Human clinical trials have produced mixed results, and the effects may vary according to the form of vitamin K used, the participants' initial metabolic health, the duration of supplementation, and the outcome measured.

One systematic review and meta-analysis, published in the Journal of Nutritional Science on January 11, 2024, examined the effects of vitamin K supplementation on cardiovascular risk factors. The review included 17 studies and reported a modest improvement in HOMA-IR, a commonly used estimate of insulin resistance. However, it did not find statistically significant improvements in most of the other cardiovascular risk factors assessed.

This is a meaningful but limited finding. It suggests that vitamin K supplementation deserves further investigation as a possible influence on insulin sensitivity, but it does not demonstrate that vitamin K2 prevents diabetes or that it should be used to treat prediabetes.

HOMA-IR is calculated using fasting glucose and fasting insulin measurements. It is useful in research, particularly when comparing groups, but it is not a direct measurement of every aspect of insulin action. It also does not replace established diagnostic tests for diabetes or prediabetes.

A modest change in HOMA-IR may indicate a physiological effect, but researchers still need to determine whether the effect persists, whether it improves longer-term glucose regulation, and whether it reduces the incidence of diabetes or cardiovascular complications.

It is also important to avoid assuming that an improvement in insulin resistance explains all potential cardiovascular effects of vitamin K2. Vascular calcification, insulin resistance, blood pressure, lipid metabolism, and atherosclerosis are related but distinct processes. A supplement might influence one outcome without having a meaningful effect on the others.

The evidence therefore supports continued research into vitamin K and metabolic health, rather than a definitive claim that vitamin K2 is an established intervention for managing prediabetes.

Source: Zhao et al. (2024), The effect of vitamin K supplementation on cardiovascular risk factors: a systematic review and meta-analysis.

https://doi.org/10.1017/jns.2023.106

8. Why Insulin Resistance Matters for Long-Term Cardiovascular Health

Understanding the significance of insulin resistance requires looking beyond blood glucose alone. Metabolic health affects several systems that contribute to cardiovascular risk, and these processes often influence one another over time.

When insulin resistance develops, the body may initially maintain relatively normal glucose levels by increasing insulin production. During this stage, a person may have no obvious symptoms. Nevertheless, the underlying metabolic changes can coexist with elevated triglycerides, reduced HDL cholesterol, increased blood pressure, or other indicators of cardiometabolic risk.

Not everyone with insulin resistance develops the same pattern of abnormalities. Genetics, age, physical activity, diet, sleep, medication use, and other individual factors influence how the condition develops.

As glucose regulation deteriorates, persistent elevations in blood glucose can contribute to damage affecting blood vessels, nerves, kidneys, and other organs. Diabetes is also associated with an increased risk of coronary artery disease, stroke, peripheral arterial disease, and heart failure.

Insulin resistance can coexist with chronic low-grade inflammation and changes in lipid metabolism. In some individuals, the liver produces more triglyceride-rich lipoproteins, while the overall balance of circulating lipids becomes less favorable. These changes may contribute to the development and progression of atherosclerosis.

However, insulin resistance is not the sole cause of cardiovascular disease. Smoking, hypertension, elevated LDL cholesterol, age, family history, chronic kidney disease, and other factors can influence cardiovascular risk independently or in combination with metabolic abnormalities.

This distinction matters because no single nutrient can be expected to address every pathway involved. Even if vitamin K2 eventually proves to have a reproducible effect on insulin sensitivity, it would not necessarily correct high LDL cholesterol, reverse established arterial plaque, or replace treatments for hypertension.

For people with prediabetes, established approaches include appropriate dietary changes, regular physical activity, adequate sleep, and medical monitoring. Depending on individual risk, healthcare professionals may also discuss medication or structured diabetes-prevention programs.

The aim is not simply to improve a laboratory value. It is to reduce the likelihood of developing diabetes and other complications while supporting long-term health.

This broader perspective also explains why lifestyle interventions remain important even when a supplement appears promising. Dietary patterns, physical activity, and sleep can affect several interconnected metabolic pathways simultaneously. Their benefits are not limited to a single biomarker.

Future studies of vitamin K2 should therefore evaluate whether any improvement in insulin resistance adds meaningful benefit to established preventive measures. Researchers should also investigate whether particular groups, such as individuals with low vitamin K status or specific metabolic conditions, respond differently from the general population.

Until these questions are answered, vitamin K2 should be regarded as an investigational nutritional factor in this context rather than a proven method of preventing diabetes or cardiovascular disease.

9. What Does a Meta-Analysis Actually Tell Us?

The term meta-analysis can sound conclusive, but it is important to understand what such a study can and cannot establish.

A meta-analysis combines results from multiple studies using statistical methods. When the included studies are sufficiently comparable, pooling their results can improve statistical precision and provide a broader assessment of the available evidence than any individual trial.

However, the quality of a meta-analysis depends heavily on the quality and comparability of the studies it includes. Combining several small studies does not automatically eliminate the limitations of those studies.

For example, one trial may examine vitamin K1 while another evaluates vitamin K2. A third may investigate a combination of vitamin K2 and vitamin D. The studies may use different doses, include participants with different health conditions, and measure different outcomes over different periods.

If these differences are substantial, the pooled estimate may not represent the expected effect of a particular intervention in a clearly defined population.

Researchers use statistical methods to assess heterogeneity, which refers to differences among study results beyond what might be expected from random variation. However, a statistical measure of heterogeneity does not explain every reason why studies differ, and low measured heterogeneity does not guarantee that the studies are clinically identical.

Another issue is publication bias. Studies reporting statistically significant findings may be more likely to be published than studies reporting no effect. If the available evidence is disproportionately composed of positive findings, a meta-analysis may overestimate the apparent benefit.

The number of included trials, their sample sizes, their methodological quality, and the precision of their estimates all influence the strength of the conclusions.

Researchers must also distinguish statistical significance from clinical significance. A result can be statistically significant but have a small effect that makes little difference to patients. Conversely, a potentially important effect may fail to reach statistical significance when a study is too small to estimate it precisely.

Confidence intervals help illustrate uncertainty. A narrow interval indicates a more precise estimate, while a wide interval suggests that the true effect could be substantially different from the central estimate. When a confidence interval includes no effect, the findings may be compatible with both a possible benefit and no meaningful difference.

The 2023 meta-analysis of vitamin K supplementation and vascular calcification reported a statistically significant pooled result for coronary artery calcification, but the estimated effect was modest and the authors called for additional high-quality trials. This is an appropriate basis for continued research, not proof that vitamin K2 prevents cardiovascular events.