefore, elevated HbA1c level in NAFLD can be related to the increased intracellular glucose levels in patients with NAFLD.2 Hyperglycemic episodes HbA1c is generally produced in direct proportions to the duration and episodes of high blood glucose concentrations. Hyperglycemic episodes, in addition to the production of advanced glycation end products such as HbA1c, also affect lipid metabolism and result in increased synthesis of triacylglycerols (TAGs). These TAGs tend to deposit in various tissues of the body, including the liver. TAG deposition in the liver parenchyma leads to fatty liver. Thus, HbA1c can be strongly linked to fat deposition in the liver and can be considered a causative factor of NAFLD.5 Oxidative stress The erythrocyte fragility that influences the lifespan of erythrocytes is positively correlated with elevated HbA1c levels. Immoderate hemolysis enhances oxidative stress. In response to oxidative stress, changes in erythrocyte morphology and reduction in membrane fluidity can occur, which can be easily captured by the liver macrophages.2 It is well-understood that overeating and consumption of energy-dense, nutritionally imbalanced, and appetite-dysregulating foods; stress; and sleep deprivation are the leading causes of metabolic derangement and IR. These perturbations eventually trigger the pathogenic spectrum of NAFLD. Lifestyle interventions such as caloric restrictions and consumption of a balanced diet, regular physical activity, and maintaining a healthy weight are proven beneficial in alleviating hepatic steatosis and liver fibrosis in patients with NAFLD.6 References 1. Chen C, et al. Biosci Rep. 2020; 40(1):BSR20193996. 2. Ma H, et al. BMC Gastroenterol. 2013;13:3. 3. Zupo R, et al. J Clin Med. 2021;10(8):1695. 4. Chen Z, et al. Lipids Health Dis. 2017;16:203. 5. Masroor M, Haque Z. J Clin Transl Hepatol. 2021;9(1):15–21. 6. Chao HW, et al. Int J Mol Sci. 2019;20(2):298. A recent study confirms that diabetic, nondiabetic, obese, and lean individuals with glycated hemoglobin > 5.7% are 4 times more prone to developing fatty liver disease.5 Insulin Resistance and Glycated Hemoglobin
4 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 Research at Himalaya Safety and Efficacy of Liv.52® DS in the Management of Nonalcoholic Fatty Liver Disease An excerpt of the study conducted by Siregar G et al published in the European Journal of Clinical and Experimental Medicine has been featured here. Abstract Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excessive fat in the liver due to factors other than alcohol use. This prospective, interventional clinical study was conducted to evaluate the clinical safety and efficacy of Liv.52 DS tablets in the management of NAFLD. Sixty patients of either sex (aged 18–65 y) who were diagnosed with NAFLD through clinical examination, laboratory tests, and ultrasound findings, and those willing to provide informed consent were included in the study. All patients received 2 Liv.52 DS tablets, BID, for 2 months. Liver function tests, ultrasound to evaluate hepatomegaly, NAFLD fibrosis score, lipid profile, hematology, and biochemical investigations were done at baseline and at the end of months 1 and 2. There was a significant improvement in hepatomegaly and liver function parameters such as aspartate transaminase and alanine transaminase. The NAFLD fibrosis score revealed that there was no progression in liver fibrosis due to NAFLD during the study period. No adverse events were reported during the study. The study demonstrated that Liv.52 DS is safe and effective in the management of NAFLD. Aim To assess the safety and efficacy of Liv.52 DS tablets in the management of nonalcoholic fatty liver disease (NAFLD) Materials and Methods Inclusion criteria This prospective interventional study included 60 patients of either sex (aged 18–65 y) who were diagnosed with NAFLD through clinical examination, laboratory tests, and ultrasound findings, and those who were willing to provide informed consent. Exclusion criteria Alcoholic individuals; patients with severe metabolic disorders, hepatic or pancreatic carcinoma, allergies, systemic diseases, and genetic disorders; and pregnant and lactating women were excluded from the study. Study procedure A detailed medical history of all the patients was obtained, and symptomatic evaluation was performed at the first visit. They were examined for the presence of steatohepatitis with hepatomegaly. All the patients were prescribed 2 Liv.52 DS tablets, BID, for 2 months. Liver function tests (LFTs; including aspartate transaminase [AST], alanine transaminase [ALT], alkaline phosphatase, g-glutamyl transferase, serum bilirubin, and albumin levels), ultrasound findings (for hepatomegaly), and NAFLD fibrosis score (to determine the severity of fibrosis due to NAFLD) were done at baseline and at the end of months 1 and 2. Statistical analysis All data were statistically analyzed using GraphPad Prism software version 6.07 (GraphPad Software, CA, USA). The data obtained from LFTs, biochemical investigations, and NAFLD fibrosis scores were analyzed using ANOVA followed by Tukey’s multiple comparison test. The ultrasound findings of hepatomegaly were analyzed using repeated measures ANOVA followed by Dunnett’s multiple comparison test. NAFLD was graded based on the NAFLD score as < - 1.455 = F0–F2; - 1.455 to 0.675 = indeterminate; and > 0.675 = F3–F4.
Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 | 5 Liv.52 DS in the Management of Nonalcoholic Fatty Liver Disease Results It was observed that the NAFLD fibrosis score reduced by the end of month 1 and further reduced by the end of month 2. Similarly, after treatment with Liv.52 DS, there was a reduction in the fibrosis score in patients with indeterminate scores. This indicates that Liv.52 DS helps reduce liver fibrosis associated with NAFLD. Table 1 shows the effect of Liv.52 DS on hepatomegaly; there was a significant improvement after the treatment. After the treatment with Liv.52 DS, the liver size significantly reduced from 17.44 ± 1.9 cm at baseline to 17.29 ± 1.77 cm by the end of month 1 and further reduced to 15.87 cm by the end of month 2 (P < .0001) (Figure). The levels of ALT and AST, which were elevated at baseline, decreased at the end of the study (Table 2). Hematological and biochemical investigation results were within normal limits. No adverse events were reported during the entire study period. The overall compliance with the treatment was good, with no treatment discontinuation. Discussion The hepatoprotective activity observed in this study can be attributed to the synergistic action of the bioactive herbs present in Liv.52 DS—Capparis spinosa, Cichorium intybus, Solanum nigrum, Terminalia arjuna, Cassia occidentalis, Achillea millefolium, and Tamarix gallica. C spinosa prevents elevation of malondialdehyde (plasma and hepatic), AST, and ALT levels. C intybus suppresses the oxidative degradation of DNA in tissue debris. S nigrum protects the DNA against oxidative damage and acts as a Table 1. Effect of Liv.52 DS on Hepatomegaly Liver Size on Ultrasonographic Screening Baseline Month 1 Month 2 Patients, n (%) Patients, n (%) Patients, n (%) > 16 cm (Hepatomegaly) 45 (75) 43 (72) 25 (42) < 16 cm (No Hepatomegaly) 15 (25) 17 (28) 35 (58) Figure. Effect of Liv.52 DS on Liver Size 5 0 10 15 20 25 Liver Size, cm Baseline Month 1 Month 2 Table 2. Effect of Liv.52 DS on LFTs (AST and ALT) Parameter Baseline Month 1 Month 2 AST, IU/L 60.33 ± 13.04 56.43 ± 15.47 54.12 ± 17.26 P < .0339a ALT, IU/L 70.68 ± 18.49 64.13 ± 22.07 P < .0215a 61.9 ± 22.7 P < .0022a Statistical test: ANOVA followed by Tukey’s multiple comparison test. Significance was fixed at P < .05. Values are represented as mean ± SD. aCompared with baseline. ALT, alanine transaminase; AST, aspartate transaminase; LFTs, liver function tests. potent scavenger of hydroxyl and diphenylpicrylhydrazyl radicals. T arjuna reduces cholesterol levels. C occidentalis modulates hepatic enzyme levels. T gallica has a beneficial effect on liver glycogen and serum proteins. Conclusion The findings of the study suggest that Liv.52 DS is safe and effective in the management of NAFLD.
6 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 Liv.52® Drops in the Management of Loss of Appetite in Children An excerpt of a clinical study conducted by Bhattacharya SS et al published in the journal The Antiseptic has been featured here. Aim To evaluate the safety and efficacy of Liv.52 Drops in the management of loss of appetite in children. Materials and Methods This open clinical trial included 70 children of either sex with a history of loss of appetite for at least 1 month. The parents were instructed to administer Liv.52 Drops orally to their children at a dosage of 15 to 20 drops, BID, for 12 weeks. The children were evaluated for appetite, nausea, and fatigue every fortnight for 3 months. Their body weight and height were also noted. All children were subjected to detailed clinical and hematological examinations and liver function tests (serum bilirubin and alanine transaminase) at entry and at the end of the study period. The primary end point was the subjective decrease in loss of appetite leading to an increase in body weight. The secondary end points were general well-being and the incidence of adverse effects, if any. Results Of the 70 children enrolled, 67 children completed the study. Most children showed significant improvement in appetite at the end of 3 months of the treatment with Liv.52 Drops (P < .01). Of the 67 children, only 6 had loss of appetite at the end of the study. Only 7 of the 30 children who reported to have nausea at entry, still had nausea at the end of the study (P < .01). Weight loss was noticed in 60 children at entry, and there was a significant weight gain at the end of every month (P < .01) in all except 5 children (Figure). The children experienced less fatigue after the treatment. There was a significant improvement in hemoglobin and serum protein levels (P < .01). There were no adverse effects reported. Conclusion These findings suggest that Liv.52 Drops are safe and effective in managing loss of appetite in children. Figure. Effect of Liv.52 Drops on Clinical Parameters of Growth in Children With Loss of Appetite aP < .05 compared with the at-entry values. 0 10 30 40 20 50 60 70 No. of Patients Loss of Appetite Weight Loss Vomiting/Nausea Baseline a a a a a a a a a At 1 month At 2 months At 3 months Research at Himalaya
In loss of appetite… Normalizes the basic appetite-satiety rhythm • Restores liver function and corrects metabolism • Normalizes appetite and increases food intake • Increases bile secretion and serum protein levels • Improves digestion and assimilation, and helps in weight gain • Does not cause drowsiness like conventional preparations Liv.52 (DROPS, SYRUP, TABLET) Restores appetite and promotes growth Liv.52—Unparalleled in liver care Dosage Infants Drops: 5–10 drops thrice daily. Children Drops: 10–20 drops thrice daily. Syrup: 5 ml twice or thrice daily. Tablet: 1 tablet thrice daily. Adults Syrup: 10 ml twice or thrice daily. Tablet: 2 tablets thrice daily.
8 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 500 mg/kg, respectively, along with CCl4, for 4 days. The results revealed that the rats treated with E alba extracts showed a significant decrease in the serum ALT, AST, ALP, and total bilirubin levels, demonstrating an effective hepatoprotective property. Histopathology of the liver showed that groups 4 and 5 exhibited high degree of protection of the liver against CCl4-induced hepatotoxicity. The outcome was comparable to that of silymarin.2 References 1. Jahan R, et al. Int Sch Res Notices. 2014;2014:385969. 2. Beedimani RS, Shetkar S. Int J Basic Clin Pharmacol. 2015;4(3):404–409. P amarus extract at doses of 100, 200, and 300 mg/kg (dissolved in 0.2 mL distilled water), respectively, for 30 days. The results showed that oral administration of P amarus extract to mice with CCl4-induced liver damage significantly mitigated the toxic effects of CCl4 in a dose-dependent manner. The findings suggest that P amarus extract has potent hepatoprotective activity.3 References 1. Dossou-Yovo HO, et al. Sci World J. 2021;2021:6650704. 2. Sidhu MC, Singh R. Plant Arch. 2020;20(2): 4901–4906. 3. Krithika R, Verma RJ. Acta Pol Pharm. 2009;66(4):439–445. herb facts Eclipta alba Eclipta alba is an annual herb that grows up to 30 to 40 cm tall. The stem is cylindrical or flat and red; the leaves are oblong, sessile to subsessile, and about 2 to 6 cm long; and the seeds are dark brown. The herb possesses anticancer, hepatoprotective, anti-inflammatory, and antimicrobial properties.1 A study evaluated the hepatoprotective activity of aqueous extract of E alba against carbon tetrachloride (CCl4)– induced hepatotoxicity in male albino rats. Thirty rats were divided into 5 groups (6 rats each): group 1 received 1 mL/kg of vehicle; group 2 (toxic control) was administered CCl4 (2 mL/kg) intraperitoneally; group 3 received silymarin (50 mg/kg) along with CCl4; and groups 4 and 5 received the aqueous extract of E alba at doses 250 and Phyllanthus amarus Sanskrit name: Bhumyamalaki English name: Stone Breaker Phyllanthus amarus is an annual, glabrous, erect herb that grows up to 60 to 75 cm tall. The stem is branched at the base and angular with numerous leaves; the roots are stout and woody; the seeds are trigonous and brownish black; and the fruit is a capsule and appears green.1,2 A study evaluated the hepatoprotective effect of P amarus plant extract against CCl4-induced liver damage in female mice models. Inbred female Swiss albino mice aged 6 to 8 weeks were considered for the study. Seventy mice were divided into 7 groups (10 mice each): group 1 served as untreated control; group 2 received CCl4 (dissolved in 0.2 mL olive oil); group 3 served as plant control and received P amarus extract (300 mg/kg) in 0.2 mL distilled water; group 4 received a high dose of CCl4 (826 mg/kg dissolved in 0.2 mL olive oil); and groups 5, 6, and 7 received a high dose of CCl4 along with Sanskrit name: Bhringaraja English name: False Daisy
Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 | 9 health news Association Between Early Childhood Lower Respiratory Tract Infections and Premature Adult Mortality A recent study published in The Lancet evaluated the association between early childhood lower respiratory tract infections (LRTIs) and the risk of premature adult mortality due to respiratory diseases. This longitudinal observational study included data of 3589 participants from the Medical Research Council, the National Survey of Health and Development (England, Scotland, and Wales). They were followed up through the ages of 26 to 73 years. Of the 3589 participants, 913 participants had LRTIs during early childhood (at < 2 y of age); they were at an increased risk of mortality due to respiratory diseases by the age of 73 years than those who did not have LRTI in early childhood (P = .021). These findings suggest that children with LRTIs by 2 years of age were almost twice likely at an increased risk of premature death from respiratory diseases as adults, and these infections account for one-fifth of respiratory-cause deaths. This association remained even after adjusting for multiple markers of childhood socioeconomic conditions and adult smoking. Childhood LRTIs were not associated with other causes of death, thus suggesting a direct connection between early childhood LRTIs and the development or prognosis of adult respiratory diseases, such as chronic obstructive pulmonary disease. Source: Allinson JP, et al. Lancet. 2023;401(10383):1183–1193. Association Between Sleep and Cardiovascular Disease–Free Life Expectancy A study published in BMC Medicine determined the differences in cardiovascular disease (CVD)–free life expectancy in people with poor sleep profiles. The selfreported sleep data of 308,683 middle-aged adults were retrieved from the UK Biobank. Of these, the data of 140,181 patients had captured primary care and inpatient records too. Their (n = 140,181) clinical sleep disorders were classified into insomnia, sleep-related breathing disorders, and other sleep disorders. The CVD-free life expectancies in women and men with poor sleep and healthy sleep were 31.46 and 33.26 and 27.96 and 30.27 years, respectively. Men with clinical insomnia or sleep-related breathing disorders lost 3.84 or 6.73 years of CVD-free life, respectively. Women with sleep-related respiratory difficulties or other sleep disorders lost 7.32 or 1.43 years of CVD-free life, respectively. This study’s findings suggest that poor sleep is negatively associated with CVD-free life, especially in patients with sleeprelated breathing disorders. Source: Huang BH, et al. BMC Med. 2023;21(1):75.
10 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 expert comments Liv.52® (DROPS, SYRUP, TABLET, DS SYRUP, DS TABLET) Unparalleled in liver care Dosage Acute viral hepatitis Drops: 5 to 10 Drops TID (infants); 10 to 20 Drops TID (children) Syrup: 5 mL TID (children); 10 mL TID (adults) Tablet: 1 Tablet TID (children); 2 Tablets TID (adults) Syrup: 5 mL BID/TID (children); 10 mL BID/TID (adults) Tablet: 1 Tablet TID (children); 2 Tablets TID (adults) Drug-induced hepatitis DS Syrup/DS Tablet: 1 to 2 Teaspoonsful/Tablets BID with anti-TB/ Alcohol-induced liver damage Syrup: 10 to 15 mL TID Tablet: 2 to 3 Tablets TID Anorexia and suboptimal growth Drops: 5 to 10 Drops TID (infants); 10 to 20 Drops TID (children) Liv.52 is a hepatospecific formulation, designed for the treatment and management of liver disorders. An InterviewWith Dr Smita Datta Doctor, does type 2 diabetes mellitus (T2DM) increase the risk of developing nonalcoholic fatty liver disease (NAFLD)? Yes, T2DM is one of the important risk factors for the development of NAFLD. T2DM is the most common metabolic disorder that contributes to the development of various liver abnormalities such as liver fibrosis, cirrhosis, NAFLD, nonalcoholic steatohepatitis (NASH), hepatocellular carcinoma, and chronic viral hepatitis. T2DM is commonly associated with insulin resistance (IR). IR promotes excess accumulation of free fatty acids (FFAs) in the peripheral adipose tissue of the liver, which results in the development of fatty liver and consequently, NAFLD and fibrosis. How are NAFLD and T2DM interconnected? NAFLD and T2DM are related bidirectionally. In patients with T2DM, the excess glucose stored in the liver undergoes glycolysis and is eventually converted into fatty acids and triglycerides. Furthermore, IR causes impairment in the secretion of very low-density lipoprotein, which in turn leads to hepatic fat accumulation and results in the development and progression of NAFLD. On the other hand, in patients with NAFLD, excess fat deposition in the liver makes the body more resistant to insulin and strains the pancreatic β cells, resulting in the development of T2DM. The coexistence of NAFLD and T2DM can increase the risk of development of NASH, liver fibrosis, and cirrhosis. What are the hepatic complications generally seen in patients with T2DM? Patients with T2DM are likely to have NAFLD and are at a high risk of developing other hepatic complications such as NASH, cirrhosis, hepatocellular carcinoma, and portal hypertension. What metabolic alterations pertaining to fatty acid metabolism occur in patients with T2DM? Many adverse metabolic alterations occur with respect to fatty acid metabolism in patients with T2DM. In these patients, severe atherogenic dyslipidemia with hypertriglyceridemia, a low level of high-density lipoprotein cholesterol, and the presence of smaller and denser low-density
Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 | 11 Chronic active hepatitis DS Syrup/DS Tablet: 2 Teaspoonsful/ Tablets BID for 6 months Early cirrhotic conditions DS Syrup/DS Tablet: 1 Teaspoonful/ Tablet TID for 6 to 12 months statin/antiretroviral treatment and chemotherapy Jaundice and anorexia during pregnancy DS Syrup/DS Tablet: 1 Teaspoonful/ Tablet BID for 8 weeks Nonalcoholic steatohepatitis (NASH) DS Tablet: 1 to 2 Tablets BID As a supportive treatment during hemodialysis DS Syrup/DS Tablet: 1 Teaspoonful/ Tablet BID for 3 to 4 months As an adjuvant to anticancer drugs DS Syrup/DS Tablet: 1 Teaspoonful/ Tablet BID for 4 months Dr Smita Datta, MD Consultant Physician Dosti Shoppe Link Mall Wadala East Mumbai 400037, Maharashtra India Patients with T2DM are at a high risk of developing NAFLD and other hepatic complications too. Inculcating healthy lifestyle practices such as consuming a balanced diet and engaging in regular physical activity can reduce the intrahepatic triacylglycerol level and improve glycemic control/insulin sensitivity in patients with both NAFLD and T2DM. lipoprotein particles can be observed. Further, there is always a risk of all these metabolic abnormalities translating into worse cardiovascular diseases in patients with T2DM. How do diet and lifestyle choices affect the incidence of NAFLD and T2DM?What are the dietary recommendations for managing NAFLD and T2DM? The development of NAFLD and T2DM is linked to lifestyle factors such as excess intake of unhealthy and calorie-dense foods and reduced physical activity. Maintaining a healthy body weight, to a great extent, helps in the management of NAFLD and T2DM. Consuming a balanced diet, for example, Mediterranean and other hypocaloric diets, and engaging in regular physical activity can help reduce the intrahepatic triacylglycerol level and improve glycemic control/insulin sensitivity in patients with both NAFLD and T2DM. Also, patients with NAFLD must avoid excess alcohol consumption, as it increases the risk of disease progression. Doctor, what medication do you prescribe for managing NAFLD in patients with T2DM? How has it benefitted them? I have found Liv.52 DS to be very useful in the management of liver disorders. Liv.52 DS, a hepatospecific formulation from Himalaya Wellness Company, is specifically designed for the treatment and management of liver disorders. In NASH and liver diseases caused by diabetes, Liv.52 DS decreases the uptake of FFAs by the hepatocytes and helps reduce fat deposition in the hepatocytes. Liv.52 DS promotes the production of new proteins responsible for the transportation of glucose into the cells, and thus, increases glucose uptake and reduces IR. We thank our field correspondents for their input and support. Ashish Dinesh Chaubey, Regional Manager Umesh Gajanan Gawand, Pharma Sales Officer HimalayaWellness Company —Editor An Interview With Dr Smita Datta
12 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 An InterviewWith Dr Sunil K Sharma Doctor, how is appetite regulated in the human body? Hunger, satiation, and satiety are the 3 components of appetite that are controlled by the brain, digestive system, endocrine system, and sensory nerves. These control systems can drive an individual’s appetite by regulating the response to the physical presence or absence of food and to different components of food. How does loss of appetite affect the body? Loss of appetite is known to affect various body systems. Loss of appetite often leads to nutritional insufficiency in infants, children, and the elderly. Hence, weight loss and undernutrition are considered as the direct results of loss of appetite. Starvation-induced protein and fat catabolism leads to loss of cellular volume and function, resulting in adverse effects on the heart, brain, liver, intestines, kidneys, and muscles. In the elderly, activation of proinflammatory cytokines due to acute and chronic diseases, sensory changes, and side effects of certain medications may also lead to loss of appetite. What are the clinical manifestations of poor appetite? Nutritional deprivation due to loss of appetite can lead to physiologic disturbances such as bradycardia, hypothermia, and hypotension. Further, dry skin, alopecia, constipation, bloating, delayed gastric emptying, osteoporosis, hypoglycemia, amenorrhea, and thyroid abnormalities also occur in individuals suffering from loss of appetite. How does loss of appetite trigger hypoglycemia? Loss of appetite accompanied by weight loss can lead to depletion of the hepatic glycogen reserve and disruption of hepatic gluconeogenesis, resulting in abnormalities of glucose metabolism and hypoglycemia. What alterations in the liver biochemistry are detected in those with a poor appetite? About 2 to 3 times elevations in aspartate transaminase and alanine transaminase are the most common laboratory abnormalities detected in individuals suffering from loss of appetite. Starvation and weight loss usually trigger elevation of transaminases. The increase in liver transaminase levels is usually due to cell death in events such as hepatocellular necrosis, hepatic inflammation, or the autophagy process. Doctor, how do you address poor appetite in all age groups? Loss of appetite can be managed using appetite stimulants, comprising vitamins B12, B3, and B6, lysine, and zinc, and by changing meal patterns and eating habits. Additionally, I prescribe Liv.52 (drops, syrup, and tablet forms), an Ayurvedic proprietary formulation from Himalaya Wellness Company, to patients complaining of loss of appetite. Liv.52 normalizes the basic appetite–satiety rhythm; improves appetite, digestion, and assimilation processes; and promotes weight gain. Dr Sunil K Sharma, MD General Physician 380-A, Gandhi Nagar Jammu 180004, Jammu and Kashmir India We thank our field correspondents for their input and support. Rajiv Koul, Regional Manager Rahul Chaman, Pharma Sales Officer HimalayaWellness Company —Editor expert comments
Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 | 13 Patient Education Effective Ways to Manage Diabetes Diabetes is on the rise worldwide and is a major cause of blindness, heart attack, stroke, and kidney failure. In 2019, diabetes was the direct cause of 1.5 million deaths globally, and 48% of all deaths due to diabetes occurred before the age of 70.1 There is no cure for diabetes, but maintaining optimal body weight, eating healthy, and being physically and mentally active can help manage the disease.2 The long-term detrimental effects of diabetes can be reduced by keeping blood glucose level within the recommended range.3 The following are a few tips that can be given to your patients to manage diabetes. Maintaining a healthy weight: Obesity is one of the major causes of type 2 diabetes (T2D). Exercising regularly and working on the muscles improves the body’s ability to use insulin and absorb glucose more efficiently. Studies suggest that brisk walking, at least for 30 minutes every day, reduces the risk of developing type 2 diabetes by 30%. For best results, one should aim for at least 150 minutes of moderate-intensity fitness activities (eg, swimming, cycling, lawn mowing, and dancing) per week.4,5 Choosing a healthy diet: Consuming whole grains (eg, brown rice, whole oats, and buckwheat) leads to low and slow increases in blood glucose and insulin, as these are slow-digesting carbohydrates. This further helps lower the glycemic index. Also, fruits (eg, apples, strawberries, blueberries, and melons), vegetables (eg, lettuce, broccoli, cucumbers, green beans, and tomatoes), pulses (eg, beans, chickpeas, and lentils), and dairy products (eg, unsweetened yogurt and milk) are beneficial. Foods with healthy fats such as unsalted nuts, seeds, avocados, olive oil, rapeseed oil, and sunflower oil are recommended. Consuming saturated fats present in red and processed meat, fried foods, cakes, biscuits, pies, and pastries must be avoided, as these can increase cholesterol and blood glucose level.5,6 Consuming less sugar and salt: Reducing sugar intake helps control blood glucose level and maintain a healthy weight. Sugary drinks, energy drinks, and fruit juices can be replaced with water, plain milk, or tea/coffee without sugar. Similarly, excess salt consumption is harmful, as it can increase the risk of hypertension. Keeping a check on daily salt intake is important. Individuals with diabetes should limit their salt intake to 6 g (1 teaspoon) per day.5 Avoiding smoking: Smoking increases the risk of T2D and various other associated complications. Smokers are at a 50% higher risk of developing T2D than nonsmokers, and heavy or chain smokers have an even higher chance. So, smoking should be avoided to help mitigate these risks.4,7 References 1. World Health Organization. Diabetes. https://www.who.int/. Published April 5, 2023. Accessed June 1, 2023. 2. Centers for Disease Control and Prevention. What is diabetes? https://www.cdc.gov/. Reviewed April 24, 2023. Accessed June 1, 2023. 3. BetterHealth Channel. Diabetes: long-term effects. https://www.betterhealth.vic.gov. au/. Reviewed March 23, 2021. Accessed June 1, 2023. 4. Harvard T.H. Chan. Simple steps to preventing diabetes. https://www.hsph.harvard. edu/. Accessed June 1, 2023. 5. Diabetes UK. 10 Tips for healthy eating with diabetes. https://www.diabetes.org.uk/. Accessed June 1, 2023. 6. American Diabetes Association. Get smart on carbs. https://diabetes.org/. Accessed June 12, 2023. 7. Mayo Clinic. Diabetes care: 10 ways to avoid complications. https://www.mayoclinic. org/. Published January 29, 2022. Accessed June 1, 2023.
14 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 Technologic Advances A Novel Liquid Biopsy Approach for the Diagnosis of Nonalcoholic Steatohepatitis and Liver Fibrosis A new liquid biopsy test that uses the peripheral monocyte proteins perilipin (PLIN)-2 and Ras-related protein (RAB)- 14 and specific algorithms to detect nonalcoholic steatohepatitis (NASH) and liver fibrosis has been developed. Conventional liver biopsy is considered the gold standard for the diagnosis of NASH and its progressive forms. However, there is a need for a more reliable and noninvasive diagnostic technique to predict NASH progression. This novel liquid biopsy approach quantifies the PLIN2 protein found on isolated hepatocytes and the RAB14 protein found on hepatic stellate cells in patients with obesity and nonalcoholic fatty liver disease (NAFLD), respectively, and generates algorithms for the accurate detection and staging of NASH and liver fibrosis. Study Design and Procedure This multicenter study included a discovery cohort (n = 100; aged 46.9 ± 10.5 y) from the BRAVES trial and a validation cohort (n = 150; aged 43.4 ± 11.9 y) from the LIBRA trial. Both study groups mostly included women with histologically proven NAFLD or NASH (with or without fibrosis). NASH was detected using the PLIN2 algorithm that included parameters such as mean florescence intensity (MFI), waist circumference (WC), triglyceride, alanine transaminase (ALT), and the presence or absence of diabetes mellitus as covariates. Liver fibrosis was detected using the RAB14 algorithm that included parameters such as MFI, age, WC, high-density lipoprotein cholesterol, plasma glucose, and ALT level as covariates. The study used neural network (NN) classifiers to detect NASH and NASH stages and logistic bootstrap-based regression to measure the accuracy of predicting liver fibrosis. NASH and fibrosis predictions The NN analysis for the detection of NASH using PLIN2 showed an accuracy, sensitivity, and specificity of 93%, 95%, and 90%, respectively, in the discovery cohort and 92%, 88%, and 100%, respectively, in the validation cohort. The detection of liver fibrosis using RAB14 had an accuracy, sensitivity, and specificity of 86.4%, 96.0%, and 45.8%, respectively, in the discovery cohort, and 82.4%, 96.9%, and 34.5%, respectively, in the validation cohort. Both the PLIN2 and RAB14 biomarkers showed better efficiency than the conventional fibrosis-4 score and aspartate transaminase to platelet ratio methods and were also comparable to ultrasound 2-dimensional shear wave elastography. Thus, the detection of NASH severity and liver fibrosis using the PLIN2 and RAB14 algorithms, respectively, was accurate. Quantification of PLIN2 and RAB14 to detect NASH and liver fibrosis, respectively, is scalable to an analytical capacity of up to 800 samples per day. Therefore, PLIN2 and RAB14 have the potential to replace invasive liver biopsy– based histologic assessment for the detection of NASH and liver fibrosis. Source: Angelini G, et al. Gut. 2023;72:392–403.
Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 | 15 The Liver and the Body Nonalcoholic Fatty Liver Disease Increases the Risk of Irritable Bowel Syndrome: Decoding the Liver–Gut Interaction Nonalcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) are 2 highly prevalent clinical conditions with overlapping pathophysiologies. NAFLD and IBS (Rome III or Rome IV diagnostic criteria) have been found to have common etiologic factors such as unhealthy dietary pattern and obesity, gut dysbiosis, and uncontrolled immune responses. Both NAFLD and IBS significantly affect the quality of life. Various preclinical studies reveal a high prevalence of IBS in patients with NAFLD. The plausible association between NAFLD and IBS may be because of the following factors: Expression of Proinflammatory Cytokines Proinflammatory cytokines have been reported to play an important role in the development of IBS symptoms mediated by toll-like receptors. • Increased expression of tumor necrosis factor-α influences the peripheral and central nervous systems to become hypersensitive and the gut to become hypomotile. • Increased expressions of interleukin (IL)-6 affects the stimulation of gut submucosal neurons and intestinal barrier integrity. • Increased levels of IL-1β and IL-6 and decreased level of IL-10 influence gut homeostasis. Cross-Talk of the Liver–Brain–Gut Neural Arc The communication between the gut and liver is relayed from the liver to the brain by the autonomic nervous system. Such communication mediated by the peripheral regulatory T-cells is necessary for maintaining immune homeostasis and preventing uncontrolled inflammatory responses. Gut Dysbiosis The bile salts and antimicrobial molecules are generally transported from the liver to the intestinal lumen through the biliary tract. This safe passage controls unrestricted bacterial overgrowth and ensures gut eubiosis. In NAFLD, the ineffective clearance of microbial byproducts and inhibition of bacterial overgrowth leads to gut dysbiosis. These alterations in the gut microbiota eventually affect intestinal permeability, intestinal motility, and visceral hypersensitivity, and result in IBS. Thus, it is imperative to evaluate the presence of the clinical features of IBS in patients with NAFLD and ensure timely medical intervention. Sources: Purssell H, et al. World J Hepatol. 2021;13(12):1816–1827. Wu S, et al. BMC Med. 2022;20:262.
16 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 Liver Health Associations journal Facts Therapeutic Advances in Gastroenterology Image source: https://www.google.com/ search?rlz=1C1GCEU_enIN1020IN1020&q=therapeut ic+advances+in+gastroenterology&tbm=isch&sa=X &ved=2ahUKEwiV0ZuGi8X_AhXEVWwGHTr9AAcQ0pQ JegQIDhAB&biw=1366&bih=625&dpr=1 Diabetes Mellitus • The 4 metabolic abnormalities observed in diabetic patients are obesity, increased endogenous glucose output, abnormal insulin action, and insulin secretion dysfunction.1 • More than 90% of patients with diabetes have type 2 diabetes mellitus.1 • Diabetic patients are at an increased risk of tuberculosis, severe gram-positive infections, hospital-acquired postoperative infections, urinary tract infections, and tropical diseases.2 • Diabetic patients are 1.5 times more likely to experience cognitive dysfunction and dementia.3 • Disruption of intestinal flora can cause diabetes as intestinal permeability, inflammation, the immune system, and energy metabolism are affected.4 • Overnutrition affects diversity and stability of the intestinal flora and increases pathogenic microflora, causing low-grade inflammation in the gut that could lead to insulin resistance and diabetes mellitus.4 References 1. Guo H, et al. Int J Mol Sci. 2023;24(8):6978. 2. Harding JL, et al. Diabetologia. 2019;62(1): 3–16. 3. Varghese SM, et al. Front Public Health. 2022;10:822062. 4. Aydin OC, et al. World J Clin Cases. 2023;11(1):65–72. Therapeutic Advances in Gastroenterology is a peer-reviewed, open access journal launched in 2008. The journal publishes original articles, reviews, and scholarly comments on research and innovative studies pertaining to all areas of gastrointestinal and hepatic disorders. The journal exclusively publishes clinical research studies. It caters to an international audience of clinicians and researchers in gastroenterology and related disciplines, thus, providing an online platform for disseminating recent research and findings in the field. International Society of Liver Surgeons The International Society of Liver Surgeons (ISLS) was founded in 2016 to foster both academic and educational developments in the surgical treatment of liver and biliary diseases. The ISLS aims to disseminate scientific advances in hepatopancreato-biliary (HPB) surgery; liver transplantation; and laparoscopic, robotic, and endoscopic treatments of liver diseases. Its mission is to bring together surgical and medical experts from around the globe who treat patients with hepatobiliary and pancreatic diseases to improve the understanding of these diseases and enhance research capacity. The ISLS also comprises the ISLS Study Groups Platform, a unique platform that aims at increasing the survival rate and improving the quality of life of people suffering from liver diseases by creating awareness about the latest developments in liver transplantation and HPB surgery. https://www.isls-liversurgeon.org/
Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 | 17 DOCTORS’ FEEDBACK Liv.52 is a hepatospecific formulation, designed for the treatment and management of liver disorders. Liv.52 has a wide spectrum of therapeutic applications. Liv.52 restores the metabolic efficiency of the liver, minimizes damage to the hepatic parenchyma, and accelerates the rate of recovery in various liver disorders like infectious hepatitis, drug-induced hepatitis, and alcoholic liver diseases. Liv.52 is a valuable adjuvant during prolonged illness. In anorexia, Liv.52 improves appetite, digestion, and assimilation. Liv.52 also prevents the complications of nonalcoholic steatohepatitis (NASH). Liv.52 is one of the world’s most enduring phytomedicines, accredited with more than 250 studies, and is available in a wide range of dosage forms to suit the requirement of patients of all age groups. Liv.52 is safe even for long-term use. Here are some clinical experiences with Liv.52, shared by a few eminent doctors. I have been prescribing Liv.52 for several years to patients with fatty liver, hepatitis, cholangitis, and anorexia. I have seen excellent results in 7 weeks of therapy. Dr Harsha Sharma MBBS, MS Jagadhri 135003, Haryana Liv.52 is a supportive liver tonic for all age groups of patients. I have seen very good results in cases of hepatoxicity and fatty liver. Dr Simple Hinduja BAMS Nagpur 440002, Maharashtra Liv.52 is effective in increasing appetite in patients, and also gives a sense of overall well-being. Dr Pradeep Prahlad MBBS, MRSH, MIRCGP Bhopal 462001, Madhya Pradesh I have been prescribing Liv.52 for more than 4 years to both adult as well as pediatric patients. I have seen very good results in liver disorders and digestive disorders. Liv.52 is very effective in complaints of loss of appetite in pediatric patients. Dr Deepak Soni BAMS Ambikapur 497001, Chhattisgarh I have been prescribing Liv.52 for many years to elderly patients with loss of appetite and anorexia. Also, Liv.52 gives good results when given along with antibiotics and in anti-Koch treatment. Dr Shailesh Zadbuke MBBS, DCP Solapur 413213, Maharashtra I have been practicing since 1994 and have been prescribing Liv.52 for many years. I recommend Liv.52 in loss of appetite, NAFLD, and other liver problems. I have seen very good results. Dr Shilpa N Jackson MD, DAc, BHMS, MG Hom, FAIS Mumbai 421003, Maharashtra
18 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 Ayurveda trends Inauguration of Shanghai Cooperation Organization’s First International Conference and Expo on Traditional Medicine ICMR and Ayush Ministry Sign MoA to Promote Research in Integrated Medicine The first business-to-business (B2B) global conference and expo on traditional medicine under the Shanghai Cooperation Organization (SCO) was inaugurated on March 2, 2023, in Guwahati, Assam, India. Mr Sarbananda Sonowal (Union Minister of Ayush, Government of India) inaugurated the conference that was attended by more than 150 delegates from 17 countries. The inaugural ceremony was graced by Dr Mahendra-bhai Munjpara (Union Minister of State for Ayush andWomen and Child Development, Government of India), Dr Thet Khaing Win (Union Minister of Health, Government of Myanmar), Safiyya Mohamed Saeed (Deputy Minister of Health, Government of Maldives), and Vaidya Rajesh Kotecha (Secretary, Ministry of Ayush, Goverment of India). The conference and expo provided a good opportunity for regulatory bodies, industries, and business leaders in the SCO and partner countries to work toward expanding different aspects of traditional medicine (ie, products, services, education, skill development, cosmetics, and herbal extracts) and further improving the trade among various countries, thereby, taking traditional medicine to greater heights. Additionally, sessions on Regulatory Framework for Traditional Medicine Products with detailed presentations by the SCO members of India, Kazakhstan, Kyrgyzstan, Pakistan, Russia, China, Tajikistan, and Uzbekistan were part of this event. Such discussions on innovation and the display of products of native importance will foster an environment for better cooperation and economic partnerships with bigger market access among the SCO countries. Source: SCO’s first international conference, expo on traditional medicine inaugurated by Sarbananda Sonowal. ANI. March 3, 2023. https://www.aninews.in/news/national/general-news/ scos-first-international-conference-expo-on-traditional-medicine-inaugurated-by-sarbanandasonowal20230303004848/. Accessed June 7, 2023. In order to boost India’s health care infrastructure and to integrate and bring the Ayush sector to the mainstream, the Ministry of Ayush and the Indian Council of Medical Research (ICMR) signed a Memorandum of Agreement (MoA) on May 11, 2023. The MoA aims at collaboration and cooperation in health care research in integrated medicine. The agreement was signed by Vaidya Rajesh Kotecha (Secretary, Ministry of Ayush) and Dr Rajiv Bahl (Secretary, Department of Health Research and Director General, ICMR) in the presence of other esteemed members. The MoA envisages exploring the scope of integrative health research and strengthening research capacity. It also aims at exploring the possibilities of working on public health research, taking initiatives to identify disease conditions of national importance, and conducting high-quality clinical trials jointly to provide promising therapies, thus, generating evidence for wider acceptance of the Ayush system. Furthermore, a joint working group will be established from both parties who will meet quarterly to check for the future scope of collaboration and work on the deliverables. Both parties will also implement joint research programs as well as supervise the mentioned activities. Additionally, the parties will conduct seminars, conferences, and workshops and will seek active participation from researchers interested in integrative health care. Source: ICMR signs MoA with Ayush ministry. New Delhi Times. May 12, 2023. https://www. newdelhitimes.com/icmr-signs-moa-with-ayush-ministry/. Accessed June 6, 2023.
RkJQdWJsaXNoZXIy MjAwNDg=