Cited by 663Nutritional Studies and DietFatty Acid Research and HealthCardiovascular Health and Risk Factors

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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

Singh, Ram B, Dubnov, Gal, Niaz, Mohammad A, Ghosh, Saraswati, Singh, Reema, Rastogi, Shanti S, Manor, Orly, Pella, Daniel, Berry, Elliot M·2002·The Lancet

DOI 10.1016/s0140-6736(02)11472-3

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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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A Mediterranean dietary style influences TNF–alpha and VCAM–1 coronary blood levels in unstable angina patients
Serrano-Martínez, M., Palacios, M., Martínez-Losa, E., Lezaún, R., Maraví, C., Prado, M., Martínez, J. A., & Martínez‐González, M. Á. (2004) · European Journal of Nutrition · doi:10.1007/s00394-004-0532-9 · Cited by 78
“The use of a Mediterranean-type diet for the prevention of coronary heart disease has recently been assessed using randomized studies [ 11 , 32], and also a number of observational studies have suggested that a diet with a moderate alcohol intake, mainly from red wine, and rich in olive oil, vegetables, fruits, fish,…”
Method
Dietary risk factors for rheumatic diseases
Choi, H. K. (2005) · Current Opinion in Rheumatology · doi:10.1097/01.cco.0000152664.87204.3c · Cited by 78
Mediterranean diet and mortality in Switzerland: an alpine paradox?
Vormund, K., Braun, J., Rohrmann, S., Bopp, M., Ballmer, P. E., & Faeh, D. (2014) · European Journal of Nutrition · doi:10.1007/s00394-014-0695-y · Cited by 80
“This could explain why we found an inverse and not a positive association with CVD mortality [44, 45].”
Result
Long-term impact of mediterranean diet on cardiovascular disease prevention: A systematic review and meta-analysis of randomized controlled trials
Sebastian, S. A., Padda, I., & Johal, G. (2024) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2024.102509 · Cited by 82
Nutritional Composition of Selected Wild Plants in the Diet of Crete
Zeghichi, S., Καλλιθράκα, Σ., Simopoulos, A. P., & Kypriotakis, Z. (2003) · KARGER eBooks · doi:10.1159/000069928 · Cited by 77
High ω-3 Fatty Acid Content in Alpine Cheese
Hauswirth, C. B., Scheeder, M. R. L., & Beer, J. H. (2003) · Circulation · doi:10.1161/01.cir.0000105989.74749.dd · Cited by 75
The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes
Jovanovski, E., Li, D., Ho, H. V. T., Djedovic, V., Marques, A. D. C. R., Shishtar, E., Mejía, S. B., Sievenpiper, J. L., de Souza, R. J., Duvnjak, L. S., et al. (2017) · Medicine · doi:10.1097/md.0000000000006531 · Cited by 77
Disease modification and cardiovascular risk reduction: two sides of the same coin?
Hall, F. C., & Dalbeth, N. (2005) · Rheumatology · doi:10.1093/rheumatology/kei012 · Cited by 71
Why and How the Indo-Mediterranean Diet May Be Superior to Other Diets: The Role of Antioxidants in the Diet
Singh, R. B., Fedačko, J., Fatima, G., Magomedova, A. G., Watanabe, S., & Elkilany, G. E. N. (2022) · Nutrients · doi:10.3390/nu14040898 · Cited by 76
Simplified lipid guidelines: Prevention and management of cardiovascular disease in primary care.
Allan, G. M., Lindblad, A. J., Comeau, A., Coppola, J., Hudson, B., Mannarino, M., McMinis, C., Padwal, R. S., Schelstraete, C., Zarnke, K. B., et al. (2015) · Europe PMC (PubMed Central) · Cited by 70
Dietary patterns and cardiometabolic health: Clinical evidence and mechanism
Wang, W., Liu, Y., Li, Y., Luo, B., Lin, Z., Chen, K., & Liu, Y. (2023) · MedComm · doi:10.1002/mco2.212 · Cited by 89
The effects of a lifestyle-focused text-messaging intervention on adherence to dietary guideline recommendations in patients with coronary heart disease: an analysis of the TEXT ME study
Santo, K., Hyun, K. K., de Keizer, L., Thiagalingam, A., Hillis, G. S., Chalmers, J. P., Redfern, J., & Chow, C. K. (2018) · International Journal of Behavioral Nutrition and Physical Activity · doi:10.1186/s12966-018-0677-1 · Cited by 72
Dietary interventions and nutritional supplements for heart failure: a systematic appraisal and evidence map
Khan, M. S., Khan, F., Fonarow, G. C., Sreenivasan, J., Greene, S. J., Khan, S. U., Usman, M., Vaduganathan, M., Fudim, M., Anker, S. D., et al. (2021) · European Journal of Heart Failure · doi:10.1002/ejhf.2278 · Cited by 69
Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis
Jenkins, D. J. A., Josse, A. R., Beyene, J., Dorian, P., Burr, M. L., Labelle, R., Kendall, C. W. C., & Cunnane, S. C. (2008) · Canadian Medical Association Journal · doi:10.1503/cmaj.070261 · Cited by 69
Effects of soluble fiber (Plantago ovatahusk) on plasma lipids, lipoproteins, and apolipoproteins in men with ischemic heart disease
Solà, R., Godàs, G., Ribalta, J., Vallvé, J.-C., Girona, J., Anguera, A., Ostos, M., Recalde, D., Salazar, J., CASLAKE, M. J., et al. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/85.4.1157 · Cited by 69
Atherosclerotic risk factors and renal function in the elderly: the role of hyperfibrinogenaemia and smoking. Results from the Italian Longitudinal Study on Ageing (ILSA)
Baggio, B., Budakovic, A., Perissinotto, E., Maggi, S., Cantaro, S., Enzi, G., Grigoletto, F., & for the ILSA Working Group (2004) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfh553 · Cited by 68
“It is interesting that variations in diet composition, in particular a balanced ratio of n-6/n-3 essential fatty acids, modulate plasma fibrinogen levels [ 28 ], and the present findings seem to confirm this.”
Background
Antiproliferative Terpenoids from Almond Hulls (Prunus dulcis): Identification and Structure−Activity Relationships
Amico, V., Barresi, V., Condorelli, D. F., Spatafora, C., & Tringali, C. (2006) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf052812q · Cited by 68
Daily Self-Monitoring of Body Weight, Step Count, Fruit/Vegetable Intake, and Water Consumption: A Feasible and Effective Long-Term Weight Loss Maintenance Approach
Akers, J. D., Cornett, R. A., Savla, J. T., Davy, K. P., & Davy, B. M. (2012) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2012.01.022 · Cited by 66
Managing Cardiovascular Risk in Patients With HIV Infection
Stein, J. H. (2005) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/01.qai.0000147525.26746.07 · Cited by 61
Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic acid levels in postmenopausal women
Giltay, E. J., Duschek, E., Katan, M., Zock, P. L., Neele, S. J. M., & Netelenbos, J. C. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1820399 · Cited by 68
“In addition, the protective effect of dietary -linolenic acid against cardiovascular disease (de Lorgeril et al. 1994, Singh et al. 1997, 2002 ) might require its conversion to EPA and DHA.”
Nutraceuticals in Cardiovascular Prevention: Lessons from Studies on Endothelial Function
Zuchi, C., Ambrosio, G., Lüscher, T. F., & Landmesser, U. (2010) · Cardiovascular Therapeutics · doi:10.1111/j.1755-5922.2010.00165.x · Cited by 66
“However, the effect on clinical outcome, that is all-cause mortality, cardiac and sudden death, and stroke, is still unclear [99–101].”
Background
Mediterranean diet and cancer risk
Gallus, S., Bosetti, C., & Vecchia, C. L. (2004) · European Journal of Cancer Prevention · doi:10.1097/00008469-200410000-00013 · Cited by 65
“…et al., 2000), cardiovascular diseases (de Lorgeril et al., 1994; Renaud et al., 1995; Hu and Willett, 2002; Martinez-Gonzalez et al., 2002; Singh et al., 2002), as well as several common neoplasms (Tavani and La Vecchia, 1995; de Lorgeril et al., 1998; Trichopoulou et al., 2000; La…”
Background
Food and Western Disease Health and Nutrition from an Evolutionary Perspective
Lindeberg, S. (2009) · Cited by 64
Diet and Inflammation in Alzheimer’s Disease and Related Chronic Diseases: A Review
Gardener, S. L., Rainey‐Smith, S. R., & Martins, R. N. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150765 · Cited by 66
“The MeDi has also been associated with lower risk for dyslipidaemia [210, 221], hypertension [209, 210, 221, 222], abnormal glucose metabolism [209, 221], obesity [223], and CVD [221, 224–226] which, as discussed earlier, are all risk factors for AD, and in the case of obesity and CVD, are also associated with increas…”
Bioavailability of Dietary Polyphenols and the Cardiovascular Diseases
Shivashankara, K. S., & Acharya, S. N. (2010) · The Open Nutraceuticals Journal · doi:10.2174/1876396001003010227 · Cited by 67
A systematic review and meta-analysis of the impact of ω-3 fatty acids on selected arrhythmia outcomes in animal models
Matthan, N. R., Jordan, H. S., Chung, M., Lichtenstein, A. H., Lathrop, D. A., & Lau, J. (2005) · Metabolism · doi:10.1016/j.metabol.2005.05.026 · Cited by 64
“In particular, fish oil intake appears to have a significant impact on the incidence of sudden death in humans, with a decrease reported in 4 of 6 randomized controlled trials [2-5], 2 prospective cohort studies [6,7], and 1 case control study [8].”
Background
Expression of concern: Indo-Mediterranean Diet Heart Study
Horton, R. C. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67006-7 · Cited by 63
Fatty acids and CHD
Woodside, J. V., & Kromhout, D. (2005) · Proceedings of The Nutrition Society · doi:10.1079/pns2005465 · Cited by 64
Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women
Bloomer, R. J., Kabir, M. M., Canale, R. E., Trepanowski, J. F., Marshall, K. E., Farney, T. M., & Hammond, K. G. (2010) · Lipids in Health and Disease · doi:10.1186/1476-511x-9-94 · Cited by 62
“While we did note a reduction of blood pressure, as well as a decrease in total (19%) and LDL cholesterol (23%) with the Daniel Fast in just three weeks, findings similar to those noted for other plant-based diets [19-21], we also noted a decrease in HDL-C (14%).”
Result
A M editerranean diet improves H b A 1c but not fasting blood glucose compared to alternative dietary strategies: a network meta‐analysis
Carter, P., Achana, F. A., Troughton, J., Gray, L. J., Khunti, K., & Davies, M. J. (2013) · Journal of Human Nutrition and Dietetics · doi:10.1111/jhn.12138 · Cited by 64
Association of carbohydrate and fat intake with metabolic syndrome
Kwon, Y., Lee, H. S., & Lee, J. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2017.06.022 · Cited by 62
“Several clinical tr i ls and cohort studies consistently support the importance of CHO and fat quality [7, 9-11].”
Background
Alpha-Linolenic Acid
Harris, W. S. (2005) · Circulation · doi:10.1161/circulationaha.105.545640 · Cited by 61
Omega-3 enriched egg production: the effect ofα-linolenicω-3 fatty acid sources on laying hen performance and yolk lipid content and fatty acid composition
Antruejo, A. E., Azcona, J. O., García, P. T., Gallinger, C. I., Rosmini, M. R., Ayerza, R., Coates, W. E., & Pérez, C. D. (2011) · British Poultry Science · doi:10.1080/00071668.2011.638621 · Cited by 60
“An increasing number of epidemiological and controlled studies, however, have demonstrated that -linolenic fatty acids from plants also reduce the risk of CHD (Mantzioris et al., 2000; Bemelmans et al., 2002; Singh et al., 2002; Baylin et al., 2003; Zhao et al., 2004; Campos et al., 2008).”
Background
Nutrition, Lipids, and Cardiovascular Disease
Kuller, L. H. (2006) · Nutrition Reviews · doi:10.1111/j.1753-4887.2006.tb00230.x · Cited by 61
Effects of an Indo-Mediterranean Diet on the Omega-6/Omega-3 Ratio in Patients at High Risk of Coronary Artery Disease: The Indian Paradox
Pella, D., Dubnov, G., Singh, R. B., Sharma, R. K., Berry, E. M., & Manor, O. (2003) · KARGER eBooks · doi:10.1159/000073793 · Cited by 58
A Mediterranean Diet Is Cost-Effective in Patients with Previous Myocardial Infarction
Dalziel, K., Segal, L., & de Lorgeril, M. (2006) · Journal of Nutrition · doi:10.1093/jn/136.7.1879 · Cited by 59
Diet, Lifestyle, and Longevity—The Next Steps?
Rimm, E. B. (2004) · JAMA · doi:10.1001/jama.292.12.1490 · Cited by 58
Semen Quality and Sperm Function Loss by Hypercholesterolemic Diet Was Recovered by Addition of Olive Oil to Diet in Rabbit
Saez Lancellotti, T. E., Boarelli, P. V., Romero, A. A., Funes, A. K., Cid-Barria, M., Cabrillana, M. E., Monclus, M. A., Simón, L., Vicenti, A. E., & Fornés, M. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0052386 · Cited by 57
“Olive oil, the principal fat of Mediterranean diet, is known to improve several cardiovascular risk factors at relatively high doses together with intensive modifications of dietary habits [49,63].”
Background
Relative validity and reproducibility of a 14-item semi-quantitative food frequency questionnaire for cardiovascular prevention
Laviolle, B., le Froger-Bompas, C., Guillo, P., Sevestre, A., Letellier, C., Pouchard, M., Daubert, J., & Paillard, F. (2005) · European Journal of Cardiovascular Prevention & Rehabilitation · doi:10.1097/01.hjr.0000186625.98604.5d · Cited by 57
Mediterranean Diet and Cardiovascular Health
Giugliano, D., & Esposito, K. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1352.012 · Cited by 58

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
ORCID: Singh, Ram B
Singh, Reema
Manor, Orly
Pella, Daniel
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
DOI: 10.1016/s0140-6736(02)11472-3
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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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

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