| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Original Research Paper |
Nutritional Immunology Laboratory (M.S.S., L.S.L., S.N.M.) Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University
Lipid Laboratory (A.H.L., E.J.S.) Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University
Department of Pathology, Sackler Graduate School of Biomedical Sciences (S.N.M.)Tufts University, Boston, Massachusetts
Department of Community Medicine, School of Medicine (B.G.) Tufts University, Boston, Massachusetts
School of Family Ecology and Nutrition (M.S.S.) University of Puerto Rico at Rio Piedras, San Juan, Puerto Rico
Address correspondence to: Simin Nikbin Meydani, DVM, PhD, Chief, Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111. E-mail: smeydani@hnrc.tufts.edu
ABSTRACT
Objective: The immunologic effects of isocaloric reduced- and low-fat diets and a voluntary calorie-restricted low-fat diet resulting in weight loss were compared to the immunologic effects of an average American diet in hyperlipidemic individuals.
Methods: Ten hyperlipidemic subjects were studied during three six-week weight maintenance phases: baseline (BL) [35% fat {14% saturated fat (SFA), 13% monounsaturated fat (MUFA), 8% polyunsaturated fat (PUFA)} and 147 mg cholesterol (C)/1000 kcal], reduced-fat (RF) [26% fat (4% SFA, 11% MUFA, 11% PUFA) and 45 mg C/1000 kcal], and low-fat (LF) [15% fat (5% SFA, 5% MUFA, 3% PUFA) and 35 mg C/1000 kcal] diets followed by 12-week, low-fat calorie reduced phase (LFCR).
Results: During the last phase, the subjects’ weight significantly decreased (p = 0.005). Cholesterol levels were significantly reduced during all phases, compared to BL diet (p < 0.05). Delayed-type hypersensitivity (DTH) was assessed using Multi-test CMI. Maximum induration diameters were 22.7, 25.4, 30.5, 34.5 mm for BL, RF, LF and LFCR diets, respectively. Subjects on the LFCR diets had significantly higher DTH compared to the BL diet (p = 0.005). No significant effect of diet was observed on lymphocyte proliferation or interleukin (IL)-1, IL-2 and prostaglandin (PG) E2 production.
Conclusions: These data suggest that low-fat diets (15% energy), under conditions which result in weight loss, do not compromise and may enhance the immune response of middle-aged and elderly hyperlipidemic subjects. The results of this study provide support for the hypothesis that moderate caloric restriction in humans may have a beneficial effect on cell-mediated immunity such as those reported in calorie-restricted rodents.
Key words: low-fat diet, calories restriction, weight loss, immune response, hypercholesterolemia
INTRODUCTION
Over the last two decades, evidence has accumulated which indicates a variety of potential ways in which elevated blood cholesterol levels alter immune function [1]. Stimulated lymphocytes from individuals with familial hypercholesterolemia [2,4] or from hyperlipidemic patients with nephrotic syndrome [3] had significantly reduced expression of low-density lipoprotein receptors (LDL-R) when compared to normolipidemic individuals. These patients have also been shown to have a reduced expression of interleukin-2 receptors (IL-2R). These factors, combined with the lymphocytes’ need for appropriate receptor-mediated uptake of lipoprotein-transported fatty acids and cholesterol, and IL-2 for optimal proliferation [2,5], may result in potentially depressed or deficient lymphocytic responses to foreign antigens in hypercholesterolemic individuals.
Dysregulation of immune functions as a result of elevated blood cholesterol levels has also been shown to play a role in atherogenesis. Hypercholesterolemic patients had a three- to fourfold increase in peripheral blood mononuclear cell (PBMC) mRNA transcripts for IL-8, a chemokine which is involved both in recruitment and activation of polymorphonuclear (PMN) leukocytes [7], which in turn may augment local oxidative events and result in increased susceptibility of LDL to oxidation. Increased infiltration of macrophages and subsequent phagocytosis of oxidized LDL results in the generation of foam cells and contributes to the formation of atherosclerotic lesions [8].
For high-risk individuals, the National Cholesterol Education Program Expert Panel (NCEP) recommends reducing total fat intake to 30% of energy, saturated fat to <7% of energy and cholesterol to <200 mg/day. A reduction in fat intake frequently results in reduction of caloric intake due to the high caloric density of fat and spontaneous weight loss. In turn, spontaneous weight loss is often a result. Both caloric restriction and weight loss have been shown to contribute to changes in immune functions, which can either be beneficial or potentially harmful, depending on the health status of the study population. Calorie restriction has been shown to result in enhancement of immunocompetence and prolongation of life in non-obese animal models [9,10]; however, the immunological benefits of calorie restriction were markedly reduced in obese ob/ob mice compared to lean older mice [11].
Weight loss has been associated with both decreases and increases in measures of immunity, depending on the amount, duration and conditions of the weight loss [12,13]. Short-term fasting (14 days) in obese subjects who lost an average of 9.4 kg produced increases in DTH skin responses, serum immunoglobulin levels, monocyte bactericidal capacity and natural killer cell activity, while producing a 19% decrease in lymphocyte proliferation [14]. A trend (not statistically significant) for increases in DTH skin responses was seen in obese individuals after losing an average of 13 kg while on an all protein, very low calorie diet (370 kcal/day); however, a decrease in the number of circulating CD4+ T cells resulted in a decrease in the CD4+/CD8+ ratio and subsequent functional test of lymphocyte proliferation [15]. These parameters of immunity returned to normal after the diet was discontinued and refeeding occurred; however, the authors expressed concern over the potential clinical implications of long-term use of the all protein, very low calorie diet [15]. More recent controlled investigations have reported significant decreases in neutrophils, monocytes and natural killer cells in obese individuals relative to non-obese controls after a 12-week dietary intervention (1200–1300 kcal/day based on a self-maintained food exchange system), which resulted in an average loss of 9.9 kg [16].
In an attempt to answer questions about what functional immunological changes may occur in hypercholesterolemic individuals as a result of placing them on a reduced-fat diet (<30 E% fat) or a more restrictive low-fat diet (15 E% fat) and what beneficial or potentially harmful immunological effects may result from spontaneous weight loss, a study was conducted to model the immunological implications of using the NCEP Step 2 diet and 15 E% low-fat diet therapies for treating hypercholesterolemia.
SUBJECTS AND METHODS
Subjects
Ten (six male and four postmenopausal female) healthy nonsmokers 
40 years of age and with LDL-C concentrations >130 mg/dL were recruited from the Boston area for this immunological study, which was part of a larger study established to evaluate the effect of NCEP Step II diets on lipoprotein metabolism of hyperlipidemic individuals [17,18]. Volunteers underwent a screening procedure, which included a medical history, physical examination, routine urinalysis and blood clinical chemistry profile. They did not present evidence of any chronic disease, including hepatic, renal, thyroid or cardiac dysfunction, nor were they taking medications known to affect plasma lipid levels (lipid-lowering drugs, ß-adrenergic blocking agents, diuretics or hormones) or medications known to adversely affect immune responses. In addition, subjects did not take aspirin or non-steroidal anti-inflammatory drugs on a regular basis, nor less than 72 hours before blood draws. All volunteers enrolled in the study agreed to abstain from vitamin supplements for 30 days prior to and during the study and to abstain from alcohol for the duration of the study. Two male subjects dropped out of the study due to personal reasons, and an additional subject was unable to complete immunologic blood draws of the study, resulting in a final cohort of seven (four male, three female) subjects. Due to the nature of the statistical analysis (paired comparisons), data presented in this report represent the seven subjects who completed the study protocol. All procedures were approved by the Human Investigation Review Committee of Tufts University Health Sciences. Informed, written consent was obtained from all participants.
Study Design
All subjects participated in each of three, six-week, isocaloric, weight maintenance study phases. First, subjects consumed a baseline (BL) diet similar in fat content to that currently consumed in the United States, which provided 16% of calories as protein, 49% as carbohydrate and 35% as fat [14% saturated fat (SFA), 13% monounsaturated fat (MUFA), 8% polyunsaturated fat (PUFA)] and 147 mg cholesterol/1000 kcal. Next, the subjects consumed a reduced fat (RF) diet containing 16% of calories as protein, 58% as carbohydrate and 26% as fat (4% SFA, 11% MUFA, 11% PUFA) and 45 mg cholesterol/1000 kcal. During the third six-week period, the subjects ate a low fat (LF) isocaloric diet containing 17% of calories as protein, 68% as carbohydrate and 15% as fat (5% SFA, 5% MUFA, 3% PUFA) and 35 mg cholesterol/1000 kcal. Each diet was consumed for six weeks at levels which maintained stable body weights. Previous studies indicate that plasma lipid levels stabilize after subjects have been on a specific diet for four weeks [18] and that there is no effect of diet order on the study outcome measures [17].
The fourth phase of the study was designed to provide the same nutrient composition as the LF diet phase, but it allowed the subjects to determine, in part, their caloric intake. This final diet was conceived to test the hypothesis that drastically reducing the fat content of the diet would result in spontaneous weight loss and subsequently benefit plasma lipid profiles. To accomplish this aim within the context of a metabolic study protocol, subjects were provided with and were required to consume two thirds of their caloric intake on the LF (isocaloric, weight maintenance) diet phase (all food components were reduced proportionally). Participants were then provided with an additional two thirds of their caloric intake in the form of 200 kcal portions of frozen entrees and muffins normally present in their diet, the composition of which was similar to that of the LF diet. The subjects were instructed that they were required to consume the first two thirds of the food provided and thereafter could self-determine how much additional food they would consume from the provided entrees or muffins. In the most extreme cases, subjects could either have consumed one third less or one third more calories than they consumed on the LF isocaloric diet; however, subjects were asked simply to consume the amount of additional food with which they felt comfortable, without purposely refraining from eating or trying to lose weight. The fourth diet phase was continued for an additional six weeks (12 weeks total) so that potential effects of self-selected caloric intake on changes in body weight and/or lipid concentrations could be better monitored and detected. According to the results, subjects reduced the amount of calories consumed on this last 12-week diet phase; it was therefore named accordingly—the low fat, calorie restricted (LFCR) diet phase.
Triplicate preparations of each complete meal cycle (three days) for each diet phase were analyzed by Hazleton Laboratories America, Inc. The macronutrient composition, fatty acid profile and cholesterol content of the diets are shown in Table 1 [17]. In general, there was good agreement between the analytical and calculated data except for cholesterol, which was overestimated in the food composition tables.
|
Biochemical Analyses
Blood collections (three collections on different dates at the end of each phase) from fasted subjects (12 hours) were made in tubes containing 0.1% EDTA, and very low density lipoprotein (VLDL) was isolated from plasma with a single ultracentrifugational spin (density 1.006 g/mL, 39,000 rpm for 18 hours at 4°C). Plasma and the 1.006-g/mL infranate were assayed for total cholesterol and triglyceride with an Abbott Diagnostics ABA-200 bichromatic analyzer using enzymatic reagents [19]. HDL-C was measured as described previously [20]. Non-HDL-C (total cholesterol minus HDL-C) was determined in nonfasting plasma after HDL-C precipitation. The lipid assays were standardized through the Lipid Standardization Program of the Centers for Disease Control and Prevention (Atlanta, GA). Coefficients of variation, both within-run and between-run, were less than 5% for these assays.
Delayed-Type Hypersensitivity Skin Response
Multitest CMI [trademark] (Connaught Laboratories, Inc., Swiftwater, PA), a skin patch device with seven common antigens (tetanus, diphtheria, streptococcus, tuberculin, candida, trichophyton, proteus) and a glycerin control, was administered on the forearm by a trained nurse who was blinded to study treatment assignment. Indurations 2 mm were considered positive and were measured at 24 hours and 48 hours by the same investigator in a manner blinded to dietary intervention. The total number of positive responses was recorded, and the sum of the average of individual indurations (mm) was recorded as the induration index. Based on the manufacturer’s recommendation, the maximum DTH skin response to antigens between the 24 hour and 48 hour readings was also analyzed in an attempt to reduce interindividual variability in responses to antigens.
Mononuclear Cell Isolation
Thirty mL of blood from fasted subjects (12 hours) were drawn into sodium heparin vacuum tubes. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood using Ficoll-Paque (Pharmacia Biotech, Piscataway, NJ) density gradient centrifugation. The mononuclear cell "buffy layer" was isolated and washed three times in complete media: RPMI 1640 (Sigma, St. Louis, MO) with 100 x 103 U penicillin/L (Gibco BRL, NY) and 100 mg streptomycin/L (Gibco BRL, NY), 2 mmol glutamine/L (Gibco BRL, NY) and 25 mmol/L HEPES (Sigma, St. Louis, MO). Trypan blue staining was used to assess cell viability, and lymphocytes were counted in a hemocytometer under a light microscope.
Lymphocyte Proliferation
Lymphocyte proliferation cultures were prepared in triplicate (96-well, flat-bottomed plates; Falcon [trademark], Becton Dickinson and Co., Lincoln Park, NJ) with 1 x 109 cells/L in 10% autologous plasma. Cells were stimulated with phytohemagglutinin (PHA-P; Difco, Detroit, MI) or concanavalin A (ConA; Sigma, St. Louis, MO) at 0.5, 5, and 50 mg/L. Cultures were incubated in 5% CO2 at 37°C. Cells were harvested onto glass filter paper at 72 hours using a cell harvester (PHD, Cambridge, MA) following a 4 hour tritiated thymidine (3H Td) pulse (18.5 kBq in 20 µL complete media added to 1 x 105 cells/well). Incorporation of 3H Td into newly synthesized DNA was counted in a Beta scintillation counter (Beckman Instruments, Palo Alto, CA), and corrected counts per minute were converted to Bq.
Interleukin-2 and Prostaglandin E2 Production
Interleukin-2 (IL-2) and prostaglandin E2 (PGE2) cultures were prepared by plating 1 x 109 cells/L (24-well, flat-bottomed plates; Falcon [trademark], Becton Dickinson and Co., Lincoln Park, NJ) in 10% autologous plasma. PBMC were stimulated by PHA-P and ConA (10 mg/L) for 48 hours in 5% CO2 at 37°C, after which supernatants were harvested and frozen at -70°C until analysis.
A standard bioassay using the human IL-2 sensitive CTLL-2 murine cytotoxic cell line (developed in our lab from CTLL; ATCC, Rockville, MD) was used to determine the amount of IL-2 produced by the 48 hour cultures. Units of IL-2 activity were calculated by computer using probit analysis [21], previously described in detail [22].
PGE2 production was measured by RIA as previously described [22]. PGE2 antibody (polyclonal rabbit 
-globulin) was kindly provided by J. Dupont (Iowa State University, Ames, IA) and M. Mathias (Colorado State University, Fort Collins, CO).
Interleukin-1 Production
Interleukin-1ß (IL-1ß) cultures were prepared by plating 5 x 109 cells/L (in 0.5 mL complete media containing 2% autologous plasma) into wells (24-well, flat-bottomed plates; Falcon [trademark], Becton Dickinson and Co., Lincoln Park, NJ) which contained either 0.5 mL complete media, 20 organisms heat-killed Staphylococcus epidermis (S. epi.)/cell, or 1 µg LPS (Escherichia coli 0111:B4)/L (Sigma, St. Louis, MO). Plates were incubated for 24 hours (5% CO2 at 37°C), at which time they were frozen at -70°C until the end of the study. All plates from each subject were then submitted to a cycle of three freeze/thaws in order to complete cell lysis. The contents of the wells (cell lysates and supernatants) were analyzed by RIA specific for IL-1ß (no cross-reactivity with GM-CSF, IFN-
, ß, or ) as previously described [23].
Fatty Acid Analysis
Transesterification and separation of plasma fatty acids were performed as previously described [24]. Peaks were identified and validated by chromatography of mixtures of authentic fatty acid methyl esters. Data were normalized by comparing the areas of the fatty acid peaks with the area of the internal standard peak, heptadecanoic acid, after appropriate corrections were made. Values presented are percentages of the total area of the identified fatty acid peaks.
Statistical Analysis
On three different occasions, in vitro immunologic tests were performed for each subject at the end of each dietary period; means of the three measures were calculated for comparisons and used for analyses. Differences between the RF, LF or LFCR diet phases and the BL average American diet were compared using paired Student’s t test or Wilcoxon signed rank test, depending on the distribution of the data (SYSTAT for Macintosh, Versions 5.2 and 6.1; SYSTAT, Evanston, IL). Bonferroni adjustments were made for multiple comparisons, significance being defined by a p value 
0.017. Pearson correlation coefficients were also calculated for potential associations between changes in BMI or plasma fatty acid profiles and changes in immune parameters. Due to the nature of paired analyses, data from the number of subjects who completed the study were utilized (n = 7).
RESULTS
The mean age of the subjects at the start of the study was 63 years (53 to 73 years) (Table 2). The women tended to have a higher BMI than men (27.7 and 25.1, respectively). According to the clinical guidelines for the identification, evaluation and treatment of overweight and obesity in adults established by the National Institutes of Health [25], the interval for healthy weight and BMI is 18.5 to 24.9, followed by overweight (BMI = 25.0 to 29.9) and obese (BMI 30) [25]. The mean BMI of all subjects combined was 26.2, largely due to the fact that one subject with a BMI of 35 skewed the mean value upward; for this reason the medians are shown, reflecting a lower group value of 25.2. Three subjects had BMIs of 23 to 24 (desirable/healthy), two subjects had a BMI of 25 and one a value of 26 (lower scale of overweight), and only one subject had a value of 35 (obese). The isocaloric reduced fat (RF) and low fat (LF) diet phases produced very little fluctuation in weight, according to the weight maintenance study design: -0.18% (RF) and -0.06% (LF). On the other hand, allowing subjects to adjust their caloric intake (LFCR diet phase) produced voluntary caloric restriction or restrained eating which resulted in weight loss (-5.1%, an average of 3.61 kg over a period of 12 weeks; (p < 0.005, paired t test with Bonferroni corrections for multiple comparisons). Subsequently, a significant decrease in BMI also occurred, bringing the average value down to 25.2 ± 1.4 (p 0.017, Wilcoxon signed rank test with Bonferroni corrections for multiple comparisons), a value that nearly falls within the desirable range of 18.5 to 24.9 [25].
|
|
A stepwise increase in the maximum delayed-type hypersensitivity induration index was seen as dietary fat was reduced (Fig. 1), culminating in a significant, 52% increase during the LFCR diet phase after weight loss had occurred (34.5 mm ± 3.9, LFCR, vs. 22.7 mm ± 4.7, BL; p = 0.005). The stepwise increase in the DTH response may give the impression that the increase may have been the result of a boosting effect from repetitive application of antigens; however, Multitest CMI (trademark) was designed for multiple use and has successfully been employed in studies without the occurrence of such a boosting effect [22,27]. During analysis of skin responses to individual antigens, a tendency for increased response was seen for diphtheria comparing the LFCR diet to the BL diet (9.07 mm ± 2.3 vs. 3.98 m ± 0.77; p = 0.08). There were no significant changes in the number of antigens that showed positive responses when comparing reduced or low fat diet phases to baseline.
|
|
|
Constitutive production of the pro-inflammatory cytokine IL-1ß as well as interindividual variability diminished when subjects were on the RF diet compared to the BL average American diet (Table 4); however, this drop was not statistically significant (p = 0.17 after Bonferroni correction). Average constitutive IL-1ß production remained lower on the LF diet as well; however, one individual experienced a rise in IL-1ß production with weight loss on the LFCR diet, increasing the average level of production as well as the interindividual variability.
Production of IL-1ß as stimulated by S. epi. or LPS remained fairly constant regardless of dietary phase, showing no significant differences when production on RF, LF and LFCR diets was compared to production on the BL diet.
Table 5 shows plasma fatty acid levels in response to variations in the percentage of dietary fat were reported before. Of the three saturated fatty acids (cholesterol-raising fatty acids) measured, a significant reduction in plasma stearic acid was seen when dietary fat was reduced to 15 E% in the presence of weight loss (p = 0.004; median 6.01%, LFCR vs. 6.77%, BL). The reduction in stearic acid during the LF diet phase was marginally significant after Bonferroni corrections (p = 0.029; median 6.13%, LF vs. 6.77%, BL). Plasma levels of the monounsaturated fatty acid, oleic acid, were significantly greater than BL levels after the LFCR diet phase (p = 0.011). Among the five polyunsaturated fatty acids analyzed, tendencies for increases in eicosapentaenoic acid and docosahexaenoic acid were seen for the LF diet phase (p = 0.06), and a significant increase in docosahexaenoic acid was detected after the LFCR diet (p = 0.007). No significant changes were detected in plasma levels of n6 polyunsaturated fatty acids due to differences in dietary fat.
|
In support of previous findings [17,28], dietary modification of fat intake in hypercholesterolemic individuals through adoption of an NCEP Step 2 diet (RF; 29 E% fat) and a more restrictive low-fat (LF; 15 E% fat, isocaloric) diet resulted in the beneficial lowering of TC and LDL-C, with the low-fat, voluntary calorie-restricted (LFCR) diet resulting in spontaneous weight loss demonstrating the greatest cholesterol-lowering effect. In addition, the weight loss as a result of the LFCR diet phase also helped to maintain plasma triglycerides at levels comparable to those of the BL diet, avoiding the significant increase in triglycerides seen during the LF, isocaloric diet phase.
The immunologic outcomes of the six-week, isocaloric, NCEP Step 2 (RF) and lower-fat (LF) diets in hypercholesterolemic older individuals were either beneficial, as seen by significant enhancement of the lymphocyte proliferative response to ConA and PHA or showed no significant differences (delayed-type hypersensitivity skin responses and production of IL-1ß, IL-2, or PGE2) when compared to the immunological outcomes of the average American BL diet. No negative effects on immune responsiveness were detected as a result of the RF or LF diets.
The observations of increased lymphocyte proliferation as a result of lowering the fat content of the diet are supported by our previous study [31] and other published reports as well. A significant increase in lymphocyte proliferation was observed with consumption of low fat diets (about 25% E as fat) for as short as 40 days or as long as six months in other studies [32,33].
In contrast to the present study’s tendency for reduction in unstimulated production of IL-ß and no significant change in LPS- or S. epi.-stimulated production of the cytokine as a result of the RF diet, the previous report [31] reflects significant increases in production of pro-inflammatory cytokines IL-1ß and TNF- as a result of the NCEP Step 2 Diet. This discrepancy may be due to differences in the metabolic and biochemical consequences of hypercholesterolemia in subjects of the present study and those of normolipidemia in subjects from the previous study [31].
When subjects were given the option of meeting the isocaloric standards, while remaining within the limits of macronutrient diet composition, all chose to eat less food, resulting in voluntary caloric restriction (LFCR). The LFCR diet resulted in spontaneous weight loss of an average of 3.6 kg over a period of 12 weeks. Although different from the two previous diet phases, the immunological outcomes of this LFCR diet phase were also beneficial or reflected no change, posing no detrimental effects to the immune parameters measured. A significant increase in delayed-type hypersensitivity skin responses was detected as a result of the LFCR diet; however, no significant changes were found in lymphocyte proliferation or production of IL-1ß, IL-2, or PGE2.
A significant increase in DHA in the LFCR diet phase was observed. The significant increase in DTH observed in the LFCR diet phase of the present study was unlikely due to the significant increase in plasma DHA observed at the end of the same diet phase. Pearson correlation coefficients showed no significant association between change in DTH and change in plasma DHA when comparing LFCR and BL diet phases (r = -0.50, p = 0.26). In addition, Kelley et al. [1998], who investigated the effects of 6g DHA/day as part of a low-fat diet (30 E% fat), found no significant effect of DHA on the delayed-type hypersensitivity skin response of healthy young men.
Due to the significant changes in the composition of plasma lipids during the LFCR diet phase and the significant change in the DTH skin response, Pearson correlation coefficients were calculated in an attempt to identify any significant associations that may have existed between the reduction in plasma stearic acid and the increase in DTH or between the increases in oleic acid or docosahexaenoic acid and increase in DTH. However, no significant correlations were found indicating that other factors such as a change in free radical formation or hormonal changes associated with LFRC might have contributed to the increase in DTH.
One possible limitation of this study is that different dietary interventions were not applied in random order, which may potentially cause a booster effect in the DTH response or a drift in immune measures over time. However, in our previous study [39], we did not observe any significant increase in DTH response following repeated applications (three times within 4
months) in the control group; thus, we believe that the increase in DTH response following consumption of a LFCR diet is a true diet effect and not due to a boosting effect from repeated use of the DTH test.
CONCLUSION
Our results show that hypercholesterolemic individuals, slightly overweight or within ranges of healthy weight, who are following the current recommendations of a low-fat diet as lifestyle therapy for their condition are not likely to experience adverse immunological effects; rather, they may experience beneficial immunological effects if weight loss occurs. The result of our study also provides support for the hypothesis that moderate caloric restrictions in humans might have a beneficial effect on cell-mediated immunity such as those reported in calorie-restricted rodents.
ACKNOWLEDGMENTS
The authors are thankful to the volunteers who participated in this study and the staff of JM USDA-HNRCA Metabolic Research Unit. The authors also thank Stephanie Marco for the preparation of this manuscript.
FOOTNOTES
This project has been funded in part with federal funds from the U.S. Department of Agriculture, Agricultural Research Service under contract number 53-K06-01 and NIH Training Grant #T32AG00209. The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.
Received May 16, 2002. Accepted August 16, 2002.
REFERENCES
and interleukin 1ß production of diets enriched in n-3 fatty acids from vegetable oil or fish oil.Am J Clin Nutr63
:116
–122,1996
.This article has been cited by other articles:
|
|
 |
|
  S. E Kasim-Karakas, A. Tsodikov, U. Singh, and I. Jialal Responses of inflammatory markers to a low-fat, high-carbohydrate diet: effects of energy intake. Am. J. Clinical Nutrition, April 1, 2006; 83(4): 774 - 779. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
