Vitamin D deficiency is widespread globally, particularly in southern Europe including Portugal, despite abundant sunlight. Concurrently, growing evidence supports the combined use of vitamins D and K to improve calcium metabolism, skeletal integrity, and vascular health. General practitioners often prescribe vitamin D, but may overlook the co-factors needed to optimize its effect.To synthesize current evidence on the clinical benefits of combining vitamins D and K, and to assess prevalence and regional patterns of vitamin D deficiency with implications for preventive care in European general practice.We reviewed peer-reviewed meta-analyses, observational studies, and clinical trials published since 2020, using databases such as PubMed and Scopus. We included studies on adult populations with emphasis on elderly and health-conscious younger adults. Topics covered include biochemical synergy, bone and cardiovascular outcomes, and regional deficiency trends.Vitamin D and K co-regulate calcium deposition: D enhances absorption while K (particularly K2) activates proteins like osteocalcin and matrix Gla protein. Combined supplementation improves bone mineral density more than D alone and may reduce vascular calcification. Vitamin D deficiency affects 47–65% of adults in Europe; rates exceed 60% in Portugal, especially in winter and among the elderly. Northern European countries often report higher D levels due to fortification. Evidence suggests young adults also show substantial deficiency due to indoor lifestyles. While D is routinely supplemented, K is rarely co-prescribed despite its mechanistic importance.The combined use of D and K addresses the "calcium paradox"—ensuring calcium reaches bones without damaging arteries. This synergy is particularly relevant in populations at risk for osteoporosis or cardiovascular disease. For general practice, this highlights the need for updated supplementation practices, especially in regions with high deficiency rates and aging populations.General practitioners should consider co-supplementing vitamin K2 with D3 in high-risk patients, particularly in southern Europe. Targeted patient education and seasonal dosing strategies may improve long-term musculoskeletal and vascular outcomes.