The DOI matches its Crossref record.
Nutrition Intervention Trials in Linxian, China: Supplementation With Specific Vitamin/Mineral Combinations, Cancer Incidence, and Disease-Specific Mortality in the General Population
Abstract
BACKGROUND: Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers, including cancers of the esophagus and stomach. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian County, China, have one of the world's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients. PURPOSE: We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian. METHODS: Individuals of ages 40-69 were recruited in 1985 from four Linxian communes. Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period. The subjects were randomly assigned to intervention groups according to a one-half replicate of a 2(4) factorial experimental design. This design enabled testing for the effects of four combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta carotene, vitamin E, and selenium. Doses ranged from one to two times U.S. Recommended Daily Allowances. RESULTS: A total of 2127 deaths occurred among trial participants during the intervention period. Cancer was the leading cause of death, with 32% of all deaths due to esophageal or stomach cancer, followed by cerebrovascular disease (25%). Significantly (P = .03) lower total mortality (relative risk [RR] = 0.91; 95% confidence interval [CI] = 0.84-0.99) occurred among those receiving supplementation with beta carotene, vitamin E, and selenium. The reduction was mainly due to lower cancer rates (RR = 0.87; 95% CI = 0.75-1.00), especially stomach cancer (RR = 0.79; 95% CI = 0.64-0.99), with the reduced risk beginning to arise about 1-2 years after the start of supplementation with these vitamins and minerals. No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc, riboflavin and niacin, or vitamin C and molybdenum. Patterns of cancer incidence, on the basis of 1298 cases, generally resembled those for cancer mortality. CONCLUSIONS: The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population. IMPLICATIONS: The results on their own are not definitive, but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Free radicals, metals and antioxidants in oxidative stress-induced cancer
Valko, M., Rhodes, C. J., Moncol, J., Izakovic, M., & Mazur, M. (2006) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2005.12.009 · Cited by 6,680
(1994) · New England Journal of Medicine · doi:10.1056/nejm199404143301501 · Cited by 4,737
Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease
Omenn, G. S., Goodman, G. E., Thornquist, M. D., Balmes, J., Cullen, M. R., Glass, A., Keogh, J. P., Meyskens, F. L., Valanis, B., Williams, J. H., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199605023341802 · Cited by 3,638
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579
Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality
Miller, E. R., Pastor-Barriuso, R., Dalal, D., Riemersma, R. A., Appel, L. J., & Guallar, E. (2005) · Annals of Internal Medicine · doi:10.7326/0003-4819-142-1-200501040-00110 · Cited by 2,577
Hennekens, C. H., Buring, J. E., Manson, J. E., Stampfer, M., Rosner, B., Cook, N. R., Belanger, C., LaMotte, F., Gaziano, J. M., Ridker, P. M., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199605023341801 · Cited by 2,397
Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2007) · JAMA · doi:10.1001/jama.297.8.842 · Cited by 2,275
Cancer burden in the year 2000. The global picture
Parkin, D. M., Bray, F. I., & Devesa, S. S. (2001) · European Journal of Cancer · doi:10.1016/s0959-8049(01)00267-2 · Cited by 2,169
Vitamin E Supplementation and Cardiovascular Events in High-Risk Patients
(2000) · New England Journal of Medicine · doi:10.1056/nejm200001203420302 · Cited by 1,957
Antioxidants in health and disease
Young, I. S., & Woodside, J. V. (2001) · Journal of Clinical Pathology · doi:10.1136/jcp.54.3.176 · Cited by 1,949
Kushi, L. H., Byers, T., Doyle, C., Bandera, E. V., McCullough, M., Gansler, T., Andrews, K. S., Thun, M. J., & The American Cancer Society 2006 Nutrition and Physical Activity Guidelines Advisory Committee (2006) · CA A Cancer Journal for Clinicians · doi:10.3322/canjclin.56.5.254 · Cited by 1,901
Free radicals, oxidative stress, and antioxidants in human health and disease
Aruoma, O. I. (1998) · Journal of the American Oil Chemists' Society · doi:10.1007/s11746-998-0032-9 · Cited by 1,682
Selenium in human health and disease
Fairweather-Tait, S. J., Bao, Y., Broadley, M. R., Collings, R., Ford, D., Hesketh, J. E., & Hurst, R. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3275 · Cited by 1,330
Health-promoting components of fruits and vegetables in the diet.
Liu, R. H. (2013) · Advances in Nutrition · doi:10.3945/an.112.003517 · Cited by 1,310
Franz, M. J., Bantle, J. P., Beebe, C. A., Brunzell, J. D., Chiasson, J.-L., Garg, A., Holzmeister, L. A., Hoogwerf, B., Mayer-Davis, E., Mooradian, A. D., et al. (2002) · Diabetes Care · doi:10.2337/diacare.25.1.148 · Cited by 1,165
Lee, I.-M., Cook, N. R., Gaziano, J. M., Gordon, D., Ridker, P. M., Manson, J. E., Hennekens, C. H., & Buring, J. E. (2005) · JAMA · doi:10.1001/jama.294.1.56 · Cited by 1,137
Selenium in global food systems
Combs, G. F. (2001) · British Journal of Nutrition · doi:10.1079/bjn2000280 · Cited by 1,129
Targeting Free Radicals in Oxidative Stress-Related Human Diseases
Poprac, P., Jomova, K., Simunkova, M., Kollar, V., Rhodes, C. J., & Valko, M. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.04.005 · Cited by 1,107
Bouayed, J., & Bohn, T. (2010) · Oxidative Medicine and Cellular Longevity · doi:10.4161/oxim.3.4.12858 · Cited by 1,095
Vivekananthan, D. P., Penn, M. S., Sapp, S. K., Hsu, A., & Topol, E. J. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13637-9 · Cited by 1,083
Carr, A. C., & Frei, B. (1999) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.6.1086 · Cited by 940
Mirvish, S. S. (1995) · Cancer Letters · doi:10.1016/0304-3835(95)03786-v · Cited by 916
Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007176.pub2 · Cited by 924
Reich, H. J., & Hondal, R. J. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.6b00031 · Cited by 923
Sesso, H. D. (2008) · JAMA · doi:10.1001/jama.2008.600 · Cited by 913
Antioxidants Accelerate Lung Cancer Progression in Mice
Sayin, V. I., Ibrahim, M. X., Larsson, E., Nilsson, J. A., Lindahl, P., & Bergo, M. O. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007653 · Cited by 867
Health effects of vegetables and fruit: assessing mechanisms of action in human experimental studies
Lampe, J. W. (1999) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/70.3.475s · Cited by 786
Selenium for preventing cancer
Vinceti, M., Filippini, T., Del Giovane, C., Dennert, G., Zwahlen, M., Brinkman, M., Zeegers, M. P., Horneber, M., D'Amico, R., & Crespi, C. M. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005195.pub4 · Cited by 649
Antioxidant Therapy in Acute Central Nervous System Injury: Current State
Gilgun-Sherki, Y., Rosenbaum, Z., Melamed, E., & Offen, D. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.2.271 · Cited by 568
Criteria and recommendations for vitamin C intake
Levine, M. (1999) · JAMA · doi:10.1001/jama.281.15.1415 · Cited by 559
Commentary: Vitamin C: Antioxidant or Pro-Oxidant In Vivo?
Halliwell, B. (1996) · Free Radical Research · doi:10.3109/10715769609149066 · Cited by 531
New developments and novel therapeutic perspectives for vitamin C
Li, Y., & Schellhorn, H. E. (2007) · The Journal of Nutrition · doi:10.1093/jn/137.10.2171 · Cited by 508
Retinoic acid receptors: From molecular mechanisms to cancer therapy
di Masi, A., Leboffe, L., De Marinis, E., Pagano, F., Cicconi, L., Rochette-Egly, C., Lo-Coco, F., Ascenzi, P., & Nervi, C. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.12.003 · Cited by 403
Albanes, D., Heinonen, O., Huttunen, J., Taylor, P., Virtamo, J., Edwards, B., Haapakoski, J., Rautalahti, M., Hartman, A., & Palmgren, J. (1995) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/62.6.1427s · Cited by 379
Self-citationByers, T., Nestle, M., McTiernan, A., Doyle, C., Currie-Williams, A., Gansler, T., & Thun, M. (2002) · CA: A Cancer Journal for Clinicians · doi:10.3322/canjclin.52.2.92 · Cited by 336
Marine Carotenoids: Biological Functions and Commercial Applications
Vílchez, C., Forján, E., Cuaresma, M., Bédmar, F., Garbayo, I., & Vega, J. M. (2011) · Marine Drugs · doi:10.3390/md9030319 · Cited by 328
Antioxidant Supplementation during Exercise Training: Beneficial or Detrimental?
Peternelj, T.-T., & Coombes, J. S. (2011) · Sports Medicine · doi:10.2165/11594400-000000000-00000 · Cited by 314
Meydani, M. (1995) · The Lancet · doi:10.1016/s0140-6736(95)90172-8 · Cited by 310
Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial
Lin, J., Cook, N. R., Albert, C., Zaharris, E., Gaziano, J. M., Van Denburgh, M., Buring, J. E., & Manson, J. E. (2009) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djn438 · Cited by 309
Antioxidants: Its medicinal and pharmacological applications
(2010) · African Journal of Pure and Applied Chemistry · doi:10.5897/ajpac.9000020 · Cited by 284
Druesne‐Pecollo, N., Latino‐Martel, P., Norat, T., Barrandon, E., Bertrais, S., Galan, P., & Hercberg, S. (2010) · International Journal of Cancer · doi:10.1002/ijc.25008 · Cited by 283
Huang, H.-Y., Caballero, B., Chang, S., Alberg, A. J., Semba, R. D., Schneyer, C. R., Wilson, R. F., Cheng, T.-Y., Vassy, J., Prokopowicz, G., et al. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-145-5-200609050-00135 · Cited by 243
Heinrich, U., Wiebusch, M., Tronnier, H., Gärtner, C., Eichler, O., Sies, H., & Stahl, W. (2003) · The Journal of Nutrition · doi:10.1093/jn/133.1.98 · Cited by 246
Dietary vitamin C in human health
Granger, M., & Eck, P. (2018) · Advances in food and nutrition research · doi:10.1016/bs.afnr.2017.11.006 · Cited by 217
Vitamin E and All-Cause Mortality: A Meta-Analysis
L. Abner, E., A. Schmitt, F., S. Mendiondo, M., L. Marcum, J., & J. Kryscio, R. (2011) · Current Aging Sciencee · doi:10.2174/1874609811104020158 · Cited by 209
Sesso, H. D., Christen, W. G., Bubes, V., Smith, J. P., MacFadyen, J., Schvartz, M., Manson, J. E., Glynn, R. J., Buring, J. E., & Gaziano, J. M. (2012) · JAMA · doi:10.1001/jama.2012.14805 · Cited by 208
Bjelakovic, G., Nikolova, D., & Gluud, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074558 · Cited by 183
Schwingshackl, L., Boeing, H., Stelmach-Mardas, M., Gottschald, M., Dietrich, S., Hoffmann, G., & Chaimani, A. (2017) · Advances in Nutrition · doi:10.3945/an.116.013516 · Cited by 165
Determination of optimal vitamin C requirements in humans
Levine, M., Dhariwal, K., Welch, R., Wang, Y., & Park, J. (1995) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/62.6.1347s · Cited by 149
The health effects of vitamin C supplementation: A review
Bendich, A., & Langseth, L. (1995) · Journal of the American College of Nutrition · doi:10.1080/07315724.1995.10718484 · Cited by 150
The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study in Finland
Blumberg, J. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1994.tb01430.x · Cited by 114
EURRECA—Estimating Selenium Requirements for Deriving Dietary Reference Values
Hurst, R., Collings, R., Harvey, L. J., King, M., Hooper, L., Bouwman, J., Gurinovic, M., & Fairweather-Tait, S. J. (2013) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2012.742861 · Cited by 110
Macpherson, H., Pipingas, A., & Pase, M. P. (2013) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.049304 · Cited by 107
A critical assessment of some biomarker approaches linked with dietary intake
Crews, H., Alink, G., Andersen, R., Braesco, V., Holst, B., Maiani, G., Ovesen, L., Scotter, M., Solfrizzo, M., van den Berg, R., et al. (2001) · British Journal Of Nutrition · doi:10.1079/bjn2001337 · Cited by 99
Selenium accumulation in plant foods
Finley, J. W. (2005) · Nutrition Reviews · doi:10.1111/j.1753-4887.2005.tb00137.x · Cited by 104
Brassica Foods as a Dietary Source of Vitamin C: A Review
Domínguez-Perles, R., Mena, P., García-Viguera, C., & Moreno, D. A. (2014) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2011.626873 · Cited by 92
Mortensen, A., & Lykkesfeldt, J. (2014) · Nitric Oxide · doi:10.1016/j.niox.2013.12.001 · Cited by 80
Sesso, H. D., Rist, P. M., Aragaki, A. K., Rautiainen, S., Johnson, L. G., Friedenberg, G., Copeland, T., Clar, A., Mora, S., Moorthy, M. V., et al. (2022) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqac056 · Cited by 51
Reduction of cancer mortality and incidence by selenium supplementation
Combs, G. F., Clark, L. C., & Turnbull, B. W. (1997) · Medizinische Klinik · doi:10.1007/bf03041964 · Cited by 49
Metadata
- Authors
- Blot, W. J., Li, J.-Y., Taylor, P. R., Guo, W., Dawsey, S., Wang, G.-Q., Yang, C. S., Zheng, S.-F., Gail, M., Li, G.-Y., Yu, Y., Liu, B.-Q., Tangrea, J., Sun, Y.-H., Liu, F., Fraumeni, J. F., Zhang, Y.-H., & Li, B.
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 1993-09-15
- Volume
- 85
- Issue
- 18
- Pages
- 1483-1491
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2161427454
- Cited by
- 1,760
- References
- 0
- FWCI
- 99.90
- Type
- journal article
- Language
- en
- Open access
- closed
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.