Influence of fruit and vegetable juices on the endogenous formation of N-nitrosoproline and N-nitrosothiazolidine-4-carboxylic acid in humans on controlled diets
Abstract
Water, green pepper, pineapple, tomato, strawberry, carrot, and celery juices were made 46 mg/100 ml in ascorbic acid by the addition of distilled water or ascorbate. The ability of each juice to inhibit endogenous formation of N-nitrosoamino acids (NAA) in humans was determined in controlled experiments. Sixteen men consumed a standard diet low in nitrate and ascorbic acid for 18 consecutive days. Nitrate (5.24 mmol) and L-proline (4.35 mmol) were given orally on days 3, 5, 7, 9, 11, 13, 15, 17 and 18. On days 3 and 18, L-proline was immediately followed by 100 ml distilled water (positive control). On days 5, 7, 9, 11, 13, 15 and 17, L-proline was immediately followed by 100 ml juice or 46 mg ascorbate in 100 ml distilled water (treatment). Only diet was given in between dosing days to ensure baseline levels of NAA excretion. Urine was collected for 24 h following treatments and analyzed for NAA. Green pepper, pineapple, tomato, strawberry and carrot treatments significantly inhibited N-nitrosoproline (NPRO) formation relative to the positive control. Also, green pepper, pineapple and tomato juices significantly inhibited NPRO formation relative to ascorbic acid alone. Green pepper significantly inhibited N-nitrosothiazolidine-carboxylic acid formation relative to ascorbic acid alone. These data demonstrate that green pepper, tomato, pineapple, strawberry and carrot juice have greater ability to inhibit endogenous nitrosation than would be expected based solely on their ascorbate content.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
When ingested nitrate and nitrite are paired with plant- and fruit-based polyphenols and essential nutrients such as ascorbate, gastric nitrosation is inhibited.
“Excitingly, when ingested nitrate and nitrite are rather paired with plant- and fruit-based polyphenols and essential nutrients such as ascorbate, gastric nitrosation is inhibited[162,167,168]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [167]
Cited by
Sorted by citations
Vitamin C as an Antioxidant: Evaluation of Its Role in Disease Prevention
Padayatty, S. J., Katz, A., Wang, Y., Eck, P., Kwon, O., Lee, J.-H., Chen, S., Corpe, C., Dutta, A., Dutta, S. K., et al. (2003) · Journal of the American College of Nutrition · doi:10.1080/07315724.2003.10719272 · Cited by 1,949 · see citing works
“Formation of nitrosamines in the gastrointestinal tract can be decreased by administration of vitamin C [155].”
BackgroundDrinking Water Nitrate and Human Health: An Updated Review
Ward, M., Jones, R., Brender, J., De Kok, T., Weyer, P., Nolan, B., Villanueva, C., & Van Breda, S. (2018) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph15071557 · Cited by 1,576 · see citing works
“This might apply for green leafy vegetables such as spinach and rocket salad, celery or kale [77] as well as other vegetables rich in both nitrate and natural nitrosation inhibitors.”
BackgroundVitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance
Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., Dhariwal, K. R., Park, J. B., Lazarev, A., Graumlich, J. F., King, J., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3704 · Cited by 1,325 · see citing works
Mirvish, S. S. (1995) · Cancer Letters · doi:10.1016/0304-3835(95)03786-v · Cited by 916 · see citing works
Vitamin C: The known and the unknown and Goldilocks
Padayatty, S., & Levine, M. (2016) · Oral Diseases · doi:10.1111/odi.12446 · Cited by 753 · see citing works
“Stomach Prevent formation of N-nitroso compounds (Helser et al., 1992, Aditi & Graham, 2012).”
Criteria and recommendations for vitamin C intake
Levine, M. (1999) · JAMA · doi:10.1001/jama.281.15.1415 · Cited by 559 · see citing works
“Vitamin C transport will achieve Vmax in tissues,(61) LDL oxidation might be decreased compared with lower doses,(6,7) ascorbate recycling as a protective mechanism in neutrophils might be optimized,(64) and decreased nitrosation in the gastrointestinal tract might result from this dose.(67) Also, intake of 5 servings…”
BackgroundKoch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.015 · Cited by 186 · see citing works
“nutrients such as ascorbate, gastric nitrosation is inhibited [162,167,168], suggesting that the mutagenic potential of dietary”
BackgroundKobayashi, J. (2017) · Nitric Oxide · doi:10.1016/j.niox.2017.06.001 · Cited by 136 · see citing works
“In addition, the N-nitrosation reaction is inhibited by appreciable amounts of ascorbic acid that are secreted in gastric juice [79] and concurrent ingestion of fruits and vegetables that are rich in antioxidants such as polyphenols and vitamins C and E (by promoting NO generation from nitrite) [5,35,86].”
Ikken, Y., Morales, P., Martínez, A., Marín, M. L., Haza, A. I., & Rodríguez, M. I. C. (1999) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf990166n · Cited by 134 · see citing works
Inhibition of cellular transformation by berry extracts
Xue, H., Aziz, R. M., Sun, N., Cassady, J. M., Kamendulis, L. M., Xu, Y., Stoner, G. D., & Klaunig, J. E. (2001) · Carcinogenesis · doi:10.1093/carcin/22.2.351 · Cited by 121 · see citing works
Development of a reference database for assessing dietary nitrate in vegetables
Blekkenhorst, L. C., Prince, R. L., Ward, N. C., Croft, K. D., Lewis, J. R., Devine, A., Shinde, S., Woodman, R. J., Hodgson, J. M., & Bondonno, C. P. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600982 · Cited by 99 · see citing works
“This reaction, is however, 36 inhibited in the presence of antioxidant compounds such as polyphenols, vitamins C and E, 37 which are also found in vegetables [7-9].”
BackgroundChung, M. J., Lee, S. H., & Sung, N. J. (2002) · Cancer Letters · doi:10.1016/s0304-3835(02)00076-9 · Cited by 99 · see citing works
Ahluwalia, A., Gladwin, M., Coleman, G. D., Hord, N., Howard, G., Kim‐Shapiro, D. B., Lajous, M., Larsen, F. J., Lefer, D. J., McClure, L. A., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003402 · Cited by 92 · see citing works
Choi, S. Y., Chung, M. J., Lee, S., Shin, J. H., & Sung, N. J. (2006) · Food Control · doi:10.1016/j.foodcont.2005.12.006 · Cited by 67 · see citing works
“Tomatoes, green peppers, pineapples, strawberries, and carrot juice all had a greater ability to inhibit endogenous nitrosation in vivo than an equal amount of ascorbic acid taken with water alone (Helser et al., 1992).”
BackgroundAssociation between diet and esophageal cancer in Taiwan
Hung, H.-C., Huang, M., Lee, J., et al. (2004) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2004.03346.x · Cited by 62 · see citing works
Choi, S. Y., Chung, M., & Sung, N. J. (2002) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(02)00025-x · Cited by 58 · see citing works
Mills, C. E., Khatri, J., Maskell, P., Odongerel, C., & Webb, A. J. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12918 · Cited by 55 · see citing works
“found that ascorbic acid (46 mg in 100 ml water) only inhibited nitrosamine formation (as assessed by the N-nitrosoproline (NPRO) test) by 24% compared with 41–63% following ingestion of juices (100 ml) made of green pepper, pineapple, strawberry, or carrot containing an equal total amount of ascorbic acid [57].”
MethodLu, M.-J., & Chen, C. (2007) · Process Biochemistry · doi:10.1016/j.procbio.2007.06.003 · Cited by 52 · see citing works
Milner, J. A. (1994) · Springer eBooks · doi:10.1007/978-1-4615-2073-3_3 · Cited by 52 · see citing works
Feng, R., Bowman, L., Lu, Y.-J., Leonard, S., Shi, X.-L., Jiang, B.-H., Castranova, V., Vallyathan, V., & Ding, M. (2004) · Nutrition and Cancer · doi:10.1207/s15327914nc5001_11 · Cited by 36 · see citing works
Cheng, C., & Tsang, C. W. (1998) · Food Additives & Contaminants · doi:10.1080/02652039809374706 · Cited by 34 · see citing works
Nitrite-stimulated Gastric Formation of S-nitrosothiols As An Antihypertensive Therapeutic Strategy
Oliveira‐Paula, G. H., & Tanus-Santos, J. E. (2018) · Current Drug Targets · doi:10.2174/1389450119666180816120816 · Cited by 33 · see citing works
Mirvish, S. S., Grandjean, A. C., Reimers, K. J., Connelly, B. J., Chen, S. C., Morris, C. R., Wang, X., Haorah, J., & Lyden, E. R. (1998) · Nutrition and Cancer · doi:10.1080/01635589809514688 · Cited by 28 · see citing works
Food Polyphenols as Preventive Medicine
Kanner, J. (2023) · Antioxidants · doi:10.3390/antiox12122103 · Cited by 30 · see citing works
“Fruits and vegetable juices were found to decrease endogenous formation of N-nitrosoproline in human on controlled diets [71].”
BackgroundPorubin, D., Hecht, S. S., Li, Z.-Z., Gonta, M. V., & Stepanov, I. S. (2007) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0712191 · Cited by 26 · see citing works
Vitamin C: From Molecular Actions to Optimum Intake
Padayatty, S. J., Daruwala, R., Wang, Y., Eck, P., Song, J., Koh, W. S., & Levine, M. (2001) · doi:10.1201/9780203904046-13 · Cited by 25 · see citing works
Bahadoran, Z., Mirmiran, P., Kashfi, K., & Ghasemi, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094735 · Cited by 19 · see citing works
Ikken, Y., Rodríguez, M. I. C., Marín, M. L., et al. (1998) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf980657s · Cited by 19 · see citing works
Martínez, A., Ikken, Y., Rodríguez, M. I. C., Marín, M. L., Haza, A. I., Casás, C., & Morales, P. (1999) · Food Science and Technology International · doi:10.1177/108201329900500509 · Cited by 18 · see citing works
“These fruits and vegetables were selected on the basis of preliminary irr vitro assays described by several authors (Helser et al., 1992; Bronzetti, 1994; Dorant et al., 1995).”
MethodMartínez, A., Rodríguez, M. I. C., Ikken, Y., Marín, M. L., Haza, A. I., & Morales, P. (1998) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf970636i · Cited by 18 · see citing works
Oliveira‐Paula, G. H., Batista, R. I. M., Stransky, S., Conde-Tella, S. O., Ferreira, G. C., Portella, R. L., Pinheiro, L. C., de Angelis, C. D., Riascos‐Bernal, D. F., Sidoli, S., et al. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115571 · Cited by 14 · see citing works
Therapeutic Implications of Nitrite in Hypertension
Ling, W. C., Mustafa, M. R., & Murugan, D. D. (2019) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000771 · Cited by 14 · see citing works
Kim, S. Y. (2012) · Preventive Nutrition and Food Science · doi:10.3746/pnf.2012.17.4.269 · Cited by 12 · see citing works
“Phenolic compounds, which are present in high quantities in human foods and beverages derived from plant and fruits, are potent blocking agents of N-nitrosamine compound formation (26).”
BackgroundIn situ kinetics: An approach to recommended intake of vitamin C
Levine, M., Rumsey, S. C., Wang, Y., Park, J. M., Kwon, O., & Amano, N. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)81048-8 · Cited by 12 · see citing works
Water-Soluble Vitamins and Nonnutrients
Kohlmeier, M. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-387784-0.00010-9 · Cited by 14 · see citing works
(+)-Catechin is a Potent Inhibitor of Intestinal Absorption of Cholesterol in Rats
Noh, S. K., Koo, S. I., & Jiang, Y. (2003) · Preventive Nutrition and Food Science · doi:10.3746/jfn.2003.8.1.001 · Cited by 11 · see citing works
Padayatty, S. J., Levine, M., Eck, P., Wang, Y., Song, J. G., Koh, W. S., & Daruwala, R. (2001) · CRC Press eBooks · doi:10.1201/9780203904046.pt3 · Cited by 9 · see citing works
Levine, M. N., Rumsey, S. C., & Wang, Y. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)79008-6 · Cited by 9 · see citing works
Nazzaro, F., Cardinale, F., Cozzolino, A., Granese, T., & Fratianni, F. (2014) · Food and Nutrition Sciences · doi:10.4236/fns.2014.512124 · Cited by 8 · see citing works
“Phenolic compounds, present in high concentration in human foods and beverages from plant and fruits, are potent blocking agents of N-nitrosamine compound formation [19].”
BackgroundIn vitro Inhibition of N‐Nitrosomorpholine Formation by Fresh and Processed Tomatoes
Nagarajan, N., & Hotchkiss, J. H. (1999) · Journal of Food Science · doi:10.1111/j.1365-2621.1999.tb12260.x · Cited by 8 · see citing works
Self-citationSirvins, C., Goupy, P. M., Promeyrat, A., & Dufour, C. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c08445 · Cited by 4 · see citing works
Screening of Effective Components from Kale to Inhibit N - Nitrosodimethylamine Formation
정미자, 이수정, 최선영, & 성낙주 (2003) · Journal of the Korean Society of Food Science and Nutrition · doi:10.3746/jkfn.2003.32.2.223 · Cited by 3 · see citing works
Clifford, C. K. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-709-3_31 · Cited by 3 · see citing works
Lafontaine, A., Donat‐Vargas, C., Lequy, É., Lee, S., Glorennec, P., Bot, B. L., Goldberg, M., Zins, M., Jacquemin, B., & Villanueva, C. M. (2025) · Environment International · doi:10.1016/j.envint.2025.109853 · Cited by 2 · see citing works
Screening for Components to Inhibit N-Nitrosodimethylamine Formation from Tomato
(2006) · Journal of Life Science · doi:10.5352/jls.2006.16.5.794 · Cited by 2 · see citing works
Kohlmeier, M. (2003) · Elsevier eBooks · doi:10.1016/b978-012417762-8.50079-x · Cited by 2 · see citing works
Proper Nutritional Habits for Reducing the Risk of Cancer
Clifford, C. K., & McDonald, S. S. (2001) · Humana Press eBooks · doi:10.1007/978-1-59259-226-5_5 · Cited by 2 · see citing works
Inhibition of in Vitro Nitrosation of Nornicotine
Porubin, D. (2007) · Chemistry Journal of Moldova · doi:10.19261/cjm.2007.02(1).11 · Cited by 1 · see citing works
Chung, M., Lee, S.-J., Shin, J.-H., et al. (2003) · Preventive Nutrition and Food Science · doi:10.3746/jfn.2003.8.1.019
Wishnok, J. S. (2000) · Wiley eBooks · doi:10.1002/0471238961.1409201823091908.a01
Rajashree, P., Ramadoss, R., & Krishnan, R. (2024) · Oral Oncology Reports · doi:10.1016/j.oor.2024.100366
Sirvins, C. (2024) · doi:10.70675/578552b1z332ez4b45za97dz5a97925cb761
- Authors
- Helser, M. A., Hotchkiss, J. H., & Roe, D. A.
- Affiliations
- Cornell University (US)
- ORCID
- Roe, D.A.
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 1992
- Volume
- 13
- Issue
- 12
- Pages
- 2277-2280
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2046250076
- Cited by
- 52
- References
- 0
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2021: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 1 · 2012: 1
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Agriculture
- Topics
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Agricultural and Biological Sciences › Food Science › Food and Agricultural Sciences
- Keywords
- fruit and vegetable juices, N-nitrosoproline, endogenous nitrosation, proline, vitamin C, tomato juice, pineapple juice, strawberry juice, carrot juice, celery juice, nitrate, urinary excretion
- MeSH terms
- Adult, Beverages, Diet, Fruit, Humans, Male, Nitrosamines, Nitroso Compounds, Thiazoles, Vegetables, Thiazolidines
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
