Vitamin D is a group of fat-soluble Secosteroids (type of steroid with a broken ring) that plays a vital role in maintaining bone health and regulating calcium and phosphate metabolism. However, recent studies have suggested that Vitamin D may also play a role in the management of metabolic disorders, including Obesity, Type 2 Diabetes (T2D), and Metabolic Syndrome. Additionally, genetic variations may impact the relationship between Vitamin D and metabolic disorders.
The different Chemical Forms of Vitamin D:
There are two primary chemical forms of Vitamin D: Vitamin D2 (ergocalciferol) and Vitamin D3 (cholecalciferol). Vitamin D3 is produced in the skin through exposure to sunlight, while Vitamin D2 is obtained through dietary sources such as fatty fish, fortified foods, and supplements.
Vitamin D3 is the most potent and biologically active form of vitamin D, and it is metabolized in the liver to form 25-hydroxyvitamin D3 [25(OH)D3], which is the major circulating form of vitamin D. 25(OH)D3 is further metabolized in the kidneys to form the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The effects of vitamin D are mediated by the vitamin D receptor (VDR), which is expressed in various tissues, including the liver, pancreas, adipose tissue and muscle.
Role of Vitamin D in Managing Metabolic Disorders:
Obesity: Obesity is a complex metabolic disorder characterized by excess adipose tissue and an increased risk of other metabolic disorders, including T2D and metabolic syndrome. Vitamin D deficiency has been associated with an increased risk of obesity, and several studies have shown that Vitamin D supplementation can improve measures of adiposity, including body mass index (BMI) and waist circumference (1, 2). One proposed mechanism by which Vitamin D may impact adiposity is through its effects on adipose tissue. Studies have shown that 1,25(OH)2D can inhibit the differentiation of preadipocytes into adipocytes and increase lipolysis in mature adipocytes (3).
Type 2 Diabetes: T2D is a metabolic disorder characterized by insulin resistance and impaired glucose metabolism. Several studies have shown that Vitamin D deficiency is associated with an increased risk of T2D, and Vitamin D supplementation may improve glucose metabolism and insulin sensitivity. One proposed mechanism by which Vitamin D may impact glucose metabolism is through its effects on pancreatic beta cells. Studies have shown that 1,25(OH)2D can enhance insulin secretion in response to glucose stimulation.
Metabolic Syndrome: Metabolic syndrome is a cluster of metabolic disorders, including abdominal obesity, high blood pressure, insulin resistance, and dyslipidemia, that increase the risk of cardiovascular disease and T2D. Vitamin D deficiency has been associated with an increased risk of metabolic syndrome, and Vitamin D supplementation may improve several components of metabolic syndrome, including blood pressure and lipid profiles.
Bone health: Vitamin D is essential for the absorption of calcium and phosphorus, which are crucial for bone health. Low levels of vitamin D can lead to weakened bones and an increased risk of fractures, especially in older adults.
Immune system function: Vitamin D plays a critical role in the proper functioning of the immune system. It has been shown to modulate the activity of immune cells and may help to reduce the risk of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, and type 1 diabetes.
Cardiovascular health: Low levels of vitamin D have been linked to an increased risk of cardiovascular disease, including hypertension, heart attack, and stroke. Vitamin D may help to reduce inflammation and improve endothelial function, which can help to protect against these conditions.
Depression: Vitamin D deficiency has also been linked to an increased risk of depression. Adequate levels of vitamin D may help to improve mood and cognitive function.
Cancer: There is some evidence to suggest that vitamin D may help to reduce the risk of certain types of cancer, including breast, colon, and prostate cancer.
Several studies have suggested that vitamin D supplementation may improve glucose metabolism, insulin sensitivity, and lipid profile in patients with metabolic disorders. For example, a systematic review and meta-analysis of randomized controlled trials showed that vitamin D supplementation improved glycemic control and insulin sensitivity in patients with type 2 diabetes. Another study showed that vitamin D supplementation improved lipid profile and reduced the risk of metabolic syndrome in postmenopausal women.
Impact of Genetic Variations:
There is growing evidence to suggest that certain genetic variations may impact the body's ability to produce or utilize vitamin D, which can increase the risk of certain lifestyle diseases and disorders. Here are some examples (out of the many) of how genes and genetic variations may be associated with vitamin D and health outcomes:
Vitamin D receptor (VDR) gene: The VDR gene codes for a protein that is involved in the absorption and metabolism of vitamin D. Certain variations in this gene may impact the body's ability to use vitamin D effectively, which can increase the risk of bone disorders such as osteoporosis, as well as autoimmune diseases, cardiovascular disease, and some types of cancer.
CYP2R1 gene: The CYP2R1 gene codes for an enzyme that is involved in the conversion of vitamin D to its active form. Variations in this gene may impact the body's ability to produce active vitamin D, which can increase the risk of bone disorders and other health problems.
GC gene: The GC gene codes for a protein that is involved in transporting vitamin D in the bloodstream. Certain variations in this gene may impact the levels of vitamin D in the body, which can increase the risk of various diseases and disorders, including autoimmune diseases, cardiovascular disease, and cancer.
DHCR7 gene: The DHCR7 gene codes for an enzyme that is involved in the production of vitamin D in the skin. Variations in this gene can impact the body's ability to produce vitamin D, which can increase the risk of various health problems.
In conclusion, vitamin D supplementation helps to improve glucose metabolism, insulin sensitivity, and lipid profile in patients with metabolic disorders. However, the effects of vitamin D may vary depending on the chemical form and dose of vitamin D, as well as the genetic variations in the different associated genes. Personalized approaches to improve the effects of vitamin D may be necessary to account for genetic variability.
Song HR, Lee EJ. Vitamin D and metabolic disorders. J Obes Metab Syndr. 2020;29(2):87-101. doi:10.7570/jomes20015
Mousa A, Naderpoor N, de Courten MPJ, Scragg R, de Courten B. Vitamin D supplementation for improvement of chronic low-grade inflammation in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2018;76(5):380-394. doi:10.1093/nutrit/nuy003
Rosen CJ, Adams JS, Bikle DD, et al. The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev. 2012;33(3):456-492. doi:10.1210/er.2012-1000
Forouhi NG, Ye Z, Rickard AP, et al. Circulating 25-hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies. Diabetologia. 2012;55(8):2173-2182. doi:10.1007/s00125-012-2544-y
Chiu KC, Chu A, Go VLW, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004;79(5):820-825. doi:10.1093/ajcn/79.5.820
Mathieu C, Gysemans C, Giulietti A, Bouillon R. Vitamin D and diabetes. Diabetologia. 2005;48(7):1247-1257. doi:10.1007/s00125-005-1802-7
Ford ES, Ajani UA, McGuire LC, Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care. 2005;28(5):1228-1230. doi:10.2337/diacare.28.5.1228
Rosenblum JL, Castro VM, Moore CE, Kaplan LM. Calcium and vitamin D supplementation is associated with decreased abdominal visceral adipose tissue in overweight and obese adults. Am J Clin Nutr. 2012;95(1):101-108. doi:10.3945/ajcn.111.018978
Tai K, Qi X, Zhao B, et al. Association of vitamin D receptor gene polymorphisms with Type 2 diabetes and metabolic syndrome among the Chinese Han population: a meta-analysis. Diabet Med. 2016;33(11):1508-1518. doi:10.1111/dme.13070
Vaidya A, Forman JP. Vitamin D and hypertension: current evidence and future directions. Hypertension. 2010;56(5):774-779. doi:10.1161/HYPERTENSIONAHA.110.157876
Wang TJ, Zhang F, Richards JB, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010;376(9736):180-188. doi:10.1016/S0140-6736(10)60588-0
Ahn J, Yu K, Stolzenberg-Solomon R, et al. Genome-wide association study of circulating Vitamin D levels. Hum Mol Genet. 2010;19(13):2739-2745. doi: 10.1093/hmg/dd