Ames BN, Elson-Schwab I, Silver EA. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K (m)): relevance to genetic disease and polymorphisms. Am J Clin Nutr. 2002 Apr;75(4):616-58.
Amminger GP, Berger GE, Schafer MR, Klier C, Friedrich MH, Feucht M. Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study. Biol Psychiatry. 2006 Aug 22; [Epub ahead of print].
Department of Molecular and Cellular Biology, University of California, Berkeley, USA. [email protected]
As many as one-third of mutations in a gene result in the corresponding enzyme having an increased Michaelis constant, or K(m), (decreased binding affinity) for a coenzyme, resulting in a lower rate of reaction. About 50 human genetic dis-eases due to defective enzymes can be remedied or ameliorated by the administration of high doses of the vitamin component of the corresponding coenzyme, which at least partially restores enzymatic activity. Several single-nucleotide polymorphisms, in which the variant amino acid reduces coenzyme binding and thus enzymatic activity, are likely to be remediable by raising cellular concentrations of the cofactor through high-dose vitamin therapy. Some examples include the alanine-to-valine substitution at codon 222 (Ala222-->Val) [DNA: C-to-T substitution at nucleo-tide 677 (677C-->T)] in methylenetetrahydrofolate reductase (NADPH) and the cofactor FAD (in relation to cardiovascular disease, migraines, and rages), the Pro187-->Ser (DNA: 609C-->T) mutation in NAD(P):quinone oxidoreductase 1 [NAD(P)H dehy-drogenase (quinone)] and FAD (in relation to cancer), the Ala44-->Gly (DNA: 131C-->G) mutation in glucose-6-phosphate 1-dehydrogenase and NADP (in relation to favism and hemolytic anemia), and the Glu487-->Lys mutation (present in one-half of Asians) in aldehyde dehydrogenase (NAD + ) and NAD (in relation to alcohol intolerance, Alzheimer disease, and cancer).
PMID: 11916749 [PubMed - indexed for MEDLINE]
Arnold GL, Hyman SL, Mooney RA, Kirby RS. Plasma amino acids profiles in children with autism: potential risk of nutritional deficiencies. J Autism Dev Disord. 2003 Aug;33(4):449-54.
Department of Pediatrics, University of Rochester Medical Center, Rochester, New York 14642, USA. [email protected]
The plasma amino acid profiles of 36 children with autism spectrum disorders were reviewed to determine the impact of diet on amino acid patterns. Ten of the children were on gluten and casein restricted diets administered by parents, while the other 26 consumed unrestricted diets. No amino acid profile specific to autism was identified. However, children with autism had more essential amino acid deficiencies consistent with poor protein nutrition than an age/gender matched control group. There was a trend for children with autism who were on restricted diets to have an increased prevalence of essential amino acid deficiencies and lower plasma levels of essential acids including the neurotransmitter precursors tyrosine and tryptophan than both controls and children with autism on unrestricted diets. These data indicate that larger, more focused studies of protein nutrition in children with autism are needed in order to determine the extent to which restricted diets might place the developing brains of children with autism at risk from protein malnutrition. The high rate of tryptophan and tyrosine deficiency in this group is also of concern given their role as neurotransmitter precursors.
PMID: 12959424 [PubMed - indexed for MEDLINE]
Baker SB, Worthley LI. The essentials of calcium, magnesium and phosphate metabolism: part I. Physiology. Crit Care Resusc. 2002 Dec;4(4):301-6.
Department of Critical Care Medicine, Flinders University of South Australia, Adelaide, South Australia. PART I
OBJECTIVE: To review the components of calcium, phosphate and magnesium metabolism that are relevant to the critically ill patient in a two-part presentation. DATA SOURCES: A review of articles reported on calcium, phosphate and magnesium disorders in the critically ill patient. SUMMARY OF REVIEW: Calcium, phosphate and magnesium have important intracellular and extracellular functions with their metabolism often linked through common hormonal signals. A predominant portion of total body calcium is unionised within bone and serves an important structural function. Intracellular and extracellular ionised calcium changes are often linked and have important secretory and excitatory roles. The extracellular ionised calcium is carefully regulated by parathyroid hormone and vitamin D, whereas calcitonin is secreted largely in response to hypercalcaemia. Phosphorous is needed for bone structure although it also has an important role in cell wall structure, energy storage as ATP, oxygen transport and acid-base balance. Ionised calcium, in as far as it controls PTH secretion, indirectly controls urinary phosphate excretion. When plasma phosphate increases, tubular reabsorption also increases up to a maximum (TmPO4), thereafter phosphate is excreted. The minimum oral requirement for phosphate is about 20 mmol/day. Magnesium is a predominantly intracellular ion that acts as a metallo-coenzyme in more than 300 phosphate transfer reactions and thus has a critical role in the transfer, storage and utilisation of energy within the body. Extracellular magnesium concentrations are largely controlled by the kidneys with the renal tubular maximum reabsorption (TmMg) controlling the plasma magnesium concentration. CONCLUSIONS: In the critically ill patient calcium, magnesium and phosphate metabolism, are often disturbed with an alteration in intake, increased liberation from bone and damaged tissue and reduced excretion (e.g. during renal failure), causing alterations in extracellular concentrations and subsequent disordered organ function.
PMID: 16573443 [PubMed] PART II
Department of Critical Care Medicine, Flinders University of South Australia, Adelaide, South Australia.
OBJECTIVE: To review the components of calcium, phosphate and magnesium metabolism that are relevant to the critically ill patient, in a two-part presentation. DATA SOURCES: A review of articles reported on calcium, phosphate and magnesium disorders in the critically ill patient. SUMMARY OF REVIEW: Abnormal calcium metabolism in the critically ill patient often presents with an alteration in plasma ionised calcium. The characteristic clinical features of an acute reduction in ionised plasma calcium include tetany, laryngospasm, paraesthesia, confusion, hallucinations, seizures and, rarely, hypotension all of which resolve with intravenous calcium administration. The clinical features of an acute increase in plasma ionised calcium include anorexia, nausea, vomiting, constipation, polyuria, weakness, lethargy, hypotonia and ectopic calcification and, depending on the aetiology, may require intravenous saline, frusemide, diphosphonate, glucocorticoid or calcitonin. Acute hypophosphataemia may present with paraesthasia, confusion, seizures, weakness, hypotension and heart failure and in the critically ill requires intravenous sodium or potassium phosphate. Hyperphosphataemia is often associated with renal failure and if severe usually presents with the clinical features of the associated hypocalcaemia. The clinical features of hypomagnesaemia include confusion, delerium, seizures, weakness, cramps, tetany and tachyarrhythmias, all of which resolve with intravenous magnesium sulphate. Hypermagnesaemia is usually associated with excess magnesium administration in a patient with renal failure and if severe can cause areflexia, hypotonia, respiratory and cardiac arrest. Intravenous calcium chloride will rapidly reverse the cardiovascular abnormalities. CONCLUSIONS: Calcium, phosphate and magnesium functions are closely linked with abnormal plasma levels of these compounds often causing similar cardiovascular and neurological features.
PMID: 16573444 [PubMed]
Barthelemy C, Garreau B, Leddet I, Sauvage D, Domenech J, Muh JP, Lelord G. Biological and clinical effects of oral magnesium and associated magnesium-vitamin B6 administration on certain disorders observed in infantile autism. Therapie. 1980 Sep-Oct;35(5):627-32. [Article in French]
Bell JG, Sargent JR, Tocher DR, Dick JR. Red blood cell fatty acid compositions in a patient with autistic spectrum disorder: a characteristic abnormality in neurodevelopmental disorders? Prostaglandins Leukot Essent Fatty Acids. 2000 Jul-Aug;63(1-2):21-5.
Nutrition Group, Institute of Aquaculture, Stirling, UK. [email protected]
The fatty acid compositions of red blood cell (RBC) phospholipids from a patient with autistic spectrum disorder (ASD) had reduced percentages of highly unsaturated fatty acids (HUFA) compared to control samples. The percentage of HUFA in the RBC from the autistic patient was dramatically reduced (up to 70%) when the sample was stored for 6 weeks at -20 degrees C. However, only minor HUFA reductions were recorded in control samples stored similarly, or when the autistic sample was stored at -80 degrees C. A similar instability in RBC HUFA compositions upon storage at -20 degrees C has been recorded in schizophrenic patients. In a number of other neurodevelopmental conditions, including attention deficit hyperactivity disorder (ADHD) and dyslexia, reduced concentrations of RBC HUFA have been recorded. The extent and nature of these aberrations require further assessment to determine a possible common biochemical origin of neurodevelopmental disorders in general. To facilitate this, a large scale assessment of RBC fatty acid compositions in patients with ASD, and related disorders, should be performed as a matter of urgency. Supplementing cells in culture with the tryptophan metabolite indole acrylic acid (IAA) affected the levels of cellular HUFA and prostaglandin production. Indole acroyl glycine (IAG), a metabolite of IAA excreted in urine, is found in high concentrations in patients with neurodevelopmental disorders including ASD, ADHD, dyslexia, Asperger's syndrome and obsessive compulsive disorder. Copyright 2000 Harcourt Publishers Ltd.
PMID: 10970708 [PubMed - indexed for MEDLINE]
Boris M, Goldblatt A, Galanko J, James SJ. Association of MTHFR gene variants with autism. J Am Phys Surg. 2004: 9(4):106-108.
Bronner F. Extracellular and intracellular regulation of calcium homeostasis. ScientificWorldJournal. 2001 Dec 22;1:919-25.
Department of BioStructure and Function, University of Connecticut Health Center, Farmington, CT 06030-6125, USA. [email protected]
An organism with an internal skeleton must accumulate calcium while maintaining body fluids at a well-regulated, constant calcium concentration. Neither calcium absorption nor excretion plays a significant regulatory role. Instead, isoionic calcium uptake and release by bone surfaces causes plasma calcium to be well regulated. Very rapid shape changes of osteoblasts and osteoclasts, in response to hormonal signals, modulate the available bone surfaces so that plasma calcium can increase when more low-affinity bone calcium binding sites are made available and can decrease when more high-affinity binding sites are exposed. The intracellular free calcium concentration of body cells is also regulated, but because cells are bathed by fluids with vastly higher calcium concentration, their major regulatory mechanism is severe entry restriction. All cells have a calcium-sensing receptor that modulates cell function via its response to extracellular calcium. In duodenal cells, the apical calcium entry structure functions as both transporter and a vitamin D--responsive channel. The channel upregulates calcium entry, with intracellular transport mediated by the mobile, vitamin D-dependent buffer, calbindin D9K, which binds and transports more than 90% of the transcellular calcium flux. Fixed intracellular calcium binding sites can, like the body's skeleton, take up and release calcium that has entered the cell, but the principal regulatory tool of the cell is restricted entry.
PMID: 12805727 [PubMed - indexed for MEDLINE]
Bu B, Ashwood P, Harvey D, King IB, Water JV, Jin LW. Fatty acid compositions of red blood cell phospholipids in children with autism. Prostaglandins Leukot Essent Fatty Acids. 2006 Apr;74(4):215-21.
Department of Pathology, M.I.N.D. Institute, University of California at Davis, 2805 50th Street, Sacramento, CA 95817, USA.
We compared the compositions of fatty acids including n-3, n-6 polyunsaturated fatty acids, trans- and cis-monounsaturated fatty acids, and saturated fatty acids in the red blood cell membranes of 40 children with autism (20 with early onset autism and 20 with developmental regression) and age-matched, 20 typically developing controls and 20 subjects with non-autistic developmental disabilities. The main findings include increased levels of eicosenoic acid (20:1n9) and erucic acid (22:1n9) in autistic subjects with developmental regression when compared with typically developing controls. In addition, an increase in 20:2n6 and a decrease in 16:1n7t were observed in children with clinical regression compared to those with early onset autism. Our results do not provide strong evidence for the hypothesis that abnormal fatty acid metabolism plays a role in the pathogenesis of autism spectrum disorder, although they suggest some metabolic or dietary abnormalities in the regressive form of autism.
PMID: 16581239 [PubMed - indexed for MEDLINE]
Calingasan NY, Huang PL, Chun HS, Fabian A, Gibson GE. Vascular factors are critical in selective neuronal loss in an animal model of impaired oxidative metabolism. J Neuropathol Exp Neurol. 2000 Mar;59(3):207-17.
Weill Medical College of Cornell University at Burke Medical Research Institute, White Plains, New York 10605, USA.
Thiamine deficiency (TD) models the cellular and molecular mechanisms by which chronic oxidative deficits lead to death of select neurons in brain. Region- and cell-specific oxidative stress and vascular changes accompany the TD-induced neurodegeneration. The current studies analyzed the role of oxidative stress in initiating these events by testing the role of intercellular adhesion molecule-1 (ICAM-1) and endothelial nitric oxide synthase (eNOS) in the selective neuronal loss that begins in the submedial thalamic nucleus of mice. Oxidative stress to microvessels is known to induce eNOS and ICAM-1. TD increased ICAM-1 immunoreactivity in microvessels within the submedial nucleus and adjacent regions 1 day prior to the onset of neuronal loss. On subsequent days, the pattern of ICAM-1 induction overlapped that of neuronal loss, and of induction of the oxidative stress marker heme oxygenase-1 (HO-1). The intensity and extent of ICAM-1 and HO-1 induction progressively spread in parallel with the neuronal death in the thalamus. Targeted disruption of ICAM-1 or eNOS gene, but not the neuronal NOS gene, attenuated the TD-induced neurodegeneration and HO-1 induction. TD induced ICAM-1 in eNOS knockout mice, but did not induce eNOS in mice lacking ICAM-1. These results demonstrate that in TD, an ICAM-1-dependent pathway of eNOS induction leads to oxidative stress-mediated death of metabolically compromised neurons. Thus, TD provides a useful model to help elucidate the role of ICAM-1 and eNOS in the selective neuronal death in diseases in which oxidative stress is implicated.
PMID: 10744059 [PubMed - indexed for MEDLINE]
Chez MG, Buchanan CP, Aimonovitch MC, Becker M, Schaefer K, Black C, Komen J. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol. 2002 Nov;17(11):833-7.
Research Division, Autism and Epilepsy Specialty Services of Illinois, Ltd, Lake Bluff, IL 60044, USA. [email protected]
L-Carnosine, a dipeptide, can enhance frontal lobe function or be neuroprotective. It can also correlate with gamma-aminobutyric acid (GABA)-homocarnosine interaction, with possible anticonvulsive effects. We investigated 31 children with autistic spectrum disorders in an 8-week, double-blinded study to determine if 800 mg L-carnosine daily would result in observable changes versus placebo. Outcome measures were the Childhood Autism Rating Scale, the Gilliam Autism Rating Scale, the Expressive and Receptive One-Word Picture Vocabulary tests, and Clinical Global Impressions of Change. Children on placebo did not show statistically significant changes. After 8 weeks on L-carnosine, children showed statistically significant improvements on the Gilliam Autism Rating Scale (total score and the Behavior, Socialization, and Communication subscales) and the Receptive One-Word Picture Vocabulary test (all P < .05). Improved trends were noted on other outcome measures. Although the mechanism of action of L-carnosine is not well understood, it may enhance neurologic function, perhaps in the enterorhinal or temporal cortex.
PMID: 12585724 [PubMed - indexed for MEDLINE]
Chugani DC, Sundram BS, Behen M, Lee ML, Moore GJ. Evidence of altered energy metabolism in autistic children. Prog Neuropsychopharmacol Biol Psychiatry. 1999 May;23(4):635-41.
Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, USA. [email protected]
1. In this pilot study, the authors investigated the hypotheses there are increased concentrations of lactate in brain and plasma and reduced brain concentrations of N-acetyl-aspartate (NAA) in autistic children. 2. NAA and lactate levels in the frontal lobe, temporal lobe and the cerebellum of 9 autistic children were compared to 5 sibling controls using MRS. Plasma lactate levels were measured in 15 autistic children compared to 15 children with epilepsy. 3. Preliminary results show lower levels of NAA cerebellum in autistic children (p = 0.043). Lactate was detected in the frontal lobe in one autistic boy, but was not detected any of the other autistic subjects or siblings. 4. Plasma lactate levels were higher in the 15 autistic children compared to 15 children with epilepsy (p = 0.0003). 5. Higher plasma lactate in the autistic group is consistent with metabolic changes in some autistic children. The findings of altered brain NAA and lactate in autistic children suggest that MRS may be useful characterizing regional neurochemical and metabolic abnormalities in autistic children.
PMID: 10390722 [PubMed - indexed for MEDLINE]
Coleman M, Steinberg G, Tippett J, Bhagavan HN, Coursin DB, Gross M, Lewis C, DeVeau L. A preliminary study of the effect of pyridoxine administration in a subgroup of hyperkinetic children: a double-blind crossover comparison with methylphenidate. Biol Psychiatry. 1979 Oct;14(5):741-51.
A small sample of six patients with the putative "hyperkinetic syndrome" participated in a research protocol comparing administration of pyridoxine, methylphenidate, and placeboes. The children had had low whole blood serotonin levels and a history of previous responsiveness to methylphenidate. The results of the double-blind clinical evaluation showed trends suggesting that both pyridoxine and methylphenidate were more effective than placebo in suppressing the symptoms of hyperkinesis. Pyridoxine elevated whole-blood serotonin levels, methylphenidate did not. Clinical and laboratory evidence indicated that the pyridoxine effects persisted after the 3-week period when the vitamin had been given in this experimental design.
PMID: 497303 [PubMed - indexed for MEDLINE]
Deluca HF. The vitamin D system: a view from basic science to the clinic. Clin Biochem. 1981 Oct;14(5):213-22.
Vitamin D produced in the skin and absorbed in the small intestine must be modified metabolically before it can function. It is ultimately converted to a hormone in the kidney that stimulates intestine, bone and kidney to mobilize calcium and phosphorus. This results in normal bone development and normal neuromuscular function. The vitamin D hormone appears to act by a nuclear mechanism to facilitate a target organ response. Finally the vitamin D hormone is produced in response to the need for calcium and phosphorus. The calcium need is interpreted by the parathyroid gland that in turn secretes parathyroid hormone. The parathyroid hormone stimulates production of the vitamin D hormone. This constitutes the vitamin D endocrine system that plays an important role not only in calcium homeostasis but in phosphate homeostasis and in calcium economy of the body. A number of disease states including hypoparathyroidism, pseudohypoparathyroidism, renal osteodystrophy, certain types of vitamin D-resistant rickets and osteoporosis can in part be related to disturbance in the vitamin D endocrine system. Thus measurement of the vitamin D hormone and its precursor will be of great value in diagnosis of metabolic bone disease and most importantly, the availability of new vitamin D compounds will play an important role in the treatment of these bone diseases.
PMID: 7037225 [PubMed - indexed for MEDLINE]
Dhawan M, Kachru DN, Tandon SK. Influence of thiamine and ascorbic acid supplementation on the antidotal efficacy of thiol chelators in experimental lead intoxication. Arch Toxicol. 1988;62(4):301-4.
Industrial Toxicology Research Centre, Lucknow, India.
The influence of the administration of thiamine (vitamin B1), ascorbic acid (vitamin C) or their combination on the efficacy of two thiol metal chelators, viz. alpha-mercapto-beta-(2-furyl) acrylic acid (MFA) and 2,3-dimercaptosuccinic acid (DMS), in counteracting lead (Pb) toxicity was investigated in rats. Ascorbic acid or its combination with thiamine enhanced the urinary elimination of Pb, reduced the hepatic and renal burden of Pb, and reversed the Pb-induced inhibition of the activity of blood delta-aminolevulinic acid dehydratase (delta-ALA-D). All these effects were more evident in DMS- than in MFA-treated rats. The combination of MFA and DMS treatments further improved the performance of the animals in enhancing urinary Pb excretion and in reducing Pb hepatic levels.
PMID: 3240094 [PubMed - indexed for MEDLINE]
Dickinson VA, Block G, Russek-Cohen E. Supplement use, other dietary and demographic variables, and serum vitamin C in NHANES II. J Am Coll Nutr. 1994 Feb;13(1):22-32.
Nutritional Sciences Program, University of Maryland.
OBJECTIVE: Our objective was to evaluate the effect of regular use of nutritional supplements on serum vitamin C levels in a multivariable regression model, taking into account other dietary and demographic variables which may affect nutritional status. METHODS: We analyzed NHANES II data for subjects age 3 to 74. Analysis was limited to regular supplement users and nonusers, excluding irregular users. Multivariable regression analysis was performed with SUDAAN, incorporating sample weights and accounting for the complex survey design. RESULTS: Regular supplement users had substantially higher serum vitamin C levels than nonusers (p < 0.001). The magnitude of the effect of supplement use on serum vitamin C was 0.23-0.33 mg/dL in children and teens, and 0.36-0.46 mg/dL in adults. In adults who smoked, bottom quartile vitamin C levels were 0.3 mg/dL in men and 0.4 mg/dL in women who did not use supplements, compared to 0.9 and 1.1 mg/dL in regular supplement users. There was a significant interaction of smoking and supplement use in men (p < 0.001). CONCLUSION: Regular supplement use has a strong impact on serum vitamin C levels, independent of other dietary and demographic characteristics of supplement users which may favor improved nutritional status.
PMID: 8157850 [PubMed - indexed for MEDLINE]
Dolske MC, Spollen J, McKay S, Lancashire E, Tolbert L. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry. 1993 Sep;17(5):765-74.
Department of Psychiatry, University of Alabama at Birmingham.
1. This study presents the results of a 30-week double-blind, placebo-controlled trial exploring the effectiveness of ascorbic acid (8g/70kg/day) as a supplemental pharmacological treatment for autistic children in residential treatment. 2. Residential school children (N = 18) were randomly assigned to either ascorbate-ascorbate-placebo treatment order group or ascorbate-placebo-ascorbate treatment order group. Each treatment phase lasted 10 weeks and behaviors were rated weekly using the Ritvo-Freeman scale. 3. Significant group by phase interactions were found for total scores and also sensory motor scores indicating a reduction in symptom severity associated with the ascorbic acid treatment. 4. These results were consistent with a hypothesized dopaminergic mechanism of action of ascorbic acid.
PMID: 8255984 [PubMed - indexed for MEDLINE]
Fernstrom JD. Can nutrient supplements modify brain function? Am J Clin Nutr. 2000 Jun;71(6 Suppl):1669S-75S.
University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA. [email protected]
Over the past 40 y, several lines of investigation have shown that the chemistry and function of both the developing and the mature brain are influenced by diet. Examples are the effect of folate deficiency on neural tube development during early gestation, the influence of essential fatty acid deficiency during gestation and postnatal life on the development of visual function in infants, and the effects of tryptophan or tyrosine intake (alone or as a constituent of dietary protein) on the production of the brain neurotransmitters derived from them (serotonin and the catecholamines, respectively). Sometimes the functional effects are clear and the underlying biochemical mechanisms are not (as with folate and essential fatty acids); in other cases (such as the amino acids tyrosine and tryptophan), the biochemical effects are well understood, whereas the effect on brain function is not. Despite the incomplete knowledge base on the effects of such nutrients, investigators, physicians, and regulatory bodies have promoted the use of these nutrients in the treatment of disease. Typically, these nutrients have been given in doses above those believed to be required for normal health; after they have been given in pure form, unanticipated adverse effects have occasionally occurred. If this pharmacologic practice is to continue, it is important from a public safety standpoint that each nutrient be examined for potential toxicities so that appropriate purity standards can be developed and the risks weighed against the benefits when considering their use.
PMID: 10837313 [PubMed - indexed for MEDLINE]
Filipek PA, Juranek J, Nguyen MT, Cummings C, Gargus JJ. Relative carnitine deficiency in autism. J Autism Dev Disord. 2004 Dec;34(6):615-23.
Department of Pediatrics, College of Medicine, University of California, Irvine, CA, USA. [email protected]
A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine (p < 0.001), and pyruvate (p = 0.006) were significantly reduced while ammonia and alanine levels were considerably elevated (p < 0.001) in our autistic subjects. The relative carnitine deficiency in these patients, accompanied by slight elevations in lactate and significant elevations in alanine and ammonia levels, is suggestive of mild mitochondrial dysfunction. It is hypothesized that a mitochondrial defect may be the origin of the carnitine deficiency in these autistic children.
PMID: 15679182 [PubMed - indexed for MEDLINE]
Friedman SD, Shaw DW, Artru AA, Richards TL, Gardner J, Dawson G, Posse S, Dager SR. Regional brain chemical alterations in young children with autism spectrum disorder. Neurology. 2003 Jan 14;60(1):100-7.
Department of Radiology, University of Washington School of Medicine, Seattle 98105-6099, USA.
OBJECTIVE: The authors evaluated regional brain chemistry for evidence of increased neuronal packing density in autism. METHODS: Forty-five 3- to 4-year-old children with autism spectrum disorder (ASD), 13 children with typical development (TD), and 15 children with delayed development (DD) were studied using dual-echo proton echoplanar spectroscopic imaging (32 x 32 matrix-1 cm(3) voxels) to measure brain chemical concentrations and relaxation times. Chemical quantification was corrected for tissue partial volume and relative measures of chemical relaxation (T(2r)) were calculated from the paired echoes. Measures from averaged and individual regions were compared using analysis of variance corrected for multiple comparisons. RESULTS: ASD subjects demonstrated reduced N-acetylaspartate (NAA) (-10%), creatine (Cre) (-8%), and myo-inositol (-13%) concentrations compared to TD controls and prolonged NAA T(2r) relative to TD (7%) and DD (9%) groups. Compared to DD subjects, children with ASD also demonstrated prolonged T(2r) for choline (10%) and Cre (9%). Regional analyses demonstrated subtle patterns of chemical alterations in ASD compared to the TD and DD groups. CONCLUSIONS: Brain chemical abnormalities are present in ASD at 3 to 4 years of age. However, the direction and widespread distribution of these abnormalities do not support hypothesis of diffuse increased neuronal packing density in ASD.
PMID: 12525726 [PubMed - indexed for MEDLINE]
Gaull GE. Taurine in pediatric nutrition: review and update. Pediatrics. 1989 Mar;83(3):433-42.
Department of Pediatrics, Northwestern University School of Medicine, Chicago.
Taurine was long considered an end product of the metabolism of the sulfur-containing amino acids, methionine and cyst(e)ine. Its only clearly recognized biochemical role had been as a substrate in the conjugation of bile acids. Taurine is found free in millimolar concentrations in animal tissues, particularly those that are excitable, rich in membranes, and generate oxidants. Various lines of evidence suggest one major nutritional role as protecting cell membranes by attenuating toxic substances and/or by acting as an osmoregulator. The totality of evidence suggests that taurine is nonessential in the rodent, it is an essential amino acid in the cat, and it is conditionally essential in man and monkey. Absence from the diet of a conditionally essential nutrient does not produce immediate deficiency disease but, in the long term, can cause problems. Taurine is now added to many infant formulas as a measure of prudence to provide improved nourishment with the same margin of safety for its newly identified physiologic functions as that found in human milk. Such supplementation can be justified by the finding of improved fat absorption in preterm infants and in children with cystic fibrosis, as well as by salutary effects on auditory brainstem-evoked responses in preterm infants. Experimental findings in animal models and in human cell models provide further justification for taurine supplementation of infant formulas.
PMID: 2645571 [PubMed - indexed for MEDLINE]
Geoghegan M, McAuley D, Eaton S, Powell-Tuck J. Selenium in critical illness. Curr Opin Crit Care. 2006 Apr;12(2):136-41.
Department of Adult and Paediatric Gastroenterology, St Bartholomew's and the Royal London Hospital School of Medicine and Dentistry, Queen Mary University of London, London, UK. [email protected]
PURPOSE OF REVIEW: Selenium is a trace element essential to human health. Critical illness is associated with the generation of oxygen free radicals resulting in a condition of oxidative stress. Supplementing critically ill patients with antioxidant nutrients may improve survival. Selenium levels can be low due to redistribution to high-priority organs and dilution associated with aggressive resuscitation of the patient. The purpose of this review is to investigate the benefit of selenium supplementation in critically ill patients. RECENT FINDINGS: Most of the selenium-supplementation trials were performed in relatively small patient populations presenting with trauma, sepsis, burns and adult respiratory distress syndrome. Widely varying doses of selenium of between 200 and 1000 microg were used, either alone or in combination with other antioxidants. Significant improvements have been demonstrated in length of hospital stay, rate of infection and need for haemodialysis in these patients. However, no trial has demonstrated a statistically significant improvement in mortality. Two recent meta-analyses suggest a trend towards reduced mortality with selenium supplementation. SUMMARY: Selenium, by supporting antioxidant function, may be associated with a reduction in mortality. To demonstrate this large, well-designed randomized trials are required.
PMID: 16543790 [PubMed - indexed for MEDLINE]
Goebel L, Driscoll H. Scurvy. www.emedicine.com. 7-15-05.
Grattan-Smith PJ, Wilcken B, Procopis PG, Wise GA. The neurological syndrome of infantile cobalamin deficiency: developmental regression and involuntary movements. Mov Disord. 1997 Jan;12(1):39-46.
Department of Paediatric Neurology, Westmead Hospital, Sydney, Australia.
Developmental regression is the presenting symptom of most infants with cobalamin (Vitamin B12) deficiency. We present a report of three infants with cobalamin deficiency in which the infants also developed a movement disorder. In each case the mother was a vegetarian and the infant was exclusively breast-fed. In two of the infants, a striking movement disorder consisting of a combination of tremor and myoclonus particularly involving face, tongue, and pharynx appeared 48 h after the initiation of treatment with intramuscular cobalamin. This was associated with marked changes in plasma amino acid levels. Paradoxically, the onset of the movement disorder coincided with overall neurological improvement. The third infant had a persistent focal tremor, which appeared before the commencement of treatment. The movements slowly abated during a 3-6 week period. The presence of a movement disorder in cobalamin deficiency has received less attention than other features, but in a mild form is probably common. It may offer an early clue to the diagnosis before the onset of profound neurological deterioration. The cause of the severe movement disorder that can appear after treatment is not known.
PMID: 8990052 [PubMed - indexed for MEDLINE]
Horvath K, Perman JA. Autistic disorder and gastrointestinal disease. Curr Opin Pediatr. 2002 Oct;14(5):583-7
Hunt C, Chakravorty NK, Annan G, Habibzadeh N, Schorah CJ. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam Nutr Res. 1994;64(3):212-9.
Food & Nutrition Department, Huddersfield University.
A randomised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections (bronchitis and bronchopneumonia). Patients were assessed clinically and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day, or placebo. This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection. Using a clinical scoring system based on major symptoms of the respiratory condition, patients supplemented with the vitamin fared significantly better than those on placebo. This was particularly the case for those commencing the trial most severely ill, many of whom had very low plasma and white cell vitamin C concentrations on admission. Various mechanisms by which vitamin C could assist this type of patient are discussed.
PMID: 7814237 [PubMed - indexed for MEDLINE]
Imura K, Okada A. Amino acid metabolism in pediatric patients. Nutrition. 1998 Jan;14(1):143-8.
Department of Pediatric Surgery, Osaka Medical Center and Research Institute for Maternal and Child Health, Japan.
As with energy requirements, protein requirements are relatively much greater in infants and decline progressively with age. Amino acid metabolism in pediatric patients is characterized by the following differences. The requirement for essential amino acids in neonates is larger than that in adults. Because of low activity of phenylalanine hydroxylase and cystathionase, hyperphenylalaninemia and hypermethioninemia tend to occur, whereas tyrosine and cysteine tend to be deficient. In addition to cysteine and tyrosine, histidine, lysine, arginine and taurine are considered as semiessential amino acids. Nowadays there are different kinds of amino acid formulas to satisfy these specific requirements, and most of these formulas are intended to normalize the plasma aminogram. However, the nutritional benefit of these formulas for growth and development is still not completely proven, and the pharmacological use for specific diseases is expected with some modification of these formulas.
PMID: 9437700 [PubMed - indexed for MEDLINE]
James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7.
Department of Pediatrics, University of Arkansas for Medical Sciences, and the Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA. [email protected]
BACKGROUND: Autism is a complex neurodevelopmental disorder that usually presents in early childhood and that is thought to be influenced by genetic and environmental factors. Although abnormal metabolism of methionine and homocysteine has been associated with other neurologic diseases, these pathways have not been evaluated in persons with autism. OBJECTIVE: The purpose of this study was to evaluate plasma concentrations of metabolites in the methionine transmethylation and transsulfuration pathways in children diagnosed with autism. DESIGN: Plasma concentrations of methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), adenosine, homocysteine, cystathionine, cysteine, and oxidized and reduced glutathione were measured in 20 children with autism and in 33 control children. On the basis of the abnormal metabolic profile, a targeted nutritional intervention trial with folinic acid, betaine, and methylcobalamin was initiated in a subset of the autistic children. RESULTS: Relative to the control children, the children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione. This metabolic profile is consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized glutathione) in children with autism. The intervention trial was effective in normalizing the metabolic imbalance in the autistic children. CONCLUSIONS: An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.
PMID: 15585776 [PubMed - indexed for MEDLINE]
Johnson S. Micronutrient accumulation and depletion in schizophrenia, epilepsy, autism and Parkinson's disease? Med Hypotheses. 2001 May;56(5):641-5.
Zinc has several crucial functions in brain development and maintenance: it binds to p53, preventing it from binding to supercoiled DNA and ensuring that p53 cause the expression of several paramount genes, such as the one that encodes for the type I receptors to pituitary adenine cylase-activator peptide (PACAP), which directs embryonic development of the brain cortex, adrenal glands, etc.; it is required for the production of CuZnSOD and Zn-thionein, which are essential to prevent oxidative damage; it is required for many proteins, some of them with Zn fingers, many of them essential enzymes for growth and homeostasis. For example, the synthesis of serotonin involves Zn enzymes and since serotonin is necessary for melatonin synthesis, a Zn deficiency may result in low levels of both hormones. Unfortunately, Zn levels tend to be low when there is excess Cu and Cd. Moreover, high estrogen levels tend to cause increased absorption of Cu and Cd, and smoking and eating food contaminated with Cd result in high levels of the latter. Furthermore, ethanol ingestion increases the elimination of Zn and Mg (which acts as a cofactor for CuZnSOD).Increased Cu levels may also be found in people with Wilson's disease, which is a rather rare disease. However, the heterozygote form (only one faulty copy of the chromosome) is not so rare. Therefore, the developing fetus of a pregnant women who is low in Zn and high in Cu may experience major difficulties in the early development of the brain, which may later manifest themselves as schizophrenia, autism or epilepsy. Similarly, a person who gradually accumulates Cu, will tend to experience a gradual depletion of Zn, with a corresponding increase in oxidative damage, eventually leading to Parkinson's disease. Also discussed are the crucial roles of histidine, histamine, vitamin D, essential fatty acids, vitamin E, peroxynitrate, etc. in the possible oxidative damage involved in these mental diseases. Copyright 2001 Harcourt Publishers Ltd.
PMID: 11388783 [PubMed - indexed for MEDLINE]
Johnston CS, Thompson LL. Vitamin C status of an outpatient population. J Am Coll Nutr. 1998, 17(4)366-370.
Department of Family Resources and Human Development, Arizona State University, Tempe 85287-2502, USA.
OBJECTIVE: To determined the prevalence of vitamin C deficiency (plasma vitamin C concentrations less than 11.4 mumol/L) and vitamin C depletion (plasma vitamin C concentrations from 11.4 to less than 28.4 mumol/L) in an outpatient population. SUBJECTS AND METHODS: A consecutive sample of patients presenting at a health maintenance organization laboratory for outpatient procedures was utilized. Plasma vitamin C concentrations were determined in 350 females and 144 males, aged 6 to 92 years (mean +/- SD: 46.7 +/- 18.7 years). RESULTS: The mean plasma vitamin C concentration for all subjects was 32.4 +/- 13.6 mumol/L. Mean plasma vitamin C did not vary by sex, race, or fasted state. Diabetics had a significantly lower mean plasma vitamin C concentration (25.6 +/- 10.8 mumol/L) compared to patients presenting for general check-up/gynecological exams (33.5 +/- 14.8 mumol/L) or pregnancy exams (32.4 +/- 9.7 mumol/L). Six percent of subjects had plasma vitamin C concentrations indicative of vitamin C deficiency (n = 31), and 30.4% of the sample were vitamin C depleted (n = 150). The prevalence of vitamin C deficiency or vitamin C depletion did not differ by race or visit category. CONCLUSIONS: Surprisingly high rates of vitamin C deficiency and vitamin C depletion were evident among generally healthy, middle class patients visiting a health care facility for routine health exams, gynecological exams, and pregnancy exams.
PMID: 9710847 [PubMed - indexed for MEDLINE]
Jonas C, Etienne T, Barthelemy C, Jouve J, Mariotte N. Clinical and biochemical value of Magnesium + vitamin B6 combination in the treatment of residual autism in adults. Therapie. 1984 Nov-Dec;39(6):661-9. Article in French
Kidd PM. Autism, an extreme challenge to integrative medicine. Part 2: medical management. Altern Med Rev. 2002 Dec;7(6):472-99.
Kleijnen J, Knipschild P. Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans. Biol Psychiatry. 1991 May 1;29(9):931-41.
Department of Epidemiology/Health Care Research, University of Limburg, The Netherlands.
Fifty-three controlled trials of the effects of niacin, vitamin B6, and multivitamins on mental functions are reviewed. The results are interpreted with emphasis on the methodological quality of the trials. It turns out that virtually all trials show serious short-comings: in the number of participants, the presentation of baseline characteristics and outcomes, and the description of changes in concomitant treatments. Only in autistic children are some positive results are found with very high dosages of vitamin B6 combined with magnesium, but further evidence is needed before more definitive conclusions can be drawn. For many other indications (hyperactive children, children with Down's syndrome, IQ changes in healthy schoolchildren, schizophrenia, psychological functions in healthy adults and geriatric patients) there is no adequate support from controlled trials in favor of vitamin supplementation.
PMID: 1828703 [PubMed - indexed for MEDLINE]
Kornreich L, Bron-Harlev E, Hoffmann C, Schwarz M, Konen O, Schoenfeld T, Straussberg R, Nahum E, Ibrahim AK, Eshel G, Horev G. Thiamine deficiency in infants: MR findings in the brain. Am J Neuroradiol. 2005 Aug;26(7):1668-74.
Department of Imaging, Schneider Children's Medical Center of Israel, Petah Tiqva.
BACKGROUND AND PURPOSE: Thiamine deficiency is extremely rare in infants in developed countries. To our knowledge, its MR findings in the brain have not been reported. The purpose of this study was to investigate the brain MR findings in infants with encephalopathy due to thiamine deficiency. METHODS: The study group included six infants aged 2-10 months with encephalopathy who had been fed with solely soy-based formula devoid of thiamine from birth. All underwent MR evaluation at admission and follow-up (total of 14 examinations). In one patient, MR spectroscopy (MRS) was performed. RESULTS: In five patients T2-weighted, fluid-attenuated inversion recovery, or proton-attenuated sequences showed bilateral and symmetric hyperintensity in the periaqueductal area, basal ganglia and thalami. Five had lesions in the mammillary bodies, and three, in the brain stem. In all six patients, the frontal region (cortex and white matter) was clearly involved. At presentation, MRS of the periaqueductal area showed a lactate doublet. On long-term follow-up, three of four patients had severe frontal damage; in two, this occurred as part of diffuse parenchymal loss, and in one, it was accompanied by atrophy of the basal ganglia and thalami. CONCLUSION: Thiamine deficiency in infants is characterized by involvement of the frontal lobes and basal ganglia, in addition to the lesions in the periaqueductal region, thalami, and the mammillary bodies described in adults. MRS demonstrates a characteristic lactate peak.
PMID: 16091511 [PubMed - indexed for MEDLINE]
Kozielec T, Starobrat-Hermelin B. Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD). Magnes Res. 1997 Jun;10(2):143-8.
Department of Family Medicine, Pomeranian Medical Academy, Szczecin, Poland.
A positive influence of magnesium in the prevention and treatment of hyperactivity in children is more and more frequently raised in the literature. The aim of our work was to estimate magnesium contents in children with attention deficit hyperactivity disorder, (ADHD). The investigations comprised 116 children (94 boys and 20 girls), aged 9-12 years, with recognized ADHD. In 68 out of 116 patients examined ADHD occurred with other coexisting disorders specific to the developmental age and in the remaining 48 patients it occurred together with disruptive behaviour. Magnesium levels have been determined in blood serum, red blood cells and in hair with the aid of atomic absorption spectroscopy. Magnesium deficiency was found in 95 per cent of those examined, most frequently in hair (77.6 per cent), in red blood cells (58.6 per cent) and in blood serum (33.6 per cent) of children with ADHD. The conclusion from the investigations is that magnesium deficiency in children with ADHD occurs more frequently than in healthy children. Analysis of the material indicated the correlation between levels of magnesium and the quotient of development to freedom from distractibility.
PMID: 9368235 [PubMed - indexed for MEDLINE]
Kushak R, Winter W, Farber N, Buie T. Gastrointestinal symptoms and intestinal disaccharidase activities in children with autism. J Pediatr Gastroenterol Nutr. 2005 Oct: 41(4):508.
Lelord G, Muh JP, Barthelemy C, Martineau J, Garreau B, Callaway E. Effects of pyridoxine and magnesium on autistic symptoms—initial observations. J Autism Dev Disord. 1981 Jun;11(2):219-30.
In an open trial, a heterogeneous group of 44 children with autistic symptoms were treated with large doses of vitamin B6 and magnesium. Clinical improvement with worsening on termination of the trial was observed in 15 children. Thirteen responders and 8 nonresponders were retested in a 2-week, crossover, double-blind trial, and the responses to the open trial were confirmed.
PMID: 6765503 [PubMed - indexed for MEDLINE]
Lelord G, Callaway E, Muh JP. Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children. Acta Vitaminol Enzymol. 1982;4(1-2):27-44.
In 1973 Rimland reported that some autistic children responded favorably to high doses of vitamin B6. Since this finding, different studies were performed to identify apparently B6 responsive subjects and to critically evaluate clinical and biological B6 responsiveness. Magnesium was included because large doses of B6 might increase irritability. 44 patients (mean age 9.3 years) were examined. All selected children had marked autistic symptoms. The children received a complete diagnostic work-up, including psychiatric, psychological, neurological and medical evaluation. Clinical data were scored using an estimate of global clinical state and numerical rating on a 18 item scale (Behavior Summarized Evaluation). In a first open trial 15 out of 44 children exhibited moderate clinical improvement with worsening on termination of the trial. Thirteen responders and 8 non responders were re-tested in a 2-week crossover, double-blind trial and the responses to the open trial were confirmed. Biochemical data analysis revealed that a significant decrease in urinary homovanillic acid (HVA) levels was observed during B6-Mg administration. During B6-Mg treatment, middle latency evoked potentials exhibited a significant increase of amplitude.
PMID: 7124567 [PubMed - indexed for MEDLINE]
Levy J. Immunonutrition: the pediatric experience. Nutrition. 1998 Jul-Aug;14(7-8):641-7.
Children's Digestive Health Center, Columbia University College of Physicians and Surgeons, New York, New York 10032-3784, USA.
The health benefits of specific nutrients in the diet are reviewed as they pertain to the pediatric population and its unique needs. Secretory immunoglobulins, lysozyme, interferon, and growth factors, among others, are known to confer immunological advantages to breast milk. Inhibition of bacterial pathogens, as well as permissive growth of a protective colonic ecoflora occur as a result of various cellular and biochemical mechanisms at play. The immunomodulatory properties of minerals such as iron, zinc, and selenium, are presented and the newly recognized protective role of vitamin A and its importance in developing countries and in conditions of compromised nutrition are discussed. The review also covers the role of arginine, glutamine, and nucleotides in adaptive responses of the developing gut and in pathologic states such as necrotizing enterocolitis, short bowel syndrome, and inflammatory bowel disease. Probiotics (specific microbial feeds with potential benefits to the host), and prebiotics (dietary components such as complex carbohydrates able to change the colonic microenvironment fostering colonization with non-enteropathogens) are areas of current interest because they offer alternatives for the management of the growing problem of multiple antibiotic resistance and overwhelming infections in the hospitalized patient.
PMID: 9684269 [PubMed - indexed for MEDLINE]
Li J, Lin JC, Wang H, Peterson JW, Furie BC, Furie B, Booth SL, Volpe JJ, Rosenberg PA. Novel role of vitamin K in preventing oxidative injury to developing oligodendrocytes and neurons. J Neuroscience. 2003 Jul: 23(13):5816-5826.
Department of Neurology, Division of Neuroscience, Children's Hospital, Boston, MA 02115, USA.
Oxidative stress is believed to be the cause of cell death in multiple disorders of the brain, including perinatal hypoxia/ischemia. Glutamate, cystine deprivation, homocysteic acid, and the glutathione synthesis inhibitor buthionine sulfoximine all cause oxidative injury to immature neurons and oligodendrocytes by depleting intracellular glutathione. Although vitamin K is not a classical antioxidant, we report here the novel finding that vitamin K1 and K2 (menaquinone-4) potently inhibit glutathione depletion-mediated oxidative cell death in primary cultures of oligodendrocyte precursors and immature fetal cortical neurons with EC50 values of 30 nm and 2 nm, respectively. The mechanism by which vitamin K blocks oxidative injury is independent of its only known biological function as a cofactor for gamma-glutamylcarboxylase, an enzyme responsible for posttranslational modification of specific proteins. Neither oligodendrocytes nor neurons possess significant vitamin K-dependent carboxylase or epoxidase activity. Furthermore, the vitamin K antagonists warfarin and dicoumarol and the direct carboxylase inhibitor 2-chloro-vitamin K1 have no effect on the protective function of vitamin K against oxidative injury. Vitamin K does not prevent the depletion of intracellular glutathione caused by cystine deprivation but completely blocks free radical accumulation and cell death. The protective and potent efficacy of this naturally occurring vitamin, with no established clinical side effects, suggests a potential therapeutic application in preventing oxidative damage to undifferentiated oligodendrocytes in perinatal hypoxic/ischemic brain injury.
PMID: 12843286 [PubMed - indexed for MEDLINE]
Liebscher DH, Liebscher DE. About the misdiagnosis of magnesium deficiency. J Am Coll Nutr. 2004 Dec;23(6):730S-1S.
Self-Help Organisation on Mineral Imbalances, Task Force Magnesium-Deficiency Tetany, Rummelsburger Str. 13, D-10315 Berlin, Germany. [email protected]
The experience of our self-help organisation shows that the reason patients with symptoms of magnesium (Mg) deficiency do not get Mg therapy is acceptance of an inappropriate lower limit of the reference values for serum Mg concentration. The commonly designated low limit of the normal range seems to have been selected from values obtained for symptomatic patients. It is below levels that exist in patients with marginal deficiencies that can predispose to development of pathologic findings, so that the prevalence and importance of this disease is insufficiently considered. The lower reference limit of the normal population is erroneously regarded as a diagnostic criterion that excludes Mg deficiency when the serum level is even slightly above the reference limit that only excludes normality at lower levels. It is a statistical error to use the confidence limits of the normal population as the exclusion limit for those with abnormal Mg status.
PMID: 15637222 [PubMed - indexed for MEDLINE]
Litov RE, Combs GF Jr. Selenium in pediatric nutrition. Pediatrics. 1991 Mar;87(3):339-51.
Mead Johnson Research Center, Bristol-Myers Squibb Company, Evansville, Indiana 47721-0001.
Se is an essential nutrient that provides antioxidant protection in concert with vitamin E. Several selenoproteins have been identified, but only one, SeGSHpx, has a known function, that of neutralizing toxic hydroperoxides. Plasma Se concentration, being responsive to changes in Se intake, is the most practical and widely used measure of nutritional Se status. The plasma Se concentrations of the majority of healthy infants and children fall within the range of 50 to 150 micrograms/L. Although SeGSHpx activity measures the metabolically functional form of Se, the lack of a standardized analytical method has limited its usefulness as an index of nutritional Se status. Se deficiency was first observed in animals, but it is now recognized to occur in humans. Two human diseases associated with severe nutritional Se deficiency have been reported from China: a juvenile cardiomyopathy named Keshan disease and a chondrodystrophy named Kaschin-Beck disease. Long-term TPN, which provides negligible amounts of intrinsic Se, has been demonstrated in some cases to result in biochemical and clinical impairment. Although there are no consistent signs and symptoms characteristic of TPN-associated Se deficiency in addition to the low blood selenium levels, some patients will experience leg muscle pain and altered serum transaminase and creatine kinase activities. These manifestation of Se deficiency usually take years to develop. Recent information about the amount of dietary Se needed to maximize plasma SeGSHpx activity in adult men has allowed for better estimates of the Se requirement for humans. Recommended daily dietary allowances published recently by the National Academy of Sciences have been revised for infants and children in this paper by making appropriate adjustments for the protein requirements of these age-groups. These recommended intakes for Se can generally be met by consuming adequate amounts of cereals, meat, eggs, dairy products, human milk, and infant formula, which are good sources of highly available Se and are of low risk of providing excess amounts of Se. Suboptimal Se intakes by pregnant women may predispose their infants to low Se status at birth, which in turn may affect the infants ability to maintain adequate Se status during the first few months of life. In those situations where protein intake is restricted, such as in phenylketonuria and maple syrup urine disease, Se-supplemented formulas should be used. The most critical situation for Se supplementation is in pediatric patients receiving long-term TPN therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
PMID: 2000274 [PubMed - indexed for MEDLINE]
Lonsdale D, Shamberger RJ, Audhya T. Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study. Neuro Endocrinol Lett. 2002 Aug;23(4):303-8.
Preventive Medicine Group, 24700 Center Ridge Road, Westlake, OH 44145, USA. [email protected]
OBJECTIVES: In a Pilot Study, the clinical and biochemical effects of thiamine tetrahydrofurfuryl disulfide (TTFD) on autistic spectrum children were investigated. SUBJECTS AND METHODS: Ten children were studied. Diagnosis was confirmed through the use of form E2, a computer assessed symptom score. For practical reasons, TTFD was administered twice daily for two months in the form of rectal suppositories, each containing 50 mg of TTFD. Symptomatic responses were determined through the use of the computer assessed Autism Treatment Evaluation Checklist (ATEC) forms. The erythrocyte transketolase (TKA) and thiamine pyrophosphate effect (TPPE), were measured at outset and on completion of the study to document intracellular thiamine deficiency. Urines from patients were examined at outset, after 30 days and after 60 days of treatment and the concentrations of SH-reactive metals, total protein, sulfate, sulfite, thiosulfate and thiocyanate were determined. The concentrations of metals in hair were also determined. RESULTS: At the beginning of the study thiamine deficiency was observed in 3 out of the 10 patients. Out of 10 patients, 6 had initial urine samples containing arsenic in greater concentration than healthy controls. Traces of mercury were seen in urines from all of these autistic children. Following administration of TTFD an increase in cadmium was seen in 2 children and in lead in one child. Nickel was increased in the urine of one patient during treatment. Sulfur metabolites in urine did not differ from those measured in healthy children. CONCLUSIONS: Thiamine tetrahydrofurfuryl disulfide appears to have a beneficial clinical effect on some autistic children, since 8 of the 10 children improved clinically. We obtained evidence of an association of this increasingly occurring disease with presence of urinary SH-reactive metals, arsenic in particular.
PMID: 12195231 [PubMed - indexed for MEDLINE]
Mahadik SP, Scheffer RE. Oxidative injury and potential use of antioxidants in schizophrenia. Prostaglandins Leukot Essent Fatty Acids. 1996 Aug;55(1-2):45-54.
Department of Psychiatry and Health Behavior, Medical College of Georgia, USA.
There is increasing evidence that oxidative injury contributes to pathophysiology of schizophrenia, indicated by the increased lipid peroxidation products in plasma and CSF, and altered levels of both enzymatic and non-enzymatic antioxidants in chronic and drug-naive first-episode schizophrenic patients. The increased plasma lipid peroxidation is also supported by concomitant lower levels of esterified polyunsaturated essential fatty acids of red blood cell plasma membrane phospholipids. Because membrane phospholipids play a critical role in neuronal signal transduction, oxidative damage of these lipids may contribute to the proposed altered neurotransmitter receptor-mediated signal transduction and thereby alter information processing in schizophrenia. Adjunctive treatment with antioxidants (e.g. vitamins E and C, beta-carotene and quinones) at the initial stages of illness may prevent further oxidative injury and thereby ameliorate and prevent further possible deterioration of associated neurological and behavioral deficits in schizophrenia.
PMID: 8888122 [PubMed - indexed for MEDLINE]
Martineau J, Barthelemy C, Garreau B, Lelord G. Vitamin B6, magnesium, and combined B6-Mg: therapeutic effects in childhood autism. Biol Psychiatry. 1985 May;20(5):467-78.
This article reports the behavioral, biochemical, and electrophysiological effects of four therapeutic crossed-sequential double-blind trials with 60 autistic children: Trial A--vitamin B6 plus magnesium/magnesium; Trial B--vitamin B6 plus magnesium; Trial C--magnesium; and Trial D--vitamin B6. Therapeutic effects were controlled using behavior rating scales, urinary excretion of homovanillic acid (HVA), and evoked potential (EP) recordings. The behavioral improvement observed with the combination vitamin B6-magnesium was associated with significant modifications of both biochemical and electrophysiological parameters: the urinary HVA excretion decreased, and EP amplitude and morphology seemed to be normalized. These changes were not observed when either vitamin B6 or magnesium was administered alone.
PMID: 3886023 [PubMed - indexed for MEDLINE]
Megson MN. Is autism a G-alpha protein defect reversible with natural vitamin A? Med Hypotheses. 2000 Jun;54(6):979-83.
Pediatric and Adolescent Ability Center, Richmond, VA 23226, USA.
Autism may be a disorder linked to the disruption of the G-alpha protein, affecting retinoid receptors in the brain. A study of 60 autistic children suggests that autism may be caused by inserting a G-alpha protein defect, the pertussis toxin found in the DPT vaccine, into genetically at-risk children. This toxin separates the G-alpha protein from retinoid receptors. Those most at risk report a family history of at least one parent with a pre-existing G-alpha protein defect, including night blindness, pseudohypoparathyroidism or adenoma of the thyroid or pituitary gland.Natural vitamin A may reconnect the retinoid receptors critical for vision, sensory perception, language processing and attention. Autism spectrum disorders have increased from 1 in 10 000 in 1978 to 1 in 300 in some US communities in 1999. Recent evidence indicates that autism is a disorder of the nervous system and the immune system, affecting multiple metabolic pathways.
PMID: 10867750 [PubMed
Moon J. The role of vitamin D in toxic metal absorption: a review. J Am Coll Nutr. 1994 Dec;13(6):559-64.
National College of Naturopathic Medicine, Portland Oregon 97216.
Vitamin D increases intestinal calcium and phosphate absorption. Not so well known, however, is that vitamin D stimulates the co-absorption of other essential minerals like magnesium, iron, and zinc; toxic metals including lead, cadmium, aluminum, and cobalt; and radioactive isotopes such as strontium and cesium. Vitamin D may contribute to the pathologies induced by toxic metals by increasing their absorption and retention. Reciprocally, lead, cadmium, aluminum, and strontium interfere with normal vitamin D metabolism by blocking renal synthesis of 1,25-dihydroxyvitamin D. This is the first review of the role of the vitamin D endocrine system in metal toxicology.
PMID: 7706586 [PubMed - indexed for MEDLINE]
Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A. Vitamin B12 and folate depletion in cognition: a review. Neurol India. 2004 Sep;52(3):310-8.
Dipartimento Fisiologia e Patologia, Università degli Studi, Trieste, Italy. [email protected]
In cross-sectional studies, low levels of folate and B12 have been shown to be associated with cognitive decline and dementia Evidence for the putative role of folate, vitamin B12 in neurocognitive and other neurological functions comes from reported cases of severe vitamin deficiencies, particularly pernicious anemia, and homozygous defects in genes that encode for enzymes of one-carbon metabolism. The neurological alterations seen in these cases allow for a biological role of vitamins in neurophysiology. Results are quite controversial and there is an open debate in literature, considering that the potential and differential role of folate and B12 vitamin in memory acquisition and cognitive development is not completely understood or accepted. What is not clear is the fact that vitamin B12 and folate deficiency deteriorate a pre-existing not overt pathological situation or can be dangerous even in normal subjects. Even more intriguing is the interaction between B12 and folate, and their role in developing hyperhomocysteinemia. The approach to the rehabilitation of the deficiency with adequate vitamin supplementation is very confusing. Some authors suggest it, even in chronic situations, others deny any possible role. Starting from these quite confusing perspectives, the aim of this review is to report and categorize the data obtained from the literature. Despite the plausible biochemical mechanism, further studies, based on clinical, neuropsychological, laboratory and (lastly) pathological features will be necessary to better understand this fascinating biochemical riddle.
PMID: 15472418 [PubMed - indexed for MEDLINE]
Mousain-Bosc M, Roche M, Polge A, Pradal-Prat D, Rapin J, Bali JP. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism. Magnes Res. 2006 Mar;19(1):53-62.
Explorations Fonctionnelles du Système Nerveux, Centre Hospitalier Universitaire Carémeau, Nîmes, France.
Previous studies reported positive results with the use of Mg-vitamin B6 in autism. Despite these reports, this intervention remains controversial. In order to study relationships between changes in clinical symtoms and biological parameters, 33 children (mean age: 4 [1-10] years old) with clinical symptoms of pervasive developmental disorder or autism (PDD, as defined in DSM-IV) were followed for at least 6 months; another group of 36 children (same age) devoided of any known pathology was used as control. All PDD children received a magnesium-vit B6 (Mg-B6) regimen (6 mg/kg/d Mg and 0.6 mg/kg/d vit B6). Intraerythrocyte Mg2+ (Erc-Mg), serum Mg2+ (s-Mg) and blood ionized Ca2+ (i-Ca) were measured before and after treatment. Clinical symptoms of PDD were scored (0 to 4). In contrast to s-Mg or i-Ca, PDD children exhibited significantly lower Erc-Mg values than controls (2.17 +/- 0.4 versus 2.73 +/- 0.23 mmol/L; 16/33). The Mg-B6 regimen led to an increase in Erc-Mg values (2.42 +/- 0.41 (after) versus 2.17 +/- 0.4 mmol/l (before), 11/17) and this supplementation improved PDD symptoms in 23/33 children (p < 0.0001) with no adverse effects: social interactions (23/33), communication (24/33), stereotyped restricted behavior (18/33), and abnormal/delayed functioning (17/33); 15/33 children were improved in the first three groups of symptoms. When the Mg-B6 treatment was stopped, PDD symtoms reappeared in few weeks. A statistically significant relationship was found in Erc-Mg values from children before treatment and their mothers. In conclusion, this study suggests that the behavioral improvement observed with the combination vitamin B6-magnesium in PDD/autism is associated with concomitant modifications of Erc-Mg values.
PMID: 16846101 [PubMed - indexed for MEDLINE]
Mousain-Bosc M, Roche M, Rapin J, Bali JP. Magnesium VitB6 intake reduces central nervous system hyperexcitability in children. J Am Coll Nutr. 2004 Oct;23(5):545S-548S.
Department of Pediatry, CHU Nimes, 30029 Nimes Cedex, France.
OBJECTIVE: Ionic magnesium (Mg(2+)) depletion has long been known to cause hyperexcitability with convulsive seizures in rodents, effects that have been reversed by treatment with magnesium (Mg). Metabolic disorders and genetic alterations are suspected in this pathology, in which Mg(2+) transport and intracellular distribution may be reduced without change in serum Mg(2+) concentrations. We evaluated the effects of Mg(2+)/vitamin B6 regimen on the behavior of 52 hyperexcitable children (under 15 years of age) and their families. METHODS: To assess intracellular Mg(2+), we measured intra-erthrocyte Mg(2+) levels (ERC-Mg). Our reference values for normal subjects were 2.46 to 2.72 mmol/L. In 30 of the 52 hyperactive children, there were low ERC-Mg values: 2.041 +/- 0.279 mmol/L). Combined Mg(2+)/vitamin B6 intake (100 mg/day) for 3 to 24 weeks restored normal ERC-Mg values (2.329 +/- 0.386 mmol/L). RESULTS: In all patients, symptoms of hyperexcitability (physical aggressivity, instability, scholar attention, hypertony, spasm, myoclony) were reduced after 1 to 6 months treatment. Other family members shared similar symptoms, had low ERC-Mg values, and also responded clinically to increased Mg(2+)/vitamin B6 intakes. Two typical families are described. CONCLUSION: This open study indicates that hyperexcitable children have low ERC-Mg with normal serum Mg(2+) values, and that Mg(2+)/vitamin B6 supplementation can restore normal ERC-Mg levels and improve their abnormal behavior.
PMID: 15466962 [PubMed - indexed for MEDLINE]
Ohsaki Y, Shirakawa H, Hiwatashi K, Furukawa Y, Mizutani T, Komai M. Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat. Biosci Biotechnol Biochem. 2006 Apr;70(4):926-32.
Laboratory of Nutrition, Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University , Sendai, Japan.
Vitamin K (K) is essential for blood coagulation and bone metabolism in mammals. K acts as a cofactor in the posttranslational synthesis of gamma-carboxyglutamic acid from glutamic acid residues. In addition to the liver and bone, K is found in the brain, heart, kidney and gonadal tissue. However, the physiological role of K in these various organs is not yet fully understood. It is likely that K has functions other than its role as a cofactor of protein gamma-glutamyl carboxylation. We used in this study the DNA microarray technique to identify the effect of K status on gene expression in the rat liver. The expression of genes involved in the acute inflammation response was enhanced in rats fed with a K-deficient diet relative to the control and K1-supplemented diet groups. Moreover, dietary supplementation with K1 suppressed the inflammation induced by lipopolysaccharide administration. These results indicate that orally administrated K1 suppressed inflammation in the rat.
PMID: 16636460 [PubMed - indexed for MEDLINE]
Olmez A, Yalcin S, Yurdakok K, Coskun T. Serum selenium levels in acute gastroenteritis of possible viral origin. J Trop Pediatr. 2004 Apr;50(2):78-81.
Hacettepe University, Ihsan Doğramaci Children's Hospital, Department of Pediatric Neurology, Ankara, Turkey. [email protected]
Selenium, as an essential micronutrient, is required for the proper functioning of the immune system and its deficiency affects the occurrence, virulence, or disease progression of some viral infections. We conducted a study to determine the serum selenium levels of children with acute gastroenteritis of possible viral origin and the effect of the serum selenium levels on the severity and the morbidity of the disease. The study was performed prospectively on 109 children aged 2-24 months with diarrhea of less than 8 days' duration admitted to the Diarrheal Disease Training and Treatment Unit. Blood samples were taken for selenium measurement on admission and 7-10 days after the end of the disease. Forty-three healthy children formed the control group. The mean serum selenium level on admission (62.41 +/- 13.06 microg/dl) was significantly lower than the mean of the second samples 7-10 days after the end of the diarrhea (81.73 +/- 17.10 microg/dl). The mean of the control group was 74.36 +/- 10.75 microg/dl, which was lower than the mean of the second samples but higher than the first sample. The frequency of vomiting and purging on admission and at the control visit, duration of diarrhea on admission, total duration of diarrhea, dehydration, breastfeeding, sex of the patients, and severity score of the disease did not alter the serum selenium levels. No correlation was detected between serum selenium levels and the parameters above. Further studies about the changes in selenium status during infectious diseases and the effect of selenium status on related mortality and morbidity are required to determine if there is need for supplementation.
PMID: 15088795 [PubMed - indexed for MEDLINE]
Pangborn J, Baker SM. Autism: Effective Biomedical Treatments (Have We Done Everything We Can For This Child? Individuality In An Epidemic). San Diego: Autism Research Institute; 2nd Edition Sept. 2005:232-235.
Pfeiffer CC, Braverman ER. Zinc, the brain and behavior. Biol Psychiatry. 1982 Apr;17(4):513-32.
The total content of zinc in the adult human body averages almost 2 g. This is approximately half the total iron content and 10 to 15 times the total body copper. In the brain, zinc is with iron, the most concentrated metal. The highest levels of zinc are found in the hippocampus in synaptic vesicles, boutons, and mossy fibers. Zinc is also found in large concentrations in the choroid layer of the retina which is an extension of the brain. Zinc plays an important role in axonal and synaptic transmission and is necessary for nucleic acid metabolism and brain tubulin growth and phosphorylation. Lack of zinc has been implicated in impaired DNA, RNA, and protein synthesis during brain development. For these reasons, deficiency of zinc during pregnancy and lactation has been shown to be related to many congenital abnormalities of the nervous system in offspring. Furthermore, in children insufficient levels of zinc have been associated with lowered learning ability, apathy, lethargy, and mental retardation. Hyperactive children may be deficient in zinc and vitamin B-6 and have an excess of lead and copper. Alcoholism, schizophrenia, Wilson's disease, and Pick's disease are brain disorders dynamically related to zinc levels. Zinc has been employed with success to treat Wilson's disease, achrodermatitis enteropathica, and specific types of schizophrenia.
PMID: 7082716 [PubMed - indexed for MEDLINE]
Raiten DJ, Massaro T. Perspectives on the nutritional ecology of autistic children. J Autism Dev Disord. 1986 Jun;16(2):133-43.
Dietary intake was assessed in a sample population of 40 autistic and 34 control children with a 7-day diet record kept by the parent or primary caregiver. A questionnaire was completed by each participant to obtain descriptive data on nutrition and health issues, attitudes and beliefs about nutrition, and nutrition knowledge. The autistic children had significantly greater intake of all nutrients with the exception of vitamins A and C, and fat; overall adequacy of diets was similar for both groups. Parent/primary caregivers of autistic children reported a more positive belief in the relationship between diet and behavior, and a more positive attitude about the importance of nutrition. A higher incidence of food cravings, pica, and perceived eating problems were reported by the parent/caregivers of autistic children.
PMID: 3722115 [PubMed - indexed for MEDLINE]
Reddi K, Henderson B, Meghji S, Wilson M, Poole S, Hopper C, Harris M, Hodges SJ. Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by naphthoquinone (vitamin K) compounds. Cytokine. 1995 Apr;7(3):287-90.
Department of Oral and Maxillofacial Surgery, Eastman Dental Institute for Oral Healthcare Sciences, London.
Naphthoquinone vitamins (vitamins K) are widely recognized for their role in the gamma-carboxylation of specific glutamyl residues in coagulation, anti-coagulation and extra-hepatic proteins. Recently, however, there have been reports that these compounds can exert actions other than those normally associated with protein gamma-carboxylation. These observations suggest that naphthoquinones may have effects on the production of inflammatory mediators including cytokines. Fibroblasts are now recognized as a rich source of cytokines and we have examined the effect of various naphthoquinones on the production of interleukin 6 (IL-6) by lipopolysaccharide-stimulated human gingival fibroblasts. Compounds examined in this study include: phylloquinone (K1), menaquinone-4 (K2), menadione (K3), 2,3-dimethoxy-1,4-naphthoquinone (DMK) and a synthetic product of vitamin K catabolism, 2-methyl, 3-(2'methyl)-hexanoic acid-1,4-naphthoquinone (KCAT). All of these compounds are capable of inhibiting IL-6 production with a rank order of potency: KCAT > K3 > DMK > K2 > K1. The most potent compound, KCAT, inhibited IL-6 production with an IC50 of 3 x 10(-7)M. The mechanism of action of these naphthoquinones on fibroblast IL-6 production is unknown. Given that K3 and KCAT are inactive in the gamma-carboxylation reaction, we suggest that this activity is not essential for the inhibition of IL-6 production and that activity may be related to the redox capacity of these naphthoquinones.
PMID: 7640347 [PubMed - indexed for MEDLINE]
Richardson AJ. Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int Rev Psychiatry. 2006 Apr;18(2):155-72.
Department of Physiology, Human Anatomy and Genetics, University of Oxford, UK. [email protected]
Omega-3 fatty acids are dietary essentials, and are critical to brain development and function. Increasing evidence suggests that a relative lack of omega-3 may contribute to many psychiatric and neurodevelopmental disorders. This review focuses on the possible role of omega-3 in attention-deficit/hyperactivity disorder (ADHD) and related childhood developmental disorders, evaluating the existing evidence from both research and clinical perspectives. Theory and experimental evidence support a role for omega-3 in ADHD, dyslexia, developmental coordination disorder (DCD) and autism. Results from controlled treatment trials are mixed, but the few studies in this area have involved different populations and treatment formulations. Dietary supplementation with fish oils (providing EPA and DHA) appears to alleviate ADHD-related symptoms in at least some children, and one study of DCD children also found benefits for academic achievement. Larger trials are now needed to confirm these findings, and to establish the specificity and durability of any treatment effects as well as optimal formulations and dosages. Omega-3 is not supported by current evidence as a primary treatment for ADHD or related conditions, but further research in this area is clearly warranted. Given their relative safety and general health benefits, omega-3 fatty acids offer a promising complementary approach to standard treatments.
PMID: 16777670 [PubMed - indexed for MEDLINE]
Rimland B. Controversies in the treatment of autistic children: vitamin and drug therapy. J Child Neurol. 1988;3 Suppl:S68-72.
Institute for Child Behavior Research, San Diego, CA 92116.
A survey of approximately 4,000 questionnaires completed by parents of autistic children provided ratings on a variety of treatments and interventions. Among the biomedical treatments, the use of high-dosage vitamin B6 and magnesium (n = 318) received the highest ratings, with 8.5 parents reporting behavioral improvement to every one reporting behavioral worsening. Deanol (n = 121) was next most highly rated, with 1.8 parents reporting improvement to each one reporting worsening. Fenfluramine (n = 104) was third, with a ratio of 1.5:1. Thioridazine hydrochloride (Mellaril), by far the most often used drug on the list (n = 724), was fourth with a helped-worsened ratio of 1.4:1. The research literature on the use of vitamin B6-magnesium is briefly reviewed, and mention is made of recent findings regarding high-dosage folic acid in autism and biotin in Rett syndrome.
PMID: 3058789 [PubMed - indexed for MEDLINE]
Rimland, B. High dosage levels of certain vitamins in the treatment of children with severe mental disorders. In D. Hawkins & L. Pauling (Eds.), Orthomolecular Psychiatry . 1973 (pp. 513-538).
Rimland B, Callaway E, Dreyfus P. The effect of high doses of vitamin B6 on autistic children: a double-blind crossover study. Am J Psychiatry. 1978 Apr;135(4):472-5.
The authors used data from an earlier nonblind study to identify 16 autistic-type child outpatients who had apparently improved when given vitamin B6 (pyridoxine). In a double-blind study each child's B6 supplement was replaced during two separate experimental trial periods with either a B6 supplement or a matched placebo. Behavior was rated as deteriorating significantly during the B6 withdrawal.
PMID: 345827 [PubMed - indexed for MEDLINE]
Rosenberg IH. Folic acid and neural-tube defects—time for action? N Engl J Med. 1992 Dec 24;327(26):1875-7.
Department of Human Genetics and Teratology, National Institute of Hygiene, Budapest, Hungary.
BACKGROUND. The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing such during the periconceptional period. The extent to which folic acid supplementation can reduce the first occurrence of defects is not known. METHODS. We conducted a randomized, controlled trial of periconceptional multivitamin supplementation to test the efficacy of this treatment in reducing the incidence of a first occurrence of neural-tube defects. Women planning a pregnancy (in most cases their first) were randomly assigned to receive a single tablet of a vitamin supplement (containing 12 vitamins, including 0.8 mg of folic acid; 4 minerals; and 3 trace elements) or a trace-element supplement (containing copper, manganese, zinc, and a very low dose of vitamin C) daily for at least one month before conception and until the date of the second missed menstrual period or later. RESULTS. Pregnancy was confirmed in 4753 women. The outcome of the pregnancy (whether the fetus or infant had a neural-tube defect or congenital malformation) was known in 2104 women who received the vitamin supplement and in 2052 who received the trace-element supplement. Congenital malformations were significantly more prevalent in the group receiving the trace-element supplement than in the vitamin-supplement group (22.9 per 1000 vs. 13.3 per 1000, P = 0.02). There were six cases of neural-tube defects in the group receiving the trace-element supplement, as compared with none in the vitamin-supplement group (P = 0.029). The prevalence of cleft lip with or without cleft palate was not reduced by periconceptional vitamin supplementation. CONCLUSIONS. Periconceptional vitamin use decreases the incidence of a first occurrence of neural-tube defects.
PMID: 1307234 [PubMed - indexed for MEDLINE]
Schectman G, Byrd JC, Hoffmann R. Ascorbic acid requirements for smokers: analysis of a population survey. Am J Clin Nutr. 1991 Jun;53(6):1466-70.
Division of General Internal Medicine, Medical College of Wisconsin, Milwaukee 53226.
The recommended dietary allowance (RDA) of ascorbic acid for smokers was recently increased from 60 to 100 mg. To determine whether this new RDA for smokers is sufficient to reduce the risk of low serum ascorbic acid (AA) concentrations (LoC) to the same concentration as nonsmokers, we analyzed the dietary intakes and serum concentrations of AA in 11,582 adult respondents in the National Health and Nutrition Examination Survey (1976-1980). Serum AA concentrations and the risk of LoC (serum ascorbic acid levels less than 23 mumol/L) for smokers consuming different amounts of AA were compared with those for nonsmokers whose AA intake exceeded the RDA (60 mg). Serum AA concentrations were reduced, and risk of LoC increased, in smokers maintaining AA intakes greater than 60, 100, and 150 mg. Only smokers consuming greater than 200 mg AA/d had serum ascorbate concentrations and risk of LoC equivalent to nonsmokers meeting the RDA.
PMID: 2035475 [PubMed - indexed for MEDLINE
Schoon EJ, Muller MC, Vermeer C, Schurgers LJ, Brummer RJ, Stockbrugger RW. Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease? Gut. 2001 Apr;48(4):473-7.
Department of Gastroenterology and Hepatology, University Hospital Maastricht, Maastricht, the Netherlands. [email protected]
BACKGROUND: A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency. AIMS: To determine serum and bone vitamin K status in patients with Crohn's disease and to elucidate its relationship with bone mineral density. METHODS: Bone mineral density was measured in 32 patients with longstanding Crohn's disease and small bowel involvement, currently in remission, and receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K, triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding capacity of osteocalcin was calculated. Data were compared with an age and sex matched control population. RESULTS: Serum vitamin K levels of CD patients were significantly decreased compared with normal controls (p<0.01). "Free" osteocalcin was higher and hydroxyapatite binding capacity of circulating osteocalcin was lower than in matched controls (p<0.05 and p<0.001, respectively), indicating a low bone vitamin K status in Crohn's disease. In patients, an inverse correlation was found between "free" osteocalcin and lumbar spine bone mineral density (r=-0.375, p<0.05) and between "free" osteocalcin and the z score of the lumbar spine (r=-0.381, p<0.05). Multiple linear regression analysis showed that "free" osteocalcin was an independent risk factor for low bone mineral density of the lumbar spine whereas serum vitamin D was not. CONCLUSIONS: The finding that a poor vitamin K status is associated with low bone mineral density in longstanding Crohn's disease may have implications for the prevention and treatment of osteoporosis in this disorder.
PMID: 11247890 [PubMed - indexed for MEDLINE]
Schorah CJ, Downing C, Piripitsi A, Gallivan L, Al-Hazaa AH, Sanderson MJ, Bodenham A. Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients. Am J Clin Nutr. 1996 May;63(5):760-5.
Division of Clinical Sciences, University of Leeds, United Kingdom.
Plasma concentrations of the antioxidant vitamin ascorbic acid were measured by high-performance liquid chromatography in critically ill patients in whom the excessive generation of reactive oxygen species could compromise antioxidant defense mechanisms. Median concentrations of both total vitamin C (ascorbic acid and dehydroascorbic acid) and ascorbic acid in these patients were < 25% (P < 0.001) of the values found in healthy control subjects and in subjects in two other disease groups (diabetes, gastritis) in which reactive oxygen species are reported to be increased. The low values could not be explained by age, sex, intake, or treatment differences, but were associated with the severity of the illness and were not prevented by the use of parenteral nutrition containing ascorbic acid. In addition, the vitamin was less stable in blood samples taken from critically ill patients than in similar samples from subjects in the other groups. The findings indicate that antioxidant defenses could be considerably compromised in these very sick patients. If this reduces the patient's capacity to scavenge reactive species, then the potential of these species to damage DNA and lipid membranes could be increased and compromise recovery.
PMID: 8615361 [PubMed - indexed for MEDLINE]
Singh RB, Niaz MA, Agarwal P, Begom R, Rastogi SS. Effect of antioxidant-rich foods on plasma ascorbic acid, cardiac enzyme, and lipid peroxide levels in patients hospitalized with acute myocardial infarction. J Am Diet Assoc. 1995 Jul;95(7):775-80.
Heart Research Laboratory, Medical Hospital, Moradabad, UP, India.
OBJECTIVE: To determine whether a fat- and energy-reduced diet rich in antioxidant vitamins C and E, beta carotene, and soluble dietary fiber reduces free-radical stress and cardiac enzyme level and increases plasma ascorbic acid level 1 week after acute myocardial infarction. DESIGN: Randomized, single blind, controlled study. SETTING: Primary- and secondary-care research center for patients with myocardial infarction. SUBJECTS: All subjects with suspected acute myocardial infarction (n = 505) were considered for entry to the study. Subjects with definite or possible acute myocardial infarction and unstable angina (according to World Health Organization criteria) were assigned to either an intervention diet (n = 204) or a control diet (n = 202) within 48 hours of symptoms of infarction. INTERVENTIONS: Intervention and control groups were advised to consume a fat-reduced, oil-substituted diet. The intervention group was also advised to eat more fruits, vegetable soup, pulses, and crushed almonds and walnuts mixed with skim milk. MAIN OUTCOME MEASURES: Reduction in plasma lipid peroxide and lactate dehydrogenase cardiac enzyme levels, increase in plasma ascorbic acid level, and compliance with diet, especially with vitamin C intake as determined by chemical analysis. STATISTICAL ANALYSIS: A two-sample t test using one-way analysis of variance for comparison of data. RESULTS: Plasma lipid peroxide level decreased significantly in the intervention group compared with the control group (0.59 pmol/L in the intervention group and 0.10 pmol/L in the control group; 95% confidence interval of difference = 0.19 to 0.83). Lactate dehydrogenase level increased less in the intervention group than in the control group (427.7 vs 561.2 U/L; confidence interval of difference = 82.9 to 184.7). Plasma ascorbic acid level increased more in the intervention group than in the control group (23.38 vs 7.95 mumol/L; confidence interval of difference = 12.85 to 26.13). APPLICATIONS/CONCLUSIONS: Consumption of an antioxidant-rich diet may reduce the plasma levels of lipid peroxide and cardiac enzyme and increase the plasma level of ascorbic acid. Antioxidant-rich foods may reduce myocardial necrosis and reperfusion injury induced by oxygen free radicals.
PMID: 7797808 [PubMed - indexed for MEDLINE]
Sogut S, Zoroglu SS, Ozyurt H, Yilmaz HR, Ozugurlu F, Sivasli E, Yetkin O, Yanik M, Tutkun H, Savas HA, Tarakcioglu M, Akyol O. Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta. 2003 May;331(1-2):111-7.
Department of Biochemistry, Faculty of Medicine, Inönü University, Pasakosku Mahallesi 11, Sok. Ozkaracalar Apt. No: 42/4, Malatya 44200, Turkey.
BACKGROUND: There is evidence that oxygen free radicals play an important role in the pathophysiology of many neuropsychiatric disorders. Although it has not been investigated yet, several recent studies proposed that nitric oxide (NO) and other parameters related to oxidative stress may have a pathophysiological role in autism. METHODS: We assessed the changes in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and thiobarbituric acid-reactive substances (TBARS) levels in plasma as well as NO levels in red blood cells (RBC) in patients with autism (n=27) compared to age- and sex-matched normal controls (n=30). RESULTS: In the autistic group, increased RBC NO levels (p<0.0001) and plasma GSH-Px activity (p<0.0001) and unchanged plasma TBARS levels and SOD activity were detected. CONCLUSIONS: These findings indicate a possible role of increased oxidative stress and altered enzymatic antioxidants, both of which may be relevant to the pathophysiology of autism.
PMID: 12691871 [PubMed - indexed for MEDLINE]
Starobrat-Hermelin B, Kozielec T. The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test. Magnes Res. 1997 Jun;10(2):149-56.
Department of Family Medicine, Pomeranian Medical Academy, Szczecin, Poland.
Children with ADHD are 'a group at risk' as far as their further emotional and social development and educational possibilities are concerned, and the consequences of the lack of an appropriate therapy appears to be serious. Some of these children do not respond to prevailing therapy methods. It is reported that dietetic factors can play a significant role in the etiology of ADHD syndrome, and magnesium deficiency can help in revealing hyperactivity in children. The aim of our work was to assess the influence of magnesium supplementation on hyperactivity in patients with ADHD. The examination comprised 50 hyperactive children, aged 7-12 years, who fulfilled DSM IV criteria for ADHD syndrome, with recognized deficiency of magnesium in the blood (blood serum and red blood cells) and in hair using atomic absorption spectroscopy. In the period of 6 months those examined regularly took magnesium preparations in a dose of about 200 mg/day. 30 of those examined with ADHD showed coexisting disorders specific to developmental age, and 20 of them showed disruptive behaviour. The control group consisted of 25 children with ADHD and magnesium deficiency, who were treated in a standard way, without magnesium preparations. 15 members of this group showed coexisting disorders specific for developmental age, and 10 members showed disruptive behaviour. Hyperactivity was assessed with the aid of psychometric scales: the Conners Rating Scale for Parents and Teachers, Wender's Scale of Behavior and the Quotient of Development to Freedom from Distractibility. In the group of children given 6 months of magnesium supplementation, independently of other mental disorders coexisting with hyperactivity, an increase in magnesium contents in hair and a significant decrease of hyperactivity of those examined has been achieved, compared to their clinical state before supplementation and compared to the control group which had not been treated with magnesium.
PMID: 9368236 [PubMed - indexed for MEDLINE]
Sturman JA, Chesney RW. Taurine in pediatric nutrition. Pediatr Clin North Am. 1995 Aug;42(4):879-97.
Department of Developmental Biochemistry, Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
The past 20 years have seen the status of taurine change from an end product of methionine and cysteine metabolism and substance conjugated to bile acids to that of an important, and sometimes essential, nutrient. It is now added to most synthetic human infant formulas and pediatric parenteral solutions throughout the world. This article describes the research that led to this end.
PMID: 7610018 [PubMed - indexed for MEDLINE]
Sugiura I, Furie B, Walsh CT, Furie BC. Propeptide and glutamate-containing substrates bound to the vitamin K-dependent carboxylase convert its vitamin K epoxidase function from an inactive to an active state. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9069-74.
Center for Hemostasis and Thrombosis Research, Tufts University School of Medicine, Boston, MA 02111, USA.
The vitamin K-dependent gamma-glutamyl carboxylase catalyzes the posttranslational conversion of glutamic acid to gamma-carboxyglutamic acid in precursor proteins containing the gamma-carboxylation recognition site (gamma-CRS). During this reaction, glutamic acid is converted to gamma-carboxyglutamic acid while vitamin KH2 is converted to vitamin K 2,3-epoxide. Recombinant bovine carboxylase was purified free of gamma-CRS-containing propeptide and endogenous substrate in a single-step immunoaffinity procedure. We show that in the absence of gamma-CRS-containing propeptide and/or glutamate-containing substrate, carboxylase has little or no epoxidase activity. Epoxidase activity is induced by Phe-Leu-Glu-Glu-Leu (FLEEL) (9.2 pmol per min per pmol of enzyme), propeptide, residues -18 to -1 of proFactor IX (3.4 pmol per min per pmol of enzyme), FLEEL and propeptide (100 pmol per min per pmol of enzyme), and proPT28 (HVFLAPQQARSLLQRVRRANTFLEEVRK, residues -18 to +10 of human acarboxy-proprothrombin), (5.3 pmol per min per pmol of enzyme). These results indicate that in the absence of propeptide or glutamate-containing substrate, oxygenation of vitamin K by the carboxylase does not occur. Upon addition of propeptide or glutamate-containing substrate, the enzyme is converted to an active epoxidase. This regulatory mechanism prevents the generation of a highly reactive vitamin K intermediate in the absence of a substrate for carboxylation.
PMID: 9256436 [PubMed - indexed for MEDLINE
Tchantchou F, Graves M, Shea TB. Expression and activity of methionine cycle genes are altered following folate and vitamin E deficiency under oxidative challenge: modulation by apolipoprotein E-deficiency. Nutr Neurosci. 2006 Feb-Apr;9(1-2):17-24.
Department of Biological Sciences, Center for Cellular Neurobiology and Neurodegeneration Research, University of Massachusetts Lowell, Lowell, MA 01854, USA.
Folate deficiency increases neuronal oxidative damage and potentiates the deleterious effects of apolipoprotein E (ApoE) deficiency. Mice lacking ApoE (ApoE -/- mice) upregulate the expression and activity of another enzyme, glutathione synthase (GS), when deprived of folate, in an apparent attempt to compensate for increased oxidative damage. Herein, we examined the influence of ApoE and folate deficiency on expression and activity of several enzymes of the methionine cycle. Expression and activity of methylene tetrahydrofolate reductase was increased in the order ApoE +/+ < ApoE +/- < ApoE -/- in response to folate deprivation. Expression of cystathione beta synthase followed a similar pattern. By contrast, expression and activity of methionine synthase decreased following folate deprivation in the order ApoE +/+ < ApoE +/- < ApoE -/-. These studies demonstrate that folate deficiency induces compensatory regulation of methionine cycle genes, and that these effects are potentiated by ApoE deficiency in a gene-dosage manner. They further support the notion that latent genetic deficiencies, including those of methionine cycle, may contribute to Alzheimer's disease, especially in concert with age-related nutritional deficiencies.
PMID: 16910166 [PubMed - indexed for MEDLINE]
Ueland PM, Hustad S, Schneede J, Refsum H, Vollset SE. Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol Sci. 2001 Apr;22(4):195-201.
LOCUS for homocysteine and related vitamins, Armauer Hanssens hus, University of Bergen, 5021, Bergen, Norway. [email protected]
The enzyme methylenetetrahydrofolate reductase (MTHFR) directs folate species either to DNA synthesis or to homocysteine (Hcy) remethylation. The common MTHFR C677T polymorphism affects the activity of the enzyme and hence folate distribution. Under conditions of impaired folate status, the homozygous TT genotype has been regarded as harmful because it is associated with a high concentration of plasma total Hcy, increased risk of neural tube defects and colorectal neoplasias, and can also predispose individuals to adverse effects from drugs with antifolate effects. The MTHFR C677T polymorphism shows no consistent correlation with cardiovascular risk and longevity but, in combination with positive folate balance, the TT genotype is associated with decreased risk of colorectal neoplasias. Because of the high prevalence of this polymorphism in most populations, the TT variant might represent an ancestral genetic adaptation to living constraints (tissue injury or unbalanced vitamin intake) that has become a determinant of disease profiles in modern times.
PMID: 11282420 [PubMed - indexed for MEDLINE]
Vancassel S, Durand G, Barthelemy C, Lejeune B, Martineau J, Guilloteau D, Andres C, Chalon S. Plasma fatty acid levels in autistic children. Prostaglandins Leukot Essent Fatty Acids. 2001 Jul;65(1):1-7.
Laboratoire de Nutrition et Sécurité Alimentaire, INRA, domaine de Vilvert, 78352 Jouy-en-Josas cedex, France. [email protected]
Phospholipid fatty acids are major structural components of neuronal cell membranes, which modulate membrane fluidity and hence function. Evidence from clinical and biochemical sources have indicated changes in the metabolism of fatty acids in several psychiatric disorders. We examined the phospholipid fatty acids in the plasma of a population of autistic subjects compared to mentally retarded controls. Our results showed a marked reduction in the levels of 22: 6n-3 (23%) in the autistic subjects, resulting in significantly lower levels of total (n-3) polyunsaturated fatty acids (PUFA) (20%), without significant reduction in the (n-6) PUFA series, and consequently a significant increase in the (n-6)/(n-3) ratio (25%). These variations are discussed in terms of potential differences in PUFA dietary intake, metabolism, or incorporation into cellular membranes between the two groups of subjects. These results open up interesting perspectives for the investigation of new biological indices in autism. Moreover, this might have new therapeutic implications in terms of child nutrition. Copyright 2001 Harcourt Publishers Ltd.
PMID: 11487301 [PubMed - indexed for MEDLINE]
Van Gelder NM, Sherwin AL, Sacks C, Anderman F. Biochemical observations following administration of taurine to patients with epilepsy. Brain Res. 1975 Aug 29;94(2):297-306.
Amino acid analysis of plasma and urine obtained from 12 patients with epilepsy indicated that the plasma concentrations of taurine and glutamic acid were much higher than might have been expected. Glutamic acid in urine was also increased in these patients. Oral administration of taurine did not appreciably affect the levels of amino acids in plasma or urine with the exception of that of glutamic acid. In patients with an abnormal plasma concentration of glutamic acid, the administration of taurine caused glutamic acid levels to change in the direction of normal values along with a decrease in the urinary excretion of this amino acid. This action of taurine was independent of either its initial or final plasma concentration. Amino acid concentrations in the CSF were within normal range and were not influenced by taurine administration. The selective elevation of both taurine and glutamic acid in the plasma, combined with previous findings of a deficiency of these same amino acids in human and experimental epileptogenic brain, implies that some patients with epilepsy may suffer from an aberration in taurine and glutamic acid metabolism. Taurine administration appears to partially correct these biochemical abnormalities. Theoretically, such normalization of the amino acid profile in epileptogenic brain may be beneficial, but clinical signs of improvement may only become apparent after a long delay. The present study was designed to determine only the biochemical parameters implicated in taurine administration and no definite conclusions can be drawn as to the clinical efficacy of the amino acid in epilepsy. However, this study suggests that in future clinical trials investigating the potential use of taurine as an antiepileptic agent, the oral dose of taurine should not exceed 1.0 g/day and optimal doses may be as low as 0.1-0.5 g/day. In one patient who received 2.0-2.5 g of taurine/day for 2 weeks, a generalized amino aciduria occurred.
PMID: 807299 [PubMed - indexed for MEDLINE]
Vervoort LM, Ronden JE, Thijssen HH. The potent antioxidant activity of the vitamin K cycle in microsomal lipid peroxidation. Biochem Pharmacol. 1997 Oct 15;54(8):871-6.
Department of Pharmacology, Cardiovascular Research Institute, University of Maastricht, The Netherlands.
In the vitamin K cycle, vitamin K-hydroquinone, the active cofactor for gamma-glutamylcarboxylase, is continuously regenerated. The successive pathways contain oxidation of the hydroquinone to the epoxide, followed by reduction to the quinone and reduction to the hydroquinone. Vitamin K-hydroquinone is a potent radical scavenging species (Mukai et al., J Biol Chem 267: 22277-22281, 1992). We tested the potential antioxidant activity of the vitamin K cycle in lipid peroxidation reactions (thiobarbituric acid reactive substances, TBARS) in rat liver microsomes. As prooxidant we used Fe2+/ascorbate, NADPH-Fe3+/ATP, and NADPH/CCl4. Vitamin K (< or = 50 microM) on its own did not influence the formation of TBARS. In combination with 1 mM dithiothreitol (DTT), the reductive cofactor for the microsomal enzyme vitamin K epoxide reductase, vitamin K suppressed lipid peroxidation with a concentration that blocked the maximal response by 50% (IC50) of ca. 0.2 microM. Vitamin K1 (phylloquinone) and vitamin K2 (menaquinone-4) were equally active. Warfarin (5 microM) and chloro-vitamin K (50 microM), inhibitors of vitamin K epoxide reductase and gamma-glutamylcarboxylase, respectively, were able to completely abolish the antioxidant effect. Lipid peroxidation was inversely related to the amount of vitamin K hydroquinone in the reaction. Vitamin K epoxide reductase seemed sensitive to lipid peroxidation, with half of the activity being lost within 10 min during oxidation with NADPH/CCl4. The inactivation could be attenuated by antioxidants such as vitamin E, reduced glutathione, and menadione and also by a K vitamin in combination with DTT, but not by superoxide dismutase and catalase. The results show that the vitamin K cycle could act as a potent antioxidant, that the active species in all probability is vitamin K-hydroquinone, and that the primary reaction product is the semiquinone. The results also show that the reaction product is processed in the vitamin K cycle to regenerate vitamin K-hydroquinone.
PMID: 9354587 [PubMed - indexed for MEDLINE]
Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE, Walker-Smith JA. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998 Feb 28;351(9103):637-41.
Inflammatory Bowel Disease Study Group, University Department of Medicine, Royal Free Hospital and School of Medicine, London, UK.
BACKGROUND: We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. METHODS: 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. FINDINGS: Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. INTERPRETATION: We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.
PMID: 9500320 [PubMed - indexed for MEDLINE]
Walsh WJ, Glab LB, Haakenson ML. Reduced violent behavior following biochemical therapy. Physiol Behav. 2004 Oct 15;82(5):835-9.
Pfeiffer Treatment Center, 4575 Weaver Parkway, Warrenville, IL 60555, United States. [email protected]
Reduced violent behavior following biochemical therapy. We conducted an outcome study to measure the effectiveness of biochemical therapy for 207 consecutive patients presenting with a diagnosed behavior disorder. The treatment protocols were based on clinical evaluation and our past experience in the treatment of 8000 patients with behavior disorders at the Pfeiffer Treatment Center (PTC) over a 10-year period. Each test subject was screened for chemical imbalances previously found in high incidence in this population, including metal-metabolism disorders, methylation abnormalities, disordered pyrrole chemistry, heavy-metal overload, glucose dyscontrol, and malabsorption. The clinical procedure included a medical history, assay of 90 biochemical factors, and a physical examination. Standardized treatment protocols were applied for each imbalance that was identified. The frequencies of physical assaults and destructive episodes were determined using a standardized behavior scale before and after treatment, with follow-up ranging from 4 to 8 months. RESULTS: Seventy-six percent of the test subjects achieved compliance during the treatment period. The remaining 24% were reported to have discontinued the therapy. A reduced frequency of assaults was reported by 92% of the compliant assaultive patients, with 58% achieving elimination of the behavior. A total of 88% of compliant destructive patients exhibited a reduced frequency of destructive incidents and 53% achieved elimination of the behavior. Statistical significance was found for reduced frequency of assaults (t=7.74, p<0.001) and destructive incidents (t= 8.77, p<0.001). The results of this outcome study strongly suggest that individualized biochemical therapy may be efficacious in achieving behavioral improvements in this patient population.
PMID: 15451647 [PubMed - indexed for MEDLINE]
Waring RH, Klovrza LV. Sulphur metabolism in autism. J Nutr Env Med. 2000:10:25-35.
White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.
Department of Physiology, Emory University, Atlanta, Georgia 30322, USA. [email protected]
Autism is a life-long developmental disorder affecting as many as 1 in 500 children. The causes for this profound disorder are largely unknown. Recent research has uncovered pathology in the gastrointestinal tract of autistic children. The pathology, reported to extend from the esophagus to the colon, is described here along with other studies pointing to a connection between diet and the severity of symptoms expressed in autism. The evidence that there is impaired intestinal permeability in autism is reviewed, and various theories are discussed by which a leaky gut could develop. Lastly, some possible ways in which impaired gastrointestinal function might influence brain function are discussed.
PMID: 12773694 [PubMed - indexed for MEDLINE]
Whiteley P, Waring R, Williams L, Klovrza L, Nolan F, Smith S, Farrow M, Dodou K, Lough WJ, Shattock P. Spot urinary creatinine excretion in pervasive developmental disorders. Pediatr Int. 2006 Jun;48(3):292-7.
Autism Research Unit, School of Health, Natural & Social Sciences, University of Sunderland, Sunderland, UK. [email protected]
BACKGROUND: Excretion of creatinine in urine represents the end-point of endogenous energy transfer from stored adenosine triphosphate in skeletal and cardiac muscle. Measurement of urinary creatinine is commonly used to correct for total urine concentration. Various quantitative measures of compounds suspected to be either pathological to, or indicative of, possible therapeutic interventions for Pervasive Developmental Disorders (PDD) have relied extensively on spot creatinine as a ratio quantity, although this important metabolite has not been exclusively studied within this population. METHODS: Levels of urinary creatinine in spot urine samples were analyzed for a group of children diagnosed with PDD (n=24; median age, 75 months; range, 39-137 months) and a control group (n=50; median age, 109 months; range, 59-140 months). Diagnosis of PDD was confirmed using the Autism Diagnostic Interview-Revised. Samples were collected and analyzed blind for creatinine content using an improved Jaffe's reaction method. RESULTS: Controlling for sample pH and body mass index, a significant decrease in urinary creatinine concentration was found in the PDD group compared to controls using a Mann-Whitney two-tailed ranks test (P=0.001). CONCLUSION: Further studies of protein catabolism and renal function in autism are required to ascertain the relevance of decreased spot urinary creatinine excretion identified in this preliminary study. Issues regarding the use of single urine creatinine measurements and associated confounding variables are discussed in light of the findings, together with recommendations to use other internal or external standards for the quantification of urinary compounds in PDD research.
PMID: 16732798 [PubMed - indexed for MEDLINE]
Whiting SJ, Calvo MS. Dietary recommendations for vitamin D: a critical need for functional end points to establish an estimated average requirement. J Nutr. 2005 Feb;135(2):304-9.
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. [email protected]
From its inaugural value in 1941, the Recommended Dietary Allowance (RDA) for adults for vitamin D has remained close to 400 IU (10 microg) level. This original recommended intake was based on the observation that the amount of vitamin D activity in a teaspoon of cod liver oil was sufficient to prevent rickets in infants. Since that time until 1997, determination of vitamin D requirements and status was more conjecture than science. In 1997, when the recommended intake level of vitamin D was set as an adequate intake value rather than an RDA, much has been learned about metabolism of vitamin D. The circulating metabolite 25-hydroxyvitamin D is the major static indicator of vitamin D status. Using its response to diet in the absence of sun exposure, a dose-response study suggests a mean requirement of at least 500 IU (12.5 microg) from which an RDA could be set. Other factors may need adjustment, such as sun exposure and body fat. However, functional indicators of status are needed. The role of vitamin D in calcium metabolism (i.e., calciotropic functions) is better understood; bone turnover and parathyroid hormone are potential indicators. Vitamin D has noncalciotropic functions arising from extrarenal synthesis of the active metabolite 1,25 dihydroxyvitamin D involving cell proliferation and immunity, from which function indicators of status may be derived. Despite gaps in our knowledge, there are data from which new dietary reference intake values for vitamin D may be set.
PMID: 15671232 [PubMed - indexed for MEDLINE]
Young G, Conquer J. Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev. 2005 Jan-Feb;45(1):1-28.
Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Epidemiological evidence suggests that dietary consumption of the long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), commonly found in fish or fish oil, may modify the risk for certain neuropsychiatric disorders. As evidence, decreased blood levels of omega-3 fatty acids have been associated with several neuropsychiatric conditions, including Attention Deficit (Hyperactivity) Disorder, Alzheimer's Disease, Schizophrenia and Depression. Supplementation studies, using individual or combination omega-3 fatty acids, suggest the possibility for decreased symptoms associated with some of these conditions. Thus far, however, the benefits of supplementation, in terms of decreasing disease risk and/or aiding in symptom management, are not clear and more research is needed. The reasons for blood fatty acid alterations in these disorders are not known, nor are the potential mechanisms by which omega-3 fatty acids may function in normal neuronal activity and neuropsychiatric disease prevention and/or treatment. It is clear, however, that DHA is the predominant n-3 fatty acid found in the brain and that EPA plays an important role as an anti-inflammatory precursor. Both DHA and EPA can be linked with many aspects of neural function, including neurotransmission, membrane fluidity, ion channel and enzyme regulation and gene expression. This review summarizes the knowledge in terms of dietary omega-3 fatty acid intake and metabolism, as well as evidence pointing to potential mechanisms of omega-3 fatty acids in normal brain functioning, development of neuropsychiatric disorders and efficacy of omega-3 fatty acid supplementation in terms of symptom management.
PMID: 15865053 [PubMed - indexed for MEDLINE]
Zitterman A. Effects of vitamin K on calcium and bone metabolism. Curr Opin Clin Nutr Metab Care. 2001 Nov 4(6):483-487.
Department of Nutrition Science, University of Bonn, Germany. [email protected]
The K vitamins, a group of napthoquinones, are required for the carboxylation of a limited number of proteins including the bone matrix protein osteocalcin. Vitamin K1 (phylloquinone) and vitamin K2 (menaquinones), differ regarding food source (green vegetables and fermented products, respectively), bioavailability and intermediate metabolism. Epidemiological studies provide evidence for an association between a low vitamin K intake and an enhanced osteoporotic fracture risk. Doses of vitamin K1 up to 15 times the current recommended dietary allowance have successfully been used to reduce the percentage of undercarboxylated osteocalcin in the circulation. Studies demonstrating clear beneficial effects on bone health, however, are still lacking. In contrast, therapy with very high pharmacological doses of the vitamin K2 menatetrenone has impressively been used to prevent further bone mineral loss and fracture risk in osteoporotic patients.
PMID: 11706280 [PubMed - indexed for MEDLINE]
Zoroglu SS, Yurekli M, Meram I, Sogut S, Tutkun H, Yetkin O, Sivasli E, Savas HA, Yanik M, Herken H, Akyol O. Pathophysiological role of nitric oxide and adrenomedullin in autism. Cell Biochem Funct. 2003 Mar;21(1):55-60.
Department of Child and Adolescent Psychiatry, Gaziantep University Medical School, Gaziantep, Turkey. [email protected]
Several studies indicate that nitric oxide (NO) is involved in the aetiopathogenesis of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, Alzheimer's disease, Hungtington disease and stroke. Although it has not been investigated yet, several recent studies proposed that NO may have a pathophysiological role in autism. Adrenomedullin (AM), a recently discovered 52-amino acid peptide hormone, induces vasorelaxation by activating adenylate cyclase and also by stimulating NO release. AM immune reactivity is present in the brain consistent with a role as a neurotransmitter. It has been stated that NO and AM do function in the regulation of many neurodevelopmental processes. We hypothesized that NO and AM activities have been affected in autistic patients and aimed to examine these molecules. Twenty-six autistic patients and 22 healthy control subjects were included in this study. AM and total nitrite (a metabolite of NO) levels have been measured in plasma. The mean values of plasma total nitrite and AM levels in the autistic group were significantly higher than control values, respectively (p < 0.001, p = 0.028). There is no correlation between total nitrite and AM levels (r = 0.11, p = 0.31). Certainly, this subject needs much further research investigating autistic patients in earlier periods of life and with subtypes of the disorder. Copyright 2002 John Wiley & Sons, Ltd.
PMID: 12579522 [PubMed - indexed for MEDLINE]
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