![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
, 5,,
* Department of Nutrition and Food Management, Oregon State University, Corvallis, OR 97331-5103; College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331-4802 and ** Science and Technology Center, Hill's Pet Nutrition, Inc., Topeka, KS 66601-1658
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGMENT
FOOTNOTES
LITERATURE CITED
ABSTRACT 
We studied the effects of feeding experimental diets containing (n-6) to (n-3) fatty acid ratios of 31:1, 5.4:1, and 1.4:1 to 20 healthy female geriatric Beagles (9.5-11.5 y) for 8-12 wk on various indices of the immune response. Compared with the 31:1 diet, consumption of the 5.4:1 and 1.4:1 diets significantly increased (n-3) fatty acids in plasma (2.17 ± 0.64, 9.05 ± 0.64, 17.46 ± 0.64 g/100 g fatty acids, respectively, P < 0.0001). Although supplementation with (n-3) fatty acids did not significantly alter the humoral immune response to keyhole limpet hemocyanin (KLH), it significantly suppressed the cell-mediated immune response based on results of a delayed-type hypersensitivity (DTH) skin test. The DTH response after intradermal injection of KLH at 24 h was significantly lower in the group consuming the 1.4:1 diet compared with the group consuming the 5.4:1 (P = 0.02) or the 31:1 diets (P = 0.04), and remained significantly suppressed at 48 h in the group fed 1.4:1 relative to the group fed 31:1. After consumption of the 1.4:1 diet, stimulated mononuclear cells produced 52% less prostaglandin E2 (PGE2) than those from dogs fed the 31:1 diet (224 ± 74 and 451 ± 71 pmol/L, respectively, P = 0.04). Plasma concentration of 
-tocopherol was 20% lower in dogs fed the 1.4:1 diet compared with those fed the 31:1 diet (P = 0.04), and lipid peroxidation was greater in both plasma (P = 0.03) and urine (P = 0.002). These data suggest that although a ratio of dietary (n-6) to (n-3) fatty acids of 1.4:1 depresses the cell-mediated immune response and PGE2 production, it increases lipid peroxidation and lowers vitamin E concentration.
INTRODUCTION
The potential therapeutic benefits of dietary supplementation with (n-3) fatty acids, found in large concentrations in fish oil, have aroused great interest. However, experimental data are few concerning the correct ratio of (n-6) to (n-3) fatty acids in the diet that is necessary to maximize benefits (Neuringer et al. 1988
).
The beneficial effects of (n-3) fatty acids are derived in part from their effect on the immune system. Metabolism of arachidonic acid (AA),6 derived from the (n-6) fatty acid, linoleic acid, and eicosapentaenoic acid (EPA), derived from the (n-3) fatty acid, -linolenic acid, leads to the generation of eicosanoids such as prostaglandins and leukotrienes. The eicosanoids derived from AA and EPA have very similar molecular structures but markedly different biologic effects. For example, the EPA-derived eicosanoids are in general much less potent inducers of inflammation than the AA-derived eicosanoids. Consequently, a predominance of (n-6) fatty acids will result in a proinflammatory status with production of prostaglandins of the 2 series and leukotrienes of the 4 series. As the relative amount of (n-3) fatty acids increases, more prostaglandins of the 3 series and leukotrienes of the 5 series are produced. These eicosanoids are considered to be less inflammatory (Shapiro et al. 1993). A reduction in the amount of the more inflammatory products from AA, prostaglandin E2 (PGE2) and leukotriene B4, has been implicated as an underlying mechanism for the anti-inflammatory effects of fish oil (Meydani and Dinarello 1993). The immune response also may be altered by changes in the production of immunologic mediators such as cytokines. Ultimately, these effects are manifest by changes in cell-mediated immunity as demonstrated by the delayed-type hypersensitivity (DTH) skin test.
The effect of these fatty acids on the immune response may be different in older animals. Meydani, S. et al. (1991) studied the effect of dietary (n-3) fatty acids on cytokine production and lymphocyte proliferation in young and older women and found the changes to be more dramatic in older women.
A possible adverse effect of high levels of dietary (n-3) fatty acids is that their accumulation in tissues may make those tissues more vulnerable to lipid peroxidation, especially if peroxidation overwhelms the normal antioxidant mechanisms. Increased intake of (n-3) fatty acids without adequate antioxidant protection could result in increased free radicals and lipid-oxidative by-products.
Consequently, the purpose of this study was to determine the effect of feeding healthy female geriatric Beagle dogs three different diets with varying (n-6) to (n-3) ratios over an 8- to 12-wk period. We report here the effect of these three diets on in vitro and in vivo indices of the immune response, namely, 
-immunoglobin (IgG) antibody production and the DTH skin test to a specific T-dependent antigen, keyhole limpet hemocyanin (KLH), and eicosanoid production of PGE2. We also report the effect of these three diets on lipid peroxidation, obtained by measuring plasma and urine lipid peroxide levels, and on vitamin E status, obtained by measuring vitamin E concentrations in plasma.
MATERIALS AND METHODS
|
Table 1. Physical characteristics of the beagles1 |
-tocopherol acetate, 7500 mg/kg nicotinic acid, 5000 mg/kg calcium D-pantothenate, 21,770 mg/kg thiamine mononitrate, 1250 mg/kg riboflavin, 2431 mg/kg pyridoxine hydrochloride, 250 mg/kg folic acid, 50 mg/kg biotin and 50 mg/kg vitamin B-12. Calcium carbonate was used as the carrier for the mineral mix, which contained 80 g/kg zinc as zinc oxide, 6.0 g/kg manganese as manganese oxide, 280 mg/kg iodine as calcium iodate, 1.0 g/kg cobalt as cobalt carbonate, 180 mg/kg selenium as selenium selenite and 2.5 g/kg copper as copper chloride. The remaining 2% was provided by added oil. The source of oil for the (n-3) enriched diet was fish oil (Zapata Protein, Reedville, VA). The source of oil for the (n-6) enriched diet was corn oil (Mazola, Englewood Cliffs, NJ). The expected nutrient composition by weight was 71.8% moisture, 7.4% protein, 6.0% fat, 2.0% ash, 0.6% crude fiber and the remainder carbohydrate. The diets were analyzed by Woodson-Tenent Laboratories (Des Moines, IA) and shown to be within expected analytical variance of these targets. The fatty acid composition of the three diets is given in Table 2. Total vitamin E levels of the two fish oil diets were adjusted at 137 ± 8 mg/kg, the concentration in the low (n-3) diet, with an (n-6) to (n-3) fatty acid ratio of 31:1, by adding the appropriate amount of -tocopherol.
|
Table 2. Composition of selected fatty acids of the experimental diets1 |
and Krakowka et al. (1987). Briefly, cells were separated from a 1:1 dilution of blood and Dulbecco's phosphate-buffered saline (DPBS; Sigma Chemical, St. Louis, MO) by layering the blood-DPBS mixture over Histopaque 1077 (Sigma) and centrifuging 30 min at 900 × g. Cells were washed twice in Hanks' balanced salt solution (HBSS, Sigma) and resuspended in RPMI 1640 supplemented with 100,000 U/L penicillin, 100 mg/L streptomycin, 2 mmol/L L-glutamine and 10% fetal calf serum (Sigma) to the original blood volume. An aliquot of the cell suspension was used to determine cell numbers with a hemocytometer, and cell viability was assessed by trypan blue exclusion. The remaining mononuclear cells were centrifuged for 10 min at 400 × g and resuspended in RPMI 1640 containing 5% fetal calf serum for a final concentration of 2 × 109 cells/L.
70°C for subsequent PGE2 analysis. A flask containing medium only was processed identically and supernatant was harvested for use as a control. PGE2 concentration was determined by Ken Allen, Department of Food Science and Human Nutrition, Colorado State University, using RIA (Bottje et al. 1993).
, except that the ingredients were sonicated rather than ground. Briefly, 1.0 g/L KLH, 50 mL/L hexadecane, 35 mL/L Tween 80, 15 mL/L Span 80 and 2 mL/L T1501 were emulsified and added to normal saline solution. Fourteen days later (d 74), a second 0.5-mL intramuscular injection was given. One day later (d 75), the intradermal skin tests were performed. To accomplish this, a large rectangular patch was gently clipped on the lateral side of the chest of each dog. Individual disposable tuberculin syringes were filled with heat-aggregated KLH; saline (0.9%), the negative control; or histamine base (0.1 g/L), a positive control for the immediate skin test reaction of a sensitive dog when challenged with an offending antigen (Histatrol, Center Laboratories, Port Washington, NY). A 25-gauge needle was used to inject 0.05 mL of each of these intradermally. The 0.05-mL dose of heat-aggregated KLH consisted of ~3 mg of KLH. The KLH was heat aggregated according to the method of Exon et al. (1990). Briefly, 120 mg soluble KLH (Calbiochem-Novabiochem, La Jolla, CA) dissolved in 6 mL normal saline solution was heat aggregated in an 80°C water bath for 1 h. The resultant gel was centrifuged twice at 400 × g for 10 min, removing the saline layer each time. The gel was then dispersed by passing it through a 23-gauge needle once, and through a 25-gauge needle twice, carefully avoiding air bubbles. The sites of injection were marked with a felt marker. No chemical restraint was needed for the dogs. Examinations were made at 15 and 30 min, at 24, 48, 72 and 96 h, and at 7, 10 and 14 d after intradermal injections. Reactions were recorded according to the diameter of induration and erythema. According to the manufacturer's instructions, a reaction larger than the negative control was considered to be a positive reaction. If a positive reaction to the saline control was observed, the diameter of its induration was subtracted from the other positive reactions. However, by 24 h, no reactions to the saline control were noted. Histamine produced an induration typically 20 mm larger than the saline control at 15 min, after which the reaction subsided. These controls ruled out trauma or the volume of substance injected as the cause of the DTH response. The test was administered by the same person to all dogs.
Keyhole limpet hemocyanin antibody titer.
Humoral immune response was measured as antibody response to KLH. Dogs were injected intramuscularly with 0.5 mL KLH vaccine, as described above, on d 60 and 74. Serum was collected for KLH antibody titer on d 89. Humoral immune response for KLH was measured by a modification of an indirect ELISA procedure previously described by Woodard (1989). Briefly, enzyme immunoassay microtitration plates (ICN Biomedicals, Horsham, PA) were coated with 0.1 mL of DPBS (pH 7.4; 0.01 mol/L) containing 5 mg/L of KLH, covered with parafilm to prevent evaporation, and refrigerated overnight or until needed. Before use, plates were inverted to remove excess coating buffer and washed three times with DPBS containing 0.05% Tween 20. Serum samples (in quadruplicate) were then placed into wells and serial 1:2 dilutions made. The final volume in each well was 0.05 mL. Positive and negative control wells were included on each plate. Coated plates containing serum samples were incubated for 1 h at 37°C while rotating on a platform at 120 rpm. Plates were washed three times with DPBS-Tween 20 to remove unbound antibody. Antibody against dog IgG was conjugated with alkaline phosphatase (Jackson ImmunoResearch Laboratories, West Grove, PA) and diluted 1:5000 with DPBS-Tween 20. Subsequently, 0.1 mL was added to each well for a 1-h incubation at 37°C. Plates were washed three times with DPBS-Tween 20. Phosphate substrate (p-nitrophenyl phosphate disodium·6H2O; 1 g/L; Sigma) was then added to each well (0.15 mL/well). After addition of substrate, plates were allowed to incubate at room temperature until the mean absorbance of the positive control equaled 1.0. The positive control was serum from a dog vaccinated in a previous experiment. Because not all plates developed color at the same rate, a positive control serum was used rather than a specifically timed incubation. Otherwise, data from plate-to-plate and day-to-day could not be compared statistically. After allowing the positive control to reach a mean absorbance of 1.0, the entire plate was read at dual wavelengths, 405 and 492 nm, on an MR 700 spectrophotometer (Dynatech Laboratories, Alexandria, VA). The results are expressed as mean absorbance at 1:8000 and 1:16,000 dilutions of the serum.
Others.
Plasma and urine thiobarbituric reactive substances (TBARS) were measured as previously discussed (Wander et al. 1996b). The fatty acid profile of the plasma was measured by gas chromatography as previously described (Song and Wander 1991) using heptadecanoic acid as an internal standard. The concentration of the fatty acids was expressed as g/100 g fatty acids (Meydani et al. 1993). Double-bond index (DBI) was calculated in the following way: DBI = 2[18:2(n-6) + 20:2(n-6)] + 3[18:3(n-3) + 20:3(n-6)] + 4[20:4(n-6)] + 5[20:5(n-3) + 22:5(n-3)] + 6[22:6(n-3)].
). The total lipid content of plasma was described as the sum of the cholesterol and triglyceride concentrations of plasma (Thurnham et al. 1986). The -tocopherol concentration in plasma was measured simultaneously by HPLC using a fluorometric detector (Wander et al. 1996a) and expressed as µmol/L, µmol/mmol lipid, and µmol/(L·DBI). Urine creatinine was measured by the Jaffe reaction (Wander 1996b). Urine creatinine was used as an internal reference to normalize the concentration of urine TBARS.
). For one variable (PGE2), the data were blocked on weight and a 2-factor ANOVA was used. If a significant difference was found, an LSD post-hoc test (Cochran and Cox 1957) was used to determine the cause of the significant difference. Values were considered significantly different at P
0.10. The data were evaluated using the SAS (Version 6.1, SAS Institute, Cary, NC) General Linear Models procedures. All data were normally distributed about the mean and variances were equal. For all measurements, the following number of dogs comprised each group: 6, 7 and 7 for high, medium and low, respectively, (n-6) to (n-3) fatty acid ratios unless otherwise indicated.
RESULTS
DISCUSSION ACKNOWLEDGMENT 
Fig. 1.
Effect of diets of different (n-3) fatty acid concentrations on the concentration of fatty acids in plasma of geriatric Beagle dogs. Each bar represents the fatty acid concentration after the dogs had consumed the respective diets for 8 wk. Values are means ± SEM, n = 6 or 7. Significant differences were established using a one-factor ANOVA followed by a LSD post-hoc test. Within a group of fatty acids, bars with different letters above them are significantly different (P 0.05). Abbreviations used: (n-6), sum of (n-6) fatty acids; (n-3), sum of (n-3) fatty acids; PUFA, sum of polyunsaturated fatty acids; MUFA, sum of monounsaturated fatty acids; SFA, sum of saturated fatty acids.
[View Larger Version of this Image (27K GIF file)]
), the concentration in the Beagles was not affected (Fig. 2).
Fig. 2.
Effect of diets of different (n-3) fatty acid concentrations on lipid classes in plasma of geriatric Beagle dogs. Each bar represents the concentration after the dogs had consumed the respective diets for 8 wk. Values are means ± SEM, n = 6 or 7. Significant differences were established using a one-factor ANOVA followed by a LSD post-hoc test. Within a lipid class, bars with different letters above them are significantly different (P 0.05).
[View Larger Version of this Image (24K GIF file)]
-tocopherol among all dogs before supplementation occurred. After consumption of the diets, the presence of significant differences depended upon the units used to express tocopherol concentration. Plasma concentration of -tocopherol was lower in dogs fed the high (n-3) diet compared with those fed the low or medium (n-3) diet (P = 0.04) (Fig. 3). Plasma concentration of -tocopherol was also expressed as a function of plasma total cholesterol and triglyceride, and as a function of DBI. No significant difference was noted in -tocopherol concentration for dogs fed the low, medium and high (n-3) diets (16.0 ± 1.5, 16.9 ± 1.4, and 18.1 ± 1.4 µmol/mmol lipid, respectively). When plasma concentration of -tocopherol was expressed relative to the DBI, significant differences were noted among the three diet groups (P = 0.002). The value measured when the high (n-3) diet was consumed (0.346 ± 0.030 µmol/L·DBI) was significantly lower than that measured when the low (0.525 ± 0.032 µmol/L·DBI; P = 0.0007) or medium (n-3) diet was consumed (0.460 ± 0.030 µmol/L·DBI; P = 0.01). The values measured when the low and medium (n-3) diets were consumed did not differ.
Fig. 3.
Effect of diets of different (n-3) fatty acid concentrations on plasma -tocopherol concentration of plasma in geriatric Beagle dogs. Each bar represents the concentration after the dogs had consumed the respective diets for 8 wk. Values are means ± SEM, n = 6 or 7. Significant differences were established using a one-factor ANOVA followed by a LSD post-hoc test. Bars with different letters above them are significantly different (P 0.05).
[View Larger Version of this Image (30K GIF file)]
Fig. 4.
Effect of diets of different (n-3) fatty acid concentrations on lipid peroxidation in plasma and urine measured by the concentration of thiobarbituric acid reactive substances (TBARS) in geriatric Beagle dogs. Each bar represents the concentrations in plasma or urine after the dogs had consumed the respective diets for 8 wk. Values are means ± SEM, n = 6 or 7. Significant differences were established using a one-factor ANOVA followed by a LSD post-hoc test. Within a group of TBARS, bars with different letters above them are significantly different (P 0.05).
[View Larger Version of this Image (34K GIF file)]
Fig. 5.
Effect of diets of different (n-3) fatty acid concentrations on the concentration of prostaglandin E2 (PGE2) in stimulated mononuclear cells of geriatric Beagle dogs. Each bar represents the concentration after the dogs had consumed the respective diets for 8 wk. Values are means ± SEM, n = 6 or 7. Significant differences were established using a two-factor ANOVA followed by a LSD post-hoc test. Bars with different letters above them are significantly different (P 0.07).
[View Larger Version of this Image (21K GIF file)]
Fig. 6.
Effect of diets of different (n-3) fatty acid concentration on the delayed-type hypersensitivity (DTH) skin test in geriatric Beagle dogs challenged with an intradermal injection of keyhole limpet hemocyanin (KLH) to which they had been previously sensitized. Each bar represents the induration diameter after the dogs had consumed their respective diets for 75 d. Values are means ± SEM, n = 6 or 7. Significant differences were established using a one-factor ANOVA followed by a LSD post-hoc test. Bars with different letters above them are significantly different (P 0.05).
[View Larger Version of this Image (42K GIF file)]
, Kromhout et al. 1985, Meydani and Dinarello 1993, Stenson et al. 1992). Although these effects are positive, fish oil supplementation may also have negative effects such as increased lipid peroxidation (Meydani, M. et al. 1991, Wander et al. 1996b). The amount of (n-3) fatty acids or the best ratio of (n-6) to (n-3) fatty acids in the diet that would be necessary to maximize benefits and minimize negative effects has not been established.
) and lipid peroxidation may be more pronounced in this population (Harman 1982). In addition, there is a higher incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids of older women (Meydani, S. et al. 1991) and older male rats (Suzuki et al. 1985) after fish oil consumption. Our results demonstrate that feeding a diet with a high content of (n-3) fatty acids, such that the (n-6) to (n-3) fatty acid ratio is 1.4:1, has significant effects on several of these variables in healthy female geriatric Beagle dogs.
).
observed a decrease in the induration index in normolipidemic humans consuming a low fat, high fish diet for 24 wk compared with when they consumed a low fat, low fish diet. Yoshino and Ellis (1987) showed that rats fed fish oil concentrate had lower DTH responses than those fed water, oleic acid or safflower oil. The mechanism underlying the change in the DTH response is not clear. Meydani et al. (1993) showed that production of cytokines interleukin (IL)-1
, tumor necrosis factor and IL-6 by mononuclear cells was significantly lower in humans after consumption of a low fat, high fish diet compared with a low fat, low fish diet. The decrease in cytokine production may contribute to decreased antigen-presenting cell activity and thus, a decrease in DTH response. An effective immune response may also be blunted following (n-3) fatty acid consumption because dietary fats influence major histocompatibility class II (Ia) antigen expression on cellular membranes, and thus T-lymphocyte proliferation (Huang et al. 1992).
showed that diets enriched in (n-3) PUFA reduced the production of PGE2 by peripheral blood mononuclear cells from nonhuman primates in response to concanavalin A or phytohemagglutinin stimulation by >90%.
). Peripheral blood mononuclear cells from healthy elderly subjects synthesized significantly more PGE2 than did those from young subjects (Meydani et al. 1990). Increased PGE2 production has also been demonstrated in aged mice (Meydani et al. 1986). The combination of increased (n-3) fatty acid intake and aging has pronounced effects on PGE2 production. Meydani, S. et al. (1991) showed that the decrease in PGE2 production after (n-3) fatty acid supplementation was more dramatic with increasing age.
). Eicosanoids regulate the production of several cytokines. Therefore, if an increase in (n-3) PUFA intake altered eicosanoid production, then it would also be expected to affect cytokine production and hence biologic function (Meydani and Dinarello 1993). Because cells of the immune system are the main source and major target for cytokines, changing cytokine production could have profound consequences on the immune response. However, it is generally agreed that an increase, not a decrease, in the concentration of PGE2 suppresses T cell-mediated function (Meydani 1995). In this study, the decrease in both PGE2 concentration and the DTH response suggests that the suppressive effect of diets enriched in (n-3) PUFA was independent of the decrease in PGE2 production.
-tocopherol concentrations within the published normal range for Beagle dogs (58.05 ± 13.93 µmol/L; range 42.72-75.00 µmol/L) (Pillai et al. 1993), the depressed DTH response may be related to plasma vitamin E concentrations in our dogs. A deficiency in vitamin E intake has been shown to suppress the immune response in species ranging from rodents to humans (Meydani 1995). Some studies (Alexander et al. 1995) but not necessarily all (Wander et al. 1996a) have shown that high intakes of (n-3) fatty acids lower plasma concentrations of -tocopherol. Consequently, an increased concentration of -tocopherol may be required when diets high in (n-3) fatty acids are consumed (Muggli 1989). In the present study, -tocopherol concentration in each diet was similar and exceeded the calculated requirements by six to eight times, according to the formula described by Muggli (1989). Despite this, plasma -tocopherol concentration was significantly lower in dogs fed the high (n-3) fatty acid diet when the data are expressed on a molar basis. Further, this effect prevailed if the -tocopherol concentrations are expressed relative to the DBI, which is perhaps a better indication of vitamin E status when long-chain PUFA are consumed. Therefore, the suppressed DTH response in this study may be related to changes in the vitamin E status of the dogs.
measured an increase in urine TBARS and an increase in the plasma and urine concentrations of the specific thiobarbituric acid-malondialdehyde adduct in postmenopausal women given a fish oil supplement. Although the impact of lipid hydroperoxides may stem from their effect on the activity of cyclooxygenase and thus the production of PGE2 (Warso and Lands 1983), their effect may also be independent of this modulatory activity. Zoschke and Messner (1984) have shown that human lymphocyte mitogenesis was suppressed by lipid peroxidation products. A rise in lipid peroxide level induced by (n-3) fatty acids could also have contributed to the decrease in DTH skin test responses noted by Meydani et al. (1993). Therefore, the decrease in cell-medicated immunity observed in this study may be the result of an increase in the formation of lipid peroxidation products following (n-3) fatty acid supplementation. Although increased production of lipid peroxidation products in the group consuming high (n-3) might be related to decreasing -tocopherol concentration in the plasma, -tocopherol may not be the only factor protecting against oxidative stress.
, studying human peripheral blood mononuclear cell cultures, found that B cell immunoglobulin production in response to pokeweed mitogen in vitro was depressed by the addition of EPA. In the same study, B cell function assessed by measuring circulating immunoglobulin levels in response to tetanus toxoid was depressed during ingestion of fish oil. The latter study was performed on only one healthy human volunteer whose age was not disclosed. We do not know what effect, if any, age had on the B cell response in this study. Primary antibody response decreases in many species, including dogs, with age (Jaroslow et al. 1974).
-tocopherol while increasing lipid peroxidation in geriatric Beagle dogs. Further studies are required to define the appropriate level of -tocopherol to be consumed when (n-3) fatty acid supplementation occurs and the possible effect of lipid peroxidation products on immune function.
FOOTNOTES
Manuscript received 19 July 1996. Initial reviews completed 20 August 1996. Revision accepted 20 February 1997.
LITERATURE CITED
-tocopherol concentration.
J. Nutr.
1995;
125:2640-2649
-tocopherol in adult dogs.
Lipids
1993;
28:1095-1099
[Medline]
-tocopheryl acetate and fish oil on low-density-lipoprotein oxidation in postmenopausal women with and without hormone-replacement therapy.
Am. J. Clin. Nutr.
1996a;
63:184-193
-Tocopherol influences in vivo indices of lipid peroxidation in postmenopausal women given fish oil.
J. Nutr.
1996b;
126:643-652
This article has been cited by other articles:
|
|
 |
|
  R. L. Lombardi and D. J. Marino Long-Term Evaluation of Canine Perianal Fistula Disease Treated With Exclusive Fish and Potato Diet and Surgical Excision J. Am. Anim. Hosp. Assoc., November 1, 2008; 44(6): 302 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Ballou and E. J. DePeters Supplementing Milk Replacer with Omega-3 Fatty Acids from Fish Oil on Immunocompetence and Health of Jersey Calves J Dairy Sci, September 1, 2008; 91(9): 3488 - 3500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Gura, R. Strijbosch, S. Arnold, C. McPherson, and M. Puder The Role of an Intravenous Fat Emulsion Composed of Fish Oil in a Parenteral Nutrition-Dependent Patient With Hypertriglyceridemia Nutr Clin Pract, December 1, 2007; 22(6): 664 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Rodriguez-Sallaberry, C. Caldari-Torres, W. Collante, C. R. Staples, and L. Badinga Plasma Prostaglandin and Cytokine Concentrations in Periparturient Holstein Cows Fed Diets Enriched in Saturated or Trans Fatty Acids J Dairy Sci, December 1, 2007; 90(12): 5446 - 5452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
The American Animal Hospital Association and the A, AAHA/AAFP Pain Management Guidelines Task Force Me, P. Hellyer, I. Rodan, J. Brunt, R. Downing, J. E. Hagedorn, and S. A. Robertson AAHA/AAFP Pain Management Guidelines for Dogs & Cats J. Am. Anim. Hosp. Assoc., September 1, 2007; 43(5): 235 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Hall, R. A. Picton, M. M. Skinner, D. E. Jewell, and R. C. Wander The (n-3) Fatty Acid Dose, Independent of the (n-6) to (n-3) Fatty Acid Ratio, Affects the Plasma Fatty Acid Profile of Normal Dogs J. Nutr., September 1, 2006; 136(9): 2338 - 2344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Yun and P. Y. Lee Enhanced Fertility After Diagnostic Hysterosalpingography Using Oil-Based Contrast Agents May Be Attributable to Immunomodulation Am. J. Roentgenol., December 1, 2004; 183(6): 1725 - 1727. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Benatti, G. Peluso, R. Nicolai, and M. Calvani Polyunsaturated Fatty Acids: Biochemical, Nutritional and Epigenetic Properties J. Am. Coll. Nutr., August 1, 2004; 23(4): 281 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lessard, N. Gagnon, D. L. Godson, and H. V. Petit Influence of Parturition and Diets Enriched in n-3 or n-6 Polyunsaturated Fatty Acids on Immune Response of Dairy Cows During the Transition Period J Dairy Sci, July 1, 2004; 87(7): 2197 - 2210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lessard, N. Gagnon, and H. V. Petit Immune Response of Postpartum Dairy Cows Fed Flaxseed J Dairy Sci, August 1, 2003; 86(8): 2647 - 2657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Switzer, D. N. McMurray, J. S. Morris, and R. S. Chapkin (n-3) Polyunsaturated Fatty Acids Promote Activation-Induced Cell Death in Murine T Lymphocytes J. Nutr., February 1, 2003; 133(2): 496 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Field, I. R. Johnson, and P. D. Schley Nutrients and their role in host resistance to infection J. Leukoc. Biol., January 1, 2002; 71(1): 16 - 32. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
