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ORIGINAL RESEARCH COMMUNICATION |
1 From the Department of Kinesiology, Auburn University, Auburn, AL (EPP, MLM, and PWG); the Family Medicine Residency Program, Baptist Hospital, Montgomery, AL (AJM); the Department of Biology, Auburn University Montgomery, Montgomery, AL (JKT); and the School of Physical Education and Sports, University of Costa Rica, San Jose, Costa Rica (JM-J)
2 Supported by a Global Pharmaceuticals Research & Development Grant from Abbott Laboratories,
3 Reprints not available. Address correspondence to EPP, Boshell Diabetes and Metabolic Diseases Research Program, Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, 208A Greene Hall, Auburn, AL 36849. E-mail: plaisep{at}auburn.edu.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Objective:We compared the effects of aerobic exercise and 6 wk of extended-release niacin on postprandial triglycerides in men with the metabolic syndrome.
Design:Fifteen participants underwent each of 4 conditions: control—high-fat meal only (100 g fat); exercise—aerobic exercise performed 1 h before a high-fat meal; niacin—high-fat meal consumed after 6 wk of niacin; and niacin + exercise—high-fat meal consumed after 6 wk of niacin and 1 h after aerobic exercise. Temporal responses for triglyceride and insulin concentrations were measured and total (AUCT) and incremental (AUCI) areas under the curve were calculated. Differences were determined by using a 2-factor repeated-measures analysis of variance (P < 0.05 for all).
Results:Exercise lowered the triglyceride AUCI by 32% compared with control (724 ± 118 and 1058 ± 137, respectively). Niacin had no influence on the triglyceride AUCI and attenuated the triglyceride-lowering effect of exercise when combined. Niacin + exercise had no effect on the triglyceride AUCI but decreased the insulin AUCI after niacin administration.
Conclusions:Aerobic exercise lowers the postprandial triglyceride response to a high-fat meal. Niacin lowers fasting but not postprandial triglycerides and appears to influence the triglyceride-lowering effect of aerobic exercise when combined. However, exercise decreases postprandial insulin concentrations after niacin administration, which illustrates the potential metabolic benefits of exercise in persons taking niacin.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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3 risk factors that include abdominal obesity, insulin resistance, low HDL cholesterol, hypertension, and hypertryglyceridemia (1, 2). Hypertriglyceridemia is one of the most common features of the metabolic syndrome and may be characterized by elevated triglyceride concentrations in the fasted and postprandial states. Although fasting blood lipid concentrations are most often used to evaluate CVD risk, the magnitude and duration of postprandial triglyceride elevation may provide additional information regarding the metabolic capacity to remove lipids from the blood. Wideman et al (3) examined the effects of a high-fat meal in sedentary, normolipidemic males with abdominal obesity. Despite normal fasting triglyceride concentrations, males with abdominal obesity had a higher magnitude of triglyerides and a higher total triglyceride response to a high-fat meal than did normal-weight controls.
Aerobic exercise training in the presence or absence of weight loss has been shown to reduce both fasting and postprandial triglycerides (4). However, many of the health-related benefits attributed to aerobic exercise training are due to the metabolic effects of the most recent session of exercise performed. Single sessions of low-to-moderate–intensity aerobic exercise lasting for 30–90 min reduce postprandial triglyceride concentrations by 15–50% (5).
The pharmacologic effects of niacin (nicotinic acid) were first reported by Altschul et al in 1955 (6). Niacin is one of the most effective pharmacologic agents for lowering fasting triglycerides, and its use results in reductions of 20% to 50% (7–9). Although few studies have investigated the effects of niacin on postprandial triglycerides, King et al (10) found that immediate-release niacin reduced the total triglyceride area under the curve (AUCT) after a high-fat meal by 41% in persons with low HDL cholesterol.
The effects of aerobic exercise on postprandial triglycerides have been well established in healthy persons; however, there is little information regarding the influence of exercise on postprandial triglycerides in persons at risk of metabolic syndrome and CVD. Likewise, despite the efficacy of extended-release niacin on fasting blood lipids, its influence on postprandial triglycerides has not been investigated to date. In addition, the combined effects of aerobic exercise and extended-release niacin on postprandial triglycerides have not been established. Because lifestyle and pharmacologic interventions are often prescribed together to reduce the risk of metabolic syndrome and CVD, our purpose was to evaluate the independent and combined effects of a single session of moderate-intensity aerobic exercise and 6 wk of extended-release niacin on postprandial triglycerides in men with the metabolic syndrome.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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150 mg/dL) or if they presented with abdominal obesity (ie, waist girth > 100 cm) or did not smoke. Persons taking medications known to influence lipid, lipoprotein, or glucose metabolism and those with a history of or active gout, peptic ulcer disease, or liver disease were excluded from the study. Volunteers who met the initial criteria by interview were invited to the laboratory for additional preliminary screening. A venous blood sample was obtained after a 10–12-h fast and sent to a Centers for Disease Control and Prevention (CDC)–certified laboratory for measurement of baseline blood lipid and glucose concentrations. Persons who met the initial criteria were asked to return to the laboratory for further evaluation.
All volunteers were fully informed about the nature of the study and provided written informed consent via an institutionally approved form. The investigation was approved by the Auburn University Institutional Review Board.
Physiologic assessment
During the return visit to the laboratory, anthropometric measurements such as height, weight, body mass index (in kg/m2), and waist and hip circumferences and other physiologic measurements were obtained. All waist and hip circumferences were measured to the nearest 0.5 cm. Waist was defined as the narrowest portion of the torso between the umbilicus and the xiphoid process, and measurements of hip circumference were obtained at the maximal thickness of the hips or buttocks. Body composition was determined by using dual-energy X-ray absorptiometry according to the manufacturer's instructions (Lunar Prodigy; General Electric, Fairfield, CT).
Each participant then underwent a physical examination by a physician. After the physical examination, participants who were permitted to exercise performed a graded exercise test by using a standard Bruce protocol on a motor-driven treadmill to determine cardiorespiratory fitness. Twelve-lead electrocardiography was monitored throughout the treadmill test to evaluate the cardiovascular response to exercise. Breath-by-breath analysis of oxygen consumption and carbon dioxide production was averaged over 30-s intervals by using an automated system (Ultima Exercise Stress Testing System; Medical Graphics, Minneapolis, MN). Maximum oxygen uptake (
O2max) was defined as the highest observed oxygen uptake. An exercise test was considered maximal if 2 of the following criteria were met: 1) respiratory exchange ratio 1.10, 2) heart rate within 10 beats/min of the age-predicted maximum, and 3) perceived exertion rating of 18.
Dietary analysis
Volunteers who met all criteria for the study were provided a dietary and daily physical activity record to be completed from 3 d before and during all blood-sampling periods. The purpose of the dietary record was to determine the composition and quantity of foods each participant consumed during a typical week. Other than a request that participants maintain similar caloric and nutrient intakes during the blood sampling period, there was no attempt to modify dietary composition. Food logs were analyzed by using FOOD PROCESSOR for WINDOWS software (version 7.40; ESHA Research, Salem, OR). Total caloric intake and the percentages of protein, fat, and carbohydrate were estimated from the food log.
Physical activity records were used to determine average caloric expenditure before and during the blood sampling period. Participants were asked to record the amount of time spent performing a wide range of activities. Metabolic equivalents were assigned to each type of activity, and caloric expenditure was estimated from the type and duration of activity. In combination with dietary records, physical activity records were used to account for background dietary or physical activity changes that could potentially influence changes in blood lipid or glucose metabolism.
Experimental procedures
Participants who met all criteria and agreed to participate in the study were asked to record all food and drink consumed during the 3 d before blood sampling and to avoid any planned leisure-time physical activity or strenuous vocational activity on the 3 d before blood sampling. Participants then returned to the laboratory, where a baseline blood sample was obtained, and a high-fat meal was administered (control condition). Our initial goal was to characterize the postprandial triglyceride response to a high-fat meal free of any outside influences from exercise or niacin. The following day, each participant returned to the laboratory, where another baseline blood sample was obtained to determine the influence of aerobic exercise alone on postprandial triglycerides (exercise condition) compared with control. After participants provided the baseline blood sample, they were asked to walk on a treadmill at 60–70% of O2max obtained from the treadmill test until a net energy expenditure of 500 kcal was achieved. Participants were then asked to consume a high-fat meal identical to that of the previous day in the control condition. Blood was sampled over the course of 8 h after the high-fat meal in each condition.
Forty-eight hours after the high-fat meal of the exercise condition, the attending physician wrote a 6-wk prescription for extended-release niacin (Niaspan; Abbott Laboratories, Abbott Park, IL). After the niacin intervention, participants were asked to return to the laboratory, where they completed identical testing procedures conducted during the control and exercise conditions (Figure 1
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270 mL whipped heavy cream and 65 g vanilla ice cream provided in the control, exercise, niacin, and niacin + exercise conditions. The meal contained 1000 kcal and was composed of 100 g fat, 17 g carbohydrate, and 3 g protein. Each meal was identical in total caloric content and composition. Participants were required to consume the high-fat meal within 15 min.
Acute exercise intervention
All participants completed an aerobic exercise session on 2 occasions: 1) the day after the control condition and just before beginning the 6-wk niacin condition and 2) at 6 wk during the niacin condition. Treadmill walking was completed 1 h before ingestion of a high-fat meal in the exercise and niacin + exercise conditions (Figure 1
). A standard kcal equivalent of 5 kcal/L of oxygen and O2max (L/min) obtained from the graded exercise test were used to estimate the intensity and duration of exercise needed to elicit a net energy expenditure of 500 kcal before the experimental exercise session. The average exercise duration required to expend 500 kcal at the required intensity was 51 min (range: 36–75 min).
Niacin administration
Our university pharmacy filled the extended-release niacin prescription for 1 wk, and the participant was required to return to the pharmacy each week for refills. Refills of niacin were dispensed by the pharmacist only after participants completed a questionnaire at the Exercise Technology Laboratory regarding any adverse effects of niacin. Titrations of niacin occurred as follows: week 1, 500 mg/d; week 2, 1000 mg/d; and weeks 3–6, 1500 mg/d (12). Niacin was taken once a day at bedtime with 300 mg aspirin to reduce the risk of flushing. Before the exercise condition and at weekly intervals thereafter, blood samples were obtained from each participant to monitor the potential side effects of niacin.
Experimental blood sampling
Participants were asked to report to the laboratory for each condition at approximately the same time each morning, after a 10–12-h fast. Before each meal, an intravenous catheter was inserted into an antecubital vein and capped by an intermittent injection port. Blood samples were obtained before the meal and at 2-h intervals for up to 8 h after the meal. Whole blood was centrifuged at 1500 x g for 20 min to isolate serum. Aliquots of serum were stored at –70 °C before analysis. Participants were asked to remain in the laboratory during the blood sampling period.
Biochemical analysis
Clinical chemistries were conducted by a CDC-certified laboratory. Hemoglobin and hematocrit concentrations were used, according to the procedures of Dill and Costill (13), to estimate possible shifts in plasma volume associated with each condition. Serum triglyceride and glucose concentrations were analyzed by using commercially available colorimetric enzymatic kits (Raichem, Columbia, MD). Insulin concentrations were measured by using an enzyme-linked immunosorbent assay (ELISA; Millipore, Billerica, MA). The intraassay and interassay CVs for triglycerides were 1.1% and 2.7%, respectively. The intraassay and interassay CVs for glucose were 0.5% and 1.3%, respectively. Insulin concentrations were measured for all time-points collected on a participant during a single analysis. The intraassay CV for insulin was 3.3%.
Statistical analysis
Postprandial triglyceride and insulin concentrations were measured by using mean triglyceride and insulin responses from baseline and 2, 4, 6, and 8 h and the total and incremental triglyceride and insulin AUC as shown in equations 1 and 2, respectively (14):
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A within-subjects design was used with participants serving as their own controls. A control group and a placebo control were considered and ruled out because the efficacy of niacin therapy is not in question, and ethical issues about benefit for participants were a major concern for the investigators and our medical consultants. Tests for normality confirmed that all dependent variables of interest were normally distributed. Repeated-measures analysis of variance (ANOVA) was used to compare the postprandial triglyceride and insulin AUC and peak responses. A 2-factor repeated-measures ANOVA was used to compare the temporal responses over the 8-h postprandial period for each condition. Tukey-Kramer post hoc testing was used to explore significant differences determined by ANOVA. Relations between physiologic characteristics and changes in the dependent variables were determined by using Pearson product-moment correlation coefficients. Power analyses suggested that 10 participants would be required, as determined by using the variance in postprandial triglyceride AUCI, to exercise at an effect size of 0.8 and an alpha level of 0.05 (15). Data were analyzed with SAS for WINDOWS software (version 9.1; SAS Institute, Cary, NC). Significance was accepted at the P < 0.05 level.
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RESULTS |
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3 of the 5 criteria for the metabolic syndrome as defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III; 2). The cohort could be classified as being at high risk of CVD on the basis of average body mass index (34.0 ± 0.8) and waist circumference (107.9 ± 2.1 cm) (16). Percentage body fat was above the 90th percentile for men 40–60 y of age. The baseline physiologic characteristics of the participants are shown in Table 1.
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A). Exercise lowered the triglyceride AUCI by 32% from control (Figure 3B); however, the triglyceride AUCI for the niacin and niacin + exercise conditions did not differ significantly from control. Peak triglycerides in the exercise (404 ± 35 mg/dL) and niacin (400 ± 35 mg/dL) conditions were similarly lower than the control condition (490 ± 35 mg/dL). The peak triglyceride concentrations in the niacin + exercise condition (360 ± 34 mg/dL) were not significantly lower than those in the exercise or niacin condition alone. The length of time required for triglyceride concentrations to peak was between 2 and 4 h, and it was not influenced by any of the conditions.
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. Postprandial triglycerides were lowered for up to 6 h in the exercise condition compared with control. Exercise also lowered the incremental triglyceride response, which accounts for fasting triglycerides (Figure 3D; P < 0.0001). Fasting triglyceride concentrations were 37% lower after niacin administration compared with control (P < 0.0001). However, niacin had no influence on the incremental triglyceride response to a high-fat meal, and it attenuated the postprandial triglyceride-lowering effect of exercise.
Postprandial insulin and glucose responses
The insulin AUCT and AUCI were significantly greater after 6 wk of niacin compared with control (Figure 4). Niacin + exercise lowered the insulin AUCI compared with control.
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) (P = 0.005). Exercise lowered 2-h postprandial insulin concentrations by 16% after niacin administration (P = 0.02). Fasting and postprandial glucose concentrations were unchanged throughout the study. Mean (±SEM) homeostatic model assessment (HOMA) scores for the baseline fasting insulin concentrations in the control, exercise, niacin, and niacin + exercise conditions were 3.9 ± 0.8, 4.2 ± 0.5, 4.8 ± 0.7, and 5.3 ± 0.8, respectively. HOMA scores in the niacin and niacin + exercise conditions were significantly higher than those in the control condition.
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Diet and physical activity records
Caloric intake and the percentage composition of carbohydrate, fat, and protein did not differ significantly before the control condition or throughout the blood sampling periods associated with the exercise and niacin + exercise conditions, which suggested that diet did not have an appreciable influence on the results of the present study. Average daily energy expenditure was estimated from daily physical activity records. The average daily energy expenditure reported before the niacin intervention did not differ significantly from that after the niacin intervention.
Adverse reactions
Alanine aminotransferase and 
-glutamyl transferase concentrations were lower (P = 0.02 for both) in the niacin condition than in the control condition, whereas aspartate aminotransferase concentrations remained the same in both conditions. Alanine aminotransferase concentrations were 33 ± 3 and 27 ± 2 U/L at baseline in the control and niacin conditions. Aspartate aminotransferase was 23 ± 1 and 23 ± 0.9 U/L at baseline in the control and niacin conditions. Uric acid concentrations remained unchanged throughout the study period. Nine of 15 participants reported mild-to-moderate flushing—in most cases, as cutaneous redness, itching, or tingling—at some point during the intervention. Despite the rapid titration used in this investigation, there was no relation between the weekly titrations of niacin and adverse reactions. Flushing events occurred randomly throughout the study but did not last >2–3 h/event and usually did not occur on consecutive days. Fatigue was the second most commonly reported adverse reaction: 3 persons reported fatigue that remained present throughout the course of the niacin condition.
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DISCUSSION |
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The effects of aerobic exercise training on fasting and postprandial triglyceride concentrations have been attributed to the most recent session of exercise performed (17–19). Indeed, the postprandial triglyceride-lowering effect of aerobic exercise training was diminished when the exercise was performed 48 h before a high-fat meal (20, 21). In contrast, aerobic exercise performed 1–16 h before a meal reduces postprandial triglyceride concentrations by 18–50% (5). Most studies conducted to date have examined the effects of aerobic exercise performed 12–16 h before a high-fat meal on postprandial triglycerides in healthy, physically fit persons. In the current investigation, we provide evidence that moderate-intensity aerobic exercise performed 1 h before a high-fat meal lowers the triglyceride AUCI by 32% and the peak triglyceride response by 18% in men with the metabolic syndrome. Zhang et al (22) found that the triglyceride AUCI was reduced by 32% in obese hypertriglyceridemic males when exercise was performed 12 h before a high-fat meal. These results provide evidence that, in men with the metabolic syndrome, moderate-to-vigorous–intensity aerobic exercise performed 1 h before a high-fat meal reduces postprandial triglycerides to the same extent as does exercise performed 12 h before a high-fat meal.
Previous investigations have used immediate-release forms of niacin (10) or high dosages (23) to quantify the effects of niacin on postprandial triglycerides. King et al (10) found that 12 wk of immediate-release niacin reduced the triglyceride AUCT by 41% and the triglyceride AUCI by 45% in patients with hypertriglyceridemia and low HDL-cholesterol concentrations. In the current investigation, 6 wk of extended-release niacin reduced the triglyceride AUCT by 23% and the peak triglyceride response by 18%. However, the triglyceride AUCI was not changed by niacin, which suggests that, although niacin reduced fasting triglycerides and the absolute triglyceride concentrations after a meal, the increase in postprandial triglycerides relative to baseline was similar to control. The conflicting triglyceride AUCI results between the current investigation and the study by King et al (10) may be explained by differences in the methods used to calculate the incremental AUC. Instead of using the fasting triglyceride concentrations after the niacin intervention, King et al (10) used baseline triglyceride concentrations before the niacin intervention to calculate the triglyceride AUCI. In the present investigation, the triglyceride AUCI was calculated by using the baseline fasting triglyceride concentrations after the 6-wk niacin intervention.
Although we did not investigate the mechanisms by which niacin attenuates the beneficial effects of aerobic exercise on postprandial triglycerides, it is possible that aerobic exercise and niacin work by similar mechanisms to lower postprandial triglyceride concentrations. We speculate that a decrease in hepatic triglyceride secretion is primarily responsible for the changes in postprandial triglycerides after both aerobic exercise and niacin administration (15). Our data are consistent with this possibility, because the postprandial triglyceride-lowering effect of exercise was attenuated after niacin administration. We also found that fasting triglycerides were correlated with the subsequent postprandial triglyceride response (AUCT), which provides evidence that interventions designed to lower fasting triglycerides may alter the postprandial triglyceride-lowering effects of aerobic exercise. Therefore, it is possible that niacin administration reduces fasting and postprandial triglyceride secretion to the extent that aerobic exercise may provide no additional benefit, at least when performed 1 h before a high-fat meal.
Niacin administration in the current investigation led to an increase in fasting insulin concentrations and the HOMA score, which is thought to reflect a reduction in insulin sensitivity. Reductions in insulin sensitivity are common with niacin administration and are associated with rebound elevations in serum nonesterified fatty acids, because niacin concentrations gradually decrease with each dose (8). In the current investigation, we found that extended-release niacin increased postprandial insulin concentrations by 54% by 2 h after a high-fat meal. However, aerobic exercise conducted after niacin administration attenuated the postprandial rise in insulin concentrations, which provided evidence that aerobic exercise may impart a metabolic benefit to persons taking extended-release niacin.
We recognize that the absence of a crossover is an important limitation in this study; however, we wanted to characterize the postprandial triglyceride response to exercise and niacin both alone and in combination. Aerobic exercise was introduced before the administration of niacin in each subject, to be in agreement with therapeutic lifestyle changes recommended by the NCEP ATP III for sedentary persons with characteristics of the metabolic syndrome (2).
The use of niacin in clinical practice has remained limited because of a number of adverse reactions. The most common adverse reactions associated with niacin are flushing, nausea, loss of appetite, and reductions in insulin sensitivity (7, 24, 25). We found that cutaneous flushing was reported during the investigation in 60% of the participants. However, the event generally was isolated, as evidenced by 100% compliance and the absence of participant dropout. We observed a frequency and severity of reported adverse effects similar to those of previous investigations (26, 27).
In conclusion, aerobic exercise lowered the triglyceride AUCT and was the only condition that lowered the triglyceride AUCI, which suggests that exercise reduces postprandial triglyceride concentrations without necessarily reducing fasting triglycerides. In contrast, extended-release niacin reduced fasting triglycerides but had no influence on the postprandial triglyceride response to a high-fat meal. Niacin also appears to attenuate the postprandial triglyceride-lowering effect of exercise. However, aerobic exercise lowered the insulin response to a high-fat meal after 6 wk of extended-release niacin, which suggests that exercise may attenuate the rise in postprandial insulin concentrations after niacin administration. More work with each intervention will be needed to elucidate the mechanisms by which aerobic exercise and niacin alter postprandial blood lipid and glucose metabolism.
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ACKNOWLEDGMENTS |
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The authors' responsibilities were as follows—EPP: study design, data collection and analysis, and writing of the manuscript; MLM: data collection and analysis; AJM: physician oversight and screening; JKT: data analysis; JM-J: data collection; and PWG: study design, data collection, study oversight, and guidance on the writing of the manuscript. None of the authors had a personal or financial conflict of interest.
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Significantly different from control and exercise; 
Significantly different from control, exercise, and niacin; 
