Much of the human experience has moved indoors in recent times. This has certainly reduced some health risks, like being chased by a lion or injured in a field. But other health risks, sometimes surprisingly, have increased.
One of the factors that changed by moving mostly indoors is the amount of Vitamin D, sometimes called the Sunshine Vitamin, we are getting. It is naturally produced when our skin is exposed to the tanning spectrum (UV-B) of ultraviolet radiation from the sun. The most conservative guesses suggest that losing this daily sun exposure dramatically affects Vitamin D levels on a population level. About 75% of black adults, 44% of Hispanic adults, and 20% of non-Hispanic whites in the US do not have adequate Vitamin D blood levels.
While we call it a "vitamin," Vitamin D is a hormone that activates many biochemical pathways in the body. It also plays a role in the regulation of calcium. With such an impactful role on human health, it's no wonder that Vitamin D deficiencies cause many problems. This article will discuss Vitamin D's role in the body, how to detect a deficiency, and how to appropriately reestablish levels.
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What is Vitamin D?
Vitamin D is not just one molecule. It is a small collection of closely related forms with unique functions. The various forms can become present in the body through several different pathways - through internal production (sunlight + cholesterol derivative in the skin), through food (minimal), and supplementation (several different forms). The skin, liver, and kidneys are involved at various points of transformation and activity.
The majority of the Vitamin D in a healthy human body is created in the skin with the exposure of the skin to sunlight, the tanning UV-B rays, specifically. The form of Vitamin D created in the skin is Vitamin D3 or cholecalciferol. D3 is not especially active in the body. This form is also found in small amounts in some animal foods. However, foods typically lack sufficient Vitamin D to meet basic needs.
In northern latitudes, the sunlight is not intense enough to trigger this reaction from November through March. Since Vitamin D is stored in fat, some excess can be carried through the winter, but if one is somewhat low going into winter, deficiency is likely by springtime.
Another source, from some plant foods, mushrooms, and yeasts, is Vitamin D2 or ergocalciferol. This form can also be taken as a supplement, but a much higher dose is required than of D3 to make the same increase in circulating levels.
The liver converts both D2 and D3 into the predominant circulating form, Calcidiol (25-hydroxy Vitamin D or 25-hydroxycholecalciferol). This is the main storage form found in fat cells. It is what is measured by most "Vitamin D" lab tests, though it is not very biologically active.
In the kidneys, some of the Calcidiol is converted into Calcitriol (1, 25-hydroxycholecalciferol or 1,25-hydroxy Vitamin D). Calcitriol is the most active form of Vitamin D. It enters cells and switches on genes, making specific proteins. This form has a relatively short half-life. It can be tested in labs but is not the molecule of choice to indicate Vitamin D status. Because the kidneys must make it, this active form is particularly relevant for those with kidney disease, who may need to take this as a medication rather than D2 or D3.
What is Vitamin D's Role in The Body?
Vitamin D is involved in many kinds of processes in the body.
The first and most long-known role is regulating calcium levels in the blood. This aspect was first discovered because a deficiency would end up causing kids to grow with deformed (calcium deficient) long bones.
Vitamin D helps to regulate blood calcium levels through several mechanisms. Mainly, it increases calcium absorption in the intestines, leading to more calcium entering the body.
Calcitriol, the form activated by the kidneys, regulates many genes as it enters the cell and binds to the Vitamin D receptor (VDR), starting the production process of proteins coded by that gene. Some of these relate to immune function and the inflammatory response. It is known to be involved in the epigenetic regulation of at least 1000 genes. This control over the production of certain proteins means it is intimately involved in many different biochemical processes in the body.
Vitamin D Deficiency Symptoms
Typically, people with mild to moderate Vitamin D deficiency do not show specific symptoms in the short term.
Significant (severe or prolonged) Vitamin D deficiency may lead to low blood calcium levels (hypocalcemia) and excessive activity from the parathyroids (hyperparathyroidism). This may show up as:
- Muscle weakness and cramps
- Fatigue
- Depression
- Numbness and tingling around the mouth or in extremities
- Heart rhythm problems
- Seizures
A prolonged significant deficiency of Vitamin D with low blood calcium and overactive parathyroids will ultimately lead to bone damage as too much calcium is removed to try to increase blood levels. This causes Rickets in children (deformed long bones) or bone pain and easy fracturing (osteomalacia or osteoporosis) in adults.
Certain risk factors increase the likelihood of Vitamin D deficiency. These include:
Demographics
Being older than 50 can increase the risk of Vitamin D deficiency. A mismatch of skin color to latitude (i.e., being African American with dark skin in northern environments) can also increase risk since darker skin requires more Vitamin D.
Location
Living in northern lands, spending little to no time outdoors, or using sun protection all the time, can all increase the risk of Vitamin D deficiency.
Health Conditions
Being overweight or having certain conditions such as hyperparathyroidism, any disorder that decreases the absorption of nutrients in the gut, including Crohn's disease or Celiac disease, chronic kidney or liver disease, or a granuloma-forming disease, such as sarcoidosis, tuberculosis, or histoplasmosis are all associated with Vitamin D deficiency. Also, taking certain medications such as seizure medications, Cholestyramine (for cholesterol), glucocorticoids, antifungals, and HIV drugs may increase risk.
Top Health Conditions Linked to Vitamin D Deficiency
Because Vitamin D is so active in the body, it makes sense that having inadequate levels would cause major disruptions. Some of the more recent research shows strong correlations and positive responses to treatment with Vitamin D in the following conditions:
Musculoskeletal Conditions
By reducing the intestinal absorption of calcium and depleting bone stores of calcium, prolonged or severe Vitamin D deficiency is associated with the development of Osteomalacia and Osteoporosis in adults. In growing children, this same calcium deficiency can cause Rickets, leading to deformed long bones.
If blood calcium levels become too low, this can also lead to acute muscle strength loss, as Vitamin D is involved in muscle fiber differentiation and growth.
Conditions During Pregnancy
Pregnant women with Vitamin D deficiency are more susceptible to pre-eclampsia. This is likely due to the blood pressure-lowering effects of Vitamin D. The higher risk of poor birth outcomes is likely due to a combination of factors involving processes in which Vitamin D plays an important role.
Cancer
Cancers of numerous types have been associated with low Vitamin D levels. Research shows it to have a suppressive effect on the proliferation of neoplastic cells.
Diabetes
Diabetes Mellitus (type 1 and type 2) are associated with Vitamin D deficiency. The reasons are due to the numerous effects of Vitamin D on the glucose-handling system. Adequate levels of Vitamin D reduce low-grade inflammation, which is a major driver of the development of insulin resistance.
Multiple Sclerosis
The link with Vitamin D deficiency in Multiple Sclerosis is multifactorial, but the anti-inflammatory and antioxidant effects are likely among the most relevant.
Respiratory Conditions
The Vitamin D connection with respiratory tract infections, including COVID-19, is most likely related to the immunomodulatory effects of Vitamin D, including anti-inflammatory effects that may protect from cellular damage in more severe conditions.
Asthma exacerbations can be fewer with adequate Vitamin D levels. As with other inflammatory and immune-mediated conditions, the anti-inflammatory and anti-oxidant effects are likely some of the most relevant.
Brain Conditions
Depression has been associated with low Vitamin D, but it does not appear this is related to changes in levels of neurotransmitters, at least in the short term. Because depression is also associated with neuroinflammation, it is likely that the anti-inflammatory effects of Vitamin D play a role in depression, cognitive decline, and Alzheimer's.
Heart Conditions
Heart disease is driven largely by inflammation. Vitamin D also affects cardiac risk due to the blood pressure-lowering effects on the smooth muscles and lining of blood vessels.
Overall Mortality
Premature death from all causes is associated with Vitamin D deficiency.
How to Test for Vitamin D Deficiency
When testing Vitamin D, there are various options available. Testing Calcitriol (1,25-dihydroxycholecalciferol) may seem like the most useful information because it is the most active form within the cells. It may be appropriate in specific conditions, like for suspected difficulty in converting Calcidiol (25-hydroxycholecalciferol) to Calcitriol. This conversion occurs in the kidney, so testing both forms might be helpful if there is a known kidney issue.
To assess long-term stores and nutritional status, Calcidiol is the storage form. A much longer half-life makes it less prone to short-term fluctuations, making it a more stable compound to assess body stores. In general, to screen Vitamin D levels, test Calcidiol, not Calcitriol.
The lab test for Calcidiol requires either a finger prick or a blood draw but typically does not require pre-test fasting. The current recommendations from the NIH suggest that Vitamin D levels above 50 ng/mL are sufficient for most people. Deficiency is considered at levels under 30 ng/mL, and some are at risk between 30 and 50 ng/mL.
Other Beneficial Root Cause Testing
If a Vitamin D deficiency is present, it may make sense to test for other conditions that can result from a deficiency of Vitamin D. Not all conditions with increased risk with low Vitamin D status have labs associated with their diagnosis, but some do.
Bone Health Testing
As bone health is strongly correlated with Vitamin D status, a prolonged deficiency should prompt consideration of bone health status. Several markers related to bone health may appear abnormal on a comprehensive metabolic panel (CMP) which is commonly ordered. These include high serum alkaline phosphatase (ALP, a liver enzyme) and potentially low serum calcium.
Because of the feedback loop involving calcium, deficient Vitamin D leading to calcium depletion, osteomalacia, or osteoporosis (or rickets in children) is also likely associated with elevated parathyroid hormone levels.
Diabetes Testing
Both type 1 and type 2 Diabetes are associated with a low Vitamin D level. So, if low Vitamin D is found, a fasting plasma glucose test and an HbA1c are warranted. Alternatively, a pre-diabetes risk assessment can accurately determine the risk of developing diabetes in the next ten years.
Cardiac Testing
Heart disease risk is increased in association with low Vitamin D levels. So, a thorough risk assessment and early lifestyle and functional medicine interventions make sense if one has low Vitamin D levels. The BostonHeart Comprehensive Lipid Panel measures 15 cardiac-relevant lipids and is excellent for screening cardiac risk.
Cancer Screening
Cancer screening labs for men and women should also be considered since there is an association between low vitamin D and certain cancers.
Respiratory Testing
Asthma is not diagnosed by lab tests. But in more severe cases, a complete blood count with differential (CBC w/ diff) can be ordered to screen for high eosinophils or anemia (suggesting breathing difficulties may not be asthma). Environmental and food allergy testing is also reasonable to pursue since these are strongly correlated to asthma.
Cognitive Testing
A person showing signs of possible cognitive decline and having tested low in Vitamin D should also be screened for other potential causes of cognitive decline before it is assumed to be solely related to low Vitamin D levels.
Vitamin B12 deficiency can show up as apparent cognitive decline. If severe, it will show up as megaloblastic anemia on a complete blood count (CBC) with low blood B12 levels. Folate deficiency is also related to cognitive impairment and is associated with heavy alcohol consumption. Folate should be tested in anyone concerned about cognitive function who drinks heavily.
Depression is not currently diagnosed with labs. However, a complete blood count (CBC), comprehensive metabolic panel (CMP), and a basic urinalysis may show signs of underlying anemia, diabetes, or kidney disease. These should be further assessed before assuming depression is purely psychogenic.
Pregnancy Testing
If pregnancy is confirmed with a urine (HCG) pregnancy test, blood pressure should be regularly monitored to assess for any signs of pre-eclampsia.
Treatment for Vitamin D Deficiency
A range of dose regimens are used for treating Vitamin D deficiency, but all generally involve oral supplementation over time, followed by follow-up lab tests.
The form of Vitamin D supplemented will affect the dose and may depend on the kidney function of the person taking it, as the kidneys are involved in the activation of Vitamin D.
High doses over a shorter period make more sense when a severe deficiency or an acute situation depends on adequate Vitamin D Status (i.e., an acute infection or inflammatory flare). Supplementation with lower doses over a longer time is also fairly common and often adequate for those with mild to moderate deficiency. The dose may need to fluctuate depending on the time of year. Doses to significantly increase blood test results will typically be at least 5000 IU daily. This dose range tends to be 5000-10000 IU daily for a few months before re-testing.
For prevention in those with a risk factor, 400-1000 IU per day over a prolonged period is usually recommended. Vitamin D is fat-soluble and not easily removed from the body. It can quickly rise to toxic, even fatal, levels with inappropriate supplementation. Thus, unsupervised/unmonitored supplementation doses should remain under 4000 IU daily. Providers also need to be aware and careful not to prescribe an excess to the point of causing toxicity and to monitor labs closely when being more aggressive in repleting a severe deficiency.
Nutrition
Vitamin D is primarily obtained through unexposed skin exposure to UVB radiation from the sun, so diet is not a major factor in the specific treatment of deficiency.
There are not many foods that provide Vitamin D in the human diet. A few examples are mushrooms, fortified milk, salmon or fish oil, and fish livers. It is even more difficult on a vegetarian or plant-based diet, as the form in plant foods and mushrooms, D2, is not as efficient in raising blood levels of Vitamin D.
Once levels have been brought into a normal range, the following are generally recommended intakes of Vitamin D for each age group:
Infants to 12 months: 400 IU daily
Children ages 1-13: 600 IU daily
Teens ages 14-18: 600 IU daily
Adults 19-70 years old (including pregnant and breastfeeding women): 600 IU daily
Adults 71 years old and older: 800 IU daily
This can be obtained through supplementation of Vitamin D, Vitamin D enriched foods, or supplementation with cod liver oil. Unfortunately, in most locations, it would not be advisable to try to consume all the required Vitamin D through fatty fish due to other contaminants present in those food chains.
Sun Exposure
Sun exposure is the most clear-cut way to increase Vitamin D levels, but sunscreen does block the UVB (tanning) rays that trigger the reaction in the skin. The risks of excessive unprotected sun exposure to skin cancer and aging are high, though, so sun exposure must be balanced. Protection is critical during times of high solar intensity. UVB from tanning beds also triggers the formation of Vitamin D.
Other Supplements
Fish liver oil is a culturally ingrained food/supplement in many Nordic cultures where the skin is fair and vulnerable to sun damage. Solar intensity is low for producing Vitamin D much of the year. This is a simple, relatively cheap way to ensure a stable baseline intake.
If Vitamin D is low, calcium may also be being pulled from bones, so taking a calcium supplement at the same time may help to prevent further depletion of bones.
Summary
Once thought to be only important for bone development and maintenance, the widespread roles of Vitamin D in the body are now being explored. We do know there are many important roles and that many Americans do not have a lifestyle that leads to maintaining optimal levels of health.
Supplementation with high-quality Vitamin D3 supplements is the most assured way to restore and maintain adequate levels for most people. Due to the potential for toxicity with excessive dosing for too long, dosing should be carefully considered. Doses should be kept to a lower daily dose when reasonable, and serum D3 should be monitored whenever taking over 2000 IU daily.
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