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VITAMIN B6 (PYRIDOXINE)



Table of Contents
image Treatment of mild hyperhomocystinemia in vascular disease patients
image A deficiency of vitamin B6 is a plausible molecular basis of the retinopathy of patients with diabetes mellitus.
image Effect of vitamin B6 on the side effects of a low-dose combined oral contraceptive.
image Vitamin B6 in the treatment of the premenstrual syndrome - Review (1)
image Effect of vitamin B-6 on plasma and red blood cell magnesium levels in premenopausal women
image Functional capacity of the tryptophan niacin pathway in the premenarchial phase and in the menopausal age
image Incident pain caused by collapsed vertebrae in menopause. The logical background to a personal treatment protocol
image Vitamins and metals: Potential dangers for the human being
image Vitamin B6 status in cirrhotic patients in relation to apoenzyme of serum alanine aminotransferase
image Vitamin B6 concentrations in patients with chronic liver disease and hepatocellular carcinoma
image Abnormal vitamin B6 status in childhood leukemia.
image Hyperhomocysteinaemia and end stage renal disease
image Hyperhomocysteinemia confers an independent increased risk of atherosclerosis in end-stage renal disease and is closely linked to plasma folate and pyridoxine concentrations.
image High dose-B-vitamin treatment of hyperhomocysteinemia in dialysis patients.
image The activities of coenzyme Q10 and vitamin B6 for immune responses.
image Suppression of tumor growth and enhancement of immune status with high levels of dietary vitamin B6 in BALB/c mice.
image Homocysteine: Relation with ischemic vascular diseases.
image A double blind study of vitamin B-sub-6 in Down's syndrome infants: I. Clinical and biochemical results.
image A double blind study of vitamin B-sub-6 in Down's syndrome infants: II. Cortical auditory evoked potentials.
image Long-term folic acid (but not pyridoxine) supplementation lowers elevated plasma homocysteine level in chronic renal failure.
image Prospects for nutritional control of hypertension
image Unrecognized pandemic subclinical diabetes of the affluent nations: Causes, cost and prevention
image Vitamin and mineral deficiencies which may predispose to glucose intolerance of pregnancy
image Vitamin B6 alleviates the vascular complications of insulin-treated STZ-induced diabetic rats
image [Comparison of metabolism of water-soluble vitamins in healthy children and in children with insulin-dependent diabetes mellitus depending upon the level of vitamins in the diet]
image The endocrine pancreas in pyridoxine deficient rats.
image Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus.
image [Criteria of supply of vitamins B1, B2, and B6 in children with insulin-dependent diabetes mellitus]
image [Vitamin metabolism in children with insulin-dependent diabetes mellitus. Effect of length of illness, severity, and degree of disruption of substance metabolism]
image [Metabolism of B group vitamins in patients with insulin-dependent and non-insulin dependent forms of diabetes mellitus]
image [Patients with type-II diabetes mellitus and neuropathy have nodeficiency of vitamins A, E, beta-carotene, B1, B2, B6, B12 and folic acid]
image Tissue concentrations of water-soluble vitamins in normal and diabetic rats.
image Malnutrition in geriatric patients: diagnostic and prognostic significance of nutritional parameters.
image Drug therapy during pregnancy.
image Changes on levels of B6 vitamin and aminotransferase in the liver of diabetic animals.
image [Hemochromatotic cirrhosis complicating pyridoxine-sensitive hereditary sideroblastic anemia. Case report]
image [Vitamin status in diabetic neuropathy (thiamine, riboflavin, pyridoxin, cobalamin and tocopherol)]
image Failure of pyridoxine to improve glucose tolerance in diabetics.
image Pyridoxine treatment of chemical diabetes in pregnancy.
image Effects of oral contraceptives on nutritional status.
image Serum pyridoxal concentrations in patients with diabetic neuropathy.
image Abnormal tryptophan metabolism and experimental diabetes by xanthurenic acid (XA).
image Vitamin B6 treatment of gestational diabetes mellitus: studies of blood glucose and plasma insulin.
image Improvement of oral glucose tolerance in gestational diabetes by pyridoxine.
image Clinical rise of a combination containing phosphocreatinine as adjuvant to physiokinesiotherapy
image Relation between theophylline and circulating vitamin levels in children with asthma
image Nutritional status of an institutionalized aged population.
image [Acquired, vitamin B6-responsive, primary sideroblastic anemia, an enzyme deficiency in heme synthesis]
image Intakes of vitamins and minerals by pregnant women with selected clinical symptoms.
image [Anemia with hypersideroblastosis during anti-tuberculosis therapy. Cure with vitamin therapy]
image [Vitamin B 6 deficiency anemia]
image [The therapeutic approach in optic neuropathy due to methyl alcohol]
image Vitamin B6 in clinical neurology.
image The assessment of the vitamin B6 status among Egyptian school children by measuring the urinary cystathionine excretion.
image Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment.
image Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study.
image Vitamin intake: A possible determinant of plasma homocysteine among middle-aged adults
image Homocystinuria: What about mild hyperhomocysteinaemia?
image Dietary methionine imbalance, endothelial cell dysfunction and atherosclerosis
image Hyperhomocysteinemia and venous thromboembolic disease.
image Homocysteine: an important risk factor for atherosclerotic vascular disease.
image Gastrointestinal infections in children
image Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium
image New developments in pediatric psychopharmacology.
image Homocysteine, folate, and vascular disease
image [Homocysteine, a risk factor of atherosclerosis]
image [Hyperhomocysteinemia]
image [Homocysteine, a less well-known risk factor in cardiac and vascular diseases]
image Homocysteine and coronary atherosclerosis.
image Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease.
image Thiamine pyrophosphate and pyridoxamine inhibit the formation of antigenic advanced glycation end-products: comparison with aminoguanidine.
image Rationales for micronutrient supplementation in diabetes.
image Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy
image Adenosine-N6-diethylthioether-N1-pyridoximine 5'-phosphate. A novel marker for human cancer detection
image Vitamin B6 and cancer: Synthesis and occurrence of adenosine-N6-diethylthioether- N-pyridoximine-5'-phosphate, a circulating human tumor marker

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Pyridoxine treatment of chemical diabetes in pregnancy.

Am J Obstet Gynecol (UNITED STATES) Mar 1 1979, 133 (5) p499-502

Thirteen women with chemical diabetes diagnosed in late pregnancy were found to excrete excessive amounts of urinary xanthurenic acid after a tryptophan load, indicative of a relative pyridoxine (vitamin B6) deficiency. Treatment with 100 mg pyridoxine daily for 14 to 23 days restored the urinary xanthurenic acid excretion to normal in all patients. Improvement of glucose tolerance was observed in only two of the patients studied, deterioration in six, and no significant change in the remaining five. The insulin response to glucose was unaltered during pyridoxine therapy.



Effects of oral contraceptives on nutritional status.

Am Fam Physician (UNITED STATES) Jan 1979, 19 (1) p119-23

Major effects of oral contraceptives on nutritional status are elevation of triglycerides, decline in glucose tolerance, an apparent increase in the need for folate and vitamins C, B2 and B6, and a decrease in iron loss. Women at greater risk of nutritional deficits due to oral contraceptives include those who have just had a baby, are planning to have a baby later, already show nutritional deficiencies, have had recent illness or surgery, have poor dietary habits, are still growing or have a family history of diabetes or heart disease.



Serum pyridoxal concentrations in patients with diabetic neuropathy.

Aust N Z J Med (AUSTRALIA) Jun 1978, 8 (3) p259-61

Serum pyridoxal (vitamin B6) concentrations were measured in 50 patients with significant diabetic neuropathy. There were 24 males and 26 females with a mean age of 58.2 years and a mean duration of diabetes of 9.8 years. The level of pyridoxal was significantly lower in these patients when compared with randomly selected diabetic patients matched for age and sex without clinical evidence of neuropathy. There was no significant difference in the duration of the diabetes between the two groups. The results indicate an association between pyridoxal deficiency and neuropathy in diabetic patients.



Abnormal tryptophan metabolism and experimental diabetes by xanthurenic acid (XA).

Abnormal tryptophan metabolism and experimental diabetes by xanthurenic acid (XA).

1) Xanthurenic acid-insulin complex reduced insulin activity.
2) The antigenicity of xanthurenic acid-insulin was almost same as native insulin.
3) Saturated fat increased urinary xanthurenic acid in vitamin B6 deficiency.



Vitamin B6 treatment of gestational diabetes mellitus: studies of blood glucose and plasma insulin.

Am J Obstet Gynecol (UNITED STATES) Mar 15 1977, 127 (6) p599-602

Thirteen women with late pregnancy gestational diabetes mellitus were tested with an intravenous glucose tolerance test and both blood glucose and plasma insulin levels were measured. Each woman was then treated with 100 mg. of vitamin B6 per day for 2 weeks and the intravenous glucose tolerance test was then repeated. There was a statistically significant improvement in the glucose tolerance curve after the vitamin B6 treatment, with a lowering of blood glucose levels at all points on the curve except for the 5 minute value. This glucose effect occurred despite an unchanged or lowered plasma insulin level. These results suggest that a relative deficiency in vitamin B6 is associated with some cases of gestational diabetes mellitus and that the replacement of this vitamin improves the metabolic state. The low vitamin B6 levels appear to alter metabolic pathways which result in a lowering of the biologic activity of endogenous insulin.



Improvement of oral glucose tolerance in gestational diabetes by pyridoxine.

Br Med J (ENGLAND) Jul 5 1975, 3 (5974) p13-5

Fourteen pregnant women were shown by the oral glucose tolerance test to have gestational diabetes. In 13 an increased urinary xanthurenic-acid excretion after an oral load of L-tryptophan indicated a relative pyridoxine deficiency. All patients were treated with vitamin B6 (pyridoxine) 100 mg/day for 14 days by mouth, after which the pyridoxine deficiency disappeared and the oral glucose tolerance improved considerably. Only two patients then had sufficiently impaired glucose tolerance to justify the diagnosis of gestational diabetes; Our results substantiated our hypothesis that increased xanthurenic-acid synthesis during pregnancy may cause gestational diabetes. Treatment with vitamin B6 makes the production of xanthurenic-acid normal by restoring tryptophan metabolism and improves the oral glucose tolerance in patients with gestational diabetes.



Clinical rise of a combination containing phosphocreatinine as adjuvant to physiokinesiotherapy

RIABILITAZIONE (ITALY), 1976, 9/2 (51-62)

The authors make a clinical contribution to the therapeutic use of phosphocreatinine, both alone and in combination with vitamin B12, folic acid, vitamin B6 and fructose 1-6 diphosphate. The study was carried out on 24 adult patients of both sexes, suffering from neuromyolesions (paraplegia, hemiparesis, tetraparesis, neuraxitis, myopathy, radiculoneuritis) and presenting, as therapeutic indications, conditions of organic wasting, marked asthenia, cachexia, or the requirement of physical performance and intense muscular effort in connection with the use of kinesitherapy techniques. An analysis of the collected data showed that both phosphocreatinine preparations (the simple form and combined with vitaminic coenzymes) induced significant improvements in the initial symptomatology; no statistically significant difference was observed between the 2 treatments. Particular interest is placed on the finding with regard to the effect on motor re education; in fact, the 2 preparations considered phosphocreatinine influenced this parameter favourably in over half the cases investigated. The drug was excellently tolerated in all the cases studied, from both the clinical point of view and the blood chemistry standpoint. In conclusion, the results obtained make the therapeutic use of phosphocreatinine undoubtedly useful as a valid factor in association with physiokinesitherapy.



Relation between theophylline and circulating vitamin levels in children with asthma

Pharmacology (Switzerland), 1996, 53/6 (384-389)

We investigated the effect of theophylline administration on circulating vitamin levels in children with asthma. Twenty-three asthmatic children, ranging in age from 7 to 15 with a mean of 10.8 years and including 16 patients who were treated with slow-release theophylline and 7 patients not receiving any type of theophylline preparation, were enrolled in this study. They all were inpatients who had been hospitalized for the control of asthma. Steady-state serum theophylline and vitamin A, B1, B2, B6, B12 and C levels were evaluated in these patients. Circulating vitamin B1 and B6 levels were depressed in asthmatic children treated with theophylline compared to those not receiving the agent (38.4 plus or minus 1.6 (mean plus or minus SEM) vs. 46.4 plus or minus 3.5 ng/ml and 7.1 plus or minus 0.5 vs. 11.8 plus or minus 2.1 ng/ml, respectively, p < 0.05). A significant negative correlation between theophylline and circulating levels of vitamin B6 was demonstrated in the subjects of this study (r(s) = -0.657, p < 0.001). In contrast, no relationship was noted between theophylline and circulating vitamin B1 levels. Theophylline did not affect circulating vitamin A, B1, B12 or C levels. We conclude that theophylline induces depression of circulating vitamin B1 and B6 levels in asthmatic children, although a dose-dependent interaction between theophylline and vitamin B1 would be unlikely.



Nutritional status of an institutionalized aged population.

J Am Coll Nutr (UNITED STATES) 1984, 3 (1) p13-25

The nutritional status of 146 elderly residents in a long-term care facility was evaluated using biochemical and anthropometric measures. The level of nursing care required and meal locale had no significant effect on the overall nutritional status of the residents. The biochemical data indicated three nutritional problems requiring treatment and follow-up: anemia, low vitamin B6 status, and reduced albumin levels. The incidence of these problems in other groups of elderly deserves further study. Six percent of the study population were anemic, with 13% having low serum folate, 6% with low transferrin saturation, and 31% with low TIBC values suggesting more than one factor involved in the anemia. Low vitamin B6 status was observed in 28% of the population. Whether this is due to poor intake, poor absorption, or both is not known. The percentage of residents with decreased albumin levels was slightly higher than that observed in other studies of the elderly, and may be related to the more advanced age of this population.



[Acquired, vitamin B6-responsive, primary sideroblastic anemia, an enzyme deficiency in heme synthesis]

Schweiz Med Wochenschr (SWITZERLAND) Oct 10 1981, 111 (41) p1533-5

The activity of delta-aminolevulinic acid synthetase (ALAS), the rate-limiting enzyme in heme synthesis, has been found to be markedly reduced (13% of controls) in erythroblasts of a patient with acquired, primary sideroblastic anemia. Administration of vitamin B6 (pyridoxin, 200-600 mg/d) resulted in complete reconstitution of erythroblastic ALAS-activity with concomitant disappearance of all hematologic abnormalities. The findings show that the therapeutic efficacy of pyridoxin in primary sideroblastic anemia is due to its effect on defective ALAS. More generally, the data support the view that almost all features of primary sideroblastic anemia can be ascribed to a disturbance of heme synthesis in erythroblasts.



Intakes of vitamins and minerals by pregnant women with selected clinical symptoms.

J Am Diet Assoc (UNITED STATES) May 1981, 78 (5) p477-82

Toxemia in pregnancy is characterized by a combination of at least two of the following clinical symptoms: hypertension, edema, and proteinuria. In this study the dietary intakes of young pregnant women attending a Maternal and Infant Care Program at Tuskegee Institute were evaluated for selected vitamins and minerals. Women with toxemia were identified, and women without toxemia served as controls. The toxemia group generally consumed lesser amounts of vitamins and minerals than the controls. However, both groups were deficient (less than two-thirds RDA) in calcium, magnesium, vitamin B6, vitamin B12, and thiamin. Milk, meat, and grains supplied an appreciable proportion of each vitamin except vitamin A, which was found primarily in the two vegetable groups. Meat and grains contained the greatest quantities of minerals, but milk provided a relatively good proportion of potassium, calcium, magnesium, and phosphorus. Anemia was not related to the incidence of toxemia. Women exhibiting anemia consumed smaller amounts of vitamins studied than did women without anemia.



[Anemia with hypersideroblastosis during anti-tuberculosis therapy. Cure with vitamin therapy]

Nouv Rev Fr Hematol (FRANCE) Apr 14 1978, 20 (1) p99-110

The unusual occurrence of microcytic anemia with hypochromia, high iron blood levels and excess of sideroblasts in the bone marrow, observed during the treatment of tuberculosis with isoniazid and rifampicine is reported. Three particularities were noted. First, in our experience, the occurrence of this type of anemia has never been noted previously as a result of these two drugs. Secondly, the improvement of the blood abnormalities was obtained by the combined use of vitamin B6 and vitamin C. Thirdly, the anemia was associated with neuropathy, characterized by areflexia and dysesthesia, which improved with vitamin B6 therapy (but not with vitamin C). Some mechanisms are discussed as being possibly the origin of this kind of anemia, particularly a lack of vitamin B6 resulting from a massive urinary loss of pyridoxal induced by isoniazid as well as both a tissue depletion and an overconsumption of this vitamin. The anemia may be the consequence of a deficiency of hemoglobin synthesis involving probably the first step of the biosynthesis of heme.



[Vitamin B 6 deficiency anemia]

Schweiz Med Wochenschr (SWITZERLAND) Oct 11 1975, 105 (41) p1319-24

The course of spontaneous vitamin B6 deficiency anemia in a 57-year-old woman is reported. The anemia was characterized by hypochromasia of the erythrocytes, hyperferricemia, absence of hemolysis, and hyperplastic, ineffective, sideroblastic erythropoiesis of the bone marrow. It was corrected by oral vitamin B6 therapy. On interruption of the vitamin B6 herapy the anemia relapsed. On resumption of vitamin B6 medication it responded again with normalization of the hemoglobin and erythrocytes values. The hematological remission could be maintained under longterm vitamin B6 medication. The nosological significant of this rare anemia and its differentiation from other forms of anemia are discussed.



[The therapeutic approach in optic neuropathy due to methyl alcohol]

Oftalmologia (ROMANIA) Jan-Mar 1991, 35 (1) p39-42

The paper reports on the case of a 44-year-old patient suffering from toxic optic neuropathy produced by ingestion of a drink brought at second hand. The eye examination revealed the installment of bilateral blindness without the perception of light and with alteration of the general state. After the treatment with 3 perfusions/day with 22 ml ethylic alcohol, 90 degrees, in 250 ml glucosed serum 10%, 200 mg vitamin B1, 500 mg vitamin B6, nicotined xanthnol, vials II for six days, the evolution was good: VOD = 2/3 n.c.; VOS = 1/8 n.c.



Vitamin B6 in clinical neurology.

Ann N Y Acad Sci (UNITED STATES) 1990, 585 p250-60

Many conditions in clinical neurology may be responsive to pyridoxine as a therapeutic agent. The current difficulty is in trying to isolate the conditions that are most likely to respond. Treating seizures is a major part of a neurologic practice. Our current therapeutic agents are only partially successful and limited by multiple side effects. One problem is that patients often have to take these agents for an entire lifetime, further raising the risk of toxicity. If pyridoxine supplementation can improve the efficacy of currently used medications, it will be gladly accepted into our therapeutic arsenal. Headache, chronic pain, and depression all appear to run together in many of our patients. The observations that serotonin deficiency is a common thread between them and that pyridoxine can raise serotonin levels open a wide range of therapeutic options. Small studies have been carried out with mixed success. Comparison with amitriptyline in the treatment of headache appears to show about equal efficacy, although side effects would be expected to be more of a problem with the amitriptyline. Behavioral disorders are relatively common and continue to be a major problem, disrupting the lives of the patients and their families. Current treatments are not acceptable to most people because of the risk of side effects with long-term usage. If, as Dr. Feingold suggests, many of these problems are caused by "toxic" exposures to chemicals that are pyridoxine antagonists, supplementation at early ages may reduce the incidence of hyperactivity and aggressive behavior. This raises the question of safety. Is pyridoxine safe for long-term use in large segments of the population, including children? The studies on children with Down's syndrome and autism, utilizing much higher doses than are used for other therapeutic purposes, seem to indicate relative safety if carefully monitored. Studies involving large population groups with carpal tunnel syndrome, all adults, using 100-150 mg/day have shown minimal or no toxicity in five- to 10-year studies. Women self-medicating for PMS taking 500 to 5000 mg/day have shown peripheral neuropathy within one to three years. It would appear from this retrospective analysis that pyridoxine is safe at doses of 100 mg/day or less in adults. In children there is not enough data to make any sort of suggestion. Because the major neurologic complication is a peripheral neuropathy and the causes of this condition are myriad, pyridoxine may cause neuropathy only in patients with a pre-existing susceptibility to this condition.



The assessment of the vitamin B6 status among Egyptian school children by measuring the urinary cystathionine excretion.

Int J Vitam Nutr Res (SWITZERLAND) 1984, 54 (4) p321-7

A metabolic study was carried out on 19 school boys and girls (age 7-13 years) to assess their vitamin B6 status. The metabolic study was divided in five different periods, basal (A), post-methionine loading (B), one (C) and two (D) week after oral vitamin B6 therapy (50 mg/day) and post-methionine. Mean cystathionine excretion (beta mol/24 h) increased significantly (p less than 0.01) at stage B compared to mean values obtained at stage A reflecting a deficit in the vitamin B6 nutriture. Vitamin B6 therapy corrected the deficiency and the utilization of administered methionine.



Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment.

Am J Clin Nutr (UNITED STATES) Jan 1997, 65 (1) p20-9

Associations between nutritional status and cognitive performance were examined in 137 elderly (aged 66-90 y) community residents. Participants were well-educated, adequately nourished, and free of significant cognitive impairment. Performance on cognitive tests in 1986 was related to both past (1980) and concurrent (1986) nutritional status. Several significant associations (P < 0.05) were observed between cognition and concurrent vitamin status, including better abstraction performance with higher biochemical status and dietary intake of thiamine, riboflavin, niacin, and folate (rs = 0.19-0.29) and better visuospatial performance with higher plasma ascorbate (r = 0.22). Concurrent dietary protein in 1986 correlated significantly (rs = 0.25-0.26) with memory scores, and serum albumin or transferrin with memory, visuospatial, or abstraction scores (rs = 0.18-0.22). Higher past intake of vitamins E, A, B-6, and B-12 was related to better performance on visuospatial recall and/or abstraction tests (rs = 0.19-0.28). Use of self-selected vitamin supplements was associated with better performance on a difficult visuospatial test and an abstraction test. Although associations were relatively weak in this well-nourished and cognitively intact sample, the pattern of outcomes suggests some direction for further research on cognition-nutrition associations in aging.



Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study.

Am J Clin Nutr (UNITED STATES) Mar 1996, 63 (3) p306-14

We investigated the relations between plasma concentrations of homocysteine and vitamins B-12 and B-6 and folate, and scores from a battery of cognitive tests for 70 male subjects, aged 54-81 y, in the Normative Aging Study. Lower concentrations of vitamin B-12 (P=0.04) and folate (P=0.003) and higher concentrations of homocysteine (P=0.0009 ) were associated with poorer spatial copying skills. Plasma homocysteine was a stronger predictor of spatial copying performance than either vitamin B-12 or folate. The association of homocysteine with spatial copying performance was not explained by clinical diagnoses of vascular disease. Higher concentrations of vitamin B-6 were related to better performance on two measures of memory (P=0.03 and P=0.05). The results suggest that vitamins (and homocysteine) may have differential effects on cognitive abilities. Individual vitamins and homocysteine should be explored further as determinants of patterns of cognitive impairment.



Vitamin intake: A possible determinant of plasma homocysteine among middle-aged adults

Annals of Epidemiology (USA), 1997, 7/4 (285-293)

PURPOSE: Many epidemiologic studies have identified elevated plasma homocyst(e)ine as a risk factor for atherosclerosis and thromboembolic diseases. To examine the relationship between vitamin intakes and plasma homocyst(e)ine, we analyzed dietary intake data from a case-control study of 322 middle-aged individuals with atherosclerosis in the carotid artery and 318 control subjects without evidence of this disease. METHODS: All of these individuals were selected from a probability sample of 15,800 men and women who participated in the Atherosclerosis Risk in Communities (ARIC) study. RESULTS: Plasma homocyst(e)ine was inversely associated with intakes of folate, vitamin B6, and vitamin B12 (controls only for this vitamin)-the three key vitamins in homocyst(e)ine metabolism. Among nonusers of vitamin supplement products, on average each fertile increase in intake of these vitamins was associated with 0.4 to 0.7 micromol/L decrease in plasma homocyst(e)ine. An inverse association of plaine was also found with thiamin, riboflavin, calcium, phosphorus, and iron. Methionine and protein intake did not show any significant association with plasma homocyst(e)ine. CONCLUSIONS: In almost all analyses, cases and controls showed similar associations between dietary variables and plasma homocyst(e)ine. Plasma homocyst(e)ine among users of vitamin supplement products was 1.5 micromol/L lower than that among nonusers. Further studies to examine possible caused relationships among vitamin intake, plasma homocyst(e)ine, and cardiovascular disease are needed.



Homocystinuria: What about mild hyperhomocysteinaemia?

Postgraduate Medical Journal (United Kingdom), 1996, 72/851 (513-518)

Hyperhomocysteinaemia is associate risk of atherosclerotic vascular disease and thromboembolism, in both men and women. A variety of conditions can lead to elevated homocysteine levels, but the relation between high levels and vascular disease is present regardless of the underlying cause. Pooled data from a large number of studies demonstrate that mild hyperhomocysteinaemia after a standard methionine load is present in 21% of young patients with coronary artery disease, in 24% of patients with cerebrovascular disease, and in 32% of patients with peripheral vascular disease. From such data an odds ratio of 13.0 (95% confidence interval 5.9 to 28.1), as an estimate of the relative risk of vascular disease at a young age, can be calculated in subjects with an abnormal response to methionine loading. Furthermore, mild hyperhomo-cysteinaemia can lead to a two- or three-fold increase in the risk of recurrent venous thrombosis. Elevated homocysteine levels can be reduced to normal in virtually all cases by simple and safe treatment with vitamin B6, folic acid, and betaine, each of which is involved in methionine metabolism. A clinically beneficial effect of such an intervention, currently under investigation, would make large-scale screening for this risk factor mandatory.



Dietary methionine imbalance, endothelial cell dysfunction and atherosclerosis

Nutrition Research (USA), 1996, 16/7 (1251-1266)

Dietary factors can play a crucial role in the development of atherosclerosis. High fat, high calorie diets are well known risk factors for this disease. In addition, there is strong evidence that dietary animal proteins also can contribute to the development of atherosclerosis. Atherogenic effects of animal proteins are related, at least in part, to high levels of methionine in these proteins. An excess of dietary methionine may induce atherosclerosis by increasing plasma lipid levels and/or by contributing to endothelial cell injury or dysfunction. In addition, methionine imbalance elevates plasma/tissue homocysteine which may induce oxidative stress and injury to endothelial cells. Methionine and homocysteine metabolism is regulated by the cellular content of vitamins B6, B12, riboflavin and folic acid. Therefore, deficiencies of these vitamins may significantly influence methionine and homocysteine levels and their effects on the development of atherosclerosis.



Hyperhomocysteinemia and venous thromboembolic disease.

Haematologica (ITALY) Mar-Apr 1997, 82 (2) p211-9

BACKGROUND AND OBJECTIVE: In spite of the large number of reports showing that hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis and arterial occlusive disease, this metabolite of the methionine pathway is measured in relatively few laboratories and its importance is not fully appreciated. Recent data strongly suggest that mild HHcy is also involved in the pathogenesis of venous thromboembolic disease. The aim of this paper is to analyze the most recent advances in this field. EVIDENCE AND INFORMATION SOURCES: The material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. In addition the authors of the present article have been working in the field of mild HHcy as cause of venous thromboembolic disease. STATE OF ART AND PERSPECTIVES: The studies examined provide very strong evidence supporting the role of moderate HHcy in the development of premature and/or recurrent venous thromboembolic disease. High plasma homocysteine levels are also a risk factor for deep vein thrombosis in the general population. Folic acid fortification of food has been proposed as a major tool for reducing coronary artery disease mortality in the United States. Vitamin supplementation may also reduce recurrence of venous thromboembolic disease in patients with HHcy. At the present time, however, the clinical efficacy of this approach has not been tested. In addition, the bulk of evidence indicates that fasting total homocysteine determinations can identify up to 50% of the total population of hyperhomocysteinemic subjects. Patients with isolated methionine intolerance may benefit from vitamin B6 supplementation. Homocysteine-lowering vascular disease prevention trials are urgently needed. Such controlled studies, however, should not focus exclusively on fasting homocysteine determinations and folic acid monotherapy. (127 Refs.)



Homocysteine: an important risk factor for atherosclerotic vascular disease.

Curr Opin Lipidol (UNITED STATES) Feb 1997, 8 (1) p28-34

Homocysteine is an intermediate compound formed during metabolism of methionine. The results of many recent studies have indicated that elevated plasma levels of homocyst(e)ine are associated with increased risk of coronary atherosclerosis, cerebrovascular disease, peripheral vascular disease, and thrombosis. The plasma level of homocyst(e)ine is dependent on genetically regulated levels of essential enzymes and the intake of folic acid, vitamin B6 (pyridoxine), and vitamin B12 (cobalamin). Impaired renal function, increased age, and pharmacologic agents (e.g. nitrous oxide, methotrexate) can contribute to increased levels of homocyst(e)ine. Plausible mechanisms by which homocyst(e)ine might contribute to atherogenesis include promotion of platelet activation and enhanced coagulability, increased smooth muscle cell proliferation, cytotoxicity, induction of endothelial dysfunction, and stimulation of LDL oxidation. Levels of homocysteine can be reduced with pharmacologic doses of folic acid, pyridoxine, vitamin B12, or betaine, but further research is required to determine the efficacy of this intervention in reducing morbidity and mortality associated with atherosclerotic vascular disease.



Gastrointestinal infections in children

CURR. OPIN. GASTROENTEROL. (United Kingdom), 1994, 10/1 (88-97)

Gastrointestinal infections are common and important in infants and young children, particularly where poor hygiene and living conditions allow the spread of infectious agents. With increasing information about microorganisms that cause these infections and improved methods to detect them, many episodes that were once undiagnosed can now be attributed to previously unrecognized viruses, bacteria, and other pathogens. These advances facilitate better management and will permit more effective control and preventive strategies. This review highlights some recent reports about enterovirulent classes of Escherichia coli, including E. coli O157:H7, which causes the hemolytic-uremic syndrome and hemorrhagic colitis; Campylobacter species and a new Campylobacter-like organism (Arcobacterbutzlerlli Helicobacter pylori; Aeromonas species; and rotavirus. Important new information about intestinal parasites, including Giardia and Cryptosporidium, has emerged that should prove of practical use in diagnosis and management in places where these parasites are prevalent in children, particularly in parts of the world where HIV infection has become established. A newly described organism, so far called coccidian-like or cyanobacterium-like body, has been found in patients with prolonged diarrhea (including travelers and expatriate residents) in several countries; the name Cyclospora cayetanensis has been proposed for this organism. This year's review concludes with a short commentary on some recent reports about risk factors that predispose children to gastrointestinal infections, eg, nutritional status, domestic hygiene, maternal hygiene behavior, and young children gathered in communal facilities like day care centers. Immune function status is also important, and deficiencies of single nutrients such as vitamin A, pyridoxine, folic acid, iron, and zinc may also play a role.



Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium

Journal of Rheumatology (Canada), 1996, 23/6 (990-994)

Objective. To determine nutrient intake of patients with active rheumatoid arthritis and compare it with the typical American diet (TAD) and the recommended dietary allowance (RDA). Methods. 41 patients with active RA recorded a detailed dietary history. Information collected was analyzed for nutrient intake of energy, fats, protein, carbohydrate, vitamins and minerals, which were then statistically compared with the TAD and the RDA. Results. Both men and women ingested significantly less energy from carbohydrates (women 47.4% (6.4) vs 55% RDA, p = 0.0001; men = 48.9% (7.4), p = 0.025) and more energy from fat (women = 36.8% (4.5) vs 30% RDA. p = 0.001 and men = 35.2% (5.9) p = 0.02). Women ingested significantly more saturated and mono-unsaturated fat than the RDA (p = 0.02 and p = 0.04 respectively) while men ingested significantly less polyunsaturated fat (PUFA)(p = 0.0001). Both groups took in less fiber (p = 0.0001). Deficient dietary intake of pyridoxine was observed vs the RDA for both sexes (men and women p = 0.0001). Deficient folate intake was seen vs the TAD for men (p = 0.02) with a deficient trend in women (p = 0.06). Zinc and magnesium intake was deficient vs the RDA in both sexes (p values less than or equal to 0.001) and copper was deficient vs the TAD in both sexes (p = 0.004 women and p = 0.02 men). Conclusion. Patients with RA ingest too much total fat and too little PUFA and fiber. Their diets are deficient in pyridoxine, zinc and magnesium vs the RDA and copper and folate vs the TAD. These observations, also documented in previous studies, suggest that routine dietary supplementation with multivitamins and trace elements is appropriate in this population.



New developments in pediatric psychopharmacology.

J Dev Behav Pediatr (UNITED STATES) Sep 1983, 4 (3) p202-9

This is a report on recent developments in pediatric psychopharmacology: new drugs and new applications for established drugs. The drugs reviewed include imipramine, amitryptiline, lithium, piracetam, propranolol, tryptophan, clonidine, pyridoxine and fenfluramine. Putative indications include prepubertal depression, school phobia, anorexia nervosa, explosive-aggressive behavior, learning disabilities, attention deficit disorder (hyperactivity), Tourette's syndrome, autism, and the Lesch-Nyhan syndrome. Some of the information presented in this report must be regarded as "preliminary," and caution is advised in its interpretation and application. (94 Refs.)



Homocysteine, folate, and vascular disease

Journal of Myocardial Ischemia (USA), 1996, 8/2 (60-63)

Current evidence indicates that the genesis of atherosclerotic disease is multifactorial. One of the newly recognized factors that contributes to this process is raised homocysteine blood levels. A variety of atherosclerotic procd by elevated homocysteine levels, including stimulation of smooth muscle cell growth, impairment of endothelial regeneration, oxidation of LDL particles, and thrombogenesis. A generic defect may account for some instances of hyperhomocysteinemia, but the majority of persons with high levels do not have known genetic defects to account for their elevations. Low levels of folic acid, vitamin B12, and pyridoxine appear to underlie most cases of elevated homocysteine levels. Adding folic acid to the diet may reduce homocysteine levels, but a link between increasing folic acid and lower risk of atherosclerotic disease has yet to be demonstrated in clinical trials. However, increasing daily folic acid intake is not unjustified in some patients. Since this may mask B12 deficiency, a supplement of cobalamin, 1 mg/d, has been proposed. In the final analysis, a clinical trial is needed to determine the true significance of hyperhomocysteinemia. Meanwhile, physicians and patients can consider increasing the daily folate intake by eating more oranges, leafy vegetables, wheat products, and cereals.



[Homocysteine, a risk factor of atherosclerosis]

Arch Mal Coeur Vaiss (FRANCE) Dec 1996, 89 (12) p1667-71

Homocysteine is a sulphurated amino acid which, at high plasma concentrations, predisposes to thrombosis and induces focal arteriosclerosis. These characteristics have been established both in patients with homocystinuria, a genetic disease in which homocysteine accumulates in the blood, and in animals submitted to intravenous infusions of this amino acid. Many recent publications have addressed the problem of whether mild increases in plasma homocysteine predisposed to the development of the usual forms of atherosclerosis. Transverse epidemiological studies have established a correlation between homocysteine levels and atherosclerosis at all its vascular localisations, coronary, carotid and lower limb. Multivariate analysis in several prospective studies have shown plasma homocysteine to be an independent risk factor for cerebrovascular accidents and myocardial infarction. Causes of mild increases in plasma homocysteine are usually dietetic deficiencies in folic acid, vitamin B6 or B12, or genetic by mutation of the methylene-tetrahydrofolate reductase. Renal failure is also associated with a high risk in plasma homocysteine levels. However, the toxicity of homocysteine to the arterial wall at slightly elevated concentration remains speculative.



[Hyperhomocysteinemia]

Cas Lek Cesk (CZECH REPUBLIC) May 2 1996, 135 (9) p266-9

Similarly as in other inborn metabolic diseases the cause of hyperhomocysteinaemia are interactions between genetically conditioned changes most frequently due to reduced cystathionine-beta synthase activities and negative factors of the external environment. Negative environmental factors include above all a high dietary animal protein consumption which is the main methionine donor and a low intake of protein of plant origin. Another negative factor is a low intake of foods of plant origin. Fruits and vegetables are among others important sources of folic acid and pyridoxine. Substitution therapy with vitamin preparations is essential in homozygotes and in high risk heterozygotes of cystathionine beta-synthase. This treatment is also necessary during the periconception period in hyperhomocysteinaemic fertile women to reduce the risk of neurotubal defects in their future children. So far investigations are lacking which would provide evidence of a reduced risk of ischaemic heart disease and other cardiovascular diseases in isolated treatment of mildly elevated levels of plasma homocysteine. To elucidate the part played by hyperhomocysteinaemia in hastening of the atherogenetic process further studies are essential, focused on the interaction of elevated homocysteine plasma levels, dyslipoproteinaemias, hyperfibrinogenaemia and other metabolic indicators in this process. (31 Refs.)



[Homocysteine, a less well-known risk factor in cardiac and vascular diseases]

Cas Lek Cesk (CZECH REPUBLIC) May 2 1996, 135 (9) p263-5

Hyperhomocyst(e)mia (Hcy) negatively influences vascular endothelium and coagulation factors. Association of Hcy with premature arteriosclerosis (rather than atherosclerosis), stroke, myocardial infarction and peripheral arterial and venous disease was proved in clinical and epidemiological studies, even as the association with conventional risk factors like age, male sex, smoking, hypertension and hypercholesterolemia. Vitamin substitution of folates, vitamin B6 and B12 decreases Hcy blood levels, however definite evidence is still lacking, whether it results in lower incidence and mortality from cardiovascular diseases. Therefore clinical and epidemiological studies are necessary. Before the grant-application we proved in a pilot study significantly higher Hcy levels in 97 patients with manifest ischaemic heart disease than in 37 controls.



Homocysteine and coronary atherosclerosis.

J Am Coll Cardiol (UNITED STATES) Mar 1 1996, 27 (3) p517-27

Homocysteine is increasingly recognized as a risk factor for coronary artery disease. An understanding of its metabolism and of the importance of vitamins B6 and B12 and folate as well as enzyme levels in its regulation will aid the development of therapeutic strategies that, by lowering circulating concentrations, may also lower risk. Possible mechanisms by which elevated homocysteine levels lead to the development and progression of vascular disease include effects on platelets, clotting factors and endothelium. This review presents the clinical and basic scientific evidence supporting the risk and mechanisms of vascular disease associated with elevated homocysteine concentrations as well as the results of preliminary therapeutic trials.



Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease.

Eur J Clin Invest (ENGLAND) Mar 1995, 25 (3) p176-81

Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (< or = 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin ?, and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL-1) levels were above normal. At follow-up, vWF levels had decreased to 170% (P = 0.01) and TM levels had decreased to 49 ng mL- 1 (P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.



Thiamine pyrophosphate and pyridoxamine inhibit the formation of antigenic advanced glycation end-products: comparison with aminoguanidine.

Biochem Biophys Res Commun (UNITED STATES) Mar 7 1996, 220 (1) p113-9

Nonenzymatic glycation of proteins by glucose leading to the formation of toxic and immunogenic advanced glycation end products (AGEs) may be a major contributor to the pathological manifestations of diabetes mellitus, aging, and, possibly, neurodegenerative diseases such as Alzheimer's. We tested the in vitro inhibition of antigenic AGE formation on bovine serum albumin, ribonuclease A, and human hemoglobin by various vitamin B1 and B6 derivatives. Among the inhibitors, pyridoxamine and thiamine pyrophosphate potently inhibited AGE formation and were more effective than aminoguanidine, suggesting that these two compounds may have novel therapeutic potential in preventing vascular complications of diabetes. An unexpected finding was that aminoguanidine inhibited the late kinetic stages of glycation much more weakly than the early phase.



Rationales for micronutrient supplementation in diabetes.

Med Hypotheses (ENGLAND) Feb 1984, 13 (2) p139-51

Available evidence--some well-documented, some only preliminary--suggests that properly-designed nutritional insurance supplementation may have particular value in diabetes. Comprehensive micronutrient supplementation providing ample doses of antioxidants, yeast-chromium, magnesium, zinc, pyridoxine, gamma-linolenic acid, and carnitine, may aid glucose tolerance, stimulate immune defenses, and promote wound healing, while reducing the risk and severity of some of the secondary complications of diabetes. (125 Refs.)



Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy

Biochemical and Biophysical Research Communications (USA), 1996, 224/2 (358-361)

In the human, coenzyme Q10(vitamin Q10) is biosynthesized from tyrosine through a cascade of eight aromatic precursors. These precursors indispensably require eight vitamins, which are tetrahydrobiopterin, vitamins B6, C, B2, B12, folic acid, niacin, and pantothenic acid as their coenzymes. Three of these eight vitamins (the coenzyme B6 and the coenzymes niacin and folic acid) are indispensable in the biosynthesis of the four bases (thymidine, guanine, adenine, and cytosine) of DNA. One or more of the three vitamins required for DNA are known to cause abnormal pairing of the four bases, which can then result in mutations and the diversity of cancer. The coenzyme B6 required for the conversion of tyrosine to p-hydroxybenzoic acid, is the first coenzyme required in the cascade of precursors. A deficiency of the coenzyme B6 can cause dysfunctions, prior to the formation of vitamin Q10 to DNA. Former data on blood levels of Q10 and new data herein on blood levels of B6, measured as EDTA, in cancer patients established deficiencies of Q10 and B6 in cancer. This complete biochemistry relating to biosyntheses of Q10 and the DNA bases is a rationale for the therapy of cancer with Q10 and other entities in this biochemistry.



Adenosine-N6-diethylthioether-N1-pyridoximine 5'-phosphate. A novel marker for human cancer detection

Anticancer Research (Greece), 1996, 16/4 B (2201-2204)

The Schiff base conjugate of vitamin B6 with adenosine-N6-diethylthioether was originally, reported as unknown compound B6X and considered to function as a storage form for vitamin B6 utilization by tumor cells. This novel compound is present in tumor cells in culture, the blood of normal and tumor-bearing animals, and the circulation of healthy individuals and patients with various ailments including malignancies. However, its level in the blood of cancer patients is significantly much greater -a desirable feature for cancer detection. Using HPLC pair-ion, reverse phase chromatography blood samples from patients with various malignancies and ailments were screened on a blind basis for the novel compound following its extraction at pH 4.2 (1,4,5,6). The results show that the level of the vitamin B6 metabolite in the blood of cancer patients is up to 4x or higher than levels seen in the blood of normal volunteers, patients in remission or patients with other diseases. In addition, patients receiving treatment had lower levels than before treatment. Normal volunteers, cancer patients prior to treatment, cancer patients on therapy. cancer patients at remission and patients with other ailments had levels of 162.2; 601.7; 497.9; 216.5 and 179.3 (SEM range plus or minus 18.76 - 46.60), respectively. A comparison of the control, remission and other ailments groups with the cancer patient groups shows them to be significantly different (P < 0.00001) and strongly support the use of the novel vitamin B6 conjugate metabolite for detection of human cancers.



Vitamin B6 and cancer: Synthesis and occurrence of adenosine-N6-diethylthioether- N-pyridoximine-5'-phosphate, a circulating human tumor marker

Cancer Research (USA), 1996, 56/16 (3670-3677)

In the course of studies aimed at deciphering the metabolic transformations of (3,4-14C) and (3H)C6-pyridoxine hydrochloride by tumor-beariesis of a novel labeled product was observed. Its production began with the onset of tumor growth and increased as cell proliferation increased. Chemical, enzymatic, precursor labeling, and analytical tests on the isolated product indicated this product as adenosine-N6-diethylthioether-N-pyridoximine- 5'-phosphate (compound 1). In confirmation, the chemical synthesis and characterization of compound 1 are presented in this study. In addition, blood samples from 28 normal subjects, 28 cancer patients with different malignancies, and 39 patients with a variety of other than cancer ailments were screened for compound 1 on a blind basis using reverse phase ion-paired high-performance liquid chromatography. The results show that the level of the vitamin B6 conjugate in the circulation of control subjects, cancer patients in remission, and patients with other diseases was only minimal. Cancer patients with active disease had 3-4-fold higher levels (P < 0.00001). Our results also confirm previous findings regarding the structure of compound 1 and show its potential value as a circulating human tumor marker that could be successfully used for cancer detection.

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