| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Original Paper |
U.S. Department of Agriculture, ARS, Beltsville Human Nutrition Research Center, Nutrient Requirements and Functions Laboratory, Beltsville, Maryland
Address reprint requests to: Dr. Meira Fields; USDA, ARS, BHNRC, NRFL; Bldg. 307, Rm. 330, BARC-East; Beltsville, MD 20705-2350.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSREFERENCES |
|---|
Methods: Forty-eight weanling, male Sprague Dawley rats were randomly assigned to eight dietary groups differing in the levels of copper and iron and type of dietary fat (saturated or unsaturated). The diets were either deficient (0.6 µg Cu/g) or adequate (6.8 µg Cu/g) copper and either adequate (53 µg Fe/g) or high (506 µg Fe/g) iron. All diets contained starch as the sole source of dietary carbohydrate.
Results: Regardless of the type of dietary fat, three copper-deficient rats fed the high levels of dietary iron died prematurely due to ruptured hearts. Surviving rats belonging to the copper deficiency and high-dietary iron regimen developed severe anemia, enlarged hearts and livers, and exhibited the highest levels of liver iron. These rats also developed hypercholesterolemia. Triglycerides were elevated by the consumption of high iron diets.
Conclusion: Data show that levels of dietary iron, not the type of dietary fat, are potential inducers of hypertriglyceridemia. Data also show that the combination of high iron intake and dietary copper deficiency is responsible for elevating blood cholesterol.
Key words: copper deficiency, iron, hypercholesterolemia, hypertriglyceridemia, saturated fat, unsaturated fat, starch
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSREFERENCES |
|---|
Dietary means capable of elevating liver iron include: copper deficiency, saturated fat and dietary iron. Copper deficiency is associated with liver iron retention [4,5]. Saturated fat has the ability to raise liver iron by increasing iron absorption [6,7]. The consumption of high levels of dietary iron can also result in elevation of liver iron. However, excess liver iron by itself is not sufficient to raise blood cholesterol. Excess liver iron in combination with inadequate antioxidant protection is.
Copper deficiency results in inadequate antioxidant defense mechanism [8,9]. It also results in excess liver iron [4,5]. The combination of copper deficiency with excess liver iron results in generation of free radicals which induce oxidative stress [10]. Oxidative stress could have the potential to raise blood cholesterol. This hypothesis is supported by the findings that, in copper deficiency, high liver iron is associated with high levels of blood lipids [2] and the reduction of liver iron prevents free radical formation [11] and hypercholesterolemia [3].
In all our past studies, hyperlipidemia associated with copper deficiency occurred when the diet consumed contained simple sugars such as sucrose or fructose [12,13]. These sugars by themselves are lipogenic and are able to raise blood lipids [14–16]. When the copper-deficient diet contains complex carbohydrates such as starch, blood lipids are not elevated [12,13]. The consumption of fructose may mask hyperlipidemic properties of other dietary nutrients such as iron. In order to determine whether levels of iron per se and not fructose have the potential to raise blood lipids, the diets consumed by rats of the present study did not contain fructose, but they contained starch. In addition, omitting fructose from the diet prevented elevating blood lipids by the synergistic effects of fructose and saturated animal fat [16,17].
It is well recognized that diets high in saturated fat increase the risk of hypercholesterolemia and coronary heart disease [18,19]. In order to reduce blood cholesterol, the United States Department of Agriculture (USDA), Health and Human Services (HHS) and the National Academy of Sciences have recommended that dietary saturated fat be reduced or substituted with unsaturated fat [18,19]. We have recently reported that the consumption of unsaturated fat did not elevate liver iron nor did it raise blood cholesterol [20]. However, when saturated fat was consumed, liver iron was elevated and blood cholesterol was raised [20]. We, therefore, asked the question whether high levels of dietary iron will negate the protective effect of unsaturated fat against hyperlipidemia?
The present study was conducted to determine whether high levels of iron are potential inducers of blood cholesterol when a rat consumes a copper-deficient diet which contains both starch and unsaturated fat. It was the aim of this study to challenge the protective effects of both starch and unsaturated fat against hypercholesterolemia by feeding rats a copper-deficient diet supplemented with high levels of dietary iron.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSREFERENCES |
|---|
The rats were fed their respective diets for five weeks. They were allowed free access to food and distilled water. Rats were sacrificed following an overnight fast. Livers and hearts were removed, weighed and portions of liver were taken for copper and iron determinations. Blood was collected into capillary tubes for hematocrit measurements. Blood was also collected into heparinized test tubes, and plasma cholesterol and triglycerides were measured by conventional methods using the automated procedure of the CentrifiChem.
The study was designed to answer the question whether the type of dietary fat and the levels of iron and copper could affect the severity of copper deficiency. Therefore, data were analyzed by a 2x2x2 analysis of variance (ANOVA), (two types of fats, two levels of copper and two levels of iron). The main effects of fat, copper, iron and the interactions among them at p<0.05 were considered significant.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSREFERENCES |
|---|
Rats fed the copper adequate diets containing 50 µg Fe/g and corn oil were considered as normal controls. Table 1 summarizes body mass, relative organ sizes and hematocrit. Body mass was reduced by copper deficiency. The consumption of a high-iron diet caused a reduction of body mass in copper-deficient rats. Liver size was increased by copper deficiency. The combination of copper deficiency with high iron resulted in enlarged livers. Heart size was increased by copper deficiency. The largest heart size was noted in copper-deficient rats which consumed the high level of dietary iron. All copper-deficient rats were anemic. The most severe anemia was noted in copper-deficient rats which consumed the high-iron diet.
|
|
|
DISCUSSION |
|---|
The role of high iron stores as a risk for coronary heart disease has been emphasized by Salonen [23]. Interest in iron as a potential risk factor for coronary heart disease has been increased by experiments in animals showing that iron overload increases myocardial damage caused by anoxia and reperfusion and that the use of the iron chelator deferoxamine results in a decrease in myocardial damage in several animal studies [24,25,10]. This effect may result from the ability of free iron to catalyze the formation of reactive radicals such as hydroxyl radicals from superoxide and hydrogen peroxide [26]. In addition, substantial evidence supports the idea that generation of reactive oxygen species might be involved in the pathogenesis of atherosclerosis through the promotion of oxidative modifications of low-density lipoproteins (LDL), increasing its atherogenic potential [27]. These data implicate iron in the development of heart disease. Sullivan hypothesized that iron deficiency could be protective against coronary heart disease [28]. This may be the explanation for the well-known differences in coronary heart disease risk for men and women [29].
During the last few years we have suggested that the essential metalloelement iron, a major oxidant in vivo, could be involved in atherogenesis by increasing blood cholesterol and triglycerides [1–3]. This hypothesis was supported by the findings that, when rats were fed a copper-deficient diet, they exhibited liver iron retention, hypercholesterolemia and hypertriglyceridemia [1–3]. When liver iron was reduced, blood lipids were lowered [1–3]. However, it was difficult to draw a definite conclusion regarding the role of iron in hypercholesterolemia of copper deficiency because not all copper-deficient rats which consumed the copper-deficient diet developed high levels of blood lipid. The development of hyperlipidemia was dependent on the type of dietary carbohydrate fed [12,13]. When rats were fed a copper-deficient diet which contained fructose, they always developed hyperlipidemia [12,13]. However, when they were fed a copper-deficient diet which contained starch, they never exhibited high levels of blood lipids, although their livers contained excess liver iron [12,13,30]. Similarly, when fed a copper-deficient diet containing starch, no free radicals were generated [10]. We have now succeeded in inducing elevated levels of blood lipids in copper-deficient rats fed starch. These present data clearly show that the consumption of a diet inadequate in copper but supplemented or fortified with iron overrules the protective effects of starch. These data also confirm our hypothesis that the consumption of high levels of dietary iron is an inducer of hyperlipidemia, even when the diet contains starch, a non-lipogenic complex carbohydrate.
It is well known that cholesterol feeding results in marked changes in serum lipoprotein profiles and lipoprotein metabolism [31–33]. The extent to which dietary cholesterol influences total blood cholesterol and lipoprotein tends to vary depending on specific experimental conditions used. Bile acids have been used to modify the response of animals to dietary cholesterol [31,34,35]. Indeed, supplementation with cholesterol and bile acids produces hypercholesterolemia and lesions resembling human atherosclerosis [31,34,35].
The diets used in the present study contained corn oil and beef tallow. Beef tallow contains 51.4% saturated fat compared with 11.8% in corn oil. It also contains 18.9% stearic acid compared with 1.8% in corn oil, and it contains 109 mg/100 g cholesterol. Corn oil is free of cholesterol. However, regardless of the presence of cholesterol in beef tallow, hypercholesterolemia developed in rats which had been fed the low-copper, high-iron diet. Thus, regardless of the nature of dietary fat, the high intake of dietary iron worsened the effects of copper deficiency.
It is usually assumed that a diet containing saturated fat is responsible for high levels of blood lipids, which in turn lead to coronary heart disease. In order to reduce blood cholesterol, the USDA, HHS and the National Academy of Sciences have recommended that dietary saturated fat be reduced or substituted by unsaturated fat [18,19]. It has been shown that saturated fat has the ability to raise liver iron compared with unsaturated fat [6,7,30]. The increases in liver iron were associated with high levels of cholesterol and triglycerides [6,7,30]. The failure of unsaturated fat to raise blood lipids may be linked to its inability to increase liver iron [20].
One of the main purposes of the present study was to test the hypothesis that high levels of liver iron are instrumental in raising blood lipids. If iron is a major cholesterol-raising factor in copper deficiency, then the type of dietary fat should not have an effect on cholesterol when dietary iron is sufficiently increased. Data of the present study show that the combination of high iron with low copper was responsible for raising blood cholesterol. Under these dietary conditions, the type of dietary fat had no effect on levels of blood lipids. Data also show that levels of blood triglycerides were also affected by iron supplementation. Although the type of dietary fat, saturated vs. unsaturated, raised liver iron in copper-adequate rats, it had no effect on liver iron in copper deficiency. In toto: data show that levels of dietary iron, not the nature of dietary fat, are responsible for hyperlipidemia when antioxidant defense mechanism is compromised.
A large percentage of Americans take dietary supplements. The supplements most commonly used by adults are vitamin-mineral combinations such as multivitamins containing iron and single vitamins and minerals [36]. In addition, median intake of copper from food is lower than the estimated safe and adequate daily dietary intake (ESADDI) values for most age, gender and racial/ethnic subgroups [36]. The high intake of iron may raise levels of liver iron. Elevating liver iron could potentially increase risk factors associated with cardiovascular disease when antioxidant defense system is inadequate.
Received March 1, 1999. Accepted May 1, 1999.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSREFERENCES |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
