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Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomised single-blind trial
Abstract
Background The rapid emergence of coronary artery disease (CAD) in south Asian people is not explained by conventional risk factors. In view of cardioprotective effects of a Mediterranean style diet rich in alpha-linolenic acid, we assessed the benefits of this diet for patients at high risk of CAD.Methods We did a randomised, single-blind trial in 1000 patients with angina pectoris, myocardial infarction, or surrogate risk factors for CAD. 499 patients were allocated to a diet rich in whole grains, fruits, vegetables, walnuts, and almonds. 501 controls consumed a local diet similar to the step I National Cholesterol Education Program (NCEP) prudent diet.Findings The intervention group consumed more fruits, vegetables, legumes, walnuts, and almonds than did controls (573 g [SD 127] vs 231 g [19] per day p<0.001). The intervention group had an increased intake of whole grains and mustard or soy bean oil. The mean intake of alpha-linolenic acid was two-fold greater in the intervention group (1.8 g [SD 0.4] vs 0.8 g [0.2] per day, p<0.001). Total cardiac end points were significantly fewer in the intervention group than the controls (39 vs 76 events, p<0.001). Sudden cardiac deaths were also reduced (6 vs 16, p=0.015), as were non-fatal myocardial infarctions (21 vs 43, p<0.001). We noted a significant reduction in serum cholesterol concentration and other risk factors in both groups, but especially in the intervention diet group. In the treatment group, patients with pre-existing CAD had significantly greater benefits compared with such patients in the control group.Interpretation An Indo-Mediterranean diet that is rich in alpha-linolenic acid might be more effective in primary and secondary prevention of CAD than the conventional step I NCEP prudent diet.
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“In another randomized clinical trial, Singh and colleagues tested a “Indo-Mediterranean diet,” rich in whole grains, fruits, vegetables, walnuts, almonds, mustard, or soybean oil, in 1,000 Indian patients at high risk or with existing coronary heart disease, and found a significant reduction in total cardiac end points.”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [23]
In the citing paper
“Compared with patients randomized to a step I National Cholesterol Education Program prudent diet, those following the Indo-Mediterranean diet rich in α-linolenic acid experienced an approximate 50% reduction in the rate of nonfatal myocardial infarction and an approximate 60% reduction in the rate of sudden cardiac death (23).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [23]
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Fedačko, J. (2012) · The Open Nutraceuticals Journal · doi:10.2174/1876396001205010113 · Cited by 22
“Singh et al., 2002, tested an ‘Indo-Mediterranean diet’ in 1000 patients in India, with existing coronary disease or at high risk for coronary disease [38].”
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Vogel, R. A. (2005) · European Heart Journal · doi:10.1093/eurheartj/ehi638 · Cited by 22
Dietary α-linolenic acid increases the platelet count in ApoE−/− mice by reducing clearance
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Keramati, M., Kheirouri, S., & Etemadifar, M. (2023) · Food Science & Nutrition · doi:10.1002/fsn3.3809 · Cited by 21
“An inverse relationship between MeDi and various non-communicable diseases has recently been discovered (Scarmeas et al., 2006; Singh et al., 2002; Trichopoulou et al., 2000).”
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BackgroundInfluentialThe Mediterranean Diet: Socio-cultural Relevance for Contemporary Health Promotion
Phull, S. (2015) · The Open Public Health Journal · doi:10.2174/1874944501508010035 · Cited by 25
“Due to its proven track record in preventing diet related disease, promoting an adapted Mediterranean Diet has been discussed as a tool for prevention of cardiovascular disease in South Asian populations [58].”
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Mediterranean Diet and Essential Tremor
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“Since the classical studies by Keys [10,11] much evidence has confirmed the beneficial effects on health of the Mediterranean diet [12–14], and various experimental and clinical studies are now detecting the mechanisms via which olive oil exerts its biological effects [15,16].”
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“Another important component of flaxseed, α-linolenic acid (about 57% of all fatty acids in flaxseed oil) has been proven to have a modest cardioprotective effect (Rajaram, 2014; Singh et al., 2002).”
BackgroundCosta, S. S., ., D. B. O., ., A. M. M., ., G. O. D. M., ., J. L. P. C., ., S. Z., Negrelle, R. R. B., & de Oliveira, L. F. B. (2006) · Journal of Biological Sciences · doi:10.3923/jbs.2006.840.846 · Cited by 19
High Omega-6/Omega-3 Fatty Acid Ratio Diets and Risk of Noncommunicable Diseases
Chaves, H., Singh, R. B., Khan, S., Wilczyńska, A., & Takahashi, T. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813148-0.00014-1 · Cited by 22
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“For example, a large clinical trial with a median follow-up of 4.8 years indicated that following a Med Diet did not lead to reduced HF risk compared to controls [9], this fi nding is not universal [10].”
InfluentialNutrition in Transition from Homo sapiens to Homo economicus
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“…from two nutritional interventions promoting a Mediterranean diet in secondary prevention indicated that a Mediterranean diet could lead to a significant reduction of recurrence rate of myocardial infarction (de Lorgeril et al. 1994; Renaud et al. 1995; de Lorgeril et al. 1999; Singh et al. 2002).”
Diet, serum homocysteine levels and ischaemic heart disease in a Mediterranean population
Vrentzos, G. E., Papadakis, J. A., Malliaraki, N. E., Zacharis, E. A., Mazokopakis, E. E., Margioris, A. N., Ganotakis, E. S., & Kafatos, A. (2004) · British Journal Of Nutrition · doi:10.1079/bjn20041145 · Cited by 18
“This could be achieved by increasing the consumption of folate, not only from foods rich in folate (de Lorgeril et al. 1994; Singh et al. 2002), but also with low doses of folate supplements (Brouwer et al. 1999b; Jacques et al. 1999; Riddell et al. 2000; Rampersaud et al. 2003).”
BackgroundHealthful Properties of Olive Oil Minor Components
Visioli, F., Bogani, P., & Galli, C. (2006) · Padua Research Archive (University of Padova) · doi:10.1016/b978-1-893997-88-2.50012-2 · Cited by 17
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State of the Art Reviews: Relationship Between Diet/ Physical Activity and Health
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BackgroundKatsarou, A. L., Vryonis, M. M., Protogerou, A. D., Alexopoulos, E. C., Achimastos, A. D., Papadogiannis, D. E., Chrousos, G. P., & Darviri, C. (2013) · Primary Health Care Research & Development · doi:10.1017/s1463423612000679 · Cited by 16
“Email: KatsarouAlexia@gmail.com r Cambridge University Press 2013 Primary Health Care Research & Development 2014; 15: 38–45 doi:10.1017/S1463423612000679 RESEARCH role in the control of high BP is currently examined (Rainforth et al., 2007; Khan et al., 2008; Spruill, 2010).”
BackgroundInfluentialOmega-6 fatty acids and coronary artery disease: The pros and cons
Dubnov‐Raz, G., & Berry, E. M. (2004) · Current Atherosclerosis Reports · doi:10.1007/s11883-004-0084-8 · Cited by 16
What to 'eat and chew' in acute myocardial infarction?
Singh, R. B. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehl035 · Cited by 16
Deshmukh, A., Sood, V., Lal, B. B., Khanna, R., Alam, S., & Sarin, S. K. (2024) · Pediatric Obesity · doi:10.1111/ijpo.13163 · Cited by 15
Veronese, N., Gianfredi, V., Volpe, M., Zanetti, M., Onder, G., Silano, M., Nucci, D., Fontana, L., Laviano, A., Sieber, C., et al. (2025) · Nutrition Reviews · doi:10.1093/nutrit/nuaf263 · Cited by 15
Study of Functional Foods Consumption Patterns Among Decedents Dying Due to Various Causes of Death
Singh, R. B., Visen, P., Sharma, D., Sharma, S., Mondo, R., Sharma, J. P., Sharma, M., Tokunaga, M., Takahashi, T., Mishra, S., et al. (2015) · The Open Nutraceuticals Journal · doi:10.2174/1876396001508010016 · Cited by 15
Perfecting the Plate: Adding Cardioprotective Compounds to the Diet
Cordova, A. C., Sumpio, B. J., & Sumpio, B. E. (2011) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2011.09.023 · Cited by 14
Cardiovascular Disease Risk Factors in Adolescent British South Asians and Whites: A Pilot Study
Hemmings, S., Conner, A., Maffulli, N., & Morrissey, D. (2011) · Postgraduate Medicine · doi:10.3810/pgm.2011.03.2268 · Cited by 15
“As well as improving triglyceride levels, dietary interventions may potentially have a beneficial effect on body composition and ultimately reduce cardiovascular risk later on in adulthood.(53) Given the multifactorial nature of the influences on dietary choices and physical activity, this pilot study highlights the n…”
BackgroundGlobalization of Diets and Risk of Noncommunicable Diseases
Fedačko, J., Takahashi, T., Singh, R. B., Pella, D., Chibisov, S. M., Hristová, K., Pella, D., Elkilany, G. N., Tomar, R. S. S., & Juneja, L. R. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813148-0.00006-2 · Cited by 16
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Alimentación saludable basada en la evidencia
Calañas-Continente, A. (2005) · Endocrinología y Nutrición · doi:10.1016/s1575-0922(05)74649-0 · Cited by 17
The Indo-Mediterranean diet revisited
Mann, J. I. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67005-5 · Cited by 14
Diet and rheumatoid arthritis: Red meat and beyond
Choi, H. K. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20732 · Cited by 14
Rai, S. K., Gortmaker, S. L., Hu, F. B., Kanaya, A. M., Kandula, N. R., Sun, Q., & Bhupathiraju, S. N. (2023) · Obesity · doi:10.1002/oby.23759 · Cited by 16
“An India-based randomized trial evaluated the potential cardioprotective effect of an Indo-Mediterranean diet (which encouraged high intakes of fruits, vegetables, nuts, whole grains, legumes, and mustard seed or soybean oil) among individuals considered to be at high risk for coronary artery disease [35].”
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“…de Lorgeril et al. 1996; Singh et al. 2002; Delgado-Lista et al. 2022); cardiovascular death (De Lorgeril et al. 1994; de Lorgeril et al. 1996; Singh et al. 2002; Delgado-Lista et al. 2022); overall mortality (De Lorgeril et al. 1994; de Lorgeril et al. 1996); revascularisation; ischaemic…”
InfluentialMultiple Risk Factor Interventions for Primary Prevention of CVD in LMIC: A Cochrane Review
Uthman, O. A., Hartley, L., Rees, K., Taylor, F. C., Ebrahim, S. B. J., & Clarke, A. (2016) · Global Heart · doi:10.1016/j.gheart.2016.03.639 · Cited by 13
Cardiovascular prevention: Mediterranean or low-fat diet?
Temporelli, P. L. (2023) · European Heart Journal Supplements · doi:10.1093/eurheartjsupp/suad097 · Cited by 14
“In addition, a 2019 critical review analyzing the effects of the Mediterranean Diet highlighted the need for new data on secondary prevention, because the only two existing significant studies were either too short(13) or had some important limitations.(14) Thus, although several guidelines also recommend the Mediterr…”
BackgroundHealth Effects of Eating Walnuts
Simopoulos, A. P. (2004) · Food Reviews International · doi:10.1081/fri-120028832 · Cited by 13
“…as the Nurses Health Study, show a beneficial effect of ALA relative to coronary heart disease, both in the primary prevention (Hu et al., 1999; Ascherio et al., 1996) and in the secondary prevention (de Lorgeril and Salen, 2000; de Lorgeril et al., 1994; Renaud et al., 1995; Singh et al., 2002).”
BackgroundInfluentialRed Yeast Rice for Dyslipidemia in Statin-Intolerant Patients
Becker, D. J., & Gordon, R. Y. (2010) · Annals of Internal Medicine · doi:10.7326/0003-4819-152-2-201001190-00026 · Cited by 13
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Dietary fatty acids and CHD: from specific recommendations to dietary patterns
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Dietary fat composition and cardiac events in patients with type 2 diabetes
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“Additionally, few randomized controlled trials evaluated the effects of the intake of n-3 PUFA on diabetic CVD and only patients with previous macrovascular disease [35,36,38] or with high cardiovascular risk [39] were included.”
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Managing cardiovascular risk in patients with metabolic syndrome
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FATTY ACIDS | Omega-3 Polyunsaturated
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Ancient Concepts of Nutrition and the Diet in Hunter-gatherers
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“However, it was recently shown that certain dietary habits may actually prevent further MIs [3, 4 ] and/or subsequent mortality [5].”
BackgroundTraditional Management of Chronic Stable Angina
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“Another intervention study, the Indo-Mediterranean Diet Heart Study, has reported fewer cardiac end points, sudden cardiac deaths and non-fatal MI in the intervention compared with the control group((66)).”
ResultAcute cyclooxygenase inhibition and baroreflex sensitivity in lean and obese adults
Alkhateeb, A. A., Limberg, J. K., Barnes, J. N., Joyner, M. J., Charkoudian, N., & Curry, T. B. (2016) · Clinical Autonomic Research · doi:10.1007/s10286-016-0389-z · Cited by 12
“The use of antiinflammatory agents in obese adults can improve metabolic abnormalities associated with obesity, such as insulin sensitivity [19], and an antiinflammatory diet can decrease cardiovascular disease risk [21].”
Diet and the risk for Alzheimer's disease
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Food choice and obesity in black America: creating a new cultural diet
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Effects of Mediterranean diets and nutrigenomics on cardiovascular health
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“A study by Singh et al. (2002) on 1,000 patients with a previous history of heart attacks or those having at least one main risk factor for coronary heart disease examined the benefit of MedDiet, precisely an Indo-MedDiet, on the incidence of CVDs (115 cases).”
InfluentialIdentification of nutritionally adequate mixtures of vegetable oils by linear programming
Darmon, N., Darmon, M. Y., & Ferguson, E. (2006) · Journal of Human Nutrition and Dietetics · doi:10.1111/j.1365-277x.2006.00669.x · Cited by 11
Cardiovascular Benefits of the Mediterranean Diet
Pineo, C., & Anderson, J. J. B. (2008) · Nutrition Today · doi:10.1097/01.nt.0000303326.76566.9f · Cited by 11
Nutrition in Chronocardiology: We are Indebted Professor Franz Halberg
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Brassica Nigra: Ethopharmacological Review of a Routinely Used Condiment
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Western diets and risk of non-communicable diseases
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Prevenção cardiovascular em pacientes com diabetes: revisão baseada em evidências
Furtado, M. V., & Polanczyk, C. A. (2007) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302007000200022 · Cited by 11
Les acides gras essentiels de la famille des oméga-3 et la santé de la mère et de l'enfant
Blondeau, N., & Schneider, S. M. (2006) · Nutrition Clinique et Métabolisme · doi:10.1016/j.nupar.2006.04.008 · Cited by 13
Nutritional Predictors and Modulators of Insulin Resistance
Pella, D., Singh, R. B., Otsuka, K., Chiang, C., & Joshi, S. (2004) · Journal of Nutritional & Environmental Medicine · doi:10.1080/13590840410001695220 · Cited by 11
Milano, A., Kabbaha, S., & Thorlund, K. (2022) · Human Nutrition & Metabolism · doi:10.1016/j.hnm.2022.200175 · Cited by 10
Preventive Therapies in Peripheral Arterial Disease
Shah, A. J., Pavlatos, N., & Kalra, D. K. (2023) · Biomedicines · doi:10.3390/biomedicines11123157 · Cited by 12
Pierucci, P., Misciagna, G., Ventura, M. T., Inguaggiato, R., Cisternino, A. M., Guerra, V., Suppressa, P., Resta, F., & Sabbà, C. (2011) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2010.12.002 · Cited by 12
Dietary and pharmacological energy restriction and exercise for healthspan extension
Cagigas, M. L., Ciutiis, I. D., Masedunskas, A., & Fontana, L. (2025) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2025.04.001 · Cited by 12
Toxicity of fatty acids on ECV-304 endothelial cells
Masi, L. N., Portioli-Sanches, E. P., de Lima, T. M., & Curi, R. (2011) · Toxicology in Vitro · doi:10.1016/j.tiv.2011.06.011 · Cited by 9
Aceite de oliva y prevención cardiovascular: más que una grasa
Pérez‐Martínez, P., López‐Miranda, J., Delgado‐Lista, J., Lopez‐Segura, F., & Jiménez, F. P. (2006) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/s0214-9168(06)73688-9 · Cited by 9
Pabón, G. M., & Perdomo, M. D. P. B. (2005) · Revista de la Facultad de Medicina · Cited by 9
Fedačko, J., Singh, R. B., Chaithiraphan, S., Vargová, V., Tomlinson, B., Meester, F. D., Gvozdjáková, A., & Moesgaard, S. (2010) · The Open Nutraceuticals Journal · doi:10.2174/18763960010030300154 · Cited by 9
Schumacher, T. L., Burrows, T. L., Neubeck, L., Redfern, J., Callister, R., & Collins, C. E. (2016) · Public Health Nutrition · doi:10.1017/s1368980016001543 · Cited by 9
“Singh (2002)((53)) Indo-Mediterranean diet CTRL: NCEP Step 1 INT: NCEP Step 1 with ↑ whole grains, legumes, F&V, nuts, mustard/soyabean oil 1 week food record Not stated Provide instruction, Unclear Significant differences (P<0·001) between INT & CTRL at 2 years: ↑ total fibre (23 g/d), ↑ soluble fibre (12 g/d), ↑ fru…”
Watanabe, S. (2019) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2019.17.003006 · Cited by 10
Omega-3-PUFA, Omega-6-PUFA and Mitochondria
Gvozdjáková, A., Pella, D., Kucharská, J., Otsuka, K., & Singh, R. B. (2008) · Springer eBooks · doi:10.1007/978-1-4020-6714-3_19 · Cited by 9
Dietary macronutrients, genetic variation, and progression of coronary atherosclerosis among women
Kalantarian, S., Rimm, E. B., Herrington, D. M., & Mozaffarian, D. (2014) · American Heart Journal · doi:10.1016/j.ahj.2014.01.001 · Cited by 8
Phokaewvarangkul, O., Kantachadvanich, N., Buranasrikul, V., Phoumindr, A., Phumphid, S., Jagota, P., & Bhidayasiri, R. (2023) · Journal of Movement Disorders · doi:10.14802/jmd.23021 · Cited by 8
“21,23 Similar to India, modification of Medi diet components and adaptation to the Korean-style Medi diet (KORMED) has been achieved by adding flavor-ful ingredients familiar to Koreans (such as fermented soybeans and garlic) to olive oil as an alternative to seasonings.”
Can Nuts Consumption Modulate Cardiovascular Diseases? Report of a Case and Review of Literature
Vargová, V. (2011) · The Open Nutraceuticals Journal · doi:10.2174/1876396001104010088 · Cited by 8
Dubnov‐Raz, G., & Berry, E. M. (2004) · Metabolic Syndrome and Related Disorders · doi:10.1089/1540419042441885 · Cited by 8
Singh, R., Garg, R., Anjum, B., Singh, R. K., Mahdi, A. A., Verma, N., Meester, F. D., Wilkzynska, A., Dharwadkar, S. M., Takahashi, T., et al. (2012) · Cited by 8
Linseed oil inclusion in sea bream diets: Effect on fatty acid composition during ice storage
Alonso, P. Á. C., Caballero, M. J., de Larriva, R. M., Ginés, R., Montero, D., & Izquierdo, M. S. (2010) · European Journal of Lipid Science and Technology · doi:10.1002/ejlt.200900240 · Cited by 8
Sotos‐Prieto, M., Zulet, M. Á., & Corella, D. (2009) · Medicina Clínica · doi:10.1016/j.medcli.2009.01.033 · Cited by 8
Hristová, K., Shiue, I., Pella, D., Singh, R. B., Chaves, H., Basu, T. K., Ozimek, L., Rastogi, S., Takahashi, T., Wilson, D., et al. (2014) · Nutrition · doi:10.1016/j.nut.2013.12.013 · Cited by 8
Atherothrombosis: management of patients at risk
Mas, J. (2005) · International Journal of Clinical Practice · doi:10.1111/j.1368-5031.2005.00512.x · Cited by 8
Diet Quality in 116 Norwegian Men and Women with Coronary Heart Disease
Andersen, J. R., Søgnen, E. H., & Natvig, G. K. (2005) · European Journal of Cardiovascular Nursing · doi:10.1016/j.ejcnurse.2005.11.001 · Cited by 8
Antioxidants and cardiovascular disease
Miller, E. R., & Appel, L. J. (2005) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780198525738.003.0015 · Cited by 8
Pella, D., Singh, R. B., Tomlinson, B., & Kong, C.-W. (2003) · Progress in experimental cardiology · doi:10.1007/978-1-4615-0455-9_34 · Cited by 8
Metadata
- Authors
- Singh, R. B., Dubnov, G., Niaz, M. A., Ghosh, S., Singh, R., Rastogi, S. S., Manor, O., Pella, D., & Berry, E. M.
- Affiliations
- Teerthanker Mahaveer Medical College & Research Centre (IN)
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Berry, Elliot M
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 360
- Issue
- 9344
- Pages
- 1455-1461
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2093983853
- Cited by
- 663
- References
- 39
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 11 · 2023: 14 · 2022: 12 · 2021: 25 · 2020: 11 · 2019: 19 · 2018: 25 · 2017: 18 · 2016: 19 · 2015: 25 · 2014: 25 · 2013: 21 · 2012: 37
- FWCI
- 57.17
- Type
- journal article
- Language
- en
- Update notices
- expression_of_concern (2005-07-30)
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
- Keywords
- coronary artery disease, alpha-linolenic acid, dietary intervention, angina pectoris, myocardial infarction, sudden cardiac death, whole grains, nuts, fruits and vegetables, serum cholesterol, secondary prevention, South Asian populations
- MeSH terms
- Angina Pectoris, Coronary Artery Disease, Female, Humans, Male, Middle Aged, Myocardial Infarction, Risk Factors, Proportional Hazards Models, Survival Analysis, Single-Blind Method, Disease Progression, Diet, Mediterranean
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