In the News

Vitamin K2 Impact on Oxidative Stress, ATP Production: New Evidence

Vitamin K Shows Evidence of Brain Benefits in Rats

Cases of cognitive decline in older people more than doubles in ten years

How Obesity Can Rewire the Immune System and the Response to Immunotherapy--and How to Change That

Vitamin K2 Impact on Oxidative Stress, ATP Production: New Evidence

IECN 2022 poster presentation highlights the non-canonical role of MenaQ7^® Vitamin K2 on vascular calcification, widening cardio evidence and potential sports applications.

MARCQ-EN-BAROEUL, FRANCE AND EAST BRUNSWICK, NJ (29 MAR 2022) – A poster presented 25 March 2022 at the 2nd International Electronic Conference on Nutrients (IECN) detailed recent research showing that MenaQ7® Vitamin K2 as MK-7 countered induced oxidative stress in vascular smooth muscle cells, ultimately lowering oxidative stress while increasing ATP production. The global event focuses on nutrition support for immunity and countermeasure effects on infection, inflammation, and oxidative stress.

The poster, "Non-Canonical Role of MK-7 in Vascular Smooth Muscle Cells" [1], was presented to the prestigious audience by PhD student Asim Cengiz Akbulut, Department of Biochemistry, CARIM, Maastricht University, with the support of his supervisor and senior author on the abstract Prof. Leon Schurgers, Professor of Biochemistry of Vascular Calcification and Vice-Chair of Biochemistry at CARIM, Maastricht University. Akbulut shared recent findings from a cellular study where the vitamin K pathway was antagonized by warfarin, inducing oxidative stress in vascular smooth muscle cells (SMCs), contributing to pathological phenotype perpetuating vascular calcification and cardiovascular disease.

After introducing Vitamin K2 as MK-7 (as MenaQ7^®), measurements were taken of ATP, oxidative stress, extracellular vesicles (EV). Key findings include: interference with vitamin K metabolism by warfarin results in increased intracellular oxidative stress and EV secretion, MK7 counteracts intracellular oxidative stress, both under normal conditions and warfarin-induced, and MK7 increases ATP (adenosine triphosphate) production, even in the presence of warfarin.

The authors concluded: "Our experiments show that in primary human SMCs, MK-7 lowers oxidative stress and EV release and increases ATP production. This pathway points to a non-canonical role of MK-7 in the prevention of vascular calcification, unrelated to its canonical role as cofactor for the posttranslational modification of MGP."

Since 2004, NattoPharma (now Gnosis by Lesaffre) has worked closely with the Maastricht University in documenting the benefits of the company's exclusive vitamin K2 as MK-7 brand MenaQ7^®. These new findings are in line with previous research eliminating that vitamin K2 decreases oxidative stress[2], as well as the non-canonical role of K2 inhibiting inflammatory markers[3].

"We are incredibly encouraged by the results of this study highlighting the potential of Vitamin K2 as MK-7 for healthy aging, as oxidative stress is involved in several age-related conditions, such as increased cardiovascular risk, chronic kidney conditions, and neurodegenerative disorders," explains Hogne Vik, Gnosis by Lesaffre Chief Medical Officer. "This contributes nicely to our already substantial body of research showing MenaQ7 is a cardio-protective nutrient and reaffirms why the medical community is interested in the ongoing study of this important nutrient for the betterment of global health.

"Further, evidence showing MenaQ7 increased the production of ATP shines highlights K2 as MK-7 as a potentially essential nutrient for sports nutrition,” concludes Vik. “While it is preliminary data, we are excited about the next steps of this important research to validate the additional health benefits and applications.”

References:

1 https://sciforum.net/paper/view/12401

2 https://www.atherosclerosis-journal.com/article/S0021-9150(19)31253-5/fulltext

3 https://pubmed.ncbi.nlm.nih.gov/27200471/

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.

Vitamin K Shows Evidence of Brain Benefits in Rats

In a new study conducted in rats, scientists report evidence that vitamin K could help protect against aging-related cognitive declines associated with Alzheimer’s disease and other forms of dementia.

“Vitamin K2 demonstrated very promising impact in hindering aging-related behavioral, functional, biochemical and histopathological changes in the senile aging brain,” said Mohamed El-Sherbiny, PhD, of AlMaarefa University in Saudi Arabia, the study’s senior author. “Vitamin K2 can be proposed to be a promising approach to attenuate age-related disorders and preserve cognitive functions in aging individuals.”

Abdulrahman Aloufi, a medical student working in El-Sherbiny’s laboratory at AlMaarefa University, will present the findings at the American Association for Anatomy annual meeting during the Experimental Biology (EB) 2022 meeting, held in Philadelphia April 2–5.

Dementia is a form of cognitive impairment that interferes with daily life and is different from normal memory lapses that occur with aging. In the U.S., it is estimated that more than six million people are currently living with Alzheimer’s, one of the most common types of dementia.

Vitamin K is a group of compounds that includes vitamin K1, found in leafy greens and some other vegetables, and vitamin K2, found in meats, cheeses and eggs. Previous studies have linked vitamin K with processes involved in brain functioning, and some studies have associated vitamin K deficiencies with Alzheimer’s disease and dementia.

The new study elucidates some of the biological pathways through which vitamin K appears to help preserve cognitive functioning. The researchers investigated the effects of menaquinone-7 (MK-7), a form of vitamin K2, in 3-month-old rats, an age at which rats have reached maturity. One group of rats received supplemental MK-7 for 17 months while the other group did not.

The researchers used validated tests including a maze, swim test and sociability test to assess the rats’ cognitive functioning and depressive-like and anxiety behavior. These tests revealed that rats that received MK-7 performed better than those that did not. Vitamin K supplementation was associated with reduced evidence of cognitive impairment, depression and anxiety, along with improved spatial memory and learning ability.

At the end of the study, the researchers examined the rats’ brain tissues for insights on the biological pathways involved. The results suggest that vitamin K supplementation affects pathways involving the proteins NLRP3, caspase-1, and Nrf-2, which are involved in inflammation and antioxidant activity. It also appears to promote the expression of tyrosine, an amino acid that helps preserve cognitive functions.

In addition to various forms of vitamin K found naturally in foods, vitamin K supplements are commercially available. However, researchers cautioned that more studies are needed to determine whether the new findings translate from rats to humans and to identify the optimal source and dose of vitamin K to reap potential brain benefits. People taking certain blood thinners and other medications are advised to avoid vitamin K supplements and foods rich in vitamin K.

“Further clinical studies will be required to assess the appropriate dosage for protection against Alzheimer’s, especially in those treated with vitamin K antagonists,” said El-Sherbiny.

Cases of cognitive decline in older people more than doubles in ten years

The researchers set out to see if there had been an increase in the numbers of older people who were reporting their first concerns about memory loss or cognitive decline to their doctor and what their chances of developing dementia were after consultation.

The study, published today in Clinical Epidemiology, looked at data from more than 1.3m adults aged between 65 and 99 years old*, taken between 2009 and the end of 2018. The researchers identified 55,941 adults who had spoken to their GP about memory concerns and 14,869 people who had a record of cognitive decline.

For every 1,000 people that were observed for one year in 2009, there was one new case of cognitive decline being recorded. By 2018, for every 1,000 people that were observed for one year, there were three new cases of cognitive decline being recorded.

Lead author and PhD candidate Brendan Hallam (UCL Epidemiology & Health Care) said: “This is an important study which sheds new light on how prevalent memory concerns and cognitive decline are among the older generation in the UK and how likely these symptoms might progress to a dementia diagnosis.

“The study showed that while memory concern rates had remained stable, incidences of cognitive decline, a step beyond memory concern, had more than doubled between 2009 and 2018.

“There has been a drive in the past decade to encourage people to seek help earlier from their doctors if they are worried about their memory and we found that among those over 80, women and people living in more deprived areas were more likely to have a record of memory concern or cognitive decline, and their symptoms were more likely to progress to dementia diagnosis.”

The study also showed that within three years of following up a person from the date when the doctor reported a memory concern, 46% of people would go on to develop dementia. For people with cognitive decline, 52% would go on to develop dementia.

Co-author, Professor Kate Walters (UCL Epidemiology & Health Care) explained: “People who have been noted in their health records as having concerns about their memory are at just under 50% chance of developing dementia within the next three years.”

Brendan Hallam also outlined “Memory concerns and cognitive decline are not only hallmark symptoms of dementia, but they also predict a high risk of developing dementia. It is important for GPs to identify people with memory concerns as soon as possible to deliver recommendations to improve memory and allow timely diagnosis of dementia.”

The authors note one potential limitation of the present study is the potential variations in which GPs record memory concerns and memory decline. They also say more research is needed to better understand the discrepancy between rates of memory symptoms and cognitive decline in the general population and those recorded in primary care.

This work was carried out within the APPLE-Tree programme that is supported by the ESRC/NIHR [ES/S010408/1]. Brendan Hallam was funded by an ESRC studentship [ES/P000592/1].

How Obesity Can Rewire the Immune System and the Response to Immunotherapy--and How to Change That

When mice with atopic dermatitis—a common type of allergic skin inflammation—are treated with drugs that target the immune system, their thickened, itchy skin generally heals quickly. But scientists have now discovered that the same treatment in obese mice makes their skin worse instead. That is because obesity changes the molecular underpinnings of allergic inflammation, both in mice and humans.

A team of researchers at Gladstone Institutes, the Salk Institute for Biological Studies, and UC San Francisco discovered how obesity can change the immune system and, potentially, how clinicians might be able to better treat allergies and asthma in obese people. Photo: Michael Short/Gladstone Institutes

A team of researchers at Gladstone Institutes, the Salk Institute for Biological Studies, and UC San Francisco discovered how obesity can change the immune system and, potentially, how clinicians might be able to better treat allergies and asthma in obese people. Photo: Michael Short/Gladstone Institutes

For the new study, researchers at Gladstone Institutes, the Salk Institute for Biological Studies, and UC San Francisco (UCSF) teamed up. Their findings, reported in the journal Nature, shed light on how obesity can change the immune system and, potentially, how clinicians might be able to better treat allergies and asthma in obese people.

"We're living in an era when the rate of obesity is increasing around the world," says Alex Marson, MD, PhD, director of the Gladstone-UCSF Institute of Genomic Immunology and a senior author of the study. "Changes in diet and body composition can affect the immune system, so we have to think about how diseases that involve the immune system might differ between individuals."

"Our findings demonstrate how differences in our individual metabolic states can have a major impact on inflammation, and how available drugs might be able to improve health outcomes," says Ronald Evans, PhD, senior author of the study, and director of Salk's Gene Expression Laboratory and the March of Dimes Chair in Molecular and Developmental Biology at Salk.

Different Types of T Cell Responses

A recent study estimated that about half of the adults in the United States will be classified as obese by the year 2030. Researchers also know that obesity, sometimes classified as a chronic inflammatory state, alters the immune system in myriad ways. Clinicians have reported that people with obesity often seem to have different courses of disease—from infections and allergies to cancer—and respond differently to some treatments.

During his graduate studies at Salk and subsequent research in the Marson lab, Sagar Bapat, MD, PhD—now a pathologist and faculty at UCSF—wanted to know, at a molecular level, how obesity affected atopic dermatitis. He discovered that when mice were made obese by eating a high-fat diet prior to the induction of dermatitis, they developed more severe disease than lean animals. To understand why, he and his colleagues analyzed the immune cells and molecules that were active in each group of mice.

"What we were expecting to see in the obese mice was just a greater degree of the same kind of inflammation," says Bapat. "Instead, we saw a completely different kind of inflammation."

The body's helper T cells, which help protect against infection but also become overactive in autoimmune disease or allergies, can be grouped into three classes: TH1, TH2, and TH17 cells. Scientists had considered atopic dermatitis a TH2 disease; that means the TH2 cells are the ones causing the skin inflammation.

In lean mice with atopic dermatitis, Bapat and his colleagues indeed found that the TH2 cells were active. In obese mice with the same condition, however, TH17 cells were activated. At a molecular level, it meant that atopic dermatitis was completely different in the obese mice, raising the question of whether the drugs that work in lean animals would also be effective in obese animals.

Changing a Drug's Effectiveness

In recent years, scientists have developed drugs aimed at treating atopic dermatitis by dampening the response of TH2 cells. When Bapat and his colleagues treated obese mice with one of these drugs, not only did it not ease their atopic dermatitis, it actually made the disease significantly worse.

"The treatment became a robust anti-treatment," says Bapat. "This suggests that you can have identical twins show up to the hospital with the same disease, but if one is obese and one is lean, maybe the same drug won't work on both."

The researchers suspected that dysfunction in a protein called PPAR-gamma might be mediating the link between obesity and inflammation. In 1995, Evans and his team discovered that PPAR-gamma was a master regulator of fat cells and a target of an approved drug for diabetes.

When the scientists treated obese mice with atopic dermatitis with one of these PPAR-gamma activating drugs, called rosiglitazone, the animals' skin improved and the molecular profile of their disease switched back from TH17 to TH2 inflammation. Moreover, the drugs aimed at the TH2 inflammation were then, almost as in lean mice, able to improve the obese animals' atopic dermatitis.

"Essentially, we immunologically 'de-fattened' obese mice without changing their body weight," says Bapat.

Back to Patients

The team also analyzed data from human patients with allergic disease, including 59 patients with atopic dermatitis as well as hundreds of people with asthma (another condition that similarly involves a reaction from the immune system) enrolled in a large existing longitudinal study. They found that obese people were more likely to have indications of TH17 inflammation or decreased signs of the expected TH2 inflammation.

Although more studies on people are needed, the data hint that in humans and mice alike, obesity causes a switch in inflammation that has consequences for the pathology of allergic disease and the effectiveness of immune therapies that target TH2-associated inflammation.

"What we'd like to know more about now is exactly how the T cell switch happens," says senior author Ye Zheng, PhD, an associate professor in the NOMIS Center for Immunobiology and Microbial Pathogenesis at Salk. "There are more details here to uncover that could have relevance for a host of diseases related to allergy and asthma."

Already, however, the new study points toward the utility of combining the therapy that targets TH2 inflammation with a PPAR-gamma drug like rosiglitazone to treat obese patients with atopic dermatitis.

"This is a case where our scientific discovery could have a very safe and quick application to therapy in people," says Evans. "Our preclinical findings suggest that these already FDA approved drugs may have a unique co-treatment benefit in certain patients."

About the Study

The paper "Obesity Alters Pathology and Treatment Response in Inflammatory Disease" was published in the journal Nature on March 30, 2022.