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American Journal of Clinical Nutrition, Vol. 70, No. 5, 817-825, November 1999
© 1999 American Society for Clinical Nutrition

Original Research Communications

Dietary fish as a major component of a weight-loss diet: effect on serum lipids, glucose, and insulin metabolism in overweight hypertensive subjects1,2,3

Trevor A Mori, Danny Q Bao, Valerie Burke, Ian B Puddey, Gerald F Watts and Lawrence J Beilin

1 From the Department of Medicine, The University of Western Australia and The West Australian Heart Research Institute, Perth.

2 Supported by a grant from the National Health and Medical Research Council of Australia (to LJB and IBP). The fish was kindly donated by Kailis & France Pty Ltd (Perth, Western Australia) and King Oscar Fine Foods Pty Ltd (Melbourne) subsidized the cost of the canned sardines.

3 Address reprint requests to TA Mori, University Department of Medicine, Medical Research Foundation Building, Box X 2213 GPO, Perth, Western Australia 6847. E-mail: tmori{at}cyllene.uwa.edu.au.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Obesity in hypertensive patients is associated with dyslipidemia and insulin resistance, both of which are improved by weight control. n-3 Fatty acids have diverse effects on mechanisms underlying atherosclerosis, including a decrease in serum triacylglycerols and an increase in HDL2 cholesterol.

Objective: The objective was to examine whether dietary fish enhances the effects of weight loss on serum lipids, glucose, and insulin in 69 overweight, treated hypertensive patients.

Design: Overweight patients being treated for hypertension were randomly assigned to either a daily fish meal (3.65 g n-3 fatty acids), a weight-loss regimen, the 2 regimens combined, or a control group for 16 wk.

Results: Sixty-three subjects completed the study. Weight decreased by a mean (±SEM) of 5.6 ± 0.8 kg with energy restriction. Weight loss decreased fasting insulin (P = 0.003) and the area under the curve for insulin (P = 0.003) and glucose (P = 0.047) during an oral-glucose-tolerance test. The greatest decrease occurred in the fish + weight-loss group. There was no independent effect of fish on glucose or insulin. Fish increased HDL2 cholesterol (P = 0.004) and decreased HDL3 cholesterol (P = 0.026) without altering total, LDL, or HDL cholesterol. Weight loss had no effect on these variables. Fasting triacylglycerols fell significantly with fish consumption (29%) and weight loss (26%). The fish + weight-loss group showed the greatest improvement in lipids: triacylglycerols decreased by 38% (P < 0.001) and HDL2 cholesterol increased by 24% (P = 0.04) compared with the control group.

Conclusions: Incorporating a daily fish meal into a weight-loss regimen was more effective than either measure alone at improving glucose-insulin metabolism and dyslipidemia. Cardiovascular risk is likely to be substantially reduced in overweight hypertensive patients with a weight-loss program incorporating fish meals rich in n-3 fatty acids.

Key Words: Fish • n-3 fatty acids • weight control • obesity • lipids • glucose • insulin • hypertension • humans


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Hypertension in overweight subjects is associated with insulin resistance (1–3), dyslipidemia (2), and endothelial dysfunction (4). Treatment of hypertension with drugs such as diuretics and ß-blockers may worsen insulin resistance or adversely affect the serum lipid profile. Nonpharmacologic management of hypertension, therefore, offers advantages as an adjunct or alternative to drug therapy. Current recommendations for the initial management of overweight hypertensive patients include weight loss through energy restriction (5, 6). Dietary fish or fish-oil supplementation is another possible approach (7–11). Several population studies, for example, have suggested that regular consumption of even small amounts of dietary fish may reduce the risk of cardiovascular disease (12), findings supported by one randomized controlled trial (13). In addition to lowering high blood pressure, fish and fish oils rich in n-3 fatty acids can modify a variety of cellular processes associated with lipid metabolism, atherosclerosis, thrombosis, and inflammation (14). However, a possible adverse effect of large amounts of n-3 fatty acids is impairment of glucose tolerance in persons with type 2 diabetes (15–17), although this has not been confirmed in untreated hypertensive (18) or dyslipidemic subjects (19).

Because n-3 fatty acids have been shown to decrease serum triacylglycerols and increase HDL2 cholesterol (20, 21), we hypothesized that the combination of weight loss and daily fish consumption would result in additive or synergistic effects on blood lipids, while possibly attenuating any adverse effects of n-3 fatty acids on glucose-insulin metabolism. To investigate this, we conducted a randomized controlled trial examining the independent and combined effects of weight loss and consumption of fish rich in n-3 fatty acids on serum lipids, glucose, and insulin metabolism in overweight patients being treated for hypertension.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
Overweight, nonsmoking men and postmenopausal women aged 40–70 y receiving antihypertensive treatment for >=3 mo were recruited from the general community by media advertising. Entry criteria included a body mass index (BMI; in kg/m2) >25, a systolic blood pressure between 125 and 180 mm Hg, and a diastolic blood pressure <110 mm Hg (on 2 separate days with a Dinamap 1846 SX/P monitor; Critikon Inc, Tampa, FL). Subjects were not taking lipid-lowering or antiinflammatory drugs, had a usual consumption of not more than one fish meal per week, and drank <175 g ethanol/wk. Sixty-nine of the 248 subjects screened satisfied the entry criteria. The study was approved by the Ethics Committee of the Royal Perth Hospital and all subjects gave written consent.

Dietary education and study design
During a 4-wk familiarization period, subjects were advised to continue their usual diet and alcohol intake and baseline measurements were performed. Subjects were matched for sex, age, and BMI, and randomly assigned to 1 of 4 groups. They were asked to maintain their weight or were assigned to a weight-loss group and were then further randomly assigned to include a fish meal as part of their daily diet or to continue their energy-restricted diet. Thus, the 4 groups were as follows: control group (weight-maintaining diet), fish group (weight-maintaining diet plus fish daily), weight-loss group (energy-restricted diet), and fish + weight-loss group (energy-restricted diet plus fish daily).The weight-loss groups followed an individual dietary program in which their energy intake was decreased by 2000–6500 kJ/d for 12 wk, to achieve a 5–8-kg weight loss, and was then adjusted for an additional 4 wk to maintain their body weight (22). The subjects who had been assigned to consume fish daily (ie, the fish group and the fish + weight-loss group) continued to do so during these 4 wk. All subjects were encouraged to maintain their usual lifestyle during the 16-wk intervention.

All subjects were given written and verbal instructions by a dietitian on how to complete 3-d (2 weekdays and 1 weekend day) dietary records once every month throughout the intervention, and dietary intake was monitored by the dietitian. Those allocated to the energy-restricted diets (ie, the weight-loss group and the fish + weight-loss group) were instructed to reduce their fat intake to <30% of total energy by replacing high-fat foods with low-fat alternatives, by increasing fruit and vegetable intakes, and by replacing refined carbohydrates with complex carbohydrates such as whole-grain bread and cereals. All subjects were advised to not add salt to their food, to avoid eating high-salt foods, and to consume low-salt foods. Those volunteers who were assigned to the weight-maintaining groups were seen every 2 wk by the dietitian, who determined whether the subjects had maintained their usual eating habits and reminded them not to make any changes to their usual diet other than salt reduction. These same subjects were offered instruction on how to follow a weight-loss program on completion of the study. The 2 groups that consumed fish followed a diet similar to one used in our previous studies (23, 24) and were instructed to eat one fish meal daily. To aid in compliance, we provided subjects a variety of previously analyzed fish free of cost. Daily fish meals were prepared from frozen filleted Greenland turbot ({approx}200 g), canned sardines ({approx}106 g), canned tuna ({approx}102 g), and canned salmon ({approx}54 g) providing {approx}3.5, 4.1, 3.2, and 3.8 g n-3 fatty acids/d, respectively (Table 1Go). Menus included all varieties of the fish and provided {approx}3.65 g n-3 fatty acids/d.


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  		TABLE 1. Analysis of the fish used in the study1
 
Lifestyle assessment and anthropometry
Alcohol intake, physical activity, and use of antihypertensive and other medications were recorded daily by subjects and monitored every other week by the investigators over the 16-wk intervention period. All other measurements were recorded at baseline and at the end of the intervention. Weight was measured with an electronic scale with the subjects wearing no shoes and light clothing; height was measured with a stadiometer.

Oral-glucose-tolerance test and serum lipids
An oral-glucose-tolerance test (OGTT) was carried out at baseline and at the end of the intervention with a 75-g glucose load dissolved in 200 mL water after a 10-min rest in the supine position. Glucose and insulin concentrations were determined at 0, 60, and 120 min according to standard methods with an autoanalyzer. Serum for the analysis of lipids and lipoproteins, measured twice at baseline and twice at the end of the intervention, was immediately frozen after collection in liquid nitrogen and stored at –80°C. Samples were assayed in batches by using methods described previously (24).

Plasma phospholipid and fish fatty acids
Plasma (1 mL) prepared from blood collected into EDTA-containing tubes was extracted with CHCl3:CH3OH (2:1, 5 mL). The phospholipid fraction was obtained from total lipid extracts by thin-layer chromatography with a solvent system of hexane:diethyl ether:acetic acid:methanol (170:40:4:4, by vol) on silica gel 60 F254-precoated aluminium sheets (Merck, Darmstadt, Germany). Fatty acid methyl esters were prepared by treating phospholipid extracts with 4% H2SO4 in methanol at 90°C for 20 min and analyzed by gas-liquid chromatography with a model 5980A gas chromatograph equipped with a 3393A computing integrator (Hewlett-Packard, Rockville, MD). The column was a BPX70 (25 m x 0.32 mm, 0.25-mm film thickness; SGE, Ringwood, Victoria, Australia) with a temperature program from 150 to 210°C at 4°C/min and with nitrogen as the carrier gas at a split ratio of 30:1. Peaks were identified by comparing them with a known standard mixture. Individual fatty acids were calculated as a relative percentage with the evaluated fatty acids set at 100%. Total n-3 (20:5, 22:5 and 22:6) and n-6 (20:3, 20:4, and 22:4) fatty acids were measured in plasma phospholipids. Fish fats (Table 1Go) were determined by using similar methods in homogenized flesh drained of oil (sardines) or brine (tuna and salmon) (24).

Statistical methods
Dietary records were analyzed by using DIET/1 (version 4; Xyris, Brisbane, Australia), which is based on the Australian food-composition database NUTTAB 1995A (25). Data were analyzed by using SPSS (SPSS Inc, Chicago) or SAS (SAS Institute Inc, Cary, NC) software with the general linear model (GLM) adjusted for baseline values to assess the main and interactive effects of the fish and reduced-fat, energy-restricted diets. Treatment effects refer to significant differences between groups in postintervention values adjusted for baseline values. Significance levels were adjusted for multiple comparisons by the Bonferroni method. Values are reported as means ± SEMs.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Study population
Sixty-three of the 69 subjects who entered the trial completed the 16-wk intervention. Withdrawals were due to inability to maintain the schedule of laboratory visits or compliance with the diets. Baseline characteristics of the 4 groups were not significantly different, confirming that subjects were well matched (Table 2Go). The additive effects of fish consumption and weight loss on blood pressure were reported elsewhere (26).


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  		TABLE 2. Clinical and biochemical characteristics of subjects at baseline1
 
Antihypertensive medication taken by the patients included acetylcholinesterase inhibitors, ß-blockers, diuretics, and calcium channel blockers. Forty-one of the 63 patients were taking a single antihypertensive medication, 17 (27%) were taking 2 medications, and 5 (8%) were taking >=3 medications. There were no significant differences between groups with respect to the type or number of antihypertensive agents taken.

Changes in weight
The 2 energy-restricted diets resulted in a mean weight loss of 5.6 ± 0.8 kg (P < 0.0001) during the first 12 wk of the intervention, with no further weight loss during the final 4 wk of weight stabilization (Figure 1Go). Weights at baseline and at the end of intervention were, respectively, 91.6 ± 4.0 and 86.4 ± 3.5 kg in the weight-loss group and 89.2 ± 4.2 and 83.3 ± 4.3 kg in the fish + weight-loss group. There was no significant change in weight (0.2 ± 0.3 kg) in the 2 groups that maintained their usual energy intake. Weights at baseline and at the end of intervention were, respectively, 91.5 ± 4.0 and 91.4 ± 4.1 kg in the control group and 100.6 ± 4.7 and 101.1 ± 4.9 kg in the fish group.



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  		FIGURE 1. Mean (±SEM) changes ({triangleup}) in weight from baseline to the end of the 16-wk intervention in the control ({square}; n = 16), fish ({blacksquare}; n = 17), weight-loss ({circ}; n = 16), and fish + weight-loss (•; n = 14) groups.

 
Energy and macronutrient intakes
There were no significant differences in total energy and nutrient intakes between the groups at baseline (Table 3Go). At completion of the intervention, total energy, sodium (P = 0.001), and potassium (P = 0.022) intakes and the percentage of total fat, saturated fat, and monounsaturated fat had decreased significantly from baseline in the 2 weight-loss groups. There was also a significant main effect of weight loss on higher protein and carbohydrate intakes as a percentage of energy. The fish diet was associated with a significantly higher intake of protein and polyunsaturated fat as a percentage of energy intake. Alcohol consumption and physical activity levels did not change significantly during the intervention in any group. There were no significant interactions between dietary macronutrients postintervention.


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  		TABLE 3. Total energy and macronutrient intakes at baseline and changes during the intervention1
 
Plasma phospholipid fatty acids
The fatty acid composition of plasma phospholipids at baseline was not significantly different between groups (Table 2Go). Changes in total n-6 and n-3 polyunsaturated fatty acids from baseline to the end of the intervention indicated compliance with the regular fish intake in the 2 fish-eating groups (Figure 2Go). The addition of fish to the diet significantly increased the percentage composition of n-3 fatty acids in the fish group (5.81 ± 0.99%) and in the fish + weight-loss group (5.02 ± 0.88%) and significantly decreased n-6 fatty acids in the fish group (-2.69 ± 0.55) and in the fish + weight-loss group (-2.11 ± 0.64%).



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  		FIGURE 2. Mean (±SEM) changes ({triangleup}) in the percentage of plasma phospholipid n-3 (20:5, 22:5, and 22:6) and n-6 (20:3, 20:4, and 22:4) fatty acids after the 16-wk intervention in the control (n = 16), fish (n = 17), weight-loss (n = 16), and fish + weight-loss (n = 14) groups. There was a significant treatment effect with both fatty acids, P < 0.0001 (ANOVA). *Significantly different from the control group, P < 0.0001.

 
Glucose and insulin
At baseline, there were no significant differences between groups in fasting blood glucose or insulin concentrations or in the area under the curve (AUC) for glucose and insulin after the OGTT (Table 2Go). Postintervention, however, there were significant differences between the groups in fasting insulin and in the AUC for insulin and glucose during the OGTT, after baseline values were adjusted for. In the weight-loss groups, there were significant reductions in fasting insulin (–4.05 pmol/L, 29%) and in the AUC for insulin (–2516 pmol•min/L, 28%) and glucose (–71 mmol•min/L, 8%) during the OGTT (Figure 3Go). Although dietary fish had no significant independent effects on changes in blood glucose and insulin, the fish + weight-loss group had the greatest decrease from baseline in fasting insulin (–4.28 pmol/L, 33%) and in the AUC for glucose (-81 mmol•min/L, 9%) and insulin (–2846 pmol•min/L, 32%). The decrease in fasting insulin and in the AUC for insulin in the 2 weight-loss groups was significantly different from the small increase in values in the fish group. There were no significant interactions between fish diets and weight loss on glucose or insulin indexes.



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  		FIGURE 3. Mean (±SEM) changes ({triangleup}) from baseline to the end of the 16-wk intervention in fasting serum glucose and insulin and in the area under the curve (AUC) for insulin and glucose in the control (n = 16), fish (n = 17), weight-loss (n = 16), and fish + weight-loss (n = 14) groups. The general linear model was used to assess treatment, main, and interactive effects on postintervention values adjusted for baseline values. There were no significant interactions between fish diets and weight loss on glucose and insulin indexes. {triangleup}Fasting insulin: treatment effect (P = 0.019), main effect of weight loss (P = 0.003); {triangleup}glucose AUC: main effect of weight loss (P = 0.047); {triangleup}insulin AUC: treatment effect (P = 0.018), main effect of weight loss (P = 0.003). *Significantly different from the control group, P < 0.05. {dagger}Significantly different from the weight-loss and fish + weight-loss groups, P < 0.05.

 
Serum lipids and lipoproteins
Baseline serum lipids and lipoproteins were not significantly different between groups (Table 2Go). There was no significant main effect of fish consumption on total or LDL cholesterol (Figure 4Go). Weight loss was associated with a small decrease of 0.18 mmol/L (NS) in total cholesterol, but there was no change in LDL cholesterol. Relative to the control group, fasting triacylglycerol concentrations decreased by –0.57 mmol/L (29%) in the fish group, by –0.51 mmol/L (26%) in the weight-loss group, and by –0.76 mmol/L (38%) in the fish + weight-loss group. There was no significant effect of fish consumption on total HDL cholesterol (0.04 mmol/L) (Figure 5Go). However, fish consumption increased HDL2 cholesterol by 0.08 mmol/L (24%) and decreased HDL3 cholesterol significantly by 0.04 mmol/L (5%). HDL2 cholesterol increased in the fish and fish + weight-loss groups by 21% and 24%, respectively. The fish + weight-loss group showed the greatest improvement in dyslipidemia, with a significant decrease in triacylglycerol concentrations of 0.76 mmol/L (38%) and a significant increase in HDL2 cholesterol of 0.08 mmol/L (24%) compared with the control group. There were no significant interactions between fish diets and weight loss on lipid indexes.



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  		FIGURE 4. Mean (±SEM) changes ({triangleup}) from baseline to the end of the 16-wk intervention in serum total cholesterol, LDL cholesterol, and triacylglycerols in the control (n = 16), fish (n = 17), weight-loss (n = 16), and fish + weight-loss (n = 14) groups. The general linear model was used to assess treatment, main, and interactive effects on postintervention values adjusted for baseline values. There were no significant interactions between fish diets and weight loss on any of the variables shown. {triangleup}Cholesterol: main effect of weight loss (P = 0.088); {triangleup}triacylglycerols: treatment effect (P = 0.0001), main effect of weight loss (P = 0.002), main effect of fish (P < 0.001). **Significantly different from the control group, P < 0.001.

 


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  		FIGURE 5. Mean (±SEM) changes ({triangleup}) from baseline to the end of the 16-wk intervention in serum HDL, HDL2, and HDL3 cholesterol in the control (n = 16), fish (n = 17), weight-loss (n = 16), and fish + weight-loss (n = 14) groups. The general linear model was used to assess treatment, main, and interactive effects on postintervention values adjusted for baseline values. There were no significant interactions between fish diets and weight loss on any of the variables shown. {triangleup}HDL2 cholesterol: treatment effect (P = 0.036), main effect of fish (P = 0.004); {triangleup}HDL3 cholesterol: main effect of fish (P = 0.026). *Significantly different from the control group, P < 0.05. {dagger}Significantly different from the fish and the fish + weight-loss groups, P < 0.05.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Incorporation of a daily fish meal rich in n-3 fatty acids into a reduced-fat, energy-restricted diet resulted in substantial improvements in glucose and insulin metabolism as well as in serum lipids in obese individuals being treated for hypertension. This dietary approach conferred greater benefits than did a fish diet or a weight-loss program alone. These findings complement those of our previous report, which showed that combining a daily fish meal with a weight-loss regimen led to additive effects on ambulatory blood pressure and decreased heart rate (26). The effects were greatest on waking blood pressures, which fell by 6.0 and 3.0 mm Hg (systolic and diastolic, respectively) with dietary fish alone, 5.5 and 2.2 mm Hg with weight loss alone, and 13.0 and 9.3 mm Hg with fish and weight loss combined relative to control values (26). Dietary fish, but not weight loss, also significantly decreased 24-h (P = 0.036) and waking (P = 0.013) ambulatory heart rates (26).

The effect of the combination of fish and weight loss on the glucose-insulin axis was of interest in that, whereas there was no significant effect of fish consumption in participants in the non-energy-restricted groups, the combination of fish consumption and weight loss improved glucose and insulin metabolism. Improved insulin sensitivity in the fish + weight-loss group might have been related to changes in fatty acid delivery to the liver as a result of both the profound reduction in postprandial lipemia associated with n-3 fatty acids (27) and a reduction in abdominal fat cell mass.

The effects of n-3 fatty acids on glycemic control, particularly in patients with type 2 diabetes, remain a controversial issue. Most (15, 16, 28–33) but not all (31, 34) reviews have suggested that n-3 fatty acids have adverse effects on indexes related to glycemia. Controlled trials in hypertensive (18) and dyslipidemic (19) subjects, however, showed no adverse effects on glucose tolerance. A meta-analysis by Friedberg et al (34) showed that although there was a tendency to increased fasting blood glucose concentrations in patients with type 2 diabetes, blood glucose concentrations decreased significantly in patients with type 1 diabetes. It was noted that in type 2 diabetes, doses of up to 3 g n-3 fatty acids/d are safe and effective for lowering triacylglycerols without adversely altering glycemia (34). In contrast, our group reported that in patients with type 2 diabetes, the same regimen of fish feeding as used in the present study led to a small increase in glycated hemoglobin and a significant increase in self-monitored glucose concentrations relative to control values, an effect that was prevented by concomitant regular exercise (17). These results contrast with reports that adverse effects on glycemic control were observed more often (35–38), but not always (39), after large doses of n-3 fatty acids (4–10 g/d). Either a transient effect or no effect after lower doses (2.5–4 g/d) was observed (36, 40–42). Note, however, that even 3 g n-3 fatty acids/d has been shown to increase blood glucose concentrations in patients with type 2 diabetes (43, 44). Effects of n-3 fatty acids on glycemia have been ascribed to increased hepatic glucose production, diminished insulin secretion (15), or both, or to increased gluconeogenesis from glycerol without changes in total hepatic glucose production (40). The present study supports previous findings of improvements in glucose tolerance with weight loss in obese subjects (45). It has also been shown that dietary n-3 fatty acids, if combined with a weight-loss program, can be consumed without compromising glycemic control.

Previous studies showed reproducible decreases in triacylglycerols with n-3 fatty acid consumption (20, 21, 24) or weight loss (22), whereas changes in total, LDL, and HDL cholesterol after n-3 fatty acid intake have been variable (20, 21). These contradictory findings can be explained, in part, by variations in the amount of n-3 fatty acids consumed and by the severity and type of the subjects' lipoprotein disorder. We showed previously that the background concentration of dietary fat has a critical influence on serum lipid responses to n-3 fatty acids (24). Fish or fish oil incorporated into a diet providing 40% of energy as fat increased total, HDL, HDL2, and LDL cholesterol, but decreased triacylglycerols (24). In contrast, when fish was incorporated as part of a diet providing 30% of energy as fat, total and LDL cholesterol and triacylglycerols all decreased, and only HDL2 cholesterol increased (24). In the present study, optimal changes in lipids occurred in the fish + weight-loss group, with a decrease in triacylglycerols of 0.76 mmol/L (38%) and an increase in HDL2 cholesterol of 0.08 mmol/L (24%) compared with the control group. Therefore, the direction of the changes in serum lipids in the fish + weight-loss group was not different from, albeit smaller than, that we reported previously in men with increased cardiovascular risk who were placed on an isoenergetic diet providing 30% of energy as fat, which included a daily fish meal for 12 wk (24). In that study, triacylglycerols decreased by 0.38 mmol/L (23%) and HDL2 cholesterol increased by 0.06 mmol/L (15%).

Changes in serum lipids after weight loss in overweight patients have been well documented. We reported previously that overweight, middle-aged men following a dietary regimen similar to the one described herein lost 7.7 kg over 18 wk (22). This loss was associated with a decrease in total cholesterol of 0.40 mmol/L (P = 0.07), a decrease in triacylglycerols of 0.81 mmol/L (P < 0.001), and an increase in HDL cholesterol of 0.11 mmol/L (P < 0.05). Increases in HDL cholesterol with energy reduction have been reported in some (6, 46) but not all (6) studies. In the present study, a 5.6-kg weight loss did not lead to any significant main effects on HDL, HDL2, or HDL3 cholesterol. Energy restriction led to a nonsignificant decrease in total cholesterol of 0.18 mmol/L, which was somewhat less than that we reported previously (22). Triacylglycerols decreased significantly by 0.51 mmol/L with weight loss, confirming the findings of our previous study (22). Our use of a 4-wk stabilization period at the end of the intervention may have accounted for the difference in results between this and other studies in which energy restriction was maintained throughout.

In epidemiologic terms, the increase in HDL2 cholesterol in the fish group (equivalent to 0.07 mmol/L, 21%) and in the fish + weight-loss group (equivalent to 0.08 mmol/L, 24%) could markedly decrease the incidence of cardiovascular disease (47), given that HDL2 cholesterol is the subfraction of HDL cholesterol that may be most protective against cardiovascular disease (48). It is also noteworthy that total HDL cholesterol increased by 0.04 mmol/L after dietary fish consumption. An increment of 0.026 mmol/L in HDL cholesterol predicts a 2–3% reduction in coronary risk (49). Although there has been controversy over whether hypertriglyceridemia is an independent risk factor for coronary artery disease, several population studies strongly suggest that elevated plasma triacylglycerols are a significant risk factor, particularly in individuals with type 2 diabetes or impaired glucose tolerance (50). In addition, elevated triacylglycerols are a risk factor for cardiovascular disease, independent of HDL-cholesterol concentrations (51), with a relative risk of 1.3 and 1.8 for a 1-mmol/L increase in triacylglycerols in men and women, respectively. Findings from the Physicians' Health Study further showed that triacylglycerol concentrations are a strong and independent predictor of future risk of myocardial infarction, particularly when the total cholesterol concentration is also elevated (52). Therefore, the significant decrease in triacylglycerols achieved with either weight loss or fish consumption in the present study may represent a substantial reduction in risk in these patients.

Although most of our volunteers completed the study, they were self-selected and thus are unlikely to represent the general population of obese hypertensive patients. Furthermore, one could argue that the level of compliance seen with both weight loss and dietary fish intake could not be readily achieved in the usual clinical situation. However, weight control has been one of the more effective strategies in hypertension-prevention programs in the United States (53–55). There are also studies suggesting that long-term consumption of fish is easily achieved (14), especially if one adopts a dietary regimen similar to the one advised in the present study, which included a wide variety of fish and preparation options.

Fish-oil concentrates provide another option for lowering blood pressure in obese hypertensive patients. However, daily fish consumption offers greater dietary benefits because as fish consumption increases, meat consumption likely decreases, resulting in a decrease in saturated and total fat intakes without changes in protein and other macronutrients.

In summary, the present study showed that the incorporation of fish into an energy-restricted, fat-reduced diet has significant beneficial effects on glucose, insulin, and lipid metabolism. These effects in conjunction with our previous findings—significant reductions in blood pressure and heart rate with weight loss and fish consumption (26) and anticipated changes in vascular function (56), hemostasis (14), and platelet function (57) with high intakes of n-3 fatty acids from fish—are likely to substantially reduce the risk of cardiovascular disease in obese hypertensive patients.


   ACKNOWLEDGMENTS
 
We acknowledge the technical assistance of Lynette McCahon and Ken Robertson, the nursing assistance of Jessie Prestage and Di Dunbar, and the diet counseling of Nella Gianguilio.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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Received for publication November 23, 1998. Accepted for publication March 19, 1999.




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