Vitamin K2 — A New Hope for Osteoarthritis Relief

• GRP levels are significantly higher in osteoarthritis — The researchers selected 26 patients diagnosed with osteoarthritis who were undergoing knee replacement surgery and 31 individuals without osteoarthritis undergoing knee-related procedures for non-cartilage-related issues.

Their analysis revealed that GRP levels were significantly higher in the osteoarthritic group, with a mean of 419.61 ng/mL, compared to 382.18 ng/mL in the non-osteoarthritic group.

• MGP levels are also elevated in osteoarthritic joints — The study also found that MGP levels were elevated in osteoarthritic patients, with averages of 67.76 ng/mL versus 53.49 ng/mL in the controls. Calcium ion levels were also notably higher in those with osteoarthritis, indicating a link between calcium metabolism and joint degeneration.

• Age influences MGP but not GRP — Interestingly, the study identified a positive correlation between MGP levels and age, reducing its specificity as an osteoarthritis biomarker. In contrast, GRP levels showed no significant age-related variation, making GRP a more reliable indicator of this condition.

• GRP and MGP protect against calcium buildup — The elevated GRP and MGP are believed to play a protective role against unwanted calcium deposits in the joints, which lead to further cartilage damage.

• Vitamin K is essential for GRP and MGP function — Vitamins K1 and K2 are essential for these proteins to function properly (although vitamin K2 is more important for these proteins in tissues outside the liver), as it helps them bind calcium effectively. Without adequate vitamin K, the ability of GRP and MGP to prevent calcium buildup is compromised, exacerbating osteoarthritis symptoms.

• Vitamin K1 is lower in OA patients — Individuals with OA had lower serum K1 levels than healthy controls.

• Low plasma K1 is linked to mobility limitations — Plasma K1 levels below 0.5 nmol/L were associated with more severe mobility limitations, while a threshold of 1 nmol/L was identified for OA prevention.

• K1 supplementation slows joint deterioration — A clinical trial using 500 micrograms of K1 per day for three years showed a 47% reduction in joint space narrowing in K1-deficient patients.

• Higher dietary K1 intake reduces OA severity — Studies found a correlation between higher K1 intake and decreased OA severity.

• Vitamin K2 is unevenly distributed in OA joints — In OA patients, higher K2 levels were found in the outer part of the knee joint compared to the inner part. However, only one included study specifically examined K2 distribution in knee joints.

• Lower vitamin K1 levels are linked to more severe osteoarthritis — A study⁵ found that OA patients had reduced plasma phylloquinone levels compared to healthy controls. “Increased plasma phylloquinone level was linked to increased medial cartilage thickness,” the authors reported. “Subjects with vitamin K deficiency was found to have higher scores of Western Ontario McMaster Scale (WOMAC), which reflects an increased severity of the disease.”

• Vitamin K1 regulates calcification in joint cartilage — Vitamin K1 acts as a cofactor for γ-glutamyl carboxylase, an enzyme that activates γ-carboxyglutamate (Gla)-containing proteins, which regulates calcification. By activating these proteins, vitamin K1 mitigates the inappropriate buildup of calcium in joint cartilage, which contributes to cartilage degradation and joint pain, both hallmarks of osteoarthritis.

• Vitamin K1 supports MGP function to prevent cartilage calcification — By activating MGP, which is essential in inhibiting bone morphogenetic protein-mediated cartilage calcification. By activating these proteins, vitamin K1 maintains the structural integrity of the cartilage, inhibiting the calcification process that leads to osteoarthritis.

“Gla-rich proteins also inhibit inflammatory cascade in monocytic cell lines, but this function might be independent of vitamin K-carboxylation,” the authors added.⁶

• Higher vitamin K1 intake correlates with healthier joints — The researchers also found a notable correlation between higher vitamin K1 intake and healthier joints, with individuals showing fewer signs of joint degeneration, such as reduced bone spur formation and preserved joint space width. These structural improvements are important markers of how vitamin K influences joint health.

• Vitamin K1 deficiency leads to increased joint damage — Additionally, the findings revealed that insufficient vitamin K1 levels, as indicated by higher plasma levels of inactive MGP, were linked to more severe osteoarthritis symptoms like meniscus damage, osteophytes and bone marrow lesions. This indicates that inadequate vitamin K1 prevents the proper activation of MGP, allowing calcification and inflammation to progress unchecked.

• Even subclinical vitamin K deficiency contributes to osteoarthritis — The research concluded that even subclinical vitamin K deficiency was associated with the development of radiographic knee osteoarthritis and cartilage lesions, underscoring the nutrient’s essential role in avoiding cartilage damage. Maintaining adequate vitamin K levels, therefore, preserves cartilage integrity and helps delay or prevent the onset of osteoarthritis.⁷

• Vitamin K2 strengthens bones and cartilage and reduces joint pain — The study used both animal models and laboratory experiments. In animal-induced osteoarthritis, vitamin K2 was administered to observe its effects on joint health.

In parallel, cartilage cells were treated with vitamin K2 in a controlled lab environment to determine its direct impact on these cells. The findings revealed that vitamin K2 not only increased bone mass and cartilage thickness but also significantly reduced joint pain and structural damage.⁹

• Vitamin K2 prevents cartilage cell death — The results showed that vitamin K2 increases the production of GPX4, a protein that protects cells from ferroptosis, a type of programmed cell death that contributes to cartilage degradation in osteoarthritis. By boosting GPX4 levels, vitamin K2 keeps cartilage cells alive and functioning properly.

• Vitamin K2 blocks inflammation-driven cartilage damage — Vitamins K2 protects the cartilage from excessive breakdown by interfering with the MAPK/NFκB signaling pathway, which is responsible for promoting inflammation and further cartilage damage in osteoarthritis.¹⁰

• Vitamin K2’s effects are dose-dependent — The research showed that vitamin K2’s effects are dose-dependent. Higher doses of vitamin K2 led to greater increases in GPX4 expression and more significant reductions in markers of cartilage degradation.¹¹

• Vitamin K2 reduces oxidative stress and cellular damage — The research showed that vitamin K2 treatment improved cartilage cell viability, keeping more cells healthy and active, as well as reduced the levels of reactive oxygen species (ROS), which are harmful molecules that cause oxidative stress and damage to cells.

Moreover, vitamin K2 lowered the levels of intracellular malondialdehyde (MDA), a marker of lipid peroxidation, a process that damages cell membranes.¹²

• Choose eggs from properly fed chickens — Most commercial egg sources — even free-range organic — have high PUFA levels as they are fed grains like soy and corn. Ideally chickens should be fed rice, barley and split peas.

• Eggs from low-PUFA-fed chickens are superior — I personally eat six egg yolks a day from chickens who are fed this and have 80% less linoleic acid than regular chickens.

• How egg yolks compare as a leading MK-4 source — Below is a comprehensive overview of egg yolks as a top source of MK-4, along with additional dietary sources and considerations.

1. Eat more leafy greens — Vitamin K1 (phylloquinone) is found in all photosynthetic plants, with green leafy vegetables being the primary dietary source.

2. Add vitamin K2-rich foods into your diet — Prioritize foods naturally rich in vitamin K2, especially the MK-7 form, which is more bioavailable and remains active in the body longer. Fermented foods like natto are the most potent source, delivering approximately 11 micrograms (mcg) of K2 MK-7 per gram of serving.

Other good options include sauerkraut made with K2-producing bacteria and certain cheeses like Gouda, brie and Edam. Homemade fermented vegetables prepared with starter cultures designed to enhance K2 production provide up to 500 mcg of K2 per 2-ounce serving. Additionally, grass fed beef, butter and eggs are far superior to grain-fed options, offering significantly higher levels of this essential nutrient.

3. Consider supplementing with vitamin K2 MK-7 — Take 180 to 200 mcg of vitamin K2 MK-7 daily to activate proteins that prevent inappropriate calcium deposits in your joints. This form is more effective for targeting joint tissues and preserving cartilage integrity because it has better absorption and a longer half-life. For optimal absorption, consume it with a meal containing healthy fats.

4. Combine vitamin K2 with vitamin D3 and magnesium threonate — Enhance calcium metabolism by pairing vitamin K2 with vitamin D3 and magnesium threonate daily. This combination works synergistically — vitamin K2 directs calcium to bones instead of soft tissues, while vitamin D3 aids in its absorption.

To determine your ideal dosage for magnesium, take magnesium citrate first, gradually increasing your dose until you experience loose stools, then reduce it slightly — that’s your ideal dose. Afterward, transition to magnesium threonate, which doesn’t cause loose stools like magnesium citrate.

5. Replace vegetable oils with healthy fats — Remove vegetable oils from your diet, as they worsen inflammation and contribute to joint damage. Instead, choose nutrient-dense, anti-inflammatory alternatives such as tallow, ghee or grass fed butter.

Focus on consuming whole, unprocessed foods to further reduce inflammatory triggers and support your body’s natural repair processes. This change not only protects your joints but also enhances the effectiveness of vitamin K2 in maintaining cartilage integrity and promoting overall joint health.