Vitamin K2 has long been incorporated into supplements to support overall health and wellness; it’s also strongly linked to the maintenance of bone density through its ability to modulate calcium ion concentrations in the body.
Although vitamin K2’s benefits for bone and heart health are well known, several recent studies have highlighted that supplementation with the vitamin may also enhance several aspects of cognitive health.
With interest in cognitive health on the rise in the nutraceutical industry, formulators are increasingly looking for efficacious ingredients to boost the brain benefits of their supplements.
To find out why vitamin K2 may be a great option for this, Annabel Kartal-Allen spoke to Katarzyna Maresz, former President of the International Science and Health Foundation.
Staving off neuroinflammation and degeneration
Dr Maresz’s most recent discovery on the impact of vitamin K2 supplementation has found it to be beneficial in terms of reducing neuroinflammation and degeneration: “This mechanistic study points towards K2’s potential role in supporting a healthy brain as well as cognitive function.”1
She adds: “The administration of K2 provided by Gnosis by Lesaffre was found to support neurological function by creating a favourable balance of activity; it reduced the expression of genes associated with neurodegeneration, such as PSEN1 and BACE1, as well as inflammation (IL-1β and IL-6) whilst simultaneously upregulating genes ADAM10 and ADAM17 — both of which protect against amyloid formation.”
Higher serum concentrations of vitamin K2 were associated with a 17–20% reduction in the risk of dementia or mild cognitive impairment
K2 for a reduced dementia risk
Not only can vitamin K2 potentially ward off neuroinflammation, but it may also show promise in diminishing the risk of dementia, Katarzyna explains: “A trial that examined the role of aortic stiffness owing to calcification as a contributing factor to dementia noted that the condition is impacted by the status of active matrix Gla protein (MGP) — the most potent inhibitor of vascular calcification — when activated by vitamin K2 as MK-7.”2
MenaQ7 is the only clinically validated ingredient of this format for cardiovascular health and its contribution to the reduction of aortic stiffness could highlight its ability to reduce the risk of dementia in older individuals.
A review titled “Vitamin K2 Holds Promise for Alzheimer’s Prevention and Treatment,” published in Nutrients, supports this sentiment.3
It concludes that K2 may have the potential to slow down Alzheimer’s disease (AD) pathogenesis: “This review saw researchers consider the antiapoptotic and antioxidant effects of vitamin K2 and how this would impact neuroinflammation, mitochondrial dysfunction, cognition, cardiovascular health and comorbidities associated with AD,” notes Dr Maresz: “They also considered the physiological roles of vitamin K2 in the context of AD.”
Another study corroborating this is Booth et al.’s work, which indicated that higher serum concentrations of vitamin K2 were associated with a 17–20% reduction in the risk of dementia or mild cognitive impairment.4 
Dr Maresz clarifies: “Although this last paper discusses K2 as MK-4, we already know that MK-7 is more bioavailable than MK-4 and our studies have shown that MenaQ7 K2 as MK-7 supplementation is able to improve extrahepatic vitamin K status. An animal model has also shown that MenaQ7 is able to increase the MK-4 levels in the brain, so this finding is still applicable.”
“Vitamin K2 as MK-7 presents promise for Alzheimer’s in that it helps to address some of the age-related changes, such as vascular damage, that are commonly associated with disease onset and progression. By helping to alleviate some of the vascular calcification that impedes blood flow, K2 could prove to be a useful addition to currently available therapies.”
It should be noted, emphasises Dr Maresz, that there is a significant knowledge gap when it comes to Alzheimer’s disease pathogenesis and what impact vitamin K2 truly has on it, “so a lot more research will be necessary to validate this claim.”
The vitamin is implicated in sphingolipid metabolism — a group of functional lipids implicated in the proliferation, differentiation and survival of brain cells
Strengthening cognitive performance
Although vitamin K2 has shown promise in terms of reducing the risk of degenerative diseases such as AD, there is also growing evidence that suggests it can positively impact cognitive performance, Katarzyna explains: “There has been a lot more interest in the role of vitamin K in brain functionality recently, especially when discussing cognition. When Alisi et al. collated the recent research in this area — although not definitive — there was a definite correlation between vitamin K intake and cognitive performance.”
According to the review discussed above, in vitro and animal studies have suggested that “vitamin K2 has some involvement in the antiapoptotic and anti-inflammatory pathways mediated by Growth Arrest Specific Gene 6 and Protein S,” which may suggest its role in brain cell development and survival.5 As well as this, the vitamin is implicated in sphingolipid metabolism — a group of functional lipids implicated in the proliferation, differentiation and survival of brain cells.
Dr Maresz reiterates the link between cardiovascular health and cognition, mentioning another systemic review published in Frontiers in Aging and Neuroscience: “Perhaps most telling were the findings from the “Association of Aortic Stiffness and Cognitive Decline: A Systemic Review and Meta-Analysis” paper." 6
"The authors concluded that “aortic stiffness measured by aortic PWV was inversely associated with memory and processing speed, and could be an independent predictor for cognitive impairment — especially for older individuals.” 
Katarzyna Maresz, former President of the International Science and Health Foundation
This, again, relates to the cardiovascular mechanism of vitamin K2 and its ability to improve arterial elasticity, which was shown in a 3-year MenaQ7 cardiovascular study in which PWV was a measurement.7
Improving depression symptoms
With mounting evidence pointing towards the positive impacts that vitamin K2 can have on cognitive health, researchers also wanted to examine whether it also plays a part in improving mental health.
An analysis of National Health and Nutrition Examination Surveys (NHANES) 2011-2014 in 2023 delved into the relationship between nutrient intake and cognitive function in older adults, finding that vitamin K is associated with better cognitive function scores and an inverse relationship with depression scores in older females aged 60 and older.8
Can K2 banish migraines?
Expanding on the neuroinflammation study by Dr Maresz and her colleagues, Dr Sola Aoun Bahous from the Lebanese American University — a member of the Gnosis Vitamin K2 Scientific Advisory Board — presented the hypothesis that vitamin K2 deficiency in patients suffering from migraine with aura may contribute to the enhanced cardiovascular risk seen in the patient population.9 The trial is currently under way.
Katarzyna elaborates: “In the new study, patients will be randomised to either receive the vitamin K2 supplement (as MenaQ7) or a placebo for 24 weeks. Arterial stiffness will be measured at the beginning, at 3 months and at the end of the study. Clinical and standardised questionnaires will be used to assess the frequency of migraines throughout the study. The endpoints are an assessment of changes in monthly migraine days as compared with baseline, as well as changes in arterial stiffness.”10
According to the researchers, the purpose of this study is to “test if vitamin K2 supplementation might help to prevent migraine attacks, as well as investigate the impact of vitamin K2 supplementation on arterial stiffness in this group of patients.”
“A lot of the industry research we’re seeing points towards the potential that vitamin K2 has in improving cognitive health, as well as enhancing mood. We still don’t know the true reach of its ability to influence health and well-being … and doing more to find out the full extent of its power is essential,” concludes Dr Maresz.
References
1 M. Orticello, et al., “Amyloidogenic and Neuroinflammatory Molecular Pathways Are Contrasted using Menaquinone 4 (MK4) and Reduced Menaquinone 7 (MK7R) in Association with Increased DNA Methylation in SK-N-BE Neuroblastoma Cell Line,” Cells 13, 58 (2024).
2 C. Cui, et al., “Aortic Stiffness is Associated with Increased Risk of Incident Dementia in Older Adults,” J. Alzheimer’s Dis.66(1), 297–306 (2018).
3 A. Popescu and M. German, “Vitamin K2 Holds Promise for Alzheimer’s Prevention and Treatment,” Nutrients 13, 2206 (2021).
4 S. Booth, et al., “Association of Vitamin K with Cognitive Decline and Neuropathy in Community Dwelling Older Persons,” Alzheimer’s Dement. 8, e12255 (2022).
5 L. Alisi, et al., “The Relationships Between Vitamin K and Cognition: A Review of Current Evidence,” Front. Neurol. 10, 239 (2019).
6 Q. Liu, et al., “Association of Aortic Stiffness and Cognitive Decline: A Systemic Review and Meta-Analysis,” Front. Aging Neurosci. 13, 680205 (2021).
7 M.H.J. Knapen, et al., “Menaquinone-7 Supplementation Improves Arterial Stiffness in Healthy Postmenopausal Women. A Double-Blind Randomized Clinical Trial,” Thromb. Haemost. 113(5), 1135–1144 (2015).
8 P.P. Devarshi, et al., “Higher Intake of Certain Nutrients Among Older Adults is Associated with Better Cognitive Function: An Analysis of NHANES 2011–2014,” BMC Nutr. 9(1), 142 (2023).
9 A.G. Mansour, et al., “Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case Control Study,” Headache 60(3), 589–599 (2019).
10 https://classic.clinicaltrials.gov/ct2/show/NCT05943457.
