Journal of Nutrition

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Crowe, F. L.
Right arrow Articles by Green, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Crowe, F. L.
Right arrow Articles by Green, T. J.
© 2008 American Society for Nutrition J. Nutr. 138:551-555, March 2008

Nutrient Requirements and Optimal Nutrition

Lowering Plasma Homocysteine Concentrations of Older Men and Women with Folate, Vitamin B-12, and Vitamin B-6 Does Not Affect the Proportion of (n-3) Long Chain Polyunsaturated Fatty Acids in Plasma Phosphatidylcholine1,2

Francesca L. Crowe3, C. Murray Skeaff3,*, Jennifer A. McMahon3, Sheila M. Williams4 and Timothy J. Green3

3 Department of Human Nutrition and 4 Department of Social and Preventive Medicine, University of Otago, Dunedin 9054, New Zealand

* To whom correspondence should be addressed. E-mail: murray.skeaff{at}otago.ac.nz.


   ABSTRACT
TOP
 ABSTRACT
Introduction
 Subjects and Methods
 Results
 Discussion
 LITERATURE CITED
 
There is evidence to suggest that folate, homocysteine, or both affect the (n-3) long chain PUFA composition of tissues; however, this evidence is derived largely from experiments with animals and small observational studies in humans. Results from randomized controlled trials are needed. The objective of this study was to determine whether homocysteine lowering with a B vitamin supplement affects the proportion of (n-3) long-chain PUFA in plasma phosphatidylcholine. We conducted a double-blind, placebo-controlled, randomized clinical trial involving 253 participants, 65 y or older, with plasma homocysteine concentrations of at least 13 µmol/L. Participants in the vitamin group (n = 127) took a daily supplement containing 1000 µg folate, 500 µg vitamin B-12, and 10 mg vitamin B-6 for 2 y. The fatty acid composition of plasma phosphatidylcholine was measured at baseline and at 2 y. Plasma homocysteine concentrations during the course of the study were 4.4 µmol/L lower in the vitamin group than in the placebo group. The proportions of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids in plasma phosphatidylcholine did not differ between the vitamin and placebo groups at 2 y; the mean differences after adjusting for baseline values and sex were –0.03 (99% CI: –0.22, 0.16), 0.03 (99% CI: –0.03, 0.09), and –0.02 (99% CI: –0.27, 0.24) mol%, respectively. Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 had no effect on the proportion of (n-3) long-chain PUFA in plasma phosphatidylcholine.


   Introduction
TOP
 ABSTRACT
 Introduction
Subjects and Methods
 Results
 Discussion
 LITERATURE CITED
 
Results from case control and cohort studies suggest that elevated circulating concentrations of homocysteine are associated with increased risk of cardiovascular disease, independent of traditional risk factors such as smoking, blood pressure, serum lipids, and obesity (1,2). Particularly persuasive evidence, in this respect, is the observation of higher cardiovascular risk in homozygous carriers of the 677C-T polymorphism on the methylenetetrahydrofolate reductase gene, a genotype that confers naturally higher homocysteine concentrations (3,4).

Recently, the causal nature of the association between homocysteine and cardiovascular disease has been called into question, because the results of several large, randomized, controlled trials have not shown reduced incidence of cardiovascular disease after homocysteine-lowering with B-vitamins (folate, B-12, and B-6) (5–7). This apparent contradiction between the observational evidence and results of the clinical trials raises the possibility that the positive association between serum homocysteine and cardiovascular risk in the case control and cohort studies may be confounded by 1 or more unmeasured cardiovascular risk factors.

There has been speculation that one of these confounding risk factors may be plasma (n-3) long chain PUFA. The 2 major (n-3) long chain PUFA, eicosapentaenoic acid and docosahexaenoic acid, exert a range of biochemical and physiological effects consistent with cardioprotection (8). Accumulated evidence from observation studies and randomized controlled trials indicates that (n-3) long chain PUFA lower the risk of cardiovascular disease (9).

Results of experimental animal model studies suggest that low folate status (10) or increased exposure to homocysteine (11) decreases the proportion of (n-3) long chain PUFA in tissues, whereas intramuscular injection of folate (12) increases the proportion of these fatty acids. However, the evidence from studies of humans for an association between folate, homocysteine, and plasma or blood cell (n-3) long chain PUFA is limited. In a study of 22 men with aggressive and hostile behavior, folate concentrations and docosahexaenoic acid in erythrocytes were correlated (r = 0.57; P = 0.005) (13); however, the results from another study involving 44 patients with depressive disorders showed plasma homocysteine concentrations were not significantly correlated with (n-3) long chain PUFA composition of plasma or erythrocyte lipids (14). Recently, Dullemeijer et al. (15) reported no correlation between plasma or erythrocyte folate concentrations and the proportion of eicosapentaenoic acid or docosahexaenoic acid in plasma cholesterol ester (r = 0.04; P = 0.21). In a randomized controlled trial, pregnant women supplemented with folic acid from gestation wk 22 until delivery had a very small but significant increase in the proportion of docosahexaenoic acid in total plasma fatty acids (16).

In this study, we used a randomized placebo-controlled trial to test the hypothesis that homocysteine-lowering with the B-vitamins, folate, vitamin B-12, and vitamin B-6 affects the proportion of (n-3) long chain PUFA in plasma phosphatidylcholine.


   Subjects and Methods
TOP
 ABSTRACT
 Introduction
 Subjects and Methods
Results
 Discussion
 LITERATURE CITED
 
This randomized controlled study was part of a 2-y trial to determine whether B-vitamins improved cognitive function in older men and women (17). The fatty acid composition of plasma phosphatidylcholine is a secondary endpoint of the trial.

    Participants. Participants 65 y or older were recruited from local service clubs (e.g. Rotary International) and by advertising in newspapers as well as by direct mailings. Participants were excluded if: they were taking medications known to interfere with folate metabolism; their physician told them they had probable dementia; they were taking vitamin supplements containing folic acid, vitamin B-12, or vitamin B-6; or they were being treated for or had a history of depression, stroke, transient ischemic attacks, or diabetes. Volunteers were screened for plasma homocysteine and creatinine; those with a fasting homocysteine concentration <13 µmol/L or a plasma creatinine >133 µmol/L for men and 115 µmol/L for women were excluded. Written informed consent was obtained from each participant prior to screening and the University of Otago Human Ethics Committee approved the study.

    Study design. Participants were stratified using the median values of age and homocysteine concentration from the screening population and randomized to receive a B-vitamin supplement or placebo. Participants were asked to consume 1 capsule daily for 2 y. Participants were provided with a 6-mo supply of capsules and asked to return every 6 mo to obtain a new supply. Participants returned unused capsules every 6 mo and these were counted to assess compliance.

    Supplements. The treatment capsules contained the microcrystalline cellulose as a filler plus 1000 µg folate (L-5-methyltetrahydrofolate, calcium salt), 500 µg vitamin B-12 (cyanocobalamin), and 10 mg vitamin B-6 (pyridoxine). The placebo capsules contained a blend of magnesium stearate and the filler (Merck Eprova). The investigators and the participants were blinded to the contents of the supplements.

    Laboratory methods. An overnight fasting blood sample was collected at baseline and every 6 mo thereafter. Plasma and serum were obtained by centrifuging the whole blood at 1650 x g; 15 min at 4°C within 2 h of collection. Blood samples were stored at –80°C until analyzed. Total homocysteine was measured using the IMx (Abbott Laboratories) fluorescence polarization immunoassay, measuring total L-homocysteine in plasma. Plasma folate concentrations were determined using a microbiological method on 96-well microplates, exactly as described by O'Broin and Kelleher (18) with chloramphenicol resistant Lactobacillus casei as the test microorganism. Plasma vitamin B-12 was measured using the ADVIA Centaur vitamin B-12 assay, a competitive immunoassay using direct chemiluminescent technology. Plasma total cholesterol was measured enzymatically using Roche diagnostic kits on a Cobas Mira Analyzer (Roche Diagnostics). CV for these assays were 6.7% for plasma homocysteine, 7.7% for plasma folate, 5.6% for plasma vitamin B-12, and 1.0% for plasma total cholesterol.

Methylene tetrahydrofolate reductase genotype was determined by amplifying DNA using PCR and subject to restriction by HinfI according to the method of Frosst et al. (19).

Lipids were extracted from 400 µL of plasma according to the method of Bligh and Dyer (20). Plasma phosphatidylcholine was separated by TLC using a solvent system of chloroform:methanol:acetic acid:water (50:37.5:3.5:2 by volume) according to Holub and Skeaff (21). The fatty acid composition was analyzed using a DB-225 narrowbore column (30-m x 0.25-mm i.d.; film thickness, 0.25 µm; J&W Scientific) on a HP-6890 gas chromatograph with flame ionization detection (Agilent). The fatty acid results are reported as percent of total fatty acids on a molar basis (i.e. mol%). Precision of the fatty acid measurement was determined by repeat analysis of a pooled plasma sample; 1 pooled sample was analyzed for every 20 samples. The CV for eicosapentaenoic [20:5(n-3)], docosapentaenoic [22:5(n-3)], and docosahexaenoic [22:6(n-3)] acids in plasma phosphatidylcholine were 1.6, 2.7, and 3.7%, respectively.

    Statistical methods. Differences in characteristics of participants in the vitamin and placebo groups at baseline were determined using a Fisher's exact test for categorical variables and Student's t test for continuous variables. Multiple regression analyses were used to estimate the differences in plasma homocysteine and folate at 2 y after adjustment for baseline values between the placebo group and the treatment group. Likewise, multiple regression analyses, adjusting for baseline fatty acid composition and sex, were used to estimate the differences in the fatty acid composition of plasma phosphatidylcholine at 2 y. Due to the large number of comparisons, differences in fatty acid composition were considered significant at P < 0.01. All analyses were undertaken using Stata Statistical Software: Release 9 for Macintosh (StataCorp).

The sample size of the study was designed on the primary endpoint-scores on tests of cognition. We estimated that 100 participants in each of the vitamins and placebo group would be required to detect a minimum treatment effect size of 0.4 with a power of 80% and 2-sided {alpha} at 0.05 (17). Values in the text are means (99% CI).


   Results
TOP
 ABSTRACT
 Introduction
 Subjects and Methods
 Results
Discussion
 LITERATURE CITED
 
Results in Figure 1 show the study participation and follow-up. The fatty acid composition of plasma phosphatidylcholine was measured in 253 participants at baseline and 243 participants at y 2. Participants who completed 2 y of the trial (n = 243) reported taking 98% of their tablets. The baseline characteristics of participants are presented in Table 1.


Figure 1
View larger version (13K):
[in this window]
[in a new window]

  		FIGURE 1  Study participation and follow-up.

 

View this table:
[in this window]
[in a new window]

  		TABLE 1 Baseline characteristics of older men and women in the placebo and B vitamin groups1

 
At 2 y, plasma homocysteine was lower in the vitamin group than the placebo group (–4.4 µmol/L; 99% CI: –5.5, –3.4 µmol/L) (Fig. 2A). Plasma folate concentrations were significantly higher in the vitamin than the placebo group (50; 99% CI: 44, 56 nmol/L) (Fig. 2B).


Figure 2
View larger version (8K):
[in this window]
[in a new window]

  		FIGURE 2  Plasma homocysteine (A), folate (B), and vitamin B-12 (C) concentrations in older men and women who took a B vitamin supplement (n = 117–127) or a placebo (n = 119–126) for 2 y. Values are means ±99% CI. *Different from the placebo group after adjusting for baseline values, P < 0.001.

 
None of the proportions of fatty acids in phosphatidylcholine measured differed between the placebo and vitamin groups after 2 y of treatment (Table 2). The adjusted mean differences in the proportion of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids between the vitamin and the placebo group were –0.03 (99% CI: –0.22, 0.16), 0.03 (99% CI: –0.03, 0.09), and –0.02 (99% CI: –0.27, 0.24) mol%, respectively.


View this table:
[in this window]
[in a new window]

  		TABLE 2 Fatty acid composition of plasma phosphatidylcholine in older men and women who took a B vitamin supplement or a placebo for 2 y1

 

   Discussion
TOP
 ABSTRACT
 Introduction
 Subjects and Methods
 Results
 Discussion
LITERATURE CITED
 
The results of our study showed that lowering plasma homocysteine concentrations by 4.4 µmol/L for 2 y with high intakes of folate, vitamin B-12, and vitamin B-6 did not alter the (n-3) long chain fatty acid composition of plasma phosphatidylcholine. This finding does not support the hypothesis that homocysteine or high intakes of folate, vitamin B-12, or vitamin B-6 influence the metabolism of (n-3) fatty acids in the body.

Krauss-Etschmann et al. (16) recently reported the outcome of a 2 x 2 factorial, placebo-controlled trial of fish oil and folate supplementation on plasma docosahexaenoic acid in which pregnant women consumed 400 µg of 5-methyltetrahydrofolate daily from wk 22 of gestation to delivery. There was a folate treatment x time interaction (P = 0.047) on the proportion of docosahexaenoic acid but not eicosapentaenoic acid (P = 0.081) in maternal plasma; however, the magnitude of the effect of folate on docosahexaenoic acid was very small. In contrast to the finding in maternal plasma, there was no effect of folate supplementation on docosahexaenoic acid proportions in cord blood plasma (P = 0.095). Krauss-Etschmann et al. (16) suggested that folate supplementation may increase maternal docosahexaenoic acid, a possibility that warrants elucidation in larger trials. It is possible that the difference between these findings and those we report simply reflects the different physiological state of the participants in the 2 studies, pregnant compared with nonpregnant. We also cannot exclude the possibility that our study reflects the absence of long-term effects, whereas the results reported by Kraus-Etschmann reflect transient changes.

Our trial had several design features that made it particularly suited for testing the hypothesis that folate, homocysteine, or both affect docosahexaenoic acid status. The 2-y duration of our trial ensured that plasma vitamin concentrations were maintained at high and steady-state concentrations in plasma (22) and presumably in other tissues, such as liver, for long enough to detect an effect on plasma docosahexaenoic acid if one existed. Participants had high plasma homocysteine concentrations at baseline, 13 µmol/L or higher, and the vitamin supplement lowered homocysteine concentration by 4.4 µmol/L compared with placebo. Despite the long duration of supplementation and large difference in homocysteine concentrations between the treatment and placebo groups, there was no difference in docosahexaenoic acid in plasma phosphatidylcholine at 2 y; even the outer CI of the mean difference (–0.27 mol% and 0.24 mol%) exclude meaningful effects when compared with those caused by small changes in intake of docosahexaenoic acid (23).

The hypothesis that folate deficiency or increased homocysteine concentrations affect (n-3) long chain PUFA composition of tissues originated from results of experiments with animals exposed to folate-deficient diets or extremely high concentrations of homocysteine, physiological conditions and exposures that are quite different to those faced by our participants, who were selected for having a serum homocysteine concentration 13 µmol/L or higher. Adult rats fed a folate-deficient diet for 6 wk had decreased eicosapentaenoic and docosahexaenoic acid composition of plasma and platelet lipids compared with rats fed a folate-replete diet (10). Chick embryos injected with homocysteine (0, 100, 200, and 300 µmol/kg egg) during the first 3 d of embryonic development, had a marked decrease in the percentage of total fatty acids as docosahexaenoic acid in egg phospholipids at 11 d of embryonic development (11). Finally, i.m. injection of 5-methyl tetrahydrofolate (150 µg/d) into rats for 15 d resulted in a higher proportion of docosahexaenoic acid in plasma and erythrocyte phospholipids compared with saline-injected animals (12).

Two mechanisms have been proposed through which folate and homocysteine may exert an effect on docosahexaenoic acid. Durand et al. (10) have suggested that by reducing homocysteine concentrations, folate may reduce the generation of reactive oxygen species and thus spare docosahexaenoic acid, which is a major target for lipid peroxidation. The second mechanism is more complex and is based on the involvement of folate in liver synthesis of phosphatidylcholine through its regulation of 1-carbon metabolism (13). Synthesis of phosphatidylcholine in the liver and secretion into lipoproteins is a major route for the appearance of docosahexaenoic acid into plasma. Despite the plausibility of the proposed mechanisms, the exact metabolic steps that would account for the preferential increase in docosahexaenoic acid as compared with other (n-6) or (n-3) long chain PUFA have not been elucidated.

We chose phosphatidylcholine in plasma as the biomarker of (n-3) fatty acid status, because this lipid constitutes the majority of plasma phospholipids (24) and the percentage of total fatty acids as (n-3) long chain PUFA in plasma phospholipid is markedly higher than in plasma triacylglycerol or cholesterol ester (25). Furthermore, the strong association between the (n-3) long chain PUFA composition of plasma phospholipid and that of erythrocytes, platelets, or leukocytes (24,26–28) suggests the result would be generalizable to these cells.

In conclusion, existing evidence for the effect of folate, homocysteine, or both on docosahexaenoic acid composition of tissue is equivocal. The results of our study provide convincing clinical trial evidence that a folate, vitamin B-12, and vitamin B-6 supplement lowers plasma homocysteine concentrations but does not alter docosahexaenoic acid composition of plasma phosphatidylcholine.


   FOOTNOTES
 
1 Supported by an Otago Research Grant and the Otago Medical Research Foundation (Laurenson Award). Merck Eprova donated the vitamin and placebo capsules. Back

2 Author disclosures: F. L. Crowe, C. M. Skeaff, J. A. McMahon, S. M. Williams, and T. J. Green, no conflicts of interest. Back

Manuscript received 4 October 2007. Initial review completed 17 October 2007. Revision accepted 8 December 2007.


   LITERATURE CITED
TOP
 ABSTRACT
 Introduction
 Subjects and Methods
 Results
 Discussion
 LITERATURE CITED
 

1. The Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288:2015–22.[Abstract/Free Full Text]

2. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002;325:1202.[Abstract/Free Full Text]

3. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. MTHFR 677C->T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA. 2002;288:2023–31.[Abstract/Free Full Text]

4. Lewis SJ, Ebrahim S, Davey Smith G. Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate? BMJ. 2005;331:1053.[Abstract/Free Full Text]

5. Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354:1578–88.[Abstract/Free Full Text]

6. Lange H, Suryapranata H, De Luca G, Borner C, Dille J, Kallmayer K, Pasalary MN, Scherer E, Dambrink J-HE. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med. 2004;350:2673–81.[Abstract/Free Full Text]

7. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567–77.[Abstract/Free Full Text]

8. Schmidt EB, Skou HA, Christensen JH, Dyerberg J. N-3 fatty acids from fish and coronary artery disease: implications for public health. Public Health Nutr. 2000;3:91–8.[Medline]

9. Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ. 2006;332:752–60.[Abstract/Free Full Text]

10. Durand P, Prost M, Blache D. Pro-thrombotic effects of a folic acid deficient diet in rat platelets and macrophages related to elevated homocysteine and decreased n-3 polyunsaturated fatty acids. Atherosclerosis. 1996;121:231–43.[Medline]

11. Miller RR, Leanza CM, Phillips EE, Blacquire KD. Homocysteine-induced changes in brain membrane composition correlate with increased brain caspase-3 activities and reduced chick embryo viability. Comp Biochem Physiol B Biochem Mol Biol. 2003;136:521–32.[Medline]

12. Pita ML, Delgado MJ. Folate administration increases n-3 polyunsaturated fatty acids in rat plasma and tissue lipids. Thromb Haemost. 2000;84:420–3.[Medline]

13. Umhau JC, Dauphinais KM, Patel SH, Nahrwold DA, Hibbeln JR, Rawlings RR, George DT. The relationship between folate and docosahexaenoic acid in men. Eur J Clin Nutr. 2006;60:352–7.[Medline]

14. Assies J, Lok A, Bockting CL, Weverling GJ, Lieverse R, Visser I, Abeling NG, Duran M, Schene AH. Fatty acids and homocysteine levels in patients with recurrent depression: an explorative pilot study. Prostaglandins Leukot Essent Fatty Acids. 2004;70:349–56.[Medline]

15. Dullemeijer C, Durga J, Brouwer IA, Verhoef P. Erythrocyte folate and plasma DHA in the FACIT study. Lancet. 2007;370:216.[Medline]

16. Krauss-Etschmann S, Shadid R, Campoy C, Hoster E, Demmelmair H, Jimenez M, Gil A, Rivero M, Veszpremi B, et al. Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. Am J Clin Nutr. 2007;85:1392–400.[Abstract/Free Full Text]

17. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006;354:2764–72.[Abstract/Free Full Text]

18. O'Broin S, Kelleher B. Microbiological assay on microtitre plates of folate in serum and red cells. J Clin Pathol. 1992;45:344–7.[Abstract/Free Full Text]

19. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–3.[Medline]

20. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37:911–7.[Medline]

21. Holub B, Skeaff C. Nutritional regulation of cellular phosphatidylinositol. Methods Enzymol. 1987;141:234–44.[Medline]

22. Lamers Y, Prinz-Langenohl R, Bramswig S, Pietrzik K. Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006;84:156–61.[Abstract/Free Full Text]

23. Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr. 2006;83:S1467–76.[Abstract/Free Full Text]

24. Prisco D, Filippini M, Francalanci I, Paniccia R, Gensini GF, Abbate K, Neri Serneri GG. Effect of n-3 polyunsaturated fatty acid intake on phospholipid fatty acid composition in plasma and erythrocytes. Am J Clin Nutr. 1996;63:925–32.[Abstract/Free Full Text]

25. von Houwelingen AC, Kester AD, Kromhout D, Hornstra G. Comparison between habitual intake of polyunsaturated fatty acids and their concentrations in serum lipid fractions. Eur J Clin Nutr. 1989;43:11–20.[Medline]

26. Mantzioris E, James MJ, Gibson RA, Cleland LG. Differences exist in the relationships between dietary linoleic and alpha-linolenic acids and their respective long-chain metabolites. Am J Clin Nutr. 1995;61:320–4.[Abstract/Free Full Text]

27. Prisco D, Paniccia R, Bandinelli B, Filippini M, Francalanci I, Brunelli T, Giusti B, Abbate R. Relationship between plasma and platelet phospholipid fatty acid composition in healthy subjects. Platelets. 1996;7:69–73.

28. Skeaff CM, Duffield AJ. Fish oil consumption causes a rapid change in the n-3 fatty acid composition of plasma, platelet, and erythrocyte phospholipids. Eur J Clin Nutr. 1998;52:S65.[Medline]





This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Crowe, F. L.
Right arrow Articles by Green, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Crowe, F. L.
Right arrow Articles by Green, T. J.

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2008 by American Society for Nutrition