Interleukin-1-induced anorexia in the rat. Influence of prostaglandins.

The anorexia associated with acute and chronic inflammatory or infectious conditions is poorly understood. Our objectives were to explore the anorexigenic effects of interleukin-1 (IL-1) in the rat. Recombinant human (rh) IL-1 beta, murine (rm) IL-1 alpha and to a lesser extent rhIL-1 alpha significantly reduced food intake at greater than or equal to 4.0 micrograms/kg i.p. but not at lower doses, in young (200-250 g) meal-fed rats on chow diets. The anorexic effect appears to be mediated by prostaglandins since pretreatment with ibuprofen completely blocked it, and a fish oil based diet abolished it, in comparison to corn oil or chow diets. Fish oil feeding also decreased basal and IL-1 stimulated prostaglandin E2 production by tissues in vitro (liver, brain, peritoneal macrophages) and in the whole body. Constant intravenous infusions of lower doses of IL-1 also diminished food intake, though intravenous boluses did not (reflecting rapid renal clearance). Chronic daily administration of IL-1 caused persistent inhibition of food intake for 7-17 d in chow and corn oil fed rats, but had no effect in fish oil fed rats. There was an attenuation of the effect (tachyphylaxis) after 7 d in corn oil and chow fed rats, but slowed weight gain and lower final weights were observed after 17-32 d of daily IL-1. Old (18-20 mo Fisher 344) rats showed less sensitivity to IL-1 induced anorexia. In conclusion, IL-1 is anorexigenic in the rat, but this is influenced by the structural form of IL-1, the route and chronicity of administration, the source of dietary fat, and the age of the animal. The ability of prior fat intake to influence the anorexic response to IL-1 represents a novel nutrient-nutrient interaction with potential therapeutic implications.

Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment.

Reductions in dietary fat, saturated fat, and cholesterol have been recommended to reduce the risk of heart disease in our society. The effects of these modifications on human cytokine production and immune responses have not been well studied. 22 subjects > 40 yr of age were fed a diet approximating that of the current American (14.1% of calories as saturated fatty acids, [SFA], 14.5% monounsaturated fatty acids [MUFA], 6.1% [n-6] polyunsaturated fatty acids [PUFA], 0.8% [n-3] PUFA, and 147 mg cholesterol/1,000 calories) for 6 wk, after which time they consumed (11 in each group) one of the two low-fat, low-cholesterol, high-PUFA diets based on National Cholesterol Education Panel (NCEP) Step 2 recommendations (4.0-4.5% SFA, 10.8-11.6% MUFA, 10.3-10.5% PUFA, 45-61 mg cholesterol/1,000 calories) for 24 wk. One of the NCEP Step 2 diets was enriched in fish-derived (n-3) PUFA (low-fat, high-fish: 0.54% or 1.23 g/d eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] [121-188 g fish/d]) and the other low in fish-derived (n-3) PUFA (low-fat, low-fish [0.13% or 0.27 g/d EPA and DHA] [33 g fish/d]). Measurements of in vivo and in vitro indexes of immune responses were taken after each dietary period. Long-term feeding of low-fat, low-fish diet enriched in plant-derived PUFA increased blood mononuclear cell mitogenic response to the T cell mitogen Con A, IL-1 beta, and TNF production and had no effect on delayed-type hypersensitivity skin response, IL-6, GM-CSF, or PGE2 production. In contrast, the low-fat, high-fish diet significantly decreased the percentage of helper T cells whereas the percentage of suppressor T cells increased. Mitogenic responses to Con A and delayed-type hypersensitivity skin response as well as the production of cytokines IL-1 beta, TNF, and IL-6 by mononuclear cells were significantly reduced after the consumption of the low-fat, high-fish diet (24, 40, 45, 35, and 34%, respectively; P < 0.05 by two-tailed Student's t test except for IL-1 beta and TNF, which is by one-tailed t test). Our data are consistent with the concept that the NCEP Step 2 diet that is high in fish significantly decreases various parameters of the immune response in contrast to this diet when it is low in fish. Such alterations may be beneficial for the prevention and treatment of atherosclerotic and inflammatory diseases but may be detrimental with regard to host defense against invading pathogens.

Effect of vitamin E on hydrogen peroxide production by human vascular endothelial cells after hypoxia/reoxygenation.

Changes in oxidative stress status play an important role in tissue injury associated with ischemia -- reperfusion events such as those that occur during stroke and myocardial infarction. Endothelial cells (EC) from human saphenous vein and aorta were incubated for 22 h and found to take up vitamin E from media containing 0-60 mM vitamin E in a dose-dependent manner. EC supplemented with 23 or 28 mM vitamin E in the media for 22 h were maintained at normoxia (20% O2, 5% CO2, and balance N2) or exposed to hypoxic conditions (3% O2, 5% CO2, and balance N2) for 12 h, followed by reoxygenation (20% O2) for 30 min. Saphenous EC supplemented with 23 mM vitamin E produced less (p < 0.05) H2O2 than unsupplemented controls, both at normoxic condition (supplemented: 4.9 +/- 0.05 vs. control: 10.9 +/- 1.3 pmol/min/10(6) cells) and following hypoxia/reoxygenation (supplemented: 6.4 +/- 0.78 vs. control: 17.0 +/- 2.7 nmol/min/10(6) cells). In contrast, aortic EC, which were found to have higher superoxide dismutase and catalase activity than EC from saphenous vein, did not produce any detectable levels of H2O2. Following hypoxia/reoxygenation, the concentration of vitamin E in supplemented saphenous EC was 62% lower than cells maintained at normoxia (0.19 +/- 0.03 vs. 0.5 +/- 0.12 nmoles/10(6) cells, p < 0.001); in aortic EC vitamin E content was reduced by 18% following reoxygenation (0.86 +/- 0.16 vs. 0.70 +/- 0.09 nmoles/10(6) cells, p < 0.05). Therefore, enrichment of vitamin E in EC decreases H2O2 production and thus may reduce the injury associated with ischemia-reperfusion events.

Effect of vitamin E on human aortic endothelial cell responses to oxidative injury.

Reactive oxygen species produced by the cells present in the arterial wall may cause oxidative damage to cellular components altering endothelial cell (EC) function. Changes in the EC function appear to play a key role in the pathogenesis of atherosclerosis. Human aortic endothelial cells (HAEC) were employed to investigate the protective role of vitamin E upon exposure of endothelial cells to oxidative stress in vitro. HAEC assimilate d-alpha-tocopherol from the media in a dose-dependent manner. Exposure of HAEC to 16.5 mM of the free radical generator 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) for 16 h decreased cell viability (assessed by trypan blue exclusion) from 90 to 28%. HAEC preincubated with vitamin E at 15, 30, and 60 microM prior to the AAPH exposure resulted in a dose-dependent increase in resistance to oxidative stress and increased cell viability by 37, 66, and 85%, respectively. An increase in prostacyclin (PGI2) production by HAEC in response to AAPH exposure was correlated positively with cell damage and negatively with vitamin E concentration. Interleukin (IL)-1 production also increased in parallel with cell damage induced by AAPH. Vitamin E treatment significantly reduced IL-1 production after AAPH exposure. This modulatory role of vitamin E on HAEC function following exposure to an oxidative stress may reflect its antioxidant protection against lipid peroxidation.

In vitro supplementation with different tocopherol homologues can affect the function of immune cells in old mice.

Alpha-tocophorel (T) is the most common form of vitamin E inplasma and tissues. Alpha-T is also believed to be superior to its homologues beta-T, gamma-T, and delta-T in antioxidant activity. Biological activity of alpha-T has been intensively studied in a number of bodily systems. In contrast, the other homologues have received little attention beyond the evaluation of their relative antioxidant activity. We as well as others have previously shown that alpha-T can enhance cell- mediated immune function of aged animals and humans. Gamma-T is a principal form of vitamin E in the American diet and some cooking oils contain substantial amount of beta-T and delta-T. Thus it is of public health interest to compare their biological effects with than of alpha-t in various systems. In this study, we used an in vitro supplementation protocol to determine immunologic effects of these T homologues on murine splenocytes. The results showed that all four T homologues enhance both spontaneous and mitogen-stimulated lymphocyte proliferation (LP) and the maximal enhancement produced by them was of the same magnitude. The dose range to produce maximal enhancement varied with different homologues. The efficiency was in the order of beta-T approximately delta-T > alpha-T. Interestingly, at 50 (optimal for alpha-T) and 150 micromol/L, while alpha-T enhanced LP, all the other homologues inhibited LP. This inhibition was found to be due to their cytotoxicity at these levels. T homologues had a differential effect on interleukin (IL)-2 and prostaglandin (PG)E(2) production. IL-2 production by mouse splenocytes was not affected by alpha-T or beta-T, but was increased by gamma-T and delta-T. All T homologues, except for beta-T, inhibited PGE(2) alpha-T. Thus, all the T homologues enhance LP. However, the dose required to reach maximal enhancement varies among the homologues. On the other hand, they have a differential effect on IL-2 and PGE(2) production. The difference in nature and magnitude of the effect on immune function does not correlate with their reported relative antioxidant activity and might be due to minor differences in their structure important to their other biological activities.

Effect of functional food ingredients: vitamin E modulation of cardiovascular diseases and immune status in the elderly.

Increased accumulation of free radicals over time reduces the effectiveness of antioxidant defense mechanisms and heightens the vulnerability of older individuals to a variety of oxidative insults and associated pathologic conditions. Both nutritive and nonnutritive components of foods may slow declines in certain body functions. Ingestion of vitamin E, an antioxidant nutrient, in amounts above current recommendations may reduce the risk of cardiovascular disease, enhance immune status, and otherwise modulate important degenerative conditions associated with aging. Early adoption of proper dietary habits helps adults to maintain quality of life as they age. Increased intake of vitamin E through selection of foods with large amounts of that vitamin and daily consumption of 5-8 servings of fruit and vegetables may reduce risk for cardiovascular disease and improve immune function in later life.

Effect of plasma metabolites of (+)-catechin and quercetin on monocyte adhesion to human aortic endothelial cells.

BACKGROUND: Flavonoids may exert their health benefit in cardiovascular disease by modulating monocyte adhesion in the inflammatory process of atherosclerosis. Most in vitro studies used forms of flavonoids present in food rather than forms that appear in plasma after ingestion. OBJECTIVES: We tested the effects of plasma metabolites of (+)-catechin and quercetin on the modulation of monocyte adhesion to human aortic endothelial cells (HAEC) and on the production of reactive oxygen species (ROS). DESIGN: Plasma extracts of flavonoid metabolites were prepared after intragastric administration of pure compounds to rats. The plasma preparations contained sulfate or glucuronide conjugates or both and methylated forms. We measured adhesion of U937 monocytic cells to HAEC and the production of ROS in HAEC when cells were pretreated with either pure compounds or plasma extracts from control or treated rats. Adhesion assays were performed with HAEC stimulated with interleukin (IL)-1 beta or U937 cells activated with phorbol myristyl acetate; ROS were measured after challenging HAEC with IL-1 beta or hydrogen peroxide. RESULTS: Pretreatment of HAEC with (+)-catechin metabolites inhibited U937 cell adhesion to IL-1 beta-stimulated cells, whereas pretreatment with intact (+)-catechin had no effect. Generation of ROS in hydrogen peroxide-stimulated HAEC was inhibited by (+)-catechin, its metabolites, and control plasma extract, whereas ROS generation in IL-1 beta-stimulated HAEC was inhibited by (+)-catechin metabolites only. In contrast, quercetin inhibited U937 cell adhesion to IL-1 beta-stimulated HAEC, whereas its metabolites were not effective. CONCLUSIONS: Metabolic conversion of flavonoids such as (+)-catechin and quercetin modifies the flavonoids' biological activity. Metabolites of flavonoids, rather than their intact forms, may contribute to the reported effects of flavonoids on reducing the risk of cardiovascular disease.

Photon activation analysis as a new technique for body composition studies.

A study was undertaken to demonstrate the usefulness of the recently developed photon activation analysis (PAA) technique for in vivo body composition studies. PAA can be used for direct measurement of total-body oxygen, nitrogen, and carbon. Sequential measurements were made on rats fed diets of 0%, 4.2%, or 20% protein for 6 1/2 wk, and significant changes in body composition were noted. In addition, rats of different ages, strains, nutritional states, and degrees of obesity were included in a comparison of PAA results in vivo with results from chemical analysis after sacrifice of the animals. High positive correlations were found between PAA measurements of carbon and chemical analysis measurements of fat and between PAA measurements of oxygen and chemical analysis measurements of total-body water. A low positive correlation was found between PAA measurements of nitrogen and chemical analysis measurements of protein.

Fatty acid-related functions.

The first recommendations for specific nutrient quantities that must be obtained to support health were made by the US Department of Agriculture before 1939. Hazel Stiebeling was the leader of this effort and the scientific background was published in the Yearbook of Agriculture. The recommendations clearly stated that food must be available to provide the nutrients to support health. The science of nutrition in the United States is engaged in the most thorough review and reexamination of the recommended dietary allowances in at least a generation of nutrition scientists. There is a new awareness of nutrition complexity and the likelihood of identification of new essential nutrients. This meeting was devoted to the search for functional endpoints to reach quantitative estimates of dietary substances needed to support a function. Included in that concept is determining a range of individual needs and identifying factors that alter these needs. We give the rationale for endpoints of fatty acid metabolism related to platelets and the risk of thrombosis, give the rationale for the recommendation for a new nutrient, and show the necessity for including nutrient interaction in the determination of needs for two nutrients.

Assessment of the safety of high-dose, short-term supplementation with vitamin E in healthy older adults.

The effect of daily supplementation of 800 mg dl alpha-tocopheryl acetate for 30 d on general health, nutrient status, hepatic and renal function, intermediary metabolism, hematological status, plasma nutrients and antioxidant status, thyroid hormones, and urinary creatinine concentrations was studied in 32 healthy elderly (> 60 y) people who participated in a double-blind, placebo-controlled, residential trial. The subjects reported no side effects due to the supplements. Supplementation had no effect on body weight, plasma total protein, albumin, glucose, total cholesterol and triglycerides, conjugated and unconjugated bilirubin, alkaline phosphatase, indicators of hepatic and renal function, hematologic status, thyroid hormones, or serum and urinary creatinine concentrations and creatinine clearance. Supplementation did cause a significant increase in serum vitamin E, and a small (5%) but significant (P < 0.05) increase in plasma zinc in the vitamin E-supplemented group. Thus, short-term supplementation with 800 mg vitamin E/d has no adverse effect on healthy older adults.

Immunologic effects of marine- and plant-derived n-3 polyunsaturated fatty acids in nonhuman primates.

The effect of marine- and plant-derived n-3 polyunsaturated fatty acids (PUFAs) on T cell-mediated immune response was studied in cynomolgus monkeys. Animals were first fed a 14-wk baseline diet; 10 animals were then fed diets containing 1.3% or 3.3% of energy as eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) which the other 10 were fed diets containing 3.5% or 5.3% of energy as alpha-linolenic acid (ALA) for two consecutive 14-wk periods. Both diets significantly decreased the percentage of T cells (except 1.3% EPA + DHA), T helper cells (except 1.3% EPA + DHA and 3.5% ALA), and T suppressor cells. Proliferative response of lymphocytes to T cell mitogens significantly increased after the diet containing 3.3% EPA + DHA. Interleukin 2 production significantly increased after the diets containing 1.3% and 3.3% EPA + DHA. No significant changes in mitogenic response or interleukin 2 production were found after ALA diets. Feeding 1.3% or 3.3% EPA + DHA or 5.3% ALA significantly suppressed prostaglandin E2 production in response to T cell mitogens. Plasma tocopherol concentrations were decreased significantly only in monkeys fed ALA diets. We conclude that after adjustment for the tocopherol concentration, marine-derived n-3 PUFAs but not plant-derived n-3 PUFAs increased T cell-mediated mitogenic response and interleukin 2 production. This is most likely due to diet-induced quantitative differences in cellular fatty acid composition and, thus, in prostaglandin E2 production and tocopherol status.

Carotenoid and tocopherol concentrations in plasma, peripheral blood mononuclear cells, and red blood cells after long-term beta-carotene supplementation in men.

To determine the effects of long-term beta-carotene supplementation on concentrations of carotenoids and tocopherols in plasma and in blood cells, fasting blood was collected from 73 randomly selected physicians from the Boston area who are participating in the Physicians Health Study (PHS). The PHS is a randomized, placebo-controlled, double-blind study. In 1982, 22,071 male physicians were assigned to one of four treatments (325 mg aspirin alone, 50 mg beta-carotene alone, both, or neither) every other day. Plasma, peripheral blood mononuclear cells (PBMCs), and red blood cells (RBCs) from physicians who have participated in the study for approximately 12 y were analyzed for carotenoids and tocopherols. Compared with the placebo group, the supplemented group had higher beta-carotene concentrations in plasma (1.73+/-0.16 compared with 0.54+/-0.06 micromol/L0, RBCs (91.5+/-9.7 compared with 31.2+/-4.2 pmol/g hemoglobin), and PBMCs (61.6+/-10.3 compared with 15.5+/-2.5 pmol/10(7) cells). There were no differences in other carotenoids or tocopherols in plasma, RBCs, and PBMCs between these two groups. The beta-carotene concentrations. Plasma cryptoxanthin correlated with both RBC and PBMC cryptoxanthin concentrations but plasma lycopene correlated only with PBMC lycopene concentrations. These data suggest that plasma may not be the best indicator of carotenoid status. Furthermore, long-term beta-carotene supplementation in men results in higher beta-carotene concentrations in plasma, RBCs and PBMCs without lowering concentrations of other carotenoids or tocopherols.

Effect of vitamin E supplementation on prostaglandin concentrations in aspirin-induced acute gastric injury in aged rats.

Nonsteroidal antiinflammatory drugs (NSAIDs), such as aspirin, frequently cause gastric mucosal injury in the elderly. Impairment of prostaglandin synthesis is a crucial step by which aspirin attenuates mucosal defense capacity. Vitamin E has been shown to decrease prostanoid concentrations, which implies an ulceropermissive effect of vitamin E. To assess the effect of vitamin E on aspirin-induced gastric injury and mucosal prostanoid concentrations, 20 male rats aged 20 mo were divided into two groups and fed diets containing either 30 (physiologic requirement) or 500 mg all-rac-alpha-tocopheryl acetate/kg. After 6 wk, all rats received two intragastric doses of aspirin (1.4 mumol/kg body wt). A third group of six animals fed the high-vitamin E diet received a vehicle solution without aspirin. Mucosal samples for vitamin E and prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane A2 measurements were collected. The prevalence and degree of mucosal lesions were not significantly different among all groups. Rats fed the high-vitamin E diet had significantly higher mucosal vitamin E concentrations than rats fed the low-vitamin E diet. Mucosal concentrations of all three prostanoids were 95% lower in aspirin-treated rats than in controls (P = 0.0001 in all instances). The high-vitamin E diet group had significantly lower mucosal 6-keto-prostaglandin F1 alpha concentrations (P = 0.02) than the low-vitamin E diet group, indicating decreased prostacyclin formation, whereas concentrations of prostaglandin E2 and thromboxane A2 were similar in the aspirin-treated groups. Aspirin markedly reduced mucosal prostanoid concentrations in rats, without apparent effects on gastric injury, whereas vitamin E supplementation significantly reduced mucosal 6-keto-prostaglandin F(1 alpha) concentrations. Nevertheless, vitamin E supplementation did not result in more gastric injury in aspirin-treated rats than in controls.

Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects.

The effect of vitamin E supplementation on the immune response of healthy older adults was studied in a double-blind, placebo-controlled trial. Subjects (n = 32) resided in a metabolic research unit and received placebo or vitamin E (800 mg dl-alpha-tocopheryl acetate) for 30 d. Alpha-tocopherol content of plasma and peripheral blood mononuclear cells (PBMCs), delayed-type hypersensitivity skin test (DTH), mitogen-stimulated lymphocyte proliferation, as well as interleukin (IL)-1, IL-2, prostaglandin (PG) E2, and serum lipid peroxides were evaluated before and after treatment. In the vitamin E-supplemented group 1) alpha-tocopherol content was significantly higher (p less than 0.0001) in plasma and PBMCs, 2) cumulative diameter and number of positive antigen responses in DTH response were elevated (p less than 0.05), 3) IL-2 production and mitogenic response to optimal doses of concanavalin A were increased (p less than 0.05), and 4) PGE2 synthesis by PBMCs (p less than 0.005) and plasma lipid peroxides (p less than 0.001) were reduced. Short-term vitamin E supplementation improves immune responsiveness in healthy elderly individuals; this effect appears to be mediated by a decrease in PGE2 and/or other lipid-peroxidation products.

Short- and long-term beta-carotene supplementation do not influence T cell-mediated immunity in healthy elderly persons.

Supplementation of healthy elderly persons with beta-carotene has been considered a way to enhance immune responses. In study 1 the short-term effect of beta-carotene (90 mg/d for 3 wk) on immunity was assessed in a randomized, double-blind, placebo-controlled longitudinal comparison of healthy elderly women. In study 2 the long-term effect of beta-carotene (50 mg every other day for 10-12 y) on immunity was assessed in a randomized, double-blind, placebo-controlled longitudinal comparison of men enrolled in the Physicians' Health Study. Subjects from both studies taking active supplements had significantly greater plasma beta-carotene concentrations than did subjects taking placebo. The pre- to postintervention change in delayed-type hypersensitivity skin test responses between beta-carotene and placebo groups in the short-term study was not significantly different, nor was the response between treatment groups in the long-term study. There were no significant effects due to beta-carotene supplementation on in vitro lymphocyte proliferation, production of interleukin 2, or production of prostaglandin E2 as a result of short- or long-term beta-carotene supplementation. In addition, there were no differences in the profiles of lymphocyte subsets [total T cells (CD3+), T helper cells (CD4+), T cytotoxic-suppressor cells (CD8+), and B cells (CD19+)] due to short- or long-term beta-carotene supplementation, nor were there differences in percentages of CD16+ natural killer cells or activated lymphocytes (cells expressing interleukin 2 transferrin receptor) due to long-term beta-carotene supplementation. Consistent results from these two trials show that beta-carotene supplementation did not have an enhancing or suppressive effect on T cell-mediated immunity of healthy elderly.

Assessment of the safety of supplementation with different amounts of vitamin E in healthy older adults.

We showed previously that supplementation for 30 d with 800 IU (727 mg) vitamin E/d did not adversely affect healthy elderly persons. We have now assessed the effects of 4 mo of supplementation with 60, 200, or 800 IU (55, 182, or 727 mg) all-rac-alpha-tocopherol/d on general health, nutrient status, liver enzyme function, thyroid hormone concentrations, creatinine concentrations, serum autoantibodies, killing of Candida albicans by neutrophils, and bleeding time in 88 healthy subjects aged >65 y participating in a double-blind, placebo-controlled trial. No side effects were reported by the subjects. Vitamin E supplementation had no effect on body weight, plasma total proteins, albumin, glucose, plasma lipids or the lipoprotein profile, total bilirubin, alkaline phosphatase, serum aspartate aminotransferase, serum alanine aminotransferase, lactate dehydrogenase, serum urea nitrogen, total red blood cells, white blood cells or white blood cell differential counts, platelet number, bleeding time, hemoglobin, hematocrit, thyroid hormones, or urinary or serum creatinine concentrations. Values from all supplemented groups were within normal ranges for older adults and were not significantly different from values in the placebo group. Vitamin E supplementation had no significant effects on plasma concentrations of other antioxidant vitamins and minerals, glutathione peroxidase, superoxide dismutase, or total homocysteine. There was no significant effect of vitamin E on serum nonspecific immunoglobulin concentrations or anti-DNA and anti-thyroglobulin antibodies. The cytotoxic ability of neutrophils against Candida albicans was not compromised. Thus, 4 mo of supplementation with 60-800 IU vitamin E/d had no adverse effects. These results are relevant for determining risk-to-benefit ratios for vitamin E supplementation.

Natural killer cell activity in elderly men is enhanced by beta-carotene supplementation.

Natural killer (NK) cell activity has been postulated to be an immunologic link between beta-carotene and cancer prevention. In a cross-sectional, placebo-controlled, double-blind study we examined the effect of 10-12 y of beta-carotene supplementation (50 mg on alternate days) on NK cell activity in 59 (38 middle-aged men, 51-64 y; 21 elderly men, 65-86 y) Boston area participants in the Physicians' Health Study. No significant difference was seen in NK cell activity due to beta-carotene supplementation in the middle-aged group. The elderly men had significantly lower NK cell activity than the middle-aged men; however, there was no age-associated difference in NK cell activity in men supplemented with beta-carotene. beta-carotene-supplemented elderly men had significantly greater NK cell activity than elderly men receiving placebo. The reason for this is unknown; however, it was not due to an increase in the percentage of NK cells, nor to an increase in interleukin 2 (IL-2) receptor expression, nor to IL-2 production. beta-carotene may be acting directly on one or more of the lytic stages of NK cell cytotoxicity, or on NK cell activity-enhancing cytokines other than IL-2, such as IL-12. Our results show that long-term beta-carotene supplementation enhances NK cell activity in elderly men, which may be beneficial for viral and tumoral surveillance.

Assessing the effect of fatty acids on prostate carcinogenesis in humans: does self-reported dietary intake rank prostatic exposure correctly?

BACKGROUND: Dietary fatty acids may influence prostate carcinogenesis. Although the standard for assessing dietary effects in humans is the semiquantitative food-frequency questionnaire, the extent to which self-reported intake correctly ranks prostatic exposure is unknown. OBJECTIVE: The objective was to examine the correlation between reported intakes of different fatty acids and their concentrations in prostate tissue. DESIGN: This was a cross-sectional study of 52 men undergoing surgical resection of the prostate gland. Usual dietary intake of saturated, total unsaturated, oleic, and linoleic fatty acids over the previous year was estimated with use of a 122-item version of the Health Habits and History Questionnaire. Concentrations in prostate tissue were measured directly by use of gas chromatography in healthy tissue collected at the time of surgery and were expressed as a percentage of total fatty acids. Correlations with 4 measures of dietary intake [g/d, g/d adjusted for total daily energy intake, % of total fat (as g/d), and % of total energy] were evaluated by Spearman's rank-order correlation coefficients. RESULTS: Linoleic acid concentrations in prostate tissue were significantly correlated with dietary intake expressed as g/d adjusted for total energy [r = 0.29 (95% CI: 0.03, 0.49), P = 0.04], % of total fat [r = 0.36 (0.14, 0.550), P = 0.008], and % of total energy [r = 0.28 (0.04, 0.49), P = 0.042], but not as g/d. Although mean concentrations of saturated, total unsaturated, and oleic fatty acids in prostate tissue resembled mean intakes for the group, prostatic concentrations did not correlate with individual intakes. CONCLUSION: Self-reported intake of fatty acids is a satisfactory marker of prostatic exposure at the group level, but, with the exception of linoleic acid, does not correctly rank individuals with respect to intensity of exposure.

Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects.

BACKGROUND: We have shown that the age-associated increase in prostaglandin E(2) production contributes to the decline in T cell-mediated function with age. Black currant seed oil (BCSO), rich in both gamma-linolenic (18:3n-6) and alpha-linolenic (18:3n-3) acids, has been shown to modulate membrane lipid composition and eicosanoid production. OBJECTIVE: Our objectives were to 1) test whether dietary supplementation with BCSO can improve the immune response of healthy elderly subjects, and 2) determine whether the altered immune response is mediated by a change in the factors closely associated with T cell activation. DESIGN: A randomized, double-blind, placebo-controlled (soybean oil) study was conducted to examine the effect of 2 mo of BCSO supplementation on the immune response of 40 healthy subjects aged >/=65 y. In vivo immune function was determined by delayed-type hypersensitivity skin response. Peripheral blood mononuclear cells (PBMCs) were tested for in vitro immune response. RESULTS: In subjects supplemented with BCSO, the total diameter of induration at 24 h and individual responses to tetanus toxoid and Trichophyton mentagrophytes were significantly higher than their baseline values. The change in response to tetanus toxoid was significantly different from that of the placebo group. The BCSO group showed a significant increase in proliferative response of PBMCs to the T cell mitogen phytohemagglutinin that was not significantly different from that observed in the placebo group. BCSO had no effect on concanavalin A-induced mitogenic response, interleukin 2 and -1beta production, and PBMC membrane fluidity. Prostaglandin E(2) production was significantly reduced in the BCSO-supplemented group, and this change was significantly different from that of the placebo group. CONCLUSION: BCSO has a moderate immune-enhancing effect attributable to its ability to reduce prostaglandin E(2) production.

Dietary antioxidants modulation of aging and immune-endothelial cell interaction.

Oxidative damage by free radicals, which is the basis for the free radical theory of aging, has been well investigated within the context of oxidant/antioxidant balance. Age-associated disorders are believed to be associated with the time-dependent shift in the antioxidant/prooxidant balance in favor of oxidative stress. In this brief review, the importance of dietary antioxidant intervention on longevity and age-associated changes in bodily functions and diseases are discussed. Evidence has indicated that increasing the endogenous antioxidants defense system and modulation of free radical production by dietary restrictions contribute to increased longevity in animal models. Thus, increasing dietary intake of antioxidants is believed to increase longevity. Earlier studies have shown some increase in median life span in animal models. It was found that supplementing middle-aged (18 months) C57/BL mice with various antioxidants (vitamin E, glutathione, melatonin, and strawberry extract) had no effect on longevity as measured by the average age of death. Therefore, dietary antioxidant supplementation seems unlikely to increase longevity when begun in middle age; supplementation started in early life might be more effective. However, in middle-aged mice, vitamin E was effective in reducing lung viral titer when animals were exposed to influenza virus. Vitamin E supplementation improves cell-mediated immunity in mice and in humans. In addition to modulating the oxidation of low-density lipoproteins, vitamin E can modulate immune/endothelial cells interactions, thus reducing the risk of cardiovascular disease (CVD), a major cause of morbidity and mortality in elderly. Thus, antioxidants such as vitamin E from food sources or supplements appear to be promising for successful aging by improving immune function, and reducing the risk of several age-associated chronic diseases, such as CVD.