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• Micronutrients


  Required by the body in lesser quantities (micrograms to milligrams)
• Micronutrients


  • Central role in metabolism and maintenance of tissue function
• The role of micronutrients

  • Cofactors in metabolism
  • Coenzymes in metabolism
  • Genetic control
  • Antioxidants
• Damage is limited by mechanisms that include direct quenching of oxidant activity by tocopherols (vitamin E) or carotenoids (vitamin A), or enzyme systems to dispose of the products of oxidation—superoxide dismutase (either zinc/copper or manganese dependent) and glutathione peroxidase (selenium dependent)
• Vitamins


  Complex, essential organic substances that perform a variety of metabolic functions and perform the same functions in different forms of life
• With the exception of vitamin D, micronutrients are not produced in the body and must be derived from the diet
• Though people only need small amounts of micronutrients, consuming the recommended amount is important
• At least half of children worldwide younger than 5 years of age suffer from vitamin and mineral deficiencies
• Thiamine (vitamin B1)


  Cofactor (TPP) for multiple enzymes involved in glucose breakdown. Deficiency can result in ATP depletion and often affects highly aerobic tissues such as the brain, nerves, and heart first.
• Thiamine deficiency


  • With heart involvement, it is called wet beriberi and is characterized by high-output heart failure, edema, and dyspnea on exertion
  • When the nervous system is involved, it is called dry beriberi, characterized by polyneuritis and symmetrical muscle wasting
  • Damage to the medial dorsal nucleus of the thalamus and the mammillary bodies in the brain can result in Wernicke encephalopathy or Wernicke-Korsakoff syndrome

  
• Thiamine deficiency often is part of the presentation in patients with alcohol use disorder secondary to malnutrition and malabsorption, in addition to patients suffering from malnutrition
• Riboflavin (vitamin B2)


  Key component of coenzymes involved with the growth of cells, energy production, and the breakdown of fats, steroids, and medications

  
• Riboflavin and coenzymes


  • FMN is required for l-amino acid oxidase, cytochrome C reductase
  • FAD is required as a coenzyme for pyruvate dehydrogenase complex, succinate dehydrogenase, α-ketoglutarate dehydrogenase complex, xanthine oxidase

  
• Riboflavin deficiency


  • Leads to cheilosis (inflammation of lips and fissures of the mouth) and corneal vascularization
  • Can lead to brain and heart disorders and some cancers
  • Disorders of the thyroid can increase the risk of a deficiency
  • Often occurs with other nutrient deficiencies, such as in those who are malnourished

  
• Niacin (vitamin B3)


  • Works in the body as a coenzyme, with more than 400 enzymes dependent on it for various reactions
  • Utilized in redox reactions (as NAD+ and NADP+)
  • Helps to convert nutrients into energy, create cholesterol and fats, create and repair DNA, and exert antioxidant effects

  
• Niacin's metabolic function


  • To form the nicotinamide ring of the coenzymes NAD and NADP
  • Helps release energy from nutrients
  • NAD is required as a coenzyme for pyruvate dehydrogenase complex and α-ketoglutarate dehydrogenase complex
  • NADP is required for reactions involving glucose-6-phosphate dehydrogenase and 6-phosphate gluconate dehydrogenase

  
• Groups at risk for niacin deficiency

  • Limited diets
  • Chronic alcoholism
  • Carcinoid syndrome

  
• Pantothenic acid (vitamin B5)


  A component of coenzyme A and fatty acid synthase, necessary for energy production and the formation of hormones

  
• Pyridoxine (vitamin B6)


  • Converted to pyridoxal phosphate (PLP) and is part of reactions including transamination, decarboxylation, and glycogen phosphorylase
  • Critical for the formation of red blood cells

  
• Pyridoxine deficiency


  • Can result in sideroblastic anemia, hyperirritability, convulsions, peripheral neuropathy, and mental confusion
• Biotin (vitamin B7)


  • Necessary for the metabolism of protein, fats, and carbohydrates
  • Helps to regulate signals sent by cells and the activity of genes
  • Functions as a coenzyme in reactions involving CO2, e.g. pyruvate carboxylase, propionyl CoA carboxylase, acetyl CoA carboxylase
• Biotin deficiency


  • Initial symptoms are: hair loss, dry skin, brittle hair, fungal infections, seborrheic dermatitis, and rashes
  • Other symptoms include: fatigue, anemia, nausea, appetite loss, conjunctivitis, depression, dandruff, psoriasis, eczema, and loss of muscular reflexes
  • Prolonged deficiency can lead to muscle pain, heart problems, anemia, and depression
  • Alcoholism can increase the risk of biotin deficiency

  
• Folic acid (vitamin B9)


  • Helps to form DNA and RNA and is involved in protein metabolism
  • Plays a key role in breaking down homocysteine
  • Needed to produce healthy red blood cells and is critical during periods of rapid growth, such as during pregnancy and fetal development

  
• CO2


  E.g. pyruvate carboxylase; propionyl CoA carboxylase; acetyl CoA carboxylase

  
• Biotin deficiency


  • Deficiency is very rare
  • Initial symptoms: hair loss, dry skin, brittle hair, fungal infections, seborrheic dermatitis, and rashes
  • Other symptoms: fatigue, anemia, nausea, appetite loss, conjunctivitis, depression, dandruff, psoriasis, eczema, and loss of muscular reflexes
  • Prolonged deficiency can lead to muscle pain, heart problems, anemia, and depression
  • Alcoholism can increase the risk of biotin deficiency

  
• Folic acid (Vitamin B9)


  • Helps to form DNA and RNA and is involved in protein metabolism
  • Plays a key role in breaking down homocysteine
  • Needed to produce healthy red blood cells and is critical during periods of rapid growth, such as during pregnancy and fetal development
  • The Recommended Dietary Allowance for folate is listed as micrograms (mcg) of dietary folate equivalents (DFE). Men and women ages 19 years and older should aim for 400 mcg DFE. Pregnant and lactating women require 600 mcg DFE and 500 mcg DFE, respectively. People who regularly drink alcohol should aim for at least 600 mcg DFE of folate daily since alcohol can impair its absorption

  
• Tetrahydrofolate


  • Coenzyme form of folic acid
  • Carrier of single carbon and involved in single carbon transfer reactions
  • Involved in the generation of dTMP from dUMP (pyrimidine synthesis) in a reaction catalyzed by thymidylate synthase

  
• Folic acid deficiency


  • Deficiency is rare because it is found in a wide range of foods
  • Conditions that may put people at increased risk: alcoholism, pregnancy, intestinal surgeries or digestive disorders that cause malabsorption, genetic variants
  • Signs of deficiency can include: megaloblastic anemia; weakness, fatigue; irregular heartbeat; shortness of breath; difficulty concentrating; hair loss; pale skin; mouth sores

  
• Cobalamin (Vitamin B12)


  • Essential for erythropoiesis and development and functioning of the nervous system
  • Binds to the protein in the foods, in the stomach, hydrochloric acid and enzymes unbind vitamin B12 into its free form. From there, vitamin B12 combines with a protein called intrinsic factor so that it can be absorbed further down in the small intestine
  • The Recommended Dietary Allowance for men and women ages 14 years and older is 2.4 micrograms (mcg) daily. For pregnancy and lactation, the amount increases to 2.6 mcg and 2.8 mcg daily
  • B12 used as descriptor for the cobalamins: contain cobalt and corrin ring; possess biological vitamin activity. Some corrinoids have no vitamin B12 activity. Methylcobalamin, Deoxyadenosylcobalamin

  
• Cobalamin deficiency


  • May lead to pernicious anemia and subacute combined degeneration of the spinal cord
  • The macrocytic megaloblastic anemia from B12 deficiency presents similarly to folate deficiency, and to differentiate them, it is imperative to obtain serum homocysteine and methylmalonic acid levels. In folate deficiency, homocysteine will elevate, but methylmalonic acid levels will be normal. In vitamin B12 deficiency, both homocysteine and methylmalonic acid levels will present as elevated
  • Additionally, B12 deficiency will present with neurologic symptoms, whereas folate deficiency will not
  • Factors that may cause vitamin B12 deficiency: avoiding animal products, lack of intrinsic factor, medications that cause decreased stomach acid, intestinal surgeries or digestive disorders that cause malabsorption

  
• Cobalamin deficiency and nerve damage

  • Nerve damage caused by cobalamin deficiency: methylcobalamin required in conversion of homocysteine to methionine; causes lack of methionine used to make myelin. Occurs over a long period of time (decades) and may cause: confusion or change in mental status (dementia) in severe or advanced cases; depression; loss of balance, numbness and tingling of hands and feet

  
• Enzymes dependent on cobalamin

  • Methylmalonyl CoA mutase: converts methyl malonyl CoA into succinyl CoA; B12 deficiency causes accumulation of methylmalonyl CoA and urinary excretion of methylmalonic acid, which provides a means of assessing vitamin B12 nutritional status
  • Leucine aminomutase
  • Methionine synthase: synthesis of methionine (affects myelin production)
• A healthy diet (WHO, April 2020)

  • Energy intake (calories) should be in balance with energy expenditure. To avoid unhealthy weight gain, total fat should not exceed 30% of total energy intake
  • Intake of saturated fats should be less than 10% of total energy intake, and intake of trans-fats less than 1% of total energy intake, with a shift in fat consumption away from saturated fats and trans-fats to unsaturated fats, and towards the goal of eliminating industrially-produced trans-fats
  • Limiting intake of free sugars to less than 10% of total energy intake is part of a healthy diet. A further reduction to less than 5% of total energy intake is suggested for additional health benefits
  • Keeping salt intake to less than 5 g per day (equivalent to sodium intake of less than 2 g per day) helps to prevent hypertension, and reduces the risk of heart disease and stroke in the adult population