Key points are not available for this paper at this time.
To estimate in vivo α-linolenic acid (ALA; C18:3n-3) conversion, 29 healthy subjects consumed for 28 days a diet providing 7% of energy from linoleic acid (C18:2n-6) and 0.4% from ALA. On day 19, subjects received a single bolus of 30 mg of uniformly labeled 13CALA and for the next 8 days 10 mg twice daily. Fasting plasma phospholipid concentrations of 12C- and 13C-labeled ALA, eicosapentaenoic acid (EPA; C20:5n-3), docosapentaenoic acid (DPA; C22:5n-3), and docosahexaenoic acid (DHA; C22:6n-3) were determined on days 19, 21, 23, 26, 27, and 28. To estimate hepatic conversion of n-3 fatty acids, a tracer model was developed based on the averaged 13C data of the participants. A similar tracee model was solved using the averaged 12C values, the kinetic parameters derived from the tracer model, and mean ALA consumption. ALA incorporation into plasma phospholipids was estimated by solving both models simultaneously. It was found that nearly 7% of dietary ALA was incorporated into plasma phospholipids. From this pool, 99.8% was converted into EPA and 1% was converted into DPA and subsequently into DHA.The limited incorporation of dietary ALA into the hepatic phospholipid pool contributes to the low hepatic conversion of ALA into EPA. A low conversion of ALA-derived EPA into DPA might be an additional obstacle for DHA synthesis. To estimate in vivo α-linolenic acid (ALA; C18:3n-3) conversion, 29 healthy subjects consumed for 28 days a diet providing 7% of energy from linoleic acid (C18:2n-6) and 0.4% from ALA. On day 19, subjects received a single bolus of 30 mg of uniformly labeled 13CALA and for the next 8 days 10 mg twice daily. Fasting plasma phospholipid concentrations of 12C- and 13C-labeled ALA, eicosapentaenoic acid (EPA; C20:5n-3), docosapentaenoic acid (DPA; C22:5n-3), and docosahexaenoic acid (DHA; C22:6n-3) were determined on days 19, 21, 23, 26, 27, and 28. To estimate hepatic conversion of n-3 fatty acids, a tracer model was developed based on the averaged 13C data of the participants. A similar tracee model was solved using the averaged 12C values, the kinetic parameters derived from the tracer model, and mean ALA consumption. ALA incorporation into plasma phospholipids was estimated by solving both models simultaneously. It was found that nearly 7% of dietary ALA was incorporated into plasma phospholipids. From this pool, 99.8% was converted into EPA and 1% was converted into DPA and subsequently into DHA. The limited incorporation of dietary ALA into the hepatic phospholipid pool contributes to the low hepatic conversion of ALA into EPA. A low conversion of ALA-derived EPA into DPA might be an additional obstacle for DHA synthesis. α-Linolenic acid (ALA; C18:3n-3) is an essential fatty acid of the n-3 family that is present in unhydrogenated canola and soybean oils and in foods prepared with these oils (1Voskuil D.W. Feskens E.J. Katan M.B. Kromhout D. Intake and sources of alpha-linolenic acid in Dutch elderly men.Eur. J. Clin. Nutr. 1996; 50: 784-787Google Scholar, 2Ollis T.E. Meyer B.J. Howe P.R. Australian food sources and intakes of omega-6 and omega-3 polyunsaturated fatty acids.Ann. Nutr. Metab. 1999; 43: 346-355Google Scholar, 3Kris-Etherton P.M. Taylor D.S. Yu-Poth S. Huth P. Moriarty K. Fishell V. Hargrove R.L. Zhao G. Etherton T.D. Polyunsaturated fatty acids in the food chain in the United States.Am. J. Clin. Nutr. 2000; 71: 179-188Google Scholar). Humans are unable to synthesize ALA because they lack the necessary Δ-15 desaturase enzymes (4Innis S.M. Essential fatty acid requirements in human nutrition.Can. J. Physiol. Pharmacol. 1993; 71: 699-706Google Scholar, 5Bezard J. Blond J.P. Bernard A. Clouet P. The metabolism and availability of essential fatty acids in animal and human tissues.Reprod. Nutr. Dev. 1994; 34: 539-568Google Scholar, 6Connor W.E. Alpha-linolenic acid in health and disease.Am. J. Clin. Nutr. 1999; 69: 827-828Google Scholar). Therefore, ALA must be provided in adequate amounts through the diet. After consumption, ALA can be converted in the liver into longer and more unsaturated fatty acids such as eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3). These latter two fatty acids, which are also present in fatty fish, play an essential role in many physiological processes (7Simopoulos A.P. Human requirement for N-3 polyunsaturated fatty acids.Poult. Sci. 2000; 79: 961-970Google Scholar). Whether ALA is a useful source for EPA and DHA synthesis depends on the efficacy of ALA conversion. Several animal and human intervention studies have examined the effects of diets rich in ALA on n-3 fatty acid metabolism and accretion in tissues (8Blank C. Neumann M.A. Makrides M. Gibson R.A. Optimizing DHA levels in piglets by lowering the linoleic acid to alpha-linolenic acid ratio.J. Lipid Res. 2002; 43: 1537-1543Google Scholar, 9Abedin L. Lien E.L. Vingrys A.J. Sinclair A.J. The effects of dietary alpha-linolenic acid compared with docosahexaenoic acid on brain, retina, liver, and heart in the guinea pig.Lipids. 1999; 34: 475-482Google Scholar, 10James M.J. Ursin V.M. Cleland L.G. Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids.Am. J. Clin. Nutr. 2003; 77: 1140-1145Scopus (276) Google Scholar). Although the results indicate that ALA is converted, these studies only allow a qualitative or semiquantitative description of n-3 metabolism. In contrast, the use of stable isotopes offers a means to assess quantitatively the in vivo conversion of ALA (11Brenna J.T. Use of stable isotopes to study fatty acid and lipoprotein metabolism in man.Prostaglandins Leukot. Essent. Fatty Acids. 1997; 57: 467-472Google Scholar). Nevertheless, quantification of the separate conversion reactions remains complex. The few studies that were performed with deuterated or 13C-labeled ALA tracers mostly used area under the curve (AUC) values, which give a global impression of n-3 fatty acid conversion (12Burdge G.C. Jones A.E. Wootton S.A. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men.Br. J. Nutr. 2002; 88: 355-363Google Scholar, 13Burdge G.C. Wootton S.A. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women.Br. J. Nutr. 2002; 88: 411-420Google Scholar, 14Emken E.A. Adlof R.O. Duval S.M. Nelson G.J. Effect of dietary docosahexaenoic acid on desaturation and uptake in vivo of isotope-labeled oleic, linoleic, and linolenic acids by male subjects.Lipids. 1999; 34: 785-791Google Scholar, 15Emken E.A. Adlof R.O. Gulley R.M. Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males.Biochim. Biophys. Acta. 1994; 1213: 277-288Google Scholar). Compartmental modeling, however, provides more accurate of the parameters the n-3 fatty acid The study to to the conversion of ALA in was by of alpha-linolenic acid metabolism in adult Lipid Res. Scholar). In that the conversion of ALA was examined of a single of deuterated ALA, which was compared with ALA In of n-3 fatty acids were in plasma the fatty acid of plasma phospholipids more hepatic n-3 fatty acid metabolism. Therefore, to use to ALA conversion of amounts of uniformly labeled 13CALA for and of ALA and polyunsaturated fatty acids were in plasma phospholipids. healthy and in the male was of the results because of and the The mean of the 29 subjects was use a stable for the study or of and a of The study was by the of and was from tracer study was of a dietary intervention that the effects of polyunsaturated fatty acids on this of the only data from the were which subjects received the diet. the of the and or food for days and was using the Dutch food and was a diet that or energy requirement The Scholar). To this diets were with amounts of energy The of the diet consumed the of of energy and fatty acids, fatty acids, linolenic acid and the of the diet was EPA and DHA intakes were To these subjects received products such as and that were from an The as as the which was of a of and from and were by The on energy the products provided of or of In subjects were dietary the and of other food The use of or was the study was were to energy by compared with the acid of the Fatty fatty fatty fatty α-linolenic in a ALA, α-linolenic was from as fatty acid tracer with an of The of was in and into with a of such that 10 mg of day 19, 10 days the of the a was subjects for and from for received an bolus of 30 mg of the next 8 days subjects consumed 8 and 8 On these was Fasting were days the tracer and 28 was into and for 30 from the of the plasma were in and After the from were in the from plasma were to a of the with as an J. M. A for the and of from animal Scholar). were using an and and into fatty acid M.A. of in and using Lipid Res. Scholar, G. of of in a Lipid Res. Scholar). The were and by means of a a The was used with as the of as A.E. G. essential fatty acid and to the essential fatty acid J. Nutr. Scholar). the and the were The of the and for 10 to in of It for and to and was for 13C of the of ALA, docosapentaenoic acid and DHA were determined on a with a and as the of The was were used to a of the of ALA, and the was for and to for the was for and to for 13C of the were as as and in and of Scholar). 13C 13C The were for the to the 13C-labeled fatty acids through and It was that these additional were the concentrations of the labeled and fatty acids were derived to the C. G. to kinetic data in stable tracer J. Physiol. and is the in of a fatty acid as determined by parameters such as ALA and the 12C and 13C n-3 fatty acid concentrations in the plasma phospholipid pool a of n-3 fatty acid conversion was using by means of the A model was for fatty acid and as the C. A. P. and for tracer and Scholar). The model developed from the mean data was to data using and The in a of the The of a tracer study is to on tracer which can be used to the kinetic of the or tracee C. D. G. in From to Scholar). on the of the tracer is by the into a model from which the and of tracer can be C. A. is to that which is of model of Scholar). a model developed based on the mean tracer data of the 29 participants. were used to the of model a tracee model that incorporated the kinetic parameters derived from the tracer the averaged of the tracee of the 29 and mean dietary ALA The tracer and tracee models were solved to estimate the incorporation of into plasma model for n-3 conversion. and the plasma ALA, and DHA tracee phospholipid the dietary of tracee ALA. The into the and DHA tracee phospholipid are by and The tracer model is in The was from to In with the of ALA into the of the model of a of and that the amounts of 13C-labeled ALA, and in plasma phospholipids. the 13CALA tracer was the the which a into plasma phospholipids as ALA. The ALA tracer is from the or through the conversion as by the and The the of tracer from the plasma phospholipid pool that is of from to The of tracer that is from is n-3 fatty acid concentrations were in plasma phospholipids as by the results were in of and is based on the of the of which was to be the plasma was plasma was was to be of R.A. Scholar). The of the model and that were the model are The of the tracer the The was that was of tracer from the A of 30 was by the of The tracer a which processes the of in the and the of the tracer in the ALA plasma phospholipid In model, the of a of Several models were with a and the model was to the of the the was After the can two is or in the plasma phospholipid The which is the of ALA tracer that is as as the of ALA tracer that is incorporated into ALA plasma phospholipids The for can be or incorporated into and The of of in the plasma phospholipid is as this be determined as an for were were to model was In contrast, in the of the model or in of the tracee Therefore, was to the to the tracer of was by a as in the description of the tracee The tracer present in the plasma phospholipid pool was by a single The of the ALA tracer from is by and the that was and into EPA is by The was as was to solving the The of the and the averaged ALA tracer data is in The of the is in the were on or the of the was as because was in the an and the of the next The of the model that from the plasma ALA phospholipid for ALA, the also a the were because of the to synthesize EPA from ALA, to the on the for ALA, the EPA the curve the of the study an was which was the and of the can be by a conversion of EPA into DPA or by an of labeled EPA from the The latter was by an additional into the EPA from the was estimated by models in which was as a or and was as or to was only was was and was as model was as was and the EPA data the Although from be that of labeled EPA from the pool with the from the DPA as the for the in is that the of EPA to DPA is that of ALA to EPA. the 13C-labeled DPA in plasma derived from through The from DPA was from and was The of the that DPA was by the of the which be for was to The curve of the DPA was also from of ALA and EPA. only was the curve the from the was to that the conversion of EPA into DPA is the conversion of ALA into EPA. the curve of the the two data the this that was into the DPA a was the EPA and DPA The of the was 30 because this in the description of the data through the DPA data with a model the through the DPA data with the tracer The of DHA in the plasma phospholipid was by a single and a single of The was be The of the DHA however, that this model the of DHA the of the study that additional into the DHA was to the Therefore, two other models were model a from ALA to and the other model a from EPA to DHA. and were other were or were only the conversion in the liver from ALA to DHA more physiological the conversion of plasma EPA to the model with in the and for the tracer through the DHA data with a model the through the DHA data with the tracer The the model are in The of that were of the tracer model parameters and derived of in a The from the tracer model were used to and of the tracee the tracee is in a and the are from the tracer model, the that the tracee n-3 fatty acid that can be In the present concentrations of the tracee n-3 fatty acids the tracer as from the results of the can be from the tracee model is to the tracer model and the The with tracee fatty acids are to of the 13C-labeled tracer fatty acids that are A the tracee and tracer models is that the tracee model additional The into of the tracee model the of tracee ALA and is as a other and were into the and DHA to estimate the incorporation of dietary ALA into the ALA plasma phospholipid a was which be solved by the tracer and tracee models simultaneously. The of the and the for the are that for the of the tracer model, the of the tracer in the ALA was To a more accurate estimate for incorporation into the ALA plasma phospholipid additional was provided by the of dietary ALA and the of tracee n-3 fatty acids into plasma phospholipids. The was based on the to the tracee in a the of tracee ALA into the ALA is to the of tracee ALA that is from this ALA in the plasma phospholipid pool can from dietary ALA as as from ALA in It was to estimate both the and was on the of or the of the and the dietary Therefore, that of the tracee ALA from the diet. The was derived as the ALA from was as or the of the ALA tracee the of tracee ALA in plasma and plasma estimated as of The dietary ALA into the plasma ALA phospholipid was by the from the into was as the ALA uptake be as because the into the from be as or The tracer and tracee models were by the and both models were solved simultaneously. the tracee model was was that the tracee fatty acids and DHA in plasma phospholipids from the of these were which that the and DHA were also other Therefore, and were into the The in were by the fatty acid concentrations with of the of the 29 which was The tracee from to was by the tracee with the the of was by tracee with the The of fatty acid from to was as the of from The of the be determined for and DHA. the tracee into was to the of the separate the of was as The of the tracee n-3 fatty acids, the tracee as as the are in The incorporation of dietary ALA into plasma phospholipids and the conversion to n-3 fatty acid in and amounts of dietary ALA, are in of the tracee model parameters and derived of tracee ALA from EPA DHA DPA from EPA DHA from DHA EPA DPA DHA α-linolenic docosahexaenoic docosapentaenoic eicosapentaenoic in a of dietary ALA into plasma phospholipids and conversion to n-3 fatty acid in and amounts of dietary on of 29 on of 29 and ALA or of dietary ALA into ALA of dietary ALA converted EPA DPA of dietary ALA into ALA of dietary ALA converted EPA DPA in a ALA, α-linolenic docosahexaenoic docosapentaenoic eicosapentaenoic were using averaged data from the 29 The ALA mg or mg or of dietary ALA was incorporated as ALA into plasma phospholipids. this ALA pool, was converted to which to of ALA The of the ALA plasma phospholipid pool, which was to of ALA in the was converted to DHA in the liver, in the plasma phospholipids as DHA. 1% of the EPA in plasma which was to of ALA consumption, was converted to DPA from the plasma phospholipid pool was converted to DHA. the of ALA from the diet that was converted to DHA was can be from the based on the were that was of of the tracee fatty acids into the and DHA plasma phospholipid to or of the into the EPA plasma phospholipid pool that was derived from the ALA plasma phospholipid EPA have from which to be consumed the of the as of these products was the It is also that this EPA was derived from ALA, which was consumed or the tracer study and in tissues other plasma phospholipids. the of the into the DPA plasma phospholipid pool, of into the DHA was DHA from sources for the mean into the DHA the based on were to the based on the averaged be to the estimated for derived from the tracer In this was to this in in a to the these was to to from or from of tracer that a from the DHA is to of and on of 29 on of 29 and into ALA from EPA ALA ALA EPA DPA of into EPA into DPA into DHA in a modeling, found that nearly 7% of ALA was incorporated into plasma phospholipids. 99.8% of ALA from this pool was subsequently converted to only 1% of the EPA plasma phospholipid pool was converted to DPA was used for the synthesis of DHA. the the n-3 is to be the desaturation that is necessary for the conversion of ALA to M.J. in the and of fatty Lipid Res. Scholar, S. of human and on n-3 and polyunsaturated fatty Scholar, of and by a Biophys. Res. 2002; Scholar, Essential fatty acid synthesis and in Leukot. Essent. Fatty Acids. 2003; Scholar). study that this is the as nearly EPA in the plasma phospholipid pool was derived from the ALA plasma phospholipid into the hepatic phospholipid pool is a for ALA conversion to DHA. a few studies have used stable isotopes to quantitatively study ALA metabolism in (12Burdge G.C. Jones A.E. Wootton S.A. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men.Br. J. Nutr. 2002; 88: 355-363Google Scholar, 13Burdge G.C. Wootton S.A. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women.Br. J. Nutr. 2002; 88: 411-420Google Scholar, 14Emken E.A. Adlof R.O. Duval S.M. Nelson G.J. Effect of dietary docosahexaenoic acid on desaturation and uptake in vivo of isotope-labeled oleic, linoleic, and linolenic acids by male subjects.Lipids. 1999; 34: 785-791Google Scholar, 15Emken E.A. Adlof R.O. Gulley R.M. Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males.Biochim. Biophys. Acta. 1994; 1213: 277-288Google Scholar, of alpha-linolenic acid metabolism in adult Lipid Res. Scholar, S. P. of and diets on the of n-3 fatty acid metabolism in human J. Clin. Nutr. 2003; 77: Scholar, G. of dietary alpha-linolenic acid on the conversion and of 2000; Scholar). From and Gulley E.A. Adlof R.O. Gulley R.M. Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males.Biochim. Biophys. Acta. 1994; 1213: 277-288Google estimated that conversion of ALA to was on a diet rich in fatty acids and on a diet. estimated that only of dietary ALA was converted to The n-3 conversion by and Gulley E.A. Adlof R.O. Gulley R.M. Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males.Biochim. Biophys. Acta. 1994; 1213: 277-288Google have to the use of A. of bolus of acid in J. Clin. 1999; have that compared with modeling, in two and to for the conversion of into acid and with values, is to be more as for the and of ALA and plasma phospholipid fatty acid to hepatic conversion. which more ALA also have an from the stable studies of and (12Burdge G.C. Jones A.E. Wootton S.A. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men.Br. J. Nutr. 2002; 88: 355-363Google Scholar, 13Burdge G.C. Wootton S.A. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women.Br. J. Nutr. 2002; 88: 411-420Google however, that only amounts of the labeled products of ALA are incorporated into plasma In the present also in the 13C-labeled n-3 fatty acid of plasma which were by in the n-3 fatty acids were low to be for phospholipids and plasma also of fatty acids, and that of these hepatic n-3 conversion From the studies of and (12Burdge G.C. Jones A.E. Wootton S.A. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men.Br. J. Nutr. 2002; 88: 355-363Google Scholar, 13Burdge G.C. Wootton S.A. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women.Br. J. Nutr. 2002; 88: 411-420Google can be estimated that in only of the 13CALA plasma pool was found in plasma fatty acids a of and these were and G.C. Wootton S.A. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women.Br. J. Nutr. 2002; 88: 411-420Google Scholar). of plasma 13CALA was found in the plasma fatty acid other 13C-labeled n-3 fatty acids were (12Burdge G.C. Jones A.E. Wootton S.A. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men.Br. J. Nutr. 2002; 88: 355-363Google Scholar). are also for hepatic n-3 fatty acid conversion, as they a of 13CALA that and by the 13C-labeled n-3 are present in these fatty acids be derived from conversion the and from conversion the are from from tissues through the of which a fatty acid from a phospholipid to are also in the and the n-3 from plasma the pool on hepatic ALA conversion, because these fatty acids are of the from the plasma phospholipid the are of the 13C-labeled n-3 are by the and n-3 conversion in by the liver might hepatic ALA conversion, as for plasma are in n-3 Kromhout D. G. of polyunsaturated fatty acids and concentrations in J. Clin. Nutr. 43: Scholar). Therefore, of other n-3 fatty acid pool in the model the of the ALA of the other be a the of the ALA be by an from the ALA by into the other of alpha-linolenic acid metabolism in adult Lipid Res. were the to use to n-3 conversion in In to that only of ALA from plasma was used for EPA synthesis. from the plasma EPA pool was converted to and of DPA was converted to DHA. plasma be the for the quantification of hepatic n-3 fatty acid conversion. The results and of of alpha-linolenic acid metabolism in adult Lipid Res. be to other in In tracer on the day was of dietary ALA and on the other 8 days was In contrast, of alpha-linolenic acid metabolism in adult Lipid Res. a single bolus of mg of deuterated in a by a and a tracer bolus as as of the dietary ALA the study of the kinetic of the n-3 fatty acids be C. D. G. in From to Scholar). study and that of of alpha-linolenic acid metabolism in adult Lipid Res. is the of of the stable in other of alpha-linolenic acid metabolism in adult Lipid Res. the ALA tracer as a single provided the tracer in this to the longer and metabolism of ALA and to for DHA. It by G. of dietary alpha-linolenic acid on the conversion and of 2000; that of a single bolus of of DHA only and and Wootton (12Burdge G.C. Jones A.E. Wootton S.A. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men.Br. J. Nutr. 2002; 88: 355-363Google also DHA a of days in plasma or fatty acids of a single bolus of It is for the of tracer the A. of bolus of acid in J. Clin. 1999; Scholar). The estimated of to acid and of to acid a of tracer were compared with the estimated a single bolus of the tracer of model is that the hepatic conversion of dietary ALA. Although is that in the liver is the for n-3 fatty acid conversion, studies with that other such as are also to ALA J.T. to in A stable tracer Lipid Res. Scholar). the n-3 fatty acid conversion might have from the present can that the limited incorporation of dietary ALA into the phospholipid pool contributes to the low hepatic conversion of dietary ALA to EPA. found that the conversion of EPA to which an might be an additional the hepatic n-3 The the and of M. and of as as the of and of the of model The V. V. in and for the of the was by the for an of Dutch food the for and and and with from the Dutch The model was by of for
Goyens et al. (Sun,) studied this question.