Micronutrients Alleviating Nutritional Disorders By Nutraceuticals

Ever since the discovery of vitamins, there has been a great interest in deciphering the effects of food constituents on human health. The requirements for a healthy life with a balanced metabolism (metabolic homeostasis) and preservation of the body cell mass require a protein balance having all the essential amino acids, fatty acids, carbohydrates, and micronutrients (1,2).

Approximately 40 micronutrients (the vitamins, essential minerals, and other compounds needed in small amounts for normal metabolism) are required in human diet (Tables 5.1, 5.2). Obtaining maximum health and life span requires metabolic harmony. For each micronutrient, metabolic harmony requires an optimal intake (i.e., to give maximal life span); deficiency distorts metabolism in numerous and complicated ways, many of which may lead to DNA damage (3-7). Many micronutrient minerals and vitamins act as substrates or cofactors in key DNA maintenance reactions, and the exact concentration of these in the cell may be critical. Suboptimal levels of key micronutrients will thus lead to impaired activity of enzymes needed for genomic stability in man, producing effects similar to inherited genetic disorders or exposure to carcinogens (Tables 5.1, 5.2) (3-7). In fact, a deficiency of some micronutrients (folic acid, vitamin B12, vitamin B6, niacin, vitamin C, vitamin E, selenium, iron, or zinc) appears to mimic exposure to radiation or chemicals by causing single and double strand breaks in DNA, oxidative lesions, or both (4-12). Chromosomal aberrations such as double strand breaks are a strong predictive factor for human cancer.

In adults, superoxide, hydrogen peroxide, and hydroxy radicals (produced by some 1010 free radicals per cell each day) can potentially cause in the order of 106 mutational alterations of DNA per cell per day. Fortunately, the activities of these dangerous mutagens are countered by antioxidants, DNA repair, the removal of persistent alterations by apoptosis (normally a cellular program is activated, that causes the cell to self destruct), differentiation, necrosis, and activation of the immune system so that only about one mutation per cell per day persists (13). By old age, many mutations have accumulated because the repair system is not working properly, and as a consequence, cancer may occur. However, the increased consumption of dietary antioxidants such as vitamins C and E, quercetin (flavonoid), and carotenoids (zeaxanthin and lycopene) can diminish DNA oxidation and therefore, less cancer incidence is presented (3,13-18).

The U.S. Recommended Dietary Allowances (RDAs) for micronutrients refer to daily levels of intake of essential nutrients, at or above defined minimum values, judged by the Food and Nutrition Board to be adequate to meet the known nutrients needed for practically all healthy persons and to prevent deficiency diseases. The level of daily requirement for each nutrient varies with age, sex, and physiological status (e.g., pregnancy, lactation, disease related stress) (Tables 5.1, 5.2) (19). RDAs are established by estimating the requirement for the absorbed nutrient, adjusting for incomplete utilization of the ingested nutrient, and incorporating a safety factor to account for variability among individuals (19).

Also, now it is known that vitamins, minerals, and other dietary components consumed at varying levels, higher than RDAs, are significant contributors to the reduction of risks of chronic diseases such as cancers, cardiovascular diseases, and degenerative diseases associated with aging (Alzheimer's, premature aging). Their role in maintaining human genomic stability is likely to be critical to alleviating the classical nutritional deficiency diseases which include scurvy (vitamin C), anemia (folic acid, iron), and pellagra (niacin) (Tables 5.1, 5.2) (4-7,17,20,21).

While deficiencies of dietary energy (i.e., calories) and protein currently affect more than 800 million people in food insecure regions, incredibly, micronutrient malnutrition, known as "hidden hunger," now afflicts over 40% of the world population, especially the most vulnerable being in many developing nations (resource-poor women, infants, and children), and a surprisingly large amount of people in the advanced countries, where food diversity, abundance, and supply are excellent, but also poor food eating habits are common and in both cases the numbers are rising (4,22-25). Even though micronutrients are needed in minute quantities (i.e., micrograms to milligrams per day), they have tremendous impact on human health and well-being (Tables 5.1, 5.2) (22,26,27). Insufficient dietary intake of these microcomponents impairs the functions of the brain, the immune and reproductive systems, and energy metabolism (26,27).

At present, deficiencies of iron, vitamin A and iodine are of the most concern to the community and healthcare systems. Unfortunately, for zinc there is a lack of a simple, quick, and cheap clinical screening test for determining marginal zinc deficiency in humans. Specialists in zinc nutrition suggest that its deficiency presents similar problems as caused by a deficiency of iron (10,22,24,25,28). Iron, zinc, and vitamin A all play important roles in brain development, and when deficiencies of these micronutrients are manifest during pregnancy, or even for up to two years postpartum, permanent damage to offspring is possible. Thereafter, further loss of cognitive ability is found (10,22,24-31).

Iodine deficiency is the greatest single cause of preventable brain damage and mental retardation in the world today. More than 2 billion people around world live in iodine deficiency environments. Deficiency in iodine occurring in late infancy and childhood have been demonstrated to produce mental retardation, delayed motor development, and stunted growth, occurrence of neuromuscular disorders, and speech and hearing defects. Even mild iodine deficiency has been reported to decrease intelligence quotients by 10-15 points (22,31).

Rapid growth during fetal development, infancy, childhood, and adolescence demand greater amount of micronutrients, when their deficiency can cause developmental abnormalities (22,25). In addition to multiple micronutrient deficiencies (those of vitamin A and C, decreased iron absorption), interactions between micronutrient deficient conditions and infectious diseases may become significant. These effects can complicate health care efforts to control various diseases such as vitamin A deficiency and measles, and increased severity of measles leading to vitamin A deficiency blindness and death. Malaria and hookworm infections are also associated with Fe deficiency anemia (22,25,30,32).

Plants synthesize and accumulate an astonishingly diverse array of vitamins, and nutraceuticals that have health-promoting properties (33,34). Many naturally occurring compounds have health promoting or disease preventing properties beyond the mere provision of nutrients for basic nutrition (1,34-36). In this way, plants not only constitute the base of the human food chain but they are also important means to improve human health and well-being, with the exception of vitamin B12 and D. A diverse and well-balanced plant-based diet, that includes mixed sources of grains, fruits, and vegetables, can ensure the proper micronutrient nutrition and health at all stages of the life cycle (Tables 5.1, 5.2) (18,20,21,37-39). It is known that seeds are good sources of lipid-soluble vitamins, but tend to have low levels of bioavailable iron, zinc, and calcium, whereas leafy vegetables can supply most minerals and vitamins. Fruits provide water-soluble vitamins and several types of carotenoids but generally are minor sources of certain minerals. Thus, concentrations of very few individual plant foods are able to supply all the daily recommended intake of any micronutrient in an average or reasonable serving size (20-22,37-39). Unfortunately, many people do not consume a sufficiently diverse diet. In fact, many low-income families from the developing world subsist with a simple diet formed mainly of a staple food (i.e., maize, soybean, beans, wheat, tubers, root) that are poor sources of many micronutrients (2,16,20-25,27,37-39). Heavy and monotonous consumption of cereal-based foods with low concentrations and diminished bioavailability of iron and zinc has been considered a major reason for the current widespread deficiency of both minerals in developing countries (16,20-25,27,37-39). Furthermore, even in developed nations, the average intake of fruits and vegetables may fall below official recommendations (19,21).

Table 5.1

Minerals: Dietary allowances per day and safe upper intake limit values, sources, deficiency and importance on human genomic stability.

Deficiency

Deficiency

Deficiency

Minerals

Safe Upper Maximum Intake Limits Adult (Relative to RDAl> RDA)e

Predominant Food Sources

Some Classical

Nutritional Disorders and Diseases

DNA Damage (Negative Effecton Genomic Stability)

New Health Effects

Functions on Genomic Stability

Selenium

70 ng

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