Vitamin D is one of the fat-soluble vitamins and is also a steroid hormone. Although vitamin D is manufactured in skin from a reaction with ultraviolet (UV) light, there appears to be a conditional need for exogenous vitamin D for many people.
There are seven identified forms of vitamin D, of which two forms are most commonly known: D2 (ergocalciferol) and D3 (cholecalciferol). The most familiar form is vitamin D2, which is also the most common commercial form because it can be readily prepared from plant materials that contain the compound ergosterol. Vitamin D3 is the form that animals (including humans) synthesize from cholesterol. This happens when a form of cholesterol (7-dehydro) travels to the skin and interacts with UV light. D3 and its active metabolites, 25-hydroxy and 1,25-dihydroxycholecalciferol, are considered to be the most potent forms.1
Dietary forms of vitamin D are absorbed together with fats from food. Any condition that results in a diminished ability to absorb fat will result in a diminished ability to absorb vitamin D. This can include conditions like Crohn’s disease or weight loss surgeries, such as gastric bypass or duodenal switch.
As with all steroid hormones, the synthesis of vitamin D begins with cholesterol. 7-dehydrocholesterol travels to the surface of the skin where, in the presence of adequate sunlight, it is converted to cholecalciferol. Cholecalciferol, in turn, is metabolized first in the liver to 25-hydroxycholecalciferol, then in the kidneys to the active hormone 1,25dihydroxycholecalciferol. It is estimated that in the summer, 15 minutes three times a week of exposing the hands, arms, and face (without sunscreen) to early morning or late afternoon sun will make all the vitamin D one needs. Dark-skinned individuals require 5- to 10-times this exposure, as greater amounts of melanin inhibit the skin’s ability to produce vitamin D.2,3
The recommended dietary allowance (RDA) of vitamin D is 600IU (15mcg) for individuals aged 1 to 70 years and increases to 800IU (20mcg) for those over the age of 70 years. Few foods contain vitamin D. Examples of foods high in vitamin D include cod liver oil (1,360IU/Tbsp), trout (645IU/3oz), salmon (570IU/3oz), fortified 2% milk (120IU/cup), fortified plant-based milks (100–144IU/cup), fortified cereal (80IU/serving), and egg yolks (44IU/1 large egg).2
Impact on Health
Vitamin D is important for bone health. 1,25-dihydroxy-D3 stimulates the production of a protein in the digestive system called calbindin. Calbindin allows the body to absorb calcium from the digestive system into the blood stream. Additionally, vitamin D acts upon the digestive system directly to make it more permeable to calcium. Vitamin D further regulates blood calcium levels, being able to both increase and decrease levels based on demand. Vitamin D is also critical to the ability of the body to deposit calcium in bone. This is part of a complex interaction between 1,25-dihydroxy-D3 and parathyroid hormone. When both hormones are present in adequate levels, they work together to stimulate bone synthesis, but when vitamin D is low, the relative excess of parathyroid hormone stimulates a pathway by which more bone is broken down and lost. It is important to note that because of the interrelationship of vitamin D and calcium, low vitamin D can create the symptoms of low calcium. Additionally, active vitamin D is required for the synthesis of osteocalcin, a vitamin K-dependent bone protein.4
There seems to be no relationship between vitamin D levels and cancer incidence; however, having adequate or higher levels of vitamin D might be beneficial in terms of cancer progression and mortality.2,3 Some active vitamin D analogs play a role in cell differentiation, and in some of cancers, we have evidence that vitamin D may be able to inhibit cancer cell proliferation and induce more normal cell synthesis.
Vitamin D might play a role in multiple sclerosis (MS), with some studies showing an association between high vitamin D levels and reduced risk of MS. Higher levels of vitamin D might be associated with decreased disease progression and activity in individuals with MS. However, more research must be conducted on this matter.2,3
Although observational studies have shown an association between higher vitamin D levels and reduced risk of Type 2 diabetes, evidence from clinical trials is insufficient to claim that vitamin D can help decrease the risk of developing Type 2 diabetes.2
Deficiency
Vitamin D status can become impaired for several reasons, including decreased exposure to sunlight, low dietary intake, age, skin color, and malabsorption. Individuals with lactose intolerance or those who follow ovo-vegetarian/vegan diets are also at risk.2,3 Individuals with obesity might develop vitamin D deficiency due to accumulation in subcutaneous fat.2,3 Kidney or liver disease can also contribute to deficiency if the ability to synthesize vitamin D is impaired. Sunscreen also blocks the UVB rays from the sun that are required for vitamin D production. Sunscreens with a sun protection factor (SPF) of 8 or above block virtually all vitamin D synthesis. Where you live can also have an impact. In high-latitude locations (e.g., Boston, Massachusetts; Edmonton, Canada), there are inadequate levels of UVB rays available from November to March to assure vitamin D synthesis from sun exposure. Likewise, people living in certain areas of the southern hemisphere (e.g., Cape Town, South Africa; Buenos Aries, Argentina) produce much less vitamin D during their winter months, compared summer months.5
For the most part, vitamin D deficiency is a silent condition. Bone loss, evidenced on imaging studies as osteomalacia (weakening/softening of the bone) and osteoporosis, is usually the first finding. Prolonged deficiency in children can cause rickets, in which bone mineralization fails to occur, leading to soft bones and skeletal deformities.2,3 Symptoms of osteomalacia and rickets include pain, bone deformities, hypocalcemic seizures, tetanic spasms, and dental abnormalities. Children with rickets might also experience cardiomyopathy and developmental delays.2
Toxicity
The tolerable upper intake levels for vitamin D are 2,500IU for children aged 1 to 3 years, 3,000IU for those aged 4 to 8 years, and 4,000IU for those nine years of age or older.2 Toxicity from vitamin D is a risk from supplemental sources and should be monitored in individuals who supplement at very high levels. A person cannot overdose on vitamin D from sunshine. Acute toxicity can produce anorexia, nausea, vomiting, itching, thirst, frequent urination, and agitation. There can also be renal impairment. Clinical signs of chronic excess may also include dizziness, fatigue, muscle cramping (which can be severe), muscle pain, muscle twitching, neuritis or neuropathy, and kidney stones.
Interactions
Statins might reduce the synthesis of vitamin D, and high intake of vitamin D might impair atorvastatin, lovastatin, and simvastatin. Hypercalcemia might occur in individuals, particularly older adults and those with compromised renal function or hyperparathyroidism, who take both thiazide diuretics and vitamin D supplements.2 Vitamin D may interfere with the efficacy of verapamil, a type of calcium channel blocker medication. Some drugs interfere with the absorption, metabolism, or utilization of vitamin D. Cimetidine interferes with the liver’s role in activating vitamin D; long-term use of anticonvulsants is known to disrupt bone metabolism, and vitamin D has been shown to assist in the prevention of bone loss in these cases; both orlistat (a lipase inhibitor used for weight loss) and bile acid sequesterants inhibit the absorption of vitamin D; corticosteroids interfere with the activation and metabolism of vitamin D; and sunscreens block the ability of the body to synthesize vitamin D in the skin. Other interactions may apply as well; thus, it is a good idea for individuals who are vitamin D deficient to check with their pharmacist regarding possible interactions with their prescriptions.
Conclusion
Vitamin D is clearly a complex nutrient playing many roles in long-term health and wellbeing. Clinicians should both understand the importance of getting enough vitamin D from sun, food, and supplements, as well as respect the problems that can arise from both deficiency and excess.
This article was adapted with permission from: Jacques J. Vitamin d. In: Micronutrition for the Weight Loss Surgery Patient. Edgmont, PA: Matrix Medical Communications; 2005:65–72.
Additional Sources
Brody T. Nutritional Biochemistry, Second Edition. San Diego, CA: Academic Press, 1999.
National Institutes of Health Office of Dietary Supplements. Vitamin D: fact sheet for health professionals. Updated 18 Sep 2023. Accessed 26 Jun 2024. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
Harvard T.H. Chan Public School of Health. Vitamin D. Reviewed Mar 2023. Accessed 26 Jun 2024.- https://nutritionsource.hsph.harvard.edu/vitamin-d/
Garland CF, Garland FC, Gorham ED. Calcium and vitamin D: Their potential roles in colon and breast cancer prevention. Ann N Y Acad Sci. 1999;889:107–119.
Holick MF. Vitamin D: Importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79(3):362–371.
