A Method to Estimate the Dietary α-Linolenic Acid Requirement Using Nonesterified DHA and Arachidonic Acid Oxylipins and Fatty Acids
The dietary requirement for α-linolenic acid (ALA) remains unclear, as evidenced by the absence of a Recommended Dietary Allowance (RDA) for this essential fatty acid (FA). In previous studies, we observed that the amount of dietary ALA required to maximize nonesterified (NE) DHA oxylipins appears t...
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| Veröffentlicht in: | The Journal of nutrition 2024-12, Vol.154 (12), p.3681-3692 |
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| description | The dietary requirement for α-linolenic acid (ALA) remains unclear, as evidenced by the absence of a Recommended Dietary Allowance (RDA) for this essential fatty acid (FA). In previous studies, we observed that the amount of dietary ALA required to maximize nonesterified (NE) DHA oxylipins appears to be higher than the amount required to maximize tissue esterified DHA, which have classically been used to estimate the ALA requirement. Further, we observed that dietary ALA reduces esterified arachidonic acid (ARA) and its NE oxylipins.
Since NE oxylipins and FA mediate the biological activities of FA, we examined whether these DHA and ARA pools could be used to determine the dietary ALA requirement.
Nine groups of 4-wk-old male Sprague-Dawley rats (n = 5) and 10 groups of male and female CD1 mice (n = 6) were provided 0.1–2.5 g ALA and 2 g of linoleic acid per 100 g of AIN93G-based diets. NE DHA and ARA and their oxylipins in serum, liver, kidney, and brain homogenates underwent solid phase extraction and were quantified by HPLC-MS/MS. Breakpoint analysis of transitions from increase to plateau was conducted using piecewise regression.
In response to increasing dietary ALA, NE DHA oxylipins, and DHA in serum, liver, and kidney (but not the brain) initially increased rapidly and then reached a plateau whereas ARA oxylipins and ARA tended to decrease before reaching a plateau. Thus, breakpoints were calculated for the ratios of DHA/ARA and hydroxy-DHA/hydroxy-ARA (DHAOH/ARAOH), which consisted of oxylipins synthesized via pathways common to both FA. In serum, liver, and kidney, the highest estimated breakpoint indicated an ALA requirement of ∼0.7 g/100 g diet (1.7% energy), approximately twice that of previous estimations.
This study supports the use of NE DHAOH/ARAOH or DHA/ARA as biochemical indicators of the ALA requirement. Applying this method in rats and mice indicates that the requirement is higher than previously estimated using esterified DHA alone. |
| doi_str_mv | 10.1016/j.tjnut.2024.10.023 |
| format | Article |
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Since NE oxylipins and FA mediate the biological activities of FA, we examined whether these DHA and ARA pools could be used to determine the dietary ALA requirement.
Nine groups of 4-wk-old male Sprague-Dawley rats (n = 5) and 10 groups of male and female CD1 mice (n = 6) were provided 0.1–2.5 g ALA and 2 g of linoleic acid per 100 g of AIN93G-based diets. NE DHA and ARA and their oxylipins in serum, liver, kidney, and brain homogenates underwent solid phase extraction and were quantified by HPLC-MS/MS. Breakpoint analysis of transitions from increase to plateau was conducted using piecewise regression.
In response to increasing dietary ALA, NE DHA oxylipins, and DHA in serum, liver, and kidney (but not the brain) initially increased rapidly and then reached a plateau whereas ARA oxylipins and ARA tended to decrease before reaching a plateau. Thus, breakpoints were calculated for the ratios of DHA/ARA and hydroxy-DHA/hydroxy-ARA (DHAOH/ARAOH), which consisted of oxylipins synthesized via pathways common to both FA. In serum, liver, and kidney, the highest estimated breakpoint indicated an ALA requirement of ∼0.7 g/100 g diet (1.7% energy), approximately twice that of previous estimations.
This study supports the use of NE DHAOH/ARAOH or DHA/ARA as biochemical indicators of the ALA requirement. Applying this method in rats and mice indicates that the requirement is higher than previously estimated using esterified DHA alone.</description><identifier>ISSN: 0022-3166</identifier><identifier>ISSN: 1541-6100</identifier><identifier>EISSN: 1541-6100</identifier><identifier>DOI: 10.1016/j.tjnut.2024.10.023</identifier><identifier>PMID: 39401685</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>alpha-Linolenic Acid - administration & dosage ; Animals ; Arachidonic acid ; Arachidonic Acid - administration & dosage ; Brain ; Breakpoints ; Diet ; Diet - veterinary ; dietary requirement ; Dietary supplements ; docosahexaenoic acid ; Docosahexaenoic Acids - administration & dosage ; Docosahexaenoic Acids - metabolism ; dose–response ; Esterification ; Fatty acids ; Fatty Acids - metabolism ; Female ; Kidneys ; Linoleic acid ; Linolenic acid ; Liquid chromatography ; Liver ; Liver - metabolism ; Male ; Males ; Mice ; Nutrition ; oxylipins ; Oxylipins - metabolism ; Rats ; Rats, Sprague-Dawley ; sex ; Solid phases ; α-linolenic acid</subject><ispartof>The Journal of nutrition, 2024-12, Vol.154 (12), p.3681-3692</ispartof><rights>2024 American Society for Nutrition</rights><rights>Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright American Institute of Nutrition Dec 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c267t-1700d72ea74e9307cc5c21352613bd5a32e516d2aa02532c637827bb1cad23003</cites><orcidid>0000-0001-7226-5700</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39401685$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Manson, Anne</creatorcontrib><creatorcontrib>Sidhu, Karanbir K</creatorcontrib><creatorcontrib>Fedorova, Oleksandra</creatorcontrib><creatorcontrib>La, Huy Hoang Khai</creatorcontrib><creatorcontrib>Magaji, Elizabeth</creatorcontrib><creatorcontrib>Nguyen, Le Kim Long</creatorcontrib><creatorcontrib>Winter, Tanja</creatorcontrib><creatorcontrib>Aukema, Harold M</creatorcontrib><title>A Method to Estimate the Dietary α-Linolenic Acid Requirement Using Nonesterified DHA and Arachidonic Acid Oxylipins and Fatty Acids</title><title>The Journal of nutrition</title><addtitle>J Nutr</addtitle><description>The dietary requirement for α-linolenic acid (ALA) remains unclear, as evidenced by the absence of a Recommended Dietary Allowance (RDA) for this essential fatty acid (FA). In previous studies, we observed that the amount of dietary ALA required to maximize nonesterified (NE) DHA oxylipins appears to be higher than the amount required to maximize tissue esterified DHA, which have classically been used to estimate the ALA requirement. Further, we observed that dietary ALA reduces esterified arachidonic acid (ARA) and its NE oxylipins.
Since NE oxylipins and FA mediate the biological activities of FA, we examined whether these DHA and ARA pools could be used to determine the dietary ALA requirement.
Nine groups of 4-wk-old male Sprague-Dawley rats (n = 5) and 10 groups of male and female CD1 mice (n = 6) were provided 0.1–2.5 g ALA and 2 g of linoleic acid per 100 g of AIN93G-based diets. NE DHA and ARA and their oxylipins in serum, liver, kidney, and brain homogenates underwent solid phase extraction and were quantified by HPLC-MS/MS. Breakpoint analysis of transitions from increase to plateau was conducted using piecewise regression.
In response to increasing dietary ALA, NE DHA oxylipins, and DHA in serum, liver, and kidney (but not the brain) initially increased rapidly and then reached a plateau whereas ARA oxylipins and ARA tended to decrease before reaching a plateau. Thus, breakpoints were calculated for the ratios of DHA/ARA and hydroxy-DHA/hydroxy-ARA (DHAOH/ARAOH), which consisted of oxylipins synthesized via pathways common to both FA. In serum, liver, and kidney, the highest estimated breakpoint indicated an ALA requirement of ∼0.7 g/100 g diet (1.7% energy), approximately twice that of previous estimations.
This study supports the use of NE DHAOH/ARAOH or DHA/ARA as biochemical indicators of the ALA requirement. Applying this method in rats and mice indicates that the requirement is higher than previously estimated using esterified DHA alone.</description><subject>alpha-Linolenic Acid - administration & dosage</subject><subject>Animals</subject><subject>Arachidonic acid</subject><subject>Arachidonic Acid - administration & dosage</subject><subject>Brain</subject><subject>Breakpoints</subject><subject>Diet</subject><subject>Diet - veterinary</subject><subject>dietary requirement</subject><subject>Dietary supplements</subject><subject>docosahexaenoic acid</subject><subject>Docosahexaenoic Acids - administration & dosage</subject><subject>Docosahexaenoic Acids - metabolism</subject><subject>dose–response</subject><subject>Esterification</subject><subject>Fatty acids</subject><subject>Fatty Acids - metabolism</subject><subject>Female</subject><subject>Kidneys</subject><subject>Linoleic acid</subject><subject>Linolenic acid</subject><subject>Liquid chromatography</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Males</subject><subject>Mice</subject><subject>Nutrition</subject><subject>oxylipins</subject><subject>Oxylipins - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>sex</subject><subject>Solid phases</subject><subject>α-linolenic acid</subject><issn>0022-3166</issn><issn>1541-6100</issn><issn>1541-6100</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1uEzEUhS0EomnhCZCQJTZsJlzb45nJgkXUH4oUqITo2nLsG-LRxE5tT0UegAfiRfpMOEnpggUrS_d-5_jqHELeMJgyYM2Hfpp7P-YpB16XyRS4eEYmTNasahjAczIB4LwSrGlOyGlKPQCweta9JCdiVheHTk7Irzn9gnkdLM2BXqbsNjojzWukFw6zjjv68LtaOB8G9M7QuXGWfsO70UXcoM_0Njn_g34NHlPG6FYOLb24nlPtLZ1HbdbOhifhzc_d4LbOp8P6Sue8OyzSK_JipYeErx_fM3J7dfn9_Lpa3Hz6fD5fVIY3ba5YC2BbjrqtcSagNUYazoTkDRNLK7XgKFljudbApeCmEW3H2-WSGW25ABBn5P3RdxvD3VhOVhuXDA6D9hjGpAQrYbVSdE1B3_2D9mGMvlxXKAmdbOVsbyiOlIkhpYgrtY0lwrhTDNS-JdWrQ0tq39J-WFoqqreP3uNyg_ZJ87eWAnw8AljCuHcYVTIOvUFbcjdZ2eD--8Ef0v2jlQ</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Manson, Anne</creator><creator>Sidhu, Karanbir K</creator><creator>Fedorova, Oleksandra</creator><creator>La, Huy Hoang Khai</creator><creator>Magaji, Elizabeth</creator><creator>Nguyen, Le Kim Long</creator><creator>Winter, Tanja</creator><creator>Aukema, Harold M</creator><general>Elsevier Inc</general><general>American Institute of Nutrition</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7226-5700</orcidid></search><sort><creationdate>202412</creationdate><title>A Method to Estimate the Dietary α-Linolenic Acid Requirement Using Nonesterified DHA and Arachidonic Acid Oxylipins and Fatty Acids</title><author>Manson, Anne ; Sidhu, Karanbir K ; Fedorova, Oleksandra ; La, Huy Hoang Khai ; Magaji, Elizabeth ; Nguyen, Le Kim Long ; Winter, Tanja ; Aukema, Harold M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c267t-1700d72ea74e9307cc5c21352613bd5a32e516d2aa02532c637827bb1cad23003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>alpha-Linolenic Acid - administration & dosage</topic><topic>Animals</topic><topic>Arachidonic acid</topic><topic>Arachidonic Acid - administration & dosage</topic><topic>Brain</topic><topic>Breakpoints</topic><topic>Diet</topic><topic>Diet - veterinary</topic><topic>dietary requirement</topic><topic>Dietary supplements</topic><topic>docosahexaenoic acid</topic><topic>Docosahexaenoic Acids - administration & dosage</topic><topic>Docosahexaenoic Acids - metabolism</topic><topic>dose–response</topic><topic>Esterification</topic><topic>Fatty acids</topic><topic>Fatty Acids - metabolism</topic><topic>Female</topic><topic>Kidneys</topic><topic>Linoleic acid</topic><topic>Linolenic acid</topic><topic>Liquid chromatography</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Males</topic><topic>Mice</topic><topic>Nutrition</topic><topic>oxylipins</topic><topic>Oxylipins - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>sex</topic><topic>Solid phases</topic><topic>α-linolenic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Manson, Anne</creatorcontrib><creatorcontrib>Sidhu, Karanbir K</creatorcontrib><creatorcontrib>Fedorova, Oleksandra</creatorcontrib><creatorcontrib>La, Huy Hoang Khai</creatorcontrib><creatorcontrib>Magaji, Elizabeth</creatorcontrib><creatorcontrib>Nguyen, Le Kim Long</creatorcontrib><creatorcontrib>Winter, Tanja</creatorcontrib><creatorcontrib>Aukema, Harold M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Manson, Anne</au><au>Sidhu, Karanbir K</au><au>Fedorova, Oleksandra</au><au>La, Huy Hoang Khai</au><au>Magaji, Elizabeth</au><au>Nguyen, Le Kim Long</au><au>Winter, Tanja</au><au>Aukema, Harold M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Method to Estimate the Dietary α-Linolenic Acid Requirement Using Nonesterified DHA and Arachidonic Acid Oxylipins and Fatty Acids</atitle><jtitle>The Journal of nutrition</jtitle><addtitle>J Nutr</addtitle><date>2024-12</date><risdate>2024</risdate><volume>154</volume><issue>12</issue><spage>3681</spage><epage>3692</epage><pages>3681-3692</pages><issn>0022-3166</issn><issn>1541-6100</issn><eissn>1541-6100</eissn><abstract>The dietary requirement for α-linolenic acid (ALA) remains unclear, as evidenced by the absence of a Recommended Dietary Allowance (RDA) for this essential fatty acid (FA). In previous studies, we observed that the amount of dietary ALA required to maximize nonesterified (NE) DHA oxylipins appears to be higher than the amount required to maximize tissue esterified DHA, which have classically been used to estimate the ALA requirement. Further, we observed that dietary ALA reduces esterified arachidonic acid (ARA) and its NE oxylipins.
Since NE oxylipins and FA mediate the biological activities of FA, we examined whether these DHA and ARA pools could be used to determine the dietary ALA requirement.
Nine groups of 4-wk-old male Sprague-Dawley rats (n = 5) and 10 groups of male and female CD1 mice (n = 6) were provided 0.1–2.5 g ALA and 2 g of linoleic acid per 100 g of AIN93G-based diets. NE DHA and ARA and their oxylipins in serum, liver, kidney, and brain homogenates underwent solid phase extraction and were quantified by HPLC-MS/MS. Breakpoint analysis of transitions from increase to plateau was conducted using piecewise regression.
In response to increasing dietary ALA, NE DHA oxylipins, and DHA in serum, liver, and kidney (but not the brain) initially increased rapidly and then reached a plateau whereas ARA oxylipins and ARA tended to decrease before reaching a plateau. Thus, breakpoints were calculated for the ratios of DHA/ARA and hydroxy-DHA/hydroxy-ARA (DHAOH/ARAOH), which consisted of oxylipins synthesized via pathways common to both FA. In serum, liver, and kidney, the highest estimated breakpoint indicated an ALA requirement of ∼0.7 g/100 g diet (1.7% energy), approximately twice that of previous estimations.
This study supports the use of NE DHAOH/ARAOH or DHA/ARA as biochemical indicators of the ALA requirement. Applying this method in rats and mice indicates that the requirement is higher than previously estimated using esterified DHA alone.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39401685</pmid><doi>10.1016/j.tjnut.2024.10.023</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-7226-5700</orcidid></addata></record> |
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| subjects | alpha-Linolenic Acid - administration & dosage Animals Arachidonic acid Arachidonic Acid - administration & dosage Brain Breakpoints Diet Diet - veterinary dietary requirement Dietary supplements docosahexaenoic acid Docosahexaenoic Acids - administration & dosage Docosahexaenoic Acids - metabolism dose–response Esterification Fatty acids Fatty Acids - metabolism Female Kidneys Linoleic acid Linolenic acid Liquid chromatography Liver Liver - metabolism Male Males Mice Nutrition oxylipins Oxylipins - metabolism Rats Rats, Sprague-Dawley sex Solid phases α-linolenic acid |
| title | A Method to Estimate the Dietary α-Linolenic Acid Requirement Using Nonesterified DHA and Arachidonic Acid Oxylipins and Fatty Acids |
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