aron troen | The Hebrew University of Jerusalem (original) (raw)
Papers by aron troen
Alzheimers & Dementia, Jul 1, 2017
University of S~ao Paulo, S~ao Paulo, Brazil; Department & Institute of Psychiatry Faculty of... more University of S~ao Paulo, S~ao Paulo, Brazil; Department & Institute of Psychiatry Faculty of Medicine University of S~ao Paulo, S~ao Paulo, Brazil; Laboratory of Neurosciences, Institute of Psychiatry, Faculty of Medicine, University of S~ao Paulo, S~ao Paulo, Brazil; Thomas Jefferson University College of Health Professions, Philadelphia, PA, USA; Johns Hopkins University School of Nursing, Baltimore, MD, USA; Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of S~ao Paulo, S~ao Paulo-SP, Brazil. Contact e-mail: xandamartini@usp.br
The FASEB Journal, Apr 1, 2010
Advances in Nutrition, 2022
Vitamin B-12 is a water-soluble vitamin that plays important roles in intermediary metabolism. Vi... more Vitamin B-12 is a water-soluble vitamin that plays important roles in intermediary metabolism. Vitamin B-12 deficiency has many identifiable causes, including autoimmune and other gastrointestinal malabsorption disorders, dietary deficiency, and congenital defects in genes that are involved in vitamin B-12 trafficking and functions. Another putative cause of vitamin B-12 deficiency is the high-folate-low vitamin B-12 interaction, first suspected as the cause for observed relapse and exacerbation of the neurological symptoms in patients with pernicious anemia who were prescribed high oral doses of folic acid. We propose that this interaction is real and represents a novel cause of vitamin B-12 depletion with specific etiology. We hypothesize that excessive intake of folic acid depletes serum holotranscobalamin (holoTC), thereby decreasing active vitamin B-12 in the circulation and limiting its availability for tissues. This effect is specific for holoTC and does not affect holohaptocorrin, the inert form of serum vitamin B-12. Depletion of holoTC by folic acid in individuals with already low vitamin B-12 status further compromises the availability of vitamin B-12 coenzymes to their respective enzymes, and consequently a more pronounced state of biochemical deficiency. This hypothesis is drawn from evidence of observational and intervention studies of vitamin B-12-deficient patients and epidemiological cohorts. The evidence also suggests that, in a depleted state, vitamin B-12 is diverted to the hematopoietic system or the kidney. This most likely reflects a selective response of tissues expressing folate receptors with high affinity for unmetabolized folic acid (UMFA; e.g., hematopoietic progenitors and renal tubules) compared with those tissues (e.g., liver) that only express the reduced folate carrier, which is universally expressed but has poor affinity for UMFA. The biochemical and physiological mechanisms underlying this interaction require elucidation to clarify its potential public health significance. Adv Nutr 2022;13:16-33. Statement of Significance: There is significant circumstantial evidence that excess folic acid consumption exacerbates vitamin B-12 insufficiency, but a biochemical/physiological mechanism has not yet been identified. Herein it is hypothesized that excessive intake of folic acid depletes serum holotranscobalamin, thereby decreasing active vitamin B-12 in the circulation and limiting its availability for tissues.
Current Gerontology and Geriatrics Research, 2012
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2019
White matter hyperintensities (WMH) are frequently seen on brain MRI scans of older people. Usual... more White matter hyperintensities (WMH) are frequently seen on brain MRI scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMH are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease, AD). WMH are also seen in cognitively healthy people. In this collaboration of academic, clinical and pharmaceutical industry perspectives, we identify outstanding questions about WMH and their relation to cognition, dementia and AD. What molecular and cellular changes underlie WMH? What are the neuropathological correlates of WMH? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMH? What do WMH signify in people diagnosed with AD? What are the risk factors for developing WMH? What preventive and therapeutic strategies target WMH? Answering these questions will improve prevention and treatment of WMH and dementia.
Frontiers in Public Health, Mar 16, 2023
Thyroid, Aug 1, 2018
BACKGROUND Milk is a major source of iodine in human nutrition. Because both iodine content and t... more BACKGROUND Milk is a major source of iodine in human nutrition. Because both iodine content and the consumption of milk and dairy vary widely over time and populations, their contribution to iodine intake must be evaluated regularly. A recent national iodine survey found Israel's population to be mildly iodine deficient, possibly due to unmonitored changes in the food content of dietary iodine. Accounting for dairy iodine content can help guide efforts to prevent iodine deficiency. OBJECTIVES This study aimed to determine the iodine concentration of dairy products typically consumed in the Israeli diet, and to estimate iodine intake from dairy products among Israeli adults. METHODS Iodine was analyzed in 33 selected dairy products that account for 89% of the total population's dairy intake according to the "MABAT" Israeli National Health and Nutrition survey. Based on these data, the distribution of iodine intake from milk, dairy, and dairy-based foods in the adult population was calculated. RESULTS Israeli milk is rich in iodine, with a mean concentration of 22 μg/100 g. However, due to low dairy consumption, the mean iodine intake from milk and dairy was only 34 μg/day (median 23 μg/day; range: 0-337 μg/day) or 22% of the recommended daily allowance. Self-reported intake among poor, male, and Arab subgroups was even lower. CONCLUSIONS Because Israeli milk and dairy products are iodine rich, their contribution to the population's iodine intake would increase if they were consumed in greater amounts, particularly by high-risk groups. Dairy's potential contribution to iodine nutrition should be considered in recommendations for dairy consumption and iodine prophylaxis.
Journal of Functional Foods, May 1, 2016
Passion fruit is a commercially important crop. The neuroprotective activity of fruit extracts fr... more Passion fruit is a commercially important crop. The neuroprotective activity of fruit extracts from two hybrid lines of antioxidant ester thiol-rich Passiflora edulis Sims, the commercial "Passion Dream" and novel cultivar 428 ("Dena") line were studied. Crude extracts from line 428 displayed the strongest dose-dependent neuroprotective activity, preventing glutamate induced cell-death, mitochondrial depolarization and glutathione depletion, when added to the medium of cultured HT4 neurons (p < 0.05). Supplementing diet of mice with the 428 fruit-extract improved survival of dopaminergic neurons by 60% in mice injected with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MTPT) compared to control-fed MPTP-injected mice (p < 0.05). The neuroprotection conferred by passion fruit extracts in vivo and in vitro shows promise for further research into their bioactive potential for medical exploitation.
Journal of Thyroid Research, 2014
Background. Information about iodine intake is crucial for preventing thyroid diseases. Inadequat... more Background. Information about iodine intake is crucial for preventing thyroid diseases. Inadequate iodine intake can lead to thyroid diseases, including nontoxic nodular goiter (NNG). Objective. To estimate iodine intake and explore its correlation with thyroid diseases among Israeli adults living near the Mediterranean coast, where iodine-depleted desalinated water has become a major source of drinking water. Methods. Cross-sectional study of patients attending Barzilai Medical Center Ashkelon. Participants, who were classified as either NNG (= 17), hypothyroidism (= 14), or control (= 31), provided serum thyroglobulin (Tg) and completed a semiquantitative iodine food frequency questionnaire. Results. Elevated serum Tg values (Tg > 60 ng/mL) were significantly more prevalent in the NNG group than in the other groups (29% versus 7% and 0% for hypothyroidism and controls, resp., < 0.05). Mean estimated iodine intake was significantly lower in the NNG group (65 ± 30 g/d) than in controls (115 ± 60 g/d) (< 0.05) with intermediate intake in the hypothyroid group (73 ± 38 g/d). Conclusions. Elevated serum Tg values and low dietary iodine intake are associated with NNG among adult patients in Ashkelon District, Israel. Larger studies are needed in order to expand on these important initial findings.
Journal of Bone and Mineral Research, Dec 1, 2017
Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels wit... more Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B 12 , B 6 , and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B 6 (50 mg/day), and vitamin B 12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard ¼ 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B 12 or B 6 , or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease.
Progress in Neuro-psychopharmacology & Biological Psychiatry, Sep 1, 2005
Growing epidemiological evidence of associations between mildly elevated plasma homocysteine with... more Growing epidemiological evidence of associations between mildly elevated plasma homocysteine with age-related cognitive impairment, neurodegenerative and cerebrovascular disease has stimulated interest in the role of homocysteine in neurological and neuropsychiatric disorders. Homocysteine is an intermediate in the folate, vitamin B12 and B6 dependent pathways of one-carbon and sulfur amino acid metabolism. Impairments of these pathways may cause CNS dysfunction by promoting the intracellular generation of homocysteine, which is postulated to have vasotoxic and neurotoxic properties. It might also inhibit the methylation of myelin basic protein and membrane phospholipids, or disrupt biogenic amine metabolism and many other vital CNS reactions. However, it is unclear which, if any, of these putative mechanisms underlies the epidemiological associations. Genetic mouse models of hyperhomocysteinemia suggest that the primary metabolic disturbances rather than homocysteine per se may be important in determining neurological outcomes. However, severe and early developmental abnormalities in these mice limit their usefulness for understanding the relation of hyperhomocysteinemia to adult CNS disorders. Pharmacologic and dietary studies on homocysteine in rodents have reported heightened neuronal sensitivity to neurotoxic insults, neurochemical abnormalities and cerebrovascular dysfunction. Such studies are consistent with a causal relationship, but they fail to distinguish between effects that might result from a dietary imbalance and those that might be caused by homocysteine per se. Future work should be directed towards refining these models in order to distinguish between the effects of homocysteine and its determinants on neurological and behavioral outcomes that represent different CNS disorders.
Alzheimer's disease (AD) is a devastating and debilitating neurodegenerative condition, and t... more Alzheimer's disease (AD) is a devastating and debilitating neurodegenerative condition, and the most common cause of dementia among the elderly. Despite considerable advances in the cellular and molecular biology of AD, however, little progress has been made in identifying the causes of the disease.
Israel Journal of Health Policy Research, Mar 28, 2022
Background: Adequate iodine intake is essential for human health, for normal thyroid function, an... more Background: Adequate iodine intake is essential for human health, for normal thyroid function, and for attainment of full intellectual potential in children. In light of Israel's lack of a mandatory salt fortification policy, heavy reliance on desalination and low iodine intake from dairy products and seafood, there is concern in Israel that the population is iodine deficient. Indeed, the first Israeli National Iodine Survey in 2016 found a median urinary iodine concentration (UIC) of 83 µg/L among school age children, falling below the WHO's adequacy range of 100-299 µg/L for children. Methods: In the framework of the National Human Biomonitoring Program in Israel, spot urine samples and questionnaire data were collected from 166 healthy children aged 4-12 years in 2020-2021. Urinary iodine concentrations were measured at the Ministry of Health National Biomonitoring Laboratory, using mass spectrometry. An international comparison of median urinary iodine concentrations (UIC) was performed taking into consideration the levels of desalinated water per capita, and fortification policies. Results: The overall median (interquartile range [IQR]) UIC was 80.1 µg/L (44.7-130.8 µg/L) indicating that the population's iodine status has not improved in the five years that have passed since inadequacy was first identified. When comparing 13 countries with population size above 150,000, whose desalinated water per capita was at least 1 m 3 , Israel and Lebanon were the only countries with median UIC below the WHO adequacy range. Conclusions: There is an urgent need for mandatory salt fortification in Israel. Based on our international comparison, we conclude that the potential impact of desalination on iodine intake can be compensated for using the implementation of salt fortification policy. This study highlights the critical need for public health surveillance of nutritional and environmental exposures using human biomonitoring, with emphasis on vulnerable populations such as pregnant women and children.
The FASEB Journal, Apr 1, 2013
Alzheimers & Dementia, Jul 1, 2017
40–70, % women 46). No trend across measurement occasions was detected and the data were interpre... more 40–70, % women 46). No trend across measurement occasions was detected and the data were interpreted to represent usual intake levels. Paired sample t-tests showed that group-based reaction time scores significantly increased from baseline to re-assessment only in the lower intake group (p<0.001), while they remained stable in the higher intake group (p1⁄40.264). These findings indicate a protective effect of higher B vitamin intake. Conclusions: Multi-trajectory analysis has been used to interpret repeated measurement lifestyle data; here, identifying groups representing usual exposure rather than change in exposure over time. In a general population sample, it was found that a higher usual dietary B vitamins intake is associated with a slower decline in mean reaction time over 4 years. Although further (multivariable) analysis is required to provide evidence of causality, multi-trajectory analysis is a useful tool for empirically characterising lifestyle, enabling more detailed investigation of the impact of lifestyle on dementia related outcomes.
Alzheimers & Dementia, Jul 1, 2017
University of S~ao Paulo, S~ao Paulo, Brazil; Department & Institute of Psychiatry Faculty of... more University of S~ao Paulo, S~ao Paulo, Brazil; Department & Institute of Psychiatry Faculty of Medicine University of S~ao Paulo, S~ao Paulo, Brazil; Laboratory of Neurosciences, Institute of Psychiatry, Faculty of Medicine, University of S~ao Paulo, S~ao Paulo, Brazil; Thomas Jefferson University College of Health Professions, Philadelphia, PA, USA; Johns Hopkins University School of Nursing, Baltimore, MD, USA; Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of S~ao Paulo, S~ao Paulo-SP, Brazil. Contact e-mail: xandamartini@usp.br
The FASEB Journal, Apr 1, 2010
Advances in Nutrition, 2022
Vitamin B-12 is a water-soluble vitamin that plays important roles in intermediary metabolism. Vi... more Vitamin B-12 is a water-soluble vitamin that plays important roles in intermediary metabolism. Vitamin B-12 deficiency has many identifiable causes, including autoimmune and other gastrointestinal malabsorption disorders, dietary deficiency, and congenital defects in genes that are involved in vitamin B-12 trafficking and functions. Another putative cause of vitamin B-12 deficiency is the high-folate-low vitamin B-12 interaction, first suspected as the cause for observed relapse and exacerbation of the neurological symptoms in patients with pernicious anemia who were prescribed high oral doses of folic acid. We propose that this interaction is real and represents a novel cause of vitamin B-12 depletion with specific etiology. We hypothesize that excessive intake of folic acid depletes serum holotranscobalamin (holoTC), thereby decreasing active vitamin B-12 in the circulation and limiting its availability for tissues. This effect is specific for holoTC and does not affect holohaptocorrin, the inert form of serum vitamin B-12. Depletion of holoTC by folic acid in individuals with already low vitamin B-12 status further compromises the availability of vitamin B-12 coenzymes to their respective enzymes, and consequently a more pronounced state of biochemical deficiency. This hypothesis is drawn from evidence of observational and intervention studies of vitamin B-12-deficient patients and epidemiological cohorts. The evidence also suggests that, in a depleted state, vitamin B-12 is diverted to the hematopoietic system or the kidney. This most likely reflects a selective response of tissues expressing folate receptors with high affinity for unmetabolized folic acid (UMFA; e.g., hematopoietic progenitors and renal tubules) compared with those tissues (e.g., liver) that only express the reduced folate carrier, which is universally expressed but has poor affinity for UMFA. The biochemical and physiological mechanisms underlying this interaction require elucidation to clarify its potential public health significance. Adv Nutr 2022;13:16-33. Statement of Significance: There is significant circumstantial evidence that excess folic acid consumption exacerbates vitamin B-12 insufficiency, but a biochemical/physiological mechanism has not yet been identified. Herein it is hypothesized that excessive intake of folic acid depletes serum holotranscobalamin, thereby decreasing active vitamin B-12 in the circulation and limiting its availability for tissues.
Current Gerontology and Geriatrics Research, 2012
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2019
White matter hyperintensities (WMH) are frequently seen on brain MRI scans of older people. Usual... more White matter hyperintensities (WMH) are frequently seen on brain MRI scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMH are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease, AD). WMH are also seen in cognitively healthy people. In this collaboration of academic, clinical and pharmaceutical industry perspectives, we identify outstanding questions about WMH and their relation to cognition, dementia and AD. What molecular and cellular changes underlie WMH? What are the neuropathological correlates of WMH? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMH? What do WMH signify in people diagnosed with AD? What are the risk factors for developing WMH? What preventive and therapeutic strategies target WMH? Answering these questions will improve prevention and treatment of WMH and dementia.
Frontiers in Public Health, Mar 16, 2023
Thyroid, Aug 1, 2018
BACKGROUND Milk is a major source of iodine in human nutrition. Because both iodine content and t... more BACKGROUND Milk is a major source of iodine in human nutrition. Because both iodine content and the consumption of milk and dairy vary widely over time and populations, their contribution to iodine intake must be evaluated regularly. A recent national iodine survey found Israel's population to be mildly iodine deficient, possibly due to unmonitored changes in the food content of dietary iodine. Accounting for dairy iodine content can help guide efforts to prevent iodine deficiency. OBJECTIVES This study aimed to determine the iodine concentration of dairy products typically consumed in the Israeli diet, and to estimate iodine intake from dairy products among Israeli adults. METHODS Iodine was analyzed in 33 selected dairy products that account for 89% of the total population's dairy intake according to the "MABAT" Israeli National Health and Nutrition survey. Based on these data, the distribution of iodine intake from milk, dairy, and dairy-based foods in the adult population was calculated. RESULTS Israeli milk is rich in iodine, with a mean concentration of 22 μg/100 g. However, due to low dairy consumption, the mean iodine intake from milk and dairy was only 34 μg/day (median 23 μg/day; range: 0-337 μg/day) or 22% of the recommended daily allowance. Self-reported intake among poor, male, and Arab subgroups was even lower. CONCLUSIONS Because Israeli milk and dairy products are iodine rich, their contribution to the population's iodine intake would increase if they were consumed in greater amounts, particularly by high-risk groups. Dairy's potential contribution to iodine nutrition should be considered in recommendations for dairy consumption and iodine prophylaxis.
Journal of Functional Foods, May 1, 2016
Passion fruit is a commercially important crop. The neuroprotective activity of fruit extracts fr... more Passion fruit is a commercially important crop. The neuroprotective activity of fruit extracts from two hybrid lines of antioxidant ester thiol-rich Passiflora edulis Sims, the commercial "Passion Dream" and novel cultivar 428 ("Dena") line were studied. Crude extracts from line 428 displayed the strongest dose-dependent neuroprotective activity, preventing glutamate induced cell-death, mitochondrial depolarization and glutathione depletion, when added to the medium of cultured HT4 neurons (p < 0.05). Supplementing diet of mice with the 428 fruit-extract improved survival of dopaminergic neurons by 60% in mice injected with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MTPT) compared to control-fed MPTP-injected mice (p < 0.05). The neuroprotection conferred by passion fruit extracts in vivo and in vitro shows promise for further research into their bioactive potential for medical exploitation.
Journal of Thyroid Research, 2014
Background. Information about iodine intake is crucial for preventing thyroid diseases. Inadequat... more Background. Information about iodine intake is crucial for preventing thyroid diseases. Inadequate iodine intake can lead to thyroid diseases, including nontoxic nodular goiter (NNG). Objective. To estimate iodine intake and explore its correlation with thyroid diseases among Israeli adults living near the Mediterranean coast, where iodine-depleted desalinated water has become a major source of drinking water. Methods. Cross-sectional study of patients attending Barzilai Medical Center Ashkelon. Participants, who were classified as either NNG (= 17), hypothyroidism (= 14), or control (= 31), provided serum thyroglobulin (Tg) and completed a semiquantitative iodine food frequency questionnaire. Results. Elevated serum Tg values (Tg > 60 ng/mL) were significantly more prevalent in the NNG group than in the other groups (29% versus 7% and 0% for hypothyroidism and controls, resp., < 0.05). Mean estimated iodine intake was significantly lower in the NNG group (65 ± 30 g/d) than in controls (115 ± 60 g/d) (< 0.05) with intermediate intake in the hypothyroid group (73 ± 38 g/d). Conclusions. Elevated serum Tg values and low dietary iodine intake are associated with NNG among adult patients in Ashkelon District, Israel. Larger studies are needed in order to expand on these important initial findings.
Journal of Bone and Mineral Research, Dec 1, 2017
Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels wit... more Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B 12 , B 6 , and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B 6 (50 mg/day), and vitamin B 12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard ¼ 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B 12 or B 6 , or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease.
Progress in Neuro-psychopharmacology & Biological Psychiatry, Sep 1, 2005
Growing epidemiological evidence of associations between mildly elevated plasma homocysteine with... more Growing epidemiological evidence of associations between mildly elevated plasma homocysteine with age-related cognitive impairment, neurodegenerative and cerebrovascular disease has stimulated interest in the role of homocysteine in neurological and neuropsychiatric disorders. Homocysteine is an intermediate in the folate, vitamin B12 and B6 dependent pathways of one-carbon and sulfur amino acid metabolism. Impairments of these pathways may cause CNS dysfunction by promoting the intracellular generation of homocysteine, which is postulated to have vasotoxic and neurotoxic properties. It might also inhibit the methylation of myelin basic protein and membrane phospholipids, or disrupt biogenic amine metabolism and many other vital CNS reactions. However, it is unclear which, if any, of these putative mechanisms underlies the epidemiological associations. Genetic mouse models of hyperhomocysteinemia suggest that the primary metabolic disturbances rather than homocysteine per se may be important in determining neurological outcomes. However, severe and early developmental abnormalities in these mice limit their usefulness for understanding the relation of hyperhomocysteinemia to adult CNS disorders. Pharmacologic and dietary studies on homocysteine in rodents have reported heightened neuronal sensitivity to neurotoxic insults, neurochemical abnormalities and cerebrovascular dysfunction. Such studies are consistent with a causal relationship, but they fail to distinguish between effects that might result from a dietary imbalance and those that might be caused by homocysteine per se. Future work should be directed towards refining these models in order to distinguish between the effects of homocysteine and its determinants on neurological and behavioral outcomes that represent different CNS disorders.
Alzheimer's disease (AD) is a devastating and debilitating neurodegenerative condition, and t... more Alzheimer's disease (AD) is a devastating and debilitating neurodegenerative condition, and the most common cause of dementia among the elderly. Despite considerable advances in the cellular and molecular biology of AD, however, little progress has been made in identifying the causes of the disease.
Israel Journal of Health Policy Research, Mar 28, 2022
Background: Adequate iodine intake is essential for human health, for normal thyroid function, an... more Background: Adequate iodine intake is essential for human health, for normal thyroid function, and for attainment of full intellectual potential in children. In light of Israel's lack of a mandatory salt fortification policy, heavy reliance on desalination and low iodine intake from dairy products and seafood, there is concern in Israel that the population is iodine deficient. Indeed, the first Israeli National Iodine Survey in 2016 found a median urinary iodine concentration (UIC) of 83 µg/L among school age children, falling below the WHO's adequacy range of 100-299 µg/L for children. Methods: In the framework of the National Human Biomonitoring Program in Israel, spot urine samples and questionnaire data were collected from 166 healthy children aged 4-12 years in 2020-2021. Urinary iodine concentrations were measured at the Ministry of Health National Biomonitoring Laboratory, using mass spectrometry. An international comparison of median urinary iodine concentrations (UIC) was performed taking into consideration the levels of desalinated water per capita, and fortification policies. Results: The overall median (interquartile range [IQR]) UIC was 80.1 µg/L (44.7-130.8 µg/L) indicating that the population's iodine status has not improved in the five years that have passed since inadequacy was first identified. When comparing 13 countries with population size above 150,000, whose desalinated water per capita was at least 1 m 3 , Israel and Lebanon were the only countries with median UIC below the WHO adequacy range. Conclusions: There is an urgent need for mandatory salt fortification in Israel. Based on our international comparison, we conclude that the potential impact of desalination on iodine intake can be compensated for using the implementation of salt fortification policy. This study highlights the critical need for public health surveillance of nutritional and environmental exposures using human biomonitoring, with emphasis on vulnerable populations such as pregnant women and children.
The FASEB Journal, Apr 1, 2013
Alzheimers & Dementia, Jul 1, 2017
40–70, % women 46). No trend across measurement occasions was detected and the data were interpre... more 40–70, % women 46). No trend across measurement occasions was detected and the data were interpreted to represent usual intake levels. Paired sample t-tests showed that group-based reaction time scores significantly increased from baseline to re-assessment only in the lower intake group (p<0.001), while they remained stable in the higher intake group (p1⁄40.264). These findings indicate a protective effect of higher B vitamin intake. Conclusions: Multi-trajectory analysis has been used to interpret repeated measurement lifestyle data; here, identifying groups representing usual exposure rather than change in exposure over time. In a general population sample, it was found that a higher usual dietary B vitamins intake is associated with a slower decline in mean reaction time over 4 years. Although further (multivariable) analysis is required to provide evidence of causality, multi-trajectory analysis is a useful tool for empirically characterising lifestyle, enabling more detailed investigation of the impact of lifestyle on dementia related outcomes.