Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.

OBJECTIVE: Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS: During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS: The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS: AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION: CTRI/2020/06/025557.

Withania somnifera as a safer option to hydroxychloroquine in the chemoprophylaxis of COVID-19: Results of interim analysis.

OBJECTIVES: To study the efficacy and safety of Withania somnifera (WS, Ashwagandha) in the prophylaxis against COVID-19 in high risk health care workers (HCW) in comparison to hydroxychloroquine (HCQ). To evaluate the general physical and mental health benefits of Ashwagandha. METHODS: A 16 week randomized prospective, open-label, parallel efficacy, two arm, multi-centre study. The primary efficacy measure was 'failure of prophylaxis' as confirmed COVID-19 by quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) at any time during the study period. This study on 400 participants from three centres was designed to establish non-inferiority for WS to HCQ for prophylaxis against COVID-19 at 80 % power and significance p < 0.025, one-sided. The interim analysis was carried out on 160 participants after completion of 8 weeks. RESULTS: Participants in both the arms were well-matched at the baseline characteristics. Forty participants in the HCQ group and 26 participants in the WS group reported mild AE. The symptoms of confirmed COVID-19 were found to be 3.7 % (95 % CI 1.3-10.5 %) in the HCQ and 1.3 % (95 % CI 0.02-6.7 %) in the WS arm amongst the first 160 participants completing 8 weeks. CONCLUSION: Our intent was to explore a safer option to HCQ. We report that WS was not found inferior to HCQ and its efficacy was within the 15 % non-inferiority margin set a priori. WS as an immunomodulator has other clinical benefits including reducing mental stress. The final report of this study is expected by end of August 2021.

Efficacy and Safety of Turmeric Extracts for the Treatment of Knee Osteoarthritis: a Systematic Review and Meta-analysis of Randomised Controlled Trials.

PURPOSE OF THE REVIEW: Finding appropriate pharmacological options to treat osteoarthritis (OA) remain challenging. We aimed to determine the efficacy and safety of all types of turmeric extracts for the management of knee OA. RECENT FINDINGS: Sixteen RCTs of up to 16 weeks duration including 1810 adults with knee OA were included. Eleven RCTs compared the efficacy of turmeric extracts with placebo and five with active comparators (NSAIDs). The overall risk bias of included RCTs was moderate. Turmeric extracts significantly reduced knee pain (SMD - 0.82, 95% CI - 1.17 to - 0.47, I2 = 86.23%) and improved physical function (SMD - 0.75, 95% CI - 1.18 to - 0.33, I2 = 90.05%) compared to placebo but had similar effects compared to NSAIDs. BMI was the major contributor to heterogeneity in the placebo-controlled studies (explained 37.68% and 67.24%, respectively, in the models) and modified the effects of the turmeric on pain and physical function with less improvement with higher BMI (SMD 0.26 95% CI 0.04 to 0.48; SMD 0.48 95% CI 0.21 to 0.74). No significant between-group differences were reported for either biochemical markers or imaging outcomes. Turmeric extracts had 12% fewer adverse events than NSAIDs and similar rates to placebo. Turmeric extract is a safe and effective option for the symptomatic management of knee OA, compared to placebo or NSAIDs. However, current evidence from short-term studies is heterogeneous and has moderate risk of bias leading to some uncertainty about the true effect.

Long term effectiveness of RA-1 as a monotherapy and in combination with disease modifying anti-rheumatic drugs in the treatment of rheumatoid arthritis.

BACKGROUND: Data on long term use of Ayurvedic drugs is sparse. They may prove useful if combined with modern medicine in certain clinical situations (integrative medicine). We present the results of a long term observational study of RA-1 (Ayurvedic drug) used in the treatment of rheumatoid arthritis (RA). OBJECTIVE: The objective was to study safety of long term use of RA-1 for treatment of rheumatoid arthritis (RA). MATERIALS AND METHODS: On completion of a 16 week randomized controlled study, 165 consenting volunteer patients were enrolled into a three year open label phase (OLP) study. Patients were symptomatic with persistent active disease and naïve for disease modifying anti-rheumatic drugs (DMARD). 57 patients were on fixed low dose prednisone. Patients were examined every 10-14 weeks in a routine rheumatology practice using standard care norms. They continued RA-1 (Artrex ™, 2 tablets twice daily) throughout the study period and were generally advised to lead a healthy life style. Based on clinical judgment, rheumatologist added DMARD and/or steroids (modified if already in use) to patients with inadequate response; chloroquine and/or methotrexate commonly used. Treatment response was assessed using American College of Rheumatology (ACR) efficacy measures and ACR 20% improvement index standard update statistical software (SAS and SPSS) were used; significant at p < 0.05. RESULTS: 158, 130 and 122 patients respectively completed evaluations at 1, 2 and 3 year primary end point. The ACR 20 response (range 34-40%) remained stable over three years (p = 0.33). Patients improved optimum for several measures by one year (p < 0.05) and this was sustained. The use of steroids varied from 42 to 49% patients at yearly end points (mean daily dose 5 mg prednisone); correspondingly the use of DMARD varied from 20 to 34% patients. 40% patients on RA-1 did not require DMARD/steroids for control of disease. 77% patients reported adverse events, albeit mild and mostly gut related, and not causing withdrawal. Several study limitations (especially self-selection) were reduced by the high patient retention and consistency in drug use. CONCLUSION: RA-1 is safe and effective in the long term management of symptomatic active chronic RA. DMARDs and/or steroids can be used judiciously along with RA-1 to treat difficult disease/flares. Further studies are required to evaluate RA-1 in early RA. This paves way for research and application of integrative therapeutic approach in clinical medicine.

An open label, prospective, clinical study on a polyherbal formulation in osteoarthritis of knee.

BACKGROUND: Currently, though pharmacological, mechanical, and surgical interventions are used, there is no known cure for osteoarthritis (OA). OBJECTIVES: The main aim of the study was to assess the efficacy and safety of "TLPL/AY/03/2008", a polyherbal formulation on knee joint pain assessed on visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). MATERIALS AND METHODS: It was an open label, single center, prospective, clinical study conducted in 36 patients of OA Knee. Two capsules of 'TLPL/AY/03/2008' were given to all patients twice daily orally after meals for 180 days. RESULTS: Data describing quantitative measures are expressed as mean ± SD. Comparison of variables representing categorical data was performed using Chi-square test. The mean joint pain (as assessed on VAS) reduced significantly (59.85%; P < 0.05) and the mean WOMAC combined score, WOMAC pain sub-score, WOMAC stiffness sub-score, and WOMAC difficulty sub-score also reduced significantly at the end of the study. The mean time taken by the patients to walk 50 feet too, was reduced significantly (25.26%) at the end of the study. At the end of 4 months of the treatment, no patient needed paracetamol as rescue medicine to control pain. Most of the patients had shown good overall improvement assessed by the physician and by the patients. Majority of the patients showed excellent tolerability to the study drug. No significant change in most of the safety laboratory parameters was observed at the end of the study. CONCLUSION: The study provides good evidence in support of the efficacy and safety of the 'TLPL/AY/03/2008' in OA of knee.

Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial.

OBJECTIVE: To demonstrate clinical equivalence between two standardized Ayurveda (India) formulations (SGCG and SGC), glucosamine and celecoxib (NSAID). METHODS: Ayurvedic formulations (extracts of Tinospora cordifolia, Zingiber officinale, Emblica officinalis, Boswellia serrata), glucosamine sulphate (2 g daily) and celecoxib (200 mg daily) were evaluated in a randomized, double-blind, parallel-efficacy, four-arm, multicentre equivalence drug trial of 24 weeks duration. A total of 440 eligible patients suffering from symptomatic knee OA were enrolled and monitored as per protocol. Primary efficacy variables were active body weight-bearing pain (visual analogue scale) and modified WOMAC pain and functional difficulty Likert score (for knee and hip); the corresponding a priori equivalence ranges were ±1.5 cm, ±2.5 and ±8.5. RESULTS: Differences between the intervention arms for mean changes in primary efficacy variables were within the equivalence range by intent-to-treat and per protocol analysis. Twenty-six patients showed asymptomatic increased serum glutamic pyruvic transaminase (SGPT) with otherwise normal liver function; seven patients (Ayurvedic intervention) were withdrawn and SGPT normalized after stopping the drug. Other adverse events were mild and did not differ by intervention. Overall, 28% of patients withdrew from the study. CONCLUSION: In this 6-month controlled study of knee OA, Ayurvedic formulations (especially SGCG) significantly reduced knee pain and improved knee function and were equivalent to glucosamine and celecoxib. The unexpected SGPT rise requires further safety assessment. TRIAL REGISTRATION: Clinical Drug Trial Registry-India, www.ctri.nic.in, CTRI/2008/091/000063.

Comparative study of amrutbhallataka and glucosamine sulphate in osteoarthritis: Six months open label randomized controlled clinical trial.

BACKGROUND: AmrutBhallatak (ABFN02), a 'rasayana' drug from Ayurveda is indicated in degenerative diseases and arthritis. OBJECTIVE: To evaluate safety and efficacy of ABFN02 in osteoarthritis (OA) and compare it with Glucosamine sulphate (GS). MATERIALS AND METHODS: This was a randomized open comparative study. Ambulant OPD patients of OA knees (n = 112) were enrolled for 24 weeks. Tablets (750mg each) of GS and ABFN02 were matched. Three groups of patients: (A) GS, one tablet × twice/day × 24 weeks. (B) ABFN02, incremental pulse dosage (one tablet x twice/day × two weeks, two tablets × twice/day × two weeks, three tablets × twice/day × two weeks), two such cycles of drug and non-drug phases alternately for six weeks each (C) ABFN02 continuous dosage akin to GS. Pain visual analogue score (Pain-VAS) and Western Ontario and Mc-Master University Osteoarthritis Index (WOMAC) were the primary outcome measures. Secondary outcome measures were Health assessment questionnaire (HAQ), paracetamol consumption, 50 feet walking, physician and patient global assessment, knee stiffness, knee status, urinary CTX II, serum TNFa-SRI, SRII and MRI knee in randomly selected patients. RESULTS: ABFNO2 and GS demonstrated, adherence to treatment 87.75% and 74.3%, reduction in Pain-VAS at rest 61.05% and 57.1%, reduction in pain-VAS on activity 57.4% and 59.8%, WOMAC score drop 62.8% and 59.1% respectively. Secondary outcome measures were comparable in all groups. Safety measures were also comparable. No serious adverse events reported. However, asymptomatic reversible rise in liver enzymes was noted in the ABFNO2 group. CONCLUSIONS: ABFN02 has significant activity in OA; the formulation needs further investigation.

Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: A Government of India NMITLI arthritis project.

BACKGROUND: Results of an exploratory trial suggested activity trends of Zingiber officinale-Tinopsora cordifolia (platform combination)-based formulations in the treatment of Osteoarthritis (OA) Knees. These formulations were "platform combination+Withania somnifera+Tribulus terrestris" (formulation B) and "platform combination+Emblica officinale" (formulation C). This paper reports safety of these formulations when used in higher doses (1.5-2 times) along with Sallaki Guggul and Bhallataka Parpati (a Semecarpus anacardium preparation). MATERIALS AND METHODS: Ninety-two patients with symptomatic OA knees were enrolled in a 6 weeks investigator blind, randomized parallel efficacy 4-arm multicenter drug trial. The 4 arms were (I) formulation B, 2 t.i.d.; (II) formulation B, 2 q.i.d.; (III) platform combination+Sallaki Guggul; (IV) Bhallataka Parpati+formulation C. A detailed enquiry was carried out for adverse events (AE) and drug toxicity as per a priori check list and volunteered information. Laboratory evaluation included detailed hematology and metabolic parameters. Patients were examined at baseline, first and fourth weeks, and on completion. Standard statistical program (SPSS version 12.5) was used for analysis. RESULTS: None of the patients reported serious AE or withdrew due to any drug-related toxicity. Mild gut-related (mostly epigastric burning) AE was reported. A mild increase in liver enzymes [serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT)] without any other hepatic abnormality was reported in 2 patients (group IV). Other laboratory parameters remained normal. The mean improvement in active pain visual analog scale (1.4, CI 0.5-2.22), WOMAC (functional activity questionnaire) pain score (1.37, CI 0.22-2.5), and urinary C-TAX (cartilage collagen breakdown product) assay was maximum (NS) in group IV. Lower dose group I showed numerically superior improvement compared with higher dose group II. CONCLUSION: The results suggested that despite higher doses, standardized Ayurvedic formulations demonstrated a good safety profile. An improved efficacy and likely chondroprotective effect was shown by group IV intervention. A confirmatory drug trial with adequate power and sample size was planned based on the learning from this trial.

Comparable efficacy of standardized Ayurveda formulation and hydroxychloroquine sulfate (HCQS) in the treatment of rheumatoid arthritis (RA): a randomized investigator-blind controlled study.

Hydroxychloroquine sulfate (HCQS) is a popular disease-modifying antirheumatic drug (DMARD) despite modest efficacy and toxicity. Ayurveda (ancient India medicinal system) physicians treat rheumatoid arthritis (RA) with allegedly safer herbal formulations. We report a head-to-head comparison in an exploratory drug trial. The objective is to compare standardized Ayurvedic formulations and HCQS in the treatment of RA. One hundred twenty-one patients with active moderately severe RA (ACR 1988 classified) were randomized into a 24-week investigator-blind, parallel efficacy, three-arm (two Ayurvedic and HCQS) multicenter drug trial study; polyherb (Tinospora cordifolia and Zingiber officinale based) and monoherb (Semecarpus anacardium). Study measures included joint counts (pain/tenderness and swelling), pain visual analogue scale, global disease assessments, and health assessment questionnaire. Oral meloxicam (fixed-dosage schedule) was prescribed to all patients during the initial 16 weeks. Patients on prednisolone could continue a fixed stable dose (<7.5 mg daily). Rescue oral use of paracetamol was permitted and monitored. All groups matched well at baseline. An intent-to-treat analysis (ANOVA, significance P < 0.05) did not show significant differences by treatment groups. In the polyherb, monoherb, and HCQS arms, 44%, 36%, and 51%, respectively, showed ACR 20 index improvement. Several efficacy measures improved significantly in the HCQS and polyherb groups with no difference between the groups (corrected P). However, the latter was individually superior to monoherb. Only mild adverse events (gut and skin, and none withdrew) were reported with no differences between the groups. Forty-two patients dropped out. This preliminary drug trial controlled for HCQS demonstrated a standardized Ayurvedic polyherb drug to be effective and safe in controlling active RA. A better-designed study with a longer evaluation period is recommended.

A Randomized Controlled Exploratory Evaluation of Standardized Ayurvedic Formulations in Symptomatic Osteoarthritis Knees: A Government of India NMITLI Project.

The multidisciplinary "New Millennium Indian Technology Leadership Initiative" Arthritis Project was undertaken to validate Ayurvedic medicines. Herbal formulations in popular use were selected by expert consensus and standardized using modern tools. Our clinical strategy evolved from simple exploratory evaluations to better powered statistically designed drug trials. The results of the first drug trial are presented here. Five oral formulations (coded A, B, C, D and E), with a common base of Zingiber officinale and Tinospora cordifolia with a maximum of four plant extracts, were evaluated; with placebo and glucosamine as controls. 245 patients suffering from symptomatic OA knees were randomized into seven arms (35 patients per arm) of a double blind, parallel efficacy, multicentric trial of sixteen weeks duration. The groups matched well at baseline. There were no differences for patient withdrawals (17.5%) or adverse events (AE) of mild nature. Intention-to-treat efficacy analysis, demonstrated no significant differences (P < .05) for pain (weight bearing) and WOMAC questionnaire (knee function); placebo response was high. Based on better pain relief, significant (P < .05) least analgesic consumption and improved knee status, "C" formulation was selected for further development. Controlled exploratory drug trials with multiple treatment arms may be used to economically evaluate several candidate standardized formulations.

Efficacy and safety of Ayurvedic medicines: Recommending equivalence trial design and proposing safety index.

Ayurvedic drugs have begun to be evaluated in controlled clinical trials. The trials, often placebo controlled, are usually designed to demonstrate superiority. Though the results have been usually reported as encouraging, statistical significance has been elusive. In this melee to show efficacy, several positive results related to safety and other purported advantages with Ayurvedic drugs, including improved quality of life, easy drug availability and less cost, get drowned. Though safety is the prime concern, efficacy ultimately matters in trials. Excellent safety profile offset modest efficacy, especially for long-term management of chronic difficult to treat disorders. There is a trade-off between efficacy and safety but we have no means to put them together in a mathematical evaluation to judge the overall performance of a drug. However, we need more suitable modern science methods/techniques to unravel the true therapeutic role of Ayurvedic drugs. We propose "equivalence trials" using modern medicine benchmark as a comparator and a "safety/tolerability index" on this perspective. We believe that several Ayurvedic drugs are capable of demonstrating equal efficacy but superior safety. Our concept may also be applicable for pragmatic trials that are more suitable for Ayurvedic therapy.

Ayurveda-modern medicine interface: A critical appraisal of studies of Ayurvedic medicines to treat osteoarthritis and rheumatoid arthritis.

The potential of Ayurvedic philosophy and medicines needs to be recognized and converted into real life treatment paradigm. This article describes a comprehensive therapeutic approach used in Ayurveda and modern medicine to treat arthritis. We present concise summary of various controlled drug trials carried out by us to validate standardized Ayurvedic drugs using modern medicine protocol to treat Rheumatoid Arthritis and Osteoarthritis knees. Several of the latter are published. The trials consistently demonstrate excellent safety of Ayurvedic medicines but often fail to unequivocally show superior efficacy. Some key findings of a recently unpublished trial in OA knees are also presented to show equivalence between Ayurvedic medicine and celecoxib and glucosamine, and we speculate that equivalence trials may be a way forward. The data from the trials also supports the Ayurvedic 'Rasayana' concept of immune-modulation and healing. We need to interpret logic of Ayurveda when, adopting modern science tools in drug development and validation and much research is required. Validation of Ayurvedic medicines using the latter approach may lead to an evidence based Ayurveda - Modern Medicine interface. Also, in pursuit of finding better treatment solutions, we ought to step beyond the realm of only drugs and attempt validation of comprehensive specific treatment package as per classical Ayurveda. Finally, validation of a combined (Ayurveda and modern medicine) therapeutic approach with superior efficacy and safety is likely to be a major leap in overcoming some of the current frustrations to treat difficult disorders like arthritis using only modern medicines.

Chondroprotective Potential of Fruit Extracts of Phyllanthus emblica in Osteoarthritis.

There is a need for effective nutraceuticals for osteoarthritis care. The fruit of Phyllanthus emblica is used as a powerful rejuvenator in Ayurvedic medicine. This study measured the chondroprotective potential of P. emblica ('Amalaki') fruits in vitro. We used aqueous extracts of unprocessed P. emblica fruit powder (powder A), and the powder obtained after hot water extraction and drying of powder A (powder B). Chondroprotection was measured in three different assay systems. First, we tested the effects of both fruit powders on the activities of the enzymes hyaluronidase and collagenase type 2. Second, an in vitro model of cartilage degradation was set-up with explant cultures of articular knee cartilage from osteoarthritis patients. Cartilage damage was assayed by measuring glycosaminoglycan release from explants treated with/without P. emblica fruit powders. Aqueous extracts of both fruit powders significantly inhibited the activities of hyaluronidase and collagenase type 2 in vitro. Third, in the explant model of cartilage matrix damage, extracts of glucosamine sulphate and powder B (0.05 mg/ml) exhibited statistically significant, long-term chondroprotective activity in cartilage explants from 50% of the patients tested. This result is important since glucosamine sulphate is the leading nutraceutical for osteoarthritis. Powder A induced a statistically significant, short-term chondroprotective activity in cartilage explants from all of the patients tested. This is the first study to identify and quantitate new chondroprotective activities of P. emblica fruits. These data provide pilot pre-clinical evidence for the use of P. emblica fruits as a chondroprotective agent in osteoarthritis therapy.

The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro.

Using a validated explant model of in vitro cartilage damage, the effects of aqueous extracts of Withania somnifera (Ashwagandha) root and glucosamine sulphate (GlcS) were tested on the levels of nitric oxide (NO) and glycosaminoglycans (GAGs) secreted by knee cartilage from chronic osteoarthritis (OA) patients. W. somnifera extracts significantly decreased NO release by explants from one subset of patients (antiinflammatory response) and significantly increased levels of NO and GAGs released by explants from the second subset ('non-responders'). This is the first study showing direct, statistically significant, antiinflammatory effects of W. somnifera on human OA cartilage. It also confirmed that glucosamine sulphate exhibited statistically significant, antiinflammatory and chondroprotective activities in human OA cartilage. However, these beneficial effects of GlcS were observed in cartilage explants from 50% of patients tested ('responders'). In contrast, glucosamine significantly increased secretion of NO but not GAGs in explants from the second subset of OA patients ('non-responders'). Cartilage explants from the 11 OA patients gave differential responses to both drugs. Patient samples which responded to the antiinflammatory effects of W. somnifera did not always give a similar response to glucosamine, and vice versa. Thus, this in vitro model of human cartilage damage provides qualitative and statistically significant, quantitative pre-clinical data on antiinflammatory and chondroprotective activities of antiarthritic drugs.

The assessment of osteoporosis risk factors in Iranian women compared with Indian women.

BACKGROUND: Osteoporosis is an important public health problem in older adults. It is more common in postmenopausal women and not only gives rise to morbidity but also markedly diminishes the quality of life in this population. There is lack of information about the risk factor of osteoporosis in developing countries. In this study we aimed to assess the risk factors for osteoporosis in postmenopausal women from selected BMD centers of two developing Asian countries (Iran and India). METHODS: This study is a multicenter interview-based study conducted in selected hospitals and health centers from urban areas in Iran and India. The case group included postmenopausal osteoporotic women who were identified as patients with bone density higher than 2.5 SD below average of young normal bone density (in L1-L4) spine region interest and/or total femoral region) by using DEXA method. The controls were chosen from postmenopausal women with normal bone density (in L1-L4 spine and total femoral regions using DEXA method) matching in age groups was strategy of choice.The sample sizes included from Iran a total of 363 subjects (178 osteoporotic and 185 normal) and from India a total of 354 subjects (203 osteoporotic and 151 normal). RESULTS: The significant (p < 0.05) risk factors in present study population with their Odds Ratios (in parenthesis, respectively in Iran and India) were as follow:Lower education defined as less than class 12 or nil college (2.1) (2.7), duration of menopause greater than 5 years: (2.2) (1.4), Menarche age (after 14 years): (1.9) (1.6), Menopause age (before 45 years): (1.1) (2), Parity more than 3: (1.1) (1), Bone and joint problem (2.3) (2.2). Calcium supplementation (0.6) and HRT (0.4) were shown as protective factors and steroid therapy (3.3) was found as a risk factor in Iran. Calcium supplementation more than 1 year (0.3) was shown as a protective factor in India.Pure vegetarianism: (2.2) and Red meat consumption more than 4 times per week (1.4) was shown as a risk factor in Indian and Iranian subjects respectively. Regular consumption of Soya (0.3), almond (0.5), fish (0.5), fruits (0.4) and milk tea 4 cups per day and more (0.4) appeared to be significant protective factors in India. Regular consumption of cheese (0.5), milk (0.5), chicken (0.4), egg (0.6), fruit (0.4), tea 7 cups per day and more (0.3) were found to be significant protective factors in Iran. Exercises were shown as protective factor in Iran (0.4) and India (0.4). There were no significant differences in association of risk factors and osteoporosis between Iranian and Indian subjects. CONCLUSION: Osteoporosis in Iranian and Indian subjects also appears to be associated with several known risk factors that well described in the literature. There were no significant differences in association of risk factors and osteoporosis between Iranian and Indian subjects. It was shown a protective role of certain nutritional dietary components and also exercises in both populations and can be exploited in preventive educational strategies on osteoporosis in these populations.

Chondroprotective potential of root extracts of Withania somnifera in osteoarthritis.

This is the first report describing two novel chondroprotective activities of aqueous extracts of Withania somnifera root powder.First,these extracts had a statistically significant,short-term chondroprotective effect on damaged human osteoarthritic cartilage matrix in 50% of the patients tested. Second,these extracts caused a significant and reproducible inhibition of the gelatinase activity of collagenase type 2 enzyme in vitro.

A 32-week randomized, placebo-controlled clinical evaluation of RA-11, an Ayurvedic drug, on osteoarthritis of the knees.

BACKGROUND: The ancient Indian (Asian) Ayurvedic medicinal system uses herbomineral drugs to treat arthritis. Despite centuries of use, very few have been tested by drug trials. RA-11 (ARTREX, MENDAR), a standardized multiplant Ayurvedic drug (Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa) is currently used to treat arthritis. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of RA-11 in patients with symptomatic osteoarthritis (OA) of the knees. METHODS: A total of 358 patients with chronic knee pain were screened free-of-cost in "arthritis camps" in an Indian metropolis. Ninety patients with primary OA of the knees (ACR classification; Arthritis Rheum 1986;29:1039-1049) were found eligible (postanalgesic washout pain visual analog score [VAS] > or =40 mm in either or both knees on body weight-bearing activities) to enroll into a randomized, double-blind, placebo-controlled, parallel efficacy, single-center, 32-week drug trial (80% power to detect 25% difference, P = 0.05, 2-sided). Concurrent analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not allowed. Lifestyle and/or dietary restrictions, as per routine Ayurveda practices, were not imposed. Pain VAS (maximum pain in each knee recorded by the patient during the preceding 48 hours) and modified WOMAC (Western Ontario McMaster University OA Index, Likert scale, version 3.0) were the primary efficacy variables. The WOMAC section on "physical function difficulty" was modified for Indian use and validated before the trial. Routine laboratory testing was primarily done to monitor drug safety. At baseline, the groups (active = 45, placebo = 45) were well matched for several measures (mean pain VAS: active = 6.17; placebo = 6.5). RESULTS: 1) EFFICACY: Compared with placebo, the mean reduction in pain VAS at week 16 (active = 2.7, placebo = 1.3) and week 32 (active = 2.8, placebo = 1.8) in the active group was significantly (P <0.05, analysis of variance [ANOVA]) better. Similarly, the improvement in the WOMAC scores at week 16 and week 32 were also significantly superior (P <0.01, ANOVA) in the active group. 2) SAFETY: Both the groups reported mild adverse events (AE) without any significant difference. 3) Withdrawals: Twenty-eight patients were discontinued. None reported drug-related toxicity. The majority failed follow up/compliance. No differences were observed between the groups. CONCLUSION: This controlled drug trial demonstrates the potential efficacy and safety of RA- 11 in the symptomatic treatment of OA knees over 32 weeks of therapy.

Pain and disability, perceptions and beliefs of a rural Indian population: A WHO-ILAR COPCORD study. WHO-International League of Associations for Rheumatology. Community Oriented Program for Control of Rheumatic Diseases.

OBJECTIVE: The WHO-ILAR Community Oriented Program for Control of Rheumatic Diseases (COPCORD) primarily aims to estimate the burden of rheumatic-musculoskeletal symptoms/disorders (RMS). We investigated data on pain and disability, perceptions and beliefs in the first rural community based COPCORD study in India. METHODS: A total of 4092 adults were interviewed (response rate 89%) in a population survey (Stage 1) in Bhigwan village in 1996 using modified COPCORD core questionnaires. Twenty-one trained volunteers completed the survey in 5 weeks. Those reporting RMS were identified (Phase 1) to complete a self-evaluation questionnaire (Phase 2) prior to rheumatological evaluation (Phase 3). Phase 2 included questions on perceptions and beliefs regarding pain, effect on life, work and socioeconomic factors, disability, and therapy; only the moderate and severe grades were considered significant. Patients marked their pain sites on a manikin during the presurvey week. A validated modified Health Assessment Questionnaire disability index (HAQDI) in the local language evaluated functional disability. RESULTS: RMS were the predominant ailments reported by 746 adult villagers (18.2%; 95% CI 17.1, 19.2). Moderate pain of > 2 years' duration was reported by almost 60% of RMS patients. Neck (6%), lumbar (11.4%), shoulder (7.4%), elbow (6.5%), wrist (6.4%), hand (6.1%), knee (13.2%), calf (6.6%), and ankle (6.5%) were the common painful sites, predominantly in women; 91%, 89%, and 31% with RMS reported a significant grade of pain, RMS illness, and disturbed sleep, respectively. In the age group 25-54 years, 21% of those with RMS perceived a significant effect on work ability, while less than 20% of those with RMS admitted a similar effect on their personal life (including finances). About 10% with RMS had ceased to work because of RMS. Among RMS subjects 21% scored a significant HAQDI, but many more reported significant difficulty (HAQ) in the individual items of walking, hygiene (squatting), arising (from sitting cross-legged), reaching, and occupational/household chores; this corresponded to the dominant pain sites in low back and lower limbs. Oral tobacco use was reported to be significantly greater (p < 0.001) in the RMS patients. Past trauma was recalled by 23% of patients, and many connected this to their RMS. Modern medicines were consumed by 55% of patients with RMS. Among patients, 86% and 65% expected "pain relief" and "cure," respectively, from their doctor; 23% of patients wanted greater sympathy and attention. However, 21% of patients had never visited a doctor and were only identified by the COPCORD study. CONCLUSION: The findings of this study (1) demonstrate that RMS, although a predominant ailment, has a modest effect on daily living in most subjects with RMS; (2) indicate there is inconsistency between the measures of pain and disability (using HAQ) and their effects; (3) describe the beliefs and expectations of the community. Based on the data and community support, the COPCORD has been continued for Stages II and III, especially with a view to health education.

Ayurvedic medicine. Core concept, therapeutic principles, and current relevance.

In the prebiblical Ayurvedic origins, every creation inclusive of a human being is a model of the universe. In this model, the basic matter and the dynamic forces (Dosha) of the nature determine health and disease, and the medicinal value of any substance (plant and mineral). The Ayurvedic practices (chiefly that of diet, life style, and the Panchkarama) aim to maintain the Dosha equilibrium. Despite a holistic approach aimed to cure disease, therapy is customized to the individual's constitution (Prakruti). Numerous Ayurvedic medicines (plant derived in particular) have been tested for their biological (especially immunomodulation) and clinical potential using modern ethnovalidation, and thereby setting an interface with modern medicine. To understand Ayurvedic medicine, it would be necessary to first understand the origin, basic concept and principles of Ayurveda.