In the News

VIT K INSUFFICIENCY LINKED TO BRAIN HEALTH: NEW PAPER

New evidence of how exercise can counter diabetes damage

OmegaQuant Launches HbA1c Test for People Looking to Manage & Monitor Their Blood Sugar Level

Gastrointestinal issues linked with anxiety, social withdrawal for kids with autism

Stress, Anxiety and Depression During Pregnancy May Hinder Toddler’s Cognitive Development

Mayo Clinic research finds AI-enabled ECGs may identify patients at greater risk of stroke, cognitive decline

VIT K INSUFFICIENCY LINKED TO BRAIN HEALTH: NEW PAPER

New evidence draws an association between Vitamin K insufficiency and cognitive dysfunction, further argument for the potential of Vitamin K2.

Frontiers in Nutrition published a new large-population cross-sectional study that demonstrated the association of vitamin K insufficiency with cognitive function.

In the study, “Association of Vitamin K Insufficiency with Cognitive Dysfunction in Community-Dwelling Older Adults”[1], Japanese researchers enrolled a total of 800 community-dwelling older adults (mean age = 75.9) and conducted a geriatric health examination, including a Mini-Mental State Examination (MMSE) and a blood test. Examining the concentration of undercarboxylated osteocalcin (ucOC) in serum, which is a biomarker for vitamin K insuf?ciency, they demonstrated the association of the concentration of undercarboxylated osteocalcin (ucOC) in serum, which is a biomarker for vitamin K insuf?ciency, with cognitive function. By using binary logistic regression analysis, the risk of cognitive impairment equivalent or below the mild cognitive impairment level for each tertile of ucOC was examined, with the lowest tertile as the reference.

The results showed a significant association of impaired cognitive function and concentration of ucOC in the highest tertile of ucOC, with the odds ratio of 1.65 (95% CI, 1.06 to 2.59, P = 0.028). When the analysis was repeated with each domain of MMSE score*, the highest tertile of ucOC was associated with impaired orientation, calculation, and language.

The finding of the present study was in line with the previous epidemiological studies, showing that lower vitamin K intake is associated with cognitive impairment. The researchers reported, “As far as we know, this is the first report on the significant association of single ucOC measurement and cognitive impairment. Our analysis also suggests that vitamin K insufficiency could be associated with selected categories of cognitive function. Since the single measurement of ucOC in serum is a simple and widely available method for vitamin K evaluation, it could be useful as a biomarker of neurodegenerative diseases affecting the cognitive functions.”

These results are supported by another recently published paper from Spain[2] that assessed two years of changes in dietary K intake with cognitive function measured through neuropsychological performance tests. The researchers concluded that “An increase of the intake of dietary vitamin K was associated with better cognitive function scores, independently of recognized risk factors for cognitive decline, in an older adult Mediterranean population with high cardiovascular risk.”

While the Japanese study examined “vitamin K,” there are several studies that showed that MenaQ7® Vitamin K2 as MK-7 improved K status as measured by ucOC, and these were done in healthy adult and child populations.[3,4]

“We have worked with world-renowned researchers – as NattoPharma and that work continues at Gnosis by Lesaffre – to confirm the safe and effective health benefits of MenaQ7 Vitamin K2 as MK-7. Elucidating the important mechanism of activating K-dependent proteins, including osteocalcin and Matrix Gla protein (MGP), was a foundational piece of that work,” explains Dr. Hogne Vik, chief medical officer with Gnosis by Lesaffre, who referenced an important 2021 US-based review paper highlighting Vitamin K2 as a potential strategy for Alzheimer’s disease.[5] “Based on our research and the critical work that continues, we can hypothesize that K2 supplementation could prove beneficial in the brain development of children and support healthy brain function in adults.”

Dr. Vik also noted that while Vitamin K2 as MK-4 has been noted as the main form of vitamin K in the brain, “it is important to mention that in-vivo research supports that supplementation with K2 as MK-7 increases MK-4 content in the brain tissue,” he concluded.

References:

1 Azuma K et al. Association of Vitamin K Insuf?ciency With Cognitive Dysfunction in Community-Dwelling Older Adults. Front. Nutr. (2022) 8:811831. doi: 10.3389/fnut.2021.811831

2 Camacho-Barcia L et al. Vitamin K dietary intake is associated with cognitive function in an older adult

Mediterranean population. Age Ageing. 2022 Feb 2;51(2):afab246. Doi: 10.1093/ageing/afab246.

3 Knapen MHJ et al. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013 Sep;24(9):2499-507. doi: 10.1007/s00198-013-2325-6. Epub 2013 Mar 23. PMID: 23525894.

4 Theuwissen E et al. Vitamin K status in healthy volunteers. Food Funct. 2014 Feb;5(2):229-34. doi: 10.1039/c3fo60464k. PMID: 24296867.

5 Popescu A and German M. “Vitamin K2 Holds Promise for Alzheimer’s Prevention and Treatment.” Nutrients. 2021,13,2206.

* Explanation of MMSE: The maximum MMSE score is 30 points. A score of 20 to 24 suggests mild dementia, 13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia. On average, the MMSE score of a person with Alzheimer's declines about 2 to 4 points each year.

About Gnosis by Lesaffre

Gnosis by Lesaffre harnesses the power of microorganisms and biotransformation processes like fermentation to cultivate nutritional actives, probiotics, and nutritional and functional yeasts that benefit human health and wellbeing. The team draws on its focused research and applications capabilities to collaborate with nutraceutical and pharmaceutical brands to develop game-changing products for their customers

In the about link Gnosis by Lesaffre to Gnosis by Lesaffre, biotransformation expert for human health

New evidence of how exercise can counter diabetes damage

One way exercise can counter the damage of diabetes is by enabling activation of a natural system we have to grow new blood vessels when existing ones are ravaged by this disease, scientists report.

Angiogenesis is the ability to form new blood vessels, and diabetes not only damages existing blood vessels, it hinders this innate ability to grow new ones in the face of disease and injury, say experts at the Vascular Biology Center at the Medical College of Georgia.

Endothelial cells line our blood vessels and are essential to that new blood vessel growth.

Now the MCG scientists have the first evidence that in the face of diabetes, even one 45-minute session of moderate intensity exercise enables more exosomes, submicroscopic packages filled with biologically active cargo, to deliver directly to those cells more of the protein, ATP7A, which can set angiogenesis in motion, they report in The FASEB Journal.

Not unlike the most sophisticated and efficient delivery services we have all come to rely upon, particularly during the pandemic, what exosomes carry depends on where they come from and where they are headed, says Dr. Tohru Fukai, MCG vascular biologist and cardiologist.

While he and co-corresponding author MCG vascular biologist Dr. Masuko Ushio-Fukai are not yet certain of the origin of these helpful exosomes, it's clear that one place they deliver is to endothelial cells, Fukai says.

In both an animal model of type 2 diabetes and a handful of healthy 50-something-year-olds, two weeks of volunteer running on a wheel for the mice and that one cardio session for the humans increased levels of ATP7A in the exosomes that attached to endothelial cells.

At that point, the activity did not significantly impact the weight of the mice, the scientists note, but it did also increase a marker of endothelial function and factors like, vascular endothelial growth factor, needed for angiogenesis.

Exercise also increased the amount of the powerful, natural antioxidant extracellular superoxide dismutase, or SOD3, but it's the heavier payload of ATP7A, which is also known to deliver the essential mineral copper to cells, that is key to making good use of the SOD3 present, Ushio-Fukai says.

SOD3, is an important natural antioxidant produced by vascular smooth muscle cells in the walls of blood vessels as well as skeletal muscle cells, which helps us maintain healthy levels of reactive oxygen species, or ROS. ROS is a natural byproduct of our use of oxygen that is an important cell signal, enabling a variety of functions. But in diabetes, high blood sugar levels result in high ROS levels that instead hinder important normal functions.

The Fukais have shown that ATP7A levels are reduced in diabetes. They also now have some of the first evidence that exosomes circulating in the plasma of sedentary animal models of type 2 diabetes actually impair angiogenesis when placed in a dish with human endothelial cells, as well as in an animal model of wound healing.

The scientists suggest that synthetic exosomes, already under study as drug-delivery mechanisms, could one day work as an "exercise mimetic" to improve patients' ability to grow new blood vessels when diabetes has damaged their innate ability.

In fact, they have already generated exosomes in which SOD3 is overexpressed and found improved angiogenesis and healing in a mouse model of diabetes.

The way it's supposed to work is SOD3 is naturally silenced in endothelial cells, so they must get it from other cells, notes Ushio-Fukai, hence the importance of exosome delivery. SOD3 must then bind to endothelial cells at its natural spot called the heparin-binding domain, and the copper transporter ATP7A must be present to enable SOD3 to be active there, Fukai says. Both ATP7A and the binding site are key, Fukai notes. For example, when they removed the binding site from the endothelial cells, which can happen in nature, the benefits were lost.

Once on the scene and active, SOD3 converts the ROS superoxide into hydrogen peroxide, or H2O2, another signaling ROS that helps support normal endothelial cell function. The Fukais have reported that in human endothelial cells, overexpressing SOD3 promotes angiogenesis by increasing H2O2.

A copper connection also runs throughout this process as endothelial cells regularly use a lot of copper, and ATP7A, known to transport the essential mineral that we consume in foods like nuts and whole grains, is dependent on copper itself.

Physical exercise, like running or walking on treadmill, prompts muscles to contract which in turn prompts release of exosomes into the blood.

When Fukai was a postdoc in the Emory University Section of Cardiology he was part of the research group that was the first to show that exercise increases SOD3 activity. SOD3 levels decrease with age and with some disease states like diabetes and hypertension.

Exosomes are being studied as biomarkers for a wide range of diseases like cancer and diabetes as well as precise treatment delivery tools. For example, exosomes produced by a cancer cell will hone right back to a cancer cell.

About 1 in 10 Americans have diabetes, according to the Centers for Disease Control and Prevention.

Story Source: Medical College of Georgia at Augusta University.

OmegaQuant Launches HbA1c Test for People Looking to Manage & Monitor Their Blood Sugar Level

OmegaQuant, the leader in nutritional status testing, has launched an HbA1c Test*, with a sample collection kit that allows for testing at home. This simple, safe, convenient test measures the amount of sugar (glucose) in the blood.

When glucose builds up in the blood, it binds to a protein called hemoglobin. Testing your hemoglobin A1c level is a great way to gain insight into your body’s ability to metabolize glucose.

Our bodies need glucose to function, but for many people, dysregulation of diet, stress and activity can cause glucose levels to rise undetected for too long. When blood glucose is too high for too long, negative health outcomes can result, even without the presence of diabetes.

As opposed to a fasting glucose test, the HbA1c Test captures someone’s blood sugar status over a period of three months. This offers a window of dietary intake versus a moment in time, which can help people make any necessary dietary or lifestyle adjustments to bring their blood sugar level into a healthy range.

The widely accepted optimal range for HbA1c is 4.5- 5.7%. A result between 5.7-6.2% would indicate the development of "prediabetes" and a result of over 6.2% would indicate diabetes. It is highly recommended that you discuss your test results with your healthcare provider.

Although many people may not have any physical symptoms, some signs of high blood sugar include frequent urination, increased hunger and thirst, fatigue, blurred vision, tingling or numbness in the hands or feet, and unexplained weight loss.

The new HbA1c Test from OmegaQuant is intended for health-minded individuals who want to keep an eye on their blood sugar levels. In the long-term, healthy blood sugar levels promote longevity and reduce the risk of diabetes, cardiovascular disease and cognitive impairment.

Typical HbA1c testing requires a blood draw, which is sent to a lab for analysis. However, OmegaQuant’s HbA1c Test consists of a simple finger stick and a few drops of blood. This allows people to take the test on their own time, at their convenience, in the safety of their own home.

"The HbA1c test is similar to the Omega-3 Index test in that it captures someone’s status over a period of time, in this case three months or so. This offers a more accurate picture of one’s dietary intake and could indicate that dietary or lifestyle changes are needed if their blood sugar level is not in the optimal range," said Kelly Patterson, MS, RD, LDN, CSSD, Clinical Nutrition Educator, OmegaQuant. "This test will truly help people measure, modify and monitor their blood sugar status."

*Currently the HbA1c test is only available in the US and Canada.

Gastrointestinal issues linked with anxiety, social withdrawal for kids with autism

Children with autism spectrum disorder tend to experience gastrointestinal issues, such as constipation and stomach pain, at a higher rate than their neurotypical peers. Some also experience other internalizing symptoms at the same time, including stress, anxiety, depression and social withdrawal. Until now, no studies have examined the causal relationship between gastrointestinal symptoms and internalizing symptoms.

A new study at the University of Missouri found a "bi-directional" relationship between gastrointestinal issues and internalized symptoms in children and adolescents with autism -- meaning the symptoms seem to be impacting each other simultaneously. The findings could influence future precision medicine research aimed at developing personalized treatments to ease pain for individuals with autism experiencing gastrointestinal issues.

"Research has shown gastrointestinal issues are associated with an increased stress response as well as aggression and irritability in some children with autism," said Brad Ferguson, an assistant research professor in the MU School of Health Professions, Thompson Center for Autism and Neurodevelopmental Disorders and Department of Radiology in the MU School of Medicine. "This likely happens because some kids with autism are unable to verbally communicate their gastrointestinal discomfort as well as how they feel in general, which can be extremely frustrating. The goal of our research is to find out what factors are associated with gastrointestinal problems in individuals with autism so we can design treatments to help these individuals feel better."

In the study, Ferguson and his team analyzed health data from more than 620 patients with autism at the MU Thompson Center for Autism and Neurodevelopmental Disorders under the age of 18 who experience gastrointestinal issues. Then, the team examined the relationship between the gastrointestinal issues and internalized symptoms, such as stress, anxiety, depression, and social withdrawal. Ferguson explained the findings provide more evidence on the importance of the "gut-brain axis," or connection between the brain and the digestive tract, in gastrointestinal disorders in individuals with autism.

"Stress signals from the brain can alter the release of neurotransmitters like serotonin and norepinephrine in the gut which control gastrointestinal motility, or the movement of stool through the intestines. Stress also impacts the balance of bacteria living in the gut, called the microbiota, which can alter gastrointestinal functioning," Ferguson said. "The gut then sends signals back to the brain, and that can, in turn, lead to feelings of anxiety, depression and social withdrawal. The cycle then repeats, so novel treatments addressing signals from both the brain and the gut may provide the most benefit for some kids with gastrointestinal disorders and autism."

Ferguson said an interdisciplinary team of specialists is needed to help solve this complex problem and develop treatments going forward.

Ferguson collaborates with David Beversdorf, a neurologist at the MU Thompson Center for Autism and Neurodevelopmental Disorders, who also studies gastrointestinal problems in individuals with autism. In a recent study, Beversdorf, who also has appointments in the MU College of Arts and Science and MU School of Medicine, helped identify specific RNA biomarkers linked with gastrointestinal issues in children with autism.

"Interestingly, the study from Beversdorf and colleagues found relationships between microRNA that are related to anxiety behavior following prolonged stress as well as depression and gastrointestinal disturbance, providing some converging evidence with our behavioral findings," Ferguson said.

Now, Ferguson and Beversdorf are working together to determine the effects of a stress-reducing medication on gastrointestinal issues in a clinical trial.

"I have a great relationship with Beversdorf and the MU Thompson Center Autism Research Core (ARC) that allows our team to quickly go from findings in the laboratory to clinical trials," Ferguson said.

Ferguson explained that some treatments may work for some individuals with autism but not necessarily for others.

"Our team uses a biomarker-based approach to find what markers in the body are common in those who respond favorably to certain treatments," Ferguson said. "Our goal is to eventually develop a quick test that tells us which treatment is likely to work for which subgroups of patients based on their unique biomarker signature, including markers of stress, composition of gut bacteria, genetics, co-occurring psychological disorders, or a combination thereof. This way, we can provide the right treatments to the right patients at the right time."

"Bidirectional relationship between internalizing symptoms and gastrointestinal problems in youth with autism spectrum disorder" was recently published in the Journal of Autism and Developmental Disorders. Ferguson also collaborated with Kristen Dovgan, an assistant professor in the Department of Psychology at Marist College, and Kyra Gynegrowski, an undergraduate student in the Department of Psychology at Marist College. Funding for the study was provided by the Autism Speaks Autism Treatment Network, which is now known as the Autism Care Network.

Story Source: University of Missouri-Columbia.

Stress, Anxiety and Depression During Pregnancy May Hinder Toddler’s Cognitive Development

Women’s elevated anxiety, depression and stress during pregnancy altered key features of the fetal brain, which subsequently decreased their offspring’s cognitive development at 18 months. These changes also increased internalizing and dysregulation behaviors, according to a new study by Children’s National Hospital published in JAMA Network Open. Researchers followed a cohort of 97 pregnant women and their babies. The findings further suggest that persistent psychological distress after the baby is born may influence the parent-child interaction and infant self-regulation.

This is the first study to shed light on an important link between altered in-utero fetal brain development and the long-term cognitive development consequences for fetuses exposed to high levels of toxic stress during pregnancy. While in the womb, the researchers observed changes in the sulcal depth and left hippocampal volume, which could explain the neurodevelopment issues seen after birth. Once they grow into toddlers, these children may experience persistent social-emotional problems and have difficulty establishing positive relationships with others, including their mothers. To further confirm this, future studies with a larger sample size that reflect more regions and populations are needed.

“By identifying the pregnant women with elevated levels of psychological distress, clinicians could recognize those babies who are at risk for later neurodevelopmental impairment and might benefit from early, targeted interventions,” said Catherine Limperopoulos, Ph.D., chief and director of the Developing Brain Institute at Children’s National and senior author of the study.

Regardless of their socioeconomic status, about one of every four pregnant women suffers from stress-related symptoms, the most common pregnancy complication. The relationship between altered fetal brain development, prenatal maternal psychological distress and long-term neurodevelopmental outcomes remain unknown. Studying in utero fetal brain development poses challenges due to fetal and maternal movements, imaging technology, signal-to-noise ratio issues and changes in brain growth.

All pregnant participants were healthy, most had some level of education and were employed. To quantify prenatal maternal stress, anxiety and depression, the researchers used validated self-reported questionnaires. Fetal brain volumes and cortical folding were measured from three-dimensional reconstructed images derived from MRI scans. Fetal brain creatine and choline were quantified using proton magnetic resonance spectroscopy. The 18-month child neurodevelopment was measured using validated scales and assessments.

This study builds upon previous work from the Developing Brain Institute led by Limperopoulos, which discovered that anxiety in pregnant women appears to affect the brain development of their babies. Her team also found that maternal mental health, even for women with high socioeconomic status, alters the structure and biochemistry of the developing fetal brain. The growing evidence underscores the importance of mental health support for pregnant women.

“We’re looking at shifting the health care paradigm and adopting these changes more broadly to better support moms,” said Limperopoulos. “What’s clear is early interventions could help moms reduce their stress, which can positively impact their symptoms and thereby their baby long after birth.”

Mayo Clinic research finds AI-enabled ECGs may identify patients at greater risk of stroke, cognitive decline

Atrial fibrillation, the most common cardiac rhythm abnormality, has been linked to one-third of ischemic strokes, the most common type of stroke. But atrial fibrillation is underdiagnosed, partly because many patients are asymptomatic.

Artificial intelligence-enabled electrocardiography (ECG) was recently shown to identify the presence of brief episodes of atrial fibrillation, and the ability of an AI-enabled ECG algorithm to predict atrial fibrillation up to 10 years before clinical diagnosis has been confirmed in a population-based study conducted by Mayo Clinic researchers.

A new population-based study from Mayo Clinic now offers evidence that the algorithm can help identify patients at greater risk of cognitive decline. AI-enabled ECG that shows high probability of atrial fibrillation also was associated with the presence of infarctions, or incidents of cerebral stroke, on MRI, according to the study.

The study is described in an article, "Artificial Intelligence-Enabled Electrocardiogram for Atrial Fibrillation Identifies Cognitive Decline Risk and Cerebral Infarcts," which is published in Mayo Clinic Proceedings.

Most of the infarctions observed were subcortical, meaning that they occurred in the region of the brain below the cortex. This suggests that AI-enabled ECG not only predicts atrial fibrillation, but also detects other cardiac disease markers and correlates with small vessel cerebrovascular disease and cognitive decline.

"This study finds that artificial intelligence-enabled electrocardiography acquired during normal sinus rhythm was associated with worse baseline cognition and gradual decline in global cognition and attention," says Jonathan Graff-Radford, M.D., a Mayo Clinic neurologist and the study's corresponding author. "The findings raise the question whether initiation of anticoagulation is an effective and safe preventive strategy in individuals with a high AI-ECG algorithm score for reducing the risk of stroke and cognitive decline."

Prospective controlled studies are needed to determine whether a high atrial fibrillation score on an AI-enabled electrocardiogram could be a biomarker to identify patients for anticoagulation or more aggressive stroke risk factor modification, Dr. Graff-Radford says.

The retrospective study reviewed sinus-rhythm ECG of 3,729 patients with a median age of 74 years who were enrolled in the Mayo Clinic Study of Aging between 2004 and 2020. Adjusting for demographic factors, the AI-enabled ECG atrial fibrillation score correlated with lower baseline and faster decline in global cognitive scores. About one-third of the patients who underwent ECG also had an MRI, and high atrial fibrillation probability in the ECG correlated with MRI-detected cerebral infarcts.

"Application of this AI-ECG algorithm may be another way to screen individuals not only to determine risk of atrial fibrillation, but also to identify future risk of cognitive decline and stroke," says Dr. Graff-Radford.

Research reported in the article was supported by grants from the National Institute on Aging and the National Institutes of Health. The study was made possible by the Rochester Epidemiology Project. Potential competing interests are identified in the article. Among the potential competing interests, Peter Noseworthy, M.D., a Mayo Clinic cardiologist, and Mayo Clinic have filed patents related to the application of AI to ECG for diagnosis and risk stratification.

Journalists: Video of Erika Weil, M.D., first author of the study, discussing the findings is available here.

About Mayo Clinic Proceedings
Mayo Clinic Proceedings is a monthly peer-reviewed journal that publishes original articles and reviews on clinical and laboratory medicine, clinical research, basic science research, and clinical epidemiology. The journal, sponsored by Mayo Foundation for Medical Education and Research as part of its commitment to physician education, has been published for 95 years and has a circulation of 127,000.

About Mayo Clinic
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