Relationship between circulating FGF19 & FGF21 and vitamin K
Research type
Research Study
Full title
Relationship between circulating Fibroblast Growth factors (FGF-21 & FGF-19) and vitamin K supplementation; potential impact on insulin sensitivity
IRAS ID
307822
Contact name
Geeta Hampson
Contact email
Sponsor organisation
Guy's and St Thomas' Foundation NHS Trust
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Research Question
Fibroblast Growth Factors (FGF) 19 and 21 behave like hormones. They are associated with insulin sensitivity and may be useful biomarkers of glucose and lipid metabolism. FGF21, derived from the liver, promotes weight loss, and insulin sensitivity. Clinical studies show a positive association between circulating FGF21 and obesity and type 2 diabetes mellitus (DM). In contrast, circulating FGF19, a gut hormone, is low in patients with type 2 DM and obesity.Vitamin K, a fat-soluble vitamin activates the function of vitamin K-dependent proteins (VKDPs). Vitamin K may have a positive effect on insulin sensitivity through the activation of VKDPs which includes osteocalcin (OC), a protein present in bone. However, the exact pathway remains unclear, and more research needs to be done.
We think that the factors mentioned above:FGF19 & FGF21 may be involved in vitamin K’s effect on the way the body responds to insulin. We aim to investigate the relationship between circulating FGF19 and FGF 21 with vitamin K status as well as markers of insulin resistance to understand this pathway better.
Lay Summary
We would like to thank the participants who agreed to take part in the initial clinical trial of vitamin K on bone metabolism. We are also indebted to the participants as they agreed that their samples be stored and used in further studies. We have thus been able to use the samples leftover from the initial clinical trial for the current study. The study was undertaken by a specialist trainee (Dr Eunji Kim) as part of completion of specialist training in Chemical Pathology. Dr Eunji Kim successfully submitted her dissertation based on the study findings to the Royal College of Pathologists and was awarded the FRCPath diploma in 2024.
The research was carried out at St Thomas' Hospital in the department of Chemical Pathology. We wanted to investigate whether vitamin K which is known for its effects on blood clotting, could also influence the regulation of glucose and insulin. This would be an important finding as insulin is crucial for preventing high blood glucose. The
the exact way vitamin K affects insulin and glucose metabolism is not well known. There are 2 main types of vitamin K, vitamin K1 (phylloquinone) and vitamin K2 (the menaquinones) and it is unclear which form of vitamin K may regulate insulin. We studied 2 circulating factors; Fibroblast growth factors (FGF-19 & FGF-21) which have been shown to regulate glucose and insulin sensitivity. Our hypothesis was that FGF-19 and 21 may be involved in the effects of vitamin K on insulin. Two assays were developed for the measurement of serum FGF-19 and FGF-21. The effects of VK supplementation on insulin secretion, FGF-19 and FGF-21 were evaluated in an 18-month randomised controlled trial (RCT) of vitamin K where 105 participants who were post-menopausal women. They were randomised to 3 groups; placebo or vitamin K1 (1 mg/day) or vitamin K2 (45mg/day) (35 in each arm) for 18 months. Blood samples obtained at baseline, 6 and 18 months were analysed for insulin, FGF19 and FGF21. The FGF19 and FGF21 assays were found to be sensitive, accurate, reproducible and specific for these 2 factors. There were no interferences with other circulating factors and the assay measured a wide range of concentrations found in the serum samples. The 2 factors; FGF19 and FGF21 were closely correlated. Analysis of insulin in each group at each time point showed an increase in insulin secretion from baseline at 6 and 18 months in the groups treated with Vitamin K1 and K2. This effect was more consistent in the vitamin K2 group.There was no change in insulin secretion over time in the placebo group. Although we did not find any changes in FGF19 in any group, FGF21 increased at 6 months in the group receiving vitamin K2.
In conclusion, vitamin K appears to increase insulin secretion. Vitamin K2 also increases FGF21 which may have extra effect on insulin sensitivity. This may have implications for treatment of metabolic syndrome or type 2 diabetes, although further studies in these populations are needed for confirmation.REC name
Wales REC 5
REC reference
22/WA/0105
Date of REC Opinion
4 Apr 2022
REC opinion
Favourable Opinion