The US review, published in Nutrients, considers the antiapoptotic and antioxidant effects of vitamin K2 (VK2) and its impact on neuroinflammation, mitochondrial dysfunction, cognition, cardiovascular health, and comorbidities in Alzheimer’s Disease (AD).
The authors examined a considerable body of evidence and conclude that VK2 has the potential to slow the progression of AD and contribute to its prevention.
“Our review is of importance because it highlights new, emerging research relating VK2 and AD, and, to the best of our knowledge, it is the first review to explore this connection,” they write.
The incidence of AD has significantly risen in recent years with AD a leading cause of chronic disability and death - in 2018, 50 million people worldwide were living with dementia, the review says.
“The emotional, physical, and financial toll of AD impacts not only individuals and families, but also society more broadly, and there is no treatment to cure it or to slow its progression.”
Why VK2?
VK2 is primarily sourced from fermented foods and some cheese but intake is low in Western diets and comprises just 10% of dietary vitamin K in European diets. There is currently no recommended daily intake (RDI) for VK2, despite its unique physiological role.
The authors explain: “Both VK1 and VK2 have roles in brain health via the regulation of sphingolipid metabolism. Alterations in sphingolipid metabolism have been implicated in neurodegenerative diseases such as AD, Parkinson’s disease, and Huntington’s disease. However, unlike VK1, VK2 activates a variety of extrahepatic vitamin K dependent proteins (VKDPs), which have many complex roles.”
VK2 also acts as a transcriptional regulator and has antioxidant properties. There is also convincing evidence that it has immunomodulatory and anti-inflammatory properties, and it is approved for the treatment comorbidities of AD, such as osteoporosis, and is shown to alleviate symptoms of type 2 diabetes and depression.
Neuroprotective qualities
When the effects of VK2 on apoptosis (cell death) were considered, it was noted that cells pre-treated with VK2 in one study, exhibited considerably less apoptosis (as measured by flow cytometry) and prevented neuronal death.
Pre-treatment with VK2 also decreased the amount of apoptosis signalling proteins, reduced the presence of reactive oxygen species (ROS), and increased the amount of glutathione, a powerful antioxidant. “When considered together, these studies present a convincing argument for the antiapoptotic and antioxidant properties of VK2,” the authors wrote.
They describe how its neuroprotective properties stem from the menaquinone isoform (MK-7), which supresses the production of proinflammatory cytokines and has the potential to reduce neuroinflammation and neurodegeneration. Furthermore, a 2018 test on mice (to evaluate the effects of anaesthetics) demonstrated that treatment with VK2 helped reverse the resulting cognitive delay, and it mitigated tau phosphorylation and cognitive deficits induced by sevoflurane in a similar 2020 study.
Equally, another study found that low levels of VK2 can exacerbate disruption to gut microbiome caused by antibiotic treatment and provoke gastric haemorrhage. Gut bacteria produces menaquinone (crucial to brain health), thus any change in gut microbiome can contribute to AD pathogenesis, which the authors proclaim could be alleviated by VK2 intake.
The review postulates: “We hypothesize that changes in microbiome composition would alter VK2 production and the likelihood of developing AD. Therefore, we believe that it is imperative to further explore the role of dysbiosis and VK2 production in AD.”
Finally, the review authors highlight the compelling evidence to support the effectiveness of VK2 in lowering the risk of cardiovascular disease (CVD), which numerous studies have linked to dementia. However, two studies carried out on participants aged 46 and over observed a 41% and 50% lower CVD risk after high intake of VK2.
Further investigation
Despite the evidence, the authors express surprise that none of the 121 clinical studies looking into the effects of VK2 on humans are exploring the connection between VK2 and AD.
They add that in light of the “paradigm shift” away from nonpharmacological interventions in AD research it is critically important to investigate possible connections in observational studies and randomized control trials (RCTs).
“When considered together, these studies strongly suggest that VK2 could play an important role in AD prevention and therapy.”
Source : Nutrients
Authors: Alexander Popescu, Monica German
“Vitamin K2 Holds Promise for Alzheimer’s Prevention and Treatment”