Micronutrients in Health and Disease, Second Edition

Kedar N. Prasad

• Publisher: CRC Press
• Year: 2019
• ISBN:
  9780429516610
• Edition: 2
• Topic: Medicina
• Subtopic: Nutrizione, dietetica e bariatria

Increased oxidative stress due to the production of excessive amounts of free radicals along with the effects of chronic inflammation plays a major role in the initiation and progression of most chronic diseases. In addition, increased release of glutamate plays a central role in the pathogenesis of various disorders.

This second edition of Micronutrients in Health and Disease proposes a novel concept that in order to simultaneously and optimally reduce oxidative stress, chronic inflammation, and glutamate, it is essential to increase levels of antioxidant enzymes as well as levels of dietary and endogenous antioxidant compounds at the same time. This is accomplished by activating the Nrf2 pathways and by increasing the levels of antioxidant compounds and B-vitamins through supplementation. This book proposes a mixture of micronutrients that achieves this above goal. The mixture of micronutrients together with modification in diet and lifestyle may reduce the risk of chronic diseases and in combination with standard care, may improve the management of these diseases.

KEY FEATURES

• Provides evidence in support of the idea that increased oxidative stress, chronic inflammation, and glutamate are involved in the pathogenesis of chronic diseases.

• Contains three new chapters on Huntington's disease, Autism spectra, and Prion disease.

• Discusses the role of microRNAs in the pathogenesis of chronic diseases.

• Presents information on regulation of the expression of microRNAs by reactive oxygen species and antioxidants.

Micronutrients in Health and Disease, Second Edition serves as a valuable resource for those seeking to promote healthy aging and prevent and improved management of chronic diseases.

1	Basic Facts about Micronutrients

INTRODUCTION

Micronutrients include dietary and endogenous antioxidants, vitamin D3, all B-vitamins, and certain minerals (selenium, zinc, iron, copper and manganese); whereas macronutrients primarily include lipids, carbohydrates, and proteins. Although all micronutrients are essential for growth and development, antioxidants have been subject of extensive laboratory research and clinical studies because of their potential importance in reducing oxidative stress and inflammation that could improve health and reduce the risk of chronic diseases. Before discussing the role of micronutrients in healthy aging, and prevention and improved management of diseases, it is essential to understand certain basic facts about micronutrients.

This chapter describes briefly the evolution of the antioxidant system; provides a historical prospective of some antioxidants, vitamin D3 and B-vitamins; describes the sources, solubility, distribution, storage, absorption, and functions of dietary and endogenous antioxidants; explains antioxidant defense systems and current controversies about antioxidants; and discusses the misuse of antioxidants in clinical studies. In Chapters 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23 of this volume, the detailed role of antioxidants and other micronutrients in health and disease is discussed with respect to aging and specific diseases. Several books have been published on this topic; a few are referenced at the end of this chapter.^{1,2,3,4,5,6,7,8,9,10}

EVOLUTION OF THE ANTIOXIDANT SYSTEM

Antioxidants are essential for the growth and survival of all organisms that depend on oxygen, including humans. In its early stage, Earth’s atmosphere had no oxygen. Anaerobic organisms, which can live without oxygen, thrived in the oceans and rivers. About 2.5 billion years ago, blue-green algae in the ocean acquired the ability to split water (H₂O) into hydrogen (H) and oxygen (O₂). This chemical reaction initiated the release of oxygen into the atmosphere, leading to the extinction of many anaerobic organisms due to the toxicity of oxygen. Those organisms that developed antioxidant defense systems survived—an important biological event that led to the rapid evolution of multicellular organisms that use oxygen for survival. Today, the amount of oxygen in dry air is about 21%, and in water it is about 34%.

HISTORY OF THE DISCOVERY OF MICRONUTRIENTS

Vitamin A: Night blindness, which we now know is caused by vitamin A deficiency, existed for centuries before the discovery of vitamin A. As early as about 1500 BC, the Egyptian knew how to cure this disease. Roman soldiers suffering from night blindness traveled to Egypt, where they would receive liver extract for treatment. It is now well established that liver is a rich source of vitamin A. The treatment of night blindness with liver extract was not performed outside Egypt for centuries; the medical establishment during that period must not have accepted this treatment. It was not until 1912 when Dr. McCollum of the University of Wisconsin discovered vitamin A in butter; and therefore it was initially called a “fat soluble A.” The structure of vitamin A was determined in 1930, and this vitamin was synthesized in a laboratory in 1947.

Carotenoids: In 1919 carotenoids pigments were isolated from yellow plants, and in 1930 it was found that some of the ingested carotene was converted to vitamin A. This carotene was referred to as beta-carotene.

Vitamin C: Scurvy is caused by vitamin C deficiency. The symptoms of this disease were known to Egyptians as early as 1,500 BC. In the fifth century BC, Hippocrates described the symptoms of scurvy, which included bleeding gums, hemorrhaging, and death. Native North Americans knew the cure of this disease, but knowledge of the treatment remained limited to this population. During the sea voyages of European explorers between the twelfth and sixteenth centuries, the epidemic of scurvy among sailors forced some to land in Canada where the Native people gave them extract of pine bark and needles (prepared like tea). This treatment completely cured scurvy in these sailors. In 1536 Jacques Cartier, a French explorer, brought this formulation for curing scurvy to France, but the medical establishment rejected it as fraud because it came from Native Americans, who were seen as savages. In 1593, Sir Richard Hawkins recommended that his sailors consume sour oranges and lemons. In 1770, the British Navy began recommending that ships carry sufficient lime juice for all personnel aboard. In 1928, Albert Szent-Gyorgyi, a Hungarian scientist, isolated a substance from the adrenal gland that was called hexuronic acid. This substance was vitamin C, and in 1932, it was the first vitamin to be synthesized in a laboratory.

Vitamin D: Although rickets, a bone disease, may have existed in human populations for centuries, it was not until 1645, when Dr. Daniel Whistler described the symptoms of rickets, that we now know is due to vitamin D deficiency. In 1922, Sir Edward Mellanby discovered vitamin D while working on a cure for rickets. This vitamin was later found to require sunlight for its formation. The chemical structure of vitamin D was determined by German scientist Dr. Windaus in 1930. Vitamin D3 was chemically characterized in 1936 and was considered a steroid that was effective in the treatment of rickets.

Vitamin E: In 1922, Dr. Herbert Evans from the University of California, Berkeley, observed that rats reared exclusively on whole milk grew normally but were not fertile. The fertility was restored when they were additionally fed wheat germ. However, it took another 14 years (1936) before the active substance responsible for restoring fertility was isolated. Dr. Evans named it tocopherol, from the Greek word meaning “to bear offspring” with the ending “ol” signifying its chemical status as an alcohol.

B-Vitamins: All B-vitamins were discovered in the period of 1912–1934. In 1912, the Polish-born biochemist Dr. Casimir Funk isolated the active substance from the rice husks of unpolished rice that prevented the disease beriberi. He named this substance “vitamines” because he thought they were amines, which are derived from ammonia. In 1920, the “e” was dropped when it became known that not all vitamins are amines.

SOURCES AND FORMS OF VITAMINS

Vitamin A and Beta-Carotene: The richest sources of vitamin A are liver (6.5 mg per 100 g liver) from beef, pork, chicken, turkey, and fish; carrot (0.8 mg per 100 g); broccoli leaves (0.8 mg per 100 g); sweet potatoes (0.7 mg per 100 g); kale (0.7 mg per 100 g); butter (0.7 mg per 100 g); spinach (0.5 mg per 100 g); and pumpkin (0.4 mg per 100 g). Other small sources include cantaloupe melon, eggs, apricots, papaya, and mango (40 mg to 170 mg per 100 g). Yellow and red fruits and vegetables are very rich sources of beta-carotene. One molecule of beta carotene is converted to 2 molecules of retinol in the intestinal tract. Vitamin A exists as retinyl palmitate or retinyl acetate, which is coveted into the retinol form in the body. Vitamin A can also exist as a retinoic acid in the cells. It was determined that 1 international unit (IU) equals to 0.3 μg retinol, or 0.6 μg beta-carotene. The activity of vitamin A is also expressed as retinol activity equivalent (RAE). It was determined that 1 μg RAE corresponds with 1μg retinol and 2 μg beta-carotene in oil. Vitamin A and beta-carotene and the synthetic retinoids are also available commercially.

Carotenoids: The richest sources of carotenoids are sweet potatoes, carrots, spinach, mango, cantaloupe, apricot, kale, broccoli, parsley, cilantro, pumpkins, winter squash, and fresh thyme. There are two main forms of carotenoids found in nature: alpha-carotene and beta-carotene. Beta-carotene is the more common form of carotenoids. Other carotenes include lutein, zeaxanthin, and lycopene.

Vitamin C: The richest sources of vitamin C are fruits and vegetables. They include rosehip (2000 mg per 100 g rose hip); red pepper (2000 mg per 100 g red pepper); parsley (2000 mg per 100 g parsley); guava (2000 mg per 100 g guava); kiwi (2000 mg per 100 g kiwi); broccoli (2000 mg per 100 g broccoli); lychee (2000 mg per 100 g lychee); papaya (2000 mg per 100 g papaya); and strawberry (2000 mg per 100 g strawberry). Other sources of vitamin C include orange, lemon, melon, garlic, cauliflower, grapefruit, raspberry, tangerine, passion fruit, spinach, and lime (containing about 30 to 50 mg per 100 g fruits and vegetables). Vitamin C is sold commercially as L-ascorbic acid, calcium ascorbate, sodium ascorbate, or potassium ascorbate.

Vitamin E: The richest sources of vitamin E include wheat germ oil (215 mg per 100 g oil); sunflower oil (56 mg per 100 g oil); olive oil (12 mg per 100 g oil); almond oil (39 mg per 100 g oil); hazelnut oil (26 mg per 100 g oil); walnut oil (20 mg per 100 g oil); and peanut oil (17 mg per 100 g oil). The sources for small amounts of vitamin E (0.1 to 2 mg per 100 g) include kiwi fruit, fish, leafy vegetables, and whole grains. In the United States fortified breakfast cereals are important source of vitamin E. At present, most of the natural form of vitamin E is extracted from vegetable oils, primarily soybean oil.

Vitamin E exists in eight different forms: four tocopherols (alpha-, beta-, gamma-, and delta-tocopherol) and four tocotrienols (alpha-, beta-, gamma- and delta-tocotrienol). Alpha-tocopherol has the most biological activity. Vitamin E can exist in the natural form commonly indicated as d, whereas the synthetic form is referred to as dl. The stable esterified form of vitamin E is available as alpha-tocopheryl acetate, alpha-tocopheryl succinate, and alpha-tocopheryl nicotinate. The activity of vitamin E is generally expressed in international units (IU). It is determined that 1 IU equals 0.66 mg d-alpha-tocopherol, and 1 IU racemic mixture (dl-form) equals 0.45 mg d-tocopherol.

Glutathione: Glutathione is synthesized from three amino acids, L-cysteine, L-glutamic acid, and glycine, and is present in all cells; however, the liver contains the highest amount, up to 5 mM. Glutathione exists in the cells in reduced or oxidized form. In healthy cells, more than 90% of glutathione is present in the reduced form. The oxidized form of glutathione can be converted to the reduced form by the enzyme glutathione reductase. The reduced form of glutathione acts as an antioxidant.

N-acetylcysteine (NAC): NAC is a synthetic antioxidant made from amino acid L-cysteine that has acetyl group attached. It can directly as a glutathione substitute and indirectly as a precursor of glutathione.

Alpha-lipoic acid: Alpha-lipoic acid, also called thioctic acid, exists in two forms: R-alpha-lipoic acid (natural form) and S-alpha-lipoic acid (synthetic form). It acts as an antioxidant and elevates the levels of glutathione. R-alpha-lipoic acid is found in many vegetables, such as broccoli, yams, potatoes, and brussels sprout. Red meat and organs are rich in alpha-lipoic acid.

Coenzyme Q10: In 1957, Dr. Fredrick Crane isolated coenzyme Q10, and Dr. Wolf, working under Dr. Karl Folkers, determined the structure of coenzyme Q10 in 1958.

L-carnitine: L-carnitine is synthesized from amino acids lysine and methionine and was originally discovered as a growth factor for mealworms. It is primarily synthesized in the liver and kidneys. Vitamin C is necessary for the synthesis of L-carnitine. It exists as L-carnitine, a biologically active form, and as D-carnitine, a biologically inactive form.

B-vitamins: There are 8 different B-vitamins: B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folic acid), and B12 (cyanocobalamine). The major food sources of B-vitamins include meat, eggs, vegetables, and fruits.

Minerals (selenium and zinc): Commonly used selenium is in the form of L-selenomethionine (an organic form) and sodium selenite (an inorganic form). Selenium rich foods include Brazil nuts, lima beans, brown rice, and seeds (sunflower, sesame, and flax). Zinc compounds such as zinc picolinate, zinc gluconate, zinc acetate, and zinc oxide are utilized in the supplement. Rich food sources include oyster, crab, lobster, meat, poultry, legumes, nuts, seeds, and whole grain.

SOLUBILITY OF MICRONUTRIENTS

The lipid-soluble antioxidants include vitamin A, vitamin E, carotenoids, coenzyme Q10, and L-carnitine, and water-soluble antioxidants include vitamin C, glutathione, and alpha-lipoic acid. Vitamin D3 is lipid-soluble. All B-vitamins are soluble in water. Fat-soluble vitamins should be taken with meals, so that they are more readily absorbed. Zinc gluconate is soluble in water, whereas zinc picolinate is only partially soluble in water. Selenium compounds are soluble in water.

DISTRIBUTION OF ANTIOXIDANTS IN THE BODY

Carotenoids: Beta-carotene is one of more than 600 carotenoids found in fruits, vegetables, and plants. It is commercially available in natural or synthetic forms. Natural form of beta-carotene is more effective than the synthetic form. Preparations of natural carotenoids contain primarily beta-carotene; however, the other type of carotenoids is also present. A portion of ingested beta-carotene is converted to retinol (vitamin A) in the intestinal tract before absorption, and the re...