in total plasma or serum phospholipids. We have used this t From the Department of Clinical Chemistry and the Department Norway.

Transcription

1 Omeg-3 ftty cids: essentil ftty cids with importnt biologicl effects, nd serum phospholipid ftty cids s mrkers of dietry w3-ftty cid intke13 Kristin S Bjeri e, Ann Mrl Brubkk, Kristin J Fougner, nd Torstein 1k ABSTRACT Serum phospholipid eicospentenoic (PL- PA) nd docoshexenoic cid (PL-DHA) concentrtions re ssocited with the dietry intke ofe3 ftty cids. PL-PA nd PL-DHA concentrtions mesured 4 y prt in dibetic ptients were highly correlted, with Spermn correltion coefficients of.49 (p =. 1 ) nd.64 (p =. 1 ), respectively. PL-DHA ws positively ssocited with Byley psychomotor nd mentl developmentl indexes (PD nd MD, respectively) in preterm infnts. Using multiple-regression nlysis, 64% (R2 =.639: p =. 1) of PD vrince ws explined by 1/DHA nd weight t 1 y. wheres 82% (R2 =.816: p =.1) of MD vrince ws explined by weight t 1 y. Apgr score. l/dha, nd 1/PA. l/dha ws negtively correlted with PD nd MD, wheres 1/PA ws positively correlted with MD. The results suggest tht infnt formuls should contin preformed DHA, nd tht too-high supply of PA in ddition to DHA might be hrmful in preterm infnts..lmn J Cliii Nutr 993:57(suppl):8 1S-6S. KY WORDS Dibetes mellitus. docoshexenoic cid. eicospentenoic cid, fish oil, mentl nd psychomotor development, )3 polyunsturted ftty cids. plsm phospholipid ftty cids, preterm infnts. very-low-birth-weight infnts ntroduction During the pst decde, people hve focused on the helth effects of the dietry supply of w3 ftty cids, prtly becuse those ftty cids hve been reported to protect ginst crdiovsculr nd inflmmtory diseses, s well s certin types of cncer, in humns ( 1. 2) nd prtly becuse it hs been shown tht the w3 ftty cids re essentil nutrients in dults nd chi!- dren (3-5) s well s in primtes (6). Ft ws first described s n essentil dietry component by von Groer in 1919 (7), but not until 1 y lter ws it discovered tht it ws specificlly the lck of dietry w6 ftty cids tht cused the typicl skin chnges, s well s chnges in most other orgns, seen in essentil ftty cid deficiency in rts (8). Lter, Hnsen et l (9) reported the risk for developing nd described the symptoms ofw6 ftty cid deficiency in children. From their dt, s well s those published by Holmn nd collbortors (1-12). dietry requirements could be clculted nd developed Hrld Johnsen, Kristin Midihjell, into interntionl recommended dietry llownces for w6 ftty cids (13). Although it ws well known tht neither w6 nor w3 ftty cids re synthesized by humns, it ws not until recently tht 3 ftty cids were recognized s essentil ftty cids in their own right (3, 4, 14, 1 5). However, it is still uncertin how much dietry w3 ftty cid is required to mintin helth, especilly in newborn nd preterm children ( ). Similrly, except for their serum triglyceride-lowering effect, the role of long-chin o3 ftty cids in protecting ginst crdiovsculr disese nd reducing crdiovsculr risk fctors is still unsettled. ncresing dietry intke of w3 ftty cids hs been reported to reduce the risk ( 1 8-2), or to hve no effect (2 1, 22) on crdiovsculr disese. Their reported effects on blood low-density-lipoprotein (LDL) nd high-density-lipoprotein (HDL) cholesterol re highly vrible (23), nd lthough most studies hve shown tht longchin w3 ftty cids reduce systolic blood pressure (23, 24), their reported effect on distolic blood pressure is mbiguous (24). We hve investigted whether it is possible to estimte dietry long-chin w3 ftty cid intke by nlyzing their concentrtion in totl plsm or serum phospholipids. We hve used this method to study the ssocition between dietry intke of w3 ftty cids nd blood pressure (25) nd lipoproteins (26), s well s the ssocition ofw3 ftty cids with mentl nd psychomotor development in preterm infnts (1 7, 27). Subjects nd methods Methods Plsm or serum totl phospholipid ftty cids were quntitted by gs-liquid chromtogrphy s described previously (25). t From the Deprtment of Clinicl Chemistry nd the Deprtment of Peditrics. University Hospitl of Trondheim, nd the Norwegin nstitute for Public Helth, Centre for Community Medicine, Verdl, Norwy. 2 Supported by grnts from the Nordic nsulin Fund. the Norwegin Dibetes Assocition. the Norwegin Council for Science nd the Humnities. nd the Norwegin Council on Crdiovsculr Disese. 3 Address reprint requests to KS Bjerve, Deprtment of Clinicl Chemistry. University Hospitl of Trondheim. N-76 Trondheim, Norwy. Downloded from jcn.nutrition.org t PNNSYLVANA STAT UNV PATRNO LBRARY on Februry 18, 216..lifrl J C/lit Nuir 1993:57(suppl):81S-6S. Printed in USA Americn Society for Clinicl Nutrition 81S

2 82S BJRV T AL Briefly, lipids were extrcted with n-butnol fter the ddition of butylted hydroxytoluene nd diheptdecnoylglycerophosphocholine (Sigm Chemicl. Pool. UK) s ntioxidnt nd internl stndrd, respectively. Totl phospholipids were isolted by column chromtogrphy nd trnsmethylted before ftty cids were quntitted by gs-liquid chromtogrphy. Smples of norml humn serum stored t -8 #{176}C were included s controls in ech series of nlysis. To ensure reproducibility. > 6% of the smples in ech series were controls nd 2% were regent blnks. The results were expressed s tmol ftty cid/l (nd mg ftty cid/l). The dy-to-dy coefficients of vrition (11 = 55) for 18:.!8:ln-9. l8:2n-6. 2:3n-6, 2:4n-6, 2:5n-3, 22:6n-3. nd totl phospholipid ftty cids were 3.3%, 4.9%, 3.1%. 4.%. 3.8%. 3.7%. 4.7%. nd 3.l, t men concentrtions of , 765., 59.! , 37.8, nd tmol/l ( , , 18. 1, 12., 68.7, nd 1246.S mg/l). respectively. Dietry ftty cid intke ws clculted s the men of two unnnounced 24-h dietry reclls using the Norwegin Food Tble, which provides informtion on individul ftty cids. Sttisticl nlysis ws performed by use ofthe S.S progrm (SAS nstitute nc. Cry. NC). Liner multiple-regression models were fitted by stepwise procedures nd selection of best subsets of independent vribles. Mode! dequcy ws checked with norml probbility plots nd residul nlysis. Subjects The ssocition between serum totl phospholipid ftty cid concentrtions nd dietry intke of w3 ftty cids ws studied in n dult popultion of 156 subjects recruited to enter into 1- wk dietry intervention tril with fish oil nd corn oil. Two unnnounced, stndrdized 24-h dietry reclls were recorded nd fsting blood smple ws obtined before the subjects entered the tril. The popultion hs been described in detil elsewhere (25, 26). The long-term individul reproducibility ofserum phospholipid ftty cid concentrtions ws evluted in popultion of 21 1 dibetic ptients. During ll inhbitnts in the county ofnord-tronde!g ged > 4 y (n = 54.74) were screened for the presence ofpreviously unknown dibetes in collbortion with the Ntionl Helth Screening Service. A nonfsting blood glucose test ws used for the initil screening. The finl dignosis of dibetes ws estblished by nlysing fsting blood glucose or by performing n orl glucose-tolernce test ccording to the criteri ofthe WHO expert committee recommendtions of 198 (28). From this popultion, 325 previously undignosed dibetic ptients were eligible to be included in the prospective Nord-Trondelg Omeg-3 Study. n 1989, ll subjects still live were invited to prticipte in new exmintion, t which time second blood smple ws drwn for the nlysis of serum totl phospho!ipid ftty cid concentrtions. The popultion ofpreterm infnts consisted ofll ofthe verylow-birth-weight (VLBW) infnts (n = 2 1) with birth weight < 1 5 g seen consecutively t the Deprtment of Peditrics during 7-mo period. As prt of the routine follow-up for ll such infnts, they were seen gin in the Deprtment of Peditrics fter 1 y of corrected ge. The 1-y follow-up exmintion consisted of routine blood smple nd complete clinicl exmintion tht included use of the Byley scles of infnt development (29), nd t the sme time blood smple ws tken for nlysis of plsm phospholipid ftty cids. The 2 1 infnts in whom plsm smples could be obtined were finlly included in the study. By!ey test scores were mesured before plsm phospholipid ftty cid concentrtions hd been nlyzed. The people conducting the plsm phospholipid nlysis were blinded with respect to the results from Byley test scores, nd vice vers. The study ws pproved by the locl ethics committee. Results Dietry intke mid serum p/io.spholipid w3/citti cids Figure 1 shows the ssocition between the concentrtion of plsm phospholipid eicospentenoic cid (PA) nd docoshexenoic cid (DHA) nd the dietry intke of long-chin w3 ftty cids in Norwegin, free-living popultion. The subjects were initilly grouped ccording to their reported number offish mels per week (< 2, 2, 3. nd 4 mels/wk). The men dietry intke of -linolenic cid in the groups ws 1.22, 1.!9, 1.3 1, nd 1.59 g/d, respectively. The dietry intke ofpa, DHA, nd totl long-chin w3 ftty cids ws plotted ginst the concentrtions of plsm phospholipid PA nd DHA. The ftty cid concentrtion ws plotted s geometric mens, nd dietry intkes, s medins becuse of their skewed distributions. Using m ultiple-liner-regression nlysis nd controlling for ge, gender, body mss index, lcohol intke, nd smoking, there ws sttisticlly significnt positive correltion bsed on individul observtions between incresing number of fish mels nd the concentrtion of plsm phospholipid PA (p <.!) nd plsm phospholipid DHA (p <.1). One problem encountered in using serum or plsm phospholipid w3 ftty cid concentrtions to monitor dietry w3 ftty cid intke is whether single blood test will give ny indiction ofthe long-term intke ofw3 ftty cids. To exmine the longterm stbility ofserum phospholipid w3 ftty cid concentrtions, we compred the concentrtions mesured 4 y prt in 21 1 dult dibetic ptients. Figure 2 shows the concentrtion of phospholipid PA nd DHA in these dibetic ptients during the initil screening period ( ), plotted ginst the concentrtion mesured upon reexmintion 4 y lter. Although there re some extreme outliers. there is highly significnt rnk correltion between the two mesurements. (Spermn r =.486, p =.1). n comprison, the long-term trcking of serum phospholipid DHA concentrtions ws clerly even higher (Spermn r =.636, p =.1). The results indicte tht nlysis ofplsm totl phospholipid w3 ftty cid concentrtions cn be used to quntitte indirectly dietry w3 ftty cid intke on n individul bsis. t could therefore be possible to use this blood test to study the ssocition between dietry intke of long-chin w3 ftty cids nd their effects on humn helth nd disese. Serum J)/lOs/)/iOli/)id w3 /#{225}tti cids nd psychomotor nd mentl development in preterm infnts. To test whether the dietry supply oflong-chin w3 ftty cids ws ssocited with psychomotor or mentl development in preterm infnts. we reexmined 2 1 VLBW, preterm infnts (birth weight < 1 5 g) t 1 y of corrected ge. During the reexmintion, routine blood smp!e ws tken. A subsmple ofit ws used to nlyze serum totl phospholipid ftty cid concentrtions, nd the concentrtions of PA nd DHA in serum totl phospholipids were used s indictors of the dietry intke of long-chin w3 ftty cids. The dt were nlyzed by multiple liner regression. Dependent vribles nlyzed were either the Byley Psychomotor De- Downloded from jcn.nutrition.org t PNNSYLVANA STAT UNV PATRNO LBRARY on Februry 18, 216

3 PHOSPHOLPD w3 ACDS AS DTARY MARKRS w.-j (1) A.#{149} -J () A.#{149} C) co ) -J 3 w :D w to -J Co th T Spermn r = ).. T U) S-PHOSPHOLPD PA (mol/l) r A PA #{149}DHA (G per Dy),. Totl Long-Chin N-3 (% of nergy) DTARY NTAK FG. The ssocition between plsm phospholipid eicospentenoic cid (PA) (left pnel) nd docoshexenoic cid (DHA) (right pnel) concentrtions nd dietry intke ofw3 ftty cids in free-living Norwegin popultion (mi = 156). The subjects were initilly grouped ccording the their reported number offish mels/wk (< 2. 2, 3. nd 4/ wk). The men dietry intke of -linolenic cid in the groups ws 1.22, , nd 1.59 g/d. respectively. The geometric mens of plsm totl phospholipid PA concentrtions were plotted ginst the medin dietry intke of PA (A-A. g/d). DNA (#{149}-. g/d). or totl long-chin w3 ftty cid intke (#{149}-#{149}. % of totl energy). velopmentl ndex (PD) or the Byley Mentl Developmentl ndex (MD). The independent vribles tested in the models were weight. length. nd hed circumference t birth: gesttionl ge: Apgr scores: dys on ventiltor: nthropometric dt: nd serum phospholipid ftty cid concentrtions t 1 y of corrected ge (l8:2n-6. 2:3n-6, 2:4n-6, 18:3n-3, 2:5n-3, nd 22: 6n-3). The best model fits were obtined by letting PA nd DHA enter the models in inverted form. This suggests tht incresing the dietry w3 intke hs bigger impct on MD nd PD scores in children with low compred to high intke of w3 ftty cids. As seen in Tble 1, 64% of the totl vrince in PD (R2 =.639. p =.1) ws explined by model including 1/ DHA (L/mg) nd weight (g) t 1 y. The effect of /DHA on PD when weight ws controlled for is liner nd negtively correlted ct?..5, < : :i 5 th with PD. suggesting tht high dietry intke of DHA is ssocited with n improved PD performnce. No other ftty cids or nthropometric dt entered the model. A model ineluding l/dha, 1/PA. Apgr score, nd weight t 1 y explined 82% (R2 =.816) of the vrince observed in MD. Tble 1 shows tht MD incresed with incresing concentrtions of DHA but decresed with incresing concentrtions of PA. This suggests tht infnts with low cpcity to metbolize PA into DHA will be t disdvntge if their diet does not contin sufficient preformed DHA. Discussion Two min res should be considered when the role of dietry o3 ftty cids is exmined. The first includes their phrmcologicl potentil. tht is. to wht extent cn e3 ftty cids protect i. Spermnr=.64 #{149} 8 f c#{176} Q, S-PHOSPHOLPD DHA (mo/l) r Downloded from jcn.nutrition.org t PNNSYLVANA STAT UNV PATRNO LBRARY on Februry 18, 216 FG 2. Correltion ofserum phospholipid PA (left pnel) nd DHA (right pnel) concentrtions in blood smples drwn 4 y prt in newly dignosed dibetic ptients.

4 845 BJRV T AL TABL 1 Assocition between serum totl phospholipid concentrtions of long-chin w3 ftty cids nd Byley mentl nd psychomotor development indexes* Dependent vribles ndependent (prtil correltion vribles coefficients) Totl vrince explined by l/dha 1/PA model Byley Mentl r = -.75 r =.7 R2 =.8 16 Developmentl (P =.1) (P =.5) (P =.1) ndex (MD) Byley Psychomotor r = -.66 Nt R2.639 Developmentl (P =.1) (P.1) ndex (PD) * The full multiple-liner-regression model explining the vrince observed in MD included l/dha, /PA. Apgr score. nd weight t 1 y. The full model explining the vrince in PD included only 1/ DHA nd weight t 1 y. Results re given s prtil correltion coefficients obtined when djusting for ll remining independent vribles. DHA, docoshexenoic cid: PA. eicospentenoic cid. t Not included in the model. ginst, or cure, diseses such s crdiovsculr disese nd certm types ofinflmmtory diseses. The other min re is how much nd which essentil w3 ftty cids must be present in the diet in order to secure helth or norml development. Most studies on the phrmcologicl effects hve so fr been short-term intervention studies using purified fish oils or fish ft s the source of w3 ftty cids. This type of study most often does not ddress the effect on disese, but rther the effect on known risk fctors such s blood lipids, blood pressure, pltelet ggregbility, lymphocyte function, or other reported risk fctors (1, 14, 23, 25). One problem with this type ofstudy is tht it is not possible to conclude with certinty whether beneficil effect on one or more of the risk fctors lso mens positive effect on the disese itself. Others hve studied the ssocition between crdiovsculr disese nd dietry intke of fish (19, 22) nd of w3 ftty cids (3). The problem with this type ofstudy is tht observed effects might be due to some constituent other thn w3 ftty cids in fish or in the min dietry source of w3 cids. We hve tried nother pproch to ssess the role of w3 ftty cids in humn helth nd disese, nmely, to use the concentrtion of PA nd DHA in serum or plsm totl phospholipids s indictors of the individul dietry intke of long-chin w3 ftty cids. The results presented in this pper indicte tht the concentrtion of serum totl phospholipid PA nd DHA, s well s the concentrtion of totl w3 ftty cids in plsm phospholipids, re linerly ssocited with the dietry intke of longchin co3 ftty cids. There lso seems to be resonbly good individul reproducibility in the concentrtion of serum totl phospholipid DHA, s indicted by the Spermn correltion coefficient (r =.64) when compring blood smples tken 4 y prt. The long-term individul correltion of serum phospholipid PA concentrtions ws lower but still highly significnt (Spermn r =.49). We previously used this method to show tht long-chin o3 ftty cids reduce blood pressure in dosedependent mnner nd tht w3 ftty cids supplied through norml Norwegin diet hve the sme effect on blood pressure s w3 ftty cids given s highly purified fish oil (25). The present study hs used nlysis of serum totl phospholipid w3 ftty cids nd multiple-liner-regression nlysis to investigte whether the dietry supply of w3 ftty cids is ssocited with the Byley scores of psychomotor nd mentl development indexes t 1 y of corrected ge in preterm, VLBW infnts. t hs been reported tht DHA is essentil for the norml development ofthe retin (6, 15, 3!) nd the brin (16, 17, 32). We found tht 64% of the totl vrince observed in PD ws explined by model including!/dha nd weight t 1 y. 1/ DHA ws the first independent vrible to enter the model nd ccounted for 75% ofthe totl vrince explined by the model. None ofthe other independent vribles contributed significntly to explin the observed vrince ofpd. n comprison, model including weight t 1 y. l/dha, nd 1/PA explined 82% of the observed vrince in MD: l/dha nd 1/PA ccounted for 22% nd 2% ofthe totl vrince explined by this model, respectively. Agin, no other independent vribles entered the models tested. All models gve the best fits when PA nd DHA entered with their inverted vlues, indicting tht they hd the highest impct on PD nd MD in infnts with the lowest intke of long-chin w3 cids. The multiple-regression nlysis indicted tht MD ws negtively ssocited with incresing concentrtions of PA wheres MD nd PD were positively ssocited with incresing concentrtions of DHA. Crlson et! (16) reported tht serum phospholipid rchidonic cid ws positively ssocited with MD nd the Fgns test in preterm infnts. n the present study, serum phospholipid rchidonic cid did not contribute significntly to ny ofthe models, even ifit ws forced into the model. PA hs, however. been shown to compete effectively with rchidonic cid for incorportion into cell-membrne phospholipids under conditions in which DHA hs no effect on phospholipid rchidonic cid concentrtions (32). The negtive ssocition found in this study between PA nd MD when the other independent vribles re controlled for might, therefore, reflect the sme biologicl mechnism s the positive ssocition with rchidonic cid reported by Crlson et l (32) nd suggests tht preterm infnts even t the ge of 1 y might hve reduced bility to metbolize PA into DHA. nfnt formuls, especilly those used in preterm, VLBW infnts, should therefore probbly contin either preformed DHA or -linolenic cid in higher concentrtions thn currently recommended. The results lso suggest tht potentil hrmful effect of including PA in preterm formuls must be considered nd thoroughly evluted. ] References 1. Simopoulos AP. Omeg-3 ftty cids in helth nd disese nd in growth nd development. Am Clin Nutr 199 1:54: ditoril. skimo diets nd diseses. Lncet 1983:1 : Bjerve KS. Omeg-3 ftty deficiency in mn: implictions for the requirement of lph-linolenic cid nd long-chin omeg-3 ftty cids. n: Simopoulos AP, Kifer RR, Brlow SM, eds. Helth effects ofomeg-3 polyunsturted ftty cids in sefoods. World Rev Nutr Diet 1991:66: Bjerve KS. Alph-linolenic cid deficiency in dult women. Nutr Rev 1987:45:15-9. S. Holmn RT, Johnson SB. Htch T. A cse ofhumn linolenic cid deficiency involving neurologicl bnormlities. Am Clin Nutr 1982:3: Downloded from jcn.nutrition.org t PNNSYLVANA STAT UNV PATRNO LBRARY on Februry 18, 216

5 PHOSPHOLPD w3 ACDS AS DTARY MARKRS 85S 6. Neuringer M, Connor W. n-3 ftty cids in the brin nd retin: evidence for their essentility. Nutr Rev 1986:44: von Gr#{248}er F. On the question ofthe prcticl mening of nutritionl vlue nd comments on the miniml ft requirement in the humn infnt. Biochem Z 1919:93: (in Germn). 8. Burr GO. Burr MM. On the nture nd role ofthe ftty cids essentil in nutrition. Biol Chem 193:86: Hnsen A. Wiese HF, Boelsche AN, et l. Role oflinoleic cid in infnt nutrition. Peditrics 1963:3 l(suppl): lolmn RT. Cster WO, Wiese HF. The essentil ftty cid requirement of infnts nd the ssessment of their dietry intke of linolete by serum ftty cid nlysis. Am Clin Nutr 1964:14:7- S Holmn RT. ssentil ftty cids in humn nutrition. Ads xp Med Biol 1977:83: Pulsrud JR. Pensler L, Whitten CF. et l. ssentil ftty cid deficiency in infnts induced by ft-free intrvenous feeding. Am Clin Nutr 1972:25: Food nd Agriculture Orgniztion, World Helth Orgniztion. Dietry fts nd oils in humn nutrition. Genev: FAO/WHO (Pper 3.) 14. Bjerve KS, Fischer 5, Wmmer F, gelnd T. Alph-linolenic cid nd long-chin n-3 ftty cid supplementtion in three ptients hving n-3 ftty cid deficiency: ffect on lymphocyte function. plsm nd red cell lipids, nd prostnoid formtion. Am Clin Nutr 1989:49:29-3. S. Crlson S, Cooke R, Peeples M, Werkmn SH, Tolley A. Docoshexenote (DHA) nd eicospentenote (PA) sttus of preterm infnts: reltionship to visul cuity in n-3 supplemented nd unsupplemented infnts. Peditr Res 1989:25:285A (bstr). 16. Crlson S, Slem N. ssentility of omeg-3 ftty cids in growth nd development of infnts. n: Simopoulos AP, Kifer RR, Brlow SM, eds. Helth effects of omeg-3 polyunsturted ftty cids in sefoods. World Rev Nutr Diet 1991:66: Bjerve KS. Thoresen L, Ben K. Vik T, ohnsen H, Brubkk AM. Clinicl studies with lph-linolenic cid nd long-chin n-3 ftty cids. Nutrition 1992:8: Kromhout D, Bosschieter B, Coulnder CL. The inverse reltion between fish consumption nd 2-yer mortlity from coronry hert disese. N ngi Med 1985:312: Burr ML, Fehily AM. Gilbert F, Rogers 5, et l. ffect of chnges in ft, fish, nd fibre intkes on deth nd myocrdil reinfrction: Discussion diet nd reinfrction tril (DART). Lncet 1989:2: K Fred Gey: My question is bout vegetrins. You showed interesting correltions between blood pressure nd the consumption ofeicospentenoic nd docoshexenoic cids. Vegetrins, who tend to hve rther low blood pressure, consume lot of-linolenic cid. Although plnts contin only 1% ft, bout hlf of tht is -linolenic cid. My question is, do you know nything bout direct correltion between -linolenic cid consumption nd blood pressure in vegetrins? Or. in more gener! terms, is nything known bout the reltive contribution of the vrious ftty cids of the w3 series with regrd to blood pressure when you strt s low s -linolenic cid? Kristin S Bjerve: skipped -!inolenic becuse the study design did not llow conclusions to be drwn bout whether -!inolenic cid hs specific effect on blood pressure or whether the effect 2. Dyerberg. Bng HO. A hypothesis on the development of cute myocrdil infrction in Greenlnders. Scnd Clin Lb nvest 1982:42: Curb D. Reed DM. Fish consumption nd mortlity from coronry hert disese. N ng Med 1985:313: Vollset S. Heuch. Bjelke. Fish consumption nd mortlity from coronry hert disese. N ng Med 1985:313: Hrris WS. Fish oils nd plsm lipid nd lipoprotein metbolism in humns: criticl review. Lipid Res 1989:3: Ben K. pidemiologicl nd intervention studies on the effect of mrine polyunsturted ftty cids on blood pressure. ntern Med 1989:225(suppl 1 ): Bon KH. Bjerve KS, Strume B. Grm, Thelle D. ffect of eicospentenoic nd docoshexenoic cids on blood pressure in hypertension: popultion bsed intervention tril from the Tromse Study. N ng Med 199:322: Ben KH. Bjerve. Nordey A. Hbitul fish consumption, plsm phospholipid ftty cids, nd serum lipids: the Troms#{248}study. Am Clin Nutr 1992:55: Vik T. Bjerve KS. Mck M. Brubkk A-M. Low plsm levels of docoshexenoic cid (DHA) in preterm infnts fed humn milk formul. Peditr Res 199 1:29:36A bstr. 28. World Helth Orgniztion xpert Committee on Dibetes Mellitus. Second committee report. Genev: WHO, 198. (Technicl report series 646.) 29. Byley N. Byley scle of infnt development. New York: Psychologicl Corportion, Dolecek TA. Grndits G. Dietry polyunsturted ftty cids nd mortlity in the Multiple Risk Fctor ntervention Tril (MRFT). n: Simopoulos AP. Kifer RR, Mrtin R, Brlow SM, eds. Helth effects of omeg-3 polyunsturted ftty cids in sefoods. World Rev Nutr Diet 199 1:66: Uuy RD. Birch DO, Birch, Tyson, Hoffmn DR. ffect of dietry omeg-3 ftty cids on retinl function of very-low-birthweight neontes. Peditr Res 199:28: Brekke O.-L., spevik T. Brdl T, Bjerve KS. ffects of n-3 nd n-6 ftty cids on tumor necrosis fctor cytotoxicity in WH fibrosrcom cells. Lipids 1992:27: Crlson S. Peeples M. Werkmn SH. Cooke R. Wilson WM. Archidonic cid (AA) in plsm nd red blood cell (RBC) phospholipids (PL) during follow-up ofpreterm infnts: occurrence. dietry determinnts nd functionl reltionships. n: Simopoulos AP, Kifer RR. Mrtin R, Brlow SM, eds. Helth effects of omeg-3 polyunsturted ftty cids in sefoods. World Rev Nutr Diet 1991:66:57. is only ssocited with the desturted nd elongted products PA nd DHA. would like to comment on the PA nd the DHA, though, becuse t bseline levels on ordinry food intke, blood pressure correltes only with PA, not with DHA. During the intervention phse in the study tht Bon did in Troms#{248}, blood pressure correlted both with PA nd DHA, but tht is becuse both ftty cids were given simultneously nd, therefore, both incresed in blood phospholipids during the intervention. However, in the stedy stte, before intervention strted, blood pressure correlted only with PA. Michel A Crwford: hve two points. The first is, when you tlked bout requirements of n-3 ftty cids, you gve us some figures relted to skin function. We re not sure, however, ift tht level you will be meeting the requirements for ll other functions the n-3 ftty cids hve, especilly for the brin. Downloded from jcn.nutrition.org t PNNSYLVANA STAT UNV PATRNO LBRARY on Februry 18, 216

6 86S BJRV T AL Bjerve: The figures 1 gve you re intkes clculted to give blood phospholipid concentrtion of PA nd DHA corresponding to the men concentrtions found in the Norwegin popultion. Becuse Norwy hs reltively high intke of longchin ftty cids, these figures re probbly t the upper end of wht is needed to cover the dily requirements of PA nd DHA. Crwford: The second question is bout the Byley developmentl scores nd things like tht. Premture bbies. s m sure you re well wre, re ll born t different gesttionl ges. Some of our dt suggest tht the erlier the bby is born, the lower the concentrtions of DHA in its circultion. So. there seems to be negtive correltion between the degree of premturity nd the DHA sttus. Hve you looked t this question of the developmentl scores in reltion to birth weight nd to the degree of premturity? Bjerve: fwe don t let weight t 1 yer enter the model, ll these fctors will enter. However, s soon s birth weight t 1 yer of corrected ge is included in the model, it will lso explin ll the vrition in the other vribles tht you mentioned. They. therefore, don t provide ny dditionl explntion to the model. Dvid F Horrobin: You hve shown these interesting differentil correltions of PA nd DHA with vrious prmeters, both t 1 yer of ge nd in dults, s understnd it. Wht, do you think, does this indicte for the reltionship between PA nd DHA, in both infnts nd dults? Does it men tht humns re unble to convert PA into DHA very effectively? Bjerve: Tht might be one explntion: there could be severl others. think the messge is tht we need pure PA. we need pure DHA, nd we need to compre them in clinicl trils to find out whether the different ssocitions relly reflect tht PA nd DHA hve different biologicl effects. Horrobin: Obviously. if these re custions s well s correltions, one crude interprettion would be tht you give PA to dults nd DHA to bbies. Adrin C vn Houwelingen: You showed correltions between the ftty cid contents of pltelets nd plsm. Did you ever mke such correltions between red blood cells nd plsm? And secondly, the correltions with the Byley scores were mde with plsm, if recollect well. Hve you ever tried to mke such correltion with red blood cells, becuse they re thought to be better reflection of the tissue mounts? Bjerve: Not systemticlly. We hve compred plsm phospholipid ftty cid concentrtions with red cell phospholipids in some ptients on enterl nutrition nd with pltelet ftty cids during n intervention study with fish oil nd corn oil. n both instnces. the plsm phospholipid concentrtions of PA nd DHA re highly correlted with the concentrtions found in pltelets or in red cells. s you hve probbly observed yourself. vn Houwelingen: n our hnds the ftty cid correltions between plsm nd red cell phospholipids re rther poor. Tht s why sked it. Bjerve: We found tht plsm phospholipid concentrtions of PA nd DHA correlte highly with the corresponding pltelet concentrtions. Archidonic cid is slightly less correlted. n ptients with n-3 ftty cid deficiency. rchidonic cid concentrtions in erythrocytes were positively ssocited with n-3 ftty cids.. therefore, think we still need more knowledge bout how n-3 ftty cids ffect the wy in which n-6 ftty cids enter the membrne. Downloded from jcn.nutrition.org t PNNSYLVANA STAT UNV PATRNO LBRARY on Februry 18, 216