Regular Breakfast and Blood Lead Levels among Preschool Children

Jianghong Liu1*, Linda McCauley2, Charlene Compher1, Chonghuai Yan3, Xiaoming Shen3, Herbert Needleman4 and Jennifer A Pinto-Martin1

Author Affiliations

1 University of Pennsylvania, School of Nursing, 418 Curie Blvd., Room 426, Claire M. Fagin Hall, Philadelphia, Pennsylvania 19104-6096, USA

2 Emory University, Nell Hodgson School of Nursing, 1520 Clifton Rd NE # 402, Atlanta, GA 30322-4201, USA

3 Shanghai Jiaotong University School of Medicine, 1665 Kong Jiang Road, Shanghai 200092, China

4 University of Pittsburgh, UPMC, 200 Lothrop St., Pittsburgh, PA 15213-2582, USA

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Environmental Health 2011, 10:28 doi:10.1186/1476-069X-10-28
The electronic version of this article is the complete one and can be found online at: http://www.ehjournal.net/content/10/1/28

Received: 28 October 2010
Accepted: 1 April 2011
Published: 1 April 2011

© 2011 Liu et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Previous studies have shown that fasting increases lead absorption in the gastrointestinal tract of adults. Regular meals/snacks are recommended as a nutritional intervention for lead poisoning in children, but epidemiological evidence of links between fasting and blood lead levels (B-Pb) is rare. The purpose of this study was to examine the association between eating a regular breakfast and B-Pb among children using data from the China Jintan Child Cohort Study.

Methods

Parents completed a questionnaire regarding children’s breakfast-eating habit (regular or not), demographics, and food frequency. Whole blood samples were collected from 1,344 children for the measurements of B-Pb and micronutrients (iron, copper, zinc, calcium, and magnesium). B-Pb and other measures were compared between children with and without regular breakfast. Linear regression modeling was used to evaluate the association between regular breakfast and log-transformed B-Pb. The association between regular breakfast and risk of lead poisoning (B-Pb≥10 μg/dL) was examined using logistic regression modeling.

Results

Median B-Pb among children who ate breakfast regularly and those who did not eat breakfast regularly were 6.1 μg/dL and 7.2 μg/dL, respectively. Eating breakfast was also associated with greater zinc blood levels. Adjusting for other relevant factors, the linear regression model revealed that eating breakfast regularly was significantly associated with lower B-Pb (beta = -0.10 units of log-transformed B-Pb compared with children who did not eat breakfast regularly, p = 0.02).

Conclusion

The present study provides some initial human data supporting the notion that eating a regular breakfast might reduce B-Pb in young children. To our knowledge, this is the first human study exploring the association between breakfast frequency and B-Pb in young children.

Background

Lead exposure, even at low levels, has been associated with demonstrable deficits in cognition and intelligence [1-6]. The extent and rate of lead absorption are influenced by physiologic factors including age, fasting state, and calcium and iron status [7,8]. Studies have shown that the absorption of lead in the gastrointestinal tract is more rapid in subjects who are in a fasting state [7,9,10]. In adults, the absorption rate of lead ranges from 60-80% among fasting subjects, about 10 times higher than when ingested with food [7,9]. Micronutrients are thought to interact with lead in the body and previous epidemiologic studies have shown that dietary micronutrient intakes influence B-Pb [8,11,12].

Ingested lead is absorbed at higher rates (about 40-50%) in infants and children than in adults [7,13]. Given the observed impact of fasting on lead absorption in adults, eating frequent and regular meals/snacks is recommended by health authorities for preventing lead poisoning in children [14]. In previous epidemiologic studies, B-Pb in children were positively associated with higher intakes of micronutrients such as calcium [15,16]and iron [17,18] and total calorie[11,12]. To our knowledge, however, there have been no prior epidemiology studies evaluating the link between breakfast consumption and B-Pb in children. After the phase-out of lead in gasoline in the year 2000, the mean blood lead level of children aged 0-14 years in China was 8.1 μg/dL, with 23.9% of children’s having B-Pb greater than 10 μg/dL, the level established in 1991 as an indication of concern by the US Centers for Disease Control and Prevention (CDC) and adopted by the Ministry of Health of China in 2006 [19]. In this study, we aim to test whether regular breakfast consumption predicts B-Pb or risk of lead poisoning in Chinese preschool. Study subjects are the part of the China Jintan Child Cohort Study [20].

Methods

Data collection

Institutional review board approval was obtained from the University of Pennsylvania and the ethical committee for research at Jintan Hospital in Jintan, China. Four pre-schools (Jianshe, Huacheng, Xuebu, and Huashan) were chosen to represent city, suburban, and rural areas, respectively. Between Fall 2004 and Spring 2005, 1,757 male and female children (aged 3 to 5 years) attending the four preschools were invited to participate in this study. Parents of 1,656 (94%) children signed informed consents to approve their child’s participation. A questionnaire containing questions regarding breakfast-eating habit (regular or not), demographics (gender, age, parental educations, parental occupations, and passive smoking exposure), and eating behaviors was completed by a parent. Eating breakfast regularly was defined as eating breakfast at least five days per week. We also conducted three days of 24-hours dietary recall in a subset of study population. The forms were given to the parents of children and collected by the research assistants on the following day. The intake of lunch for two weekdays at school was observed by research assistants (MPH students from South Eastern University). These dietary records were analyzed using the self-developed computerized nutrients assessment system which was similar to Food Processor (Food Processor; ESHA Research, Salem, OR).

Blood specimens of 1,344 children were collected by trained pediatric nurses using a strict research protocol to avoid lead contamination. We were not able to successfully collect blood samples from some children due to a variety of reasons (e.g. parents did not allow blood drawn, blood specimen not viable), but there were no differences in demographics between children with (n = 1344) and without blood samples (n = 312). Samples were frozen and shipped to the Research Center for Environmental Medicine of Children at Shanghai Jiaotong University for the analysis of lead and micronutrients (iron [Fe], copper [Cu], zinc [Zn], calcium [Ca], and magnesium [Mg]) concentrations in blood, using graphite furnace atomic absorption spectrophotometer [21,22]. This laboratory has participated successfully in a CDC-administered quality-control program (Blood Lead Proficiency Testing Program) for the measurement of lead in whole blood. Analysis of each specimen was conducted using a replication procedure, and the mean of the repeated measurements was taken as the final measure. Blood lead reference materials for quality control (QC) were provided by Kaulson Laboratories, New Jersey. QC samples were inserted blindly among the study samples (one QC sample in every 10 study samples. Limit of detection (LOD) of B-Pb was 1.8 ug/dL and half of LOD was imputed for 3 (0.2%) samples under LOD, which was among multiple runs (mean LOD).

Statistical analysis

Demographic characteristics of children and parents/grandparents, nutrient and blood lead levels were compared between children eating breakfast regularly and those not eating breakfast regularly (defined as breakfast consumption at least five mornings per week), using chi-square test for categorical variables and t-test or Wilcoxon rank sum test for continuous variables (means or medians). Multivariate stepwise linear regression models of the dependent variable log-transformed B-Pb were fitted including breakfast frequency (regular vs. irregular) and other covariates such as demographic characteristics (children’s age, gender, parental educations and occupations, grandparental educations), children’s nutrient levels in blood, passive smoking, breast feeding history, and breakfast type (rice/noodle, meat mostly, and fruit mostly). A final model was obtained by applying a backwards elimination procedure using variables correlated with B-Pb with a p-value < 0.10. Logistic regression analysis was also performed to examine the associations between breakfast frequency and lead poisoning (B-Pb≥10 μg/dL). All analyses were done in SAS 9.2 (SAS Institute, Cary, NC).

Results

Demographic variables for the entire sample and by regular breakfast eating groups are in Table 1. Children eating breakfast regularly had a lower median B-Pb (6.1 vs. 7.2 μg/dL, Wilcoxon test without controlling for covariates, P < 0.01) compared to those without regular breakfast consumption. Proportions of lead poisoning (B-Pb > = 10 μg/dL) were 8% among children with regular breakfast eating habit and 10% among those not eating breakfast regularly, but this difference is not statistically significant (chi-square test). Sixty-four percent of children eating breakfast regularly and 68% of children without regular breakfast had moderately high B-Pb (in the range of 5 and 10 μg/dL). There were no differences in gender and age distributions between children eating breakfast regularly and those not. Six percent (40/679) of boys and seven percent (47/564) of girls did not eat breakfast regularly. Children eating breakfast regularly tended to live in urban (41%) and suburban (39%) areas. Grandparent and parent characteristics were correlated with breakfast frequency. Grandparents of children who eat breakfast regularly were more likely to be educated. Parents of children who eat breakfast regularly were more likely to have higher education (30% of fathers and 20% of mothers finished college) and to be technicians and professional workers (39% of fathers and 30% mothers), as compared to those who did not regularly eat breakfast (13% of fathers and 8% of mothers finished college). There were no statistical differences in micronutrient levels other than higher Zinc (Zn) levels among children who ate breakfast regularly.

Table 1. Basic and nutritional factors among children

Our final linear regression model showed that higher breakfast frequency was associated with lower B-Pb (beta = -0.10 units of log-transformed B-Pb compared with children who did not eat breakfast regularly, p = 0.02) after controlling for covariates (Table 2). This beta, when calculate back to original scale of B-Pb, means that children eating breakfast regularly had 0.8 μg/dL (or 10%) lower B-Pb than those did not eat breakfast regularly after excluding the impacts of other factors. Other covariates including gender, age, living area, mother’s education, and father’s occupation were also predictors of B-Pb. While being a boy, living in a rural area, older age, and parents as professional workers were associated with higher B-Pb, children of mothers with higher education tended to have lower B-Pb. In a linear regression model of 270 children with data of calculated daily dietary intake of micronutrients (Ca, Fe, Zn, Cu, Mg, and vitamins), we did not find associations between dietary intakes of minerals and log-transformed B-Pb (data not shown). In the Logistic regression model of lead poisoning risk (Table 3), boys had 1.92 higher odds of being lead poisoning than girls, and that father’s university level education reduced the odds to 0.38 times that of father with less than high school education. Compared with 3-year-old children, 4-year or 5-year old children had about 2 time odds of being lead poisoning. Regular breakfast, however, did not predict lead poisoning (B-Pb≥10 μg/dL). Blood micronutrient levels were not associated with B-Pb or the risk of lead toxicity (data not shown).

Table 2. Final multiple linear regression of log transformed B-Pb among children (R square = 0.14)

Table 3. Multiple Logistic regression analysis of elevated B-Pb

Discussion

Previous studies showed that an empty stomach increases the absorption of lead and thus elevates B-Pb in adults, but it not clear if this effect exists in children as well. There have been no other studies directly quantifying the impact of regular breakfast consumption on lead absorption in children. In this analysis, we found that median B-Pb in those children who eat breakfast regularly was about 15% lower than that in children who do not eat breakfast regularly. This study provides important early evidence supporting the hypothesis that eating regular meals such as breakfast is associated with lower B-Pb in children. To our knowledge, this is the first human study exploring the association between breakfast frequency and B-Pb in young children. Eating frequent and regular meals (including breakfast) and snacks have been recommended by many health organizations for preventing and reducing lead poisoning in children, and these data concur. For example, the U.S. Advisory Committee on Childhood Lead Poisoning Prevention recommends that caregivers provide regular meals and snacks to young children [14].

A number of studies have shown that food in the gastrointestinal tract reduces the absorption of ingested lead in adults [7,9,10,23]. Experimental studies showed that the bioavailability of ingested lead in adults when taken with a meal was about 10 times lower than that when ingested after fasting [7]. The smaller magnitude of the influence in children (15% change) may due to relatively lower lead exposure dose in children, observational study design, and the difference in the kinetics of lead between children and adults.

The mechanisms behind the impact of fasting on gastrointestinal tract absorption of lead are not well understood. Mineral micronutrients, especially the presence of calcium and phosphate in the intestinal lumen, may play a role by competing with lead for absorption [7]. Epidemiologic studies have shown increasing dietary calcium intake is inversely associated with B-Pb in children [15,16]. Higher dietary iron intake is also associated with lower B-Pb in the U.S. children[17,18]. In the present study, however, we did not find significant associations between blood levels of these mineral micronutrients and B-Pb. We did find significantly higher blood levels of zinc in children who ate breakfast regularly, which may suggest that their dietary zinc intake was greater and perhaps competed with lead for absorption. Our analysis of dietary micronutrient intake in a subgroup of 270 children, however, did not suggest higher zinc intake in regular breakfast eaters. In previous studies, while some studies observed associations between dietary intake/supplementation (Ca, Fe, and Zn) and B-Pb [8,15-17]others did not [11,24]. In a study in the US, Gallicchio et al. did not found associations between B-Pb and daily micronutrient intakes (iron, calcium, vitamin C, or vitamin D) after controlling lead exposure and child’s age [11]. A clinical trial showed that Ca supplementation did not statistically significantly change B-Pb among children 1 to 6 years of age when B-Pb were 10- 45 μg/dL [24]. There are two possible explanations for the inconsistency with this study. First, B-Pb are lower than those in previous studies. Second, children in this study are younger than the ones in previous studies.

The associations between socio-demographic factors and B-Pb found in previous studies were also observed in the present study [19,25-29]. Some of these factors including age and gender are strongly associated with B-Pb, but not modifiable. Other factors including living area and parental education and occupation might not be possible to improve solely through public health intervention. Targeting children’s breakfast consumption habits is relatively more feasible at both the family and community levels.

Several limitations must be considered when interpreting the findings from the present study. We have no data on the key variable of environmental lead exposure, a factor that might explain the higher B-Pb and greater risk of toxicity in older children if cumulative lead exposure increases over time. Clearly, our findings regarding increased B-Pb with increasing age merit repeated measures over time together with measures of environmental lead. We have information of dietary intake of micronutrients on only 270 of the larger sample of 1344 children, and thus cannot be certain that these micronutrient intake levels are representative of the entire group. Parental report of regular breakfast consumption in their children may lead to bias and misclassification. A guide was provided to parents to answer this question. However, for those children primarily living with their grandparents, the information may be less accurate. We did not ask parents the number of days the child ate breakfast during the week but instead used an arbitrary definition of “at least 5 days per week” as an indication of regular breakfast consumption. This was suggested by our local partners who believed that this would reasonably distinguish children. Second, the association observed in this cross-sectional study may not represent a causal relationship. There may be a tendency for higher B-Pb’s to be associated with a decreased appetite for eating breakfast. Given the data collected from this study, we cannot determine to what extent appetite affected the reported breakfast consumption. Third, the lack of association in the multivariate logistic regression analysis on lead poisoning is likely due to the limited magnitude of nutritional influence at relative low exposure level [24] and the small number of children with elevated B-Pb (7.9% for children with regular breakfast and 10.4% for children with irregular breakfast). Fourth, other potential confounders (e.g., household income and drinking water source) which were not assessed or included in the multiple regression models might contribute to the lower B-Pb observed among children who ate breakfast regularly. Finally, given the impact of fasting on lead absorption, regular breakfast is expected to modify the associations between external exposure levels and B-Pb which we cannot examine in this study due to lack of external exposure data.

Our findings, if replicated in future studies, have three practical implications. First, the importance of breakfast consumption as a strategy to increase meal frequency is suggested. Second, our data suggest that the risk of lead toxicity and higher B-Pb increases over time, a finding that suggests consideration of environmental routes of lead exposure. Third, we found that parental characteristics are major determinants of children’s breakfast frequency. Children from families with higher parental education levels and technicians/professional workers are more likely to have regular breakfast. This indicates that parents play important role in increasing children’s breakfast frequency which may in turn reduce B-Pb. Promotion of parents’ and child care givers’ awareness of the importance of breakfast as a proactive protective factor in reducing childhood B-Pb should become a part of all lead prevention programs. Because both lead exposure[1-6,30-33] and malnutrition[34-37]are related to children’s negative cognitive and behavioral outcomes, promotion of regular breakfast in children can potentially enhance both physical and mental health well-being.

Conclusions

This study provided epidemiological evidence that increasing breakfast frequency could reduce B-Pb in young children. Parental or caregivers’ characteristics including education and occupation are major determinants of breakfast frequency, indicating that improving their knowledge about nutrition and B-Pb might help to prevent lead poisoning.

Drumstick Vegetable

Moringa and other highly nutritious plant resources: Strategies, standards and markets for a

better impact on nutrition in Africa. Accra, Ghana, November 16-18, 2006

1

NUTRITIONAL POTENTIAL OF DRUMSTICK LEAVES: AN INDIAN

PERSPECTIVE

Dr Vanisha S. Nambiar

Department of Foods and Nutrition

A WHO-Collaborating Center for Nutrition Research

The Maharaja SayajiRao University of Baroda

Vadodara 390002. Gujarat. India.

Email: vanisha_nam@yahoo.com

In today’s world, a double burden of malnutrition is the concern of the nutritionists, as we

see under nutrition as well as over nutrition on the rise in both the developed as well as

the developing countries. Both macro as well as micronutrient deficiencies hinder the

national economic development as well as the development of individual human

potential. Children are frequently the victims of micronutrient deficiencies and failure to

overcome micronutrient malnutrition in a sustainable fashion jeopardizes a nation’s

future.

Amongst the malnutrition in children, the most significant ones are the deficiencies of

Vitamin A (VAD), iron, calcium and folic acid. These nutrient deficiencies are generally

referred to as the “diseases of poverty in the midst of plenty”. Especially, in a bio-diverse

country, like India, where, there are plenty of plant foods available at low-cost but are

underutilized. Therefore, identification of locally available, cheap and nutritious foods is

the call of the hour. This alone is the logical and sustainable strategy to avoid both

nutritional deficiencies as well as diseases due to macro-nutrient excess.

To bring about dietary modification, it is important to both improve the availability of

plant foods. Various approaches have been suggested, these include a) Nutrition

education for communication to improve practices related to consumption of available

plant foods, often using a social marketing approach. b) Horticultural interventions. c)

Economic/food policies affecting availability, price and effective demand of nutritious

plant foods. d) Technological advances concerning food preservation, plant breeding, etc.

Out of these the food-based strategies :

curry leaves and cheap mouthwash

Curry leaves

M V Math1 & P Balasubramaniam1

  1. Mumbai

Send your letters to the editor, British Dental Journal, 64 Wimpole Street, London W1G 8YS or by email to e-mail: bdj@bda.org

Sir, it is nice to know that dental decay in children’s teeth is decreasing in the UK as reported recently in the BDJ’s news pages (BDJ2004,  197: 64)

In developing countries, (more often in the rural areas) there is higher prevalence of dental and periodontal disease due to negligence and lack of awareness and the cost of oral health care has increased in these countries.

Essential oil (EO) mouthwashes are important in oral health management1. They contain thymol, eucalyptus oil and menthol and the tepenes present have antibacterial and antifungal activity2, 3. They have broad antimicrobial effects, are microbiologically safe3, 4 and have the ability to penetrate the plaque biofilm killing the microorganisms5.

The curry leaf tree (Murraya Koenigii spreng – a green leafy vegetable) is grown all over India and other countries for its aromatic leaves which are used daily as an ingredient in Indian cuisine.

The fresh curry leaves contain 2.6% volatile essential oils (containing sesquiterpenes and monoterpenes)6 and the essential oils in the curry leaves are sufficiently soluble in water.

They contain 21000mug total carotene, 7100mug beta carotene, 93.9mug total folic acid, 0.21mg riboflavin, 0.93mg iron, 830mg calcium, 57mg phosphorus and 0.20mg zinc per 100g7.

The cold extract of curry leaves (10g of cut fresh curry leaves in 200ml of distilled water) has a pH of 6.3 to 6.4. (unpublished personal observations). Chlorophyll has been proposed as an anticariogenic agent and it also helps to reduce halitosis8.

We have observed that holding curry leaves in the mouth for 5 to 7 minutes is helpful in reducing halitosis9 and that the terpenes have been found to reduce airborne chemicals and bacteria10.

In addition to the presence of EO, the curry leaves contain chlorophyll, beta carotene and folic acid, riboflavin, calcium and zinc and all these can act on the oral tissues and help in keeping up good oral health. Chewing 2 to 4 fresh curry leaves with 10 to 15mls water in the mouth, swishing for 5 to 7 minutes and rinsing the mouth out with water can be of help in keeping good oral hygiene and as the curry leaf is a green leafy vegetable it will be safe and cheap to use as mouthwash.

Top

References

  1. Claffey N. Essential oil mouthwash: a key component in oral health management. J Clin Periodontol. 2003; 30 (suppl. 5): 22–24.
  2. Dolara P, Corte B, Ghelardini C, et al. Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh. Planta Med 2000; 66: 356–8 | Article | PubMed | ISI | ChemPort |
  3. Bernimoulin JP. Recent concepts in plaque formation. J Clin Periodontol. 2003; 30 (suppl. 5): 7–9
  4. Santos A. Evidence based control of plaque and gingivitis J Clin Periodontol. 2003; 30 (suppl. 5): 13–16
  5. Ouhayoun JP. Penetrating the plaque biofilm: impact of essential oil mouthwash. J Clin Periodontol. 2003; 30 (suppl. 5): 10–12
  6. Indian Institute of Spice Research (www.iisr.org/spices/curryleaves.htm).
  7. Gopalan C, Rama sastri BV, Balasubramanian SC. In Nutritive Value of Indian Foods, revised and updated Narasinga rao BS, Deosthale YG, Pant KC. National Institute of Nutrition ICMR Hyderabad, India. 2000.
  8. Shafer WG, Hine MK, Levy BM, Tomich CE. Dental caries. A Text Book of Oral Pathology. pp 254–262 New Delhi, Saunders, 2002.
  9. Math MV and Balasubramaniam P. Curry leaves (Murraya Koenigii spreng) and halitosis. BMJ South Asia edition 2003;19(3):211
  10. Odorchem Manufacturing Corp. Canada (www.air8solutions.com

Chemomodulatory action of curry leaf (Murraya koenigii) extract on hepatic and extrahepatic xenobiotic metabolising enzymes, antioxidant levels, lipid peroxidation, skin and forestomach papillomagenesis

Trisha Dasguptaa, A.R Raoa,Corresponding Author Informationemail address, P.K Yadavaa

Received 14 January 2003; received in revised form 1 June 2003; accepted 2 June 2003.

Abstract 

Curry leaf (Murraya koenigii) is commonly used in India as a natural flavoring agent for various food preparations. Drinking water containing 10% and 20% fresh crude curry leaf aqueous extract was given to Swiss albino mice to investigate its ability to modulate the level/activities of drug metabolising Phase I enzymes (Cytochrome P450, Cytochrome b5, Cytochrome P450 reductase and Cytochrome b5 reductase), Phase II enzymes (Glutathione S- transferase and DT- diaphorase), antioxidant parameters (Reduced glutathione, Superoxide dismutase, Catalase, Glutathione peroxidase, Glutathione reductase), lactate dehydrogenase and lipid peroxidation changes. The level of glutathione, glutathione S-transferase and DT-diaphorase was examined also in the extrahepatic organs viz., forestomach, kidney and lung. There was a significant increase in the activities of acid soluble sulfhydryl (-SH) content (from P < 0.05 to P < 0.001), glutathione- S transferase and DT-diaphorase (from P < 0.005 to P < 0.001). Antioxidative parameters were also elevated above basal value being: superoxide dismutase (P < 0.005), catalase (P < 0.001), Glutathione peroxidase (P < 0.005), and glutathione reductase (P < 0.005). Level of lipid peroxidation and lactate dehydrogenase decreased significantly. Anticarcinogenic potential of curry leaf was evaluated adopting the protocol of Benzo(a)pyrene induced forestomach and 7,12 Dimethylbenz(a)anthracene (DMBA) induced skin papillomagenesis. Chemopreventive response was measured by tumor burden (papillomas/mouse), and by the percentage of tumor bearing animals. Both the investigated dose levels of curry leaf showed a significant reduction in tumor burden (P < 0.001) as well as tumor incidence at both the tumor model system studied. Our studies strongly suggest that the curry leaf can be useful for the prevention of human stomach and skin cancers.

Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia

Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Leister F, Yang S, Krivogorsky B, Alaedini A, Yolken R.

Stanley Research Program at Sheppard Pratt, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21204, USA. fdickerson@sheppardpratt.org

Abstract

BACKGROUND: Increased immune sensitivity to gluten has been reported in schizophrenia. However, studies are inconsistent about this association.METHODS: The sample of 471 individuals included 129 with recent-onset psychosis, 191 with multi-episode schizophrenia, and 151 controls. Immunoglobulin (Ig)G and IgA antibodies to gliadin and to tissue transglutaminase, and IgG antibodies to deamidated gliadin were measured. Quantitative levels of antibodies in the psychiatric groups were compared with controls. All participants were categorized as to whether their levels of antibodies met standardized cutoffs for celiac disease. HLA DQ2 and HLA DQ8 alleles were detected by real-time polymerase chain reaction.RESULTS: Individuals with recent-onset psychosis had increased levels of IgG (odds ratio [OR] 5.50; 95% confidence interval [CI] 2.65-11.42) and IgA (OR 2.75; 95% CI 1.31-5.75) antibodies to gliadin compared with control subjects. Individuals with multi-episode schizophrenia also had significantly increased levels of IgG antibodies to gliadin (OR 6.19; 95% CI 2.70-14.16). IgG antibodies to deamidated gliadin and IgA antibodies to tissue transglutaminase were not elevated in either psychiatric group, and fewer than 1% of individuals in each of the groups had levels of these antibodies predictive of celiac disease. There were no significant differences in the distribution of the HLA DQ2/8 alleles among the groups.CONCLUSIONS: Individuals with recent-onset psychosis and with multi-episode schizophrenia who have increased antibodies to gliadin may share some immunologic features of celiac disease, but their immune response to gliadin differs from that of celiac disease.Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved

A genetic variant that disrupts MET transcription is associated with autism

 Authored by Campbell, DB, Sutcliffe JS, Ebert PJ, Militerni R., Bravaccio C., Trillo S., Elia M., Schneider C., Melmed R., Sacco R., et al. in Proc Natl Acad Sci U S A. (epub), Volume 103, Issue 45, p. 16834-16839, (2006).

This article describes a study showing that many children with autism have a mutation in a gene involved in brain development, immune system function, and digestion.

The authors describe how previous research into the genetics of autism has focused on genes involved only in brain function. In this study, they take a different approach, and focus on a gene that is also involved in the immune system and digestion. Previous studies have shown that many children with autism seem to have problems in their immune system and digestive system. After analyzing the genes of 1,231 individuals with autism, they found that this gene was significantly more likely to be altered than in the general population. Because this gene is involved in brain development as well as the function of the immune and digestive systems, the result suggests that more than one system may be affected in autism

Abstract

There is strong evidence for a genetic predisposition to autism and an intense interest in discovering heritable risk factors that disrupt gene function. Based on neurobiological findings and location within a chromosome 7q31 autism candidate gene region, we analyzed the gene encoding the pleiotropic MET receptor tyrosine kinase in a family based study of autism including 1,231 cases. MET signaling participates in neocortical and cerebellar growth and maturation, immune function, and gastrointestinal repair, consistent with reported medical complications in some children with autism. Here, we show genetic association (P = 0.0005) of a common C allele in the promoter region of the MET gene in 204 autism families. The allelic association at this MET variant was confirmed in a replication sample of 539 autism families (P = 0.001) and in the combined sample (P = 0.000005). Multiplex families, in which more than one child has autism, exhibited the strongest allelic association (P = 0.000007). In case-control analyses, the autism diagnosis relative risk was 2.27 (95% confidence interval: 1.41-3.65; P = 0.0006) for the CC genotype and 1.67 (95% confidence interval: 1.11-2.49; P = 0.012) for the CG genotype compared with the GG genotype. Functional assays showed that the C allele results in a 2-fold decrease in MET promoter activity and altered binding of specific transcription factor complexes. These data implicate reduced MET gene expression in autism susceptibility, providing evidence of a previously undescribed pathophysiological basis for this behaviorally and medically complex disorder

Elimination diets in autism spectrum disorders: any wheat amidst the chaff?

Christison GW, Ivany K.

Department of Psychiatry, Loma Linda University School of Medicine, Loma Linda, California 92354, USA. gchristison@llu.edu

Abstract

The use of complementary or alternative treatment approaches in children with autism spectrum disorders (ASDs) is increasing, and the most popular of such approaches are diets that eliminate either gluten or casein, or both. The popularity of these diets indicates a need for more rigorous research into their efficacy. Owing to significant methodological flaws, the currently available data are inadequate to guide treatment recommendations. The purpose of this review is to examine the available trials of gluten/casein diets in children with ASDs regarding the strength of their findings and also concerning points that may be useful in the design of future studies. Seven trials of these diets in ASD are critically reviewed; 6 of these were uncontrolled trials and 1 used a single-blind design. All reported efficacy in reducing some autism symptoms, and 2 groups of investigators also reported improvement in nonverbal cognition. Design flaws in all of the studies weaken the confidence that can be placed in their findings. Careful double-blind, placebo-controlled studies are needed to evaluate whether actual benefit undergirds the diets’ popularity and to provide better guidance to clinicians and caregivers. The literature currently available suggests that diets eliminating both gluten and casein (rather than either alone) should be studied first and that outcome measures should include assessments of nonverbal cognition.

Can the pathophysiology of autism be explained by the nature of the discovered urine peptides?

Reichelt KL, Knivsberg AM.

Institute of Pediatric Research, Univ of Oslo, Rikshospitalet, N-0027, Oslo, Norway. k.l.reichelt@klinmed.uio.no

Abstract

Opioid peptides derived from food proteins (exorphins) have been found in urine of autistic patients. Based on the work of several groups, we try to show that exorphins and serotonin uptake stimulating factors may explain many of the signs and symptoms seen in autistic disorders. The individual symptoms ought to be explainable by the properties and behavioural effects of the found peptides. The data presented form the basis of an autism model, where we suggest that exorphins and serotonin uptake modulators are key mediators for the development of autism. This may be due to a genetically based peptidase deficiency in at least two or more peptidases and, or of peptidase regulating proteins made manifest by a dietary overload of exorphin precursors such as by increased gut uptake.

Diets for autistic spectrum disorder

Gluten and casein free diets for autistic spectrum disorder

Millward C, Ferriter M, Calver S, Connell-Jones G.

Update in:

Abstract

BACKGROUND: It has been suggested that peptides from gluten and casein may have a role in the origins of autism and that the physiology and psychology of autism might be explained by excessive opioid activity linked to these peptides. Research has reported abnormal levels of peptides in the urine and cerebrospinal fluid of persons with autism. If this is the case, diets free of gluten and /or casein should reduce the symptoms associated with autism.

OBJECTIVES: To determine the efficacy of gluten- and/or casein- free diets as an intervention to improve behaviour, cognitive and social functioning in individuals with autism.

SEARCH STRATEGY: Electronic searching of abstracts from the Cochrane Library (Issue 3, 2003), PsycINFO (1971- May 2003), EMBASE (1974- May 2003), CINAHL (1982- May 2003), MEDLINE (1986- May 2003), ERIC (1965-2003), LILACS (to 2003) and the specialist register of the Cochrane Complementary Medicine Field (January 2004). Review bibliographies were also examined to identify potential trials.

SELECTION CRITERIA: All randomised controlled trials involving programmes which eliminated gluten, casein or both gluten and casein from the diets of individuals diagnosed with autistic spectrum disorder.

DATA COLLECTION AND ANALYSIS: Abstracts of studies identified in searches of electronic databases were read and assessed to determine whether they might meet the inclusion criteria. The authors independently selected the relevant studies from the reports identified in this way. As only one trial fitted the inclusion criteria, no meta-analysis is currently possible and data are presented in narrative form.

MAIN RESULTS: The one trial included reported results on four outcomes. Unsurprisingly in such a small-scale study, the results for three of these outcomes (cognitive skills, linguistic ability and motor ability) had wide confidence intervals that spanned the line of nil effect. However, the fourth outcome, reduction in autistic traits, reported a significant beneficial treatment effect for the combined gluten- and casein- free diet.

REVIEWERS’ CONCLUSIONS: This is an important area of investigation and large scale, good quality randomised controlled trials are needed.

Gluten In The Diet May Be The Cause Of Recurring Headaches

ScienceDaily (Feb. 14, 2001) — ST. Paul, MN – It may be worthwhile to consider how much wheat you eat if you suffer from headaches or lack of coordination and have gluten sensitivity.

Researchers found that removing or cutting back on gluten – a protein in wheat and other grains –in the diet greatly reduced these symptoms among a middle-aged study group.

The study was reported in the latest issue of Neurology, the scientific journal of the American Academy of Neurology. The study reported 10 patients with gluten sensitivity whose MRI (Magnetic Resonance Imaging) tests suggested inflammation of the central nervous system. All had experienced occasional headaches and some suffered from unsteadiness and failure of muscle coordination. After removing gluten from their diets, nine of the 10 patients in the study found full or partial relief. One patient would not try the diet.

In one of the cases, a 50-year-old man developed headaches and nausea along with confusion and agitation. He had experienced episodic headache for four years but then the attacks progressed in frequency and severity. After starting a gluten-free diet his balance improved rapidly and his headaches cleared completely. After a relaxation of the gluten-free diet, his intermittent headaches returned.

In a similar case reported elsewhere, said study author and neurologist Marios Hadjivassiliou, M.D., a 45-year-old man had suffered from migraine since childhood, and that over time his attacks had become more severe and resistant to treatment. Following the diagnosis of gluten sensitivity and introduction of the gluten-free diet, his headaches were resolved.

“Removing the trigger factor, in this case gluten, may be a therapeutic intervention for some patients with gluten sensitivity and headache,” said Hadjivassiliou.

The diagnosis of gluten sensitivity and gluten-related neurological dysfunction relies on the presence of antibodies. In addition, certain genes make some individuals more susceptible to gluten sensitivity.

A neurologist is a medical doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system.

The American Academy of Neurology, an association of more than 17,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research.

For more information about the American Academy of Neurology, visit its web site at http://www.aan.com