2. Relationship between Vitamin K and Age-Associated Diseases

The latest scientific evidence indicated that VK has a significant role in mitigating aging and preventing age-related diseases and has the potential to improve the efficacy of some medical treatments among adults over the age of 50 years. The novel role of VK on aging and age-associated diseases is mainly due to its antioxidant and anti-inflammatory effects. It focused on the most prevalent age-related diseases, including osteoporosis and bone fractures, neurodegenerative diseases, VC, CVD, and cancer, as well as metabolic disorders, mainly T2D and obesity. In addition, we presented the most recent findings on the association between VK and COVID-19 and its potential effect on reducing fatal outcomes in such cases. Specifically, the scientific data showed that VK has an integral role in bone metabolism through the carboxylation of OC, which is an important protein capable of transporting and depositing calcium in bone. MK-4 was revealed to be a more effective antiosteoporotic agent than VK1, with increased pro-osteoblastic and anti-osteoclastogenic actions achieved by inhibiting the NF-кB pathway. VitD improves OC carboxylation and, along with VK and magnesium supplementations, can be a better strategy for reducing bone fractures, a highly public health concern among the elderly. In addition, it is concluded that VK supplement could be a safe approach for reducing CVD morbidity and mortality. By activating matrix Gla protein, VK keeps calcium from accumulating in the walls of blood vessels, thus making VK a potential treatment for patients at risk for either VC or CVD. Furthermore, VK may reduce the risk for metabolic disorders, such as T2D, by improving insulin sensitivity and anti-inflammatory activity, as well as obesity, through a lipid-lowering effect. It also showed the influence VK has on age-related neurodegenerative diseases, such as AD and PD. VK is involved in the brain’s physiology and can reduce its cognitive decline by carboxylation of Gas6 protein, a VKDP that could defend against neuronal apoptosis induced by OS and Aβ. The anticancer potential of VK was summarized by several in vitro and epidemiological studies. There are multiple mechanisms where the potential anticancer agent of VK can react, including the modulation of various transcription factors, which induced antiproliferative, proapoptotic, and autophagic effects, which were found to be associated with a reduced risk of cancer. The latest evidence on VK and pulmonary disease stem from the fact that VK can activate protein S, which was recently shown to prevent the generation of inflammatory cytokines and cytokine storms detected in COVID-19 cases. Low levels of protein S, due to pneumonia-induced VK depletion, were correlated with higher thrombogenicity and possibly fatal outcomes in COVID-19 patients.

Consuming a healthy diet is vital throughout the aging process to maintain and promote wellbeing. The aging population may be at risk for many suboptimal nutrient intakes, including VK, which have been shown to be associated with adverse health outcomes highly prevalent in this age group. Thus, the intake of VK-rich diets or VK supplements could prevent age-related diseases and/or support the effectiveness of medical treatments. However, more studies are needed to formulate the exactly recommended intakes of VK, including VK1, MK-4, and MK-7, due to their distinct bioavailability and biological activities. Higher values of VK intakes are needed, especially among the elderly and people who have comorbidities conditions that are most likely to be VK deficient.