Vitamin blood levels

Vitamin D intoxication causes 25-hydroxy vitamin blood levels to go from a normal of 30—50 ng/mL to 200—400 ng/mL. At this high level, the metabohte can compete with 1 a-25-dihydroxy vitamin for receptors in the intestine and bone and induce effects usually attributed to the dihydroxy vitamin D. Thus, 25-hydroxy vitamin is beUeved to be the critical factor in vitamin D intoxication. Vitamin D2 is metabolized slower than vitamin and thus appears to be less toxic (218). 

Metabolites of vitamin D, eg, cholecalciferol (CC), are essential in maintaining the appropriate blood level of Ca ". The active metabolite, 1,25-dihydroxycholecalciferol (1,25-DHCC), is synthesized in two steps. In the fiver, CC is hydroxylated to 25-hydroxycholecalciferol (25-HCC) which, in combination with a globulin carrier, is transported to the kidney where it is converted to 1,25-DHCC. This step, which requites 1-hydroxylase formation, induced by PTH, may be the controlling step in regulating Ca " concentration. The sites of action of 1,25-DHCC are the bones and the intestine. Formation of 1,25-DHCC is limited by an inactivation process, ie, conversion of 25-HCC to 24,25-DHCC, catalyzed by 24-hydroxylase. 

Up to 80% of oral doses of ascorbic acid are absorbed in humans with intakes of less than 0.2 g of vitamin C. Absorption of pharmacological doses ranging from 0.2 g to 12 g results in an inverse relationship, with less than 20% absorption at the higher doses. A single oral dose of 3 g has been reported to approach the absorptive capacity (tissue saturation) of the human intestine. Higher blood levels can be attained by providing multiple divided vitamin C doses per day. 

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

PTH is the most important regulator of bone remodelling and calcium homeostasis. PTH is an 84-amino acid polypeptide and is secreted by the parathyroid glands in response to reductions in blood levels of ionised calcium. The primary physiological effect of PTH is to increase serum calcium. To this aim, PTH acts on the kidney to decrease urine calcium, increase mine phosphate, and increase the conversion of 25-OH-vitamin D to l,25-(OH)2-vitamin D. PTH acts on bone acutely to increase bone resorption and thus release skeletal calcium into the circulation. However, due to the coupling of bone resorption and bone formation, the longer-term effect of increased PTH secretion is to increase both bone resorption and bone formation. 

Lactic acidosis (buildup of lactic acid in the blood) may also occur with die administration of metformin. Although lactic acidosis is a rare adverse reaction, its occurrence is serious and can be fatal. Lactic acidosis occurs mainly in patients with kidney dysfunction. Symptoms of lactic acidosis include malaise (vague feeling of bodily discomfort), abdominal pain, rapid respirations, shortness of breath, and muscular pain. In some patients vitamin B12 levels are decreased. This can be reversed with vitamin B12 supplements or with discontinuation of the drug therapy. Because... 

Effects on Vitamin D Metabolism. Lead appears to interfere with the conversion of vitamin D to its hormonal form, 1,25-dihydroxyvitamin D. In children with PbB levels of 33-55 pg/dL, 1,25-dihydroxy-vitamin D levels were reduced to levels comparable to those observed in children with severe renal insufficiency (Rosen et al. 1980). In lead-exposed children with blood lead levels of 33-120 pg/dL,... 

The answers are 402-g, 403-a. (Hardman, pp 1529-1532, 1582-15853 Calcitriol (1,2.5-dihydroxyvitamin D) is the most active form of vitamin D. It is formed by the kidney. When the Ca blood level rises, the kidney produces 24,25-dihydroxyvitamin D, a much less active form. Vitamin D can be manufactured in the body by the action of sunlight on the skin. Its main action is to increase Ca absorption in the gut Thus, vitamin D subserves important hormonal functions in Ca homeostasis. 

The fibroblasts do not convert cyanocobalamin or hydroxocobalamin to methylcobalamin or adenosyl-cobalamin, resulting in diminished activity of both N5-methyltetrahydrofolate homocysteine methyltransferase and methylmalonyl-CoA mutase. Supplementation with hydroxocobalamin rectifies the aberrant biochemistry. The precise nature of the underlying defect remains obscure. Diagnosis should be suspected in a child with homocystinuria, methylmalonic aciduria, megaloblastic anemia, hypomethioninemia and normal blood levels of folate and vitamin B12. A definitive diagnosis requires demonstration of these abnormalities in fibroblasts. Prenatal diagnosis is possible. 

Fig. 5. Vitamin Ba-levels in blood upon intramuscular injection of 100 mg pyridoxine-HCl.

When utilization tests were run on a group of 18 male and 7 female human subjects, wide variations in blood level responses were found, particularly among the males.36 [Both in animals (rats) and humans the two sexes respond somewhat differently.] When 134,000 ig. of vitamin A in four different forms, viz., vitamin A alcohol, vitamin A acetate, vitamin A natural ester No. 1, and vitamin A natural ester No. 2, was fed to the group of 18 males on four different occasions, the serum levels found after 6 hours ranged from 178 to 1423 ig. per 100 ml., 122 to 1170 ig. per 100 ml., 110 to 1183 ig. per 100 ml., and 114 to 1230 ig. per 100 ml., respectively. These nearly 10-fold variations in serum levels do not, of course, indicate 10-fold variation in need, but they do show that the vitamin when given in relatively large doses does behave very differently in different individuals. 

Vitamin D is a lipid-soluble vitamin, as is vitamin A. Lipid-soluble vitamins are stored in the body, in contrast to water-soluble vitamins such as vitamin C. Excess consumption of lipid-soluble vitamins can result in excess storage and resultant toxicity. The UL for vitamin D is 50 micrograms/day. Excess consumption may raise the blood level of calcium to the extent that calcification of organs (particularly the kidneys), occurs, and formation of kidney stones may follow. 

The clinical problems that arise in the menopause are hot flushes, sweating, depression, decreased libido, increased risk of cardiovascular disease and osteoporosis. The latter results in increased incidence of hip, radial and vertebral fractures. Oestrogen is one factor controlling synthesis of active vitamin D and osteoporosis is in part due to a deficiency of vitamin D. Not surprisingly, to reduce these problems, administration of oestrogen is recommended (known as hormone replacement therapy or HRT). HRT reduces some of the risk factors for coronary artery disease since it reduces blood pressure and decreases the blood level of LDL-cholesterol and increases that of HDL-cholesterol. However, there is considerable debate about whether HRT increases the risk of breast or endometrial cancer. 

In a totally different field, studies were being carried out on children who had a deficiency of methionine synthase and an impaired ability to convert homocysteine to methionine, so that they had increased blood levels of homocysteine. It was noted that these children had an increased incidence of thrombosis in cerebral and coronary arteries. This led to a study which eventually showed that an increased level of homocysteine was a risk factor for coronary artery disease in adults. Since methionine synthase requires the vitamins, folic acid and B12, for its catalytic activity, it has been suggested that an increased intake of these vitamins could encourage the conversion of homocysteine to methionine and hence decrease the plasma level of homocysteine. This is particularly the case for the elderly who are undernourished (see Chapter 15 for a discussion of nutrition in the elderly). 

The most important adverse effect is bleeding. With coumarins, this can be counteracted by giving vitamin Ki. Coagulability of blood returns to normal only after hours or days, when the liver has resumed synthesis and restored sufficient blood levels of clotting factors. In urgent cases, deficient factors must be replenished directly (e.g., by transfusion of whole blood or of prothrombin concentrate). 

Lactation Vitamin B-12 is excreted in breast milk in concentrations that approximate the mother s vitamin B-12 blood level. Amounts of B- 2recommended by the Food and Nutrition Board, National Academy of Sciences-National Research Council (2.6 mcg/day) should be consumed during lactation. 

Blood levels of vitamin D are influenced both by dietary intake and the amount of daylight exposure to the skin. Indeed, exposure of the skin to ultraviolet light catalyzes the synthesis of vitamin D3 (cholecalciferol) from 7-dehydrocholesterol thus vitamin D is more like a hormone and not strictly a vitamin. Furthermore, the UV radiation catalyzes the synthesis of ergocalciferol from ergosterol. This latter compound is found in plants, especially yeast and fungi, but the conversion to ergocalciferol... 

The most common toxic effects of metformin are gastrointestinal (anorexia, nausea, vomiting, abdominal discomfort, and diarrhea), which occur in up to 20% of patients. They are dose-related, tend to occur at the onset of therapy, and are often transient. However, metformin may have to be discontinued in 3-5% of patients because of persistent diarrhea. Absorption of vitamin B12 appears to be reduced during long-term metformin therapy, and annual screening of serum vitamin B12 levels and red blood cell parameters has been encouraged by the manufacturer to determine the need for vitamin B12 injections. In the absence of hypoxia or renal or hepatic insufficiency, lactic acidosis is less common with metformin therapy than with phenformin therapy. 

Elevated Hey levels can also occur in nutritional deficiencies of vitamin B12 (cobalamin) and folate. Folate or vitamin B12 deficiency can even lead to tHcy levels as high as those seen in the genetic homocystinurias [13]. In addition, a reciprocal relationship between blood levels or intake of these vitamins and tHcy concentrations... 

The major form of vitamin D in both cows and human milk is 25(OH)D3. This compound is reported to be responsible for most of the vitamin D in the blood serum of exclusively breast-fed infants. Whole cows milk contains only about 0.03 pg vitamin D per 100 g and 1 litre of milk per day will supply only 10-20% of the RDA. Therefore, milk is often fortified (at the level of c. 1-10 fig 1 ) with vitamin D. Fortified milk, dairy products or margarine are important dietary sources of vitamin D. The concentration of vitamin D in unfortified dairy products is usually quite low. Vitamin D levels in milk vary with exposure to sunlight. 

The physiological role of vitamin K is in blood clotting and is essential for the synthesis of at least four of the proteins (including prothrombin) involved in this process. Vitamin K also plays a role in the synthesis of a protein (osteocalcin) in bone. Vitamin K deficiency is rare but can result from impaired absorption of fat. Vitamin K levels in the body are also reduced if the intestinal flora is killed (e.g. by antibiotics). Vitamin K toxicity is rare but can be caused by excessive intake of vitamin K supplements. Symptoms include erythrocyte haemolysis, jaundice, brain damage and reduced effectiveness of anticoagulants. 

Normal blood levels of vitamin B12 are 2 x 1(T10 M or a little more, but in vegetarians the level may drop to less than one-half this value. A deficiency of folic acid can also cause megaloblastic anemia, and a large excess of folic acid can, to some extent, reverse the anemia of pernicious anemia and mask the disease. 

Warfarin antagonists include vitamin K, barbiturates, glutethimide. rifampin, and cholestyramine. Warfarin potentiators include phenylbutazone. oxyphenbutazone, anabolic steroids, clofibrate, aspirin, hepatotoxins, disnlfirain, and metronidazole. In patients undergoing anticoagulation therapy with warfann, it has been found that cimetidine (used in therapy of duodenal ulcer) may increase anticoagulant blood levels and consequently prolong the prothrombin time. 

As a brief introductory summary, vitamin D substances perform the following fundamental physiological functions (1) promote normal growth (via bone growth) (2) enhance calcium and phosphorus absorption from the intestine (3) serve to prevent rickets (4) increase tubular phosphorus reabsorpiion (5) increase citrate blood levels (6) maintain and activate alkaline phosphatase m bone (7) maintain serum calcium and phosphorus levels. A deficiency of D substances may be manifested in the form of rickets, osteomalacia, and hypoparathyroidism. Vitamin D substances are required by vertebrates, who synthesize these substances in the skin when under ultraviolet radiation, Animals requiring exogenous sources include infant vertebrates and deficient adult vertebrates, Included there are vitamin D (calciferol ergocalciferol) and vitamin D< (activated 7-dehydrocholesterol cholecalciferol). 

Evidence for vitamin C deficiency in prematurely born infants showing hyperamino aciduria has been reported by Dustin and Bigwood (D29). In addition to the increased excretion of certain amino acids reported in common rachitis, there is also an increased output of tyrosine and phenylalanine in scurvy (Jll). The blood levels of amino acids are normal (H28). The excessive output of tyrosine and phenylalanine is considered to be related to a renal factor it is not a competitive effect due to increased excretion of serine and threonine (J13). In addition, therefore, to the increased output of certain amino acids reported in common rachitis (vide infra) there is also, in scurvy, an increased excretion of tyrosine and phenylalanine. 

Burr ML, Hurley RJ, Sweetnam PM. Vitamin C supplementation of old people with low blood levels. Gerontol Clin I 975 17 236-243. 

Iron deficiency may be present in postgastrectomy patients and occasionally this may mask an underlying megaloblastic anemia. Treatment of the iron deficiency will unmask the megaloblastic process and macrocytes will appear in the peripheral blood. Iron therapy appears able to influence the serum vitamin B12 level and Williams (W6) noted a substantial increase in the serum vitamin level following treatment with oral iron for 3 months. Of his patients, 36 had a low serum vitamin level before iron therapy, and in 26 the level rose to within the normal range. 

L2. Lau, K. S., Gottleib, C., Wasserman, L. R., and Herbert, V., Measurement of serum vitamin B12 level using radioisotope dilution and coated charcoal. Blood 26, 202-214 (1965). 

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