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1.
Ann N Y Acad Sci ; 1498(1): 108-115, 2021 08.
Article in English | MEDLINE | ID: mdl-33438290

ABSTRACT

In 2014, there was an outbreak of beriberi on Kuria, a remote atoll in Kiribati, a small Pacific Island nation. A thiamine-poor diet consisting mainly of rice, sugar, and small amounts of fortified flour was likely to blame. We aimed to design a food fortification strategy to improve thiamine intakes in Kuria. We surveyed all 104 households on Kuria with a pregnant woman or a child 0-59 months. Repeat 24-h dietary recalls were collected from 90 men, 17 pregnant, 44 lactating, and 41 other women of reproductive age. The prevalence of inadequate thiamine intakes was >30% in all groups. Dietary modeling predicted that rice or sugar fortified at a rate of 0.3 and 1.4 mg per 100 g, respectively, would reduce the prevalence of inadequate thiamine intakes to <2.5% in all groups. Fortification is challenging because Kiribati imports food from several countries, depending on price and availability. One exception is flour, which is imported from Fiji. Although resulting in less coverage than rice or sugar, fortifying wheat flour with an additional 3.7 mg per 100 g would reduce the prevalence of inadequacy to under 10%. Kiribati is small and has limited resources; thus, a regional approach to thiamine fortification is needed.


Subject(s)
Food, Fortified , Thiamine Deficiency/epidemiology , Thiamine Deficiency/prevention & control , Thiamine , Cross-Sectional Studies , Disease Management , Female , Humans , Male , Micronesia/epidemiology , Pregnancy , Prevalence , Public Health Surveillance , Surveys and Questionnaires , Thiamine/administration & dosage , Thiamine Deficiency/etiology
2.
Matern Child Nutr ; 15(3): e12805, 2019 07.
Article in English | MEDLINE | ID: mdl-30822819

ABSTRACT

Since 2001, ChildFund Kenya has supplied micronutrient fortified school meals to preschoolers from two tribes (Kamba and Maasai) attending early childhood development (ECD) centres in Emali, S.E. Kenya. Lack of information on the micronutrient status of the preschoolers prompted a cross-sectional assessment of micronutrient (iron, zinc, selenium, vitamin A, vitamin D) status and prevalence of deficiencies among the two tribes. Data on sociodemographic, health, anthropometric status, and micronutrient supply from preschool meals were collected from 287 Kamba and 213 Maasai children aged 3 to 5 years attending 23 ECD centres. Nonfasting blood samples were collected for haemoglobin and plasma biomarkers of iron, zinc, selenium, vitamin A, vitamin D, C-reactive protein (CRP), α1 -acid glycoprotein, and immunoglobin G. The prevalence of anaemia was significantly higher in Maasai children than Kamba (38%, 95% CI [31%, 45%], vs. 5%, [3%, 9%]), as well as iron deficiency and its various stages (P < 0.001). No differences were seen in the prevalence of zinc, selenium, vitamin A, or vitamin D deficiencies (all P > 0.05). Body iron, CRP, and age were significant predictors of haemoglobin concentrations for both tribes (all P < 0.006) and plasma 25-OHD for Maasai children only. The higher prevalence of iron deficiency among Maasai than Kamba children was possibly attributed to the high consumption of cow's milk (low in bioavailable iron) in place of micronutrient fortified meals together with a higher prevalence of chronic inflammation and intestinal damage.


Subject(s)
Anemia, Iron-Deficiency/ethnology , Child Nutritional Physiological Phenomena , Hemoglobins/analysis , Micronutrients/blood , Micronutrients/deficiency , Nutritional Status , Anthropometry , Biomarkers/blood , Child, Preschool , Female , Food, Fortified , Humans , Inflammation/ethnology , Iron/blood , Iron Deficiencies , Kenya/epidemiology , Male , Meals , Prevalence , Selenium/blood , Selenium/deficiency , Vitamin A/blood , Vitamin A Deficiency , Vitamin D/blood , Vitamin D Deficiency , Zinc/blood , Zinc/deficiency
3.
J Nutr ; 148(7): 1103-1108, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29901753

ABSTRACT

Background: Consumption of high-dose folic acid supplements is common throughout pregnancy and lactation in several countries, including Canada, Brazil, and the United States, and may lead to high levels of circulating unmetabolized folic acid. Objective: The objective of the study was to characterize serum and whole-blood folate forms in Canadian lactating women regularly consuming a daily high-dose folic acid supplement. Methods: One-hundred and seventeen Canadian lactating women aged between 18 and 42 y, with a geometric mean ± SD prepregnancy body mass index (kg/m2) of 23.1 ± 1.2, were enrolled in a vitamin D supplementation trial between 13 and 22 wk of gestation. As part of the trial, the women received a daily multivitamin containing 1000 µg folic acid throughout pregnancy and lactation until 8 wk postpartum. At 8 wk postpartum, serum folate forms, including folic acid and RBC total folate, were determined from nonfasted blood samples. Differences in median folate vitamer concentrations among quintiles of serum total folate status were assessed by the Wald test and quantile regression methods. A breakpoint in the relation between serum folic acid and serum total folate was modeled with the use of the segmented package in R. Results: Median serum total folate concentration among participants was 79.3 nmol/L (5th-95th percentile 30.7-186 nmol/L) and median RBC folate concentration was 2790 nmol/L (5th-95th percentile 1330-4850 nmol/L). There was a breakpoint in the relation between serum total folate and serum folic acid at 78.5 nmol/L (95% CI: 67.9, 89.1 nmol/L), below which serum folic acid was not associated with serum total folate, and above which serum folic acid increased 0.78 nmol/L (95% CI: 0.70, 0.86 nmol/L; P < 0.001) for each 1 nmol/L increase in serum total folate. Conclusions: These data demonstrate the potential for high serum folic acid concentrations proportional to overall folate concentrations in lactating women with serum total folate >80 nmol/L taking high-dose supplemental folic acid. This study was registered at clinicaltrials.gov as NCT01112891.


Subject(s)
Folic Acid/administration & dosage , Folic Acid/blood , Lactation/physiology , Adult , Female , Humans , Vitamins/administration & dosage , Vitamins/blood
4.
Public Health Nutr ; 19(16): 2897-2905, 2016 11.
Article in English | MEDLINE | ID: mdl-27269122

ABSTRACT

OBJECTIVE: To estimate the folate status of New Zealand women of childbearing age following the introduction, in 2010, of a new voluntary folic acid fortification of bread programme. DESIGN: The 2011 Folate and Women's Health Survey was a cross-sectional survey of women aged 18-44 years carried out in 2011. The survey used a stratified random sampling technique with the Electoral Roll as the sampling frame. Women were asked about consumption of folic-acid-fortified breads and breakfast cereals in a telephone interview. During a clinic visit, blood was collected for serum and erythrocyte folate measurement by microbiological assay. SETTING: A North Island (Wellington) and South Island (Dunedin) city centre in New Zealand. SUBJECTS: Two hundred and eighty-eight women, of whom 278 completed a clinic visit. RESULTS: Geometric mean serum and erythrocyte folate concentrations were 30 nmol/l and 996 nmol/l, respectively. Folate status was 30-40 % higher compared with women of childbearing age sampled as part of a national survey in 2008/09, prior to the introduction of the voluntary folic acid bread fortification programme. In the 2011 Folate and Women's Health Survey, reported consumption of fortified bread and fortified breakfast cereal in the past week was associated with 25 % (P=0·01) and 15 % (P=0·04) higher serum folate concentrations, respectively. CONCLUSIONS: Serum and erythrocyte folate concentrations have increased in New Zealand women of childbearing age since the number of folic-acid-fortified breads was increased voluntarily in 2010. Consumption of fortified breads and breakfast cereals was associated with a higher folate status.


Subject(s)
Bread , Erythrocytes/chemistry , Folic Acid/blood , Food, Fortified , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Neural Tube Defects/prevention & control , New Zealand , Nutrition Surveys , Nutritional Status , Voluntary Programs , Young Adult
5.
Nutr Rev ; 74(4): 267-80, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26946252

ABSTRACT

Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined. Observational evidence suggests that consumption of coconut flesh or squeezed coconut in the context of traditional dietary patterns does not lead to adverse cardiovascular outcomes. However, due to large differences in dietary and lifestyle patterns, these findings cannot be applied to a typical Western diet. Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease.


Subject(s)
Cardiovascular Diseases/blood , Cholesterol/blood , Cocos/chemistry , Dietary Fats/pharmacology , Plant Oils/pharmacology , Cardiovascular Diseases/etiology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Coconut Oil , Diet , Dietary Fats/adverse effects , Humans , Plant Oils/adverse effects
6.
Eur J Nutr ; 55(7): 2281-93, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26358166

ABSTRACT

PURPOSE: Consuming 30 g of nuts/day is recommended to reduce chronic disease. However, nut consumption appears far from ideal among several populations. A potential strategy to increase consumption is to add nuts to a staple, for example, bread. Whether the health benefits and acceptability of nuts persist in this form is currently unknown. Thus, we examined the effects of consuming three nut-enriched breads on postprandial glycaemia, satiety, gastrointestinal tolerance, dietary intakes, and acceptance. METHODS: In this controlled, crossover study, 32 participants were randomly allocated to receive one of four breads for 8 days each. Three breads contained either 30 g of finely sliced hazelnuts, 30 g semi-defatted hazelnut flour, or 15 g of each (amounts per 120 g bread) and were compared with a control nut-free bread. Blood glucose response was measured over 120 min, along with ratings of gastrointestinal discomfort. Appetite ratings and diet diaries were completed during each treatment period. RESULTS: Area under the blood glucose curve was significantly lower for the nut breads compared to the control bread (all P < 0.001), with no significant differences between the nut breads (all P ≥ 0.130). There were no significant differences in satiety (all P ≥ 0.135) or gastrointestinal symptoms (all P ≥ 0.102) between the breads. Acceptance was highest for the finely sliced hazelnut bread. Furthermore, consuming hazelnut-enriched bread improved diet quality, increasing monounsaturated fat, vitamin E, and dietary fibre intakes. CONCLUSION: Bread appears to be an effective and acceptable vehicle for increasing nut consumption, resulting in improved postprandial glycaemia and diet profiles. Long-term studies are now required.


Subject(s)
Bread/analysis , Food Handling , Nuts , Adolescent , Adult , Aged , Appetite , Blood Glucose/metabolism , Consumer Behavior , Corylus , Cross-Over Studies , Dietary Carbohydrates/administration & dosage , Dietary Carbohydrates/analysis , Dietary Fats/administration & dosage , Dietary Fats/analysis , Dietary Fiber/administration & dosage , Dietary Fiber/analysis , Dietary Proteins/administration & dosage , Dietary Proteins/analysis , Energy Intake , Fatty Acids/administration & dosage , Fatty Acids/analysis , Fatty Acids, Monounsaturated/administration & dosage , Fatty Acids, Monounsaturated/analysis , Fatty Acids, Unsaturated/administration & dosage , Fatty Acids, Unsaturated/analysis , Female , Flour/analysis , Humans , Male , Micronutrients/administration & dosage , Micronutrients/analysis , Middle Aged , Nutrition Assessment , Postprandial Period , Satiation , Taste , Young Adult
7.
J Nutr ; 144(1): 68-74, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24174623

ABSTRACT

National data on the blood folate status of New Zealand adults is lacking. The objective of this study was to describe the blood folate status and examine the predictors of blood folate status in a national sample of adults from New Zealand, a country with voluntary folic acid fortification. The 2008/09 New Zealand Adult Nutrition Survey was a nationwide multistage systematic random cross-sectional survey. Serum and erythrocyte folate concentrations were measured by microbiologic assay. The survey included 4721 participants aged ≥15 y, 3359 of whom provided a nonfasting blood sample. Biochemical folate status was measured in 3277 participants. The median serum and erythrocyte folate concentrations were 23 and 809 nmol/L, respectively. The prevalence of biochemical folate deficiency, defined as plasma folate <6.8 nmol/L or erythrocyte folate <305 nmol/L, was 2%. Having breakfast daily compared with never eating breakfast was associated with 53% higher serum and 25% higher erythrocyte folate concentrations; consumers of fortified yeast extract spread had 17% higher serum and 14% higher erythrocyte folate concentrations than nonconsumers; daily users of folate-containing supplements compared with nonusers had 48% higher serum and 28% higher erythrocyte folate concentrations. The prevalence of biochemical folate deficiency in New Zealand adults is low. Participants who ate breakfast more frequently, consumed folate-fortified yeast, or used a daily folate supplement had higher blood folate concentrations.


Subject(s)
Dietary Supplements , Erythrocytes/chemistry , Folic Acid/administration & dosage , Folic Acid/blood , Food, Fortified , Adolescent , Adult , Breakfast , Cross-Sectional Studies , Female , Folic Acid Deficiency/blood , Folic Acid Deficiency/epidemiology , Humans , Linear Models , Male , Middle Aged , Multivariate Analysis , New Zealand , Nutrition Surveys , Nutritional Status , Prevalence , Socioeconomic Factors , Surveys and Questionnaires , Young Adult
8.
J Sci Med Sport ; 17(4): 356-60, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24045086

ABSTRACT

OBJECTIVES: The attenuation of the number and severity of infections is of importance to athletes. Probiotics use has increased over recent years with beneficial effects believed to include improvements in immune function. Research has focused on their effectiveness for reducing the number, duration and severity of infections amongst endurance athletes. At present no research has been undertaken with team sport athletes. This randomised controlled trial aimed to determine the effectiveness of probiotics on the number, duration and severity of infections amongst elite union rugby players. DESIGN: Randomised control trial with two arms; placebo and probiotic. METHODS: Thirty elite rugby union players were allocated in random order to receive a probiotics supplement or a placebo for four weeks each. Supplements were consumed on a daily basis. There was a four week washout period between treatments. Participants completed a daily diary to identify and rate the severity of any infectious symptoms. RESULTS: During the probiotic treatment 14/30 participants never experienced a single upper respiratory tract illness (URTI) or gastrointestinal (GI) episode, compared to 6/30 on the placebo supplementation (p=0.033). The mean±standard deviation for the number of days of illness tended to be higher for the placebo, (5.8±6.6 days) than probiotic (3.4±4.6 days), (p=0.054). There was no significant difference in the severity of the symptoms between the two treatment groups (p=0.110). CONCLUSIONS: These positive effects of probiotic supplements provide evidence for the beneficial effects of daily supplementation with these probiotic strains in highly trained rugby union players.


Subject(s)
Football , Gastrointestinal Diseases/prevention & control , Probiotics/therapeutic use , Respiratory Tract Infections/prevention & control , Severity of Illness Index , Adult , Cross-Over Studies , Dietary Supplements , Gastrointestinal Diseases/microbiology , Humans , Male , Single-Blind Method , Time Factors , Young Adult
9.
Int J Sport Nutr Exerc Metab ; 22(1): 19-23, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22248496

ABSTRACT

Endurance events>10 hr are becoming increasingly popular but provide numerous physiological challenges, several of which can be attenuated with optimal nutritional intakes. Previous studies in ultraendurance races have reported large energy deficits during events. The authors therefore aimed to assess nutritional intakes in relation to performance among ultraendurance cyclists. This observational study included 18 cyclists in a 384-km cycle race. At race registration each cyclist's support crew was provided with a food diary for their cyclist. On completion of the race, cyclists were asked to recall their race food and drink intakes. All food and fluids were analyzed using a computer software package. Mean (SD) time to complete the race was 16 hr 21 min (2 hr 2 min). Mean (SD) energy intake was 18.7 (8.6) MJ, compared with an estimated energy requirement for the race of 25.5 (7.4) MJ. There was a significant negative relationship between energy intake and time taken to complete the race (p=.023, r²=-.283). Mean (SD) carbohydrate, fat, and protein intakes were 52 (27), 15.84 (56.43), and 2.94 (7.25) g/hr, respectively. Only carbohydrate (p=.015, r²=-.563) and fat intake (p=.037, r²=-.494) were associated with time taken to complete the race. This study demonstrates the difficulties in meeting the high energy demands of ultraendurance cycling. The relationship between energy intake and performance suggests that reducing the energy deficit may be advantageous. Given the high carbohydrate intakes of these athletes, increasing energy intake from fat should be investigated as a means of decreasing energy deficits.


Subject(s)
Athletic Performance/physiology , Energy Intake , Physical Endurance/physiology , Physical Fitness/physiology , Stress, Physiological , Adult , Aged , Bicycling , Diet Records , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Dietary Supplements , Female , Humans , Male , Middle Aged , Performance-Enhancing Substances/administration & dosage , Weight Loss
10.
J Am Coll Nutr ; 29(4): 365-72, 2010 Aug.
Article in English | MEDLINE | ID: mdl-21041811

ABSTRACT

BACKGROUND: Wholegrain intake is inversely related to weight gain over time, but little information is available on the role of pulses in weight control. OBJECTIVE: To compare weight loss, metabolic outcomes, and nutrient intakes in obese people assigned to a diet rich in pulses and wholegrains or a control diet. METHODS: Randomized controlled study of 18 months with 113 volunteers (body mass index [BMI] ≥ 28 kg/m(2)). Diets were based on guidelines published by the National Heart Foundation of New Zealand. The intervention group was advised to consume 2 serves of pulses and 4 serves of wholegrain foods per day as substitutions for more refined carbohydrates. RESULTS: Fiber intakes were higher, intakes of several vitamins and minerals were better maintained, and dietary glycemic index was lower in the intervention compared with the control group. Mean (standard error [SE]) weight loss at 6 months was 6.0 (0.7) kg and 6.3 (0.6) kg in the control and intervention groups, respectively, and was not different between groups (p > 0.05). Blood pressure, triglycerides, and glycemic load were lowered in both groups compared with baseline. Waist circumference was decreased at 18 months in the intervention compared with the control group (-2.8 cm; 95% confidence interval [CI]: -0.4, -5.1). CONCLUSIONS: Incorporation of pulses and wholegrain foods into a weight loss program resulted in a greater reduction in waist circumference compared with the group consuming a control diet, although no difference in weight loss was noted between groups. Retention of several nutrients was better with the pulse and wholegrain diet.


Subject(s)
Dietary Carbohydrates/pharmacology , Dietary Fiber/pharmacology , Edible Grain/chemistry , Fabaceae/chemistry , Obesity/diet therapy , Weight Loss , Adult , Blood Pressure , Dietary Fiber/administration & dosage , Female , Glycemic Index , Humans , Male , Micronutrients/administration & dosage , Middle Aged , Obesity/blood , Plant Preparations/pharmacology , Seeds/chemistry , Triglycerides/blood , Waist Circumference , Weight Loss/drug effects
11.
Int J Sport Nutr Exerc Metab ; 20(4): 307-21, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20739719

ABSTRACT

PURPOSE: This study investigated the effect of ingesting 0.3 g/kg body weight (BW) of sodium bicarbonate (NaHCO3) on physiological responses, gastrointestinal (GI) tolerability, and sprint performance in elite rugby union players. METHODS: Twenty-five male rugby players, age 21.6 (2.6) yr, participated in a randomized, double-blind, placebo-controlled crossover trial. Sixty-five minutes after consuming 0.3 g/kg BW of either NaHCO3 or placebo, participants completed a 25-min warm-up followed by 9 min of high-intensity rugby-specific training followed by a rugby-specific repeated-sprint test (RSRST). Whole-blood samples were collected to determine lactate and bicarbonate concentrations and pH at baseline, after supplement ingestion, and immediately after the RSRST. Acute GI discomfort was assessed by questionnaire throughout the trials, and chronic GI discomfort was assessed during the 24 hr postingestion. RESULTS: After supplement ingestion and immediately after the RSRST, blood HCO3⁻ concentration and pH were higher for the NaHCO3 condition than for the placebo condition (p < .001). After the RSRST, blood lactate concentrations were significantly higher for the NaHCO3 than for the placebo condition (p < .001). There was no difference in performance on the RSRST between the 2 conditions. The incidence of belching, stomachache, diarrhea, stomach bloating, and nausea was higher after ingestion of NaHCO3 than with placebo (all p < .050). The severity of stomach cramps, belching, stomachache, bowel urgency, diarrhea, vomiting, stomach bloating, and flatulence was rated worse after ingestion of NaHCO3 than with placebo (p < .050). CONCLUSIONS: NaHCO3 supplementation increased blood HCO3⁻ concentration and attenuated the decline in blood pH compared with placebo during high-intensity exercise in well-trained rugby players but did not significantly improve exercise performance. The higher incidence and greater severity of GI symptoms after ingestion of NaHCO3 may negatively affect physical performance, and the authors strongly recommend testing this supplement during training before use in competitive situations.


Subject(s)
Acid-Base Equilibrium/drug effects , Athletic Performance/physiology , Bicarbonates/blood , Football/physiology , Sodium Bicarbonate/administration & dosage , Acid-Base Equilibrium/physiology , Cross-Over Studies , Dietary Supplements , Double-Blind Method , Gastrointestinal Diseases/chemically induced , Humans , Hydrogen-Ion Concentration/drug effects , Lactic Acid/blood , Male , Oxygen Consumption/physiology , Running/physiology , Sodium Bicarbonate/adverse effects , Young Adult
12.
Neurobiol Aging ; 24(1): 57-65, 2003.
Article in English | MEDLINE | ID: mdl-12493551

ABSTRACT

An alternative pathway for dehydroepiandrosterone (DHEA) synthesis has been suggested by treating rat and human brain cells with ferrous sulfate and beta-amyloid (Abeta). To determine if this pathway exists in human brain, levels of DHEA in hippocampus, hypothalamus and frontal cortex from Alzheimer's disease (AD) patients and age-matched controls were measured. DHEA is significantly higher in AD brain than control, and was highest in AD hippocampi. Cytochrome p450 17alpha-hydroxylase, responsible for peripheral DHEA synthesis, is not present in hippocampus. DHEA levels in AD cerebrospinal fluid (CSF) were significantly higher than age-matched controls. AD serum DHEA levels are lower than CSF, and not significantly different from controls. Treatment of control hippocampus, hypothalamus and serum with FeSO(4) increases DHEA, suggesting that levels of precursor are higher in control that in AD brain. This suggests that (i). an alternative precursor is present in control brain, (ii). AD brain DHEA is formed by oxidative stress metabolism of precursor, and (iii). CSF DHEA levels and serum DHEA formation in response to FeSO(4) may serve as an indicator of AD pathology.


Subject(s)
Alzheimer Disease/metabolism , Dehydroepiandrosterone/metabolism , Oxidative Stress , Aged , Aged, 80 and over , Alzheimer Disease/blood , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Amyloid beta-Peptides/blood , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/drug effects , Amyloid beta-Peptides/metabolism , Analysis of Variance , Blotting, Western , Dehydroepiandrosterone/blood , Dehydroepiandrosterone/cerebrospinal fluid , Female , Frontal Lobe/drug effects , Frontal Lobe/metabolism , Frontal Lobe/pathology , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Humans , Hypothalamus/drug effects , Hypothalamus/metabolism , Hypothalamus/pathology , Immunohistochemistry , Iron/therapeutic use , Male , Matched-Pair Analysis , Pregnenediones/analysis , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction/methods , Steroid 17-alpha-Hydroxylase/metabolism , Sulfides/therapeutic use
13.
J Neurochem ; 83(5): 1110-9, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12437582

ABSTRACT

22R-hydroxycholesterol, a steroid intermediate in the pathway of pregnenolone formation from cholesterol, was found at lower levels in Alzheimer's disease (AD) hippocampus and frontal cortex tissue specimens compared to age-matched controls. beta-Amyloid (Abeta) peptide has been shown to be neurotoxic and its presence in brain has been linked to AD pathology. 22R-hydroxycholesterol was found to protect, in a dose-dependent manner, against Abeta-induced rat sympathetic nerve pheochromocytoma (PC12) and differentiated human Ntera2/D1 teratocarcinoma (NT2N) neuron cell death. Other steroids tested were either inactive or acted on rodent neurons only. The effect of 22R-hydroxycholesterol was found to be stereospecific because its enantiomer 22S-hydroxycholesterol failed to protect the neurons from Abeta-induced cell death. Moreover, the effect of 22R-hydroxycholesterol was specific for Abeta-induced cell death because it did not protect against glutamate-induced neurotoxicity. The neuroprotective effect of 22R-hydroxycholesterol was seen when using Abeta1-42 but not the Abeta25-35 peptide. To investigate the mechanism of action of 22R-hydroxycholesterol we examined the direct binding of this steroid to Abeta using a novel cholesterol-protein binding blot assay. Using this method the direct specific binding, under native conditions, of 22R-hydroxycholesterol to Abeta1-42 and Abeta17-40, but not Abeta25-35, was observed. These data suggest that 22R-hydroxycholesterol binds to Abeta and the formed 22R-hydroxycholesterol/Abeta complex is not toxic to rodent and human neurons. We propose that 22R-hydroxycholesterol offers a new means of neuroprotection against Abeta toxicity by inactivating the peptide.


Subject(s)
Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/toxicity , Hydroxycholesterols/pharmacology , Neurons/drug effects , Neuroprotective Agents/pharmacology , Aged , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/metabolism , Animals , Binding, Competitive/drug effects , Cell Death , Cell Line , Computer Simulation , Female , Frontal Lobe/chemistry , Glutamic Acid/toxicity , Hippocampus/chemistry , Humans , Hydroxycholesterols/chemistry , Hydroxycholesterols/metabolism , Male , Models, Molecular , Neurons/cytology , Neurons/metabolism , Neuroprotective Agents/analysis , Neuroprotective Agents/metabolism , PC12 Cells , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Peptide Fragments/toxicity , Protein Binding/physiology , Rats , Stereoisomerism , Substrate Specificity
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