From Biotics

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

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


Vitamin D Status Linked to Significantly Reduced Cancer Risk!

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


Vitamin D3 for Enhanced Cardiac Function!

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.


Pycnogenol® and Grape Seed Extract for Cognitive Function?

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


EGCG to Treat Rheumatoid Arthritis (RA)?

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


Proton Pump Inhibitors (PPIs) Increase Risk of Dementia!

While PPIs are widely used to treat gastrointestinal illnesses, recent evidence suggests they may be related to cognitive decline. A group of German researchers conducted a prospective cohort study to examine the association between the use of PPIs and the risk of incident dementia in the elderly. They used observational data (from 2004-2011) from the largest German statutory health insurer. Their analysis of 73,679 participants (≥ 75 yrs.) concluded in November 2015. The association between PPI use and dementia was analyzed using time-dependent Cox regression, adjusted for potential confounding factors such as age, sex and polypharmacy. Researchers discovered that patients receiving regular PPI medication had a significantly increased risk of incident dementia compared with patients not receiving PPIs. The researchers concluded that the avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data, and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice.

Comm, W, et al. Association of Proton Pump Inhibitors with Risk of Dementia; A Pharmacoepidemikological Claims Data Analysis. JAMA Neurol. doi:10.1001/jamaneurol.2015.4791 Published online Feb 14, 2016.


Gluten Sensitivity and Neurological Disorders – From Gut to Brain!

Gluten sensitivity (GS) may be defined as a state of heightened immunological responsiveness in genetically susceptible people. This definition does not imply bowel involvement. The authors, all affiliated with the Department of Neurology at The Royal Hallamshire Hospital, Sheffield, UK, suggest that regarding GS as principally a disease of the small bowel is a historical misconception. They state that GS can be primarily, and at times exclusively a neurological disease, and that IgG antigliadin antibody should be part of the routine investigation of all patients with neurological dysfunction of obscure aetiology, particularly patients with ataxia and peripheral neuropathy. Statistical evidence showed that patients with neurological disease of unknown aetiology were found to have a much higher prevalence of circulating antigliadin antibodies (57%) in their blood than either healthy controls (12%) or those with neurological disorders of known aetiology (5%). More celiac disease (CD) specific serological markers such as anti-endomysium and transglutaminase antibodies may have helped in diagnosing CD, but their sensitivity as markers of other manifestation of GS (where the bowel is not affected) is low. Early diagnosis and removal of the trigger factor by the introduction of a gluten-free diet may be the most promising therapeutic intervention.

Hadjivassiliou M, et al. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry 2002 72:560-563. Published by


Gluten Sensitivity- A Significant Clinical Challenge:

Besides celiac disease (CD) and wheat allergy, the most studied forms of gluten-related disorders characterized by an immune response (autoimmune in CD and IgE-mediated in wheat allergy), non-celiac gluten sensitivity (NCGS) apparently is not driven by an aberrant immune response. NCGS is characterized by a heterogeneous clinical picture with intestinal and extra-intestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but factors such as the stimulation of the innate immune system, direct cytotoxic effects of gluten, and the synergy with other wheat molecules are suspects and any one, or any combination of any and all may all play a role. Diagnostic procedures remain problematic due to the absence of efficient diagnostic markers; therefor, diagnosis is based on the symptomatic response to a gluten free diet and the recurrence of symptoms after gluten reintroduction. While the timing of gluten reintroduction in evaluating NCGS is challenging, once the determination is made, the withdrawal of gluten from the diet appears to be the correct patient management approach for those with NCGS.

Eli L, Roncoroni L, Bardella MT. Non-celiac gluten sensitivity: Time for sifting the grain. Wordl J Gastroentero. 2015 Jul 21;21(27):8221-6.


B12 Deficiency Associated With Autism, Schizophrenia and Aging!

Researchers from Northeastern, Harvard, Nova Southeastern and Boston Universities discovered that vitamin B12 levels in the brain are much lower in those with autism or schizophrenia compared to their peers at similar ages, and the elderly. Researchers measured levels of cobalamin in postmortem human frontal cortex samples from 19 weeks fetal development through age 80 among 12 individuals with autism, 9 with schizophrenia, and 43 controls. Total cobalamin was significantly lower in controls older than 60, indicating a more that 10-fold age-dependent decline in methylcobalamin levels. Methylcobalamin and adenosylcobalamin levels were more that 3-fold lower in those with autism or schizophrenia, compared with controls. Lower methylcobalamin was associated with decreased methionine synthase activity and increased levels of substrate homocysteine in those with autism. The findings are particularly significant because the differences found in brain B12 with aging, autism and schizophrenia are not seen in the blood, where B12 levels are usually measured. Researchers concluded that B12 levels, especially methylcobalamin, in human frontal cortex decrease with age, which plays a crucial role in regulating all methylation reactions, including those providing epigenetic regulation of gene expression. The vitamin deficits in autistic and schizophrenic subjects suggests that impaired methylation may be a critical pathological component of these brain disorders, as well as other neurological and neuropsychiatric conditions.

Zhang Y, et al. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia. PLOS ONE, 2016; 11(1): e0146797 DOI: 10.1371/journal.pone.0146797


Chromium for Type 2 Diabetes?

Although it has been suggested that chromium (Cr) has beneficial effects in type 2 diabetes (T2D), it has not been investigated at the population level. Researchers from Boston Children’s Hospital, Harvard Medical School, and Joslin Diabetes Center wished to examine the use and potential benefits of Cr supplementation in T2D using NHANES data. Diabetes was defined as having an HbA1c value of 6.5 or greater, or having been diagnosed with diabetes. The study cohort included 28,539 people. 58.3% reported consuming a dietary supplement (DS) in the previous 30 days, 28.8 % reported consuming a DS that contained Cr, and 0.7% consumed a DS that contained Cr in the title. The results showed that compared to nonusers, the odds of having T2D were lower in those who consumed CR containing supplements within the previous 30 days than in those who did not. In summary, the researchers showed that Cr supplementation in adults to be associated with significantly lower odds of an individual having diabetes.

DJ McIver, et al. Risk of Type 2 Diabetes Is Lower in US Adults Taking Chromium-Containing Supplements. The J of Nut. Published ahead of print Oct 7, 2015 as doi: 10.3945/jn.115.214569


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