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Vitamin K: An underrated player for major medical conditions in public health

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Vitamin K: connections with the intestinal microbiota and diet

Dietary vitamin K is a modulator of the diet-microbiome-health axis; therefore, researchers are looking for evidence of how it affects gut microbial composition and metabolic activities implicated with host health outcomes, especially in the elderly of the general population. In 2020, people over the age of 60 outnumbered children under the age of five, and this older population will nearly double to 2.1 million, overtaking young people by 2050. Therefore, there is an urgent need to implement lifestyle interventions that could effectively reduce, prevent or reverse chronic diseases related to aging.

Diet or eating pattern is a strong determinant of optimal human health. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 showed that a poor diet, i.e. low in fruits and vegetables, whole grains, and high in processed foods/sugars, is the second and third risk factor for death out of 13.5% and 14.6% of women and men globally. Similarly, the EAT-Lancet Commission argued that switching from an industrialized to a plant-based diet could avert an estimated 11 million deaths. The impact of healthy eating as a preventive and therapeutic strategy to combat aging could be as immense as it is simple.

The gut microbiome is another key factor mediating the relationship between diet and age-related health. Therefore, unraveling the interplay between diet, gut microbiome and host health could help devise a healthy strategy to promote healthy aging and narrow the gap between health and lifespan. Green vegetables are the primary source of dietary vitamin K or vitamin K1 (phylloquinone). Vitamin K2 (K2) consists of a group of menaquinones (MK-n, ranges from MK-4 to MK-13) is present in egg yolk, meat, liver, cheese, cottage cheese, natto and butter and is biosynthesized also by certain strains of intestinal bacteria.

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Vitamin K and cognitive decline: public health implications

The central nervous system has been linked to the gut microbiota through the gut-brain axis and is strongly associated with psychiatric conditions such as, anxiety, panic attacks, depression and disorders. In a recently published study, the role of vitamin K2 (MK-7) in cognitive decline associated with intestinal dysbiosis was investigated in mice. Intestinal dysbiosis was induced in mice by administering ampicillin for 14 days and vitamin K2 (0.05 mg/kg) for 21 days with or without antibiotic treatment; the altered gene expression profile of the gut microbes was then determined. This was followed by behavioral studies to evaluate cognition changes and by histopathological, oxidative, and inflammatory brain and gut findings in the three groups of animals.

With the use of antibiotics, the relative abundance of Lactobacillus, Bifidobacterium, Firmicutes e Clostridium it has shrunk. When vitamin K2 was added to the drug, their levels were restored. Cognitive impairment was observed in behavioral studies in the antibiotic group, but this decline was reversed in mice treated with both an antibiotic and vitamin K. Myeloperoxidase levels in the colon and brain increased due to intestinal dysbiosis, which was prevented by the vitamin K2. This means that this vitamin serves not only the body. Or rather, the microbiota uses vitamin K to stay healthy and then to keep us healthy. And this justifies why part of the vitamin K we need is produced by intestinal bacteria.

Role of a vitamin K-containing diet in healthy ageing

While vitamin K1 is a dietary source of vitamin K, menaquinones or vitamin K2 are a byproduct of biosynthesis in the gut microbiome. Cheese, a rich source of saturated fat, is another good source of K2. Since phylloquinone derived from ready meals might have higher bioavailability than that from fresh fruits and vegetables, the fundamental questions regarding the dietary source and bioavailability of phylloquinone and menaquinones remain unanswered. Convenience foods such as hamburgers, pizza, french fries, etc. include other sources of phylloquinone, mainly due to the vegetable oils used in their preparation, suggesting an underreporting of dietary vitamin K1 intake in current consumption data pools food.

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Elucidating the link between diet and health, such as estimating portion size, could help resolve equivocal data from epidemiological studies evaluating vitamin K nutrient intake through dietary recall. While studies have implicated many other bioactive compounds in aging research, observational studies have found that vitamin K and vitamin K dependent proteins (VKDPs) are associated with a broad spectrum of age-related diseases. Although vitamin K’s salutary impact on human health remains unclear, studies have established its effect on hallmarks of aging, such as genomic instability, cellular senescence, mitochondrial dysfunction, and epigenetic abnormalities.

Vitamin K drives cellular and macromolecular aging processes through the direct absorption of reactive oxygen species (ROS) and mitigating their damage. Its anti-inflammatory activity also arrests the low-level chronic inflammatory loads that accompany aging. Furthermore, vitamin K inhibits the activity of the inflammatory transcription factor NF-kB. The human body stores small amounts of vitamin K and its stores are depleted quickly in the absence of dietary supplements. There are studies showing that a short-term decrease in dietary vitamin K intake is not compensated by menaquinones synthesized by intestinal bacteria. In reality, unbalanced diet, Crohn’s disease, cirrhosis of the liver, chronic renal failure and antibiotic therapies could cause a vitamin K deficiency.

However, interestingly, the human body has a vitamin K recycling system that allows small amounts of vitamin K to be used in γ-carboxylation of VKDPs. They are involved in various pathophysiological pathways: for example, prothrombin is a VKDP of the coagulation system and extrahepatic Gla proteins, such as matrix Gla protein (MGP) play essential roles in bone and vascular health. Furthermore, growing data link the carboxylation of VKDPs to renal health and the onset of chronic renal disease (CRF), which represents a significant health burden both as dialysis and as pre-dialysis stages involving significant pharmacological therapies. Here too, the role of the microbiota in CKD is demonstrated, especially in dialysis and in the effects of metabolic toxins produced in case of dysbiosis.

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Conclusions

It was a surprise for scholars to discover that in fact even with a diet made up of foods with little vitamin K, there is always the possibility of compensating with other forms of vitamin K present in processed or preserved foods. Vitamin K produced by intestinal bacteria has always been judged as having little bioavailability, but the fact that both the microbiota and the body need it indicates that it certainly has its biological roles. This is why once again one of the central dogmas of traditional Japanese medicine anticipated the times of modern medicine: “Man’s health passes through the intestines”. The role of the microbiota in rheumatic, neurodegenerative diseases, diabetes and cardiovascular diseases has been demonstrated; and these alone represent 70% of the entire global health burden, excluding cancer. Given that we are talking about the most common medical conditions on the planet, it seems that we need to review our eating habits towards healthier choices.

  • By Dr. Gianfrancesco Cormaci, PhD; specialist in Clinical Biochemistry.

Scientific publications

Dai L, Mafra D et al. Nutrients 2023 Jun; 15(12):2727.

Li XY, Meng L et al. Food Res Int. 2023; 169:112749.

Chatterjee K et al. Physiol Behav. 2023; 269:114252.

Kemp JA et al. Curr Nutr Rep. 2022; 11(4):765-779.

Dai L et al. PLoS One. 2021 Feb; 16(2):e0247623.

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