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Nutrition Science

Dietary Nitrate and Nitrite Concentrations in Food Patterns and Dietary Supplements

Keller, Rosa M. BS; Beaver, Laura PhD, MS; Prater, M. Catherine; Hord, Norman G. PhD, MPH, RD

Author Information
doi: 10.1097/NT.0000000000000253
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Abstract

HEALTH BENEFITS OF DIETARY NITRATE AND NITRITE

Dietary nitrate and nitrite are found primarily in green leafy vegetables and root vegetables, such as spinach and beets, and have become popular because of potential cardiovascular health benefits.1 Dietary nitrate is reduced to nitrite in saliva by bacteria on the tongue and further metabolized to nitric oxide (NO) and various nitrogen oxide metabolites in the stomach before being circulated through the blood after absorption.2 In conditions of low oxygen availability such as living at high altitudes and exercise-induced hypoxia in muscle, nitrite can be converted into NO, a free radical gas that serves as a signaling molecule essential for endothelial function and metabolic regulation. Through these mechanisms, dietary nitrate consumption increases plasma nitrite concentration, reduces resting blood pressure, and improves vascular function.3

Current evidence suggests that endothelial dysfunction is associated with several cardiovascular risk factors including hypertension, diabetes, obesity, and atherosclerosis as a result of diminished NO production and bioavailability in the vasculature.4 Dietary sources of nitrate and nitrite restore NO homeostasis in the endothelium.5 Indeed, the blood pressure–lowering effects of the Dietary Approaches to Stop Hypertension (DASH) and other healthful dietary patterns may be attributable, in part, to nitrate and nitrite concentrations in vegetables that improve NO bioavailability.2,5,6 Human clinical trials have demonstrated the blood pressure–lowering effects of dietary nitrate in both healthy individuals and those with high blood pressure.1,7 Furthermore, dietary nitrate may also enhance the measured capacity to endure maximal exercise workload (ie, exercise tolerance) and performance in part by reducing the oxygen cost of submaximal exercise.4,6 The demonstrated cardiovascular health benefits of dietary nitrate–containing vegetables necessitate a reexamination of potential health risks and benefits associated with these foods.

RISKS ASSOCIATED WITH DIETARY NITRATE AND NITRITE

A conundrum exists concerning the potential health benefits and risks associated with consumption of dietary nitrate and nitrite. Studies indicate that a high concentration of nitrate in drinking water (eg, >50 mg/L) may cause harmful health effects such as methemoglobinemia and gastrointestinal carcinogenesis, although the evidence remains equivocal.8 The World Health Organization (WHO) used data based on risk of methemoglobinemia to set an acceptable daily intake (ADI) for nitrate of 3.7 mg/kg body weight per day, equivalent to 222 mg nitrate per day for a 60-kg adult, and nitrite of 0.07 mg/kg body weight per day, equivalent to 4.2 mg nitrite per day for a 60-kg adult.6,9 It is noteworthy that the upper limit represented by the WHO ADI corresponds to the concentration of dietary nitrate that lowers blood pressure in normotensive and hypertensive adults.4,10,11 In fact, single servings of high-nitrate foods, including spinach, arugula, and romaine lettuce, may exceed WHO ADI; these observations underscore contentious issues regarding the potential health risks and benefits of dietary nitrate and nitrite consumption.10

Nitrate and nitrite have been used in cured meats to prevent the growth of Listeria monocytogenes, botulism-causing bacteria, and contribute to their characteristic flavor and color of cured meats.7 Nitrate and nitrite are precursors of endogenously formed N-nitroso compounds or nitrosamines that are commonly associated with meats, processed meats, dairy products, and fish, whereas fruits, vegetables, sweets, and fats contain an insignificant concentration of nitrosamines.5,6 Vitamin C and flavonoids, found in a wide variety of fruits and vegetables, inhibit nitrosamine formation, whereas heme iron, found primarily in red meat, enhances nitrosamine production.12 The benefits of fruit and vegetable consumption, owing to their content of flavonoids and other nutrients may therefore mitigate the potential harmful effects of gastric formation of N-nitroso compounds.13 Food nitrate and nitrite concentrations can change as a result of processing, cooking method, and storage conditions. In most of these contexts, nitrates in foods are converted to nitrite by bacteria. As such, vegetables that have been damaged, poorly stored, pickled, fermented, or cooked increase the potential to form high nitrite levels.12,14

INTRINSIC AND EXTRINSIC FACTORS EFFECTING BIOAVAILABILITY OF DIETARY NITRATE

Health effects due to human exposure to dietary nitrate and nitrite can vary, depending on lifestyle choices and physiological and environmental factors. Environmental factors and food processing and storage methods that affect food nitrate and nitrite concentrations include the sulfate concentration of water,15 soil conditions, cooking and storage practices, and geographical location, among others.3 Physiological and lifestyle factors that influence bioavailability of nitrate include age, fitness status, smoking status, nitrate and nitrite dietary supplement use, dietary macronutrient and micronutrient composition, abundance of bacterial nitrate reductases found on the tongue, gastric acidity, atherosclerosis risk, diabetes, obesity, and other factors associated with altering vascular NO homeostasis.16,17 As such, factors intrinsic to food as well as extrinsic physiological or dietary factors must be considered in order to assess NO homeostasis in humans. Given these diverse parameters, there is a lot of inherent variability of dietary nitrate and nitrite exposure, making derivation of simplistic dietary recommendations for nitrate and nitrite consumption extremely difficult. Even so, we provide estimates of dietary nitrate and nitrite exposure from meal patterns, foods, and dietary supplements to assist with more accurate exposure assessments of these ubiquitous food components.

The World Health Organization's acceptable daily intake recommendations for nitrate can be exceeded by normal daily intakes of single foods and recommended dietary patterns, such as the Dietary Approaches to Stop Hypertension diet.

MATERIALS AND METHODS

The quantification of nitrate and nitrite in foods and supplements listed in Tables 1–3 was carried out using the hot water processing method of the UK Nitrate Residues Monitoring Program.19 Briefly, quadruplicate food and supplement samples for nitrate and nitrite analysis were prepared for extraction by mechanical disruption in distilled, deionized water and placed in clean, rinsed, glass bottles. Juices were added directly to glass bottles for processing. Bottles were wrapped in foil and heated at 60°C for 30 minutes with intermittent mixing. Control bottles containing only water were run in parallel as blanks to verify no contaminating nitrate or nitrite was present in the distilled, deionized water. Bottles were then cooled to room temperature, and samples were centrifuged at 4750 revolutions/min for 5 minutes. Supernatants for all samples were aliquoted, snap frozen in liquid nitrogen, and stored at −20°C. Nitrate and nitrite concentrations were determined by ozone chemiluminescence using standard protocols and a Sievers NOA (General Electric, Boulder, Colorado) as previously described.20 Concentrations of nitrate and nitrite were calculated with values obtained from a standard curve generated with 10 KM NaNO3 or 1 KM NaNO3 (Sigma-Aldrich, St Louis, Missouri) using Microsoft Excel and GraphPad Prism statistical software (La Jolla, California). Calculated concentrations were converted to either milligrams per serving or milligrams per 100 g for comparison. Foods presented in Table 2 were purchased from local restaurants in Corvallis, Oregon. Supplements were obtained from the manufacturer.

TABLE 1 - Nitrate Content of the 3 Treatment Groups in the Original DASH Diet Studya
Control Diet,b mg/Serving Fruit and Vegetable Diet,c mg/Serving Combination Dietd or DASH Diet, mg/Serving
Tomato—Roma 0.18 0.65 0.74
Peppers—green 1.78 4.27 8.01
Leeks 1.97 2.22 2.71
Cabbage 4.28 6 7.28
Sweet potatoes 7.5 0 10.5
Spinach 27.11 56.15 81.32
Oyster mushroom 0.01 0 0
Celery 33.78 43.72 3.97
Green beans 9.81 19.99 20.74
Zucchini 10.52 12.37 21.65
Total exposure, mg/d 96.9 145.4 156.9
Abbreviation: DASH, Dietary Approaches to Stop Hypertension.
aData reference from Obarzanek and Moore TJ.18
bPrototypical American diet as determined by the original DASH diet trial.
cFruit and vegetable diet incorporates 8 to 10 added servings of fruits and vegetables to the control diet.
dCombination diet includes 8 to 10 servings of fruits and vegetables and low fat dairy. The combination diet is also recognized as the current DASH diet plan.

TABLE 2 - Nitrate and Nitrite Content in 4 Representative Meal Patternsa–c (ie, American, Japanese, Chinese, Indian)
American Meal Pattern Japanese Meal Pattern Chinese Meal Pattern Indian Meal Pattern
Foods Serving Size Nitrate, mg/Serving Nitrite, mg/Serving Foods Serving Size Nitrate, mg/Serving Nitrite, mg/Serving Foods Serving Size Nitrate, mg/Serving Nitrite, mg/Serving Foods Serving Size Nitrate, mg/Serving Nitrite, mg/Serving
Breakfast Breakfast Breakfast Breakfast
Scrambled eggs 100 g 0.55 0.007 White rice 6 oz. 0.18 0.012 Congee 300 g 0.333 0.035 Idlid 200 g 0.14 0.002
Hash browns 56 g 7.73 0.01 Miso soup 8.1 fl. oz. 1.06 0.002 Rousonge 10 g 0.063 Peanut chutney 50 g 0.5 0.012
Orange juice 8 fl oz. 0.34 Broiled mackerel 3 oz. 0.21 0.004 Pickled mustard stem 20 g 8.007 Coffee 100 ml 0.28
Lunch Nori, dried seaweed 2 sheets 6.8 0.002 Lunch White rice 400 g 0.28 0.024
Mac and cheese 100 g 0.48 0.018 Green tea 1 bag 0.74 Steamed bun (mantou) 150 g 0.765 0.036 Lunch
Tomato soup 248 g 2.16 Lunch Gan BIan Si Ji Douf 75 g 62.19 0.007 Potato and cauliflower curry 300 g 30.33 0.041
Snack White rice 6 oz. 0.18 0.012 Braised spareribs—daikon 200 g 88.74 0.01 Rasamg 240 ml (8 fl oz.) 12.86
Potato chips—kettle cooked 56 g 24.9 0.006 Shiitake and spinach 300 g 97.97 0.016 Green tea 240 ml (1 tea bag, 2 g) 0.74 Pickled mango 30 g 0.63
Apple 100 g 0.04 Unagi nigiri 3 pieces (2.5 oz.) 0.8 0.004 Snack Snack
Dinner Pickled ginger 2 slices (0.5 oz.) 9.35 Asian pear 100 g 0.125 Curd (yogurt) 150 g 0.2
Meatloaf (pork and beef) 300 g 2.32 0.036 Snack Dinner Tea 100 ml (1/2 cup) 0.09
Side salad 60 g 36.82 Edamame 3 oz. 0.56 0.011 White rice 175 g 0.182 0.012 Dinner
Reser's Potato Salad 135 g 34.15 0.007 Orange 5 oz.
(1 medium)
1.09 Shrimp with vegetables 150 g 45.74 0.017 Rotih 250 g
(4 count)
4.57 0.012
Ice cream 65 g 0.33 0.008 Dinner Cooked eggplant 100 g 14.55 0.014 Spinach dali 400 g 46.46 0.021
White rice 150 g 0.18 0.012 Napa cabbage-tofu soup 150 ml 9.71 0.002 Curd (yogurt) 150 g 0.19
Vegetarian tofu 1 bowl (650 g) 78.98 0.032
Seaweed salad 3 oz. 0.77 0.001
Nattoj 1 cup (6 oz.) 1.31 0.012
Pickled daikon 1 oz. (4 slices) 18.43 0.001
Total (mg/d) 109.8 0.092 218.6 0.121 231.1 0.133 100.8 0.112
aFoods were processed then analyzed via Sievers NOA Chemiluminescence method (NO Analyzer, model 280i; GE Analytical Instruments, Boulder, Colorado). These amounts per serving represent a mean of 4 observations.
bThe hypothetical 1-day meals were constructed by obtaining data from online resources including the Japanese Dietetics Association and California Agriculture Magazine and from consulting individuals of each cultural heritage.
cFoods were collected from local restaurants and grocery stores in Corvallis, Oregon.
dIdli is a traditional Indian savory breakfast cake.
eRousong is a dried meat product originating from China.
fGan BIan Si Ji Dou is a dry-fried green bean dish.
gRasam is a Southern Indian soup made from tamarind, tomatoes, and spices.
hRoti is flatbread made from stone-ground whole-wheat flour.
iSpinach dal is a common Indian dish made up of beans, lentils, peas, butter spices, and spinach.
jNatto is a fermented soybean product commonly eaten in Japan.

TABLE 3 - Nitrate and Nitrite Content From a Wide Range of Commercially Available Dietary Supplements
Supplement Brands % of ADI for Nitrate of a 60-kg Adult, 3.7 mg/kg/d Nitrate, mg/Serving Nitrate, mg/100 g % of ADI for Nitrite of a 60-kg Adult (0.07 mg/kg per day) Nitrite, mg/Serving Nitrite, mg/100 g
HumanN— SuperBeets, canister 47.26 104.92 2098.42 132.77 5.58 111.52
HumanN—NeO40, 1 tablet 22.19 49.26 451.90 12.7
Nutrex Hawaii, Inc—Spirulina Pacifica 1.00 2.23 74.24 21.11 0.89 29.54
Source Naturals, Inc—Yaeyama Chlorella 0.10 0.22 7.37 0.11 0.00 0.16
Controlled Labs—Orange Oximega Greens 11.38 25.27 463.59 0.18 0.01 0.14
Garden of Life, LLC—Perfect Food–Raw Organic Green Super Food 10.34 22.96 286.94 0.08 0.00 0.04
Nature's Way Products, Inc—Garden Veggies 0.39 0.86 86.44 0.00 0.00 0.01
Nature's Way Products, Inc—Barley Grass Powder 11.22 24.91 207.65 0.05 0.00 0.02
Mars, Inc—CocoaVia 0.44 0.97 12.61 0.02 0.00 0.01
HumanN—BeetElite NeOShot 96.90 215.12 2151.24 225.09 9.45 94.54
Healthworks, LLC—Certified Organic Raw Maca Powder 0.11 0.25 6.20 0.02 0.00 0.03
Stakich, Inc—Bee Pollen 0.07 0.15 5.13 0.00 0.00 0.00
Vibrant Health—Green Vibrance 10.72 23.81 196.76 0.14 0.01 0.05
Stakich, Inc—Royal Jelly 0.01 0.01 1.11 0.00 0.00 0.00
Ultimate Nutrition, Inc—Vegetable Greens 5.21 11.56 146.38 0.08 0.00 0.05
Moringa Powder 0.48 1.06 13.09 0.00 0.00 0.00
Beet Boost 8.23 18.27 166.11 0.98 0.04 0.37
Biotta Naturals: Beet Juice 200 444.06 0.01 0.00 0.00
ADI, acceptable daily intake.

NITRATE AND NITRITE CONCENTRATIONS IN MEAL PATTERNS

We quantified the nitrate and nitrite contents of certain dietary sources of exposure from mixed dishes, foods, and meal patterns. This assessment of daily meal patterns is of paramount importance in order to assess any potential health benefits or risks resulting from consumption of dietary nitrate. The DASH dietary pattern is represented by food choices including low-fat dairy products, whole grains, and 8 to 10 servings of fruits and vegetables that serves as a food pattern recommended by US federal agencies because it has been shown to reduce blood pressure and improve cardiovascular risk factors.4,13 As such, we analyzed the vegetable nitrate and nitrite content from food recommendations from the original DASH diet study21 (Table 1). We focused on the vegetable components of the diet because approximately 80% of dietary nitrate is derived from vegetable intakes.21 The original DASH diet studies used the foods listed in Table 1; the “combination diet” listed was thereafter referred to as the DASH diet. Nitrate intakes represented by the combination diet or DASH diet increased daily nitrate by 47.1 mg/d compared with the standard American diet (Table 2), a 20% increase in the ADI resulting from increased vegetable consumption. Furthermore, Hord et al3 modeled a diet high in nitrate-rich foods in a hypothetical DASH diet and estimated a potential nitrate concentration of approximately 1.2 g nitrate per day.18,22

Foods that serve as rich sources of dietary nitrate, such as leafy green vegetables and fermented foods, are more abundant in traditional Japanese foods than standard American foods.23 We hypothesized that cultural meal patterns (Table 2) with a greater abundance and variety of vegetables would have greater dietary nitrate in the diet per day. These nitrate exposure estimates place the Japanese and Chinese meal patterns at approximately the WHO ADI of 222 mg/d for a 60-kg adult, whereas the American and Indian meal patterns were relatively lower (approximately 100 mg/d). The Indian and American meal patterns we analyzed incorporated green leafy vegetables to a lesser extent than the Japanese and Chinese diet. Nitrate levels in these 2 cultural food patterns were well below the ADI for nitrate.

These nitrate exposure estimates herein are concordant with the estimates based on in-country analysis from Japan23 and China.24 In Hong Kong, dietary exposure to nitrate from raw vegetables was estimated to be approximately 120% and 350% the ADI for average- and high-vegetable consumers, respectively.24 Leafy greens, including spinach, bok choy, and Chinese cabbage, have been associated with lower systolic and diastolic blood pressure.25 Japanese meal patterns rely on a wide variety of vegetables, indicating that dietary nitrate may in part be responsible for the lower rates of cardiovascular disease in Japan.23 It is noteworthy that dietary nitrate lowers blood pressure in normotensive individuals and, to a greater extent, in prehypertensive and hypertensive individuals.5

DIETARY SUPPLEMENTS CONTAINING NITRATE AND NITRITE

We determined the nitrate and nitrite concentrations per serving and the respective percent of ADI for 18 supplement brands in order to better understand potential exposures to nitrate and nitrite from these products (Table 3). Most of the supplement products containing high levels of nitrate do so by incorporating dehydrated or concentrated forms of vegetables or vegetable juices from which they are derived. For example, Neo40 (Humann, Austin, Texas; http://www.humann.com) is marketed to improve healthy cardiovascular function; 1 Neo40 tablet contains 22% and 450% the ADI for nitrate and nitrite, respectively (Table 3). Beet Boost, a popular performance supplement consisting of beetroot and tart cherry powder, contains approximately 20% of the ADI for nitrate. Beet Elite (Humann) is marketed as an endurance supplement by improving exercise endurance and increasing oxygen delivery in the body. One serving of Beet Elite contains approximately 97% and 225% of the ADI for nitrate and nitrite, respectively (Table 3). These claims are supported by research that utilized beetroot juice as a treatment; it is less certain, however, whether nitrate-rich supplements result in the performance benefits of beetroot juice.

HYPOTHETICAL SCENARIOS AND ESTIMATED HUMAN EXPOSURE

Quantifying nitrate and nitrite content of potential sources of exposure is critical to assess the potential health effects resulting from dietary nitrate and nitrite. Little is known about total human exposure to nitrate and nitrite, and subpopulations may have measurably different dietary nitrate and nitrite needs and exposure. Six hypothetical scenarios described (Table 4) illustrate context in which individuals may dramatically exceed nitrate and nitrite available from the normal dietary patterns described in this article. The daily exposure scenarios demonstrate that nitrate exposure can range from approximately 50% up to 250% of the ADI, whereas nitrite exposure can range from 2.2% up to approximately 300% of the ADI. An elderly person with heart disease or hypertension will have a much greater need for dietary nitrate and nitrite because of reduction of endogenous NO production.7 An adult who supplements his/her diet with a beetroot juice beverage and ½ serving of cooked beets or spinach (310 mg) exceeds the current ADI for a 60-kg adult at an easily achievable level. An endurance athlete on the DASH diet plan who is taking a supplement will have an approximately 5-fold increase in total exposure to nitrate compared with a 60-kg healthy adult on a standard American diet (Table 4). It is important to consider the health benefits of increased nitrate consumption from leafy greens and supplements while also being cognizant of the potential safety concerns associated with elevated nitrate and nitrite concentrations.

An adult who supplements his/her diet with a beetroot juice beverage or ½ cup serving of cooked beets or spinach (310 mg) exceeds the current acceptable daily intake for a 60 kg-adult at an easily achievable level.

TABLE 4 - Estimated Nitrate and Nitrite Daily Exposure in 3 Hypothetical 60-kg Adult Scenarios on an American Dieta
Population Sources of Nitrate/Nitrite Estimated Exposure, mg/d % WHO ADIb for
Nitrate Nitrite Nitrate Nitrite
Adult: 18-70 y American dieta 109.8 0.092 49 2.2
American diet + 2 cups raw spinach (60 g)c 189.8 0.530 86 12.6
DASH dietd 156.9 0.634 71 18
Adult athlete American diet + supplementation with beetroot powdere 325.0 9.542 146 227
DASH diet + beet juicef 601.0 0.699 271 22
Adult: 70 y with peripheral artery disease American diet + nitrate/nitrite supplementg 159.1 12.80 72 305
Abbreviations: ADI, acceptable daily intake; DASH, Dietary Approaches to Stop Hypertension; WHO, World Health Organization.
aThe American Diet referenced is based on the data collected and does not represent the diet of all Americans. It does not meet the recommended servings from the US Department of Agriculture guidelines for fruit and vegetable consumption.
bThe Joint Food and Agricultural Organization/WHO ADI for the nitrate ion is 3.7 mg/kg of body weight and for the nitrite ion is 0.06 mg/kg of body weight.
cOpinion of the Scientific Panel on Contaminants in the Food Chain on a request from the European Commission to perform a scientific risk assessment on nitrate in vegetables.10
dOriginal DASH diet from Vogt et al. “Dietary Approaches to Stop Hypertension: Rationale, Design, and Methods. DASH Collaborative Research Group.” J Am Diet Assoc 1999;99(8 suppl):S12–S18.
eThe beetroot powder references the nitrate and nitrite content for Beet Elite.
fBiotta Naturals: Beet Juice (250 mL).
gThe nitrate/nitrite supplement references the nitrate and nitrite content for Neo40 (HumanN, Austin, Texas).

RECOMMENDATIONS FOR DIETARY INTAKES OF NITRATE AND NITRITE: EXAMPLES OF REGULATORY AGENCY STATEMENTS AND FUTURE NEEDS

The Food Standards Australia New Zealand and the European Food Safety Authority conclude that the major sources of estimated nitrate and nitrite exposure, across different population groups, were vegetables and fruits (including juices).10,26 Processed meats only accounted for 10% of total dietary exposure to nitrite in the European survey.10,26 Consumption and exposure to dietary nitrate and nitrite is not considered an “appreciable health and safety risk”, according to the Australian agency.26 The European agency similarly quantified exposure to different concentration of nitrate-rich vegetables and found the ADI to be easily achievable when exposed to primarily leafy greens and overall, not associated with an increased cancer risk.27 The USDA nutrient database currently lacks dietary nitrate and nitrite concentrations of foods; the development of such a database would fill a critical void and allow for more accurate human exposure assessments in epidemiological studies.2

The Food Standards Australia New Zealand and European Food Standards Agency assessments give limited information regarding potential health benefits of nitrate- and nitrite-containing vegetables while concluding that overall health risks are low at normal intake levels. Given the established vasoprotective, performance-enhancing, blood pressure–lowering effects of dietary nitrates in humans, specific recommendations to encourage plant-based, nitrate-rich foods may produce significant public health benefits. Concerns regarding health risks of drinking water and food nitrate concentrations,10 taken together with the ascendency of commercial dietary nitrate–rich supplements, may necessitate an independent panel of experts from academia, industry, and governmental and nongovernmental sectors to undertake the first comprehensive, systematic review of the potential health risks and benefits of food sources of nitrates and nitrites. The US Institute of Medicine's Dietary Reference Intake paradigm may be a useful guide to the development of coherent, evidence-based approach to deriving recommendations to maximize potential health benefits and reduce potential risks associated with dietary nitrate and nitrite intakes.

Given the established vasoprotective, performance-enhancing, blood pressure–lowering effects of dietary nitrates in humans, specific recommendations to encourage plant-based, nitrate-rich foods may produce significant public health benefits.

Acknowledgments

The authors acknowledge the technical assistance of Dr Ajay Machha, Ms Micheala Zucker, and Ms Lynn Zhang.

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Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc.