This review covers the toxicology of mercury and its compounds. Special attention is paid to those forms of mercury of current public health concern. Human exposure to the vapor of metallic mercury dates back to antiquity but continues today in occupational settings and from dental amalgam. Health risks from methylmercury in edible tissues of fish have been the subject of several large epidemiological investigations and continue to be the subject of intense debate. Ethylmercury in the form of a preservative, thimerosal, added to certain vaccines, is the most recent form of mercury that has become a public health concern. The review leads to general discussion of evolutionary aspects of mercury, protective and toxic mechanisms, and ends on a note that mercury is still an "element of mystery."

The Toxicology of Mercury and Its Chemical Compounds

Low dose mercury toxicity and human health.

Objective The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were ‘expert opinion’.

Methods A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations.

Results 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only ‘strong for’ therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as ‘weak for’ based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability).

Conclusions These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.

https://ard.bmj.com/content/annrheumdis/76/2/318.full.pdf

EULAR revised recommendations for the management of fibromyalgia

Although epidemiological and biochemical evidence suggests that aluminium may be associated with Alzheimer's disease (AD), there is no convincing proof of a causal link for aluminium in disease progression. We have completed a two year, single-blind study to investigate whether the progression of dementia could be slowed by the trivalent ion chelator, desferrioxamine. 48 patients with probable AD were randomly assigned to receive desferrioxamine (125 mg intramuscularly twice daily, 5 days per week, for 24 months), oral placebo (lecithin), or no treatment. No significant differences in baseline measures of intelligence, memory, or speech ability existed between groups. Activities of daily living were assessed and videorecorded at 6, 12, 18, and 24 month intervals. There were no differences in the rate of deterioration of patients receiving either placebo or no treatment. Desferrioxamine treatment led to significant reduction in the rate of decline of daily living skills as assessed by both group means (p = 0.03) and variances (p less than 0.04). The mean rate of decline was twice as rapid for the no-treatment group. Appetite (n = 4) and weight (n = 1) loss were the only reported side-effects. We conclude that sustained administration of desferrioxamine may slow the clinical progression of the dementia associated with AD.

Intramuscular desferrioxamine in patients with Alzheimer's disease

Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.

https://cyberleninka.org/article/n/324193.pdf

Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases

The etiology of most cases of Alzheimer’s disease (AD) is as yet unknown. Epidemiological studies suggest that environmental factors may be involved beside genetic risk factors. Some studies have shown higher mercury concentrations in brains of deceased and in blood of living patients with Alzheimer’s disease. Experimental studies have found that even smallest amounts of mercury but no other metals in low concentrations were able to cause all nerve cell changes, which are typical for Alzheimer’s disease. The most important genetic risk factor for sporadic Alzheimer’s disease is the presence of the apolipoprotein Ee4 allele whereas the apolipoprotein Ee2 allele reduces the risk of developing Alzheimer’s disease. Some investigators have suggested that apolipoprotein Ee4 has a reduced ability to bind metals like mercury and therefore explain the higher risk for Alzheimer’s disease. Therapeutic approaches embrace pharmaceuticals which bind metals in the brain of patients with Alzheimer’s disease. In sum, both the findings from epidemiological and demographical studies, the frequency of amalgam application in industrialized countries, clinical studies, experimental studies and the dental state of AD patients in comparison to controls suggest a decisive role for inorganic mercury in the etiology of AD.

http://www.tracemin.com/fileadmin/uploads/pdf/en/Amalgam_Alzheimer_NEL.pdf

Alzheimer disease: mercury as pathogenetic factor and apolipoprotein E as a moderator

Amalgam studies: disregarding basic principles of mercury toxicity.

Introduction: In the present systematic review and meta-analysis, we assessed the effectiveness of different forms of balneotherapy (BT) and hydrotherapy (HT) in the management of fibromyalgia syndrome (FMS). Methods: A systematic literature search was conducted through April 2013 (Medline via Pubmed, Cochrane Central Register of Controlled Trials, EMBASE, and CAMBASE). Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Results: Meta-analysis showed moderate-to-strong evidence for a small reduction in pain (SMD �0.42; 95% CI [�0.61, �0.24]; P < 0.00001; I 2 = 0%) with regard to HT (8 studies, 462 participants; 3 low-risk studies, 223 participants), and moderate-to-strong evidence for a small improvement in health-related quality of life (HRQOL; 7 studies, 398 participants; 3 low-risk studies, 223 participants) at the end of treatment (SMD �0.40; 95% CI [�0.62, �0.18]; P= 0.0004; I 2 = 15%). No effect was seen at the end of treatment for depressive symptoms and tender point count (TPC). BT in mineral/thermal water (5 studies, 177 participants; 3 high-risk and 2 unclear risk studies) showed moderate evidence for a medium-to-large size reduction in pain and TPC at the end of treatment: SMD �0.84; 95% CI [�1.36, �0.31]; P = 0.002; I 2 = 63% and SMD �0.83; 95% CI [�1.42, �0.24]; P = 0.006; I 2 = 71%. After sensitivity analysis, and excluding one study, the effect size for pain decreased: SMD �0.58; 95% CI [�0.91, �0.26], P= 0.0004; I 2 =0 . Moderate evidence is given for a medium improvement of HRQOL (SMD �0.78; 95% CI [�1.13, �0.43]; P < 0.0001; I 2 =0%). A significant effect on depressive symptoms was not found. The improvements for pain could be maintained at follow-up with smaller effects. Conclusions: High-quality studies with larger sample sizes are needed to confirm the therapeutic benefit of BT and HT, with focus on long-term results and maintenance of the beneficial effects.

/pdf/therapeutic-benefit-of-balneotherapy-and-hydrotherapy-in-the-2x276oyp4u.pdf

Therapeutic benefit of balneotherapy and hydrotherapy in the management of fibromyalgia syndrome: a qualitative systematic review and meta-analysis of randomized controlled trials

Despite advances in the treatment of depression, one-third of depressed patients fail to respond to conventional antidepressant medication. There is a need for more effective treatments with fewer side effects. The primary aim of this study was to determine whether hyperthermic baths reduce depressive symptoms in adults with depressive disorder. Randomized, two-arm placebo-controlled, 8-week pilot trial. Medically stable outpatients with confirmed depressive disorder (ICD-10: F32/F33) who were moderately depressed as determined by the 17-item Hamilton Scale for Depression (HAM-D) score ≥18 were randomly assigned to 2 hyperthermic baths (40 °C) per week for 4 weeks or a sham intervention with green light and follow-up after 4 weeks. Main outcome measure was the change in HAM-Dtotal score from baseline (T0) to the 2-week time point (T1). A total of 36 patients were randomized (hyperthermic baths, n = 17; sham condition, n = 19). The intention-to-treat analysis showed a significant (P = .037) difference in the change in HAM-Dtotal score with 3.14 points after 4 interventions (T1) in favour of the hyperthermic bath group compared to the placebo group. This pilot study suggests that hyperthermic baths do have generalized efficacy in depressed patients. DRKS00004803
 at drks-neu.uniklinik-freiburg.de, German Clinical Trials Register (registration date 2016-02-02), retrospectively registered.

/pdf/effects-of-hyperthermic-baths-on-depression-sleep-and-heart-1z1ohhdvnd.pdf

Effects of hyperthermic baths on depression, sleep and heart rate variability in patients with depressive disorder: a randomized clinical pilot trial

We aim to present an overview of the possible influence of drinking water in general and mineral water in particular in improving glycemic parameters in persons with or without type 2 diabetes. We performed a literature search that produced 15 randomized controlled trials (RCTs) on this topic with mainly small sample sizes. We also discuss relevant observational and animal studies as well as the effects of important supplements in mineral water such as hydrogencarbonate and magnesium. There is low evidence for the positive effects of water or mineral water in improving glycemic parameters in diabetic and non-diabetic persons, and the results are heterogenous, making it difficult to reach an unequivocal conclusion. Meta-analyses of prospective cohort studies and other observational studies, studies with animal models and interventional studies using hydrogencarbonate and magnesium supplements suggest a probable positive effect of drinking water and mineral water in particular on glycemic parameters, supporting the positive results found in some of the RCTs, especially those substituting diet beverages or caloric beverages with water, or those using bicarbonate and magnesium-rich water. Regarding the high prevalence, the associated suffering and the resulting health expenditures of type 2 diabetes, it is imperative to conduct larger and more rigorous trials to answer the question whether drinking water or mineral water can improve glycemic parameters in diabetic and non-diabetic persons.

/pdf/prevention-and-therapy-of-type-2-diabetes-what-is-the-2pg0xuy3fa.pdf

Catharina Sadaghiani

Papers

Alzheimer disease: mercury as pathogenetic factor and apolipoprotein E as a moderator

Amalgam studies: disregarding basic principles of mercury toxicity.

Therapeutic benefit of balneotherapy and hydrotherapy in the management of fibromyalgia syndrome: a qualitative systematic review and meta-analysis of randomized controlled trials

Effects of hyperthermic baths on depression, sleep and heart rate variability in patients with depressive disorder: a randomized clinical pilot trial

Prevention and Therapy of Type 2 Diabetes-What Is the Potential of Daily Water Intake and Its Mineral Nutrients?