Instruct: Given a question, retrieve documents that answer the question.
Query: Can Folic Acid Be Harmful?
Iron is an essential trace metal in human metabolism. However, imbalances in iron homeostasis are prevalent worldwide and have detrimental effects on human health. Humans do not have the ability to remove excess iron and therefore iron homeostasis is maintained by regulating the amount of iron entering the body from the diet. Iron is present in the human diet in number of different forms, including heme (from meat) and a variety of non-heme iron compounds. While heme is absorbed intact, the bioavailability of non-heme iron varies greatly depending on dietary composition. A number of dietary components are capable of interacting with iron to regulate its solubility and oxidation state. Interestingly, there is an emerging body of evidence suggesting that some nutrients also have direct effects on the expression and function of enterocyte iron transporters. In addition to dietary factors, body iron status is a major determinant of iron absorption. The roles of these important dietary and systemic factors in regulating iron absorption will be discussed in this review.
BACKGROUND/AIMS: Herbal agents are popular and perceived as safe because they are supposedly 'natural'. We report 10 cases of toxic hepatitis implicating Herbalife products. METHODS: To determine the prevalence and outcome of hepatotoxicity due to Herbalife products. A questionnaire was sent to all public Swiss hospitals. Reported cases were subjected to causality assessment using the CIOMS criteria. RESULTS: Twelve cases of toxic hepatitis implicating Herbalife preparations (1998-2004) were retrieved, 10 sufficiently documented to permit causality analysis. Median age of patients was 51 years (range 30-69) and latency to onset was 5 months (0.5-144). Liver biopsy (7/10) showed hepatic necrosis, marked lymphocytic/eosinophilic infiltration and cholestasis in five patients. One patient with fulminant liver failure was successfully transplanted; the explant showed giant cell hepatitis. Sinusoidal obstruction syndrome was observed in one case. Three patients without liver biopsy presented with hepatocellular (2) or mixed (1) liver injury. Causality assessment of adverse drug reaction was classified as certain in two, probable in seven and possible in one case(s), respectively. CONCLUSIONS: We present a case series of toxic hepatitis implicating Herbalife products. Liver toxicity may be severe. A more detailed declaration of components and pro-active role of regulatory agencies would be desirable.
The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.
The growing popularity and availability of over-the-counter (OTC) health products, including vitamins, raises serious concern about vitamin toxicity. We report a case of cirrhosis in a patient with habitual daily ingestion of an OTC dietary supplement that contained 13,000 microg vitamin A and was associated with marked clinical improvement after discontinuation. This case highlights the potential for liver damage that may be associated with long-term intake of OTC vitamin supplements, and indicates the need for medical supervision of such products.
Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.
Mild to moderate hyperhomocysteinemia is a risk factor for neurodegenerative diseases. Human studies suggest that homocysteine (Hcy) plays a role in brain damage, cognitive and memory decline. Numerous studies in recent years investigated the role of Hcy as a cause of brain damage. Hcy itself or folate and vitamin B12 deficiency can cause disturbed methylation and/or redox potentials, thus promoting calcium influx, amyloid and tau protein accumulation, apoptosis, and neuronal death. The Hcy effect may also be mediated by activating the N-methyl-D-aspartate receptor subtype. Numerous neurotoxic effects of Hcy can be blocked by folate, glutamate receptor antagonists, or various antioxidants. This review describes the most important mechanisms of Hcy neurotoxicity and pharmacological agents known to reverse Hcy effects.
Contemporary reproductive aged women and their offspring are facing an unprecedented onslaught of toxicant exposures from myriad sources in their day-to-day life. Public health recommendations regarding optimal diet and nutrition in pregnancy must incorporate several considerations including safety of available foodstuffs, cultural practices and lifestyle issues. Gestational consumption of contaminated seafood remains a potential source of toxicant exposure, including mercury, for the developing child. Health care professionals responsible for the care of women and their developing children need to become apprised of: a) risks associated with toxicant bioaccumulation in pregnancy; b) ongoing information emerging in the important field of reproductive toxicology; and c) strategies within the clinical setting to facilitate nutritional sufficiency and precautionary avoidance of adverse exposure among young women.
We present a case of a 14-year-old previously healthy boy with acute hepatotoxicity after noni berry juice consumption. As the popularity of noni berry consumption continues to increase, heightened awareness of the relation between noni berry consumption and acute hepatotoxicity is important.
Large differences exist between human populations in the frequency of colonic cancer. Epidemiological evidence indicates that these differences are strongly influenced by country of residence, and a negative correlation has been found between the fiber content of the diet and frequency of colonic cancer. This has prompted the hypothesis that high-fiber diets are in some way protective. However, reanalysis of the dietary data provides equally strong support for the hypothesis that the protective element may be phytic acid (inositol hexaphosphate). This heat- and acid-stable substance is present in high concentration in many food items, including cereal grains, nuts, and seeds. Phytic acid forms chelates with various metals and suppresses damaging iron-catalyzed redox reactions. Inasmuch as colonic bacteria have been shown to produce oxygen radicals in appreciable amounts, dietary phytic acid might suppress oxidant damage to intestinal epithelium and neighboring cells. Indeed, rapidly accumulating data from animal models indicate that dietary supplementation with phytic acid may provide substantial protection against experimentally induced colonic cancer. Should further investigations yield additional support for this hypothesis, purposeful amplification of dietary phytic acid content would represent a simple method for reducing the risk of colonic carcinogenesis.
Aloe has been widely used in phytomedicine. Phytomedicine describes aloe as a herb which has anti-inflammatory, anti-proliferative, anti-aging effects. In recent years several cases of aloe-induced hepatotoxicity were reported. But its pharmacokinetics and toxicity are poorly described in the literature. Here we report three cases with aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a 55-yr-old woman were admitted to the hospital for acute hepatitis. They had taken aloe preparation for months. Their clinical manifestation, laboratory findings and histologic findings met diagnostic criteria (RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe preparations, liver enzymes returned to normal level. Aloe should be considered as a causative agent in hepatotoxicity.
Historically, concerns with fish consumption have addressed risks from contaminants (e.g., methylmercury (MeHg), and PCBs). More recently public health concerns have widened in appreciation of the specific benefits of fish consumption such as those arising from polyunsaturated fatty acids (PUFAs) in fish oil. Fish contains varying levels of PUFAs and MeHg. Since both address the same health outcomes (in opposite directions) and occur together in fish, great care must be exercised in providing public health guidance. Mozaffarian and Rimm in a recent article (JAMA. 2006, 296:1885–99) have made a strong case for the beneficial effects of PUFAs in reducing the risk of coronary heart disease, but at the same time, have also broadly discounted the increased risks of coronary heart disease posed by MeHg in fish, stating that "... among adults... the benefits of fish intake exceed the potential risks." This conclusion appears to be based on an inaccurate and insufficiently critical analysis of the literature. This literature is re-examined in light of their conclusions, and the available and appropriate public health options are considered.
The use of over-the-counter supplements is commonplace in today's health conscious society. We present an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient consumed one Herbalife shake with two multivitamin tablets of the same brand for 12 years. When calculated this equated to more than the recommended daily allowance for vitamin A consumption. Deranged liver function tests were consistent with a cholestatic process. Liver biopsy was obtained and revealed features pathognomonic of vitamin A toxicity, without the usual fibrosis. When the supplements were ceased, his jaundice and alkaline phosphatase completely normalized. This case highlights the importance of health care providers documenting non-prescribed dietary supplements and considering them in the etiology of cholestatic liver disease. Copyright 2009 Elsevier Inc. All rights reserved.
We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.
Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, and ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio-Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.
Elevated plasma homocysteine levels are associated with an increased risk of atherosclerosis and thrombosis, as well as a variety of other pathologies such as birth defects, Alzheimer's disease and other dementias, osteoporosis, diabetes and renal disease. Homocysteine metabolism is catalyzed by a number of enzymes that require B-vitamins as cofactors, and homocysteine levels are particularly responsive to folate status. The predictive power of plasma homocysteine level as a risk factor for atherothrombotic orders raised the appealing hypothesis that reduction of homocysteine levels by vitamin supplementation might result in a commensurate reduction is the risk of atherothrombotic events. Unfortunately, most clinical trials failed to show a significant benefit of vitamin supplementation on cardiovascular events, in spite of significant lowering of plasma homocysteine levels. Thus, it is not clear whether homocysteine actually plays a causal role in many pathologies with which it is associated, or whether it is instead a marker for some other underlying mechanism. A large body of data links hyperhomocysteinemia and folate status with oxidant stress. In this article I review data that suggests that homocysteine not only promotes cellular and protein injury via oxidant mechanisms, but is also a marker for the presence of pathological oxidant stress. Thus, it is possible that hyperhomocysteinemia is not a common primary cause of atherothrombotic disorders in the general population, but rather a marker of systemic or endothelial oxidant stress that is a major mediator of these disorders. Published by Elsevier Ltd.
Amnesic shellfish poisoning (ASP) is caused by consumption of shellfish that have accumulated domoic acid, a neurotoxin produced by some strains of phytoplankton. The neurotoxic properties of domoic acid result in neuronal degeneration and necrosis in specific regions of the hippocampus. A serious outbreak of ASP occurred in Canada in 1987 and involved 150 reported cases, 19 hospitalisations and 4 deaths after consumption of contaminated mussels. Symptoms ranged from gastrointestinal disturbances, to neurotoxic effects such as hallucinations, memory loss and coma. Monitoring programmes are in place in numerous countries worldwide and closures of shellfish harvesting areas occur when domoic acid concentrations exceed regulatory limits. This paper reviews the chemistry, sources, metabolism and toxicology of domoic acid as well as human case reports of ASP and discusses a possible mechanism of toxicity.
Low folate has been causatively linked to depression, but research is contradictory. An association may arise due to chance, bias, confounding or reverse causality. A systematic review of observational studies which examined the association between depression and folate was conducted. 11 relevant studies (15 315 participants; three case–control studies, seven population surveys and one cohort study) examining the risk of depression in the presence of low folate were found. Pooling showed a significant relationship between folate status and depression (odds ratio (OR)pooled unadjusted = 1.55; 95% CI 1.26 to 1.91). This relationship remained after adjustment for potential confounding (OR)pooled adjusted = 1.42; 95% CI 1.10 to 1.83). Folate levels were also lower in depression. There is accumulating evidence that low folate status is associated with depression. Much of this evidence comes from case–control and cross‐sectional studies. Cohort studies and definitive randomised‐controlled trials to test the therapeutic benefit of folate are required to confirm or refute a causal relationship.
In human pregnancies, maternal absorption of iron is markedly curtailed in the first trimester. In a murine model, iron was teratogenic in the analogous embryonic period. Although iron is a weak mutagen, it is a powerful oxidant and a catalyst of formation of hydroxyl radicals. Studies are needed to determine if there might be an association of first trimester iron supplementation with miscarriage/fetal abnormalities.
To determine the effects of different diets on the genotoxicity of human faecal water, a diet rich in fat, meat and sugar but poor in vegetables and free of wholemeal products (diet 1) was consumed by seven healthy volunteers over a period of 12 days. One week after the end of this period, the volunteers started to consume a diet enriched with vegetables and wholemeal products but poor in fat and meat (diet 2) over a second period of 12 days. The genotoxic effect of faecal waters obtained after both diets was assessed with the single cell gel electrophoresis (Comet assay) using the human colon adenocarcinoma cell line HT29 clone 19a as a target. The fluorescence and length of the tails of the comet images reflects the degree of DNA damage in single cells. The mean DNA damage, expressed as the ratio of tail intensity (fluorescence in the tail) to total intensity of the comet after incubation with faecal water from volunteers consuming diet 1 was about twice as high as for diet 2. The susceptibility of the cells incubated with faecal water to DNA damage caused by additional hydrogen peroxide treatment showed no significant differences between the two diets. Generation of oxidized pyrimidine and purine bases revealed no differences after pretreatment with both types of faecal water. The results indicate that diets high in fat and meat but low in dietary fibre increase the genotoxicity of faecal water to colonic cells and may contribute to an enhanced risk of colorectal cancer.
Background: Diverse perspectives have influenced fish consumption choices. Objectives: We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories. Methods: We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns. Discussion: There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices. Conclusion: Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts of fish consumption. In addition, policy and fishery management inter-ventions will be necessary to ensure long-term availability of fish as an important source of human nutrition.
A commercial weight loss program with a client base composed of >95% women experienced sporadic complaints of nausea and vomiting after changing its multivitamin supplier. This retrospective and observational study was designed to determine if related adverse event reports were significant, and to investigate potential mechanism for their occurrence in this group of subjects, many of whom were concurrently receiving oral contraceptives or hormone replacement therapy. Incidence of nausea, vomiting, rash, and total complaints in the 3 months following the change of the multivitamin formulation was compared with the same complaints in the 3 months before the change. In the 3 months following the multivitamin change, there were 166 complaints of nausea and vomiting, 9 complaints of rash and 194 total complaints from a group of 88,468 patients. In the 3 months before the change in the multivitamin, there had been 2 complaints of nausea and vomiting, no complaints of rash, and 11 total complaints from 88,252 patients. The difference detected by a chi-squared test was significant for all events studied; nausea and vomiting (P < 0.0001), rash (P < 0.02), and total complaints (P < 0.0001). The altered multivitamins contained added citrus bioflavanoids not included in the original formula. Citrus bioflavanoids decrease the clearance of exogenous estrogens by inhibiting cytochrome P450 enzyme systems. Elevated estrogen levels could account for the increased incidence of nausea and vomiting. This experience demonstrates that adding dietary herbal supplements to multivitamins may be associated with adverse interactions with prescription drugs.
Growing evidence from tissue culture, animal, and clinical models suggests that the flavonoid-rich fruits of the North American cranberry and blueberry (Vaccinium spp.) have the potential ability to limit the development and severity of certain cancers and vascular diseases including atherosclerosis, ischemic stroke, and neurodegenerative diseases of aging. The fruits contain a variety of phytochemicals that could contribute to these protective effects, including flavonoids such as anthocyanins, flavonols, and proanthocyanidins; substituted cinnamic acids and stilbenes; and triterpenoids such as ursolic acid and its esters. Cranberry and blueberry constituents are likely to act by mechanisms that counteract oxidative stress, decrease inflammation, and modulate macromolecular interactions and expression of genes associated with disease processes. The evidence suggests a potential role for dietary cranberry and blueberry in the prevention of cancer and vascular diseases, justifying further research to determine how the bioavailability and metabolism of berry phytonutrients influence their activity in vivo.
An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
We report a series of cases of thyroid dysfunction in adults associated with ingestion of a brand of soy milk manufactured with kombu (seaweed), and a case of hypothyroidism in a neonate whose mother had been drinking this milk. We also report two cases of neonatal hypothyroidism linked to maternal ingestion of seaweed made into soup. These products were found to contain high levels of iodine. Despite increasing awareness of iodine deficiency, the potential for iodine toxicity, particularly from sources such as seaweed, is less well recognised.
BACKGROUND: Many pregnant women use dietary supplements during pregnancy; however, relatively scant information is available on the safety of these products. Consumers of dietary supplements often rely on employees of health food stores to provide recommendations. OBJECTIVE: To evaluate recommendations made by health food store employees in the Phoenix metropolitan area regarding treatment of nausea/vomiting and migraines during pregnancy. METHODS: Phone calls were made by a disguised shopper to 155 health food stores in the greater Phoenix area. The caller posed as a woman 8 weeks' pregnant asking for recommendations for treatment of nausea/vomiting and migraines. Responses and recommendations were recorded and then compared with current scientific evidence obtained during a search of the literature using MEDLINE (1966-September 2004) as to whether or not the supplements and the methods of their use during pregnancy were contraindicated. RESULTS: Eighty-nine percent of stores offered recommendations for nausea/vomiting, and 82% provided recommendations for migraines. The use of ginger was the most recommended therapy for nausea/vomiting. Only 3.6% of respondents recommended correct usage, but failed to supply the correct dosage and duration. A total of 15 of 278 (5%) recommendations, for both nausea/vomiting and migraines, were for products contraindicated in pregnancy. CONCLUSIONS: In light of the increased use of dietary supplements by women during pregnancy, the willingness of personnel in health food stores to make any recommendations should foster concerns by patients and healthcare providers alike. Use of dietary supplements contraindicated in pregnancy could cause significant harm to the mother and/or fetus. Studies are needed to address the need for more stringent guidelines regarding health food stores and their recommendations.