Nutrition in Health and Disease
The interaction between genes and the environment plays a major role in the human life cycle from birth to death beginning with fertilization through the stages of growth, development, and aging. The role of nutrition, which can modify the genetic base, is of crucial importance in this life cycle. Human nutrition is a science that deals with nutrients and how the body assimilates them. Life maintenance requires food as well as water and oxygen. Food provides the energy required to support the body’s life sustaining processes and the materials required to build and maintain all body cells. These materials, called nutrients, undergo extremely complex processes in the body, from breakdown to release as energy and from rebuilding cells and tissues to maintain the overall health of the individual.
The satisfaction of nutritional needs is mandatory to human life from conception through growth and development and finally to the achievement of long-term survival. Diet is a major influence during the human life cycle since food preferences, influenced by likes and dislikes, mainly determine what people eat. Other influencing factors include advertising, socioeconomic and time constraints, cultural and religious beliefs, and health related concerns. In order to achieve maximum genetic potential in the human life cycle, optimal nutritional needs must be satisfied.
The understanding of the role of nutrition in health maintenance and disease prevention has advanced rapidly in the past decade. The relationship between nutritional deficiencies and chronic diseases such as cardiovascular disease and cancer, especially breast and prostate cancer, have come under close scrutiny. With increased emphasis on disease prevention and health maintenance, in 1989 the federal government issued the recommended dietary allowances for nutritional supplements1. In 1989, the National Academy of Sciences made the following recommendations.
- Reduce total fat intake to 30% or less of kcalories. Reduce saturated fat intake to less than 10% of kcalories, and the intake of cholesterol to less than 300 mg daily.
- Increase intake of starches and other complex carbohydrates.
- Maintain protein intake at moderate levels.
- Balance food intake and physical activity to maintain appropriate body weight.
- For those who drink alcoholic beverages, limit consumption to the equivalent of less than 1 oz of pure alcohol in a single day. Pregnant women should avoid alcoholic beverages.
- Limit total daily intake of salt (sodium chloride) to 6 g or less.
- Maintain adequate calcium intake.
- Avoid taking dietary supplements in excess of the RDA in any single day.
- Maintain an optimal intake of fluoride, particularly during the years of primary and secondary tooth formation and growth.
More simply, the U.S. Department of Agriculture and the U.S. Department of Human Services made the following recommendations.
- Eat a variety of foods.
- Maintain desirable body weight.
- Choose a diet low in fat, saturated fat, and cholesterol.
- Choose a diet with plenty of vegetables, fruit, and grain products.
- Use sugars in moderation.
- Use salt and sodium in moderation.
- If you drink alcoholic beverages, do so in moderation.
As early as 1990, the Surgeon General of the U.S. issued specific objectives for primary health in America. These objectives were updated in 1990 to define the national goals for the year 2000, healthy people 2000. The U.S. Surgeon General identified 21 specific nutrition related objectives to improve the nation’s health. The broad goals to be achieved by year 2000 are:
- Increase the number of healthy years for Americans.
- Reduce health disparities among segments of Americans.
- Achieve equal access to preventive health services for all Americans.
Classification of Essential Nutrients
Nutrients are classified into six major groups: proteins, carbohydrates, fats, vitamins, minerals, and water. Carbohydrates, fats, and proteins are considered the energy-yielding and tissue-building macronutrients, while the vitamins and minerals are classified as the micronutrients.
Carbohydrates contain carbon, hydrogen, and oxygen in combination to form small molecules such as monosaccharides and disaccharides (sugars) and large polysaccharide molecules such as starch.
Lipids, comprising fats and oils, also contain carbon, hydrogen, and oxygen but the proportion of oxygen is much less than that found in carbohydrates. Food fat occurs mainly in the form of triglycerides, a compound consisting of fatty acids esterified to a glycerol base. It is stored in the adipose tissues of the body and releases free fatty acids into the circulation when hydrolyzed by enzymes.
Proteins comprise chains of amino acids linked together to form high molecular weight compounds and in addition to carbon, hydrogen, and oxygen also contain nitrogen and sometimes sulfur. Specific amino acids are linked in a specific sequence to form peptide chains that are further linked to form specific proteins.
Vitamins are organic compounds which function as coenzymes in a number of enzymatic reactions involved in the production of energy and in the building of cells necessary to the maintenance of body tissues.
Minerals are inorganic elements that serve an indispensable function in enzymatic reactions involved in energy production and tissue building and also serve as structural components of bone and other body tissues.
Water is not only vital to the body as a transport medium for all nutrients and waste but is also the medium in which all vital metabolic reactions in the body occur. It is also an essential starting product of many biochemical reactions in the body involved in energy production and tissue building.
The Physiological Role of Nutrients
The three physiological components required by the human body to survive and remain healthy are: energy to do its work, building materials to maintain its form and function, and control agents to regulate these processes. The foods we eat contain both macronutrients which comprise the carbohydrates, fats, and proteins and micronutrients which comprise the vitamins and minerals.
Carbohydrates As A Source Of Concentrated Energy. The sum of all the complicated biochemical and physiologic processes by which the body produces energy to do its work, builds tissues (anabolism) and reshapes tissues (catabolism) is called metabolism. Body energy is derived from the metabolism of all three macronutrients in our food but the body reserves the carbohydrates and fat as the main source of fuel supply. Starches and sugars represent the main forms of carbohydrate foods we ingest and are the basic source of raw fuel for energy production. In order to convert the raw fuel into energy, the body must do three things:
- It must metabolize or convert the raw fuel into a refined fuel which the biological system can utilize.
- It must carry the refined fuel to parts of the body that require it.
- It must burn the refined fuel to produce energy.
The body easily accomplishes this feat through a series of intricate metabolic processes. First it digests the raw fuel, starches (polysaccharides) and sugars (disaccharides), producing a monosaccharide, glucose, as the refined fuel which is then absorbed into the blood circulation and transported to the various cells in the body in need of energy. Through the intricate metabolic pathways of glycolysis and the citric acid cycle involving a series of enzymatic reactions, the cell breaks down the glucose to yield energy. Glycolysis is the initial energy production pathway by which the six-carbon glucose is converted to an active three-carbon fragment, pyruvate, capturing energy in the high energy phosphate bonds of ATP. For every molecule of glucose metabolized to pyruvate, two molecules of ATP are generated. The oxidative decarboxylation of pyruvate with the subsequent formation of acetyl CoA is the link between glycolysis and the citric acid cycle wherein one high-energy bond is generated in each round of the cycle. Carbon dioxide and water are end products of this metabolic process.
The carbohydrates comprise a class of foods that vary from simple to complex structures. The simplest class of carbohydrates are six-carbon units and include the simple sugars glucose, fructose, galactose, and mannose. Slightly more complex are the disaccharides consisting of two six-carbon units linked together through an oxygen bridge (glyceride link) and include sucrose (cane sugar), lactose (milk sugar) and maltose. The monosaccharides linked together in sucrose are glucose and fructose, glucose and galactose in lactose, and two glucose units in maltose. The monosaccharides and disaccharides are called simple carbohydrates because they are easily broken down with immediate release of energy. The complex carbohydrates comprise the polysaccharides, which are made up of hundreds of monosaccharides connected by glyceride links. Starch is an example of a complex polysaccharide most common in human nutrition. It is the main source of dietary carbohydrates found in legumes, grains, cereals, and potatoes. Approximately 20% of the molecule is made up of glucose units linked in a straight chain called amylose while 80% of the molecule is linked in multiple branched chains called amylopectin. In the digestion process the glucose units are gradually split off to supply a constant source of energy over a period of time. The excess glucose is transported to the liver where it is converted back to a starch-like polysaccharide, glycogen, and stored as a source of energy for fasting periods.
There are certain fibrous polysaccharides which are nondigestible because humans lack the digestive enzymes necessary to break them down to simple carbohydrates. Cellulose, which forms the fibrous component of plant cell walls and is the most abundant organic compound on earth, is an example of a nondigestible polysaccharide. The rigidity of cellulose arises from its overall structure which consists of chains, or microfibrils of up to 14,000 units of D-glucose that occur in twisted rope-like bundles held together by hydrogen bonding. The insoluble polysaccharide cellulose, together with soluble nondigestible polysaccharides such as gums, mucilages, and pectins, provide valuable dietary fiber essential to health. The nutritional importance of dietary fiber is well known in gastrointestinal disease such as diverticulosis. It is also very important in the management of serum lipid and glucose levels and in risk reduction in chronic conditions such as cardiovascular disease and diabetes. For a summary of dietary fiber classes see William, SR.
Fat As A Source Of Concentrated Energy. Fats and oils are triglycerides which means that they are triesters of fatty acids and glycerol. The distinction between fats and oils is an arbitrary one, fat being a solid while oil is a liquid at room temperature. Most triglycerides in animals are termed animal fats, such as bacon and beef fat, while those in plants are termed vegetable oils, such as corn and safflower oils. Because they can be hydrolyzed or broken down to smaller molecules, fats and oils fall into the category of complex lipids while a lipid such as cholesterol that cannot be hydrolyzed is called a simple lipid. Cholesterol is the most widespread simple lipid and falls into the category of chemical compounds known as steroids. It is an important intermediate in the biosynthesis of steroid hormones and an important structural component of cell membranes of higher animals. However, because it can be synthesized from acetyl CoA, it is not a dietary necessity. High levels of blood cholesterol are associated with arteriosclerosis and cardiovascular disease. Meats and egg yolks are especially rich sources of cholesterol. Two fatty acids, linoleic acid and a-linolenic acid, are considered essential nutrients because the body cannot synthesize them. Linoleic acid occurs as a glyceride of many vegetable oils such as soybean, cottonseed, olive, peanut, corn, sunflower seed, safflower , and poppy seed while a-lenolenic occurs as a glyceride in soybean oil and most drying oils.
Fats yield twice the energy level of carbohydrates when metabolized and therefore supply a concentrated fuel source for body energy. This is especially important since excess carbohydrate, not utilized as a primary energy source, is easily converted to fat by the body and stored in the adipose tissues, fat storage sites composed of adipocytes or fat cells. Although fat from animal sources and oil from plant sources yield the same amount of energy when metabolized, they have a significantly different impact upon health. Excess dietary fat and cholesterol from animal sources are considered a serious risk factor for cardiovascular disease. The U.S. Government dietary guidelines for Americans recommend lowering daily dietary fat intake to 30% of the total Kcalories.
Measurement Of Nutrient Energy. The energy yielded by the macronutrients – carbohydrate, fat, and protein – is measured in kilocalories (kcalories or kcal). The caloric value of foods is determined in the laboratory with a calorimeter, the kcalorie being defined as the energy necessary to raise the temperature of one kilogram of water from 14.5 oC to 15.5 oC. The energy equivalents of macronutrients have been universally standardized:
One Carbohydrate Gram = 4kcal
One Fat Gram = 9kcal
One Protein Gram = 4kcal
It should be noted that alcohol can also be a source of energy, yielding 7 kcal/g. However, alcohol is an indirect source of energy, alcohol not being capable of direct utilization in the glycolytic and citric acid cycles. It is converted by the liver into fat and stored in the liver or adipose tissues of the body.
Protein Metabolism And Amino Acids As Basic Building Units. Proteins are considered among the most important compounds in the animal organism. The word protein is derived from the Greek proteios, which means primary. The name amino acid is derived from its chemical structure, amino referring to the
NH2 group and acid referring to the -COOH group. Like carbohydrates and fats, proteins contain carbon, hydrogen, and oxygen in their structure but unlike carbohydrates and fats, which contain no nitrogen, proteins contain 16% nitrogen. Proteins are made up of amino acids linked together by peptide linkages (-CONH) to form a chain. The amino acids found in proteins are a-aminocarboxylic acids with differences between amino acids due to variations in the side chain R. The general empirical formula for amino acids is:
he simplest amino acid is aminoacetic acid or glycine where R is a hydrogen atom and consequently does not contain a chiral carbon (asymetric carbon atom). All other amino acids have side chains making their a-carbons chiral. Amino acids found in proteins belong to the L-series, which means that the groups attached to the a-carbon have the same configuration as L-glyceraldehyde.
Essential And Nonessential Amino Acids. There are twenty-two known amino acids in existence and ten of these are considered essential because the body cannot synthesize them. The ten essential amino acids are arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryoptophan, and valine. Ten amino acids, capable of synthesis by the body and considered nonessential, include alanine, asparagine, aspartic acid, glutamic acid, glutamine, glycine, hydroxyproline, hydroxylysine, proline, and serine. Two amino acids, cysteine and tyrosine, are considered semiessential because of their inadequate production by the body to support their growth. The protein containing foods we eat are digested and the liberated proteins broken down into its constituent amino acids. From the resulting metabolic pool of amino acids, specific amino acids are assembled in a specific order to form specific tissue proteins, cell enzymes, and hormones such as insulin that are required by the body. In order to meet our body protein needs for tissue growth and maintenance, we need to get all the ten essential amino acids in our dietary food choices. A protein that supplies all the ten essential amino acids is called a complete protein and is derived mainly from food of animal sources such as milk, cheese, eggs, and meat but also derived from soybeans. A person following a vegetarian food diet needs to take these factors into consideration when planning a diet which will supply all the essential amino acids. The selection should include a combination of foods like grains, legumes including soybeans, and milk products.
Nitrogen Balance is the metabolic balance as measured by the nitrogen in dietary protein ingested as compared to the output of urinary nitrogen in urea. The total 24 hour urinary nitrogen excretion is determined and compared with the total protein nitrogen intake over the same 24 hour period.
nitrogen balance=protein intake (g)/6.25 minus (urinary urea nitrogen +4)
In the above formula, both protein intake and urinary urea nitrogen is determined in grams. The formula reflects the fact that the digestion and metabolism of 6.25 grams of protein yields one gram of urea nitrogen and the factor of 4 grams represents the average 24 hour nitrogen loss through feces and skin. If the nitrogen balance is equal to zero in the above formula, the body is said to be in nitrogen balance.
The body is said to be in positive nitrogen balance when the above formula yields a positive number indicating that the body takes in more nitrogen than it excretes. A positive nitrogen balance is necessary to meet increased needs for protein storage necessary for tissue building. This situation is desirable during periods of rapid growth such as in infancy, childhood, adolescence, pregnancy, and lactation. It may also be desirable in cases of recovery from illnesses and malnutrition.
The body is said to be in negative nitrogen balance when the above formula yields a negative number indicating that the body takes in less nitrogen than it excretes. A negative nitrogen balance indicates that the protein intake is inadequate and that the body is losing nitrogen by breaking down vital tissues. This situation occurs in malnutrition and certain cases of illness. It is most commonly seen in underdeveloped countries but occasionally in developed countries where there is a disproportionate intake of calories from carbohydrates and fats. Although cases of negative nitrogen balance may not become immediately apparent, eventually it will be followed by a loss of muscle tissue, impairment of vital organ function, and increased susceptibility to infection. Growth retardation results from negative nitrogen balance in children.
Primary Tissue Building. Protein accounts for about 75% of the dry matter of most tissues in the human body other than bone and adipose tissue. It is the basic fundamental structural material of every living cell in the body including muscles, internal organs, brain, nerves, skin, hair, and nails. Protein is also a vital part of the regulatory substance that comprises the enzymes, hormones, and blood plasma. All these tissues and regulatory substances must be in a continuous state of maintenance by reparation of damaged components. It is the primary function of proteins to meet the body’s growth and development needs in early life and to maintain tissue health in adult years by repairing wasting or damaged tissues.
The macronutrients, carbohydrate and fat, satisfy the major energy requirements of the human body while the macronutrient, protein, satisfies the tissue building and maintenance necessary to life and health. The complicated physiologic tasks of energy production and tissue building and maintenance occur in a highly organized manner under the control of key cell enzymes. All enzymes are proteins, some relatively simple in structure while others are very complex molecules. The word enzyme derives from the Greek language meaning “in yeast”. Enzymes are produced by living cells and catalyze specific biochemical reactions at body temperature. Even without any knowledge of their structures or functions, humans have used enzymes since prehistoric times in the production of wine, vinegar, and cheese. An enzyme is a biological catalyst. Virtually every biological reaction in the body is catalyzed by one of thousands of enzymes. The highly organized physiologic and metabolic tasks that occur under the control of key cell enzymes necessitates the presence of the micronutrients, vitamins and minerals. The micronutrients operate mainly in the role of cofactors or coenzymes in all enzymatic reactions occurring in the animal body.
The discovery of most vitamins occurred from 1900 to 1950. They were recognized as organic molecules that were essential in the diets of higher animals, higher animals having lost the capacity to synthesize them. During this era of vitamin discovery, the characteristics for classification as a vitamin were: a) essentiality as a non-caloric dietary substance, needed in minute amounts as a cofactor in enzymatic reactions, necessary to prevent a deficiency disease, and b) it could not be synthesized by the body and, therefore, it had to be supplied by the food. Vitamins are grouped according to their solubility as either fat-soluble or water-soluble; vitamins A, D, E, and K falling into the fat-soluble group and vitamins C and the B-complex group falling into the water-soluble group.
Fat-Soluble Vitamins Vitamin A, or retinol, can enter the body preformed through animal food sources or through a precursor, beta-carotene, a pigment from plant food sources which supplies the major requirements of vitamin A in human nutrition. Food sources of vitamin A include liver, egg yolks, cream, butter, fortified milk, some fruits, and beta-carotene containing plant foods such as green and yellow vegetables. For every molecule of vitamin A that is metabolized, two molecules of vitamin A are produced. One of the major roles of vitamin A or retinol is associated with its chemical structure that boasts a terminal hydroxymethyl group, which is easily oxidized to an aldehyde group. The resulting compound is called retinal, a chromophore and the light-absorbing molecule in visual pigments. A deficiency of vitamin A relates to the eye’s vision cycle adaptation to light and darkness known as night blindness. A more generalized role of vitamin A is to promote the body’s primary barrier to infection by functioning as a co-factor in enzymatic reactions necessary to the maintenance of healthy functional epithelial tissue.
Vitamin D plays an essential role in the control of calcium and phosphorus metabolism. Lack of vitamin D results in defective bone growth, a condition called rickets. Vitamin D can be synthesized in the skin by ultraviolet light irradiation of a precursor cholesterol derivative, 7-dehydrocholesterol, to pre-vitamin D3, which spontaneously isomerizes to vitamin D3, cholecalciferol. Vitamin D3 is converted into a physiologically active hormone by hydroxylation reactions occurring in the liver and kidney to form the active 1,25-dihydroxycalciferol [1,25(OH)2 D3 ] known as calcitriol, its major physiological role being the regulation of bone and mineral metabolism. More recent studies suggest a broader function of calcitriol in controlling basic cell processes related to cellular proliferation and differentiation. Most naturally occurring foods have a low content of vitamin D. Fish liver oils are a notable exception and so cod-liver oil was used for many years as a rich source of vitamin D. Today, the most reliable sources of vitamin D are fortified foods. In adults, vitamin D deficiency leads to the softening and weakening of bones, a condition known as osteomalacia. This conditon was a common occurrence in Bedouin Arab women who were clothed so that only their eyes were exposed to sunlight.
Vitamin E plays a vital role as an antioxidant or free radical inhibitor. As the term implies, a free radical inhibitor inhibits a radical reaction and in so doing it undergoes a reaction with the reactive radical to form a relatively stable and nonreactive form. Compounds with a hydroxyl group attached to an aromatic ring carbon are effective antioxidants because the radical products of these compounds are resonance stabilized and thus nonreactive compared with most other radicals. Vitamin E, or a-tocopherol, falls into this group. It acts as nature’s most potent fat-soluble antioxidant by protecting the polyunsaturated fatty acids, which are part of the integral structure of the cell membrane, from damage. Hemolytic anemia in infants, especially those born prematurely, has responded positively to vitamin E therapy. This is explicable in terms of the fact that membranes of red blood cells contain a significantly high concentration of polyunsaturated lipids and they are constantly exposed to concentrated oxygen as they circulate through the lungs. In the absence of an antioxidant, the polyunsaturated lipids are oxidized leading to the breakdown of the cell membrane and the formation and release of free radicals creating a highly destructive environment. To reemphasize, vitamin E acts as nature’s most potent antioxidant protecting the cell membrane polyunsaturated lipids from oxidative damage and the consequential breakdown of the fragile red blood cell membranes.
Vitamin K serves as an essential cofactor in the synthesis of several proteins, including prothrombin, involved in the body’s blood clotting mechanism. It is known as the prothrombogenic vitamin because of its role as a cofactor in the synthesis of the enzyme, prothrombin, which in turn, is needed to produce the fibrin for blood clots. It is often used in the control and prevention of hemorrhages and as an antidote to counteract the excess effects of anticoagulant drugs. In the presence of supporting food sources such as green, leafy vegetables, adequate amounts of vitamin K to satisfy daily requirements are synthesized by intestinal bacteria. A vitamin K deficiency can arise in patients treated with antibiotics that kill intestinal bacteria and are then placed on improper diets following surgery. Bleeding and poor wound healing could be consequences. Food sources of vitamin K are green, leafy vegetables, milk and dairy products, meat, eggs yolks, cereals, and fruits.
Vitamin C and the B-complex vitamins comprise the water-soluble group of vitamins. The B complex group of vitamins includes thiamine (B1), ribloflavin (B2), nicotinic acid or niacin (B3), pyridoxine (B6), pantothenic acid, biotin, folate, and cobalamin (B12). The water-soluble vitamins, C and B complex, cannot be stored and therefore must be replenished daily to maintain the wide range of metabolic functions these vitamins support.
Vitamin C or ascorbic acid, present in its deprotonated state under most physiological conditions, is considered to be the most important antioxidant in extracellular fluids. It plays a vital role in collagen formation and therefore is important in the building and maintenance of connective tissue. Vitamin C prevents scurvy which attacks the gums, skin, and mucous membranes. It promotes iron absorption and release to tissues for red blood cell formation. Clinical applications include the treatment of scurvy, hemorrhaging around bones and joints, infections, wound healing, and anemia. The richest source of vitamin C is citrus fruits but also found in melons, strawberries, and most green vegetables.
Vitamin B1, or thiamin, was first discovered to be the food factor in rice polishing used by early investigators to cure beriberi. It was isolated from rice bran in 1926 by Jansen and its structure later determined by Williams in 1936. Thiamine is a coenzyme in carbohydrate metabolism and therefore essential to normal growth and normal function of the heart, nerves, and muscle. A deficiency of thiamin is manifested in beriberi, gastric distress, fatigue, nerve damage, paralysis, heart failure, and especially edema of the legs. It occurs in plants and animal tissues, notably in rice husks, cereal, whole grains, legumes, yeast, liver, eggs, milk, and green, leafy vegetables.
Riboflavin, or vitamin B2, functions as a coenzyme in protein and energy metabolism and is therefore also essential to normal growth. Riboflavin for therapeutic use is produced by synthesis but several fermenting organisms have the capacity to produce large quantities of riboflavin. Concentrates for poultry and livestock feeds are produced by fermentation. A deficiency of riboflavin is manifested in ariboflavinosis, skin eruptions, swollen tongue, and eye irritations. The richest natural source of riboflavin is yeast but is also found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables.
Niacin or nicotinic acid is known as the antipellagra vitamin or pellagra preventive factor. It functions as a coenzyme in the citric acid cycle and therefore is involved in energy production. It is essential to the normal growth and health of the central nervous system. A deficiency of niacin manifests itself in pellagra, weakness, lack of energy, loss of appetite, neuritis, and confusion. Appreciable amounts are found in yeast, liver, milk, legumes, whole cereals, and peanuts.
Pyridoxine, or vitamin B6, is a coenzyme in amino acid metabolism and protein synthesis essential to heme formation and brain activity. A deficiency of pyridoxine manifests itself in anemia and central nervous system symptoms such as hyperirritability, convulsions, and neuritis. It is present in many foods; especially good sources being yeast, liver, and kidney meats but also found in milk, eggs, and vegetables.
Pantothenic acid is the starting material for the biosynthesis of coenzyme A, a key cofactor in the citric acid cycle. The latter is the major pathway for the generation of ATP and hence energy production. The citric acid cycle also provides intermediates for other important biosynthetic processes in lipid and protein metabolism. A deficiency of pantothenic acid is rare due to its widespread occurrence. It occurs everywhere in animal and plant tissues, the richest common source is in liver, but jelly of the queen bee contains six times as much as liver. Rice bran and molasses are other good sources.
Biotin is a growth factor present in minute amounts in every living cell and serves an indispensable role in numerous occurring carboxylation reactions. Biotin links covalently to pyruvate carboxylase to form a biotin enzyme complex which then reacts with acetyl coenzyme A in the presence of carbon dioxide (CO2) to form intermediates essential to the synthesis of fatty acids. Because of its presence in every cell, a natural deficiency of biotin is unknown. The richest sources are liver, kidney, pancreas, yeast, milk, egg yolk, and soy flour. Biotin has been found to be inactivated by a proteinaceous substance, avidin, in raw egg white.
Folic acid is known as the hematopoietic vitamin essential to the development of red blood cells. It is also a precursor of tetrahydrofolate (also called tetrahydropteroyl glutamate), a highly versatile carrier of one-carbon units. Mammals cannot synthesize a pteridine ring structure as found in tetrahydrofolate and therefore must obtain it from their diets or from microorganisms in their intestinal tract. Tetrahydrofolate serves as a donor of one-carbon units in a number of biosynthetic processes necessary to growth and development of red blood cells. A deficiency of folic acid manifests itself in megoblastic anemia. It occurs free or combined with one or more additional molecules of glutamic acid in liver, kidney, mushrooms, spinach, yeast, and green, leafy vegetables.
Cobalamin, or vitamin B12, has been a challenging problem in biochemistry and medicine since the discovery in 1926 that pernicious anemia could be treated by feeding the patient large amounts of liver. It was isolated in pure form in 1948 and its complex three-dimensional structure elucidated in 1956. The cobalamin molecule consists of a central cobalt atom at the core, to which are attached four substituted pyrrole rings. It forms a coenzyme with the transfer of 5 -deoxyadenosyl from ATP. The enzyme, 5 -deoxyadenosylcobalamin, catalyzes the metabolic reactions of rearrangements and methylations. It is therefore essential in the synthesis of the heme moiety of hemoglobin and normal red blood cell formation. A deficiency of vitamin B12 is manifested in pernicious anemia. It is produced by intestinal microorganisms and also found in liver, kidney, lean meats, milk, eggs, and cheese. Higher plants do not concentrate vitamin B12 from the soil and so are a poor source as compared with animal tissues. The latter factor is a nutrition concern among vegans, strict vegetarians who use no animal foods including milk, cheese and eggs. A supplement of vitamin B12 is definitely mandated for vegans, especially in periods of rapid growth throughout the life cycle such as pregnancy, infancy, childhood, and adolescence.
In spite of the obvious diversity in physiological roles, these individual water-soluble vitamins share certain characteristics significant in human nutrition: a) with the exception of cobalamin, they are all synthesized by plants and available in a diet containing plant foods, as well as animal foods; b) they are not synthesized by the body and must be provided regularly in the diet; and, finally, c) with the exception of vitamin C, which serves as a structural agent in building connective tissue, they all serve as coenzyme factors in metabolic reactions in the living cell.
The minerals are inorganic elements that are widely distributed in nature and comprise the second group of essential micronutrients. In contrast to the vitamins, which are complex organic molecules, the minerals are simple single inorganic elements. In their activated form of positive or negative ions, minerals assume a variety of physiological roles performing an impressive array of metabolic tasks.
The minerals are involved in the activation, regulation, and control of numerous metabolic processes. For example, calcium and phosphorus are required in the structural composition of hard and soft body tissues. Sodium and potassium control water balance. Iron forms the central core of the vital oxygen carrying hemoglobin molecule in red blood cells while cobalt is the central core atom of cobalamin or vitamin B12. Iodine is a substituent element of the thyroxine molecule, the thyroid hormone, which regulates body metabolism.
In contrast to the vitamins that are required in relatively minute amounts to perform their specific tasks, minerals occur in varying amounts in the body. Accordingly, minerals are classified into two groups, major minerals and trace elements, depending upon whether they occur in large or trace amounts in the body.
Major minerals are so designated simply because they occur in larger amounts in the body and not because they are more important. Elements for which their requirement is greater than 100 mg/day are classified as major minerals. The seven elements that fall in this category are calcium, phosphorus, sodium, potassium, magnesium, chlorine, and sulfur. The absorption of calcium and phosphorus through the digestive system is aided by vitamin D and hindered by binding agents such as oxalates. Both these minerals are essential in bone and tooth formation. Calcium also contributes to regulating blood clotting, nervous excitability, muscular contraction, and heart action. About 90% of the calcium is stored in bone where it can be reabsorbed by blood. Phosphorus is essential in overall metabolic processes, especially energy metabolism of the cell affecting carbohydrates, lipids, and proteins. Milk and milk products constitute the best source of calcium and phosphorus. The daily requirement of both calcium and phosphorus is 1200 mg. The loss of body calcium is manifested in rickets, osteoporosis, and tetany (decrease in ionized serum calcium). A phosphorus deficiency is manifested in bone loss and poor growth.
Sodium and potassium are readily absorbed and are major players in water and acid-base balance, sodium in extracellular fluid control and potassium in intracellular fluid control. Both sodium and potassium are involved in the regulation of nerve impulses while potassium also regulates heart action and muscle contraction and is important in protein synthesis, glycogen formation, and energy metabolism. A low serum potassium can lead to cardiac arrest. High sodium concentration in the extracellular fluid is manifested by edema while low concentration in the extracellular fluid is manifested by dehydration. The adult daily intake of sodium should not exceed 2.4 g since evidence now exists that excess dietary salt contributes to high blood pressure. The adult daily requirement of potassium is 2 to 3.5 g. The main food source for sodium is table salt but also found in baking soda, meat, and dairy products. The main food sources for potassium are fruits, vegetables, meats, whole grains, and legumes.
The absorption of magnesium is controlled by the parathyroid hormone. Magnesium is a cofactor in protein and carbohydrate metabolism and therefore essential to human metabolism. Hexokinase, an enzyme that transfers a phosphoryl group from ATP to a variety of six-carbon sugars, requires magnesium for activity, magnesium forming a complex with ATP. Magnesium is important for maintaining the electrical potential in nerve and muscle cells. A deficiency of magnesium among malnourished people, especially alcoholics, leads to tremors and convulsions. The adult daily requirement for magnesium is 280 to 350 mg. It should be noted that magnesium is the central core of chlorophyll and therefore readily available from green, leafy vegetables.
Readily absorbed chlorine is physiologically important in acid-base balance and in digestion in the form of gastric hydrochloric acid. Severe vomiting or diarrhea can manifest itself in metabolic or hypochloremic alkalosis. The daily requirement of chlorine is parallel to that of sodium and is readily available from table salt.
Sulfur is the last of the major minerals to be considered. It is absorbed in its elemental state and is a constituent of the sulfur-containing amino acid methionine. It is an essential constituent of body proteins including hair, skin, and nails. It is important in the formation of high-energy sulfur bonds in energy metabolism. As a constituent of methionine through its conversion to propionyl coA to methylmalonyl coA and then to succinyl coA, it becomes a point of entry into the citric acid cycle. The thioester bond of succinyl coA is a high energy bond. Also, as a constituent of the b-mercaptoethylamine moiety of coA, it is involved in normal body metabolism. A diet adequate in foods containing proteins – meat, dairy products, nuts and legumes – supplies adequate sulfur.
Trace minerals or elements are subdivided into two groups, ten essential trace elements requiring under 100 mg/day and eight trace elements of unclear essentiality. The essential trace elements are cobalt, chromium, copper, fluorine, iodine, iron, manganese, molybdenum, selenium, and zinc and the trace elements of unclear essentiality are aluminum, arsenic, boron, cadmium, nickel, silicon, tin, and vanadium. Essentiality in human nutrition is based in its requirement for the existence of life. In lieu of the minute amounts of trace elements present in biologic matter, the difficulty of determining their essentiality is apparent. The demonstration of essentiality experimentally is difficult because it requires the impossible task of removing it from the diet and environment. However, function and deficiency effect has served to foster our knowledge of mineral essentiality. That is, a mineral is considered essential when a deficiency of that element causes an impairment of function and when supplementation of that element alone reverses the impairment.
Examples of trace minerals that serve as enzyme catalysts are manganese, molybdenum, chromium, and copper. Manganese is a catalyst in enzymatic reactions in protein metabolism, leading to urea formation. Molybdenum is a catalyst in enzymatic reactions involved in the conversion of purines to uric acid while chromium is a catalyst in glucose metabolism and the control of sugar levels. Copper is associated with the absorption and transport of iron in energy production and hemoglobin synthesis.
Antioxidant Function Of Vitamin C, Vitamin E, And Beta-Carotene
The benefit of energy production by the aerobic metabolic processes in the human body is associated with the generation of reactive oxygen species capable of damaging biologically relevant molecules such as DNA, protein, carbohydrate, and lipid. These highly reactive species include the superoxide anion radical, hydrogen peroxide, the hydroxyl radical, molecular oxygen (O2) as well as the hypochlorite, nitric oxide, and peroxynitrite radicals. Reactive oxygen species are involved in a variety of biological processes including inflammation, carcinogenesis, radiation damage, photobiological effects and aging. A shift toward the pro-oxidants in the pro-oxidant-antioxidant balance leading to damaged products is a reflection of oxidative stress. A great deal of research interest in the biology and medicine of oxidative stress responsible for the induction of DNA damage, protein oxidation, and lipid peroxidation has developed in recent years.
The biological defense mechanisms that have developed against peroxidants are classified as prevention, interception, and repair. Enzymatic defense systems operate in the areas of prevention and repair, while nonenzymatic defense systems operate in the area of interception. The highly effective enzymatic defense systems function to neutralize the reactive oxygen species, the superoxide anion radical being enzymatically dismutated to oxygen and hydrogen peroxide16 and the hydroperoxides neutralized by the powerful enzymes catalase and hydroperoxidases.
The most important nonenzymatic defense system comprises the essential micronutrients. The key to the domain of chain-breaking antioxidants is interception. An antioxidant is “any substance that when present at low concentrations compared with those of an oxidizable substrate, significantly delays or inhibits oxidation of that substrate”. Vitamin C, vitamin E, selenium, and beta carotene fall into the group of micronutrients, the nonenzymatic antioxidants, critical to the defense mechanism of interception.
Vitamin E consists of four tocopherols – a, b, c, d – different only by the nature of the two substituents on the benzene ring of the molecule. The a-tocopherol form is the most important one in human metabolism. The basic structure of vitamin E consists of a pyranol ring attached to a benzene ring with various substituents on both rings, and hence can be named as a benzopyranol derivative. The benzopyranol ring is also referred to as a chromane ring and the reactivity of vitamin E with organic peroxyl radicals is associated with the redox properties of the chromane ring giving rise to its major biological function as an antioxidant. A series of reactions followed by the rupturing of the pyranol ring, with the consequent formation of the tocopheroxy radical, is the basis of a proposal that vitamin E functions as an in vivo antioxidant, protecting DNA and tissue lipids from free radical attack. Vitamin E reacts with and neutralizes peroxyl radicals generated from polyunsaturated fatty acids in membrane phospholipids or in lipoproteins after hydrogen abstraction and an addition of an oxygen molecule.
Vitamin C or L-ascorbic acid, considered to be the most important antioxidant in cellular fluid , is water-soluble and present in the deprotonated state under most physiological conditions. Vitamin C has been shown to be an efficient scavenger of superoxide, hydrogen peroxide, hypochlorite, the hydroxyl radical, peroxyl radical, and O2. In a group study in which dietary vitamin C was decreased from 250 to 5 mg/day, the seminal fluid vitamin C level decreased by one-half and the concentration of 8-hydroxy-2 -deoxyguanosine in sperm DNA increased almost twofold in an essentially reversible reaction. These results were interpreted to indicate that dietary vitamin C protects human sperm from endogenous oxidative DNA damage that could affect sperm integrity and increase the risk of genetic defects, particularly in populations with low vitamin C, such as smokers.
Beta-carotene (b-carotene) is the most prominent of a multitude of carotenoids with lipophilic properties. b-carotene, as most carotenoids, contains an extended system of conjugated double bonds, capable of epoxide formation, which is responsible for its antioxidant activity. In vitro studies have demonstrated that b-carotene was capable of inhibiting oxidation of unsaturated fatty acids by peroxyl radicals. The same investigators suggest that the antioxidant activity of b-carotene and other carotenoids may contribute to the protection of cell membranes from peroxidation.
One cannot discuss the importance of nutrition to life without mentioning the most essential nutrient of life, water. Although only a simple chemical composed of two atoms of hydrogen and one of oxygen (H2O), it is essential to all forms of life underlying the functions of all other nutrients. Water makes up about 60 percent of the average body weight, approximately 40 percent comprising the intracellular fluids and 20 percent the extracellular fluids. Of the extracellular fluids, about four to six percent are in the blood plasma, lymph and cerebrospinal fluid while 14 to 16 percent are in tissue fluid. Water provides the medium for the transportation of chemical substances dissolved in it and provides the medium for all metabolic reactions and the medium for maintaining a stable body temperature. The interchange of water between the blood and tissue cells takes place by a process called osmosis. Water is taken into the body by the liquid we drink and the food we eat. A small amount of water is produced in the body by the metabolism of food. The average adult requires 2.5 to 3 liters of water per day to satisfy the body’s metabolic processes. There is a constant turnover balanced between intake and output and regulated by basic mechanisms such as thirst and hormonal control.
Health Versus Nutrition and Lifestyle
Approaches to Health
Although the term health is normally associated with the absence of disease, a broader definition would include physical, mental, and social wellbeing. The ultimate goal of each individual should be to achieve his or her maximum potential of wellness within his or her own environment. This goal can only be achieved through a balance of everyday activities – work, leisure, personal goals, and lifestyle choices versus health risks. Optimal wellness represents a state of complete physical, mental, and social well-being but obviously a dynamic state exists in which a deficiency in one system is compensated by an improvement in another. Excellent physical health, for example, makes it possible for an individual to cope with the emotional stresses of everyday life.
In recent times through rapid means of communication such as radio, television, and the internet, our society has become more health conscious. In their daily newscasts, television networks present segments on various aspects of health and disease. The public is constantly being admonished with advice on changing their lifestyle to improve the physical and emotional aspects of their wellness.
Traditional Approach To Physical Health. The traditional approach to health is one that has predominated up to recent times. In this approach, an individual seeks help from a physician when the symptoms of a disease or illness appear. It is the predominant approach in acute illnesses easily cured by a specific drug or treatment. This approach is of questionable value in promoting a lifetime of health in chronic illnesses such as cardiac disease, cancer, and diseases of the aged such as Alzheimer’s and Parkinson’s Disease.
Preventive Approach To Physical Health. With the development of the new tools and concepts of modern molecular biology we are witnessing an explosive and revolutionary development in the understanding of normal and aberrant biological function and in the detection, diagnosis, and treatment of human disease. The obvious interaction of underlying genetic factors with environmental factors may be responsible for the ultimate development of a disease. Human cancers such as breast and prostate cancer are genetic diseases. That is, the wrong or aberrant gene emanating from a malfunction in DNA replication, functions in a cell at the wrong time to produce a diseased cell. We know now that genetic defects play a dominant role in the development of certain cancers, atherosclerosis, crippling forms of arthritis, and Alzheimer’s Disease. With the development of new techniques in molecular biology, genes and genetics are no longer inaccessible mysteries. The staggering success in the human genome project by our scientific and medical institutions is a reflection of the concept that effective treatment of human diseases will be achieved through an understanding of genetics. These revolutionary advances in genetics are fostering our knowledge on the identification of risk factors that predispose an individual to the development of a particular health problem or disease. Preventive measures in this area include screening programs in the asymptomatic stages to detect the risk factors followed by advocating behavioral changes in the individual to minimize the risk of disease development. Although it is somewhat of a negative approach to healthcare, it may be of real value in families with a history of an inheritable disease.
Wellness Approach To Physical And Mental Health. It must begin early in life to prevent or retard the onset of degenerative changes that lead to chronic illnesses. This wellness approach embodies the positive lifestyle choices that promote physical and mental well-being. The pursuit of positive lifestyle choices can only be motivated through knowledge of the roles genetics, nutrition, eating habits, physical exercise, and mental well-being play in the onset of degenerative changes and chronic disease.
Factors Affecting Health Status
Heredity. A factor, which is beyond an individual’s control but plays a major role in one’s health, is heredity. As stated previously, the presence of certain genes has been associated with certain diseases. It is the hope of scientists active in genetic engineering that, sometime in the foreseeable future, they will be able to correct the genetic defects responsible for disease.
Physical And Social Environment. Both physical and social environments have an impact on an individual’s health. For example, families living in homes constructed in areas of high radon concentration are exposed to continuous radiation, a causative agent in DNA damage resulting in genetic defects. The incidence of infection and disease is higher in families living in inadequate housing which lack adequate refrigeration, heating, and plumbing facilities. Children, exposed by their parents to an atmosphere of cigarette smoke, are placed at serious risk of lung disease. Water quality or contaminated water is another example of how the physical environment can affect an individual’s health status. The social environment, by setting either high or low performance expectations, can also be a determining factor in an individual’s health status. Emotional support by family and friends can always be a positive factor.
Outlook and Care are also important factors in maintaining a good health status. Mossey and Shapiro determined that “self-rated health” was a predictor of mortality among the elderly. Those whose health outlook is positive, rating their health as excellent or good, have a longer life expectancy than those whose outlook is negative. A positive outlook about one’s health suggests a positive outlook towards life in general, which supports positive adjustments to everyday occurrences affecting a person’s life. Healthcare may or may not be under an individual’s s control since financial status or income may dictate the level or quality of healthcare he or she or the family can afford. The level of education may be critical in interpreting and carrying out the instructions of a health professional as to the course to be followed in the treatment of a disease. Knowledge about disease symptoms is also important in order to identify the need to seek the advice of a qualified health professional.
Lifestyle is a typical way of life of an individual influenced by likes and dislikes, values and beliefs. It is an important factor in life because lifestyle will influence the amount and choice of foods we eat and the amount of alcohol we drink. It influences the amount of leisure time we devote to exercise such as walking, biking, running, swimming, aerobics, tennis, etc. It influences how we cope with stress, positively through active sports or relaxation or negatively through overeating, smoking, alcohol, or drug abuse. Health status is to a great extent influenced by lifestyle choices as to diet, exercise, smoking, use of addictive drugs, and stress management. The adoption of positive lifestyle choices is especially critical for those showing early signs of chronic diseases or for those who are at risk because of their genetic background.
Recommendations for a Healthy Lifestyle
These should include behavioral recommendations consistent with the promotion of good health. The basic behavioral activities that should be monitored are diet, exercise, stress management, and control of addictive behavior.
Dietary Recommendations. In 1989 the National Research Council commissioned a panel to make recommendations to assist people in reducing chronic disease risk (see p3 for a summary for these recommendations). These recommendations were based on current knowledge as to the relation of diet to chronic disease risks. Diets high in saturated fat and cholesterol lead to obesity, coronary heart disease, and increased incidence of cancer and atherosclerosis. It was suggested that the kilocalories lost in a reduced fat diet could be replaced by plant foods rich in complex carbohydrates and soluble fiber such as vegetables, fruits, grains, and legumes. Additionally, the soluble fiber found in plant foods independently functions to lower blood lipid levels and hence lowers cardiovascular risk. The protein intake among most Americans exceeds the amount necessary to maintain a nitrogen balance or a slightly positive nitrogen balance. The panel suggested that a protein intake, which exceeded twice the Recommended Dietary Allowance (RDA), was associated with an increased incidence of coronary heart disease and cancer. Because of the association of sodium with high blood pressure in genetically sensitive individuals, the panel also suggested that sodium intake be limited to 2000 mg/day. It also recommended that vitamin and mineral supplements be maintained at RDA.
Exercise is synonymous with physical fitness. One of the most important effects of exercise is energy balance and weight management. It makes possible a higher intake of food, increasing the intake of important nutrients, without additional weight gain. Physical exercise strengthens muscle fibers, prevents increase in body fat, and stimulates bone formation. By stimulating bone formation, regular physical exercise such as walking, jogging, and cycling can retard the onset of osteoporosis, common among older men and women. Regular exercise increases cardiovascular efficiency increasing oxygen consumption while decreasing heart rate and blood pressure levels during exercise and rest. It has been determined that blood pressure levels increase with age among those with sedentary lifestyles. Physical activity also assists a low fat and cholesterol diet in lowering the low-density lipoproteins (LDLs) which are responsible for transporting cholesterol to the cells thereby increasing cardiovascular risk. Simultaneously, exercise increases the levels of high-density lipoproteins (HDLs), which remove cholesterol molecules from the blood before they can enter the arterial wall thereby decreasing the risk of coronary artery disease.
Stress Management. Stress is the physiologic or psychologic reaction to normal occurrences in our daily lives. It can be precipitated by positive events such as getting married or starting a new position or by a negative event such as being fired or a death in the immediate family. Whether initiated by a positive or negative event, stress is accompanied by adverse physiologic symptoms such as gastrointestinal distress, sleep irregularity, muscle tension with accompanying headaches or a cardiovascular response resulting in constriction of blood vessels and rapid pulse. There may be no consequence with the occasional experience of one of these symptoms but continued, unalleviated stress can lead to long-term consequences such as psychological distress, leading to binge eating and obesity on one extreme or anorexia nervosa on the other. It can lead to heart disease accelerated by high blood pressure in response to stress or to peptic ulcers from gastric upset in response to increased hydrochloric acid secretion in the stomach. Behavioral changes must be undertaken to reduce the threat to physical and mental health. Effective tools in stress management are decreased consumption of alcohol, caffeine, and nicotine together with more time devoted to exercise, leisure, and relaxation.
Addictive Behavior Injurious to Health
The most common addictive behaviors injurious to health are cigarette smoking, alcohol abuse, and eating disorders.
Cigarette smoking, the most preventable cause of illness and premature death in the United States, is a major risk factor that accounts for 87% of lung cancer deaths, 21% of coronary heart disease deaths, and 18% of stroke deaths. Mortality risk from smoking increases with increase in the number of cigarettes smoked. Until recently the incidence of lung cancer in women was lower because a relatively fewer number of women were smoking. Now, however, lung cancer has surpassed breast cancer as the leading cause of death in women. The solution to the problem lies in behavior modification and the strategies necessary to cope with the physiological and psychological factors associated with nicotine addiction.
Alcohol abuse, the indiscriminate use of alcohol, has a deleterious effect on health. It contributes to malnutrition because it contributes 7 kcal/g to the diet and is devoid of essential protein, vitamins, and minerals. When alcohol calories begin to replace food calories, as is the situation in the case of alcohol abuse, the resulting decrease in intake of essential nutrients leads to malnutrition. Alcohol cannot be utilized directly for energy, being first converted to fat. It is associated with elevated LDL-cholesterol and triglyceride levels, hypertension, and liver damage. Alcohol abuse is associated with the depletion of liver stores of vitamin A, which may account for the relationship observed between alcohol consumption and cancer of the liver, breast, and pancreas. A paradox in alcohol consumption arises in the observation that low to moderate drinking, one to two drinks per day, leads to increased levels of HDL-cholesterol. This observation could be the basis of epidemiological findings that coronary heart disease risk is lower in individuals consuming one to two drinks per day. Chronic alcoholism can lead to progressive brain dysfunction creating a disorganized addictive personality. Alcohol addiction programs, which stress behavioral and lifestyle changes with good nutritional guidance following detoxification, have achieved some degree of success in this area.
Eating disorders, some form of complex addictive eating, have been found to be more prevalent among women than men. Stress, emanating from outside pressures or self-imposed, places an individual at risk for developing one of these eating disorders. Anorexia nervosa is a disorder afflicting an individual fearful of gaining weight or becoming fat, a fear fed by society, fashions, or professional commitments as in the case of ballet dancers, gymnastics or other competitive sports. These people impose a self-starvation pattern on themselves that leads to malnutrition and becomes life threatening. Bulimia nervosa characterizes an eating disorder wherein an individual consumes an enormous amount of food, thousands of kilocalories within a few hours, then pursues unorthodox means such as self-induced vomiting to prevent weight gain. Binge eating disorder is characterized by a loss of control over eating. These episodes of overeating occur periodically over the course of a week in the absence of actual hunger. The afflicted individual eats large amounts of food very rapidly until uncomfortably full. This condition obviously leads to enormous increases in body weight with accompanying health problems and requires treatment by a trained physician, psychotherapist, and dietitian.
Nutrition and Chronic Disease
Atherosclerotic Heart Disease
Coronary heart disease is by far the leading killer of men and women in the United States. It is responsible for one of every three deaths for women over 60 and one for every three deaths for men over 40. The development of atherosclerosis and heart disease is influenced by an individual’s genetic makeup, dietary habits, and lifestyle behavior. The atherogenic potential of cholesterol and low density lipoprotein (LDL) has been clearly identified over the past several decades. Increased LDL-cholesterol levels follow a diet high in cholesterol and saturated fatty acids whereas a diet high in polyunsaturated fats lowers both HDL- and LDL-cholesterol levels. We also know that soluble fiber lowers LDL-cholesterol whereas physical activity and moderate use of alcohol increase HDL-cholesterol levels. Obviously, any discovery indicating that intervention could reduce the risk of coronary heart disease would have a tremendous impact on health throughout the world population. Recent evidence11,13-15 suggests that the oxidation of lipids may enhance their atherogenicity. This raises the possibility that antioxidant vitamins, which inhibit the oxidation of lipids, may reduce the risk of coronary heart disease. Although antioxidants have been shown to possess endothelial function, inhibit platelet aggregation, and reduce atherosclerotic plaque formation in animals, the benefits of human supplementation remains to be determined by controlled epidemiologic studies. Studies undertaken to date have included descriptive and cross-sectional studies as well as analytic investigation using case-controlled and prospective cohort designs.
The Nurses Health Study and the Health Professional’s Follow-Up Study examined the relationship between antioxidant vitamin intake and the risks of coronary heart disease. The Nurses Health Study, begun in 1976, consisted of a cohort of 121,000 US female nurses. Using a computerized database, which summarized the detailed dietary questionnaires of 90,000 respondents, they compared the risk of heart disease among those in the highest intake category with those in the lowest for beta-carotene, vitamin E, and vitamin C. When they totaled the intake of these vitamins into an antioxidant score, those people in the highest quintile had a 50% reduction in the chance of a coronary artery disease event. The Health Professionals’ Follow-Up Study, consisting of a cohort of 50,000 men, yielded essentially similar results.
The Physicians Health Study was a randomized trial of beta-carotene and aspirin in the prevention of heart disease and cancer among 22,000 US male physicians. The aspirin component was terminated in 1989 due to the protective effect of aspirin in reducing myocardial infarction. In a five year follow-up among a subgroup of 333 men, 160 randomized to the beta-carotene group, there was a 50% reduction of coronary events (heart attacks, bypass or angioplasty procedures, cardiovascular deaths) among those assigned to the beta-carotene group.
In an alpha-tocopherol, beta-carotene cancer prevention study among Finnish male smokers, there was a threefold increase in serum alpha-tocopherol in subjects receiving 50 mg daily and a twofold increase in beta-carotene in subjects receiving 20 mg daily. There was an apparent increase in hemorrhagic stroke and a decrease in prostatic cancer mortality in the group receiving alpha-tocopherol. No protective effect of beta-carotene was found in the cardiovascular group but rather