Soon maybe I can sing, as Julie Andrews in the stage version of Camelot, "Tra la, it's May!" while romping over the green.
What a sublime voice. Even if I can't like Guenevere's character, the song is simply lovely.
Re: books, homeschooling and homemaking issues, political issues worldwide, archaeology, and religion.
In the absence of justice, what is sovereignty but organized robbery?- Saint Augustine
Long-term oversupplementation with folate leads to a specific and significant down-regulation in intestinal and renal folate uptake, which is associated with a decrease in message levels of hRFC, PCFT/HCP1, and FR. This regulation appears to be mediated via a transcriptional mechanism, at least for the hRFC system.
Abstract The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn’s disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD4+CD45RBhi T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of Vdr-deficient IECs with the hVDR transgene completely rescued Vdr-null mice from severe colitis and death, even though the mice still maintained a hyperresponsive Vdr-deficient immune system. Mechanistically, VDR signaling attenuated PUMA induction in IECs by blocking NF-κB activation, leading to a reduction in IEC apoptosis. Together, these results demonstrate that gut epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this anticolitic activity is independent of nonepithelial immune VDR actions.
Am J Clin Nutr. 2015 Mar;101(3):646-58. doi: 10.3945/ajcn.114.086603. Epub 2015 Jan 7.
High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice.
Christensen KE1, Mikael LG1, Leung KY1, Lévesque N1, Deng L1, Wu Q1, Malysheva OV1, Best A1, Caudill MA1, Greene ND1, Rozen R1
Our goal was to investigate the impact of high folic acid intake on liver disease and methyl metabolism.
Folic acid-supplemented diet (FASD, 10-fold higher than recommended) and control diet were fed to male Mthfr(+/+) and Mthfr(+/-) mice for 6 mo to assess gene-nutrient interactions. Liver pathology, folate and choline metabolites, and gene expression in folate and lipid pathways were examined.
Liver and spleen weights were higher and hematologic profiles were altered in FASD-fed mice. Liver histology revealed unusually large, degenerating cells in FASD Mthfr(+/-) mice, consistent with nonalcoholic fatty liver disease. High folic acid inhibited MTHFR activity in vitro, and MTHFR protein was reduced in FASD-fed mice. 5-Methyltetrahydrofolate, SAM, and SAM/S-adenosylhomocysteine ratios were lower in FASD and Mthfr(+/-) livers. Choline metabolites, including phosphatidylcholine, were reduced due to genotype and/or diet in an attempt to restore methylation capacity through choline/betaine-dependent SAM synthesis. Expression changes in genes of one-carbon and lipid metabolism were particularly significant in FASD Mthfr(+/-) mice. The latter changes, which included higher nuclear sterol regulatory element-binding protein 1, higher Srepb2 messenger RNA (mRNA), lower farnesoid X receptor (Nr1h4) mRNA, and lower Cyp7a1 mRNA, would lead to greater lipogenesis and reduced cholesterol catabolism into bile.
We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2-hit mechanism whereby mutant hepatocytes cannot accommodate the lipid disturbances and altered membrane integrity arising from changes in phospholipid/lipid metabolism. These preliminary findings may have clinical implications for individuals consuming high-dose folic acid supplements, particularly those who are MTHFR deficient.
When Chekhov saw the long winter, he saw a winter bleak and dark and bereft of hope. Yet we know that winter is just another step in the cycle of life. But standing here among the people of Punxsutawney and basking in the warmth of their hearths and hearts, I couldn't imagine a better fate than a long and lustrous winter.
- Phil, Groundhog Day
J Epidemiol Community Health. 2015 Jul;69(7):619-24. doi: 10.1136/jech-2014-204971. Epub 2015 Feb 24.This is far from a denunciation of flouride, but it indicates it could be a factor. Then, while looking up "hypothyroid" and "flouride," I found out that one of the ways scientists induce hypothyroidism in lab rats is by giving them flouride (and GABA--go, sprouts!--appears to help heal the thyroid afterward, interestingly). Further reading revealed that since 1979 it has been apparent that too much flouride in cattle can cause hypothyroidism and anemia.
Are fluoride levels in drinking water associated with hypothyroidism prevalence in England? A large observational study of GP practice data and fluoride levels in drinking water.
Peckham S1, Lowery D1, Spencer S1.Author information
- 1Centre for Health Services Studies, University of Kent, Canterbury, Kent, UK.
While previous research has suggested that there is an association between fluorideingestion and the incidence of hypothyroidism, few population level studies have been undertaken. In England, approximately 10% of the population live in areas with community fluoridation schemes andhypothyroidism prevalence can be assessed from general practice data. This observational study examines the association between levels of fluoride in water supplies with practice level hypothyroidism prevalence.METHODS:
We used a cross-sectional study design using secondary data to develop binary logistic regression models of predictive factors for hypothyroidism prevalence at practice level using 2012 data onfluoride levels in drinking water, 2012/2013 Quality and Outcomes Framework (QOF) diagnosedhypothyroidism prevalence data, 2013 General Practitioner registered patient numbers and 2012 practice level Index of Multiple Deprivation scores.FINDINGS:
We found that higher levels of fluoride in drinking water provide a useful contribution for predicting prevalence of hypothyroidism. We found that practices located in the West Midlands (a wholly fluoridated area) are nearly twice as likely to report high hypothyroidism prevalence in comparison to Greater Manchester (non-fluoridated area).INTERPRETATION:
In many areas of the world, hypothyroidism is a major health concern and in addition to other factors-such as iodine deficiency-fluoride exposure should be considered as a contributing factor. The findings of the study raise particular concerns about the validity of community fluoridation as a safe public health measure.
Prescrire Int. 2015 Oct;24(164):241-4, 246.
Hypothyroidism in adults. Levothyroxine if warranted by clinical and laboratory findings, not for simple TSH elevation.
[No authors listed]
Hypothyroidism is a common disorder due to inadequate thyroid hormone secretion. When a patient has signs and symptoms suggestive of hypothyroidism, how is it determined whether thyroid hormone replacement therapy will have a favourable harm-benefit balance? How should treatment be managed? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. The symptoms of hypothyroidism are due to slow metabolism (constipation, fatigue, sensitivity to cold, weight gain, etc.) and to polysaccharide accumulation in certain tissues, leading to hoarseness, eyelid swelling, etc. A blood TSH concentration of less than 4 or 5 mlU/L rules out peripheral hypothyroidism. TSH levels increase with age. Between 30% and 60% of high TSH levels are not confirmed on a second blood test. In overt hypothyroidism, the TSH level is high and the free T4 (thyroxine) level is low. Most of these patients are symptomatic. So-called subclinical hypothyroidism, which is rarely symptomatic, is characterised by high blood TSH levels and normal free T4 levels. The natural history of hypothyroidism depends on its cause. In chronic autoimmune thyroiditis, the most common form seen in rich countries, hypothyroidism generally worsens over time. However, other situations can lead to transient hypothyroidism that may last several weeks or months. Subclinical hypothyroidism, as the name implies, is usually asymptomatic. The risk of progression to overt hypothyroidism is about 3% to 4% per year overall but increases with the initial TSH level. Treatment guidelines are mainly based on physiological and pharmacological considerations and generally recommend levothyroxine therapy. The adverse effects of levothyroxine are signs of thyrotoxicosis in case of overdose (tachycardia, tremor, sweating, etc.). Even a slight overdose carries a risk of osteoporotic fractures and atrial fibrillation, especially in the elderly. In young adults, levothyroxine is usually started at a dose of about 1.5 microg/kg per day, taken on an empty stomach. Elderly patients and those with coronary artery disease should start at a lower dose: 12.5 to 50 microg per day. Treatment monitoring is based mainly on blood TSH assay. Dose adjustment should only be considered after 6 to 12 weeks, given the long half-life of levothyroxine. Certain drugs, such as iron and calcium, reduce the gastrointestinal absorption of levothyroxine. Enzyme inducers reduce its efficacy. In 2015, there is no robust evidence that levothyroxine therapy has any tangible benefit in patients with subclinical hypothyroidism. Some practice guidelines recommend treatment when the TSH level is above 10 mIU/L, or sometimes trial treatment for a few months for patients with symptoms suggestive of hypothyroidism. In practice, replacement therapy is needed for patients with overt hypothyroidism and a blood TSH concentration above 10 mIU/L. The main challenge is to recognise transient hypothyroidism, which does not require life-long treatment. When the TSH is only slightly elevated, there is a risk of attributing non-specific symptoms to an abnormal laboratory result and prescribing unnecessary treatment. Watchful waiting is an alternative to routine levothyroxine prescription in case of TSH elevation.
Plasma 1-carbon metabolites and academic achievement in 15-yr-old adolescents.
Nilsson TK1, Hurtig-Wennlöf A2, Sjöström M2, Herrmann W2, Obeid R2, Owen JR2, Zeisel S2. Abstract
Academic achievement in adolescents is correlated with 1-carbon metabolism (1-CM), as folate intake is positively related and total plasma homocysteine (tHcy) negatively related to academic success. Because another 1-CM nutrient, choline is essential for fetal neurocognitive development, we hypothesized that choline and betaine could also be positively related to academic achievement in adolescents. In a sample of 15-yr-old children (n = 324), we measured plasma concentrations of homocysteine, choline, and betaine and genotyped them for 2 polymorphisms with effects on 1-CM, methylenetetrahydrofolate reductase (MTHFR) 677C>T, rs1801133, and phosphatidylethanolamine N-methyltransferase (PEMT), rs12325817 (G>C). The sum of school grades in 17 major subjects was used as an outcome measure for academic achievement. Lifestyle and family socioeconomic status (SES) data were obtained from questionnaires. Plasma choline was significantly and positively associated with academic achievement independent of SES factors (paternal education and income, maternal education and income, smoking, school) and of folate intake (P = 0.009, R2 = 0.285). With the addition of the PEMT rs12325817 polymorphism, the association value was only marginally changed. Plasma betaine concentration, tHcy, and the MTHFR 677C>T polymorphism did not affect academic achievement in any tested model involving choline. Dietary intake of choline is marginal in many adolescents and may be a public health concern.-Nilsson, T. K., Hurtig-Wennlöf, A., Sjöström, M., Herrmann, W., Obeid, R., Owen, J. R., Zeisel, S. Plasma 1-carbon metabolites and academic achievement in 15-yr-old adolescents.
Those who regularly ate an omega-3-loaded margarine experienced an improvement in their ability to pay attention, compared with boys who did not, researchers report in the March 19 issue of Neuropsychopharmacology.
Pediatrics. 2005 May;115(5):1360-6.
The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder.
Developmental coordination disorder (DCD) affects approximately 5% of school-aged children. In addition to the core deficits in motor function, this condition is associated commonly with difficulties in learning, behavior, and psychosocial adjustment that persist into adulthood. Mounting evidence suggests that a relative lack of certain polyunsaturated fatty acids may contribute to related neurodevelopmental and psychiatric disorders such as dyslexia and attention-deficit/hyperactivity disorder. Given the current lack of effective, evidence-based treatment options for DCD, the use of fatty acid supplements merits investigation.METHODS:
A randomized, controlled trial of dietary supplementation with omega-3 and omega-6 fatty acids, compared with placebo, was conducted with 117 children with DCD (5-12 years of age). Treatment for 3 months in parallel groups was followed by a 1-way crossover from placebo to active treatment for an additional 3 months.RESULTS:
No effect of treatment on motor skills was apparent, but significant improvements for active treatment versus placebo were found in reading, spelling, and behavior over 3 months of treatment in parallel groups. After the crossover, similar changes were seen in the placebo-active group, whereas children continuing with active treatment maintained or improved their progress.CONCLUSIONS:
Fatty acid supplementation may offer a safe efficacious treatment option for educational and behavioral problems among children with DCD. Additional work is needed to investigate whether our inability to detect any improvement in motor skills reflects the measures used and to assess the durability of treatment effects on behavior and academic progress.
In this kind of population, delays in literacy development usually increase over time, indicating the value of early intervention. Children in the placebo group fell even more behind with spelling during the 0- to 3-month parallel-group phase, although they did show average progress in reading. In contrast, children receiving active treatment made 3 times the expected normal gain in reading age and twice the normal gain in spelling age, bringing their average scores toward normative values. In the follow-up phase, they continued to make improvements above what would be expected for chronologic age.