Heavy Metals and Migraines!

by Biotics Research

According to a study published in 2012, Migraines affect 12% of the US population. While the number of studies related to migraine pathophysiology have increased in recent years, the exact aetioloty is not well understood. Wishing to compare the levels of trace elements and heavy metals in patients with acute migraine and healthy controls, researchers conducted a prospective study comprising migraine patients and an equal number of healthy controls. International Headache Society classification was used for diagnosing migraine. Serum copper (Cu), zinc (Zn), lead (Pb), iron (Fe), cadmium (Cd), cobalt (Co), manganese (Mn) and magnesium (Mg) levels were measured and assessed. Among the case participants were 22 females and 3 males (mean age 36 yrs). Among controls there were 21 females and 4 males (mean age 42 yrs). Results showed serum levels of Cu, Mg and Zn were significantly lower in patients with acute migraines (AMA) compared to controls, while Cd , Fe, Mn and Pb levels were higher in AMA patients compared to controls. No significant difference was seen for Co between the two groups. Researchers concluded that lower Mg and Zn concentrations may be related to the frequency of migraine attacks, and their administration may reduce the frequency of such attacks. Also, trace elements and heavy metals may have a role in the genesis of considerable oxidative stress in AMA patients.

Gonullu H, et al. The levels of trace elements and heavy metals in patients with acute migraine headache. J Pak Med Asso 65: 694; 2015

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Gluten-Free Diet Impacts the Human Microbiome:

by Biotics Research

A gluten-free diet (GFD) is commonly adopted as an effective treatment for celiac disease, and is often followed to alleviate GI complaints. While we know there is an important link between diet and the gut microbiome, how a switch to a GFD affect the human gut microbiome is largely unknown. Twenty one healthy human volunteers followed a GFD for four weeks. Researchers collected stool samples from each at baseline, four during the GFD period, and four when they returned to their habitual diet (HD). They determined microbiome profiles using 16S rRNA sequencing, then processed the samples for taxonomic and imputed functional composition. They also measured six gut health-related biomarkers in all samples. Inter-individual variation in the gut microbiota remained stable during the short term GFD intervention. A number of taxon-specific differences were seen during the GDF: the most striking shift was seen for the family Veillonellaceae (class Clostridia), which was significantly reduced during the intervention. Seven other taxa also showed significant changes; the majority of them known to play a role in starch metabolism. Stronger differences in pathway activities were seen: 21 predicted pathway activity scores showed significant association to the diet change. Strong relation between the predicted activity of pathways and biomarker measurements were observed. Researchers concluded that CFD changes the gut microbiome composition and alters the activity of microbial pathways.

Bonder MJ, et al. The influence of a short-term gluten-free diet on the human gut microbiome. Genome Med. 2016 Apr 21;8(1):45. doi: 10.1186/s13073-016-0295-y.

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Important Info on US Sodium and Potassium Intakes and Their Ratio:

by Biotics Research

Sodium-to-potassium ratio (Na:K) is shown to be strongly associated with an increased risk of Cardiovascular disease (CVD) and CVD related mortality, more than either Na or K intake alone. Researchers from the NIH Office of Dietary Supplements, Department of Nutrition Science at Purdue University, and the USDA Agricultural Research Service set out to estimate the Na:K in the diet of US adults. Using data from the 2011-2012 NHANES, the National Cancer Institute method was used to estimate Na and K intakes, Na:K, and the percentage of those with Na:K < 1.0. What they found was that only 12.2% of US adults had a Na:K < 1.0, a ratio that while not necessarily ideal, would certainly be considered preferable to the 1.38 average seen for all adults, and is compatible with the WHO guidelines for reduced risk of mortality. On average, 90% consumed more than the 2300 mg/d recommended daily intake (3600 mg/d average intake) of Na, whereas less than 3% had K intakes above the recommended 4700 mg/d (2800 mg/d average intake). Their report illustrates that only about 10% of US adults have a Na:K consistent with preferred guidelines. In order to improve the risk of CVD related mortality, efforts to reduce sodium intake, with novel strategies to increase potassium intakes are warranted. These dietary modifications offer a cost-effective public health intervention strategy.

Bailey RL, et al. Estimating Sodium and Potassium Intakes and Their Ratio in the American Diet: Data from the 2011-2012 NHANES1-4. The Journal of Nutrition Apr 2016; Vol 146, No. 4; 745-750

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Long Term Multivitamin Use Linked to Lower Cardiovascular Disease (CVD) in Men!

by Biotics Research

Researchers from Harvard TH Chan School of Public Health, Karolinska Institute (Stockhilm) and Brinham and Women’s Hospital (Boston) investigated how multivitamin use is associated with the risk of CVD in men who were initially (as baseline) healthy. They studied over 18,500 male physicians (≥40 yrs) from the Physicians’ Health Study 1 cohort who were free of CVD and cancer at baseline. All self-reported lifestyle and clinical factors, plus intake of selected foods and dietary supplements. During a mean follow-up of 12.2 years, there were no significant associations observed among baseline multivitamin uses compared with nonusers for the risk of major CVD events. However, at a duration of 20 years or more, a 44% reduction of risk of major CVD events. There was no evidence of any safety concerns from long-term multivitamin use.

S Rautiainen, et al. Multivitamin Use and the Risk of Cardiovascular Disease in Men. First published April 27, 2016, doi: 10.3945/jn.115.227884 J. Nutr.

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Fish Oil for Healthy Community Dwelling Senior Women!

by Biotics Research

As we age, we typically experience a decrease in muscle mass and metabolic rate and an increase in fat mass, thereby predisposing older adults to chronic disease and functional impairment. The result is an eventual decrease in the quality of life. Researchers from the Department of Human Health and Nutritional Sciences at the University of Guelph in Canada, conducted a study to evaluate the effect of fish oil (FO) supplementation in a cohort of healthy, community-dwelling older females. They evaluated 1) metabolic rate and substrate oxidation at rest and during exercise; 2) resting blood pressure and exercise heart rates; 3) body composition; 4) strength and physical function, and; 5) blood measures of insulin, glucose, CRP and triglycerides. Twenty-four females (66 ± 1 yr) were randomly assigned to receive either 3g/day of EPA and DHA or a placebo for 12 weeks. Exercise measurements were taken before and after 12 weeks and resting metabolic measures were made before and at 6 and 12 weeks. Results showed that FO supplementation significantly increased resting metabolic rate by 14%, energy expenditure during exercise by 10%, and the rate of fat oxidation during rest by 19% and during exercise by 27%. Additionally, FO consumption lowered triglycerides by 29%, increased lean mass by 4%, and functional capacity by 7%. No changes occurred in the placebo group.

Logan SL, Spriet LL. Omega-3 Fatty Acid Supplementation for 12 Weeks Increases Resting and Exercise Metabolic Rate in Healthy Community-Dwelling Older Females. PLoS ONE 10 (12): e0144828. doi:10.1371/journal.pone.0144828 (Dec 17, 2015)

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Omega-3 Fatty Acids, Adiponectin, Leptin and Obesity:

by Biotics Research

Increased adiposity is linked to altered levels of biologically active proteins, including the hormones adiponectin and leptin. Adiponectin is negatively correlated with obesity, with lower levels associated with increased risk of death or myocardial infarction (MI). Conversely, leptin levels are positively correlated with obesity, with higher levels identified as an independent risk factor for CVD. Researchers reviewed animal and human data relating to the effects of Omega-3 (n-3) fatty acids on adiponectin and leptin. The beneficial effects of n-3 polyunsaturated fatty acids (PUFA) are not just due to the modulation of the amount and types of eicosanoids produced, but also the regulation of intracellular signaling pathways, transcription factor activity, and gene expression, resulting in the regulation of inflammation, platelet adhesion, blood pressure regulation, heart rhythm and triglycerides. The majority of available studies assessing the effect of n-3 fatty acids on adiponectin reported n-3 intake induced statistically significant increases in adiponectin levels in both animal and human models. These include studies with subjects in normal weight range, overweight and obese. Results were consistent between healthy individuals and those investigating hyperlipidemic patients with 2TDM, or recent history of MI. Of the limited studies on n-3 and circulating leptin utilizing stable weight participants, the majority demonstrated either minimal change or a reduction in leptin levels.

B Gray, F Steyn, PSW Davies and L Vitetta. Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management. European Journal of Clinical Nutrition (2013) 67, 1234-1242

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Vitamin D Status Linked to Significantly Reduced Cancer Risk!

by Biotics Research

Higher serum vitamin D [25(OH)D] concentrations have been associated with lower risk of multiple cancer types. Researchers investigated whether previously reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women 55 and older across a broad range of 25(OH)D concentrations. Data from two cohorts representing different median 25(OH)D concentrations were pooled to afford a broader range of concentrations. The analysis of over 2300 women included all invasive cancers excluding skin cancer. Breast cancer was the most common type of cancer diagnosed during the study (43% of all cancers in the pooled cohort). Results show that cancer incidence was substantially lower at higher concentrations of 25(OH)D with women with concentrations ≥40 ng/ml having a 67% lower risk of cancer than women with concentrations ≤20 ng/ml.

McDonnell SL, et al. Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study. PLOS ONE doi:10.1372/journal.pone.0152441 April 6, 2016

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Vitamin D3 for Enhanced Cardiac Function!

by Biotics Research

Vitamin D deficiency is common among older adults. Researchers from the University of Leeds designed the Vitamin D Treating Patients with Chronic Heart Failure (VINDICATE) study, involving 163 older patients already being treated for heart failure using standard accepted treatment, to learn whether vitamin D supplementation would benefit heart failure patients. They focused on patients with left ventricular systolic dysfunction. Using ejection fraction, they measured how much blood pumps away from the heart with each beat. In healthy people, the ejection fraction is generally between 60 and 70%. Study participants average ejection fraction was 26%. Compared to placebo, patients taking a daily dose of 4,000 IU of vitamin D3 for twelve months experienced up to a 34% improvement in heart function.

Witte K, Gierula J, Paton MF, et al. Vitamin D Supplementation Improves Cardiac Function in Patients with Chronic Heart Failure. American College of Cardiology 65th Annual Scientific Session. 2016.

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Pycnogenol® and Grape Seed Extract for Cognitive Function?

by Biotics Research

In this study, 44 subjects (55-70 yrs) with high oxidative stress were supplemented with Pycnogenol® daily for 12 months. Another group with comparable oxidative stress was followed as a reference group. Cognitive testing, including IQ Code, cognitive function and SBT were conducted using defined scales. Results after 12 months showed significant improvement in the supplemented group vs the reference group for all tests conducted. Researchers concluded that Pycnogenol® supplementation appears to improve cognitive function and oxidative stress in normal subjects between 55 and 70 years old.(1) Researchers at Mount Sinai School of Medicine and the University of Minnesota evaluated the ability of grape-derived polyphenols to prevent the generation of a specific form of β-amyloid (Aβ) peptide, a substance in the brain known to cause neurotoxicity associated with Alzheimer disease (AD). They administered grape seed extracts to mice genetically determined to develop memory deficits and Aβ neurotoxins similar to those found in AD. They found that the brain content of Aβ*56, a specific form of Aβ previously implicated in the promotion of AD memory loss, was substantially reduced after treatment. Their study corroborates other studies suggesting grape polyphenols may protect against cognitive decline in AD.(2, 3)

1. Belcaro G, et al. The COFU3 Study. Improvement in cognitive function, attention mental performance with Pycnogenol® in healthy subjects (55-70) with high oxidative stress. J Neurosurg Sci 2015;59: 437-46.
2. Lie P, et al. Grape Seed Polyphenolic Extract Specifically Decreases Aβ*56 in the Brains of Tg2576 Mice. Journal of Alzheimer’s Disease, Vol 26, No. 4.
3. Natural chemicals found in grapes may protect against Alzheimer’s disease. ScienceDaily, 18 July 2011

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EGCG to Treat Rheumatoid Arthritis (RA)?

by Biotics Research

EGCG, a bioactive phytochemical found in green tea, was found to regulate transforming growth factor β-activated kinase 1 (TAK1) in human rheumatoid arthritis synovial fibroblasts (RASF), indicating that TAK1 regulation may be a therapeutic target in RA. EGCG appears to effectively inhibit TAK1 by blocking its phosphorylation. As a mediator of inflammation, TAK1 is integral to the activation of downstream mitogen-activated protein kinases (MAKPs) in response to receptor stimulation by the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNF). A team of researchers led by Associate Professor Salah-uddin Ahmed of Washington State University College of Pharmacy in Spokane, analyzed the mechanism of TAK1 regulation in a pre-clinical mouse model of human RA. After 10 days of treatment with EGCG, the researchers found a significant reduction in ankle circumference, a measurement used as a surrogate for symptomatic inflammation. Authors stated that they have provided a rationale for targeting RASF TAK1 in RA and identified a unique mechanism through which EGCG inhibits the interaction between signaling molecules important in cytokine signaling, ultimately inhibiting inflammation and tissue destruction in RA.

Singh AK, Umar S, Riegsecker S, et al Regulation of transforming growth factor β-activated kinase activation by epigallocatechin-3-gallate in rheumatoid arthritis synovial fibroblasts: suppression of K63-linked autoubiquitination of tumor necrosis factor receptor-associated factor 6. Arthritis Rheum. 2016;68(2):347-358.

CP Sison (Med Editor) Rheumatoid Arthritis Advisor. March 01, 2016

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