Zinc Plus

Numerous aspects of cellular metabolism are zinc-dependent. Zinc plays important roles in growth and development, the immune response, neurological function, and reproduction. On the cellular level, the function of zinc can be divided into three categories:

Nearly 100 different enzymes depend on zinc for their ability to catalyze vital chemical reactions. Zinc-dependent enzymes can be found in all known classes of enzymes.

Zinc plays an important role in the structure of proteins and cell membranes. A finger-like structure, known as a zinc finger motif, stabilizes the structure of a number of proteins. For example, copper provides the catalytic activity for the antioxidant enzyme copper-zinc superoxide dismutase (CuZnSOD), while zinc plays a critical structural role.The structure and function of cell membranes are also affected by zinc. Loss of zinc from biological membranes increases their susceptibility to oxidative damage and impairs their function .

Zinc finger proteins have been found to regulate gene expression by acting as transcription factors (binding to DNA and influencing the transcription of specific genes). Zinc also plays a role in cell signaling and has been found to influence hormone release and nerve impulse transmission. Recently, zinc has been found to play a role in apoptosis (gene-directed cell death), a critical cellular regulatory process with implications for growth and development, as well as a number of chronic diseases.
Much of what is known about severe zinc deficiency was derived from the study of individuals born with acrodermatitis enteropathica, a genetic disorder resulting from the impaired uptake and transport of zinc. The symptoms of severe zinc deficiency include the slowing or cessation of growth and development, delayed sexual maturation, characteristic skin rashes, chronic and severe diarrhea, immune system deficiencies, impaired wound healing, diminished appetite, impaired taste sensation, night blindness, swelling and clouding of the corneas, and behavioral disturbances. Before the cause of acrodermatitis enteropathica was known, patients typically died in infancy. Oral zinc therapy results in the complete remission of symptoms, though it must be maintained indefinitely in individuals with the genetic disorder. Although dietary zinc deficiency is unlikely to cause severe zinc deficiency in individuals without a genetic disorder, zinc malabsorption or conditions of increased zinc loss, such as severe burns or prolonged diarrhea, may also result in severe zinc deficiency.
It has recently become apparent that milder zinc deficiency contributes to a number of health problems, especially common in children who live in developing countries. The lack of a sensitive indicator of mild zinc deficiency hinders the scientific study of its health implications. However, controlled trials of moderate zinc supplementation have demonstrated that mild zinc deficiency contributes to impaired physical and neuropsychological development and increased susceptibility to life-threatening infections in young children.

Individuals with severe or persistent diarrhea
Individuals with malabsorption syndromes, including celiac disease and short bowel syndrome
Individuals with inflammatory bowel disease, including Crohn's disease and ulcerative colitis
Individuals with alcoholic liver disease who have increased urinary zinc excretion and low liver zinc levels
Individuals with sickle cell anemia
Older adults (65 years and older)
Strict vegetarians: The requirement for dietary zinc may be as much as 50% greater for strict vegetarians whose major food staples are grains and legumes, because high levels of phytic acid in these foods reduce zinc absorption.

Zinc supplements in large amounts may cause diarrhea, abdominal cramps, and vomiting, usually within 3 - 10 hours of swallowing the supplements. The symptoms go away within a short period of time after the stopping the supplements.The Food and Nutrition Board at the Institute of Medicine recommends the following dietary intake for zinc:
Infants

Thiamin is a water-soluble B vitamin, known as vitamin B1 or aneurine. Isolated and characterized in the 1930s, thiamin was one of the first organic compounds to be recognized as a vitamin. Thiamin pyrophosphate (TPP) is a required coenzyme for a small number of very important enzymes. The synthesis of TPP from free thiamin requires magnesium, adenosine triphosphate (ATP), and the enzyme, thiamin pyrophosphokinase.
Beriberi, the disease resulting from severe thiamin deficiency, was described in Chinese literature as early as 2600 B.C. Thiamin deficiency affects the cardiovascular, nervous, muscular, and gastrointestinal systems. Beriberi has been termed dry, wet, or cerebral, depending on the systems affected by severe thiamin deficiency.Thiamin deficiency may result from inadequate thiamin intake, increased requirement for thiamin, excessive loss of thiamin from the body, consumption of anti-thiamin factors in food, or a combination of these factors.
Inadequate consumption of thiamin is the main cause of thiamin deficiency in underdeveloped countries. Thiamin deficiency is common in low-income populations whose diets are high in carbohydrate and low in thiamin (e.g., milled or polished rice). Breast-fed infants whose mothers are thiamin deficient are vulnerable to developing infantile beriberi. Alcoholism, which is associated with low intake of thiamin among other nutrients, is the primary cause of thiamin deficiency in industrialized countries. The Food and Nutrition Board at the Institute of Medicine recommends the following dietary intake for thiamine:
Infants

Riboflavin is a water-soluble B vitamin, also known as vitamin B2. In the body, riboflavin is primarily found as an integral component of the coenzymes, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN).
Living organisms derive most of their energy from oxidation-reduction (redox) reactions, which are processes that involve the transfer of electrons. Flavocoenzymes participate in redox reactions in numerous metabolic pathways . Flavocoenzymes are critical for the metabolism of carbohydrates, fats, and proteins. FAD is part of the electron transport (respiratory) chain, which is central to energy production. In conjunction with cytochrome P-450, flavocoenzymes also participate in the metabolism of drugs and toxins .
Glutathione reductase is a FAD-dependent enzyme that participates in the redox cycle of glutathione. The glutathione redox cycle plays a major role in protecting organisms from reactive oxygen species, such as hydroperoxides. Glutathione reductase requires FAD to regenerate two molecules of reduced glutathione from oxidized glutathione. Riboflavin deficiency has been associated with increased oxidative stress . Measurement of glutathione reductase activity in red blood cells is commonly used to assess riboflavin nutritional status .
Riboflavin deficiency alters iron metabolism . Although the mechanism is not clear, research in animals suggests that riboflavin deficiency may impair iron absorption, increase intestinal loss of iron, and/or impair iron utilization for the synthesis of hemoglobin. In humans, improving riboflavin nutritional status has been found to increase circulating hemoglobin levels. Correction of riboflavin deficiency in individuals who are both riboflavin and iron deficient improves the response of iron-deficiency anemia to iron therapy.The Food and Nutrition Board at the Institute of Medicine recommends the following dietary reference intake for riboflavin:
Infants

Vitamin B6 is a water-soluble vitamin that was first isolated in the 1930s. The phosphate ester derivative pyridoxal 5'-phosphate (PLP) is the principal coenzyme form and has the most importance in human metabolism Vitamin B6 must be obtained from the diet because humans cannot synthesize it. PLP plays a vital role in the function of approximately 100 enzymes that catalyze essential chemical reactions in the human body. For example, PLP functions as a coenzyme for glycogen phosphorylase, an enzyme that catalyzes the release of glucose from stored glycogen. Much of the PLP in the human body is found in muscle bound to glycogen phosphorylase. PLP is also a coenzyme for reactions used to generate glucose from amino acids, a process known as gluconeogenesis.
In the brain, the synthesis of the neurotransmitter, serotonin, from the amino acid, tryptophan, is catalyzed by a PLP-dependent enzyme. Other neurotransmitters, such as dopamine, norepinephrine and gamma-aminobutyric acid (GABA), are also synthesized using PLP-dependent enzymes.
PLP functions as a coenzyme in the synthesis of heme, an iron-containing component of hemoglobin. Hemoglobin is found in red blood cells and is critical to their ability to transport oxygen throughout the body. Both PL and PLP are able to bind to the hemoglobin molecule and affect its ability to pick up and release oxygen. However, the impact of this on normal oxygen delivery to tissues is not known.
Steroid hormones, such as estrogen and testosterone, exert their effects in the body by binding to steroid hormone receptors in the nucleus of the cell and altering gene transcription. PLP binds to steroid receptors in a manner that inhibits the binding of steroid hormones, thus decreasing their effects. The binding of PLP to steroid receptors for estrogen, progesterone, testosterone, and other steroid hormones suggests that the vitamin B6 status of an individual may have implications for diseases affected by steroid hormones, including breast cancer and prostate cancers.
Severe deficiency of vitamin B6 is uncommon. Alcoholics are thought to be most at risk of vitamin B6 deficiency due to low dietary intakes and impaired metabolism of the vitamin. In the early 1950s, seizures were observed in infants as a result of severe vitamin B6 deficiency caused by an error in the manufacture of infant formula. Abnormal electroencephalogram (EEG) patterns have been noted in some studies of vitamin B6 deficiency. Other neurologic symptoms noted in severe vitamin B6 deficiency include irritability, depression, and confusion; additional symptoms include inflammation of the tongue, sores or ulcers of the mouth, and ulcers of the skin at the corners of the mouth. The Food and Nutrition Board at the Institute of Medicine recommends the following dietary intake for vitamin B6:
Infants

Vitamin B12 is a water-soluble vitamin. Water-soluble vitamins dissolve in water. After the body uses these vitamins, leftover amounts leave the body through the urine.Typically, water-soluble vitamins can not be stored by the body. Vitamin B12 is special, because the body can store it for years in the liver.
Vitamin B12 has the largest and most complex chemical structure of all the vitamins. It is unique among vitamins in that it contains a metal ion, cobalt. For this reason cobalamin is the term used to refer to compounds having vitamin B12 activity. Methylcobalamin and 5-deoxyadenosyl cobalamin are the forms of vitamin B12 used in the human body. In mammals, cobalamin is a cofactor for only two enzymes, methionine synthase and L-methylmalonyl-CoA mutase.
Methylcobalamin is required for the function of the folate-dependent enzyme, methionine synthase. This enzyme is required for the synthesis of the amino acid, methionine, from homocysteine. Methionine in turn is required for the synthesis of S-adenosylmethionine, a methyl group donor used in many biological methylation reactions, including the methylation of a number of sites within DNA and RNA. Methylation of DNA may be important in cancer prevention. Inadequate function of methionine synthase can lead to an accumulation of homocysteine, which has been associated with increased risk of cardiovascular diseases.
5-Deoxyadenosylcobalamin is required by the enzyme that catalyzes the conversion of L-methylmalonyl-CoA to succinyl-CoA. This biochemical reaction plays an important role in the production of energy from fats and proteins. Succinyl CoA is also required for the synthesis of hemoglobin, the oxygen carrying pigment in red blood cells.
Vitamin B12 deficiency is estimated to affect 10%-15% of individuals over the age of 60. Vitamin B12 deficiencies occur when the body is unable to properly use the vitamin. Pernicious anemia can make the body unable to absorb vitamin B12 from the intestinal tract.Absorption of vitamin B12 from food requires normal function of the stomach, pancreas, and small intestine. Stomach acid and enzymes free vitamin B12 from food, allowing it to bind to other proteins called R proteins. In the alkaline environment of the small intestine, R proteins are degraded by pancreatic enzymes, freeing vitamin B12 to bind to intrinsic factor (IF), a protein secreted by specialized cells in the stomach. Receptors on the surface of the small intestine take up the IF-B12 complex only in the presence of calcium, which is supplied by the pancreas.The Food and Nutrition Board at the Institute of Medicine recommends the following dietary intake for vitamin B 12:
Infants

Vitamin C is a water-soluble vitamin that is necessary for normal growth and development. Vitamin C, also known as ascorbic acid and unlike most mammals, humans do not have the ability to make their own vitamin C. Therefore, we must obtain vitamin C through our diet.
Vitamin C is required for the synthesis of collagen, an important structural component of blood vessels, tendons, ligaments, and bone. Synthesis of collagen is very important for children`s health. This Vitamin C also plays an important role in the synthesis of the neurotransmitter, nor epinephrine . Neurotransmitters are critical to brain function and are known to affect mood. In addition, vitamin C is required for the synthesis of carnitine, a small molecule that is essential for the transport of fat to cellular organelles called mitochondria, for conversion to energy.
Recent research also suggests that vitamin C is involved in the metabolism of cholesterol to bile acids, which may have implications for blood cholesterol levels and the incidence of gallstones. Vitamin C is also a highly effective antioxidant. Even in small amounts vitamin C can protect indispensable molecules in the body, such as proteins, lipids (fats), carbohydrates, and nucleic acids (DNA and RNA) from damage by free radicals and reactive oxygen species that can be generated during normal metabolism as well as through exposure to toxins and pollutants (e.g. smoking). Vitamin C may also be able to regenerate other antioxidants such as vitamin E.Too little vitamin C can lead to signs and symptoms of deficiency, including:

Severe vitamin C deficiency has been known for many centuries as the potentially fatal disease, scurvy. Symptoms of scurvy include bleeding and bruising easily, hair and tooth loss, joint pain and swelling. Such symptoms appear to be related to the weakening of blood vessels, connective tissue, and bone, which contain collagen. Early symptoms of scurvy such as fatigue may result from diminished levels of carnitine , needed to derive energy from fat or decreased synthesis of the neurotransmitter norepinephrine. Scurvy is rare in developed countries because it can be prevented by as little as 10 mg of vitamin C daily. However, recent cases have occurred in children and the elderly on very restricted diets.
The Food and Nutrition Board at the Institute of Medicine recommends the following amounts of vitamin C:
Infants and Children

Women who are pregnant or breastfeeding and those who smoke need higher amounts.

Biotin is a water-soluble vitamin that is generally classified as a B-complex vitamin. After the initial discovery of biotin, nearly 40 years of research were required to establish it as a vitamin. Biotin is required by all organisms but can be synthesized only by bacteria, yeasts, molds, algae, and some plant species.Biotin is essential to growth. It helps the body break down and use food. This is called metabolism.
Biotin is attached at the active site of five mammalian enzymes known as carboxylases. The attachment of biotin to another molecule, such as a protein, is known as "biotinylation." Holocarboxylase synthetase (HCS) catalyzes the biotinylation of apocarboxylases (i.e., the catalytically inactive form of the enzyme) and of histones . Biotinidase catalyzes the release of biotin from histones and from the peptide products of carboxylase breakdown.
Although overt biotin deficiency is very rare, the human requirement for dietary biotin has been demonstrated in two different situations: prolonged intravenous feeding (parenteral) without biotin supplementation and consumption of raw egg white for a prolonged period (many weeks to years). Avidin is an antimicrobial protein found in egg white that binds biotin and prevents its absorption. Cooking egg white denatures avidin, rendering it susceptible to digestion and therefore unable to prevent the absorption of dietary biotin.
Signs of overt biotin deficiency include hair loss and a scaly red rash around the eyes, nose, mouth, and genital area. Neurologic symptoms in adults have included depression, lethargy, hallucination, and numbness and tingling of the extremities. The characteristic facial rash, together with unusual facial fat distribution, has been termed the "biotin deficient facies" by some investigators. Individuals with hereditary disorders of biotin metabolism resulting in functional biotin deficiency often have similar physical findings as well as evidence of impaired immune system function and increased susceptibility to bacterial and fungal infections.
Research indicates that biotin is broken down more rapidly during pregnancy and that biotin nutritional status declines during the course of pregnancy. Over half of pregnant women have abnormally high excretion of a metabolite thought to reflect decreased activity of a biotin-dependent enzyme. Although the level of biotin depletion is not severe enough to cause diagnostic signs or symptoms, such observations are sources of concern because subclinical biotin deficiency has been shown to cause birth defects in several animal species .Currently, it is estimated that at least one third of women develop marginal biotin deficiency during pregnancy. Indirect evidence also suggests that marginal biotin deficiency causes birth defects in humans. On balance, the potential risk for teratogenesis (abnormal development of the embryo or fetus) from biotin deficiency makes it prudent to ensure adequate biotin intake throughout pregnancy.

The Food and Nutrition Center of the Institute of Medicine has established the following recommended dietary intakes:

The terms folic acid and folate are often used interchangeably for this water-soluble B-complex vitamin. Folic acid, the more stable form, occurs rarely in foods or the human body but is the form most often used in vitamin supplements and fortified foods. Naturally occurring folates exist in many chemical forms. Folates are found in foods as well as in metabolically active forms in the human body.
The only function of folate coenzymes in the body appears to be in mediating the transfer of one-carbon units. Folate coenzymes act as acceptors and donors of one-carbon units in a variety of reactions critical to the metabolism of nucleic acids and amino acids .
Folate coenzymes play a vital role in DNA metabolism through two different pathways. The synthesis of DNA from its precursors (thymidine and purines) is dependent on folate coenzymes. A folate coenzyme is required for the synthesis of methionine, and methionine is required for the synthesis of S-adenosylmethionine (SAM). SAM is a methyl group (one-carbon unit) donor used in many biological methylation reactions, including the methylation of a number of sites within DNA and RNA. Methylation of DNA may be important in cancer prevention.
Folate coenzymes are required for the metabolism of several important amino acids. The synthesis of methionine from homocysteine requires a folate coenzyme as well as a vitamin B12-dependent enzyme. Thus, folate deficiency can result in decreased synthesis of methionine and a buildup of homocysteine. Increased levels of homocysteine may be a risk factor for heart disease as well as several other chronic diseases.
Folate deficiency is most often caused by a dietary insufficiency; however, folate deficiency can occur in a number of other situations. For example, alcoholism is associated with low dietary intake and diminished absorption of folate, which can lead to folate deficiency. Additionally, certain conditions such as pregnancy or cancer result in increased rates of cell division and metabolism, causing an increase in the body's demand for folate. Several medications may also contribute to deficiency.
Individuals in the early stages of folate deficiency may not show obvious symptoms, but blood levels of homocysteine may increase. Rapidly dividing cells are most vulnerable to the effects of folate deficiency; thus, when the folate supply to the rapidly dividing cells of the bone marrow is inadequate, blood cell division becomes abnormal resulting in fewer but larger red blood cells. This type of anemia is called megaloblastic or macrocytic anemia, referring to the enlarged, immature red blood cells.
The Food and Nutrition Board at the Institute of Medicine recommends the following dietary intake for folate:
Infants

Living organisms derive most of their energy from oxidation-reduction (redox) reactions, which are processes involving the transfer of electrons. As many as 200 enzymes require the niacin coenzymes, NAD and NADP, mainly to accept or donate electrons for redox reactions. NAD functions most often in energy producing reactions involving the degradation (catabolism) of carbohydrates, fats, proteins, and alcohol. NADP functions more often in biosynthetic (anabolic) reactions, such as in the synthesis of all macromolecules, including fatty acids and cholesterol.
Poly-ADP-ribose polymerases (PARPs) are enzymes that catalyze the transfer of many ADP-ribose units from NAD to acceptor proteins. PARPs appear to function in DNA repair and stress responses, cell signaling, transcription, regulation or apoptosis, chromatin structure, and cell differentiation, suggesting a possible role for NAD in cancer prevention. At least five different PARPs have been identified, and although their functions are not yet well understood, their existence indicates a potential for considerable consumption of NAD. A third class of enzymes (ADP-ribosyl cyclase) catalyzes the formation of cyclic ADP-ribose, a molecule that works within cells to provoke the release of calcium ions from internal storage sites and probably also plays a role in cell signaling.
The late stage of severe niacin deficiency is known as pellagra .The most common symptoms of niacin deficiency involve the skin, digestive system, and the nervous system. The symptoms of pellagra were commonly referred to as the four D's: dermatitis, diarrhea, dementia, and death. In the skin, a thick, scaly, darkly pigmented rash develops symmetrically in areas exposed to sunlight. In fact, the word "pellagra" comes from the Italian phrase for rough or raw skin. Symptoms related to the digestive system include a bright red tongue, vomiting, and diarrhea. Neurologic symptoms include headache, apathy, fatigue, depression, disorientation, and memory loss. If untreated, pellagra is ultimately fatal.The Food and Nutrition Board at the Institute of Medicine recommends the following dietary intake for niacin:
Infants

Pantothenic acid, also known as vitamin B5, is essential to all forms of life. Pantothenic acid is found throughout living cells in the form of coenzyme A (CoA), a vital coenzyme in numerous chemical reactions.
Pantothenic acid is a component of coenzyme A (CoA), an essential coenzyme in a variety of reactions that sustain life. CoA is required for chemical reactions that generate energy from food (fat, carbohydrates, and proteins). The synthesis of essential fats, cholesterol, and steroid hormones requires CoA, as does the synthesis of the neurotransmitter, acetylcholine, and the hormone, melatonin. Heme, a component of hemoglobin, requires a CoA-containing compound for its synthesis. Metabolism of a number of drugs and toxins by the liver requires CoA.
Coenzyme A was named for its role in acetylation reactions. Most acetylated proteins in the body have been modified by the addition of an acetate group that was donated by CoA. Protein acetylation affects the 3-dimensional structure of proteins, potentially altering their function. For example, acetylation reactions can alter the activity of peptide hormones. Protein acetylation appears to play a role in cell division and DNA replication and also affects gene expression by facilitating the transcription of mRNA. Additionally, a number of proteins are modified by the attachment of long-chain fatty acids donated by CoA. These modifications are known as protein acylation and appear to play a central role in cell signaling.
The acyl-carrier protein requires pantothenic acid in the form of 4'-phosphopantetheine for its activity as an enzyme. Both CoA and the acyl-carrier protein are required for the synthesis of fatty acids. Fatty acids are a component of some lipids, which are fat molecules essential for normal physiological function. Among these essential fats are sphingolipids, which are a component of the myelin sheath that enhances nerve transmission. Another example of these essential fats is the phospholipids that reside in cell membranes.
Naturally occurring pantothenic acid deficiency in humans is very rare and has been observed only in cases of severe malnutrition. Pantothenic acid deficiency in humans has been induced experimentally by co-administering a pantothenic acid antagonist and a pantothenic acid-deficient diet. Participants in this experiment complained of headache, fatigue, insomnia, intestinal disturbances, and numbness and tingling of their hands and feet.
The Food and Nutrition Center of the Institute of Medicine has established the following recommended dietary intakes:

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