A vitamin deficiency is a lack of the proper amounts of a vitamin. In addition to vitamin deficiencies, nutrient deficiencies can be observed. Although nutritional deficiencies can be observed in the malnourished (poverty, economically deprived areas, neglect, etc.,), they can also be observed in disease states and in genetic varieties in the human race.
There are thirteen vitamins which are necessary for maintenance of health. Four of these vitamins are fat-soluble (A, D, E, and K) and the nine others are water-soluble. As discussed in our introduction to vitamins
, fat-soluble vitamins are stored in the body. On the other hand, water-soluble vitamins are readily excreted. Therefore, water-soluble vitamins need to be replenished more often. Although fat-soluble vitamins are stored in the body for later use, there is a catch. Fat-soluble vitamins are more likely to be poorly absorbed in gastrointestinal disorders of fat absorption. In our discussion of fats, we reviewed the principles of fat absorption of dietary fats
. Fats, and substances we produce with "fat-like qualities", such as bile, assist in absorption of fat-soluble vitamins and dietary fat through the intestinal wall.
Existing gastrointestinal disease can therefore, inhibit the absorption of these vitamins. Gastrointestinal disorders of fat malabsorption, sprue, coeliac disease, and Crohn's disease can inhibit the absorption of certain vitamins.
Crohn's disease is a form of inflammatory bowel disease that may affect any part of the gut. It tends to affect the terminal ileum (last portion of the small intestine), colon and anorectum, with a characteristic inflammatory pattern. If the ileum is affected, then a vitamin B12
deficiency can develop since this vitamin is absorbed in the ileum. This is one of the cases where IV nutrition
may be necessary.
Ulcerative colitis, another form of inflammatory bowel disease which affects the large intestine, can also cause nutritional deficiencies. This is another case where IV nutrition
may be necessary.
Sprue is a chronic form of malabsorption syndrome (syndrome is a collection of signs and symptoms). Sprue is divided into two forms: 1)Tropical sprue, which occurs primarily in the tropics and subtropics and the cause is unknown. It may have a microbial cause and/or genetic. A bacterial cause is likely, considering administration of antibiotics can cause remission. Nevertheless, it is characterized by a malabsorption syndrome (vitamin, protein, etc.). 2) Non-tropical sprue is also known as coeliac (celiac) disease. In coeliac disease, there is a permanent intolerance to gliadin, a protein in gluten. Gluten is a protein found in wheat products. Immune reaction to gliadin leads to inflammatory reactions in the gut, with subsequent damage to the villi of the small intestine. With resulting damage to the intestine, malabsorption logically follows. Withdrawing gluten from the diet limits the damage caused to the intestines.
Microbial infections in general
In comparison to the diseases discussed above, a microbial infection of any type has the theoretical ability to damage the wall of the intestine. Various bacteria, viruses, fungi, and parasites can damage the intestines (as well as other tissues), causing malabsorption and subsequent nutritional deficiencies.
Keep in mind that although the above disease states may have a different origin, there is one entity which they all have in common: damage to the intestine, and this is what causes the deficiency. If the intestine is damaged, it cannot absorb nutrients properly. In gastrointestinal malabsorption we can observe diarrhoae, decreases in body weight, fatty stools, and associated signs of deficiencies (discussed with each nutrient in question).
Other disease states
The malabsorption syndromes discussed above primarily affect the gut. Additionally, there are other significant causes of nutritional deficiency.
The pancreas is an organ which our lives depend on. The pancreas produces and secretes enzymes which help us digest fats, proteins, carbohydrates and other substances. If this organ is damaged in any way, not only does our digestive and absorbitive capabilities decrease, but our metabolism is deranged. If the pancreas is completely damaged, we must rely on medical intervention in the way of exogenous enzymes, and insulin for life, if we are to survive, considering the pancreas normally produces these substances.
Pancreatitis is an inflammation of the pancreas. There are several common insults which can result in inflammation to this organ. Chronic alcohol abuse is the most common cause of chronic pancreatitis. Other causes are cystic fibrosis (genetic condition affecting 1 in 2000 people), conditions such as haemochromatosis, obstructed pancreatic or biliary (bile) ducts (eg. gallstones or tumour). Causes of acute (sudden) pancreatitis are alcohol binges, gallstones, trauma (road traffic accident), steroids, viruses (eg. mumps), autoimmune conditions, insect bites (scorpion and perhaps certain spiders), and drugs (eg. diuretics, azathioprine).
Any surgical procedure in which a portion of the gut is removed (eg., resection due to a tumour) can also result in malabsorption and nutritional aspects must always be considered.
As discussed, the pancreas secretes enzymes and hormones. The enzymes help to digest nutrients. The hormones function in metabolism. For example, insulin, produced by the pancreas helps to keep a proper level of blood glucose (between 3-6 millimoles, normal range) and stores excess sugars in the liver and muscle. The liver produces bile (discussed in lipids
), which helps in emulsifying dietary fats. If there is any obstruction in the pancreatic or bile duct, these secretions cannot be transported to their destination. In these cases, malabsorption will occur. If there is a genetic anomaly of an enzyme or hormone, a malabsorption can also ensue. We must remember that a hormone or enzyme must be constructed to exact specifications. If it is slightly altered, it may not work correctly. This can also lead to malabsorption. It can also lead to other disease states, such as one form of diabetes (damage to the area of the pancreas which produces insulin). There are possible defects such as a problem with the production of intrinsic factor in the parietel cells of the gastric mucosa. Intrinsic factor is needed for B12
(sometimes referred to as "extrinsic factor", differentiating it from intrinsic factor) absorption. Intrinsic factor combines with the vitamin, enabling it to be absorbed by the terminal ileum. Intrinsic factor defects or definciencies can result in a definciency of vitamin B12
. Of course, the signs and symptoms of this deficiency can take some time (months to several years) to manifest, since B12
is stored in the liver in amounts of 3000-5000 micrograms, and only trace amounts are normally lost in the urine and stool. Considering that only a few micrograms per day of vitamin B12
are required, it would take the normal individual approximately 5 years to exhaust the supply. Of course, this varies amongst individuals, and depending on several factors (nutritional state, activities such as exercise, lifestyle, genetics, and disease states) this can vary considerably. And of course, B12
and folic acid
are required for normal DNA synthesis. Definciencies lead to impaired DNA synthesis, inhibition of normal mitosis (cell division), and abnormal maturation and function of the cells produced. This is especially noticeable in cell populations that undergo a rapid rate of division, for example, (you guessed it!) your intestinal epithelium. With impaired intestinal epithelium, this compounds the absorption problem. Things can get complicated, can't they!
Definciency states can also result from psychiatric conditions. Anorexia nervosa is self- induced starvation, and bulimia is a psychiatric condition in which an individual binges on food and then induces vomiting. In patients with anorexia nervosa, weight loss is common, with subsequent deficiencies. The major complication is an increased risk of sudden death due to cardiac arrhythmia, most likely from hypokalaemia (hypokalemia), abnormally low potassium. In bulimia, the patient usually maintains a near-normal height-weight ratio. The major medical complications of bulimia relate to chronic self-induced vomiting. Electrolyte imbalances (hypokalaemia) from vomiting increase the risk of fatal arrhythmias. There is also the risk of aspiration (inhalation) of gastric contents while vomiting, and oesophageal rupture.
Genetic variants in the human population
With all the room for error in our biochemistry, it is amazing that things work as well as they do. However, genetics has its flaws and this can result in different phenotypical (gene expression) outcomes. Some gene defects or differences are so innocuous, they may never be noticed, except under exceptional circumstances. Unfortunately, on some occasions, a genetic defect or difference can severely affect an individual.
Glucose-6-phosphate dehydrogenase (G6PDH) deficiency
G6PDH is an enzyme found in the cytoplasm of cells of the liver, adipocytes, and red blood cells. G6PDH is significant in the pentose phosphate pathway of glucose metabolism to generate NADPH. NADPH (form of NADP+
, see niacin
) is the biologically active cofactor form of niacin or nicotinic acid
. These ultimately serve as coenzymes
in metabolic pathways (for glucose, etc.). NADPH is needed for 1) reduction of fatty acids, 2) keeping iron (Fe) in the normal divalent state (Fe++
in the haemoglobin of red blood cells, and 3) for glutathione reductase, an enzyme which converts glutathione into the useful (reduced) form, GSH. GSH functions in protecting enzymes with sulfur containing residues, and protects the membranes of red blood cells.
Protecting the red blood cell membrane is important. If the membrane is allowed to oxidize (thus the need for antioxidants), then it develops inconsistencies, allowing haemoglobin to leak out into the circulatory system. A genetic deficiency of G6PDH allows the red blood cells more vulnerable to oxidant drugs such as sulfonamides, chloramphenicol, and others, by causing a rapid fall in NADPH (remember, NADPH is protective). If a large portion of the red blood cell population is damaged, their haemoglobin is liberated, resulting in anaemia. There are also many other serious complications. It is estimated that approximately 10% of the male African-American population has a G6PDH deficiency.
The illustration below demostrates some of the diseases that are caused from enzyme deficiencies of a genetic background. This group of diseases is known as the sphingolipidoses, characterised by the inability to synthesize and degrade certain types of lipids (sphingolipids). Unfortunately, these diseases are fatal early in life and demonstrate the tragic outcome of a deficiency of but one specific enzyme in metabolism.