Written by Chrystal Moulton, Staff Writer. Participants with moderate intake of vegetable nitrate had a 15% lower risk of CVD.
Nitric oxide is one of the keys to cardiovascular health 1. Vegetables are the main source of nitrates especially green leafy vegetables and beets 2. Various studies which investigated the effects of inorganic nitrate cardiovascular risk have demonstrated positive results for both blood pressure and vascular function 3,4. However large prospective studies investigating the habitual intake of dietary nitrate and its association with cardiovascular disease (CVD) have not been conducted. In the current study 5, researchers investigated the association between intake of nitrate from vegetable sources and the incidence of cardiovascular disease (CVD) in the Danish Diet, Cancer, and Health Study cohort. Additionally, researchers investigated the association of intakes of vegetable nitrate with baseline systolic and diastolic blood pressure and whether these associations mediated incidence of cardiovascular disease (CVD).
The Danish Diet, Cancer, and Health Study cohort was a large prospective study started in 1993. A total of 57,053 participants were recruited into the study of which, 56,468 were without cancer at enrollment and successfully completed the food-frequency questionnaire at baseline. Participants were excluded if they had CVD or were missing any data. Participants were also excluded if they had implausible data. Participants completed a food frequency questionnaire to report average intakes of various food and beverage items over the past 12 months. Blood pressure was also taken at baseline. Nitrate intake was calculated and quantified into mg/day. Quantities of nitrate intake was broken down into quintiles for statistical analysis. Primary outcome was hospitalization with ischemic heart disease (IHD), ischemic stroke, peripheral artery disease (PAD), heart failure, hemorrhagic stroke, or atrial fibrillation (AF) as a primary or a secondary diagnosis. Participants were followed up for a maximum of 23 years from the date of enrollment until the date of emigration, death, incidence of CVD, or end of follow up (August 2017) whichever came first. Data was modeled to express hazard ratios across multivariate adjustments to account for any potential confounders of nitrate intake and CVD.
A total of 53,150 participants were included in this prospective study. The median age was 56 years old and total median vegetable nitrate intake was 59 mg/day with non-vegetable nitrate intake at 15 mg/ day. Researchers saw an inverse relationship between vegetable nitrate intake and blood pressure in a dose-dependent manner. Participants in quintile 5 (141mg/d vegetable nitrate intake) at baseline had a lower systolic (2.58 mmHg lower) and diastolic pressure (1.38 mmHg lower) than those in the lowest quintile (quintile 1: 23mg/d vegetable nitrate) [p <0.001]. This inverse relationship was maintained whether or not a participant was on anti-hypertensive medication at baseline. No association was observed for non-vegetable nitrate intake and blood pressure. The association between vegetable nitrate intake an CVD hospitalization was non-linear. Participants with moderate intake of vegetable nitrate (quintile 3) had a 15% lower risk of CVD even after multivariate adjustments compared to participants in quintile 1 (P<0.05). No additional benefits were observed for higher levels of vegetable nitrate intake. Further associations between vegetable nitrate intake and CVD subtypes can be seen in Table 1.
Table 1. Association between vegetable nitrate intake and CVD events| CVD event (subtype) | Quintile 2 (39mg/d) | Quintile 3 (59mg/d) | Quintile 5 (141mg/d) |
|---|---|---|---|
| CVD -general | 0.91 | 0.85 | 0.86 |
| Ischemic heart disease | 0.93 | 0.88 | 0.85 |
| Ischemic stroke | 0.88 | 0.83 | 0.87 |
| Heart failure | 0.91 | 0.85 | 0.86 |
| Peripheral artery disease | 0.84 | 0.74 | 0.65 |
*values are hazard ratios that are representative of multivariate adjustment for age, sex, BMI, smoking, income, marital status, education, alcohol intake, prevalent or chronic disease, hypercholesterolemia. All values are Within 95% CI, P<0.05.
Participants with moderate intake of vegetable nitrate had a 6% lower risk of hospitalization as a result of CVD [HR = 0.94], a 19% lower risk of hemorrhagic stroke [HR= 0.81], and a 15% lower risk of peripheral artery disease [HR= 0.85]. Additional analysis also showed that baseline systolic blood pressure accounted for 21.9% of the association between CVD and plant-based nitrate intake.
Overall, the study demonstrated that moderate intake of vegetable nitrates was significantly and inversely associated with the occurrence of CVD. No additional benefits were observed for higher nitrate intakes. Also, at the highest intake of vegetable nitrate, participants had lower systolic blood pressure and diastolic blood pressure compared to those in the lowest intake group. Further studies would need to explore the mechanisms that contribute to the benefits observed in this study.
Source: Bondonno, Catherine P., Frederik Dalgaard, Lauren C. Blekkenhorst, Kevin Murray, Joshua R. Lewis, Kevin D. Croft, Cecilie Kyrø et al. “Vegetable nitrate intake, blood pressure and incident cardiovascular disease: Danish Diet, Cancer, and Health Study.” European Journal of Epidemiology (2021): 1-13.
© The Author(s) 2021
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Posted July 6, 2021.
Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.
References:
- Jin RC, Loscalzo J. Vascular Nitric Oxide: Formation and Function. Journal of blood medicine. 2010;2010(1):147-162.
- Blekkenhorst LC, Prince RL, Ward NC, et al. Development of a reference database for assessing dietary nitrate in vegetables. Molecular nutrition & food research. 2017;61(8).
- Bondonno CP, Blekkenhorst LC, Liu AH, et al. Vegetable-derived bioactive nitrate and cardiovascular health. Mol Aspects Med. 2018;61:83-91.
- Jackson JK, Patterson AJ, MacDonald-Wicks LK, Oldmeadow C, McEvoy MA. The role of inorganic nitrate and nitrite in cardiovascular disease risk factors: a systematic review and meta-analysis of human evidence. Nutr Rev. 2018;76(5):348-371.
- Bondonno CP, Dalgaard F, Blekkenhorst LC, et al. Vegetable nitrate intake, blood pressure and incident cardiovascular disease: Danish Diet, Cancer, and Health Study. Eur J Epidemiol. 2021.
