“Most people are vitamin D and K deficient. This means weak bones, but also to the surprise of many people, can also mean calcium deposits in arteries which can lead to heart attacks and strokes. We included a bioavailable combination of these two fat soluble vitamins that have been shown to work together. We also included K1’s counterpart Vitamin K2 which can usually only be acquired through certain animal products or fermented foods. K2 is indispensable for its ability to direct calcium deposits where they’re supposed to go, namely, in the bone. ”
D.K.1.2 is a convenient, highly concentrated liquid vitamin D + K formula. It provides clinically useful amounts of both fat-soluble vitamins. Sweetened with glycerine, it has a pleasant taste and mixes easily in liquids. Both vitamins D and K are essential for bone and arterial health, and for maintaining normal immune function. Vitamins K1 and K2 support the deposition of calcium into the bone instead of soft tissue, such as the arterial walls and kidneys.
Highlights:
Delivers 50 mcg (2,000 IU) of vitamin D3, 200 mcg of vitamin K1, and 40 mcg of vitamin K2 (as MK-4) per dropper
Pleasant taste and convenient liquid delivery
Suitable for children, elderly, and individuals who have trouble swallowing pills
Mixes easily in liquid or can be dropped directly on the tongue
Gluten-free, soy-free, dairy-free, and non-GMO
Vitamin D
Vitamin D is a fat-soluble vitamin that is well-known to support bone health through the regulation of calcium-phosphorus homeostasis and its role in bone turnover. Low vitamin D levels have been shown to decrease bone density and increase fracture risk¹. Vitamin D receptors (VDRs) are found throughout the body and have been shown to influence the expression of thousands of genes²,³. Vitamin D is essential for the immune system as it modulates the response of the innate and adaptive immune systems by VDRs. VDR is the critical transcription factor in differentiating lymphocytes within the bone marrow into monocytes and granulocytes⁴. Vitamin D can regulate Th1 and Th2 lymphocyte balance and downregulate the expression of inflammatory cytokines overall. Vitamin 1,25(OH)D3 has been shown to heavily influence and shift the intracellular metabolism of dendritic cells and macrophages, metabolically reprogramming their role in inflammation and autoimmunity by altering the phenotypic expression of the cells⁵. In fact, research showed that priming of naive CD4+ T cells with vitamin D-treated tolerogenic dendritic cells induced the T-regulatory cells that support a healthy inflammatory response and impact autoimmune processes⁶. Low concentrations of vitamin D are associated with disrupted immune function in gastrointestinal diseases⁷,⁸. VDR regulates the innate immune response in the gut, plays a critical role in regulating endothelial tight junction protein expression, and regulates the intestinal microbiota by controlling microflora composition⁷.
In addition to its well-known support of bone health and the immune system, vitamin D may also support cardiovascular health. A systematic review and meta-analysis of randomized controlled trials showed that vitamin D supplementation, which included D3 and D2, was not statistically significant in lowering mortality. Yet, in a subgroup analysis, all-cause mortality was significantly lower with D3 than in trials using D2⁹. Vitamin D also plays a role in the brain, influencing brain development in early life and brain function in adults, and vitamin D deficiency can be associated with depressed moods and impaired cognition¹⁰-¹⁴. Epidemiological findings indicate that almost 30% of the U.S. adult population is vitamin D deficient with another 40% who are insufficient¹⁵. Vitamin D deficiency has been shown to play a role in autoimmune diseases, heart disease, and certain types of cancer⁹,¹⁶,¹⁷. Evidence indicates that vitamin D3 is far more effective in raising and maintaining serum 25(OH)D concentration, and vitamin D2 should not be considered an equivalent¹⁸,¹⁹. These factors highlight the potential clinical utility and value of supplementation with vitamin D across a variety of clinical presentations.
Vitamin K Forms, Adequate Intake for Clotting Versus for Extra-hepatic Roles
Vitamin K is a fat-soluble vitamin like vitamin D, and complements the support of bone and cardiovascular health, along with many other aspects of physiology²⁰,²¹. For example, vitamin D increases calcium absorption, whereas vitamin K improves calcium deposition in the bones while inhibiting its accumulation in the arterial walls. This explains the results from studies that show the combined supplementation of vitamins D and K to be more effective than that of either vitamin alone²⁰,²¹. Vitamin K exists in two main forms: vitamin K1 (VK1), as phylloquinone, which is found in leafy green vegetables, and vitamins K2 (VK2s), also known as menaquinones, which are found in certain animal products, fermented foods, and are also produced by gut microbiota. VK2 occurs naturally with various lengths (n = 1 to 14) of their side chains, abbreviated here as VK2 (MK-n). VK2 (MK-4) represents 90% of the total vitamin K stored in the human body. Animal studies have shown that other forms of VK2s convert into VK2 (MK-4) in all tissues, except the liver²¹.
For adults 19 years and older, the adequate intake (AI) for VK1 was set at 120 mcg for men and 90 mcg for women, but this level is only sufficient to fully activate blood-clotting proteins²². No AI has been set for VK2s and no upper level of toxicity has been established by the Institute of Medicine for VK1 or VK2s²². However, extensive evidence has revealed a variety of extra-hepatic roles for VK1 and VK2, which may require much higher intake levels of these vitamins²¹. The most researched roles involve control of calcium transport between tissues. VK1 and VK2 are transported in part to the liver to support the production of coagulation factors and to extra-hepatic tissues where they have various roles. These include: (a) carboxylation of gamma-carboxyglutamate proteins (GLA) on osteocalcin (Oc), which is involved in calcium deposition in bone and teeth; (b) carboxylation of matrix gamma-carboxyglutamate proteins (MGPs), which is involved in preventing calcium deposition in the vascular wall, heart valves, lungs, and kidneys²¹,²³. Oc and MGPs should be maximally carboxylated for optimal activity, as assessed in many studies investigating the effects of VK1 or VK2s supplementation on improving bone density and arterial elasticity or reducing progression of calcium scores in coronary arteries²¹.
Ninety percent of the vitamin K that is stored in the body is represented by VK2 (MK-4), with the rest mostly being VK1. However, each extrahepatic tissue seems to store a preferential ratio of VK1/VK2 (MK-4), such as: 90% VK1 and 10% VK2 (MK-4) in the heart, 25% VK1 and 75% VK2 (MK-4) in the arteries, and 23% VK1 and 77% VK2 (MK-4) in the bone²¹. VK2 (as MK-4) is the preferred clinical source of VK2 in dietary supplementation due to its unique structure, metabolic pathways, predominance in the body, and effects on bone and arterial health. However, since VK2 (MK-4) cannot convert to VK1, it makes sense for it to be supplemented along with a foundational serving of 1 mg of VK1 due to its own unique tissue deposition patterns and its study results on lowering the percentage of ucOC and uc-dpMGP while supporting bone and arterial health.
Vitamin K Intakes and Markers of Whole-Body Vitamin K Status
The average intake of VK1 has been estimated in the U.S. at 92.2 mcg per day (30 mcg to 222 mcg per day)²⁴, and in Europe at 211.7 mcg per day (9.1 to 991 mcg per day)²⁵. Average VK2 intakes have been estimated in a modern European population at 29.1 mcg per day (0.9 mcg to 128 mcg per day)²⁵. No survey for VK2 intake is available for the U.S. population. This implies that a significant proportion of the general population in the U.S. does not meet clotting needs for vitamin K, and moreover, does not meet the whole body needs for VK1 and VK2. Study subjects who did not supplement with vitamin K were found to have elevated baseline values of the percentage of ucOc (range, 42% to 65.5%) in American, European, and Canadian studies²¹. Similarly, baseline values of dp-ucMGP were found to be elevated (range, 319 pmol/L to 789 pmol/L)²¹. The ucOc and dp-ucMGP are considered validated laboratory markers of whole-body vitamin K status as they reflect vitamin K sufficiency for extra-hepatic tissues. Plasma VK1 and/or VK2 are not relevant markers due to the many variables involved, such as triglyceride and cholesterol levels and the timing and duration of vitamin K ingestion²¹.
Sassi F, Tamone C, D’Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018;10(11):1656. doi:10.3390/nu10111656
Tuoresmäki P, Väisänen S, Neme A, Heikkinen S, Carlberg C. Patterns of genome-wide VDR locations. PLoS One. 2014;9(4):e96105. doi:10.1371/journal.pone.0096105
Zhang Y, Wu S, Sun J. Vitamin D, vitamin D receptor and tissue barriers. Tissue Barriers. 2013;1(1):e23118. doi:10.4161/tisb.23118
Carlberg C. Nutrigenomics of vitamin D. Nutrients. 2019;11(3):676. doi:10.3390/nu11030676
Vanherwegen AS, Gysemans C, Mathieu C. Vitamin D endocrinology on the cross‑road between immunity and metabolism. Mol Cell Endocrinol. 2017;453:52-67. doi:10.1016/j.mce.2017.04.018
Vanherwegen AS, Eelen G, Ferreira GB, et al. Vitamin D controls the capacity of human dendritic cells to induce functional regulatory T cells by regulation of glucose metabolism. J Steroid Biochem Mol Biol. 2019;187:134-145. doi:10.1016/j.jsbmb.2018.11.011
Giustina A, Adler RA, Binkley N, et al. Consensus statement from 2nd International Conference on Controversies in Vitamin D. Rev Endocr Metab Disord. 2020;21(1):89-116. doi:10.1007/s11154-019-09532-w
Gubatan J, Chou ND, Nielsen OH, Moss AC. Systematic review with meta-analysis: association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2019;50(11-12):1146-1158. doi:10.1111/apt.15506
Zhang Y, Fang F, Tang J, et al. Association between vitamin D supplementation and mortality: systematic review and meta-analysis [published correction appears in BMJ. 2020;366:370]. BMJ. 2019;366:l4673. doi:10.1136/bmj.l4673
Kesby JP, Eyles DW, Burne TH, McGrath JJ. The effects of vitamin D on brain development and adult brain function. Mol Cell Endocrinol. 2011;347(1-2):121-127. doi:10.1016/j.mce.2011.05.014
Eyles DW, Burne TH, McGrath JJ. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol. 2013;34(1):47-64. doi:10.1016/j.yfrne.2012.07.001
Groves NJ, McGrath JJ, Burne TH. Vitamin D as a neurosteroid affecting the developing and adult brain. Annu Rev Nutr. 2014;34:117-141. doi:10.1146/annurev-nutr-071813-105557
Annweiler C, Dursun E, Féron F, et al. ‘Vitamin D and cognition in older adults’: updated international recommendations. J Intern Med. 2015;277(1):45-57. doi:10.1111/joim.12279
Schlögl M, Holick MF. Vitamin D and neurocognitive function. Clin Interv Aging. 2014;9:559-568. doi:10.2147/CIA.S51785
Liu X, Baylin A, Levy PD. Vitamin D deficiency and insufficiency among US adults: prevalence, predictors and clinical implications. Br J Nutr. 2018;119(8):928-936. doi:10.1017/S0007114518000491
Yamamoto E, Jorgensen TN. Immunological effects of vitamin D and their relations to autoimmunity. J Autoimmun. 2019;100:7-16. doi:10.1016/j.jaut.2019.03.002
Trehan N, Afonso L, Levine DL, Levy PD. Vitamin D deficiency, supplementation, and cardiovascular health. Crit Pathw Cardiol. 2017;16(3):109-118. doi:10.1097/hpc.0000000000000122
Logan VF, Gray AR, Peddie MC, Harper MJ, Houghton LA. Long‑term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25‑hydroxyvitamin D status over the winter months. Br J Nutr. 2013;109(6):1082-1088. doi:10.1017/S0007114512002851
Martineau AR, Thummel KE, Wang Z, et al. Differential effects on oral boluses of vitamin D vs vitamin D3 on vitamin D metabolism: a randomized controlled trial. J Clin Endocrinol Metab. 2019;104(12):5831-5839. doi:10.1210/jc.2019-00207
van Ballegooijen AJ, Pilz S, Tomaschitz A, Grübler MR, Verheyen N. The synergistic interplay between vitamins D and K for bone and cardiovascular health: a narrative review. Int J Endocrinol. 2017;2017:7454376. doi:10.1155/2017/7454376
Pizzorno JE, Murray MT. Textbook of Natural Medicine, 5th ed. St. Louis, MO: Elsevier; 2020Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. National Academy Press; 2001. Available from: https://www.ncbi.nlm.nih.gov/books/NBK222310/?term=dietary%20reference%20intakes%202001
Janssen R, Visser MPJ, Dofferhoff ASM, Vermeer C, Janssens W, Walk J. Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019. Br J Nutr. 2021;126(2):191-198. doi:10.1017/S0007114520003979
National Health and Nutrition Examination Survey 2001-2002. National Health and Nutrition Examination Survey. National Center for Health Statistics. Centers for Disease Control and Prevention. Available from: https://wwwn.cdc.gov/nchs/nhanes/Search/DataPage.aspx?Component=Examination&CycleBeginYear=2001
Gast GC, de Roos NM, Sluijs I, et al. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009;19(7):504-510. doi:10.1016/j.numecd.2008.10.004
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