Healthy Energy (Part 1 – the basics)

A few days back, I blogged on why I liked the 5 hour energy drink. I would now like to blog a little on what things I’ve found that contribute to your body’s energy and why. I am only passing on the research I’ve done to reach my own concultions on what I should and shouldn’t take to boost my energy. I’m in no way qualified to tell you what is good for you, and it is only hoped that this information maybe handy as part of considering whether you what you should and shouldn’t do to boost your energy. Please remember to treat all things as if they may be harmful to you, and do your own research as well.

“Energy is defined as the ability to do work, and metabolism represents the biochemical reactions that a cell can perform to produce energy.”

The main sources of chemical energy for most organisms are carbohydrates, fats, and protein. Energy content is expressed in calories or joules. The nutritional calorie, or kilocalorie (kcal), in foodstuffs is equivalent to 1000 calories. The energy content per gram of carbohydrate is 4 kcal (16 J); protein, 4 kcal (16 J); and fat, 9 kcal (36 J). The metabolism of foodstuffs yields chemical energy and heat.

Source: http://www.answers.com/topic/energy-metabolism?cat=technology

“Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life.”

Source: http://en.wikipedia.org/wiki/Metabolism

The term metabolism refers to all of the chemical reactions by which complex molecules taken into an organism are broken down to produce energy and by which energy is used to build up complex molecules. All metabolic reactions fall into one of two general categories: catabolic and anabolic reactions, or the processes of breaking down and building up, respectively. The best example of metabolism from daily life occurs in the process of taking in and digesting nutrients, but sometimes these processes become altered, either through a person’s choice or through outside factors, and metabolic disorders follow. Such disorders range from anorexia and bulimia to obesity. These are all examples of an unhealthy, unnatural alteration to the ordinary course of metabolism; on the other hand, hibernation allows animals to slow down their metabolic rates dramatically as a means of conserving energy during times when food is scarce.

Metabolism is like a furnace, in that it burns energy, and that is the aspect most commonly associated with this concept. But metabolism also involves a function that a furnace does not: building new material. All metabolic reactions can be divided into either catabolic or anabolic reactions. Catabolism is the process by which large molecules are broken down into smaller ones with the release of energy, whereas anabolism is the process by which energy is used to build up complex molecules needed by the body to maintain itself and develop new tissue.

Digestion is the process of breaking down food into simpler chemical compounds as a means of making nutrients absorbable by the body. This is a catabolic process, because the molecules of which foods are made are much too large to pass through the lining of the digestive system and directly into the bloodstream. Thanks to the digestive process, smaller molecules are formed and enter the bloodstream, from whence they are carried to individual cells throughout a person’s body.

The smaller molecules into which nutrients are broken down make up the metabolic pool, which consists of simpler substances. The metabolic pool includes simple sugars, made by the breakdown of complex carbohydrates; glycerol and fatty acids, which come from the conversion of lipids, or fats; and amino acids, formed by the breakdown of proteins. Substances in the metabolic pool provide material from which new tissue is constructed—an anabolic process.

For the body to function efficiently, there has to be an effective means of controlling and integrating the metabolic processes occurring in all the cells, tissues, and organs. This integration and control is mainly achieved by circulating hormones, with their release being regulated in turn partly by the nervous system and partly by direct effects of substances in the blood on the endocrine glands. An example of this integrated control of metabolism is the way in which blood glucose concentration is regulated to ensure an adequate supply of glucose to the brain. After meals, the hormone insulin acts to promote storage of glucose in the form of glycogen in the liver. The brain continuously extracts glucose from the blood to use as a fuel for its metabolic processes. In the periods between meals, this continued use of blood glucose causes the concentration to fall, which could impair brain function. However, a fall in blood glucose is detected in the pancreas and leads to the release of the hormone glucagon, which acts on the liver to cause breakdown of glycogen and release of glucose into the blood. In addition, if blood glucose falls sufficiently to affect brain metabolism, the sympathetic nervous system is activated, causing the adrenal gland to release adrenaline, which also stimulates the release of glucose from the liver; also the individual feels hungry and is prompted to eat.

The main way in which the energy contained in the macronutrients is used in metabolism is via the substance adenosine triphosphate (ATP). Cells require energy for their metabolic processes, so they contain the enzymes and organelles needed to produce ATP from the catabolism of fats, carbohydrates, and/or proteins. In most cases, the production of ATP occurs in association with the oxidation, so that the final products are ATP, carbon dioxide, and water, as illustrated below for the oxidation of glucose (C6H12O6):

C6H12O6 + 6O2 = 6CO2 + 6H2O + ATP

This is an example of aerobic metabolism, requiring the supply of oxygen and the removal of carbon dioxide from the cells by the circulating blood. Thus, in order for this predominant type of metabolism to proceed effectively in the whole body, there needs to be integration of the respiration, circulation, and supply of nutrients.

In some situations, anaerobic metabolism can occur, ATP is produced without the use of oxygen, but the energy-releasing capacity of these systems is very small compared with that of aerobic metabolism, and the anaerobic reactions lead to the production of waste products such as lactic acid which impair cell function if they are present in high concentrations.

ATP is the single most important molecule for the metabolism of almost all the cells of the body. It is used to release the energy needed for muscles to contract, for chemical bonds to be made during the synthesis of complex molecules, and for other bonds to be broken during catabolic processes. Cells do not store large quantities of ATP, but rather produce it when it is needed. Thus, most cells of the body need to regulate the concentration of ATP within them. This occurs via the effects of ATP, and its immediate breakdown product ADP (adenosine diphosphate), on the enzymes responsible for synthesizing ATP: when more ATP is used, its concentration falls, and that of ADP rises, leading to the activation of the enzyme which synthesizes more ATP. This in turn requires more oxygen to be used, and nutrients to be broken down.

An example of the complex integration of metabolism is provided by considering the processes involved in muscle contraction during exercise. This involves the brain and other parts of the nervous system in the initiation of voluntary muscle contraction and movement. Contraction can occur only if ATP is available within the muscle cells. As the ATP already present is used, so the concentration of ADP will rise, which stimulates more ATP production. At the same time the contraction of the muscles stimulates the breakdown of the intramuscular glycogen, and may also stimulate the uptake of glucose and fatty acids from the blood. The increased availability of these fuels is accompanied by stimulation of their oxidation, so the ATP concentration is maintained, and muscle contraction continues, supported by an increase in aerobic energy metabolism. For this to be possible, it is also necessary for the supply of blood to the muscles to increase, in order to deliver more oxygen and carry away more carbon dioxide and heat; the action of chemical products of local metabolism, which dilate local blood vessels, effectively links flow to requirement.

The above examples illustrate the complexity of metabolism in the human body, and show that for normal function it is essential that local processes are co-ordinated and integrated throughout the body.

Source: http://www.answers.com/Metabolism

“Enzymes are catalysts for virtually every biological and chemical reaction in the body, and digestive enzymes are crucial for the breakdown of food into nutrients that the body can absorb. Digestive enzymes, of which a variety are herbs, are used to treat a number of digestive problems and other conditions.”

The Digestive enzymes are enzymes in the alimentary tract that break down food so that the organism can absorb it. The main sites of action are the oral cavity, the stomach, the duodenum and the jejunum. They are secreted by different glands: the salivary glands, the glands in the stomach, the pancreas, and the glands in the small intestines.

Oral cavity

In the oral cavity, salivary glands secrete ptyalin. It is a type of a-amylase, which digests starch into small segments of multiple sugars and into individual soluble sugars. Secreted by small and large salivary glands.

Salivary glands also secrete lysozyme, which kills bacteria but is not classified as a digestive enzyme.

Esophagus

There are no digestive enzymes secreted in the esophagus.

Stomach

The enzymes that get secreted in the stomach are called gastric enzymes. These are the following:

· Pepsin is the main gastric enzyme. As it breaks proteins into smaller peptide fragments, it is a peptidase.

· Gelatinase, degrades type I and type V gelatin and type IV and V collagen, which are proteoglycans in meat.

· Gastric amylase degrades starch, but is of minor significance.

· Gastric lipase is a tributyrase by its biochemical activity, as it acts almost exclusively on tributyrin, a butter fat.

Small intestine

Pancreatic enzymes

The pancreas is the main digestive gland in our body. It secretes the enzymes:

· Trypsin, is a peptidase, that breaks down peptides in the small intestine.

· Chymotrypsin, also a peptidase

· Steapsin, degrades triglycerides into fatty acids and glycerol.

· Carboxypeptidase, splits peptide fragments into individual amino acids. It is a protease.

· Several elastases that degrade the protein elastin and some other proteins.

· Several nucleases that degrade nucleic acids, like DNAase and RNAase

· Pancreatic amylase that, besides starch, glycogen and cellulose, degrades most other carbohydrates.

· Bile from the liver, which emulsifies fat, allowing more efficient use of lipases in the duodenum; in converting lipids to their component fatty acid and glycerol molecules

Proper small intestine enzymes

Several peptidases.

The jejunum and ileum secretes a juice called succus entericus which contains the following:

Six types of enzymes degrade disaccharides into monosaccharides:

· Sucrase, which breaks down sucrose into glucose and fructose

· Maltase, which breaks down maltose into glucose.

· Isomaltase, which breaks down maltose and isomaltose

· Lactase, which breaks down lactose into glucose and galactose

· Intestinal lipase, which breaks down fatty acids

· Erepsin, also a protein-digesting enzyme

Source: http://www.answers.com/Digestive+enzymes

“Digestive — Pertaining to digestion.”

• d. enzymes — include salivary (amylase), gastric (pepsin), pancreatic (trypsin, chymotrypsin, amylase, lipase), small intestinal mucosa (carbohydrases including isomaltase, lactase, maltase, sucrase, trehalase).
• d. inoculant — administered mostly to neonates primarily to provide an inoculum of beneficial bacteria and protozoa essential to proper digestion and usually picked up from the environment. In many commercial products the irresistible temptation to include other materials, including dietary essential vitamins and minerals, clouds the effect of the inoculant, and may, as in iron poisoning in foals, cause disaster.
• d. system — the organs that have as their particular function the ingestion, digestion and absorption of food or nutritive elements. They include the mouth, teeth, tongue, pharynx, esophagus, stomach and intestines. The accessory organs of digestion, which contribute secretions important to digestion, include the salivary glands, pancreas, liver and gallbladder. Birds have an unusual system in that there are no teeth and no soft palate in most. There is a pregastric buffer, the crop; the stomach is separated into two organs, one secretory and one muscular, and the large intestine is replaced by a dual cecum. The rectum empties into a cloaca which is shared with the urogenital tract. The ruminant system is complicated by the presence of the forestomachs, the reticulum, rumen and omasum, and there are no upper incisor teeth. The peculiarities of horses are the greatly distended large intestine and the absence of a gallbladder.
• d. tract — the digestive system less the ancillary organs of salivary glands, liver and pancreas; the luminal organs through which food passes. See also alimentary canal.

Source: http://www.answers.com/topic/digestive?nr=1&lsc=true&cat=health

“How can I tell a great digestive enzyme product by its label?”

There are three things to look for on the label. First, you want to make sure the enzymes are plant enzymes… Aspergillus oryzae and niger (these are the most effective digestive enzymes available). Second, look for ionic minerals within the formulation. These minerals help the digestive enzymes become two to three times more active and effective. Third, look closely at the amount of protease, amylase and lipase within the formulation… 75,000 HUT for Protease, 15,000 SKB for Amylase and 5,000 LU for Lipase. These amounts are very important if you really want to help with digestion and cleaning up the blood.

Source: http://breathing.com/articles/enzymes.htm

“Protease – Any of various enzymes, including the endopeptidases and exopeptidases, that catalyze the hydrolytic breakdown of proteins into peptides or amino acids.

Lipase — Any of a group of enzymes that catalyze the hydrolysis of fats into glycerol and fatty acids.

Amylase — Any of a group of enzymes that are present in saliva, pancreatic juice, and parts of plants and catalyze the hydrolysis of starch to sugar to produce carbohydrate derivatives.

Cellulase — Any of several enzymes produced chiefly by fungi, bacteria, and protozoans that catalyze the hydrolysis of cellulose.

Lactase — An enzyme occurring in certain yeasts and in the intestinal juices of mammals and catalyzing the hydrolysis of lactose into glucose and galactose.”

Sources: http://www.answers.com/Protease ; http://www.answers.com/Lipase ; http://www.answers.com/Amylase ; http://www.answers.com/Cellulase ; http://www.answers.com/Lactase?cat=health

“Excess phenylalanine is not stored in the body and has to be broken down by a specific enzyme.”

One of the 22 a-amino acids commonly found in animal proteins. It is one of several essential amino acids needed in the diet; human beings cannot synthesize it from simpler metabolites. Young adults need about 31 mg of this amino acid per day per kg (14 mg per lb) of body weight. Phenylalanine can be degraded into simpler compounds by the enzymes of the body and is readily converted to the amino acid tyrosine. Phenylketonuria (PKU), an inherited disease that, if left untreated, results in retarded mental development in children, has been shown to be associated with the lack of activity of the enzyme that converts phenylalanine to tyrosine. This results in the buildup of phenylalanine in the blood, an event leading to several pathological consequences. The incidence of this disease, about one in every 10,000 births, is high enough to have prompted several states to institute regular screening procedures for the detection of the disease in newborns. If diagnosed early the disease can be controlled to a great extent by administering a diet very low in phenylalanine. Phenylalanine contributes to the structure of proteins into which it has been incorporated by the tendency of its side chain to participate in hydrophobic interactions (see isoleucine). This amino acid was first isolated from a natural source (lupine sprouts) in 1879; it was first chemically synthesized in 1882.

An essential amino acid; in addition to its role in protein synthesis, it is the metabolic precursor of tyrosine (and hence noradrenaline, adrenaline, and the thyroid hormones). Dietary tyrosine spares phenylalanine, so reducing the requirement.

Persons suffering from PKU must monitor their intake of protein to control the buildup of phenylalanine as their bodies convert protein into its component amino acids.

A related issue is the compound present in many sugarless gums and mints, snack foods, sugarless soft drinks (such as diet sodas including CocaCola Zero, Pepsi Max, some forms of Lipton Tea, Clear Splash flavored water), and a number of other low calorie food products. The artificial sweetener aspartame, sold under the names “Equal” and “NutraSweet”, is an ester that is hydrolyzed in the body to give phenylalanine, aspartic acid, and methanol (wood alcohol). The breakdown problems phenylketonurics have with protein and the attendant build up of phenylalanine in the body also occurs with the ingestion of aspartame, although to a lesser degree. Accordingly, all products in the U.S. and Canada that contain aspartame must be labeled: “Phenylketonurics: Contains phenylalanine.” In the UK, foods containing aspartame must carry ingredients panels that refer to the presence of ‘aspartame or E951′, and they must be labeled with a warning “Contains a source of phenylalanine”. These warnings are specifically placed to aid individuals who suffer from PKU so that they can avoid such foods.

Interestingly, the macaque genome was recently sequenced and it was found that macaques naturally have a mutation that is found in humans who have PKU.

DL-Phenylalanine is marketed as a nutritional supplement for its putative analgesic and antidepressant activities. The putative analgesic activity of DL-phenylalanine may be explained by the possible blockage by D-phenylalanine of enkephalin degradation by the enzyme carboxypeptidase A. The mechanism of DL-phenylalanine’s putative antidepressant activity may be accounted for by the precursor role of L-phenylalanine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects. D-phenylalanine is absorbed from the small intestine, following ingestion, and transported to the liver via the portal circulation. A fraction of D-phenylalanine appears to be converted to L-phenylalanine. D-phenylalanine is distributed to the various tissues of the body via the systemic circulation. D-phenylalanine appears to cross the blood-brain barrier with less efficiency than L-phenylalanine. A fraction of an ingested dose of D-phenylalanine is excreted in the urine.

Source: http://www.answers.com/Phenylalanine?cat=health

“In addition to its role in proteins, tyrosine is the precursor for the synthesis of melanin (the black and brown pigment of skin and hair), and adrenaline and noradrenaline.”

One of the amino acids, not essential for humans unless they have the hereditary disorder phenylketonuria. It is the biochemical precursor of many important catecholamines. It is found in small amounts in most proteins, especially insulin and papain (found in papaya). It is used in biochemical research and as a dietary supplement.

Tyrosine is a precursor of the adrenal hormones epinephrine and norepinephrine as well as of the thyroid hormones, including thyroxine. Melanin, the skin and hair pigment, is also derived from this amino acid. Tyrosine residues in enzymes have frequently been shown to be associated with active sites. Modification of these residues with various chemicals often results in a change in the specificity of the enzyme toward its substrates or even in total destruction of its activity. In 1846 tyrosine was obtained as a product of the degradation of the protein casein (from cheese). It was synthesized in the laboratory in 1883, and its structure was thus determined.

L-Tyrosine is sometimes recommended by practitioners as helpful for weight loss, clinical depression, Parkinson’s Disease, Attention Deficit Disorder, and phenylketonuria; however, one study found that it had no impact on endurance exercise performance.

Source: http://www.answers.com/Tyrosine?cat=health&nr=1

“One of the problems with some crash diets is that they do not provide enough essential amino acids and, in some extreme cases, have resulted in death.”

An amino acid that must be obtained from the diet so that the body can synthesize vital proteins. Nine amino acids are generally regarded as essential for humans: isoleucine, leucine, lysine, threonine, tryptophan, methionine, histidine, valine and phenylalanine. In addition, the amino acids arginine, cysteine, glycine, glutamine and tyrosine are considered conditionally essential, meaning they are not normally required in the diet, but must be supplied exogenously to specific populations that do not synthesize it in adequate amounts. (Histidine is required by infants, but it has not been fully established that it is essential for adults.) The essential amino acids must be available in the body simultaneously and in the correct proportions for protein synthesis to occur.

Source: http://www.answers.com/topic/essential-amino-acid?cat=health

“Most essential nutrients are substances that are metabolically necessary but cannot be synthesized by the organism.”

An essential nutrient is a nutrient required for normal body functioning that cannot be synthesized by the body and must be obtained from a dietary source. Some categories of essential nutrient include vitamins, dietary minerals, essential fatty acids, and essential amino acids.

All essential nutrients are toxic in large doses (see hypervitaminosis or the nutrient pages themselves below). Some can be taken in amounts larger than required in a typical diet, with no apparent ill effects. Linus Pauling said of vitamin B3, (either niacin or niacinamide), “What astonished me was the very low toxicity of a substance that has such very great physiological power. A little pinch, 5 mg, every day, is enough to keep a person from dying of pellagra, but it is so lacking in toxicity that ten thousand times as much can [sometimes] be taken without harm.” A similar statement can be made about vitamin C and some other vitamins.

List of essential nutrients

· Essential fatty acids:

1. Linolenic acid (the shortest chain omega-3 fatty acid)

2. Linoleic acid (the shortest chain omega-6 fatty acid)

3. Essential amino acids necessary for all humans:

4. Histidine

5. Isoleucine

6. Lysine

7. Leucine

8. Methionine

9. Phenylalanine

10. Threonine

11. Tryptophan

12. Valine

· Essential amino acids necessary for human children and not adults:

1. Arginine

2. Vitamins:

3. Biotin (vitamin B7, vitamin H)

4. Choline (vitamin Bp)

5. Folate (folic acid, vitamin B9, vitamin M)

6. Niacin (vitamin B3, vitamin P, vitamin PP)

7. Pantothenic acid (vitamin B5)

8. Riboflavin (vitamin B2, vitamin G)

9. Thiamine (vitamin B1)

10. Vitamin A (retinol)

11. Vitamin B6 (pyridoxine, pyridoxamine, or pyridoxal)

12. Vitamin B12 (cobalamin)

13. Vitamin C (ascorbic acid)

14. Vitamin D (Cholecalciferol, Ergocalciferol, Calcitriol)

15. Vitamin E (tocopherol)

16. Vitamin K (naphthoquinoids)

· Dietary minerals: Biochemical studies reported in 2006 indicate that the following elements (aside from H, C, N, and O) are required for human health:

1. Calcium (Ca)

2. Chloride (Cl-)

3. Cobalt (Co)

4. Copper (Cu) [3]

5. Iodine (I)

6. Iron (Fe)

7. Magnesium (Mg)

8. Manganese (Mn)

9. Molybdenum (Mo)

10. Phosphorus (P)

11. Potassium (K)

12. Selenium (Se)

13. Sodium (Na)

14. Sulfur (S)

15. Zinc (Zn)

The body’s requirements vary widely. At one extreme a 70 kg human contains 1.0 kg of calcium but only 3 mg of cobalt or 0.5 mg of bismuth.

Source: http://www.answers.com/topic/essential-nutrient?nr=1&lsc=true&cat=health

Healthy Energy (Part 2 – Facts about B12)

“Vitamin B-12 is important for the normal functioning of the brain and nervous system and for the formation of blood. It is normally involved in the metabolism of every cell of the body, especially affecting the DNA synthesis and regulation but also fatty acid synthesis and energy production.”

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. The form of cobalamin used in most supplements, cyanocobalamin, is readily converted to 5-deoxyadenosyl and methylcobalamin in the body. In mammals, cobalamin is a cofactor for only two enzymes, methionine synthase and L-methylmalonyl-CoA mutase.

Function

Cofactor for methionine synthase

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 (diagram).

Cofactor for L-methylmalonyl-CoA mutase

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.

Pernicious anemia

Pernicious anemia has been estimated to be present in approximately 2% of individuals over 60. Although anemia is often a symptom, the condition is actually the end stage of an autoimmune inflammation of the stomach, resulting in destruction of stomach cells by one’s own antibodies. Progressive destruction of the cells that line the stomach causes decreased secretion of acid and enzymes required to release food-bound vitamin B12. Antibodies to intrinsic factor (IF) bind to IF preventing formation of the IF-B12 complex, further inhibiting vitamin B12 absorption. If the body’s vitamin B12 stores are adequate prior to the onset of pernicious anemia, it may take years for symptoms of deficiency to develop. About 20% of the relatives of pernicious anemia patients also have pernicious anemia, suggesting a genetic predisposition. Treatment of pernicious anemia generally requires injections of vitamin B12 to bypass intestinal absorption. High-dose oral supplementation is another treatment option, because consuming 1,000 mcg (1 mg)/day of vitamin B12 orally should result in the absorption of about 10 mcg/day (1% of dose) by passive diffusion. In fact, high-dose oral therapy is considered to be as effective as intramuscular injection.

Food-bound vitamin B12 malabsorption

Food-bound vitamin B12 malabsorption is defined as an impaired ability to absorb food or protein-bound vitamin B12, although the free form is fully absorbable. In the elderly, food-bound vitamin B12 malabsorption is thought to result mainly from atrophic gastritis, a chronic inflammation of the lining of the stomach that ultimately results in the loss of glands in the stomach (atrophy) and decreased stomach acid production. Because stomach acid is required for the release of vitamin B12 from the proteins in food, vitamin B12 absorption is diminished. Decreased stomach acid production also provides an environment conducive to the overgrowth of anaerobic bacteria in the stomach, which further interferes with vitamin B12 absorption. Because vitamin B12 in supplements is not bound to protein, and because intrinsic factor (IF) is still available, the absorption of supplemental vitamin B12 is not reduced as it is in pernicious anemia. Thus, individuals with food-bound vitamin B12 malabsorption do not have an increased requirement for vitamin B12; they simply need it in the crystalline form found in fortified foods and dietary supplements.

Atrophic gastritis

Atrophic gastritis is thought to affect 10%-30% of people over 60 years of age, and the condition is frequently associated with infection by the bacteria, Heliobacter pylori. H. pylori infection induces chronic inflammation of the stomach, which may progress to peptic ulcer disease, atrophic gastritis, and/or gastric cancer in some individuals. The relationship of H. pylori infection to atrophic gastritis, gastric cancer, and vitamin B12 deficiency is presently an area of active research.

Other causes of vitamin B12 deficiency

Other causes of vitamin B12 deficiency include surgical resection of the stomach or portions of the small intestine where receptors for the IF-B12 complex are located. Conditions affecting the small intestine, such as malabsorption syndromes (celiac disease and tropical sprue), may also result in vitamin B12 deficiency. Because the pancreas provides critical enzymes as well as calcium required for vitamin B12 absorption, pancreatic insufficiency may contribute to B12 deficiency. Since vitamin B12 is found only in foods of animal origin, a strict vegetarian (vegan) diet has resulted in cases of vitamin B12 deficiency. Alcoholics may experience reduced intestinal absorption of vitamin B12. Individuals with acquired immunodeficiency syndrome (AIDS) appear to be at increased risk of deficiency, possibly related to a failure of the IF-B12 receptor to take up the IF-B12 complex. Long-term use of acid-reducing drugs has also been implicated in vitamin B12 deficiency (see Drug interactions).

Symptoms of vitamin B12 deficiency

Vitamin B12 deficiency results in impairment of the activities of B12-requiring enzymes. Impaired activity of methionine synthase may result in elevated homocysteine levels, while impaired activity of L-methylmalonyl-CoA mutase results in increased levels of a metabolite of methylmalonyl-CoA called methylmalonic acid (MMA). Individuals with mild vitamin B12 deficiency may not experience symptoms, although blood levels of homocysteine and/or MMA may be elevated.

Megaloblastic anemia

Diminished activity of methionine synthase in vitamin B12 deficiency inhibits the regeneration of tetrahydrofolate (THF) and traps folate in a form that is not usable by the body, resulting in symptoms of folate deficiency even in the presence of adequate folate levels. Thus, in both folate and vitamin B12 deficiencies, folate is unavailable to participate in DNA synthesis. This impairment of DNA synthesis affects the rapidly dividing cells of the bone marrow earlier than other cells, resulting in the production of large, immature, hemoglobin-poor red blood cells. The resulting anemia is known as megaloblastic anemia and is the symptom for which the disease, pernicious anemia, was named. Supplementation with folic acid will provide enough usable folate to restore normal red blood cell formation. However, if vitamin B12 deficiency is the cause, it will persist despite the resolution of the anemia. Thus, megaloblastic anemia should not be treated with folic acid until the underlying cause has been determined.

Neurologic symptoms

The neurologic symptoms of vitamin B12 deficiency include numbness and tingling of the arms and, more commonly, the legs, difficulty walking, memory loss, disorientation, and dementia with or without mood changes. Although the progression of neurologic complications is generally gradual, such symptoms are not always reversible with treatment of vitamin B12 deficiency, especially if they have been present for a long time. Neurologic complications are not always associated with megaloblastic anemia and are the only clinical symptom of vitamin B12 deficiency in about 25% of cases. Although vitamin B12 deficiency is known to damage the myelin sheath covering cranial, spinal, and peripheral nerves, the biochemical processes leading to neurological damage in B12 deficiency are not well understood.

Gastrointestinal symptoms

Tongue soreness, appetite loss, and constipation have also been associated with vitamin B12 deficiency. The origins of these symptoms are unclear, but they may be related to the stomach inflammation underlying some cases of B12 deficiency, or to the increased vulnerability of rapidly dividing gastrointestinal cells to impaired DNA synthesis.

Homocysteine and cardiovascular disease

The results of more than 80 studies indicate that even moderately elevated levels of homocysteine in the blood increase the risk of cardiovascular diseases, though the mechanism by which homocysteine increases the disease risk remains the subject of a great deal of research. The amount of homocysteine in the blood is regulated by at least three vitamins: folate, vitamin B12, and vitamin B6 (diagram). Analysis of the results of 12 homocysteine-lowering trials showed folic acid supplementation (0.5-5 mg/day) had the greatest lowering effect on blood homocysteine levels (25% decrease); co-supplementation with folic acid and vitamin B12 (mean 0.5 mg/day or 500 mcg/day) provided an additional 7% reduction (32% decrease) in blood homocysteine concentrations. The results of a sequential supplementation trial in 53 men and women indicated that after folic acid supplementation, vitamin B12 became the major determinant of plasma homocysteine levels. Some evidence indicates that vitamin B12 deficiency is a major cause of elevated homocysteine levels in people over the age of 60. Two studies found blood methylmalonic acid (MMA) levels to be elevated in more than 60% of elderly individuals with elevated homocysteine levels. An elevated MMA level in conjunction with elevated homocysteine, in the absence of impaired kidney function, suggests either a vitamin B12 deficiency or a combined B12 and folate deficiency. Thus, it is important to evaluate vitamin B12 status as well as kidney function in older individuals with elevated homocysteine levels prior to initiating homocysteine-lowering therapy. For more information regarding homocysteine and cardiovascular diseases, see the article on folic acid.

Although increased intake of folic acid and vitamin B12 has been found to decrease homocysteine levels, it is not presently known whether increasing intake of these vitamins will translate to reductions in risk for cardiovascular diseases. However, several randomized placebo-controlled trials are presently being conducted to determine whether homocysteine lowering through folic acid and other B vitamin supplementation reduces the incidence of cardiovascular diseases. A meta-analysis of data from four of the ongoing trials shows that B vitamin supplementation had no significant effect on risk of coronary heart disease or stroke, but only about 14,000 participants were included in analysis and thus any conclusions are limited. Nevertheless, the completion of ongoing clinical trials should help to answer whether or not supplemental B vitamins lower risk for cardiovascular diseases.

Cancer

Folate is required for synthesis of DNA, and there is evidence that decreased availability of folate results in strands of DNA that are more susceptible to damage. Deficiency of vitamin B12 traps folate in a form that is unusable by the body for DNA synthesis. Both vitamin B12 and folate deficiencies result in a diminished capacity for methylation reactions (diagram). Thus, vitamin B12 deficiency may lead to an elevated rate of DNA damage and altered methylation of DNA, both of which are important risk factors for cancer. A recent series of studies in young adults and older men indicated that increased levels of homocysteine and decreased levels of vitamin B12 in the blood were associated with a biomarker of chromosome breakage in white blood cells. In a double- blind, placebo-controlled study, the same biomarker of chromosome breakage was minimized in young adults who were supplemented with 700 mcg of folic acid and 7 mcg of vitamin B12 daily in cereal for two months.

Breast cancer

A case-control study compared prediagnostic levels of serum folate, vitamin B6, and vitamin B12 in 195 women later diagnosed with breast cancer and 195 age-matched women who were not diagnosed with breast cancer. Among women who were postmenopausal at the time of blood donation, the association between blood levels of vitamin B12 and breast cancer suggested a threshold effect. The risk of breast cancer was more than doubled in women with serum vitamin B12 levels in the lowest quintile (1/5) compared to women in the four highest quintiles. The investigators found no relationship between breast cancer and serum levels of vitamin B6, folate, or homocysteine. A case-control study in Mexican women (475 cases and 1,391 controls) reported that breast cancer risk for women in the highest quartile (1/4) of vitamin B12 intake was 68% lower than those in the lowest quartile. Stratification of the data revealed that the inverse association between dietary vitamin B12 intake and breast cancer risk was stronger in postmenopausal women compared to premenopausal women, though both associations were statistically significant. Because these studies were observational, it cannot be determined whether decreased serum levels of vitamin B12 or low dietary vitamin B12 intakes were a cause or a result of breast cancer. Previously, there has been little evidence to suggest a relationship between vitamin B12 status and breast cancer risk. However, high dietary folate intakes have been associated with reduced risk for breast cancer in several studies, and some studies have reported that vitamin B12 intake may modify this association.

Neural tube defects

Neural tube defects (NTD) may result in anencephaly or spina bifida, devastating and sometimes fatal birth defects. The defects occur between the 21st and 27th days after conception, a time when many women do not realize they are pregnant. Randomized controlled trials have demonstrated 60% to 100% reductions in NTD cases when women consumed folic acid supplements in addition to a varied diet during the month before and the month after conception. Increasing evidence indicates that the homocysteine-lowering effect of folic acid plays a critical role in lowering the risk of NTD. Homocysteine may accumulate in the blood when there is inadequate folate and/or vitamin B12 for effective functioning of the methionine synthase enzyme. Decreased vitamin B12 levels in the blood and amniotic fluid of pregnant women have been associated with an increased risk of NTD, suggesting that adequate vitamin B12 intake in addition to folic acid may be beneficial in the prevention of NTD.

Alzheimer’s disease and dementia

Individuals with Alzheimer’s disease often have low blood levels of vitamin B12. One study found lower vitamin B12 levels in the cerebrospinal fluid of patients with Alzheimer’s disease than in patients with other types of dementia, though blood levels of vitamin B12 did not differ. The reason for the association of low vitamin B12 status with Alzheimer’s disease is not clear. Vitamin B12 deficiency, like folate deficiency, may lead to decreased synthesis of methionine and S-adenosylmethionine, thereby adversely affecting methylation reactions. Methylation reactions are essential for the metabolism of components of the myelin sheath of nerve cells as well as neurotransmitters. Also, moderately increased homocysteine levels as well as decreased folate and vitamin B12 levels have been associated with Alzheimer’s disease and vascular dementia.

Some but not all studies have associated elevated homocysteine concentrations or decreased serum levels of vitamin B12 with an increased risk of Alzheimer’s disease. A case-control study of 164 patients with dementia of Alzheimer’s type included 76 cases in which the diagnosis of Alzheimer’s disease was confirmed by examination of brain cells after death. Compared to 108 control subjects without evidence of dementia, subjects with dementia of Alzheimer’s type and confirmed Alzheimer’s disease had higher blood homocysteine levels and lower blood levels of folate and vitamin B12. Measures of general nutritional status indicated that the association of increased homocysteine levels and diminished vitamin B12 status with Alzheimer’s disease was not due to dementia-related malnutrition. In another study, low serum vitamin B12 (< 150 pmol/L) or folate (< 10 nmol/L) levels were associated with a doubling of the risk of developing Alzheimer’s disease in 370 elderly men and women followed over three years. In a sample of 1,092 men and women without dementia followed for an average of ten years, those with higher plasma homocysteine levels at baseline had a significantly higher risk of developing Alzheimer’s disease and other types of dementia. Specifically, those with plasma homocysteine levels greater than 14 micromol/L had nearly double the risk of developing Alzheimer’s disease. A study in 650 elderly men and women reported that the risk of elevated plasma homocysteine levels was significantly higher in those with lower cognitive function scores. A prospective study in 816 elderly men and women reported that those with elevated homocysteine levels (> 15 micromol/L) had a significantly higher risk of developing Alzheimer’s disease or dementia, but vitamin B12 status was not related to risk of Alzheimer’s disease or dementia in this study. Similarly, another prospective study in 965 older adults found that vitamin B12 status was not related to the risk of Alzheimer’s disease. Further, a prospective study in 1,041 older adults, followed for a median of 3.9 years, found that vitamin B12 dietary intake was not associated with risk of developing Alzheimer’s disease.

B vitamin supplementation is commonly used to treat hyperhomocysteinemia. A recent randomized, double-blind, placebo-controlled clinical trial in 253 older individuals with plasma homocysteine concentrations equal to or greater than 13 micromol/L found that daily B vitamin supplementation (1 mg folic acid, 0.5 mg vitamin B12, and 10 mg vitamin B6) for two years did not affect measures of cognitive performance despite an average 4.36 micromol/L reduction in plasma homocysteine concentrations (33). Another randomized, double-blind, placebo-controlled study in 195 elderly adults reported that oral vitamin B12 supplementation (1 mg daily) for six months had no effect on measures of cognitive function. Several of the homocysteine-lowering trials primarily focused on assessing cardiovascular disease risk will also assess measures of cognitive function. Thus, the findings of these ongoing trials may provide insight into whether long-term B vitamin supplementation is protective against dementia.

Depression

Observational studies have found as many as 30% of patients hospitalized for depression are deficient in vitamin B12. A cross-sectional study of 700 community-living, physically disabled women over the age of 65 found that vitamin B12 deficient women were twice as likely to be severely depressed as non-deficient women. A population-based study in 3,884 elderly men and women with depressive disorders found that those with vitamin B12 deficiency were almost 70% more likely to experience depression than those with normal vitamin B12 status. The reasons for the relationship between vitamin B12 deficiency and depression are not clear but may involve S-adenosylmethionine (SAMe). Vitamin B12 and folate are required for the synthesis of SAMe, a methyl group donor essential for the metabolism of neurotransmitters whose bioavailability has been related to depression. This hypothesis is supported by several studies that have shown supplementation with SAMe improves depressive symptoms. Because few studies have examined the relationship of vitamin B12 status and the development of depression over time, it cannot yet be determined if vitamin B12 deficiency plays a causal role in depression. However, due to the high prevalence of vitamin B12 deficiency in older individuals, it may be beneficial to screen for vitamin B12 deficiency as part of a medical evaluation for depression.

Sources

Food sources

Only bacteria can synthesize vitamin B12. Vitamin B12 is present in animal products such as meat, poultry, fish (including shellfish), and to a lesser extent milk, but it is not generally present in plant products or yeast. Fresh pasteurized milk contains 0.9 mcg per cup and is an important source of vitamin B12 for some vegetarians. Those vegetarians who eat no animal products need supplemental vitamin B12 to meet their requirements. Also, individuals over the age of 50 should obtain their vitamin B12 in supplements or fortified foods like fortified cereal because of the increased likelihood of food-bound vitamin B12 malabsorption.

Most people do not have a problem obtaining the RDA of 2.4 mcg/day of vitamin B12 in food. In the United States, the average intake of vitamin B12 is about 4.5 mcg/day for young adult men, and 3 mcg/day for young adult women. In a sample of adults over the age of 60, men were found to have an average dietary intake of 3.4 mcg/day and women had an average dietary intake of 2.6 mcg/day. Some foods with substantial amounts of vitamin B12 are listed in the table below along with their vitamin B12 content in micrograms (mcg). For more information on the nutrient content of specific foods, search the USDA food composition database.

Supplements

Cyanocobalamin is the principal form of vitamin B12 used in supplements but methylcobalamin is also available as a supplement. Cyanocobalamin is available by prescription in an injectable form and as a nasal gel for the treatment of pernicious anemia. Over-the-counter preparations containing cyanocobalamin include multivitamin, vitamin B-complex, and vitamin B12 supplements.

Safety

Toxicity

No toxic or adverse effects have been associated with large intakes of vitamin B12 from food or supplements in healthy people. Doses as high as 1 mg (1000 mcg) daily by mouth or 1 mg monthly by intramuscular (IM) injection have been used to treat pernicious anemia without significant side effects. When high doses of vitamin B12 are given orally, only a small percentage can be absorbed, which may explain the low toxicity. Because of the low toxicity of vitamin B12, no tolerable upper intake level (UL) was set by the Food and Nutrition Board in 1998 when the RDA was revised.

Drug interactions

A number of drugs reduce the absorption of vitamin B12. Proton pump inhibitors (e.g., omeprazole and lansoprazole), used for therapy of Zollinger-Ellison syndrome and gastroesophageal reflux disease (GERD), markedly decrease stomach acid secretion required for the release of vitamin B12 from food but not from supplements. Long-term use of proton pump inhibitors has been found to decrease blood vitamin B12 levels. However, vitamin B12 deficiency does not generally develop until after at least three years of continuous therapy. Another class of gastric acid inhibitors known as H2-receptor antagonists (e.g., Tagamet, Pepsid, Zantac), often used to treat peptic ulcer disease, has also been found to decrease the absorption of vitamin B12 from food. Because inhibition of gastric acid secretion is not as prolonged as with proton pump inhibitors H2-receptor antagonists have not been found to cause overt vitamin B12 deficiency even after long-term use. Individuals taking drugs that inhibit gastric acid secretion should consider taking vitamin B12 in the form of a supplement because gastric acid is not required for its absorption. Other drugs found to inhibit vitamin B12 absorption from food include cholestyramine (a bile acid-binding resin used in the treatment of high cholesterol), chloramphenicol and neomycin (antibiotics), and colchicine (anti-gout medicine). Metformin, a medication for individuals with type 2 (non-insulin dependent) diabetes, decreases vitamin B12 absorption by tying up free calcium required for absorption of the IF-B12 complex. This effect is correctable by drinking milk or taking calcium carbonate tablets along with food or supplements. Previous reports that megadoses of vitamin C destroy vitamin B12 have not been supported and may have been an artifact of the assay used to measure vitamin B12 levels.

Nitrous oxide, a commonly used anesthetic, inhibits both of the vitamin B12- dependent enzymes and can produce many of the clinical features of vitamin B12 deficiency, such as megaloblastic anemia or neuropathy. Because nitrous oxide is commonly used for surgery in the elderly, some experts feel vitamin B12 deficiency should be ruled out prior to its use.

Large doses of folic acid given to an individual with an undiagnosed vitamin B12 deficiency could correct megaloblastic anemia without correcting the underlying vitamin B12 deficiency, leaving the individual at risk of developing irreversible neurologic damage. For this reason the Food and Nutrition Board of the Institute of Medicine advises that all adults limit their intake of folic acid (supplements and fortification) to 1000 mcg (1 mg) daily.

Linus Pauling Institute Recommendation

A varied diet should provide enough vitamin B12 to prevent deficiency in most individuals 50 years of age and younger. Individuals over the age of 50, strict vegetarians, and women planning to become pregnant should take a multivitamin supplement daily or eat a fortified breakfast cereal, which would ensure a daily intake of 6 to 30 mcg of vitamin B12 in a form that is easily absorbed. Higher doses of vitamin B12 supplements are recommended for patients taking medications that interfere with its absorption (see Drug interactions).

Older adults (> 50 years)

Because vitamin B12 malabsorption and vitamin B12 deficiency are more common in older adults, some respected nutritionists recommend that adults older than 50 years take 100 to 400 mcg/day of supplemental vitamin B12, an amount provided by a number of vitamin B-complex supplements.

Source: http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/

“B-12 is the most chemically complex of all the vitamins.”

Structure

B-12 is the most chemically complex of all the vitamins. The structure of B-12 is based on a corrin ring, which is similar to the porphyrin ring found in heme, chlorophyll, and cytochrome. The central metal ion is Co (cobalt). Four of the six coordination sites are provided by the corrin ring, and a fifth by a dimethylbenzimidazole group. The sixth coordination site, the center of reactivity, is variable, being a cyano group (-CN), a hydroxyl group (-OH), a methyl group (-CH3) or a 5′-deoxyadenosyl group (here the C5′ atom of the deoxyribose forms the covalent bond with Co), respectively, to yield the four B-12 forms mentioned above. The covalent C-Co bond is one of first examples of carbon-metal bonds in biology. The hydrogenases and, by necessity, enzymes associated with cobalt utilization, involve metal-carbon bonds.

Synthesis

Vitamin B-12 cannot be made by plants or animals, as the only type of organism that have the enzymes required for the synthesis of B-12 is bacteria. The total synthesis of B-12 was reported by Robert Burns Woodward and Albert Eschenmoser, and remains one of the classic feats of total synthesis.

Species from the following genera are known to synthesize B-12: Aerobacter, Agrobacterium, Alcaligenes, Azotobacter, Bacillus, Clostridium, Corynebacterium, Flavobacterium, Micromonospora, Mycobacterium, Nocardia, Propionibacterium, Protaminobacter, Proteus, Pseudomonas, Rhizobium, Salmonella, Serratia, Streptomyces, Streptococcus and Xanthomonas. Industrial production of B-12 is through fermentation of selected microorganisms. The most used species are Pseudomonas denitrificans and Propionibacterium shermanii, often genetically engineered and grown under special conditions to enhance yield.

Functions

Coenzyme B-12’s reactive C-Co bond participates in two types of enzyme-catalyzed reactions.

Rearrangements in which a hydrogen atom is directly transferred between two adjacent atoms with concomitant exchange of the second substituent, X, which may be a carbon atom with substituents, an oxygen atom of an alcohol, or an amine.

Methyl (-CH3) group transfers between two molecules.

In humans, only two corresponding coenzyme B-12-dependent enzymes are known:

Methylmalonyl Coenzyme A mutase (MUT) which uses the AdoB-12 form and reaction type 1 to catalyze a carbon skeleton rearrangement (the X group is -COSCoA). MUT’s reaction converts MMl-CoA to Su-CoA, an important step in the extraction of energy from proteins and fats (for more see MUT’s reaction mechanism). This functionality is lost in vitamin B-12 deficiency, and can be measured clinically as an increased methylmalonic acid (MMA) level. Unfortunately, an elevated MMA, though sensitive to B-12 deficiency, is probably overly sensitive, and not all who have it actually have B-12 deficiency. For example, MMA is elevated in 90-98% of patients with B-12 deficiency; however 25-20% of patients over the age of 70 have elevated levels of MMA, yet 25-33% of them do not have B-12 deficiency. For this reason, MMA is not routinely recommended in the elderly. The “gold standard” test for B-12 deficiency continues to be low blood levels of the vitamin.

The MUT function cannot be affected by folate supplementation, and which is necessary for myelin synthesis (see mechanism below) and certain other functions of the central nervous system. Other functions of B-12 related to DNA synthesis related to MTR dysfunction (see below) can often be corrected with supplementation with the vitamin folic acid, but not the elevated levels of homocysteine, which is normally converted to methionine by MTR.

5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), also known as methionine synthase. This is a methyl transfer enzyme, which uses the MeB-12 and reaction type 2 to catalyze the conversion of the amino acid Hcy back into Met (for more see MTR’s reaction mechanism).[13] This functionality is lost in vitamin B-12 deficiency, and can be measured clinically as an increased homocysteine level in vitro. Increased homocysteine can also be caused by a folic acid deficiency, since B-12 helps to regenerate the tetrahydrofolate (THF) active form of folic acid. Without B-12, folate is trapped as 5-methyl-folate, from which THF cannot be recovered unless a MTR process reacts the 5-methyl-folate with homocysteine to produce methionine and THF, thus decreasing the need for fresh sources of THF from the diet. THF may be produced in the conversion of homocysteine to methionine, or may be obtained in the diet. It is converted by a non-B12-dependent process to 5,10-methylene-THF, which is involved in the synthesis of thymine. Reduced availability of 5,10-methylene-THF results in problems with DNA synthesis, and ultimately in ineffective production cells with rapid turnover, in particular blood cells, and also intestinal wall cells which are responsible for absorption. The failure of blood cell production results in the once-dreaded and fatal disease, pernicious anemia. All of the DNA synthetic effects, including the megaloblastic anemia of pernicious anemia, resolve if sufficient folate is present (since levels of 5,10-methylene-THF still remain adequate with enough dietary folate). Thus the best known function of B-12 (that which is indirectly involved with DNA synthesis and restoration of cell-division and anemia) is actually a facultative function which is mediated by B-12 conservation of active folate which can be used for DNA production.

If folate is present in quantity, then of the two absolutely B-12 dependent reactions, the MUT reaction shows the most direct and characteristic secondary effects, focusing on the nervous system. Since the late 1990’s folic acid has begun to be added to fortify flour in many countries, so that folate deficiency is now more rare. At the same time, since DNA synthetic-sensitive tests for anemia and erythrocyte size are routinely done in even simple medical test clinics (so that these folate mediated-biochemical effects are more often directly detected), the MTR dependent effects of B-12 deficiency are becoming apparent not as anemia (as they were classically), but now mainly as an elevation of homocysteine in the blood and urine (homocysteinuria). This condition may result in long term damage to arteries and in clotting (stroke and heart attack), but is difficult to separate from other processes associated with atherosclerosis and aging.

The B-12 dependent MTR reactions may have neurological effects through an indirect mechanism. Adequate methionine (which must otherwise be obtained in the diet) is needed to make S-adenosyl-methionine, which is in turn necessary for methylation of myelin sheath phospholipids. In addition, SAMe is involved in the manufacture of certain neurotransmitters, catecholamines and in brain metabolism. These neurotransmitters are important for maintaining mood, possibly explaining why depression is associated with B-12 deficiency. Methylation of the myelin sheath phospholipids may also depend on adequate folate, which in turn is dependent on MTR recycling, unless ingested in relatively high amounts.

The specific myelin damage resulting from from B-12 deficiency has also been connected to B-12 reactions related to MUT, which is needed to convert methylmalonyl coenzyme A into succinyl coenzyme A. Failure of this second reaction to occur results in elevated levels of methylmalonic acid (MMA), a myelin destabilizer. Excessive MAA will prevent normal fatty acid synthesis, or it will be incorporated into fatty acid itself rather than normal malonic acid. If this abnormal fatty acid subsequently is incorporated into myelin, the resulting myelin will be too fragile, and demyelination will occur. Although the precise methanism(s) are not known with certainty, the result is subacute combinded degeneration of central nervous system and spinal cord. [15] Whatever the cause, it is known that B-12 deficiency causes neuropathies, even if folic acid is present in good supply, and therefore anemia is not present.

Human absorption and distribution

The human physiology of vitamin B-12 is complex, and therefore is prone to mishaps leading to vitamin B-12 deficiency. The vitamin as it occurs in foods enters the digestive tract bound to proteins, known as salivary R-binders. Stomach proteolysis of these proteins requires an acid pH, and also requires proper pancreatic release of proteolytic enzymes. (Even small amounts of B-12 taken in supplements bypasses these steps and thus any need for gastric acid, which may be blocked by antacid drugs).

The free B-12 then attaches to gastric intrinsic factor, which is generated by the gastric parietal cells. If this step fails due to gastric parietal cell atrophy (the problem in pernicious anemia), sufficient B-12 is not absorbed later on, unless administered orally in relatively massive doses (500 to 1000 mcg/day).

The conjugated vitamin B-12-intrinsic factor complex (IF/B-12) is then normally absorbed by the terminal ileum of the small bowel. Absorption of food vitamin B-12 therefore requires an intact and functioning stomach, exocrine pancreas, intrinsic factor, and small bowel. Problems with any one of these organs makes a vitamin B-12 deficiency possible.

Once the IF/B-12 complex is recognized by specialized ileal receptors, it is transported into the portal circulation. The vitamin is then transferred to transcobalamin II (TC-II/B12), which serves as the plasma transporter of the vitamin. Genetic deficiencies of this protein are known, also leading to functional B-12 deficiency.

For the vitamin to serve inside cells, the TC-II/B-12 complex must bind to a cell receptor, and be endocytosed. The transcobalamin-II is degraded within a lysozyme, and the B-12 is finally released into the cytoplasm, where it may be transformed into the proper coenzyme, by certain cellular enzymes (see above).

Hereditary defects in production of the transcobalamins and their receptors may produce functional deficiencies in B-12 and infantile megaloblastic anemia, and abnormal B-12 related biochemistry, even in some cases with normal blood B-12 levels.

The total amount of vitamin B-12 stored in body is about 2,000-5,000 mcg in adults. Around 80% of this is stored in the liver. 0.1 % of this is lost per day by secretions into the gut as not all these secretions are reabsorbed. How fast B-12 levels change depends on the balance between how much B12 is obtained from the diet, how much is secreted and how much is absorbed. B-12 deficiency may arise in a year if initial stores are low and genetic factors unfavourable or may not appear for decades. In infants, B-12 deficiency can appear much more quickly.

History of B-12 as a treatment for pernicious anemia

B-12 deficiency is the cause of pernicious anemia, a usually-fatal disease of unknown etiology when it was first described in medicine. The cure was discovered by accident. George Whipple had been inducing anemia in dogs by bleeding them, and then conducting experiments in which he fed them various foods to observe which diets allowed them fastest recovery from the anemia produced. In the process, he discovered that ingesting large amounts of liver seemed to most-rapidly cure the anemia of blood loss, and hypothesized that therefore liver ingestion be tried for pernicious anemia, an anemic disease of the time with no known cause or cure. He tried this and reported some signs of success in 1920. After a series of careful clinical studies George Minot and William Murphy set out to partly isolate the substance in liver which cured anemia in dogs, and found that it was iron. They found further that the partly isolated water-soluble liver-substance which cured pernicious anemia in humans, was something else entirely different — and which had no effect at all on canines under the conditions used. The specific factor treatment for pernicious anemia, found in liver juice, had been found by this coincidence. These experiments were reported by Minot and Murphy in 1926, marking the date of the first real progress with this disease, though for several years, patients were still required to eat large amounts of raw liver or to drink considerable amounts of liver juice.

In 1928, the chemist Edwin Cohn prepared a liver extract that was 50 to 100 times more potent than the natural liver products. The extract was the first workable treatment for the disease. For their initial work in pointing the way to a working treatment, Whipple, Minot, and Murphy shared the 1934 Nobel Prize in Physiology or Medicine.

The active ingredient in liver was not isolated until 1948 by the chemists Karl A. Folkers of the United States and Alexander R. Todd of Great Britain. The substance was a cobalamin called vitamin B-12. It could also be injected directly into muscle, making it possible to treat pernicious anemia more easily.

The chemical structure of the molecule was determined by Dorothy Crowfoot Hodgkin and her team in 1956, based on crystallographic data. Eventually, methods of producing the vitamin in large quantities from bacteria cultures were developed in the 1950’s, and these led to the modern form of treatment for the disease.

Symptoms and damage from deficiency

Vitamin B-12 deficiency can potentially cause severe and irreversible damage, especially to the brain and nervous system. At levels only slightly lower than normal, a range of symptoms such as fatigue, depression, and poor memory may be experienced. However, these symptoms by themselves are too nonspecific to diagnose deficiency of the vitamin.

Vitamin B-12 deficiency has the following pathomorphology and symptoms:

Pathomorphology includes: A spongiform state of neural tissue along with edema of fibers and deficiency of tissue. The myelin decays, along with axial fiber. In later phases, fibric sclerosis of nervous tissues occurs. Those changes apply to dorsal parts of the spinal cord, and to pyramidal tracts in lateral cords.

In the brain itself, changes are less severe: they occur as small sources of nervous fibers decay and accumulation of Astrocytes, usually subcortically located, an also round hemorrhages with a torus of glial cells. Pathological changes can be noticed as well in the posterior roots of the cord and, to lesser extent, in peripheral nerves.

Clinical symptoms : The main syndrome of vitamin B-12 deficiency is Addison’s and Biermer’s disease. It is characterized by a triad of symptoms:

1) anemia with bone marrow promegaloblastosis (Megaloblastic anemia) 2) gastrointestinal symptoms; 3) neurological symptoms.

Each of those symptoms can occur either alone or along with others. The neurological complex, defined as myelosis funicularis, consists of the following symptoms: 1) impaired perception of deep touch, pressure and vibration, abolishment of sense of touch, very annoying and persistent paresthesias; 2) ataxia of dorsal cord type; 3) decrease or abolishment of deep muscle-tendon reflexes; 4) pathological reflexes – Babinski, Rossolimo and others, also severe paresis.

During the course of disease, mental disorders can occur: irritablity, focus/concentration problems, depressive state with suicidal tendencies, paraphrenia complex. These symptoms may not reverse after correction of hematological abnormalities, and the chance of complete reversal decreases with the length of time the neurological symptoms have been present.

Sources

Vitamin B-12 is naturally found in foods of animal origin including meat (especially liver and shellfish) and milk products. Animals, in turn, must obtain it directly or indirectly from bacteria, and these bacteria may inhabit a section of the gut which is posterior to the section where B-12 is absorbed. Thus, Herbivorous animals must either obtain B-12 from bacteria in their rumens, or (if fermenting plant material in the hindgut) by reingestion of cecotrope feces. Eggs are often mentioned as a good B-12 source, but they also contain a factor that blocks absorption. Certain insects such as termites contain B-12 produced by their gut bacteria, in a manner analogous to ruminant animals. An NIH Fact Sheet lists a variety of food sources of vitamin B-12.

Plants only supply B-12 to humans when the soil containing B-12-producing microorganisms has not been washed from them. Vegan humans who eat only washed vegetables must take special care to supplement their diets accordingly. According to the U.K. Vegan Society, the only reliable vegans sources of B-12 are foods fortified with B-12 (including some plant milks, some soy products and some breakfast cereals), and B-12 supplements. Fortified breakfast cereals are a particularly valuable source of vitamin B-12 for vegetarians and vegans.

While lacto-ovo vegetarians usually get enough B-12 through consuming dairy products, vitamin B-12 may be found to be lacking in those practicing vegan diets who do not use multivitamin supplements or eat B-12 fortified foods, such as fortified breakfast cereals, fortified soy-based products, and fortified energy bars. Claimed sources of B-12 that have been shown through direct studies of vegans to be inadequate or unreliable include, laver (a seaweed), barley grass, and human gut bacteria. People on a vegan raw food diet are also susceptible to B-12 deficiency if no supplementation is used. However, the more alkaline intestines of vegans are better able to metabolize hydroxocobalamin, a more efficient cobalamin than cyanocobalamin.

The Vegan Society, the Vegetarian Resource Group, and the Physicians Committee for Responsible Medicine, among others, recommend that vegans either consistently eat foods fortified with B-12 or take a daily or weekly B-12 supplement.

Cyanocobalamin is converted to its active forms, first hydroxocobalamin and then methylcobalamin and adenosylcobalamin in the liver. The sublingual route, in which B-12 is presumably or supposedly absorbed more directly under the tongue, has not proven to be necessary or helpful. A 2003 study found no significant difference in absorption for serum levels from oral vs. sublingual delivery of 500 micrograms of cobalamin. However, if patient has inborn errors in the methyltransfer pathway (cobalamin C disease, combined methylmalonic aciduria and homocystinuria), treating with intravenous or intramuscular hydroxocobalamin is needed.

Vitamin B-12 can be supplemented in healthy subjects also by liquid, strip, nasal spray, or injection. B-12 is available singly or in combination with other supplements.

Injection is sometimes used in cases where digestive absorption is impaired, but there is some evidence that this course of action may not be necessary with modern high potency oral supplements (such as 500 to 1000 mcg or more). These supplements carry such large doses of the vitamin that the many different components of the B-12 absorption system are not required, and enough of the vitamin (only a few mcg a day) is obtained simply by mass-action transport across the gut. Even pernicious anemia can be treated entirely by the oral route.

For the much lower amounts of B-12 found in food sources, however, oral absorption is complex and requires stomach acid, and also specific intestinal transport proteins (intrinsic factor) produced in the stomach. Lack of function in these systems is the causes of much of the increased risk in many elderly persons who develop B-12 deficiency later in life. However, it can be treated with a simple high dose oral B-12 supplement. Cyanocobalamin is also sometimes added to beverages including Diet Coke Plus and many energy drinks, in some cases with over 80 times the recommended intake.[citation needed] However, 500 mcg would be needed to reverse biochemical signs of vitamin B-12 deficiency in older adults.

Source: http://en.wikipedia.org/wiki/Vitamin_B12

“High doses of mineral supplements can also lead to side effects and toxicity. Mineral-supplement poisoning does occur occasionally due to excessive and unusual intake of iron-containing supplements, including some multivitamins, but is not common.”

Before 1998, several deaths per year were typically associated with pharmaceutical iron-containing supplements, especially brightly-colored, sugar-coated, high-potency iron supplements, and most deaths were children. The effects of toxic doses of vitamin A. Manifestations include bone fragility, xeroderma, nausea, headache, and loss of hair.

A problem with vitamins A, D, B6, and folic acid, at levels of intake from supplements considerably higher than might be obtained from foods, although hypervitaminosis A and D may result from (enriched) foods.

Overdose can occur when taking megadoses of the active form of vitamin A. Amounts above what is being utilized by the body accumulate in the liver and fatty tissues. Symptoms may include dry lips and skin, bone and joint pain, liver and spleen enlargement, diarrhea, vomiting, headaches, blurry or double vision, confusion, irritability, fatigue, and bulging fontanel (soft spot on the head) in infants; these are most often reversible, but a doctor should be contacted if a known overdose occurs. Very high levels of vitamin A may also create deficiencies of vitamins C, E, and K. Symptoms will generally appear within six hours following an acute overdose, and take a few weeks to resolve after ceasing the supplement. Children are more sensitive to high levels of vitamin A than adults are, so instructions on products designed for children should be followed with particular care. Vitamin supplements should always be kept out of reach of children.

As vitamin A is fat-soluble, disposing of any excesses taken in through diet is a lot harder than with water-soluble vitamins B and C. In chronic cases, hair loss, drying of the mucous membranes, fever, insomnia, fatigue, weight loss, bone fractures, anemia, and diarrhea can all be evident on top of the symptoms associated with less serious toxicity.

Hypercalcaemia (or Hypercalcemia) is an elevated calcium level in the blood. (Normal range: 9-10.5 mg/dL or 2.2-2.6 mmol/L). It can be an asymptomatic laboratory finding, but because an elevated calcium level is often indicative of other diseases, a diagnosis should be undertaken if it persists. It can be due to excessive skeletal calcium release, increased intestinal calcium absorption, or decreased renal calcium excretion.

Hypercalcemia per se can result in fatigue, depression, confusion, anorexia, nausea, vomiting, constipation, pancreatitis or increased urination “Bones, stones, groans, and psychic moans” is a saying which will help you remember the signs and symptoms of hypercalcemia; if it is chronic it can result in urinary calculi (renal stones or bladder stones). Abnormal heart rhythms can result, and EKG findings of a short QT interval and a widened T wave suggest hypercalcemia.

Symptoms are more common at high calcium levels (12.0 mg/dL or 3 mmol/l). Severe hypercalcemia (above 15-16 mg/dL or 3.75-4 mmol/l) is considered a medical emergency: at these levels, coma and cardiac arrest can result.

Very high intakes of supplements of vitamin B6, (pyridoxine), in excess of 200 mg/day, far greater than could be obtained from food, lead to nerve damage.

An overdose of pyridoxine can cause a temporary deadening of certain nerves such as the proprioceptory nerves; causing a feeling of disembodiment common with the loss of proprioception. This condition is reversible when supplementation is stopped.[4]

Because adverse effects have only been documented from vitamin B6 supplements and never from food sources, this article only discusses the safety of the supplemental form of vitamin B6 (pyridoxine). Although vitamin B6 is a water-soluble vitamin and is excreted in the urine, very high doses of pyridoxine over long periods of time may result in painful neurological symptoms known as sensory neuropathy. Symptoms include pain and numbness of the extremities, and in severe cases difficulty walking. Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day. However, there have been a few case reports of individuals who developed sensory neuropathies at doses of less than 500 mg daily over a period of months. None of the studies, in which an objective neurological examination was performed, found evidence of sensory nerve damage at intakes of pyridoxine below 200 mg/day. In order to prevent sensory neuropathy in virtually all individuals, the Food and Nutrition Board of the Institute of Medicine set the tolerable upper intake level (UL) for pyridoxine at 100 mg/day for adults. Because placebo-controlled studies have generally failed to show therapeutic benefits of high doses of pyridoxine, there is little reason to exceed the UL of 100 mg/day. Studies have shown, however, that in the case of individuals diagnosed with autism, high doses of vitamin B6 given with magnesium have been found to be extremely beneficial.

Folic acid in general and specifically leucovorin are usually well-tolerated. However, there are some uncommon side effects that include skin rashes, itching, vomiting, nausea, diarrhea, and difficulty breathing. Although extremely rare, seizures have occurred in some patients taking leucovorin. Since leucovorin is taken with chemotherapeutic drugs, some side effects may be due to drug interaction.

“RDI, dietary reference intakes, is a set of nutritional guidelines concerning the intake of vitamins and minerals from food rather than supplements.”

From the Institute of Medicine of the USA National Academy (IOM), it is the system is used by both the United States and Canada. It is intended for the general public and health professionals.

Applications include:

· Food labels in the United States and Canada

· Composition of diets for schools, prisons, hospitals or nursing homes

· Industries developing new food stuffs

· Healthcare policy makers and public health officials

In 1997, at the suggestion of the Institute of Medicine of the National Academy, the RDA became one part of a broader, more detailed set of dietary guidelines, called the Dietary Reference Intake.

The current Dietary Reference Intake recommendation is composed of:

· Estimated Average Requirements (EAR), expected to satisfy the needs of 50% of the people in that age group.

· Reference Daily Intake (RDI), the daily dietary intake level of a nutrient considered sufficient to meet the requirements of nearly all (97–98%) healthy individuals in each life-stage and gender group.

· Adequate Intake (AI), where no RDI has been established, but the amount established is somewhat less firmly believed to be adequate for everyone in the demographic group.

· Tolerable upper intake levels (UL), to caution against excessive intake of nutrients (like vitamin D) that can be harmful in large amounts.

The RDI is used to determine the Recommended Daily Value (RDV) which is printed on food labels in the U.S. and Canada.

Source: http://www.answers.com/topic/dietary-reference-intake?nr=1&lsc=true&cat=health

Healthy Energy (Part 3 – Facts about Fatigue)

“Fatigue may be defined as a subjective state in which one feels tired or exhausted, and in which the capacity for normal work or activity is reduced.”

Everyone experiences fatigue occasionally. It is the body’s way of signaling its need for rest and sleep. But when fatigue becomes a persistent feeling of tiredness or exhaustion that goes beyond normal sleepiness, it is usually a sign that something more serious is amiss.

Physically, fatigue is characterized by a profound lack of energy, feelings of muscle weakness, and slowed movements or central nervous system reactions. Fatigue can also trigger serious mental exhaustion. Persistent fatigue can cause a lack of mental clarity (or feeling of mental “fuzziness”), difficulty concentrating, and in some cases, memory loss.

There is, however, no commonly accepted definition of fatigue when it is considered in the context of health and illness. This lack of definition results from the fact that a person’s experience of fatigue depends on a variety of factors. These factors include culture, personality, the physical environment (light, noise, and vibration), availability of social support through networks of family members and friends, the nature of a particular fatiguing disease or disorder, and the type and duration of work or exercise. The experience of fatigue associated with disease will be different for someone who is clinically depressed, is socially isolated, and is out of shape, as compared to another person who is not depressed, has many friends, and is aerobically fit.

Some researchers regard fatigue as a defense mechanism that promotes the effective regulation of energy expenditures. According to this theory, when people feel tired they take steps to avoid further stress (physical or emotional) by resting or by avoiding the stressor. They are then conserving energy. Since chronic fatigue is not normal, however, it is a common symptom of some mental disorders, a variety of physical diseases with known etiologies (causes), and medical conditions that have no biological markers although they have recognizable syndromes (patterns of symptoms and signs).

Fatigue is sometimes described as being primary or secondary. Primary fatigue is a symptom of a disease or mental disorder, and may be part of a cluster of such symptoms as pain, fever, or nausea. As the disease or disorder progresses, however, the fatigue may be intensified by the patient’s worsening condition, by the other disease symptoms, or by the surgical or medical treatment given to the patient. This subsequent fatigue is called secondary.

Fatigue is a common experience. It is one of the top ten symptoms that people mention when they visit the doctor. Some people, however, are at higher risk for developing fatigue. The risk for women is about 1.5 times the risk for men, and the risk for people who do not exercise is twice that of active people. Some researchers question whether women really are at higher risk, since women are more likely than men to go to the doctor with health problems; also, men are less likely to admit they feel fatigued. Other risk factors include obesity, smoking, use of alcohol, high stress levels, depression, anxiety, and low blood pressure. Having low blood pressure is usually considered desirable in the United States, but is regarded as a treatable condition in other countries. Low blood pressure or postural hypotension (sudden lowering of blood pressure caused by standing up) may cause fatigue, dizziness, or fainting.

The management of fatigue depends in large measure on its causes and the person’s experience of it. For example, if fatigue is acute and normal, the person will recover from feeling tired after exertion by resting. In cases of fatigue associated with influenza or other infectious illnesses, the person will feel energy return as they recover from the illness. When fatigue is chronic and abnormal, however, the doctor will tailor a treatment program to the patient’s needs. There are a variety of approaches that include:

· Aerobic exercise. Physical activity increases fitness and counteracts depression.

· Hydration (adding water). Water improves muscle turgor, or tension, and helps to carry electrolytes.

· Improving sleep patterns. The patient’s sleep may be more restful when its timing and duration are controlled.

· Pharmacotherapy (treatment with medications). The patient may be given various medications to treat physical diseases or mental disorders, to control pain, or to manage sleeping patterns.

· Psychotherapy. There are several different treatment approaches that help patients manage stress, understand the motives that govern their behavior, or change maladaptive ideas and negative thinking patterns.

· Physical therapy. This form of treatment helps patients improve or manage functional impairments or disabilities.

Source: http://www.answers.com/fatigue?cat=health

“A stimulant is any substance that causes an increase in activity in various parts of the nervous system or directly increases muscle activity.”

Cerebral, or psychic, stimulants act on the central nervous system and provide a temporary sense of alertness and well-being as well as relief from fatigue. Drugs such as caffeine and the amphetamines belong in this category, and several groups of drugs chemically similar to antihistamines and phenothiazines also act as mild psychic stimulants (see psychopharmacology). Cocaine, besides its effect as a local anesthetic, also stimulates the central nervous system, producing excitement and erratic behavior. The hallucinogenic drugs are also central nervous system stimulants.

A second class of stimulants that affect the medulla and spinal cord includes derivatives of niacinamide (nicotinic acid amide) and other chemically diverse compounds; they are sometimes used to speed the return to wakefulness after anesthesia or to counteract barbiturate poisoning. Ammonia, in smelling salts, is also a medullary stimulant; the alkaloid strychnine is a spinal-cord stimulant.

Other substances act mainly on the autonomic nervous system. Drugs that stimulate the parasympathetic portion of the autonomic nervous system, such as pilocarpine, physostigmine, and neostigmine, cause contracted pupils, salivation and sweating, slowed heartbeat, and lowered blood pressure. Drugs such as norepinephrine, epinephrine, and other catecholamines and synthetic analogs stimulate the sympathetic portion of the autonomic nervous system, resulting in dilated pupils, rapid heartbeat, and increased blood pressure. Because the sympathetic and parasympathetic systems have opposing physiological effects, stimulation of one system amounts to depression of the other. Some of the alkaloids from the ergot fungus act by direct stimulation of smooth muscle, inducing contractions in uterine and intestinal muscle.

Source: http://www.answers.com/topic/stimulant?nr=1&lsc=true&cat=health

“Adrenaline increases heart rate, the depth and rate of breathing, and metabolic rate.”

Also known as epinephrine. The so-called ‘fight or flight’ hormone secreted by the inner part of the adrenal gland. It prepares the body for action by its stimulatory effects on muscles, circulation, and carbohydrate and fat metabolism. Adrenaline increases heart rate, the depth and rate of breathing, and metabolic rate. It also improves the force of muscular contractions and delays the onset of fatigue. Its actions oppose those of insulin. Adrenaline accelerates fat mobilization and encourages the conversion of glycogen to glucose.

Adrenaline and adrenaline-related drugs are sometimes used in sport as stimulants. Although these drugs can improve performance, they may produce harmful side-effects such as heart beat irregularities. Consequently, they are on the International Olympic Committee’s list of banned substances.

Source: http://www.answers.com/topic/adrenaline?cat=health

“Foods and drinks (and other substances) that stimulate the consumer to enhanced mental alertness, increased or prolonged physical activity, uninhibited conviviality, or fierce fighting are called “stimulants.””

This definition is intentionally a narrow one. It excludes the great majority of nourishing foods, for example, because a nourishing meal in itself produces, alongside a feeling of well-being, somnolence (sleepiness) rather than alertness and activity. It also excludes substances such as cannabis and opium (both occasionally taken as foods) that depress mental and physical activity: these are sedatives, not stimulants.

We must distinguish enhanced mental alertness from hallucination, the tendency to see what isn’t there; hallucinogens are, therefore, also excluded. Other exclusions include appetizers, which stimulate the appetite for food, and aphrodisiacs, which (to the extent that such foods really exist) stimulate sexual appetites and energies.

Using foods that have a stimulant effect provides ways of intentionally adjusting the body’s metabolism, which carries risks. There is a good reason why a nourishing meal produces sleepiness: after such a meal, the body is occupied with digestion. Postponing or interrupting that activity may produce digestive disturbance. In any case, increased alertness and physical activity will eventually be paid for in greater-than-usual exhaustion, and there may be other undesirable aftereffects. For example, it may be necessary to compensate for the aftereffects of stimulants by using them again. If the desired effect lessens after frequent use, increased quantities might be needed. In this way, regular use turns into dependence and addiction.

It is even more true of stimulants than of foods in general that their use is not independent of its social context, but no simple generalization is possible. Some of the foods discussed here are nearly always taken in company, as part of a social ritual. Some are nearly always taken as part of, or immediately before or after, a meal. Some, however, are customarily taken when one is not in company and not eating a meal; such habits may vary from one culture to another. External observers focusing on individual psychology may see the solitary use of stimulant foods as posing a personal, social, or criminal problem, while social use might be perceived as no problem or as a different kind of problem. Furthermore, observers focusing on social groups will find users of these stimulant foods to be unexpectedly protective, even nationalistic, about the preferred means of preparing them, which may vary widely.

Stimulant foods have been identified, like nearly all other foods and like many thousands of medicinal plants, in the course of very long-term unrecorded experiments: each human community explores its environment, notes animals and plants that may be of use, finds ways to use them, sometimes begins to farm them, and to trade in them. The stimulant effects of these foods were discovered empirically, as were their associated side-effects and dangers. In the last two centuries, chemists and nutrition scientists have identified their active constituents, making possible for the first time a scientific explanation of their effects.

In general, stimulant foods and drinks are either taken in a neutral vehicle, such as hot water, or they are slowly extracted by chewing. Nonfood stimulants are often taken as smoke or snuff. These various methods all ensure gradual absorption with relatively little interference from other foods. Alcoholic drinks are unusual because they are frequently taken without admixture and often contain strong flavorings: however, water is the principal constituent of most alcoholic drinks, and more water is often added.

Most traditional cultures had one, or at the most two, familiar stimulants. Globalization has changed this, producing such effects as the worldwide fashion for coffee; the worldwide marketing of chocolate, instant coffee, and the “cola” drinks; and the complex social interplay between alternative stimulants of almost equal status, neatly symbolized by the ritual question at breakfast in a French hotel, “Café? Thé? Chocolat?” (Coffee? Tea? Hot chocolate?)

Caffeine

Caffeine is among the commonest of stimulants worldwide. It is the chief active constituent in coffee and tea, which are familiar in practically every country, and in maté, guaraná, and cola nut, which are popular in South America and West Africa. It is present in smaller quantities in some other stimulant foods, including chocolate.

Coffee. Coffee consists of the roasted, ground beans of Coffea arabica. Native to Ethiopia, its use spread in late medieval times to Yemen; from there it rapidly became popular around the Mediterranean. Both Arabs and Europeans encouraged its further spread. Details of its use vary. Boiling water is added; commonly sugar is used as a flavoring, and sometimes milk or cream. Often coffee is drunk after meals, but it is also often taken between meals, both by groups as a social drink and by workers as a stimulant. Several substances have been used as coffee substitutes. Most of them had the advantages of being cheap and of tasting somewhat like coffee but the disadvantage of containing little or no caffeine. These substitutes have now been overtaken in popularity by instant coffee, a soluble product manufactured from the beans of Coffea robusta, which does contain caffeine.

Tea. Tea is made from the dried leaves of Camellia sinensis, native to southern China. The use of tea was already spreading beyond China in the ninth century; like coffee, it became popular in Europe in the seventeenth century and its use then spread worldwide. Again, like coffee, details of its use vary. Boiling water is usually poured onto the leaves, which are then allowed to steep for a few minutes. The resulting liquid is much lighter in flavor and color than coffee. Some add sugar to it: fewer, notably the British, add milk; some drink it iced. Tea is more often taken between meals than during meals; like coffee, it is used both as a social drink and by workers as a stimulant.

Caffeine beverages in South America. Maté, also called Paraguayan tea, is made by pouring boiling water onto the dried and roasted leaves of yerba maté (Ilex paraguariensis). Most of the leaves that are used come from wild trees gathered from the forests of southern South America. Maté is traditionally a social drink, made in a gourd or a silver pot and sucked through a shared straw or silver tube. It is drunk while still extremely hot, so added pleasure is provided by watching the reactions of unskillful foreigners who burn their lips and mouths while trying to drink it. It is usually taken without sugar, but sometimes orange zest is added as a flavoring. Maté is the national beverage of Argentina and Paraguay but has never spread beyond the region. The plant is a relative of European holly (Ilex aquifolium), whose leaves have occasionally been used to make a narcotic drink; more importantly, it is related to yaupon or Carolina tea (Ilex vomitoria) and other species that have been used to make stimulating and narcotic drinks by North Americans both before and after European settlement.

Guaraná (Paullinia cupana) is a tropical plant native to Brazil. Its seeds are traditionally roasted, pounded, and made into cakes called “Brazilian chocolate.” They have this name not because they can be eaten solid, like modern chocolate bars, but because in pre-Columbian Mexico travelers used to carry similar cakes of powdered cacao for use in making an instant chocolate drink. Like those, cakes of guaraná are traditionally crumbled into water by tired travelers in Brazil, making a stimulating drink particularly rich in caffeine. Guaraná is now also used as a flavoring for soda, candy, and liqueurs.

Caffeine in Africa. The cola nut, a rich source of caffeine, is the usual native stimulant of West and Central Africa. It might rather be called a seed, since eight or ten of them are found in each fruit of the trees Cola nitida and C. acuminata. These seeds are white, pink, or red: the white ones are said to be the best. They are customarily chewed before meals: they have a bitter flavor but, perhaps as a result of this, foods and drinks taken afterwards seem sweet (water, taken after cola, tastes “like white wine and sugar,” according to one observer). Apart from this effect as an appetizer, cola nuts have a high reputation among their traditional users, as stimulant, digestive, and aphrodisiac. Alongside caffeine, they contain theobromine (as does chocolate) and kolanin, a heart stimulant. Cola nuts can also be ground into powder and mixed with water as a drink, and cola extract is used to flavor sodas and candies: the names of Coca-Cola and Pepsi-Cola allude to cola nuts, which may well be an ingredient in these products.

Theobromine

Theobromine is the chief active ingredient in cacao beans, the seeds of the tropical tree Theobroma cacao. These beans, fermented, roasted, and ground, are the raw material for chocolate, the traditional stimulant of Mexico, familiar worldwide. In pre-Columbian civilizations, chocolate was used as a drink: the ground cacao was mixed into hot water, which was then poured from a height into the serving cup to produce the much-desired foam. Flavors (chili, vanilla, or others) and color (notably annatto) might be added. Popularized in Europe by the Spanish, chocolate became successively a sugary drink and a milky drink; many other flavorings were tried, including the cinnamon now favored in Mexico. Eventually (in the nineteenth century) chocolate was made into bars to be eaten solid, and in many countries this is now its most familiar form. In the Maya and Aztec civilizations, chocolate was a social drink, taken after dinner, serving as a stimulant (and, according to some, an aphrodisiac). Whole chocolate contains caffeine as well as theobromine, and it is also rich in cocoa butter, making it an extremely nourishing food and, therefore, unlikely to produce aftereffects such as exhaustion.

Nicotine

Tobacco, the fermented leaf of Nicotiana tabacum, is usually smoked; in that form it cannot be classified as a food. It can be chewed, however. In Western cultures, chewed tobacco has been typical of sailors and other manual workers subjected to extreme weather conditions that make smoking difficult. Tobacco’s active ingredient, nicotine, a deadly poison in the pure state, acts as a stimulant when slowly absorbed.

In Australia, another plant, Duboisia hopwoodii, has leaves and flowers very rich in nicotine. Aborigines dry and grind the leaves, mix them with the ash of certain other plants, and roll them into balls, called “pituri,” for chewing. These are used by solitary workers and travelers as a stimulant to stave off tiredness and hunger; they are also exchanged as a sign of friendship. They are, or were, used by warrior groups in preparation for a battle. There is a definite advantage in chewing ash in pituri (and also with coca and betel nut), because alkalis in the ash detach the active stimulant substance, in this case nicotine, from the plant acids, allowing it to be more rapidly absorbed. The use of ash in this way has developed, apparently independently, in Australia, southeastern Asia, and South America.

Cocaine

Coca is the dried leaf of a plant species native to western South America, Erythroxylum coca, and of a second species, E. novogranatense, which developed under cultivation. Coca leaves were known as a stimulant to the pre-Columbian peoples of the Andean region, and continued to be used by them and their Spanish conquerors. Their use is extremely widespread in South America. As with the nicotine plants, the principal use of coca leaves has been as a stimulant for workers and travelers. The usual way is to take some leaves, mix them with the ash of burnt coca or another wood, roll the mixture into a ball, and chew it. Coca leaves, like chocolate, are really nourishing, a property that tends to reduce the severity of the exhaustion that usually follows the use of stimulants. The active constituent of coca leaves was isolated (and named cocaine) in 1860. When taken in the pure form, cocaine was found to be a useful medicinal drug but also highly addictive. It was among the first stimulants to arouse strong medical and governmental disapproval. In the early twentieth century, many countries made it illegal. The name of Coca-Cola alludes to coca, and the early recipe for the product contained cocaine, like other soft drinks of the period.

Some other species of genus Erythroxylum contain cocaine or similar compounds and are used as stimulants by various South American peoples: E. cataractum by the Cubeo of Colombia; E. fimbriatum and E. macrophyllum by the Bora and Huitoto of Peru.

Other Stimulants

Betel. The commonest traditional stimulant of southern and southeastern Asia is betel. Like pituri and coca, betel is customarily made up as a chewing packet that includes ash. The active ingredient, arecoline, is contained in the areca nut or betel nut (the nut of the palm Areca catechu), which is cut into long narrow pieces and placed inside the packet along with a “lime” made from burnt coral and oyster shells. The packet is formed from a leaf of the betel pepper vine (Piper betle). In traditional households, the betel chews are made up each day from fresh supplies; as with pituri, it is a sign of friendship and hospitality to offer a chew to any visitor. The habitual chewing of betel eventually stains the mouth red and the teeth black. When it is first tried, betel can produce feelings of anxiety, excitement, and vertigo; to those who use it regularly, it is a mild stimulant.

Khat. Coffee, when it was introduced to Yemen from across the Red Sea, was not the country’s first stimulant. That position belongs to khat (or qat), the leaf of Catha edulis. Khat is used in Yemen, Saudi Arabia, and a large area of East Africa from Ethiopia and Somalia to Mozambique and South Africa. It had not spread outside the region until some Americans acquired the taste for it while they were in Somalia with United Nations troops during the early 1990s. Khat is often taken as a tea, made by pouring boiling water onto the dried or fresh leaves. Fresh leaves can also be chewed; in this form its effect is said to be stronger than coffee but not as strong as alcohol. When chewed, khat is often used socially because it enlivens conversation. The principal active constituent in khat is cathinone, now classified as an illegal drug in the United States; however, cathinone is only present in fresh leaves. The second active constituent, cathine, which is still present in the dried leaves, is an appetite suppressant.

A milder stimulant of the same general type is Mormon tea, the leaf of Ephedra nevadensis. These leaves contain the active ingredient pseudoephedrine, and are made into a tea with boiling water.

Kava. The root of the plant kava-kava, Piper methysticum, is the source of kava, a familiar stimulant used in Hawaii and other Pacific islands. The fresh root is chopped or ground and then soaked and squeezed in water to produce a milky, spicy liquid, which is traditionally served in half coconut shells. Kava is a social drink whose effect is to produce a condition physically resembling drunkenness, though with apparent clarity of mind. The principal active constituents are known as kavalactones.

Kratom. Kratom, a stimulant indigenous to Thailand and little known elsewhere, consists of the leaves of Mitragyna speciosa. These leaves can be smoked or made into a tea. The active constituent is mitragynine, which, like cocaine, is a stimulant at low doses but a narcotic at higher doses.

Alcohol

Alcohol is an atypical stimulant because it is not naturally present in any fresh plant. It is produced from the fermentation by yeast of plant sugars. One starting point is a fruit juice. Grape juice makes wine; apple juice makes (hard) cider; pear juice makes perry. Several other fruits are used in various parts of the world. A second starting point is malted cereal: barley is the commonest choice, and the result is beer. Plant saps can be used if they contain sufficient sugar: liquid cane sugar is so used in India, while pulque, a Mexican alcoholic drink, is made from the sap of the maguey (Agave atrovirens). Finally, honey, mixed with water, can be used, and the result is mead (a beverage that figures importantly in the Old English epic Beowulf ). There are two common adjustments to the process: adding cane or beet sugar to the original juice gives the yeast more raw material to work with, producing more alcohol; distilling the final product achieves much greater concentrations of alcohol, resulting in “hard liquor.”

Wine and beer are both ancient inventions, going back to southwestern Asia several thousand years B.C.E. But yeasts are naturally present in the air; therefore, alcoholic drinks might have been invented or discovered many times in human history; certainly, the origin of pulque is independent of those of wine and beer.

Alcoholic drinks have most generally, in traditional societies, been used as social drinks, and they have commonly been used in a ritualistic way as well. Their production is linked with the seasons (in general the required juices are available only when fruit is ripe, and the fermentation process takes time); therefore, by contrast with most other stimulants, the discovery of alcoholic drinks and the annual vintage (especially of wine) tend to be celebrated in major festivals. In many cultures, the ordinary, everyday consumption of alcohol follows precise rules, tending to ensure, for example, that everyone drinks equally. Both in the major festivals and in everyday social drinking, it is commonly the case that drunkenness is aimed at, at least to the extent of the loss of inhibitions, but sometimes going all the way to unconsciousness.

Like kava—and unlike many stimulants—alcohol tends to produce enhanced mental activity accompanied by physical incapacity. In traditional societies, travelers used coca, maté, guaraná, pituri, and other stimulants to keep them going; they would not use alcohol or kava till they had arrived. Likewise, coffee, tea, and some similar stimulants may enhance one’s ability to drive safely, for a certain period, while kava and alcohol impair it.

Source: http://www.answers.com/topic/stimulant?nr=1&lsc=true&cat=health

“Alcohol is no great friend to the athlete, nor is it to those on a weight-loss diet. Each gram of pure alcohol provides 7 Calories (7000 calories) of energy.”

In medicine, it is used as a tincture and antiseptic but its greatest use is in drinks. It is quickly absorbed into the bloodstream from the mouth cavity and stomach. After absorption, it acts as a depressant on the central nervous system. This may have the beneficial effect of reducing feelings of fatigue but it also reduces judgement, self-control, and concentration. Reactions are slowed by alcohol and muscular coordination is impaired. Alcohol also acts as a diuretic, stimulating the kidneys to eliminate more urine which can result in dehydration.

In addition, alcoholic beverages often contain sugar and other nutrients, increasing their calorific value. A single measure of spirits contains about 50 Calories, and one pint of lager contains about 170 Calories. Drinking too much alcohol can lead to obesity because some is converted to fat. Despite its relatively high energy content, alcohol is a poor energy source compared with carbohydrate because it cannot be used directly by muscles, and because of its adverse effects. Before it can be used by heart muscle and skeletal muscle, alcohol has to be broken down in the liver to acetate or acetaldehydes. The breakdown is relatively slow which is why alcohol can remain in the bloodstream for several hours. Alcohol can also inhibit the conversion of glycogen to glucose in the liver. If it is ingested during prolonged exercise it can increase the likelihood of hypoglycaemia (abnormally low blood sugar).

Moderate drinking has not been linked to any significant health problems. On the contrary, several studies have shown that it can be beneficial and may reduce the risk of coronary heart disease by preventing platelets in the blood from sticking together. However, chronic, heavy drinking is a significant health risk: it can shrink the brain; it irritates the stomach and small intestine, resulting in malabsorption and deficiencies of vitamins and minerals; it can damage the liver and cause cirrhosis; and it can adversely affect the cardiovascular system, increasing the risk of heart attacks. Heavy drinking is not compatible with a healthy, active lifestyle.

Alcoholism is a major cause of malnutrition. The reasons are threefold. First, alcohol interferes with central mechanisms that regulate food intake and causes food intake decreases. Second, alcohol is rich in energy (7.1 kcal/g), and like pure sugar most alcoholic beverages are relatively empty of nutrients. Increasing amounts of alcohol ingested lead to the consumption of decreasing amounts of other foods, making the nutrient content of the diet inadequate, even if total energy intake is sufficient. Thus chronic alcohol abuse causes primary malnutrition by displacing other dietary nutrients. Third, gastrointestinal and liver complications associated with alcoholism also interfere with digestion, absorption, metabolism, and activation of nutrients, and thereby cause secondary malnutrition.

It is important to note that although ethanol is rich in energy, its chronic consumption does not produce the expected gain in body weight. This may be attributed, in part, to damaged mitochondria and the resulting poor coupling of oxidation of fat metabolically utilizable with energy production. The microsomal pathways that oxidize ethanol may be partially responsible. These pathways produce heat rather than adenosine triphosphate (ATP) and thereby fail to couple ethanol oxidation to useful energy-rich intermediates such as ATP. Thus, perhaps because of these energy considerations, alcoholics with higher total caloric intake do not experience expected weight gain despite physical activity levels similar to those of the non-alcohol-consuming overweight population.

Source: http://www.answers.com/Alcohol?nr=1&lsc=true&cat=health

“Despite its presence in many energy drinks, taurine has not been shown to be energy-giving, however the results of the studies into taurine usage have shown that taurine might help to reduce muscle fatigue.”

In recent years, taurine has become a common ingredient in energy drinks. Taurine is often used in combination with bodybuilding supplements such as creatine and anabolic steroids, partly due to recent findings in mice that taurine alleviates muscle fatigue in strenuous workouts and raises exercise capacity. Taurine is also used in some contact lens solutions.

Taurine has also been shown in diabetic rats to decrease weight and decrease blood sugar.

Taurine is conjugated via its amino terminal group with the bile acids chenodeoxycholic acid and cholic acid to form the bile salts sodium taurochenodeoxycholate and sodium taurocholate (see bile). The low pKa (1.5) of taurine’s sulfonic acid group ensures that this moiety is negatively charged in the pH ranges normally found in the intestinal tract and thus improves the surfactant properties of the cholic acid conjugate. Taurine is the only known naturally occurring sulfonic acid.

Taurine has also been implicated in a wide array of other physiological phenomena including inhibitory neurotransmission, long-term potentiation in the striatum/hippocampus, membrane stabilization, feedback inhibition of neutrophil/macrophage respiratory bursts, adipose tissue regulation, and calcium homeostasis.

Recent studies show that taurine supplements taken by mice on a high-fat diet prevented them from becoming overweight. Studies have yet to be done on the effect of taurine on obesity in humans. Currently taurine is being tested as an anti-manic treatment for bipolar depression. Recent studies have also shown that taurine can influence (and possibly reverse) defects in nerve blood flow, motor nerve conduction velocity, and nerve sensory thresholds in experimental diabetic neuropathic rats. Taurine levels were found to be significantly lower in vegans than in a control group on a standard American diet. Plasma taurine was 78% of control values, and urinary taurine 29%.

Taurine is named after the Latin taurus, which means bull, as it was first isolated from ox bile in 1827 by Austrian scientists Friedrich Tiedemann and Leopold Gmelin. It is often called an amino acid, even in scientific literature, but as it lacks a carboxyl group it is not strictly an amino acid. It does contain a sulfonate group and may be called an amino sulfonic acid. Small polypeptides have been identified which contain taurine but to date no aminoacyl tRNA synthetase has been identified as specifically recognizing taurine and capable of incorporating it onto a tRNA. Also, while taurine is present in both bull semen and urine, the taurine used in energy drinks such as Red Bull is not taken from these sources.

Source: http://www.answers.com/Taurine