Nutrient Interactions

Effect of Long-Term Fish Oil Supplementation on Vitamin E Status and Lipid Peroxidation in Women1 MOHSEN MEYDANI, FELICIA NATIELLO,* BARRY GOLD/TV/ NANCY FREE/ MARGO WOODS/ ERNST SCHAEFER,* JEFFREY B. BLÜMBERG, AND SHERWOOD L GORBACtf U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111; *uniuersita Scienze Farmacologiche, Milan, Italy and ^Community Health, Tufts University School of Medicine, Boston, MA 02111 Epidemiological data suggest that consumption of fish may protect against coronary heart disease (1, 2). Furthermore, recently accumulated evidence from animal experiments and human trials have widely promoted fish oils and (rz-3)fatty acid concentrates of fish oils for the prevention of cardiovascular and in flammatory diseases (1, 3, 4). Fish oils have also been found to have a hypolipidemic effect by lowering total triglycéridesand cholesterol in the circulating blood (5) and by decreasing platelet aggregation through thromboxane reduction (1). However, the substitution of membrane fatty acids with potentially unstable (n-3) fatty acids from fish oil may potentiate peroxidation of cellular membranes and increase the re quirement for vitamin E, a membrane antioxidant. Feeding fish oil has been a classical method for the induction of vitamin E deficiency in animals (6). With renewed interest in fish oil for the prevention of a variety of diseases, the potential harmful effects of fish oil products have been overlooked. Long-term ingestion of fish oil supplements, in addition to pro ducing vitamin E deficiency, may introduce peroxidized fatty acids or degraded products and con taminants, including ma Iondialdehyde (MDA) 2 (7). At present, accumulated evidence indicates that oxidative damage to tissue plays an important role in

ABSTRACT Fifteen young (22-35 y) and 10 older (51-71 y) women received six capsules of fish oil (ProMega)/d, providing a total of 1,680 mg eicosapentaenoic (EPA), 720 mg docosahexaenoic (DMA), 600 mg other fatty acids, and 6 Id vitamin E. Blood was collected before and after 1, 2 and 3 mo of supplementation. Compliance was confirmed by the significant increase in plasma EPA and DHA in all women. Older women had a significantly higher increase in EPA and DHA than did young women (10-fold increases in EPA and 2.5-fold increases in DHA vs. 8-fold in EPA and 2-fold in DHA for older and young women, respectively). The decrease in the arachidonic acid:EPA ratio was more dramatic in the older women. Plasma total triglycérides(TG) decreased significantly, and the ratio of polyunsaturated fatty acids to saturated fatty acids was significantly (P < 0.01) increased. Plasma vitamin E levels did not change signif icantly after supplementation; however, after 3 mo of supplementation by young women, plasma vitamin E was significantly lower than after 1 mo. The vitamin E: TG ratio was significantly increased and vitamin E:(EPA + DHA) significantly decreased. All women showed a significant increase in plasma lipid peroxide through mo 2 of supplementation. After 2 mo, older women had significantly higher lipid peroxide levels than young women. The lipid peroxide:TG ratio, which declined by mo 3, was still significantly higher than baseline. These data indicate that although long-term fish oil supplemen tation may be beneficial in reducing plasma total TG, susceptibility of plasma lipids to free radical attack is potentiated. Furthermore, the decrease in plasma vi tamin E:(EPA + DHA) and increase in plasma lipid peroxide, particularly in the older subjects, indicates that vitamin E content of fish oil capsules may not be suffi cient to provide adequate antioxident protection. J. Nutr. 121: 484-491, 1991.

'This work was supported by National

INDEXING KEY WORDS:

•vitamin E •llpld peroxides •flsh oil •humans •age

0022^166/91

$3.00 ©1991 American

Cancer Institute

Grant

CA45128, American Cancer Society Grant PDT254B, Tufts School of Nutrition-National Institutes of Health Biomedicai Research Grant 2S07RR07179-12, and U.S. Department of Agriculture Con tract 53-3K06-510. Abbreviations used: DHA, docosahexanoic acid; EPA, ei cosapentaenoic acid; MDA, malondialdchydc; PUFA, polyunsatu rated fatty acids; SFA, saturated fatty acids; TG, triglycéride;UFA, unsaturated fatty acids. Institute

of Nutrition.

Received 26 March 1990. Accepted 8 August 1990. 484

Downloaded from https://academic.oup.com/jn/article-abstract/121/4/484/4754632 by Washington University in St. Louis user on 12 April 2018

FISH OIL AND VITAMIN E INTERACTION

the pathology of several human diseases including atherosclerosis, stroke, emphysema and cancer (8). With long-term fish oil supplementation, without adequate antioxidant protection, in vivo peroxidation of (zj-3) fatty acids may contribute to the onset or progression of some of the age-associated diseases. In this study, we investigated the potential change of plasma lipid peroxides of young and older healthy women following long-term supplementation with commercially available fish oil capsules.

MATERIALS AND METHODS Subjects and experimental design. Fifteen healthy young (22-35 y) and 10 healthy older (51-71 y) women were recruited from the Boston area for this study. Excluded from the study were subjects with unusual dietary habits, high alcohol consumption [> 0.148 L (5 oz.) of alcohol per wk] as well as subjects with histories of cancer, heart disease, arthritis, hypertension, diabetes, renal or liver disease, or ir regular menstrual cycles. Also excluded from the study were subjects using vitamin supplements or prescribed medication, such as oral contraceptives, corticosteroids, antibiotics, aspirin, nonsteroidal antiinflammatory drugs and subjects over 110% or under 90% of their ideal body weights. After initial screening, blood samples were analyzed for standard clinical chemistry and leukocyte differential test. The proposed study was fully explained to each subject, and informed consent was obtained. The pro tocol was approved by the Human Investigation Review Committee of the New England Medical Center Hospitals. Before entering the study, prospective female subjects were interviewed by a nutritionist to ensure that they consumed diets similar to the typical American diet (35-40% of energy from fat; 300-400 mg cholesterol/d) and had normal eating habits (e.g., frequent dieters, food bingers and vegetarians were excluded). Each subject's usual diet was supplemented with (n-3) fatty acids contained in six capsules of Pro-Mega (Parke Davis, Warner Lambert Co., Morris Plains, NJ) daily for 12 wk. Each Pro-Mega capsule contained 280 mg of eicosapentaenoic acid (EPA), 120 mg of docosahexaenoic acid (DHA), 100 mg of other fatty acids and 1 IU of d-a-tocopherol (vitamin E). Each subject therefore received a daily total of 1680 mg of EPA, 720 mg of DHA, 600 mg of other fatty acids and 6 iu of vitamin E. The total amount of fat contributed by the fish oil capsules was 3 g or 1.5% of their energy intake. Compliance was verified by measurement of total plasma fatty acids. For each time point, blood samples were collected on 2 consecutive d from young women during the follicular phase of their menstrual cycle (d 4—7) and on 2 consecutive d from older women. Blood Downloaded from https://academic.oup.com/jn/article-abstract/121/4/484/4754632 by Washington University in St. Louis user on 12 April 2018

485

samples were collected at baseline and at the end of 1, 2 and 3 mo of supplementation with fish oil. Blood was collected in tubes containing 0.1% EDTA. Plasma was separated from erythrocytes by centrifugation at 1000 x g for 20 min at 4'C. Aliquots of plasma were stored under nitrogen at -70'C for fatty acid, triglycéride,vitamin E and lipid peroxide anal ysis. Plasma samples collected at different time points from each subject were analyzed at same time for specific biochemical measurements. This procedure was adopted to reduce variation among days in ana lytical methods. The means of two determinations for each time point performed in each consecutive plasma samples were used for statistical analysis. Fatty acid analysis. Analysis and transesterification of plasma fatty acids were performed as fol lows: 100 \¡Lof a solution containing 40 mg of heptadecenoic acid in 100 mL of isooctane was added to each tube in which a plasma sample was analyzed. The isooctane was evaporated under a stream of ni trogen. Plasma (100 pi) was added to the tube fol lowed by the addition of 2 mL of methanol:benzene (4:1, v/v). Then, 200 \¡Lof acetyl chloride was added while the solution was stirred. The tubes were capped and heated at 100'C for 1 h. The tubes were cooled to room temperature, and 5 mL of 6% (wt/v) &¡CO3 solution was mixed thoroughly. The tubes were then centrifugea for 20 min (900 x g at 4*C). The benzene layer was removed and added to a gas chromatography vial ready for analysis. The extract was injected into a Hewlett-Packard 5890 gas-liquid Chromato graph fitted with a 105-m silica capillary column (RTX 2330, Restek Corp., Port Matilda, PA) and de tected with a flame ionization detector. The fatty acid methyl esters of over 40 fatty acids (13:0 to 28:0, including cis and trans configurations) are separated by this method. Peaks were identified and the pro cedure was validated by chromatography of mixtures of authenticated fatty acid methyl esters. A com puter-integrator was used to store the data, to inte grate and identify peaks to calculate the percentages of fatty acid families and to merge the results with other data files for statistical analysis. Each chromatogram was reviewed to ensure that it had been properly identified and integrated. Triglycéride analysis. Triglycéride (TG) measurement was obtained with an Abbott Diag nostic ABA-200 biochromatic analyzer (Irving, TX) using enzymatic reagents (9). Assay was standardized through participation in the Centers for Disease Control-National Heart, Lung and Blood Institute Standardization Program. Vitamin E analysis. Plasma vitamin £was ana lyzed by the HPLC method described earlier (10). Tocol (gift from Hoffmann-LaRoche, Nutley, NJ) was used as an internal standard (11), and eluted peaks were detected with a Perkin-Elmer 650-15 fluores cence spectrophotometer (Norwalk, CT).

MEYDANI ET AL.

486

lApid peroxide analysis. Lipid peroxides in the plasma were measured by the thiobarbituric acid method of Yagi (12), and malonaldehyde-bis(dimethylacetal) (Aldrich Chemical, Milwaukee, WI) was used as a standard with each set of plasma samples analyzed for lipid peroxide level. Thiobarbi turic acid reactive substances were calculated as MDA equivalent. Statistical analysis. Data were analyzed using a VAX-11/780 computer (Digital Equipment Co., Maynard, MA) and Scientific Software package RS/1 (BBN Research Systems, Cambridge, MA). Statistical analysis was carried out with SAS software (SASInsti tute, Inc., Cary, NC). The data were subjected to ANOVA with repeated measures to test the relative effects of fish oil treatment and age on the measured parameters. A general linear models procedure uti lizing a least squares mean differences test was used to determine statistical significance between the means in each age group.

RESULTS The volunteers reported no side effects due to in gestion of the fish oil capsules. The subjects main tained their weight through the study. Compliance was confirmed by the significant increase in plasma EPA and DHA (Table 1) in all women. Plasma fatty acids. Table 1 shows that older women had a significantly greater increase in EPA (P < 0.001) and DHA (P < 0.05) than did young women (10-fold increase for EPA and 2.5-fold increase for DHA in older women vs. 8-fold increase for EPA and 2-fold increase for DHA in young women). More detailed results on the change of fatty acid com position with fish oil supplementation will be re ported elsewhere. However, note that after fish oil supplementation, plasma linoleic acid level decreased in young women (34.54 ±0.86 vs. 32.30 ±0.65%

normalized concentration; P < 0.05). Dihomogamma linoleic acid, following fish oil supplementation, decreased significantly (P < 0.001) in both age groups (1.49 ±0.04 vs. 1.05 ±0.09% normalized concen tration in young women, 1.65 ±0.06 vs. 0.93 ±0.05% normalized concentration in older women). Although arachidonic acid reduction was not significant, the arachidonic acid:EPA ratio was decreased signifi cantly (P < 0.001) in both age groups, and the re duction was more dramatic in the older women (12.67 ±1.38 vs. 1.63 ±0.31) than in young women (11.00 ± 1.38 vs. 0.83 ±0.07) (13-fold decrease in older women vs. 8-fold decrease in young women). The ratio of total unsaturated fatty acids (UFA) to saturated fatty acids (SFA) did not change significantly, whereas the ratio of polyunsaturated fatty acids (PUFA) to SFA in both age groups significantly (P < 0.01) increased after fish oil supplementation. No significant difference was found between the two age groups for the latter ratio. Plasma triglycéride.Figure 1 shows that the level of plasma total TG at baseline level was significantly (P < 0.05) higher in older women than in young women (0.89 ±0.13 vs. 0.55 ±0.06 mg/mL). Plasma total TG in both age groups decreased significantly after fish oil supplementation (30% reduction in older women and 22% reduction in young women). Plasma vitamin E. The concentration of cc-tocopherol prior to fish oil supplementation was signifi cantly (P < 0.05) higher in older women than in young women (13.65 ±1.49 vs. 8.45 ±1.37 ¿ig/mL).Plasma a-tocopherol level of both age groups did not change significantly after fish oil supplementation (Fig. 2). However, in young women, plasma a-tocopherol at mo 3 relative to mo 1 of fish oil supplementation was significantly (P < 0.05) decreased. The relative concen trations of plasma oc-tocopherol:TG are depicted in Figure 3. At baseline, the oc-tocopherol:TG ratio was essentially the same for both age groups. The cc-tocopherohTG ratio after fish oil supplementation was

TABLE 1 Change in plasma fatty acid composition

before and after 3 mo of (n-3) fatty acid supplementation

Older women

Young women (n - 14) Fatty acid1

Before

After

in young and older women1

Before

|n - 9)

After

concentrationEPA % Normalized (20:5n-3)DHA 0.051.78 ± 0.493.53 ± 0.061.76 ± 0.254.51 ± |22:6n-3)UFA:SFAPUFA:SFA0.63 0.131.99 ± 0.261.99 ± 0.152.17 ± 0.272.15 ± 0.030.89 ± 0.030.98 ± 0.070.86 ± 0.051.02 ± ±0.025.04 ±0.020.00010.00010.97000.00900.72 ±0.037.43 ±0.020.00010.00010.86000.0003 'Results are expressed as means ±SEM.A general linear models procedure utilizing a least squares mean differences test was performed for mean comparisons in each age group. Abbreviations used: EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; UFA, unsaturated fatty acids; SFA, saturated fatty acids,PUFA, polyunsaturated fatty acids. Downloaded from https://academic.oup.com/jn/article-abstract/121/4/484/4754632 by Washington University in St. Louis user on 12 April 2018

p i" i' 'i 487

FISH OIL AND VITAMIN E INTERACTION

16 i 14

I o I-I o o

121086 4 OLDER WOMEN

OLDER WOMEN YOUNG WOMEN

2

YOUNG WOMEN

0.0 1

2

Month FIGURE 1 Change of plasma total triglycéridewith fish oil supplementation. Results are expressed as means ±SEM for 15 young and 10 older women. A general linear models procedure utilizing a least squares mean differences test was performed for mean comparisons in each age group. Means in a curve not sharing a common letter are significantly different (P < 0.05).

significantly increased in both young and older women. However, older women showed a relatively greater increase than did young women (44 vs. 18%). The relationship of a-tocopherol to plasma fatty acids was further investigated and presented in Table 2. The relative concentration of a-tocopherol:UFA or PUFA did not change significantly after 3 mo of fish oil supplementation, whereas concentration of a-to copherol relative to total of EPA + DHA significantly decreased. This reduction was 4.9-fold for older women and 3.6-fold for young women. Plasma lipid peroxides. Figure 4 shows the change of plasma lipid peroxide (expressed as MDA equiva lent) with fish oil supplementation. Both age groups exhibited a significant increase of plasma MDA up to mo 2 of fish oil supplementation, following which the level declined but still tended to be greater than the level before supplementation. Prior to fish oil supple mentation, the level of plasma MDA was not signifi cantly different between the two groups. However, after 2 mo the older women had significantly (P < 0.01) higher MDA levels than did young women (6.23 ±0.75 vs. 4.05 ±0.45 nmol/mL). Change in the ratio of plasma MDA:TG with fish oil supplementation is shown in Figure 5. Both age groups showed a signif icant increase of MDA:TG ratio, which reached a Downloaded from https://academic.oup.com/jn/article-abstract/121/4/484/4754632 by Washington University in St. Louis user on 12 April 2018

Month FIGURE 2 Change of plasma a-tocopherol with fish oil supplementation. Results are expressed as means ±SEM for 15 young and 10 older women. A general linear models procedure utilizing a least squares mean differences test was performed for mean comparisons in each age group. Means in a curve not sharing a common letter are significantly different (P < 0.05).

maximum point after 2 mo, trien decreased at 3 mo of fish oil supplementation,- again, the level was still significantly higher than before fish oil supplementa tion. No difference in this ratio between young and older women was observed before or after fish oil supplementation.

DISCUSSION The results of this study indicate that although dietary supplementation with fish oil has beneficial effects on health by lowering plasma TG, it substan tially increases the highly oxidizable (n-3) fatty acids of plasma. Einsella et al. (13) reported that (n-3) fatty acids increase in other tissues. This alteration in fatty acid composition makes tissue and plasma more sus ceptible to free radical attack and lipid peroxidation. In the process of refining and deodorizing fish oil extracts, the natural antioxidants are destroyed (14). Manufacturers of fish oil capsules add synthetic anti oxidants and vitamin E to prevent this highly un stable oil from oxidation and to extend the product's shelf-life (14). The observation that dietary fish oil supplementation for 3 mo increased the plasma lipid peroxides in young and older women suggests that the presence of 1 iu of vitamin E in each capsule con-

MEYDANI ET AL.

488

26 24 22 20 18

o

i

16 14

C

12 10

8 6 4

OLDER WOMEN

OLDER WOMEN

YOUNG WOMEN

YOUNG WOMEN

2

£0123

«

0

Month

FIGURE 3 Change in the ratio of plasma ct-tocopherol to total triglycéride (TG) with fish oil supplementation. Results are expressed as means ±SEM for 15 young and 10 older women. A general linear models procedure utilizing a least squares mean differences test was performed for mean comparisons in each age group. Means in a curve not sharing a common letter are significantly different [P < 0.05).

taining 280 mg of EPA and 120 mg of DHA may not be sufficient to protect the tissue from free radical attack and lipid peroxidation. Both young and older women demonstrated a sig nificant elevation in plasma MDA up to mo 2 of supplementation, with a slight decrease at mo 3; values were still greater than baseline although not

1

2

Month FIGURE 4 Change of plasma lipid peroxides with fish < supplementation. Results are expressed as means ±SEMof malondialdehyde (MDA) equivalent of lipid peroxides for 15 young and 10 older women. A general linear models pro cedure utilizing a least squares mean differences test was performed for mean comparisons in each age group. Means in a curve not sharing a common letter are significantly different (P < 0.05).

significantly elevated (Fig. 4). These changes were not influenced by the significant reduction in total TG (Fig. 5). The significant elevation in the concentration of EPA and DHA with five and six double bonds, and the decrease of fatty acids with lower number of double bonds ¡linoleicand dihomogamma linoleic acids with 2 and 3 double bonds, respectively) should

TABLE 2

Plasma a-tocopherol to plasma fatty add ratios before and after 3 mo of (n-3) fatty acid supplementation in young and older women1 14)a-T:fatty

Young women (n -

9)Before0.195

women (n =

acid1a-T:UFA

±0.023 ±0.024 0.6200 0.284 ±0.033 0.268 ±0.031 0.7300 0.0003Older 5.590 ±0.860After0.208 1.140 ±0.140P0.6800 0.0001 'Results are expressed as means ±SEM.A general linear models procedure utilizing a least squares mean differences test was performed for mean comparisons in each age group. 1Abbreviations used: o-T, d-a-tocopherol; UFA, unsaturated fatty acids; FUFA, polyunsaturated fatty acids; EPA, eicosapentaenoic acid; DHA, docosahcxaenoic acid. ±0.019 ±0.220 a-T:PUFA 0.193 ±0.034 0.172 ±0.025 a-T:EPA + DHABefore0.137 3.790 ±0.630After0.123 1.060 ±0.150P0.8700

Downloaded from https://academic.oup.com/jn/article-abstract/121/4/484/4754632 by Washington University in St. Louis user on 12 April 2018

FISH OIL AND VITAMIN E INTERACTION

14 i

OLDER WOMEN YOUNG WOMEN

Month FIGURE 5 Change in the ratio of plasma lipid peroxides (MDA) to total triglycéride(TG) with fish oil supplementa tion. Results are expressed as means ±SEM for 15 young and 10 older women. A general linear models procedure uti lizing a least squares mean differences test was performed for mean comparisons in each age group. Means in a curve not sharing a common letter are significantly different [P < 0.05).

be regarded as the main contributory factor. The higher the number of double bonds, the greater the chance of free radical insult and the greater the yield of MDA per number of double bonds (15). In addition, the increase in plasma PUFA:SFA ratio (Table 1) may be a contributing factor in the increase of plasma MDA in this study. Decreased hepatic secretion of VLDL has been con sidered to be the major contributing factor for the hypotriglyceridemic effect of fish oil (1, 16—18). This effect is reported to occur with concomitant en hancement of peroxisomal ß-oxidationof fatty acids and increases in catalase and glutathione-S-transferase activity (19, 20). Some glutathione-S-transferases have glutathione peroxidase activity toward organic hydroperoxides (21). Thus, fatty acid hydroperoxides would be good substrates for glutathione-S-transfer ases, which reduce them to the corresponding al cohol. Therefore, the decreased plasma MDA at the end of mo 3 of fish oil supplementation in this study might result from an adoptive enzymatic response of Downloaded from https://academic.oup.com/jn/article-abstract/121/4/484/4754632 by Washington University in St. Louis user on 12 April 2018

489

body, i.e., glutathione-S-transferase induction, to reduce (n-3) fatty acids hydroperoxides generated from oxidative metabolism. In this study, older women demonstrated a more dramatic change in the plasma fatty acid composition than did young women (Table 1), and the plasma MDA of the older women at mo 2 of fish oil supple mentation was significantly higher than that of the young women (Fig. 4). Increased intestinal fatty acid absorption and decreased fatty acid metabolism with aging (22, 23) may account for the significant increase in plasma (n-3) fatty acids in older women. In addi tion, older women were postmenopausal, a condition in which female hormones are reduced (24), as was the case in this study (data not shown). Female hor mones (including estradici, estriol and estrone) have been reported to have the antioxidant capacity to reduce plasma lipid peroxides (25). Therefore, these age-associated physiological changes (i.e., increased intestinal absorption and the decreased level of female hormones) and the higher level of fish oil fatty acids might be contributing factors for the relatively higher MDA level observed in the plasma of older women supplemented with fish oil capsules for 3 mo. We reported earlier (26) that fish oil diets reduced plasma and tissue vitamin £in mice and that this effect was more pronounced in aged animals. In creased requirement for vitamin E with high intake of PUFA has been suggested (27). However, the rela tionship may not be linear because a high intake of PUFA may also impair the absorption of vitamin E from the intestines (28, 29). Muggli (30) has proposed a mathematical equation for estimating the vitamin E requirement based on the amount and number of double bonds present in PUFA. Muggli indicated that the typical commercially available fish oil supple ments do not contain an adequate amount of vitamin E. Our analysis of commercially available fish oil supplements has demonstrated that some contain less than 1 lu vitamin E per capsule and have lower vi tamin E to (n-3) fatty acid ratio (31). Based on the present study, intake of these products for 3 mo may compromise vitamin E status and potentiate lipid peroxidation. Furthermore, results of this study demonstrated that plasma vitamin E was not in creased despite the daily intake of 6 lu of vitamin E in Pro-Mega fish oil capsules. The expression of vitamin E per unit of total lipid has been suggested to be a better estimate of vitamin E status (32). However, in this study, where the plasma fatty acid composition was dramatically changed to a highly oxidizable fatty acid and the level of TG decreased without significant change of plasma vitamin E, the expression of vi tamin E per unit of TG or per unit of total lipid can be misleading in evaluating vitamin E status. In addi tion, despite the increased plasma vitamin E:TG, young and older women demonstrated a substantial decrease in a-tocopherol:(EPA + DHA) (Table 2) and a

490

MEYDANI ET AL.

significant increase in plasma MDA, suggesting that concentration of vitamin E in plasma and possibly in the other tissues was not adequate to protect highly oxidizahle PUFA from oxygen-free radical attack. Thus, vitamin E content of fish oil supplements may not be sufficient to protect users from oxidative damage. Our findings are particularly important for aged subjects known to have a higher level of plasma lipid peroxides (33), patients with diabetes and liver diseases (34, 35), patients under adriamycin therapy (36, 37) and patients with other conditions in which lipid peroxidation may be augmented with indiscrim inate consumption of fish oil and its (n-3) fatty acid concentrates. Doubling or tripling of vitamin E content of fish oil supplements has been proposed to prevent the possible harmful effect of these products with regard to their long-term use (30). However, increasing the vitamin E content of fish oil supple ments should be considered carefully, particularly with respect to the modulation of prostaglandins and leukotrienes, which are known to be affected by these nutrients (1, 13, 38-40).

LITERATURE CITED 1. Herold, P. M. & Kinsclla, J. E. (1986) Fish oil consumption and decreased risk of cardiovascular disease: a comparison of findings from Animal and human feeding trials. Am. J. Clin. Nutr. 43: 566-598. 2. Glomset, J. A. (1985) Fish, fatty acids, and human health. N. Engl. J. Med. 312: 1253-1255. 3. Kromhout, D., Bosschieter, E. B. & Coulander, C. de L. (1985) The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N. F.ngl. J. Med. 312: 1205-1209. 4. Kagawa, Y., Nishizawa, M., Suzuki, M., Miyatake, T., Hamamoto, T., Goto, K., Motonaga, E., Izumikawa, H., Hirata, H., & Ehihara, A. (1982) Eicosapolyenoic acid of serum lipids of Japanese islanders with low incidence of cardiovascular disease. J. Nutr. Sci. Vitaminol. 28: 441-443. 5. Hams, W. S. &. Conner, W. E. (1980) The effects of salmon oil upon plasma lipids, lipoproteins and triglycéride clearance. Trans. Assoc. Am. Physicians 43: 143-155. 6. MacKenzie, G. G., MacKenzie, J. B. & McCollum, E. U. (1941) Uncomplicated vitamin E deficiency in the rabbit and its relation to the toxicity of cod liver oil. J. Nutr. Sci. 21: 225-234. 7. Piche, L. A., Draper, H. H. &. Cole, P. D. (1988) Malondialdehyde excretion by subjects consuming cod liver oil versus a concentrate of n-3 fatty acids. Lipids 23: 370-371. 8. I lai li we 11,B. (1987) Oxidan ts and human disease: some new concepts. FASES J. 1: 358-364. 9. McNamara, J. R. & Schaefer, E. J. (1987) Automated enzymatic standardized lipid analyses for plasma and lipoprotein frac tions. Clin. Chini. Acta 1266: 1-8. 10. Meydani, M., Cohn, J. S., Macauley, J. B., McNamara, J. R., Blumberg, J. B. &. Schaefer, E. J. (1989) Postprandial changes in the plasma concentration of a- and y-tocopherol in human subjects fed a fat-rich meal supplemented with fat-soluble vitamins. J. Nutr. 114: 1252-1258. 11. Handelman, G. J., Epstein, W. L., Machlin, L. J., Van Kuijk, J.GJVI. &.Dratz, E. A. (1988) Biopsy method for human adipose with vitamin E and lipid measurements. Lipids 23: 598-604. 12. Yagi, K. (1984) In: Methods in Enzymology (Packer, L. ed.), vol. Downloaded from https://academic.oup.com/jn/article-abstract/121/4/484/4754632 by Washington University in St. Louis user on 12 April 2018

105, pp. 328-331, Academic Press, New York, NY. 13. Kinsella, J. E., Lokesh, B., German, B. J., Swanson, J. &. Zunig, M. (1987) Eicosan oid synthesis and membrane enzymes are affected by dietary fat level and ratios of n-6 and n^3 polyunsaturated fatty acids. In: Proceedings of the AOCS Short Course on Polyunsaturated Fatty Acids and Eisosanoids (Lands, W.E.M., ed.), pp. 416-421, American OU Chemists' Society, Champaign, IL. 14. Lands, W.E.M. (1986) Fish and Human Health, Academic Press, Orlando, PL. 15. Bruna, E., Petit, E., Beijean-Leymarie, M., Huynh, S. & Nouvelot, A (1989) Specific susceptibility of docosahexaenoic acid and eicosapentaenoic acid to peroxidation in aqueous solution. Lipids 24: 970-975. 16. Nestel, P. J., Connor, W. E., Reardon, M. F., Connor, S., Wong, S. & Boston, R. (1984) Suppression by diets rich in fish oil of very low density lipoprotein production in man. J. Clin. Invest. 74: 82-89. 17. Wong, S. H., Nestel, P. J., Trimble, R. P., Storere, G. B., fflman, R. J. &. Topping, D. L. (1984) The adaptive effects of dietary fish and safflower oil on lipid and lipoprotein metabolism in perfused rat liver. Biochim. Biophys. Acta 792: 103-109. 18. Phillipson, B. E., Rothrock, D. W., Connor, W. E., Harris, W. S. & Ulingworth, D. R. (1985) Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia. N. Engl. J. Med. 312: 1210-1216. 19. Yamazaki, R. K., Shen, T. &. Schade, G. B. (1987) A diet rich in (n-3) fatty acids increases peroxisomal ß-oxidationactivity and lowers plasma triglycerols without inhibiting glutathione-dependent detoxification activities in the rat liver. Biochim. Biophys. Acta 920: 62-67. 20. Wade, A. E. &.Bunce, O. R. (1987) Influence of dietary omega-3 and omega-6 fatty acids on drug and carcinogen metabolism and on the promotion of DMBA induced mammary tumors. In: Proceedings of the AOCS Short Course on Polyunsaturated Fatty Acids and Eicosanoids (Lands, W.E.M., éd.), pp. 544-548, American Oil Chemists' Society, Champaign, IL. 21. Tu, C.PX). &. Reddy, C. C. (1985) On the multiplicity of rat liver glutathione-S-transferases. J. Biol. Chem. 260: 9961-9964. 22. Hollander, D., Dadufalza, V. D. &. Sletten, E. G. (1984) Does essential fatty acid absorption change with aging? J. Lipid Res. 25: 129-134. 23. Suzuki, H., Hayakawa, S., Tamura, S., Wada, S. &. Wada, O. (1985) Effect of age on the modification of rat plasma lipids by fish and soybean oil diets. Biochim. Biophys. Acta 836: 390-393. 24. Goldin, B. R., Adelcreutz, H., Gorbach, S. L., Woods, M. N., Dwyer, J. T., Cordon, T., Bohn, E. &.Gershoff, S. N. (1986) The relationship between estrogen levels and diets of Caucasian American and oriental immigrant women. Am. J. Clin. Nutr. 44: 945-953. 25. Yagi, K. &. Komura, S. (1986) Inhibitory effect of female hor mones on lipid peroxidation. Biochem. Int. 13: 1051-1055. 26. Meydani, S. N., Shapiro, A. C., Meydani, M., Macauley, J. B. &. Blumberg, J. B. (1987) Effect of age and dietary fat (fish oil, com oil, and coconut oil) on tocopherol status of C57/BL6 Nia mice. Lipids 22: 345-350. 27. Draper, H. H. (1980) Nutrient interrelationships. In: Vitamin E, A Comprehensive Treatise (Machlin, L. J., éd.), pp. 272-288, Marcel Dekker, New York, NY. 28. Gallo-Torres, H. E. (1980) Absorption. In: Vitamin E, A Com prehensive Treatise (Machlin, L. J., éd.), pp. 170-267, Marcel Dekker, New York, NY. 29. Leka, L. S., Remaly, K. M., Bizinkauskas, P. A. &. Meydani, M. (1989) Effects of fish oil on intestinal absorption of vitamin E in the rat. FASEB J. 3: A951 (abs.). 30. Muggli, R. (1989) Dietary fish oils increase the requirement for vitamin E in humans. In: Health Effects of Fish and Fish Oil (Chandra, R. K., éd.),pp. 201-210, ARTS Biomedicai Pub lishers and Distributors, St. John's, Newfoundland, Canada.

FISH OIL AND VITAMIN E INTERACTION

491

31. Shapiro, A. C., Meydani, S. N., Meydani, M., Morrow, F., Blumberg, J. B., Endres, S. & Dinarello, C. A. (1989) The effect of fish oil supplementation on plasma alpha-tocopherol, retinol levels. In: Health Effects of Fish and Fish Oil (Chandra, R. K., éd.), pp. 537-546, ARTS Biomedicai Publishers and Dis tributors, St. John's, Newfoundland, Canada.

(Yagi, K., éd.), pp. 255-269, Academic Press, New York, NY. 37. Baird, M. B. &. Hough, N. L. (1987) Enhancement of adriamycin toxicity and lipid peroxidation by dietary fish oils. In: Proceedings of the AOCS Short Course on Polyunsaturated Fatty Acids and Eicosanoids (Lands, W.E.M., éd.), pp. 501-503, American Oil Chemists' Society, Champaign, IL.

32. Farrell, P. M., Mischler, E. H. &. Gutcher, G. R. (1982) Evalu ation of vitamin E deficiency in children with lung disease. Ann. New York Acad. Sci. 393: 96-106. 33. Poubelle, P., Chaintreuil, J., Bensadoun, J., Blotman, F., Simon, L. & Crastes de Faulet, A (1982) Plasma 1ipoperoxidcs and aging. Biomed. 36: 164-166. 34. Yagi, K. (1987) Lipid peroxides and human diseases. Chem. Phys. Lipids 45: 337-351. 35. Suematsu, T. & Abe, H. (1982) Liver and serum lipid peroxide levels in patients with liver disease. In: Lipid Peroxides in Biology and Medicine (Yagi, K., éd.), pp. 285-293, Academic Press, New York, NY. 36. Ogura, R. (1982) Adnamycm-induced lipid peroxidation and its protection. In: Lipid Peroxidation in Biology and Medicine

38. Mosconi, C., Colue, S., Medini, L., Straglio t to, E., Madcrna, P., Tremoli, E. &.Galli, C. (1988) Vitamin E influences the effects of fish oil on fatty acids and eicosanoid production in plasma and circulating cells in the rat. Biochem. Pharmacol. 17: 3415-3421. 39. Meydani, S. N., Meydani, M., Verdón, C. P., Shapiro, A C., Blumberg, f. B. &. Hayes, K. C. (1986) Vitamin E supplemen tation suppresses prostaglandin E synthesis and enhances the immune response of aged mice. Mech. Aging Dev. 34: 191-201. 40. Meydani, M, Meydani, S. N., Macauley, J. B. &.Blumberg, J. B. (1985) Influence of dietary vitamin E and selenium on the exvivo synthesis of prostaglandins E2 in brain regions of young and old rats. Prostaglandins Leukotrienes Med. 18: 337-346.

Downloaded from https://academic.oup.com/jn/article-abstract/121/4/484/4754632 by Washington University in St. Louis user on 12 April 2018

Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women.

Fifteen young (22-35 y) and 10 older (51-71 y) women received six capsules of fish oil (Pro-Mega)/d, providing a total of 1,680 mg eicosapentaenoic (E...
1MB Sizes 0 Downloads 0 Views