A Look at the Protective Power of Vitamins D3 and K2
Ah, that summer sun—how we all look forward to it, at the beach, poolside, park, patio, or just walking down the street on a midsummer day. Our mood lifts. Our bodies feel stronger. In essence, we feel more vital. But alas, autumn and winter are not far behind, and bring with them shorter days, longer nights, and for many, a slump in mood that seems abetted by darkness, as well as seasonal colds and flus as we shiver through winter’s wind and snow or rain. Why can’t it be eternal summer? Or if it can’t, are there ways we can mimic summer’s blessings by supporting our body nutritionally?Supplemental vitamin D is one such tool that helps us to combat winter’s challenges. Most of life on earth is dependent on the sun for energy, warmth and often, vitamin D.1 For humans, vitamin D3 (cholecalciferol) is literally light transformed. During exposure to sunlight, a molecule in our skin called 7-dehydrocholesterol absorbs ultraviolet B radiation, which is the initial reaction in the process of several steps which are necessary for conversion to the active form of vitamin D3. Vitamin D3 is then metabolized in the liver into 25-hydroxyvitamin D (the form we measure) and in the kidneys to 1,25-dihydroxyvitamin D (the biologically active form).
Receptors for vitamin D are widely expressed throughout the body, being found in over 36 different cell types.2 In 2012, a remarkable feat of sequencing revealed that the human genome itself literally has thousands of binding sites for vitamin D, reaffirming how fundamental this vitamin is for the body.3 And yet, there is widespread vitamin D deficiency—as many as a billion people worldwide are deficient in vitamin D, according to a 2017 review.4 Vitamin D deficiency has been linked to numerous health issues: autoimmune disease, allergies, certain cancers, depression, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, type 2 diabetes, and cardiovascular disease, to name a few.5,6,7,8,9,10,11,12,13 Vitamin D3 is also the precursor to a class of D3-related hormones that have numerous functions in the body beyond balancing levels of calcium.
Vitamin D synthesis is influenced by season, time of day, latitude, altitude, as well as less well known factors of air pollution, skin pigmentation, aging, and whether or not you use sunscreen.14 One of the most dramatic factors is latitude, and in the shorter days of winter, the skin makes very little vitamin D at above 37 degrees north or below 37 degrees south of the equator.15 As the 37th parallel defines the southern borders of Utah, Colorado, and Kansas, and the northern borders of Arizona, New Mexico, and Oklahoma, this represents a large population of the US. Anyone living to the north of this line, including major cities such as San Francisco, Chicago, New York, St. Louis, Denver, Boston, and Seattle, are at an increased risk of winter vitamin D deficiency. Even people living in regions with abundant sunlight year-round often do not get enough sun exposure to ensure vitamin D adequacy, as winter simply adds to the burden of long hours in offices, commutes by train, subway or car, and evenings spent indoors.
Vitamin D supplementation is not only important for reversing or preventing deficiency, but also for healthy immune system function and mood.16,17 Adequate levels of vitamin D are necessary for the innate immune system, our body’s first defenders, to function normally, preventing infection by bacterial, fungal, and viral invaders.18 Lower vitamin D levels are associated with larger tonsil size and recurrent tonsillopharyngitis in children,19 as well as increased incidence of upper respiratory infection (URTI) and community acquired pneumonia in adults.20,21 Vitamin D supplementation also may help prevent URTI in children with asthma.22Vitamin D deficiency has been found in many studies to be associated with depression, which a recent systematic review and meta-analysis of observational studies and randomized controlled trials also reaffirmed.23 Supplementation of vitamin D was associated with an improvement in vitamin D levels as well as depression scale scores in patients with seasonal affective disorder, while those in the light therapy group only had improvements in their vitamin D levels.24 Although larger meta-analysis have failed to show an impact of vitamin D supplementation on mood in a broad population, improvements have been seen in smaller studies with an overweight or obese population,25 patients with major depressive disorder,26 and women with seasonal depressive symptoms.27
In addition to its importance for mood and immune function, vitamin D is important for maintaining healthy bones. Without it, the body can't absorb the calcium it ingests, and may borrow calcium from bones, increasing the risk of osteoporosis and fractures.28 It is important to note, however, that vitamin D should not be supplemented alone. Scientific studies, especially focusing on bone health and vascular calcification, find that supplementing with vitamin K at the same time is important.29,30,31 Vitamin K is important for arterial health and assists vitamin D in accomplishing many of its activities in the body.32 Vitamin K helps direct calcium deposition to the bone matrix, by activating osteocalcin. Vitamin K deficiency may be associated with soft tissue calcification and lower bone mineral density.33Certain forms of vitamin K are more active in the body than others. Menaquinone-7, or MK-7, is a highly bioactive form of vitamin K2.34 MK-7 also has been shown to have a longer half-life than vitamin K1, resulting in more stable serum levels. Similarly, for vitamin D, vitamin D3 has been shown to be up to 3 times more effective than vitamin D2 (calciferol) at raising the body’s serum 25-hydroxyvitamin D levels.35 Absorption of both vitamin D and K also can be dramatically improved when they are provided in a nanoemulsified format.
1 Holick M. Phylogenetic and evolutionary aspects of vitamin D from phytoplankton to humans. Verebrate Endocrinology: Fundamentals and Biomedical Implications Academic Press, Inc (Harcourt Brace Jovanovich) Orlando, FL 1989;3:7-43.
2 Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr. 2008 Aug;88(2):491S-499S. View Full Paper
3 Carlberg C, Seuter S, Heikkinen S. The first genome-wide view of vitamin D receptor locations and their mechanistic implications. Anticancer Res. 2012 Jan;32(1):271-82. View Full Paper
4 Kim M. Pfotenhauer, Jay H. Shubrook. Vitamin D Deficiency, Its Role in Health and Disease, and Current Supplementation Recommendations. J Am Osteopath Assoc. 2017 May 1;117(5):301-305. View Abstract
5 Grant WB. The prevalence of multiple sclerosis in 3 US communities: the role of vitamin D. Prev Chronic Dis. 2010;7:A89-A90. View Full Paper
6 Antico A, Tampoia M, Tozzoli R, et al. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. 2012;12:127–36 View Abstract
7 Mohr SB, Garland CF, Gorham ED, et al. The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. Diabetologia. 2008;51:1391–8. doi: 10.1007/s00125-008-1061-5. View Abstract
8 Schultz M, Butt AG. Is the north to south gradient in inflammatory bowel disease a global phenomenon? Expert Rev Gastroenterol Hepatol. 2012;6:445–7. View Abstract
9 ieira VM, Hart JE, Webster TF, Weinberg J, Puett R, Laden F, et al. Association between residences in U.S. northern latitudes and rheumatoid arthritis: A spatial analysis of the Nurses’ Health Study. Environ Health Perspect. 2010;118:957–61. View Abstract
10 Bouillon R, Carmeliet G, Verlinden L, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–76. doi: 10.1210/er.2008-0004.View Abstract
11 Iho S, Takahashi T, Kura F, et al. The effect of 1,25-dihydroxyvitamin D3 on in vitro immunoglobulin production in human B cells. J Immunol. 1986;136:4427–31. View Abstract
12 Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med (Berl) 2010;88:441–50. View Abstract
13 Gowda U, Mutowo MP, Smith BJ, et al. Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials. Nutrition. 2015 Mar;31(3):421-9 View Abstract
14 Wacker M, Holick M. Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol. 2013 Jan 1;5(1):51-108. View Full Paper
16 Peterson AL, Murchison C, Zabetian C et al. Memory, mood, and vitamin D in persons with Parkinson's disease. J Parkinsons Dis. 2013;3(4):547-55 View Full Text
17 Frandsen TB, Pareek M, Hansen JP et al. Vitamin D supplementation for treatment of seasonal affective symptoms in healthcare professionals: a double-blind randomised placebo-controlled trial
18 White JH. Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect Immun. 2008 Sep;76(9):3837-43. View Full Paper
19 Yildiz I, Unuvar E, Zeybek U, et al. The role of vitamin D in children with recurrent tonsillopharyngitis. Ital J Pediatr. 2012 Jun 8;38:25. View Full Paper
20 Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009 Feb 23;169(4):384-90. View Full Paper
21 Quraishi SA, Bittner EA, Christopher KB, Camargo CA Jr. Vitamin D status and community-acquired pneumonia: results from the third National Health and Nutrition Examination Survey. PLoS One. 2013 Nov 15;8(11):e81120. View Full Paper
22 Xiao L, et al. Vitamin D supplementation for the prevention of childhood acute respiratory infections: a systematic review of randomised controlled trials. Br J Nutr. 2015 Aug 27:1-9. View Abstract
23 Anglin RE, Samaan Z, Walter SD, McDonald SD. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013 Feb;202:100-7.View Full Paper
24 Gloth FM 3rd, Alam W, Hollis B. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. J Nutr Health Aging. 1999;3(1):5-7. View Abstract
25 Jorde R, Sneve M, Figenschau Y, et al. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med. 2008 Dec;264(6):599-609. View Abstract
26 Sepehrmanesh Z, Kolahdooz F, Abedi F, et al. Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial. J Nutr. 2016 Feb;146(2):243-8. View Abstract
27 Shipowick CD, Moore CB, Corbett C, Bindler R. Vitamin D and depressive symptoms in women during the winter: a pilot study. Appl Nurs Res. 2009 Aug;22(3):221-5. View Abstract
28Raef H, Al-Bugami M, Balharith S. Updated Recommendations for the Diagnosis and Management of Osteoporosis: A Local Perspective Ann Saudi Med. 2011 Mar-Apr; 31(2): 111–128. View Full Paper
29 Iwamoto J, Takeda T, Ichimura S. Treatment with vitamin D3 and/or vitamin K2 for postmenopausal osteoporosis. Keio J Med. 2003 Sep;52(3):147-50. View Abstract
30 Iwamoto J, Takeda T, Ichimura S. Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. J Orthop Sci. 2000;5(6):546-51 View Full Paper
31 El Asmar MS, Naoum JJ, Arbid EJ. Vitamin k dependent proteins and the role of vitamin k2 in the modulation of vascular calcification: a review. Oman Med J. 2014 May;29(3):172-7. View Full Paper
32 Bügel S. Vitamin K and bone health in adult humans. Vitam Horm. 2008;78:393-416 View Abstract
33 Inaba N, et al. Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials. J Nutr Sci Vitaminol (Tokyo). 2015;61(6):471-80. View Abstract
34 Schurgers LJ, et al. itamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007;109:3279-83. View Full Paper
35 Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84(4):694-7. View Full Paper