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An inhibitor persistently decreased enteric methane emission from dairy cows with no negative effect on milk production
Open accessAbstract
A quarter of all anthropogenic methane emissions in the United States are from enteric fermentation, primarily from ruminant livestock. This study was undertaken to test the effect of a methane inhibitor, 3-nitrooxypropanol (3NOP), on enteric methane emission in lactating Holstein cows. An experiment was conducted using 48 cows in a randomized block design with a 2-wk covariate period and a 12-wk data collection period. Feed intake, milk production, and fiber digestibility were not affected by the inhibitor. Milk protein and lactose yields were increased by 3NOP. Rumen methane emission was linearly decreased by 3NOP, averaging about 30% lower than the control. Methane emission per unit of feed dry matter intake or per unit of energy-corrected milk were also about 30% less for the 3NOP-treated cows. On average, the body weight gain of 3NOP-treated cows was 80% greater than control cows during the 12-wk experiment. The experiment demonstrated that the methane inhibitor 3NOP, applied at 40 to 80 mg/kg feed dry matter, decreased methane emissions from high-producing dairy cows by 30% and increased body weight gain without negatively affecting feed intake or milk production and composition. The inhibitory effect persisted over 12 wk of treatment, thus offering an effective methane mitigation practice for the livestock industries.
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“3-nitrooxypropanol is the latest developed and promising inhibitor for methanogenesis,127 which has been shown to reduce methane emissions in ruminant animals by up to 40%.128,129”
From Technologies and perspectives for achieving carbon neutrality (2021) · cites this paper as [128]
In the citing paper
“3-nitrooxypropanol (3-NOP) has been shown to reduce methane emissions by up to 30% (Hristov et al., 2015; Jayanegara et al., 2018).”
From Addressing global ruminant agricultural challenges through understanding the rumen microbiome: past, present, and future (2018) · cites this paper as Hristov et al., 2015
In the citing paper
“This enzyme catalyzes the last step of methane-forming reactions (Duin et al., 2016) and its inhibition can result in a reduction in rumen methanogenesis (up to 30%) without negative effects to the animal (Hristov et al., 2015).”
From Addressing global ruminant agricultural challenges through understanding the rumen microbiome: past, present, and future (2018) · cites this paper as Hristov et al., 2015
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“…vaccination, nutritional supplements or animal selection; the effectiveness of such approaches and their economic benefits are the subject of a large body of work (Martin et al., 2008; Boadi et al., 2004; Smith et al., 2008; Montes et al., 2013; Nisbet et al., 2020; Hristov et al., 2015).”
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BackgroundBiomethane: The energy storage, platform chemical and greenhouse gas mitigation target
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BackgroundDesigning synbiotics for improved human health
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“Inhibition of methanogenesis shifts respiration to acetogenesis, and actually promotes energy harvest by cows while decreasing the environmental burden of methane production (Hristov et al., 2015).”
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“Ruminant production systems are a significant source of greenhouse gas (GHG) emissions worldwide, with enteric methane accounting for approximately 10–12% of global methane emissions [1,2].”
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“In addition, there is potential for resistance to develop after long-term exposure to compounds, although the results from two studies with 3NOP are encouraging (Hristov et al. 2015; Romero-Perez et al. 2015).”
ResultAlmeida, A. K., Cowley, F. C., McMeniman, J. P., Karagiannis, A., Walker, N. D., Tamassia, L. F. M., McGrath, J. J., & Hegarty, R. S. (2023) · Journal of Animal Science · doi:10.1093/jas/skad237 · Cited by 31
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Methanotrophy: A Biological Method to Mitigate Global Methane Emission
Rani, A., Pundir, A., Verma, M., Joshi, S., Verma, G., Andjelković, S., Babić, S., Milenković, J., & Mitra, D. (2024) · Microbiology Research · doi:10.3390/microbiolres15020042 · Cited by 31
Meo-Filho, P., Ramirez-Agudelo, J. F., & Kebreab, E. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2410863121 · Cited by 31
“Various authors ( 26 , 34 ), have provided insights into the mode of action of halogenated compounds like bromoform.”
InfluentialMilk metabolome relates enteric methane emission to milk synthesis and energy metabolism pathways
Fernandes, E. C. A., van Gastelen, S., Dijkstra, J., Hettinga, K. A., & Vervoort, J. J. M. (2016) · Journal of Dairy Science · doi:10.3168/jds.2015-10248 · Cited by 31
Environmental Sustainability of Livestock Production
Rotz, A. C. (2020) · Meat and Muscle Biology · doi:10.22175/mmb.11103 · Cited by 33
Alemu, A. W., Shreck, A. L., Booker, C. W., McGinn, S. M., Pekrul, L. K. D., Kindermann, M., & Beauchemin, K. A. (2020) · Journal of Animal Science · doi:10.1093/jas/skaa394 · Cited by 31
Ramin, M., Fant, P., & Huhtanen, P. J. (2021) · Journal of Dairy Science · doi:10.3168/jds.2020-19644 · Cited by 31
“Indigestible NDF concentration was determined for feed and fecal samples as described by Huhtanen et al. (1994). A sample size of 2 g was weighed into polyester bags of 11.5-μm pore size and incubated for 288 h in triplicates in the rumen of 3 cannulated cows fed a grass silage-based diet (60:40 forage-to-concentrate…”
BackgroundMethodInfluentialSource Partitioning of Methane Emissions and its Seasonality in the U.S. Midwest
Chen, Z., Griffis, T. J., Baker, J. M., Millet, D. B., Wood, J. D., Dlugokencky, E. J., Andrews, A. E., Sweeney, C., Hu, C., & Kolka, R. K. (2018) · Journal of Geophysical Research Biogeosciences · doi:10.1002/2017jg004356 · Cited by 31
“Hristov et al. (2015) showed that enteric emissions varied from 400 to 500 g CH4 d 1 and 290 to 390 g CH4 d 1 over a 12 week period without/with the use of an inhibitor (3NOP), respectively.”
BackgroundShinkai, T., Takizawa, S., Fujimori, M., & Mitsumori, M. (2023) · Animal Bioscience · doi:10.5713/ab.23.0301 · Cited by 40
“An increase in body weight was previously reported following 3-NOP treatment in dairy cows [36].”
BackgroundHernández, A., KHOLIF, A. E., Elghandour, M. M. M. Y., Camacho, L. M., Cipriano, M., Salem, A. Z. M., Cruz, H., & Ugbogu, E. A. (2017) · Journal of Cleaner Production · doi:10.1016/j.jclepro.2017.01.070 · Cited by 30
“Methane is the major GHG emitted from enteric fermentation through the typical digestive process of ruminants (Hristov et al., 2015).”
BackgroundNitrocompounds as potential methanogenic inhibitors in ruminant animals: A review
Zhang, Z., Cao, Z., Wang, Y.-L., Wang, Y., Yang, H., & Li, S. (2017) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2017.12.010 · Cited by 31
Methanogenesis in animals with foregut and hindgut fermentation: a review
de la Fuente, G., Yáñez-Ruíz, D. R., Seradj, A. R., Balcells, J., & Belanche, A. (2019) · Animal Production Science · doi:10.1071/an17701 · Cited by 33
Li, H., Zhang, X., Deng, F., Han, X., Xiao, C., Han, S., & Wang, Z. (2019) · Trees · doi:10.1007/s00468-019-01914-6 · Cited by 30
3-NOP: Mutagenicity and genotoxicity assessment
Thiel, A., Schoenmakers, A., Verbaan, I. A. J., Chenal, E., Etheve, S., & Beilstein, P. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.11.010 · Cited by 30
Costigan, H., Shalloo, L., Egan, M., Kennedy, M., Dwan, C., Walsh, S., Hennessy, D., Walker, N. D., Zihlmann, R., & Lahart, B. (2024) · Journal of Dairy Science · doi:10.3168/jds.2024-24772 · Cited by 29
Angellotti, M., Lindberg, M., Ramin, M., Krizsan, S. J., & Danielsson, R. (2025) · Journal of Dairy Science · doi:10.3168/jds.2024-25258 · Cited by 40
“It has been established that supplementation of dairy cow diets with halogenated compounds or other methanogen-inhibiting compounds, such as 3-nitroxypropanol, leads to an increase in metabolic H 2 concentration in the rumen (Hristov et al., 2015; Roque et al., 2019; Stefenoni et al., 2021).”
Barnett, M. C., & Hegarty, R. S. (2016) · Animal Production Science · doi:10.1071/an15339 · Cited by 29
Energy and Economic Balance between Manure Stored and Used as a Substrate for Biogas Production
Mazurkiewicz, J. (2022) · Energies · doi:10.3390/en15020413 · Cited by 28
New temperate seaweed targets for mitigation of ruminant methane emissions: an in vitro assessment
Mihaila, A. A., Glasson, C. R. K., Lawton, R. J., Muetzel, S., Molano, G., & Magnusson, M. E. (2022) · Applied Phycology · doi:10.1080/26388081.2022.2059700 · Cited by 31
“…with previous in vitro and in vivo studies with Asparagopsis (Kinley et al., 2020; Machado et al., 2018; Roque et al., 2021; Stefenoni et al., 2021) and other antimethanogenic products (Hristov et al., 2015; Machado et al., 2016a; Martinez-Fernandez et al., 2016, 2017; Mitsumori et al., 2012).”
BackgroundAlemu, A. W., Gruninger, R. J., Zhang, X., O’Hara, E., Kindermann, M., & Beauchemin, K. A. (2023) · Journal of Animal Science · doi:10.1093/jas/skad001 · Cited by 29
Zhang, Q., Wu, S., Zou, X., Ruan, S., KHOLIF, A. E., Hu, L., Chen, X., & Zhou, W. J. (2022) · Journal of Cleaner Production · doi:10.1016/j.jclepro.2022.133338 · Cited by 27
Joshi, K., Shabani, E., Kabir, S. M. F., Zhou, H., McClements, D. J., & Park, J. H. (2023) · Foods · doi:10.3390/foods12173161 · Cited by 27
“Therefore, there is considerable interest in reducing the total amount of these foods, especially meat, in the human diet to improve its sustainability and reduce its adverse environmental impacts [4,5].”
BackgroundMa, X., Räisänen, S. E., Garcia-Ascolani, M. E., Bobkov, M., He, T., Islam, Z., Li, Y., Peng, R., Reichenbach, M., Serviento, A. M., et al. (2024) · Journal of Dairy Science · doi:10.3168/jds.2023-24460 · Cited by 28
Moate, P. J., Jacobs, J. L., Hannah, M. C., Morris, G. L., Beauchemin, K. A., Alvarez-Hess, P. S., Eckard, R., Liu, Z., Rochfort, S. J., Wales, W. J., et al. (2018) · Journal of Dairy Science · doi:10.3168/jds.2017-14334 · Cited by 28
Low-carbon cows: From microbial metabolism to the symbiotic planet
Folkers, A., & Opitz, S. (2022) · Social Studies of Science · doi:10.1177/03063127221077987 · Cited by 27
“In fact, studies suggest that cows may even get fatter and produce more milk when given the inhibitor (Hristov et al., 2015) because they can use some of the valuable energy they otherwise just burp out.”
BackgroundInfluentialLiu, Z., Wang, K., Nan, X., Yang, L., Wang, Y., Zhang, F., Cai, M., Zhao, Y., & Xiong, B. (2022) · Journal of Dairy Science · doi:10.3168/jds.2022-22207 · Cited by 27
“This result was similar to the previous studies that supplementation of 3-NOP to cows did not affect DMI (Haisan et al., 2014; Reynolds et al., 2014; Hristov et al., 2015; Lopes et al., 2016; Haisan et al., 2017).”
BackgroundResultInfluentialEikanger, K. S., Kjær, S. T., Dörsch, P., Iwaasa, A. D., Alemu, A. W., Schei, I., Pope, P. B., Hagen, L. H., & Kidane, A. (2024) · Livestock Science · doi:10.1016/j.livsci.2024.105495 · Cited by 26
Li, Z., Lei, X., Chen, X., Yin, Q., Shen, J., & Yao, J. (2021) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-021-00645-4 · Cited by 25
“The supply dose of FUM was based on the data published previously [17], while that of NPD was based on a previous 3-NOP study [6] and a mice study [19].”
BackgroundMethodJin, W., Meng, Z., Wang, J., Cheng, Y., & Zhu, W. (2017) · Current Microbiology · doi:10.1007/s00284-017-1261-7 · Cited by 24
Cristobal-Carballo, O., McCoard, S. A., Cookson, A. L., Ganesh, S., Lowe, K., Laven, R. A., & Muetzel, S. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.710914 · Cited by 24
Weimar, M. R., Cheung, J., Dey, D., McSweeney, C. S., Morrison, M., Kobayashi, Y., Whitman, W. B., Carbone, V., Schofield, L. R., Ronimus, R. S., et al. (2017) · Applied and Environmental Microbiology · doi:10.1128/aem.00396-17 · Cited by 26
Martins, L. F., Maigaard, M., Johansen, M., Lund, P., Ma, X., Niu, M., & Hristov, A. N. (2025) · Journal of Dairy Science · doi:10.3168/jds.2024-25653 · Cited by 23
Malyugina, S., Holik, S., & Horký, P. (2025) · Frontiers in Animal Science · doi:10.3389/fanim.2025.1610376 · Cited by 37
Sarteshnizi, F. R., Seıfdavatı, J., Abdi‐Benemar, H., Salem, A. Z. M., Sharifi, R. S., & Mlambo, V. (2018) · Journal of Cleaner Production · doi:10.1016/j.jclepro.2018.05.268 · Cited by 23
Metadata
- Authors
- Hristov, A. N., Oh, J., Giallongo, F., Frederick, T. W., Harper, M. T., Weeks, H. L., Branco, A. F., Moate, P. J., Deighton, M. H., Williams, S. R. O., Kindermann, M., & Duval, S.
- Affiliations
- Pennsylvania State University (US)
- Departamento de Zootecnia, Universidade Estadual de Maringá, PR 87020-900, Brazil;
- Department of Economic Development Jobs Transport and Resources (AU)
- Animal Nutrition and Health, DSM Nutritional Products, Basel CH-4002, Switzerland;
- Research Centre for Animal Nutrition and Health, DSM Nutritional Products France, Saint Louis Cedex 68305, France
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-07-30
- Volume
- 112
- Issue
- 34
- Pages
- 10663-10668
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4553761
- OpenAlex
- W2145651012
- Cited by
- 496
- References
- 59
- Citations by year
- 2026: 54 · 2025: 49 · 2024: 58 · 2023: 48 · 2022: 48 · 2021: 53 · 2020: 40 · 2019: 42 · 2018: 35 · 2017: 31 · 2016: 34 · 2015: 4
- FWCI
- 74.95
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-08-12)
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Ruminant Nutrition and Digestive Physiology
- Physical Sciences › Environmental Science › Ecology › Agriculture Sustainability and Environmental Impact
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- enteric methane, 3-nitrooxypropanol, methane inhibitors, dairy cattle, Holstein cows, methane mitigation, milk production, milk protein, lactose yield, weight gain, ruminant methane emissions, feed intake, fiber digestibility
- MeSH terms
- Medicago sativa, Animals, Animal Feed, Archaea, Energy Intake, Carbon Dioxide, Cattle, Zea mays, Female, Fermentation, Gases, Hydrogen, Lactation, Methane, Milk, Rumen, Weight Gain, Greenhouse Effect, Dietary Supplements, Propanols
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