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VITAMIN D

Vitamin-D
THE GIST

OVERVIEW

Vitamin D is a group of fat-soluble secosteroids that are of tremendous importance for human life.

SYNONYMS

OTHER COMMON NAMES

Vitamin D, Vitamin D3, cholecalciferol.

IN A NUTSHELL

TOP BENEFITS

Supports bone health

Supports cognitive function

Supports a healthy mood

Supports cardiovascular health

Supports general immune health

Supports upper respiratory health

DEFINITION

WHAT IS VITAMIN D?

Vitamin D is an essential fat-soluble vitamin. It is found in animal foods—fatty fish are a good source—where, because it is fat-soluble, it concentrates in fat. But a large amount of the body stores of vitamin D are not obtained from the diet; it is produced from skin exposure to sunlight. This is true for humans and animals. In addition to fatty fish, other animal foods such as dairy and eggs will have varying amounts of vitamin D depending on whether the food has been fortified with vitamin D (most milk has been) and whether the animal the product originated from had sufficient exposure to sunlight (or ate food that did). In addition to milk, some milk alternatives (such as beverages made from soy, almond, or oats), ready-to-eat breakfast cereals, orange juices, margarine and other food products can be fortified with vitamin D. Mushrooms can also be a good source of vitamin D, but again this will be dependent on their exposure to sunlight. Vitamin D is usually supplemented as either vitamin D2 (Ergocalciferol) or D3 (Cholecalciferol). Of the two, vitamin D3 is considered superior for supporting healthy vitamin D levels [1]. Vitamin D is essential for general health, and is especially important for supporting the health of bones, the brain and nervous system, the heart, and the immune system.

SOURCE

MARCO’S GROUNDS VITAMIN D SOURCING

Vitamin D3 is produced from wild crafted lichen, which is responsibly harvested from a sustainable source. Vitamin D3 is Non-GMO, gluten-free, and vegan.

DOSING

DOSING PRINCIPLES AND RATIONALE

Since much of the body stores of vitamin D are made from sunlight exposure, and the intensity of sunlight varies seasonally, especially in more northern locations, maintaining optimal vitamin D status throughout the year can be a challenge. A combination of a diet with insufficient vitamin D (estimated to occur in 95% of adults [2]) and inadequate sun exposure exacerbates this challenge. Because of these challenges, many adults do not have adequate vitamin D status. To ensure against inadequacy, in the United States and the European Union the recommended dietary allowance for adults is currently set at 600-800 IU/day, with the exact amount varying by age; however, a dose of 800 IU is considered 100% of the daily value (DV) for supplement labeling. Vitamin D follows hormetic principles (see Marco’s Grounds Dosing Philosophy). The key point is that vitamin D3 is not a more-is-better vitamin. In fact, for general immune support and upper respiratory health, as an example, evidence suggests that an average person would be better off taking amounts closer to the DV than amounts several times higher [3]. When determining the dose of vitamin D3 to include in a product, our goal is to ensure we’ve supplied enough to support healthy function, while being within the hormetic range. Taking vitamin D (and other fat-soluble compounds) with food that contains fat is recommended for better absorption.

VITAMIN D ROLE IN OUR FORMULATION

FOCUS
0%
MEMORY
0%
CLARITY
0%
MOOD
100%

VITAMIN D KEY MECHANISMS

Brain function

Supports memory [4, 5]

Supports working memory [6]

Protects from cognitive impairment [7–9]

Supports the expression of neurotrophic factors (NT-3, BDNF, GDNF, CNTF, and NGF) [10–12]

Supports neurogenesis [6, 10]

Supports neuronal structure [13–15] [7, 16]

Modulates brain antioxidant defenses and oxidative stress [7, 17–19]

Modulates neural cytokine signaling [7, 14, 20]

Supports neuroprotective functions [7, 13, 17, 18, 21, 22]

Mood

Supports positive affect [19, 23–25]

Supports a calm/relaxed mood [24–26]

Immunity

Supports general immune health [3 ,27, 28]

Supports innate immunity [29, 30]

Supports adaptive immunity [31–38]

Supports mucosal immunity [39–47]   

Supports immune tolerance [31, 33–38, 48–52]

Supports immune balance [31, 53]

Supports healthy dendritic cell function [29,30]

Supports healthy natural killer cell function [30]

Supports healthy microglia function [14, 54–59] 

Supports healthy T cell function [31–38] 

Supports healthy B cell function [31, 33, 34, 48–51]  

Gut microbiota

Supports a healthy gut microbiota [60–66]

Cardiometabolic health

Supports healthy cardiovascular function [67–70]

Supports healthy insulin levels [19,71,72]

Supports healthy glucose levels [19]

Healthy aging

Supports balance during aging (i.e., may help reduce risk of falls) [73, 74]

Supports healthy bone function during aging [74, 75]

Supports healthy muscle function during aging [74]

Supports healthspan extension (Caenorhabditis elegans) [76]

Supports mitochondrial function [77, 78]  

Supports Nrf2 function [79–86]

Synergies

Vitamin D is involved in intestinal absorption and homeostasis of minerals such as calcium and magnesium [87, 88]

Vitamin K is potentially synergistic with vitamin D [89]​

VITAMIN D DEEP DIVE

References

  1. Autier, P., Gandini, S., & Mullie, P. (2012). A systematic review: influence of vitamin D supplementation on serum 25-hydroxyvitamin D concentration. The Journal of Clinical Endocrinology & Metabolism, 97(8), 2606-2613.
  2. Reider, C. A., Chung, R. Y., Devarshi, P. P., Grant, R. W., & Hazels Mitmesser, S. (2020). Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005–2016 NHANES. Nutrients, 12(6), 1735.
  3. Martineau, A. R., Jolliffe, D. A., Greenberg, L., Aloia, J. F., Bergman, P., Dubnov-Raz, G., … & Grant, C. C. (2019). Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technology Assessment, 23(2), 1-44.
  4. Pettersen, J. A. (2017). Does high dose vitamin D supplementation enhance cognition?: A randomized trial in healthy adults. Experimental Gerontology, 90, 90-97.
  5. Darwish, H., Haddad, R., Osman, S., Ghassan, S., Yamout, B., Tamim, H., & Khoury, S. (2017). Effect of vitamin D replacement on cognition in multiple sclerosis patients. Scientific reports, 7, 45926.
  6. Morello, M., Landel, V., Lacassagne, E., Baranger, K., Annweiler, C., Féron, F., & Millet, P. (2018). Vitamin D improves neurogenesis and cognition in a mouse model of Alzheimer’s disease. Molecular neurobiology, 55(8), 6463-6479.
  7. Yamini, P., Ray, R. S., & Chopra, K. (2018). Vitamin D 3 attenuates cognitive deficits and neuroinflammatory responses in ICV-STZ induced sporadic Alzheimer’s disease. Inflammopharmacology, 26(1), 39-55.
  8. Alrefaie, Z. (2015). Vitamin D3 improves decline in cognitive function and cholinergic transmission in prefrontal cortex of streptozotocin-induced diabetic rats. Behavioural Brain Research, 287, 156-162.
  9. Durk, M. R., Han, K., Chow, E. C., Ahrens, R., Henderson, J. T., Fraser, P. E., & Pang, K. S. (2014). 1α, 25-Dihydroxyvitamin D3 reduces cerebral amyloid-β accumulation and improves cognition in mouse models of Alzheimer’s disease. Journal of Neuroscience, 34(21), 7091-7101.
  10. Shirazi, H. A., Rasouli, J., Ciric, B., Rostami, A., & Zhang, G. X. (2015). 1, 25-Dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation. Experimental and molecular pathology, 98(2), 240-245.
  11. Brown, J., Bianco, J. I., McGrath, J. J., & Eyles, D. W. (2003). 1, 25-dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neuroscience letters, 343(2), 139-143.
  12. Naveilhan, P., Neveu, I., Wion, D., & Brachet, P. (1996). 1, 25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor. Neuroreport, 7(13), 2171-2175.
  13. Goudarzvand, M., Javan, M., Mirnajafi-Zadeh, J., Mozafari, S., & Tiraihi, T. (2010). Vitamins E and D3 attenuate demyelination and potentiate remyelination processes of hippocampal formation of rats following local injection of ethidium bromide. Cellular and molecular neurobiology, 30(2), 289-299.
  14. Wergeland, S., Torkildsen, Ø., Myhr, K. M., Aksnes, L., Mørk, S. J., & Bø, L. (2011). Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. PloS one, 6(10), e26262.
  15. Chabas, J. F., Stephan, D., Marqueste, T., Garcia, S., Lavaut, M. N., Nguyen, C., … & Feron, F. (2013). Cholecalciferol (vitamin D 3) improves myelination and recovery after nerve injury. Plos one, 8(5), e65034.
  16. Landfield, P. W., & Cadwallader–Neal, L. (1998). Long-term treatment with calcitriol (1, 25 (OH) 2 vit D3) retards a biomarker of hippocampal aging in rats. Neurobiology of aging, 19(5), 469-477.
  17. Shinpo, K., Kikuchi, S., Sasaki, H., Moriwaka, F., & Tashiro, K. (2000). Effect of 1, 25‐dihydroxyvitamin D3 on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by L‐buthionine sulfoximine and 1‐methyl‐4‐phenylpyridine. Journal of Neuroscience Research, 62(3), 374-382.
  18. Jang, W., Park, H. H., Lee, K. Y., Lee, Y. J., Kim, H. T., & Koh, S. H. (2015). 1, 25-Dyhydroxyvitamin D 3 attenuates L-DOPA-induced neurotoxicity in neural stem cells. Molecular neurobiology, 51(2), 558-570.
  19. Sepehrmanesh, Z., Kolahdooz, F., Abedi, F., Mazroii, N., Assarian, A., Asemi, Z., & Esmaillzadeh, A. (2016). 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. The Journal of nutrition, 146(2), 243-248.
  20. Nashold, F. E., Miller, D. J., & Hayes, C. E. (2000). 1, 25-dihydroxyvitamin D3 treatment decreases macrophage accumulation in the CNS of mice with experimental autoimmune encephalomyelitis. Journal of neuroimmunology, 103(2), 171-179.
  21. Wang, J. Y., Wu, J. N., Cherng, T. L., Hoffer, B. J., Chen, H. H., Borlongan, C. V., & Wang, Y. (2001). Vitamin D3 attenuates 6-hydroxydopamine-induced neurotoxicity. Brain research, 904(1), 67-75.
  22. Brewer, L. D., Thibault, V., Chen, K. C., Langub, M. C., Landfield, P. W., & Porter, N. M. (2001). Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons. Journal of Neuroscience, 21(1), 98-108.
  23. Högberg, G., Gustafsson, S. A., Hällström, T., Gustafsson, T., Klawitter, B., & Petersson, M. (2012). Depressed adolescents in a case‐series were low in vitamin D and depression was ameliorated by vitamin D supplementation. Acta Paediatrica, 101(7), 779-783.
  24. Fazelian, S., Amani, R., Paknahad, Z., Kheiri, S., & Khajehali, L. (2019). Effect of Vitamin D supplement on mood status and inflammation in Vitamin D deficient Type 2 diabetic women with anxiety: A randomized clinical trial. International journal of preventive medicine, 10.
  25. Penckofer, S., Byrn, M., Adams, W., Emanuele, M. A., Mumby, P., Kouba, J., & Wallis, D. E. (2017). Vitamin D supplementation improves mood in women with type 2 diabetes. Journal of Diabetes Research, 2017.
  26. Eid, A., Khoja, S., AlGhamdi, S., Alsufiani, H., Alzeben, F., Alhejaili, N., … & Tarazi, F. I. (2019). Vitamin D supplementation ameliorates severity of generalized anxiety disorder (GAD). Metabolic Brain Disease, 34(6), 1781-1786.
  27. Martens, P. J., Gysemans, C., & Verstuyf, A. (2020). Vitamin D’s Effect on Immune Function. Nutrients, 12(5), 1248.
  28. Vanherwegen, A. S., Gysemans, C., & Mathieu, C. (2017). Regulation of immune function by vitamin D and its use in diseases of immunity. Endocrinology and Metabolism Clinics, 46(4), 1061-1094.
  29. Barragan, M., Good, M., & Kolls, J. K. (2015). Regulation of dendritic cell function by vitamin D. Nutrients, 7(9), 8127-8151.
  30. Al-Jaderi, Z., & Maghazachi, A. A. (2013). Effects of vitamin D3, calcipotriol and FTY720 on the expression of surface molecules and cytolytic activities of human natural killer cells and dendritic cells. Toxins, 5(11), 1932-1947.
  31. Terrier, B., Derian, N., Schoindre, Y., Chaara, W., Geri, G., Zahr, N., … & Piette, J. C. (2012). Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation. Arthritis research & therapy, 14(5), 1-10.
  32. Khoo, A. L., Koenen, H. J., Chai, L. Y., Sweep, F. C., Netea, M. G., van der Ven, A. J., & Joosten, I. (2012). Seasonal variation in vitamin D 3 levels is paralleled by changes in the peripheral blood human T cell compartment. PloS one, 7(1), e29250.
  33. Bock, G., Prietl, B., Mader, J. K., Höller, E., Wolf, M., Pilz, S., … & Pieber, T. R. (2011). The effect of vitamin D supplementation on peripheral regulatory T cells and β cell function in healthy humans: a randomized controlled trial. Diabetes/metabolism research and reviews, 27(8), 942-945.
  34. Prietl, B., Treiber, G., Mader, J. K., Hoeller, E., Wolf, M., Pilz, S., … & Pieber, T. R. (2014). High-dose cholecalciferol supplementation significantly increases peripheral CD4+ Tregs in healthy adults without negatively affecting the frequency of other immune cells. European journal of nutrition, 53(3), 751-759.
  35. Penna-Martinez, M., & Badenhoop, K. (2017). Inherited variation in vitamin D genes and type 1 diabetes predisposition. Genes, 8(4), 125.
  36. Rafiee, M., Gharagozloo, M., Ghahiri, A., Mehrabian, F., Maracy, M. R., Kouhpayeh, S., … & Rezaei, A. (2015). Altered Th17/Treg ratio in recurrent miscarriage after treatment with paternal lymphocytes and vitamin D3: a double-blind placebo-controlled study. Iranian Journal of Immunology, 12(4), 252-262.
  37. Piantoni, S., Andreoli, L., Scarsi, M., Zanola, A., Dall’Ara, F., Pizzorni, C., … & Tincani, A. (2015). Phenotype modifications of T-cells and their shift toward a Th2 response in patients with systemic lupus erythematosus supplemented with different monthly regimens of vitamin D. Lupus, 24(4-5), 490-498.
  38. Giacomet, V., Vigano, A., Manfredini, V., Cerini, C., Bedogni, G., Mora, S., … & Zuccotti, G. V. (2013). Cholecalciferol supplementation in HIV-infected youth with vitamin D insufficiency: effects on vitamin D status and T-cell phenotype: a randomized controlled trial. HIV clinical trials, 14(2), 51-60.
  39. Scott, J. M., Kazman, J. B., Palmer, J., McClung, J. P., Gaffney‐Stomberg, E., & Gasier, H. G. (2019). Effects of vitamin D supplementation on salivary immune responses during Marine Corps basic training. Scandinavian journal of medicine & science in sports, 29(9), 1322-1330.
  40. He, C. S., Fraser, W. D., Tang, J., Brown, K., Renwick, S., Rudland-Thomas, J., … & Gleeson, M. (2016). The effect of 14 weeks of vitamin D3 supplementation on antimicrobial peptides and proteins in athletes. Journal of sports sciences, 34(1), 67-74.
  41. Zeng, Y., Luo, M., Pan, L., Chen, Y., Guo, S., Luo, D., … & Zhang, R. (2020). Vitamin D signaling maintains intestinal innate immunity and gut microbiota: potential intervention for metabolic syndrome and NAFLD. American Journal of Physiology-Gastrointestinal and Liver Physiology, 318(3), G542-G553.
  42. De Filippis, A., Fiorentino, M., Guida, L., Annunziata, M., Nastri, L., & Rizzo, A. (2017). Vitamin D reduces the inflammatory response by Porphyromonas gingivalis infection by modulating human β-defensin-3 in human gingival epithelium and periodontal ligament cells. International Immunopharmacology, 47, 106-117.
  43. Subramanian, K., Bergman, P., & Henriques-Normark, B. (2017). Vitamin D promotes pneumococcal killing and modulates inflammatory responses in primary human neutrophils. Journal of innate immunity, 9(4), 375-386.
  44. Su, D., Nie, Y., Zhu, A., Chen, Z., Wu, P., Zhang, L., … & Xiao, Z. (2016). Vitamin D signaling through induction of paneth cell defensins maintains gut microbiota and improves metabolic disorders and hepatic steatosis in animal models. Frontiers in physiology, 7, 498.
  45. Roggenbuck, M., Anderson, D., Barfod, K. K., Feelisch, M., Geldenhuys, S., Sørensen, S. J., … & Gorman, S. (2016). Vitamin D and allergic airway disease shape the murine lung microbiome in a sex-specific manner. Respiratory research, 17(1), 1-18.
  46. Merriman, K. E., Kweh, M. F., Powell, J. L., Lippolis, J. D., & Nelson, C. D. (2015). Multiple β-defensin genes are upregulated by the vitamin D pathway in cattle. The Journal of steroid biochemistry and molecular biology, 154, 120-129.
  47. Lopez-Lopez, N., Gonzalez-Curiel, I., Castaneda-Delgado, J., Montoya-Rosales, A., Gandara-Jasso, B., Enciso-Moreno, J. A., & Rivas-Santiago, B. (2014). Vitamin D supplementation promotes macrophages’ anti-mycobacterial activity in type 2 diabetes mellitus patients with low vitamin D receptor expression. Microbes and infection, 16(9), 755-761.
  48. Agarwal, S., Singh, S. N., Kumar, R., & Sehra, R. (2019). Vitamin D: A Modulator of Allergic Rhinitis. Indian Journal of Otolaryngology and Head & Neck Surgery, 71(3), 2225-2230.
  49. Krysiak, R., Kowalcze, K., & Okopień, B. (2019). Selenomethionine potentiates the impact of vitamin D on thyroid autoimmunity in euthyroid women with Hashimoto’s thyroiditis and low vitamin D status. Pharmacological Reports, 71(2), 367-373.
  50. Krysiak, R., Szkróbka, W., & Okopień, B. (2019). The effect of vitamin D and selenomethionine on thyroid antibody titers, hypothalamic-pituitary-thyroid axis activity and thyroid function tests in men with Hashimoto’s thyroiditis: A pilot study. Pharmacological Reports, 71(2), 243-247.
  51. Buondonno, I., Rovera, G., Sassi, F., Rigoni, M. M., Lomater, C., Parisi, S., … & D’Amelio, P. (2017). Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind placebo-controlled study. PloS one, 12(6), e0178463.
  52. Askmark, Håkan, et al. “Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D 3: A pilot study.” European journal of neurology 19.12 (2012): 1554-1560.
  53. Baeke, F., Takiishi, T., Korf, H., Gysemans, C., & Mathieu, C. (2010). Vitamin D: modulator of the immune system. Current opinion in pharmacology, 10(4), 482-496.
  54. de Oliveira, L. R. C., Mimura, L. A. N., Fraga-Silva, T. F. D. C., Ishikawa, L. L. W., Fernandes, A. A. H., Zorzella-Pezavento, S. F. G., & Sartori, A. (2020). Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation. Frontiers in Pharmacology, 11, 161.
  55. Lee, P. W., Selhorst, A., Lampe, S. G., Liu, Y., Yang, Y., & Lovett-Racke, A. E. (2020). Neuron-Specific Vitamin D Signaling Attenuates Microglia Activation and CNS Autoimmunity. Frontiers in Neurology, 11, 19.
  56. Verma, R., & Kim, J. Y. (2016). 1, 25-Dihydroxyvitamin D3 facilitates M2 polarization and upregulates TLR10 expression on human microglial cells. Neuroimmunomodulation, 23(2), 75-80.
  57. Kim, J. S., Ryu, S. Y., Yun, I., Kim, W. J., Lee, K. S., Park, J. W., & Kim, Y. I. (2006). 1α, 25-Dihydroxyvitamin D3 protects dopaminergic neurons in rodent models of Parkinson’s disease through inhibition of microglial activation. Journal of Clinical Neurology, 2(4), 252-257.
  58. Garcion, E., Sindji, L., Nataf, S., Brachet, P., Darcy, F., & Montero-Menei, C. N. (2003). Treatment of experimental autoimmune encephalomyelitis in rat by 1, 25-dihydroxyvitamin D 3 leads to early effects within the central nervous system. Acta neuropathologica, 105(5), 438-448.
  59. Garcion, E., Sindji, L., Nataf, S., Brachet, P., Darcy, F., & Montero-Menei, C. N. (2003). Treatment of experimental autoimmune encephalomyelitis in rat by 1, 25-dihydroxyvitamin D 3 leads to early effects within the central nervous system. Acta neuropathologica, 105(5), 438-448.
  60. Charoenngam, N., Shirvani, A., Kalajian, T. A., Song, A., & Holick, M. F. (2020). The effect of various doses of oral vitamin D3 supplementation on gut microbiota in healthy adults: A randomized, double-blinded, dose-response study. Anticancer Research, 40(1), 551-556.
  61. Malaguarnera, L. (2020). Vitamin D and microbiota: Two sides of the same coin in the immunomodulatory aspects. International Immunopharmacology, 79, 106112.
  62. Naderpoor, N., Mousa, A., Fernanda Gomez Arango, L., Barrett, H. L., Dekker Nitert, M., & de Courten, B. (2019). Effect of vitamin d supplementation on faecal microbiota: A randomised clinical trial. Nutrients, 11(12), 2888.
  63. Ghaly, Simon, Nadeem O. Kaakoush, Frances Lloyd, Terence McGonigle, Danny Mok, Angela Baird, Borut Klopcic et al. “High Dose Vitamin D supplementation alters faecal microbiome and predisposes mice to more severe colitis.” Scientific reports 8, no. 1 (2018): 1-12.
  64. Bashir, M., Prietl, B., Tauschmann, M., Mautner, S. I., Kump, P. K., Treiber, G., … & Pieber, T. R. (2016). Effects of high doses of vitamin D 3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract. European journal of nutrition, 55(4), 1479-1489.
  65. Kanhere, M., He, J., Chassaing, B., Ziegler, T. R., Alvarez, J. A., Ivie, E. A., … & Tangpricha, V. (2018). Bolus weekly Vitamin D3 supplementation impacts gut and airway microbiota in adults with cystic fibrosis: a double-blind, randomized, placebo-controlled clinical trial. The Journal of Clinical Endocrinology & Metabolism, 103(2), 564-574.
  66. Garg, M., Hendy, P., Ding, J. N., Shaw, S., Hold, G., & Hart, A. (2018). The effect of vitamin D on intestinal inflammation and faecal microbiota in patients with ulcerative colitis. Journal of Crohn’s and Colitis, 12(8), 963-972.
  67. Wang, L., Manson, J. E., Song, Y., & Sesso, H. D. (2010). Systematic review: vitamin D and calcium supplementation in prevention of cardiovascular events. Annals of internal medicine, 152(5), 315-323.
  68. Zittermann, A., Frisch, S., Berthold, H. K., Götting, C., Kuhn, J., Kleesiek, K., … & Koerfer, R. (2009). Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. The American journal of clinical nutrition, 89(5), 1321-1327.
  69. Dobnig, H., Pilz, S., Scharnagl, H., Renner, W., Seelhorst, U., Wellnitz, B., … & Maerz, W. (2008). Independent association of low serum 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Archives of internal medicine, 168(12), 1340-1349.
  70. Witham, M. D., Nadir, M. A., & Struthers, A. D. (2009). Effect of vitamin D on blood pressure: a systematic review and meta-analysis. J. of Hypertension, 27(10), 1948-1954.
  71. Nazarian, S., Peter, J. V. S., Boston, R. C., Jones, S. A., & Mariash, C. N. (2011). Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose. Translational research, 158(5), 276-281.
  72. Borissova, A. M., Tankova, T., Kirilov, G., Dakovska, L., & Kovacheva, R. (2003). The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. International journal of clinical practice, 57(4), 258-261.
  73. Broe, K. E., Chen, T. C., Weinberg, J., Bischoff‐Ferrari, H. A., Holick, M. F., & Kiel, D. P. (2007). A higher dose of vitamin D reduces the risk of falls in nursing home residents: a randomized, multiple‐dose study. Journal of the American Geriatrics Society, 55(2), 234-239.
  74. Sato, Y., Iwamoto, J., Kanoko, T., & Satoh, K. (2005). Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovascular diseases, 20(3), 187-192.
  75. Bischoff-Ferrari, H. A., Willett, W. C., Wong, J. B., Stuck, A. E., Staehelin, H. B., Orav, E. J., … & Henschkowski, J. (2009). Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Archives of internal medicine, 169(6), 551-561.
  76. A Messing, J., Heuberger, R., & A Schisa, J. (2013). Effect of vitamin D3 on lifespan in Caenorhabditis elegans. Current aging science, 6(3), 220-224.
  77. Singla, M., Rastogi, A., Aggarwal, A. N., Bhat, O. M., Badal, D., & Bhansali, A. (2017). Vitamin D supplementation improves simvastatin‐mediated decline in exercise performance: A randomized double‐blind placebo‐controlled study: Journal of Diabetes, 9(12), 1100-1106.
  78. Sinha, A., Hollingsworth, K. G., Ball, S., & Cheetham, T. (2013). Improving the vitamin D status of vitamin D deficient adults is associated with improved mitochondrial oxidative function in skeletal muscle. The Journal of Clinical Endocrinology & Metabolism, 98(3), E509-E513.
  79. Chen, L., Yang, R., Qiao, W., Zhang, W., Chen, J., Mao, L., … & Miao, D. (2019). 1, 25‐Dihydroxyvitamin D exerts an antiaging role by activation of Nrf2‐antioxidant signaling and inactivation of p16/p53‐senescence signaling. Aging Cell, 18(3), e12951.
  80. Tao, S., Zhang, H., Xue, L., Jiang, X., Wang, H., Li, B., … & Zhang, Z. (2019). Vitamin D protects against particles‐caused lung injury through induction of autophagy in an Nrf2‐dependent manner. Environmental toxicology, 34(5), 594-609.
  81. Zhang, H., Xue, L., Li, B., Zhang, Z., & Tao, S. (2019). Vitamin D protects against alcohol‐induced liver cell injury within an NRF2–ALDH2 feedback loop. Molecular nutrition & food research, 63(6), 1801014.
  82. Rao, Z., Zhang, N., Xu, N., Pan, Y., Xiao, M., Wu, J., … & Chen, Y. (2017). 1, 25-Dihydroxyvitamin D Inhibits LPS-Induced High-Mobility Group Box 1 (HMGB1) Secretion via Targeting the NF-E2-Related Factor 2–Hemeoxygenase-1–HMGB1 Pathway in Macrophages. Frontiers in immunology, 8, 1308.
  83. Zhu, C. G., Liu, Y. X., Wang, H., Wang, B. P., Qu, H. Q., Wang, B. L., & Zhu, M. (2017). Active form of vitamin D ameliorates non-alcoholic fatty liver disease by alleviating oxidative stress in a high-fat diet rat model. Endocrine journal, 64(7), 663-673
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