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To the Editor: Metabolic abnormalities in type 2 diabetes are associated with increased platelet sensitivity to proaggregants and decreased platelet sensitivity to endogenous antiaggregants.^1-2 Thus, patients with type 2 diabetes have an increased risk of developing atherosclerosis and cardiovascular complications.²

Consumption of tomato products has been found to be inversely correlated with incidence of acute coronary events, development of early atherosclerosis, and mortality from heart disease.³ Furthermore, clarified tomato juice has been shown to inhibit human platelet aggregation in vitro^4-5 and in an animal model.⁶ We examined whether consumption of tomato juice clarified by filtration could inhibit platelet aggregation in patients with type 2 diabetes or impaired glucose tolerance.

Methods
Patients with type 2 diabetes (n = 18) or impaired glucose tolerance (n = 2) without prior history of thromboembolic events were recruited from the community using media advertising. Fourteen men and 6 women aged 43 to 82 years with a mean (SD) body mass index of 30.5 (4.9) provided written informed consent to participate in the study. Two of the participants reported being smokers. None were taking aspirin, other antiplatelet medications, or nonsteroidal anti-inflammatory drugs. The study was a double-blind, parallel-group clinical trial using permuted block randomization in which participants were assigned to consume 250 mL of clarified tomato juice (n = 10; 7 men and 3 women) or placebo tomato-flavored beverage (n = 10; 7 men and 3 women) daily for 3 weeks. Six participants in the active intervention group and 7 participants in the control group had good glycemic control (glycosylated hemoglobin [HbA_1c] level <7%), while 3 in the active intervention group and 2 in the placebo group had moderate glycemic control (HbA_1c level, 7%-9%) and 1 in each group had poor glycemic control (HbA_1c level >9%).

Participants were instructed not to alter their usual diet for the duration of the study. The intake of tomato-based products did not change, as confirmed by 3-day weighed-food records before (n = 10 per group) and during (n = 9 per group) supplementation. Fasting blood samples were collected at baseline and the morning after the last day of supplementation. Citrated blood obtained from each patient was sequentially centrifuged to produce both platelet-rich plasma (PRP) and platelet-poor plasma (PPP). Within 3 hours of blood draw, 2 separate aliquots of PRP from each patient were stimulated with 1 mg/L of collagen and platelet aggregation was measured for 5 minutes with constant stirring at 37°C by a turbidimetric method in a dual-channel aggregometer (Chrono-log Corp, Haverton, Pa). Aggregation was reported as the mean of the readings from each pair of aliquots. Platelet-poor plasma from each patient was used as that patient's reference in the aggregation experiments. The area under the curve (AUC) was calculated for the aggregation graphs. Research protocols were approved by the human research ethics committee at the University of Newcastle and the Hunter Area research ethics committee and all participants provided written informed consent.

The paired t test was used to analyze normally distributed data and the Mann-Whitney test to analyze nonnormally distributed data, as determined by the Anderson-Darling test. Comparisons between active intervention and placebo groups were performed after calculating the postsupplementation value minus the baseline value. Differences within each group were determined by comparing baseline values with postsupplementation values.

Results
No significant differences were observed in mean (SD) fasting HbA_1c levels following supplementation with tomato juice (7.1% [1.2%] vs 6.9% [1.0%]; P = .55) or placebo beverage (6.7% [1.0%] vs 6.6% [1.0%]; P = .68).

Mean (SD) baseline platelet aggregation values between the active and placebo groups were found to be significantly different using the Mann-Whitney test (AUC, 18730 [2783] vs 15294 [2131]; P = .01); however, the baseline values did not correlate significantly with the magnitude of change in response to either treatment (r = 0.28; P = .23). Platelet aggregation decreased following supplementation with tomato juice as compared with the placebo group (AUC, –4963 [3262] vs –370 [2274]; P = .002) (Figure 1). Platelet aggregation was significantly lower after 3 weeks of supplementation with tomato juice compared with baseline (AUC, 13767 [4658] vs 18730 [2783]; P = .001). No difference was observed in the placebo group between baseline and postsupplementation (AUC, 15294 [2131] vs 14924 [3334]; P = .85).

View larger version (29K): [in this window] [in a new window] Figure. Platelet Aggregation Values at Baseline and After Supplementation With Tomato Juice or Placebo Beverage

Comment
We found that consumption of tomato juice by individuals with type 2 diabetes inhibited platelet aggregation after 3 weeks. Antiplatelet medical therapies have been shown to reduce the risk of cardiovascular complications in type 2 diabetes. Larger randomized controlled trials are needed to determine whether consumption of tomato juice can improve cardiovascular outcomes in individuals with type 2 diabetes.

Dr Garg had full access to all of the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analyses.

Funding/Support: Masterfoods Australia/New Zealand supplied the materials and allowed use of their facilities for the preparation of the tomato juice and placebo beverage.

Role of the Sponsors: Masterfoods Australia/New Zealand had no input in the conduct or reporting of the study. Novo Nordisk contributed to the cost of analysis, but had no role in the conduct, analysis, or reporting of these data.

Sheryl A. Lazarus, BS
Department of Nutrition and Dietetics
Faculty of Health
University of Newcastle

Kerry Bowen, PhD, FRACP
Diabetes Education Centre
Royal Newcastle Hospital

Manohar L. Garg, PhD, APD
manohar.garg{at}newcastle.edu.au
Department of Nutrition and Dietetics
Faculty of Health
University of Newcastle
Newcastle, Australia

1. Vinik AI, Erbas T, Park TS, Nolan R, Pittenger GL. Platelet dysfunction in type 2 diabetes. Diabetes Care. 2001;24:1476-1485. FREE FULL TEXT 2. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA. 2002;287:2570-2581. FREE FULL TEXT 3. Willcox JK, Catignani GL, Lazarus S. Tomatoes and cardiovascular health. Crit Rev Food Sci Nutr. 2003;43:1-18. FULL TEXT | ISI | PUBMED 4. Dutta-Roy AK, Crosbie L, Gordon MJ. Effects of tomato extract on human platelet aggregation in vitro. Platelets. 2001;12:218-227. FULL TEXT | ISI | PUBMED 5. Lazarus SA, Garg ML. Tomato extract inhibits human platelet aggregation in vitro without increasing basal cAMP levels. Int J Food Sci Nutr. 2004;55:249-256. FULL TEXT | ISI | PUBMED 6. Yamamoto J, Taka T, Yamada K, et al. Tomatoes have natural anti-thrombotic effects. Br J Nutr. 2003;90:1031-1038. FULL TEXT | ISI | PUBMED

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2004;292:805-806.