Vitamin D, 25-Hydroxy

Optimal Result: 30 - 100 ng/mL, or 74.88 - 249.60 nmol/L.

What is Vitamin D?

Vitamin D is a fat-soluble vitamin in a family of compounds that includes vitamins D1, D2, and D3.

Vitamin D is both a nutrient we eat and a hormone our bodies make. It is a fat-soluble vitamin that has long been known to help the body absorb and retain calcium and phosphorus; both are critical for building bone.

Also, laboratory studies show that vitamin D can: 

- reduce cancer cell growth,

- help control infections

- and reduce inflammation.

Many of the body’s organs and tissues have receptors for vitamin D, which suggest important roles beyond bone health, and scientists are actively investigating other possible functions.

Vitamin D helps your body absorb calcium and maintain strong bones throughout your entire life.

Vitamin D must go through several processes in your body before your body can use it. The first transformation occurs in the liver. Here, your body converts vitamin D to a chemical known as 25-hydroxyvitamin D, also called calcidiol.

What are sources of Vitamin D?

Your body produces vitamin D when the sun’s UV rays contact your skin. Other good sources of the vitamin include fish, eggs, and fortified dairy products. It’s also available as a dietary supplement.

Few foods naturally contain vitamin D, though some foods are fortified with the vitamin.

For most people, the best way to get enough vitamin D is taking a supplement because it is hard to eat enough through food. Vitamin D supplements are available in two forms:

→ Vitamin D2 (“ergocalciferol” or pre-vitamin D)

→ Vitamin D3 (“cholecalciferol”).

Both are also naturally occurring forms that are produced in the presence of the sun’s ultraviolet-B (UVB) rays, hence its nickname, “the sunshine vitamin,” but D2 is produced in plants and fungi and D3 in animals, including humans.

Vitamin D production in the skin:

Vitamin D production in the skin is the primary natural source of vitamin D, but many people have insufficient levels because they live in places where sunlight is limited in winter, or because they have limited sun exposure due to being inside much of the time. Also, people with darker skin tend to have lower blood levels of vitamin D because the pigment (melanin) acts like a shade, reducing production of vitamin D (and also reducing damaging effects of sunlight on skin, including skin cancer).

What is the recommended dietary allowance (=RDA) for Vitamin D?

The Recommended Dietary Allowance for vitamin D provides the daily amount needed to maintain healthy bones and normal calcium metabolism in healthy people. It assumes minimal sun exposure.

  • RDA: The Recommended Dietary Allowance for adults 19 years and older is 600 IU (15 mcg) daily for men and women, and for adults >70 years it is 800 IU (20 mcg) daily.
  • UL: The Tolerable Upper Intake Level is the maximum daily intake unlikely to cause harmful effects on health. The UL for vitamin D for adults and children ages 9+ is 4,000 IU (100 mcg).

Global and regional prelevance of Vitamin D deficiency:

Many people may not be meeting the minimum requirement for the vitamin. NHANES data found that the median intake of vitamin D from food and supplements in women ages 51 to 71 years was 308 IU daily, but only 140 IU from food alone (including fortified products).

Worldwide, an estimated 1 billion people have inadequate levels of vitamin D in their blood, and deficiencies can be found in all ethnicities and age groups. In the U.S., about 20% of White adults and 75% of Black adults have blood levels of vitamin D below 50 nmol/L.

In industrialized countries, doctors are seeing the resurgence of rickets, the bone-weakening disease that had been largely eradicated through vitamin D fortification.

There is scientific debate about how much vitamin D people need each day and what the optimal serum levels should be to prevent disease. The Institute of Medicine (IOM) released in November 2010 recommendations increasing the daily vitamin D intake for children and adults in the U.S. and Canada, to 600 IU per day. The report also increased the upper limit from 2,000 to 4,000 IU per day. Although some groups such as The Endocrine Society recommend 1,500 to 2,000 IU daily to reach adequate serum levels of vitamin D, the IOM felt there was not enough evidence to establish a cause and effect link with vitamin D and health benefits other than for bone health. Since that time, new evidence has supported other benefits of consuming an adequate amount of vitamin D, although there is still not consensus on the amount considered to be adequate.

How is the Vitamin D level tested?

A 25-hydroxy vitamin D test is the best way to monitor vitamin D levels. The amount of 25-hydroxyvitamin D in your blood is a good indication of how much vitamin D your body has. The test can determine if your vitamin D levels are too high or too low.

The test is also known as the 25-OH vitamin D test and the calcidiol 25-hydroxycholecalcifoerol test. It can be an important indicator of osteoporosis (bone weakness) and rickets (bone malformation).

Why is a 25-hydroxy vitamin D test done?

Your doctor may request a 25-hydroxy vitamin D test for several different reasons. It can help them figure out whether too much or too little vitamin D is causing bone weakness or other abnormalities. It can also monitor people who are at risk for having a vitamin D deficiency.

Those who are at high risk of having low levels of vitamin D include:

- people who don’t get much exposure to the sun
- older adults
- people with obesity
- babies who are breastfed only (formula is usually fortified with vitamin D)
- people who have had gastric bypass surgery
- people who have a disease that affects the intestines and makes it difficult for the body to absorb nutrients, such as Crohn’s disease

Your doctor may also want you to do a 25-hydroxy vitamin D test if they’ve already diagnosed you with a vitamin D deficiency and want to see if treatment is working.

How to evaluate the results of a 25-hydroxy vitamin D test:

Results will depend on your age, sex, and the testing methods used. Results can also slightly vary from lab to lab.

According to the Office of Dietary Supplements (ODS), levels of vitamin D are measured by the 25-hydroxy level in nanomoles/liter (nmol/L) or nanograms/milliliter (ng/mL). The results can indicate the following:

Deficiency: less than 30 nmol/L (12 ng/mL)
Potential deficiency: between 30 nmol/L (12 ng/mL) and 50 nmol/L (20 ng/mL)
Normal levels: between 50 nmol/L (20 ng/mL) and 125 nmol/L (50 ng/mL)
High levels: higher than 125 nmol/L (50 ng/mL)

If your vitamin D levels are low and you are having symptoms of bone pain, a doctor may recommend a special scan to check bone density. Doctors use this painless scan to evaluate a person’s bone health.

What is the relationship between Vitamins D and K?

Vitamins D and K are both fat-soluble vitamins and play a central role in calcium metabolism. Vitamin D promotes the production of vitamin K-dependent proteins, which require vitamin K for carboxylation in order to function properly.

What are the functions of Vitamin D?

One of the main functions of vitamin D is to maintain adequate calcium levels in the blood. There are two ways in which vitamin D can achieve this:

  1. Improving calcium absorption: Vitamin D enhances the absorption of calcium from the food you eat.
  2. Taking calcium from bone: When you do not consume enough calcium, vitamin D maintains its blood levels by drawing on the body’s main calcium supply — your bones.

Maintaining adequate blood levels of calcium is essential. While calcium is best known for its role in bone health, it has many other vital functions in the body. During periods of insufficient calcium intake, your body has no other choice but to use the calcium reserves in your bones, even though that may cause bone loss and osteoporosis over time. Getting enough vitamin D helps the growth and development of bones and teeth. It may also provide improved resistance to certain diseases.

Vitamin D has many potential benefits. It may reduce the risk of certain diseases, help improve mood and reduce depression symptoms, and help with weight management.

In addition to its primary function, research suggests that vitamin D may also play a role in:

→ Reducing the risk of multiple sclerosis (MS). A 2018 review of population-based studies found that low levels of vitamin D are linked with an increased risk of MS.

→ Decreasing the chance of heart disease. Low vitamin D levels have been linked to increased risk of heart diseases such as hypertension, heart failure, and stroke. But it’s unclear whether vitamin D deficiency contributes to heart disease or simply indicates poor health when you have a chronic condition.

→ Reducing the likelihood of severe illnesses. Although studies are mixed, vitamin D may make severe flu and COVID-19 infections less likely. A recent review found that low vitamin D levels contribute to acute respiratory distress syndrome.

→ Supporting immune health. People who do not have adequate vitamin D levels might be at increased risk of infections and autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease.

→ Vitamin D may regulate mood and reduce depression. Research has shown that vitamin D might play an important role in regulating mood and decreasing the risk of depression. A review of 7,534 people found that those experiencing negative emotions who received vitamin D supplements noticed an improvement in symptoms. Vitamin D supplementation may help people with depression who also have a vitamin D deficiency. Another study identified low vitamin D levels as a risk factor for more severe fibromyalgia symptoms, anxiety, and depression.

→ It might support weight loss. People with higher body weights have a greater chance of low vitamin D levels. In one study, people with obesity who received vitamin D supplements in addition to following a weight loss diet plan lost more weight and fat mass than the members of the placebo group, who only followed the diet plan. In an older study, people taking daily calcium and vitamin D supplements lost more weight than subjects taking a placebo supplement. The researchers suggest that the extra calcium and vitamin D may have had an appetite-suppressing effect. The current research doesn’t support the idea that vitamin D would cause weight loss, but there appears to be a relationship between vitamin D and weight.

References:

Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al., editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011. Available from: https://www.ncbi.nlm.nih.gov/books/NBK56070/ doi: 10.17226/13050

Sizar O, Khare S, Goyal A, et al. Vitamin D Deficiency. [Updated 2023 Feb 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532266

Wang S. Epidemiology of vitamin D in health and disease. Nutr Res Rev. 2009 Dec;22(2):188-203. doi: 10.1017/S0954422409990151. PMID: 19860998.

Cui A, Zhang T, Xiao P, Fan Z, Wang H, Zhuang Y. Global and regional prevalence of vitamin D deficiency in population-based studies from 2000 to 2022: A pooled analysis of 7.9 million participants. Front Nutr. 2023 Mar 17;10:1070808. doi: 10.3389/fnut.2023.1070808. PMID: 37006940; PMCID: PMC10064807.

van Ballegooijen AJ, Pilz S, Tomaschitz A, Grübler MR, Verheyen N. The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review. Int J Endocrinol. 2017;2017:7454376. doi: 10.1155/2017/7454376. Epub 2017 Sep 12. PMID: 29138634; PMCID: PMC5613455.

Sintzel MB, Rametta M, Reder AT. Vitamin D and Multiple Sclerosis: A Comprehensive Review. Neurol Ther. 2018 Jun;7(1):59-85. doi: 10.1007/s40120-017-0086-4. Epub 2017 Dec 14. PMID: 29243029; PMCID: PMC5990512.

Penckofer S, Kouba J, Byrn M, Estwing Ferrans C. Vitamin D and depression: where is all the sunshine? Issues Ment Health Nurs. 2010 Jun;31(6):385-93. doi: 10.3109/01612840903437657. PMID: 20450340; PMCID: PMC2908269.

Makrani AH, Afshari M, Ghajar M, Forooghi Z, Moosazadeh M. Vitamin D and fibromyalgia: a meta-analysis. Korean J Pain. 2017 Oct;30(4):250-257. doi: 10.3344/kjp.2017.30.4.250. Epub 2017 Sep 29. PMID: 29123619; PMCID: PMC5665736.

Khosravi ZS, Kafeshani M, Tavasoli P, Zadeh AH, Entezari MH. Effect of Vitamin D Supplementation on Weight Loss, Glycemic Indices, and Lipid Profile in Obese and Overweight Women: A Clinical Trial Study. Int J Prev Med. 2018 Jul 20;9:63. doi: 10.4103/ijpvm.IJPVM_329_15. PMID: 30123437; PMCID: PMC6071442.

Links:

https://www.hsph.harvard.edu/nutritionsource/vitamin-d/

https://medlineplus.gov/vitaminddeficiency.html

https://www.webmd.com/diet/guide/vitamin-d-deficiency

https://health.unl.edu/9-vitamin-d-deficiency-symptoms-and-10-high-vitamin-d-foods

https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/vitamin-d-deficiency/faq-20058397

https://www.yalemedicine.org/conditions/vitamin-d-deficiency

https://www.uptodate.com/contents/vitamin-d-deficiency-beyond-the-basics

https://wwwn.cdc.gov/nchs/nhanes/vitamind/analyticalnote.aspx

https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

https://www.nhlbi.nih.gov/news/2022/vitamin-d-heart-health-where-benefits-begin-and-end

What does it mean if your Vitamin D, 25-Hydroxy result is too high?

High vitamin D blood levels generally result from taking too many vitamin pills and other nutritional supplements. High doses of vitamin D can result in a condition called hypervitaminosis D. Hypervitaminosis is a rare but serious condition that could put you at risk for liver or kidney problems.

High levels are rarely due to consuming too much of the vitamin through foods or sun exposure.

Can too much vitamin D be harmful?

Getting too much vitamin D (known as vitamin D toxicity) can be harmful. Signs of toxicity include nausea and vomiting, poor appetite, constipation, weakness, and weight loss.

Very high levels of vitamin D can damage the kidneys. It also raises the level of calcium in your blood. High levels of blood calcium (hypercalcemia) can cause confusion, kidney failure, and irregular heartbeat (arrhythmia).

Most cases of vitamin D toxicity happen when someone overuses vitamin D supplements. You cannot get too much vitamin D from sun exposure because the skin limits the amount of vitamin D it makes.

Risks of getting too much vitamin D:

Vitamin D toxicity can lead to an increase in your blood calcium levels. This can result in a variety of health issues, such as:

- nausea
- apathy
- vomiting
- abdominal pain
- dehydration
- confusion
- increased thirst

It is advised to not take daily vitamin D supplements containing more than 4,000 IU unless monitored under the supervision of your doctor.

Symptoms of toxicity:

- Anorexia
- Weight loss
- Irregular heart beat
- Hardening of blood vessels and tissues due to increased blood levels of calcium, potentially leading to damage of the heart and kidneys

The Recommended Dietary Allowances for vitamin D are as follows:

- infants (0–12 months): 10 mcg (400 IU)
- children and teens: 15 mcg (600 IU)
- adults ages 18–70: 15 mcg (600 IU)
- adults over age 70: 20 mcg (800 IU)
- pregnant or breastfeeding women: 15 mcg (600 IU)

What does it mean if your Vitamin D, 25-Hydroxy result is too low?

Low blood levels of 25-hydroxy vitamin D usually mean one (or more) of the following:

- you are not eating a balanced, complete diet

- your intestines are not absorbing the vitamin properly

- you are not spending enough time outside to absorb adequate vitamin D levels through sun exposure

Other causes for a vitamin D deficiency:

- darker skin pigment

- kidney or liver failure, which prevents the body from adequately processing vitamin D

- certain medications

- certain types of cancer, such as lymphoma

- a family history of vitamin D deficiency or childhood rickets

- celiac disease

- cystic fibrosis

- a condition affecting the pancreas, such as exocrine pancreatic insufficiency

Other people at high risk of vitamin D deficiency include:

- People with inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or other conditions that disrupt the normal digestion of fat. Vitamin D is a fat-soluble vitamin that depends on the gut’s ability to absorb dietary fat.

- People who are obese tend to have lower blood vitamin D levels. Vitamin D accumulates in excess fat tissues but is not easily available for use by the body when needed. Higher doses of vitamin D supplementation may be needed to achieve a desirable blood level. Conversely, blood levels of vitamin D rise when obese people lose weight.

- People who have undergone gastric bypass surgery, which typically removes the upper part of the small intestine where vitamin D is absorbed.

Several factors can affect your ability to get adequate vitamin D from sunlight alone:

You may be less likely to absorb enough vitamin D from the sun if you:

→ live in an area with high pollution
→ use sunscreen
→ spend most of your time indoors
→ live in a big city where buildings block sunlight
→ have darker skin (The higher the levels of melanin, the less vitamin D your skin can absorb.)

These factors can increase your risk of vitamin D deficiency. That’s why it’s important to get some of your vitamin D from non-sunlight sources.

What are the symptoms of vitamin D deficiency?

The symptoms of a vitamin D deficiency in adults may include:

→ tiredness, aches, and pains
→ severe bone or muscle pain or weakness
→ stress fractures, especially in your legs, pelvis, and hips

Possible treatment options:

If you receive a diagnosis of vitamin D deficiency, a healthcare professional will likely recommend that you take vitamin D supplements. If you have a severe deficiency, they may instead recommend high dose vitamin D tablets or liquids.

You should also make sure to get vitamin D through sunlight and the foods you eat.

Conditions resulting from prolonged vitamin D deficiency:

- Rickets: A condition in infants and children of soft bones and skeletal deformities caused by failure of bone tissue to harden.

- Osteomalacia: A condition in adults of weak and softened bones that can be reversed with supplementation. This is different than osteoporosis, in which the bones are porous and brittle and the condition is irreversible.

It has been suggested that vitamin D deficiency may play a role in certain conditions, such as fibromyalgia, chronic fatigue syndrome, and multiple sclerosis.

However, a firm causal link between vitamin D deficiency and other conditions, along with the therapeutic benefits of vitamin D supplementation, have yet to be established.

What are the symptoms of vitamin D deficiency?

Most people with vitamin D deficiency do not notice any symptoms. Others may notice vague symptoms that may be signs of any number of conditions.  

Possible symptoms include:

- Muscle pain

- Bone pain

- Increased sensitivity to pain

- A tingly, "pins and needles" sensation in the hands or feet

- Muscle weakness in body parts near the trunk of the body, such as the upper arms or thighs

- Waddling while walking, due to muscle weakness in the hips or legs

- A history of broken bones

- Muscle twitches or tremors

- Muscle spasms

- Bowed legs (when the deficiency is severe)

How is vitamin D deficiency treated?

Eating more vitamin D-rich foods is not usually sufficient to correct vitamin D deficiency, so your doctor is likely to recommend treatment with supplements.  

The dosage of vitamin D that doctors recommend may vary, depending on severity, age, weight and whether you’re pregnant or breastfeeding. Prescription-strength doses and dietary supplements are available. Some prescription doses are given weekly, rather than daily.  

Types of vitamin D supplementation include:

→ Vitamin D2 supplements (ergocalciferol), which are derived from a plant source.
→ Vitamin D3 supplements (cholecalciferol), which come from an animal source.

Calcidiol, a medication that’s a form of vitamin D3, which may be prescribed when an individual has a health condition that leads to malabsorption, like cystic fibrosis or celiac disease.

It is also important to make sure you are consuming enough calcium. People who have adequate levels of both vitamin D and calcium are able to lower their risk of fractures, but this is not the case when people only have adequate levels of vitamin D and inadequate levels of calcium.  

Depending on other health conditions, your doctor may also prescribe:  

→ Medications to help strengthen bones and to lower the risk of osteoporosis and fractures

→ Ensuring a normal vitamin D level in patients with fat malabsorption issues, including cystic fibrosis and Crohn’s disease, can be challenging and may require very high doses of supplements.  

Some doctors also recommend exposing the skin on your arms, legs and/or face to natural sunlight for 15 minutes, three or more times per week, which helps your skin produce vitamin D. Other doctors discourage this, because direct exposure to sunlight without sunscreen may increase the risk of skin cancer.

Vitamin D dosing:

The recommended dose of vitamin D depends upon the nature and severity of the vitamin D deficiency.

In people who do not have problems absorbing vitamin D:

In people whose 25-hydroxyvitamin D (25[OH]D) is <12 ng/mL (30 nmol/L), treatment usually includes 50,000 international units (1250 micrograms) of vitamin D2 or D3 by mouth once or twice per week for six to eight weeks, and then 800 to 1000 international units (20 to 25 micrograms), or more, of vitamin D3 daily thereafter.

In people whose 25(OH)D is 12 to 20 ng/mL (30 to 50 nmol/L), treatment usually includes 800 to 1000 international units (20 to 25 micrograms) of vitamin D3 by mouth daily. However, some individuals may need higher doses. The "ideal" dose of vitamin D is determined by testing the individual's 25(OH)D level and increasing the vitamin D dose if the level is not within normal limits. Once a normal level is achieved, continued therapy with 800 international units (20 micrograms) of vitamin D per day is usually recommended.

In people whose 25(OH)D is 20 to 30 ng/mL (50 to 75 nmol/L), treatment with 600 to 800 international units (15 to 20 micrograms) of vitamin D3 by mouth daily is usually sufficient to maintain levels in the target range.

In infants and children whose 25(OH)D is <20 ng/mL (50 nmol/L), treatment usually includes 1000 to 2000 international units (25 to 50 micrograms) of vitamin D2 by mouth per day (depending on the child's age) for two to three months. Children with rickets (softening of the bones, which can be seen on an X-ray) may need higher doses of vitamin D and should have medical follow-up to ensure that the rickets resolves.

In people who have diseases or conditions that prevent them from absorbing vitamin D normally, the recommended dose of vitamin D will be determined on an individual basis.

Are other vitamins or minerals needed?

During treatment for vitamin D deficiency, it is important to consume at least 1000 mg of calcium per day for premenopausal women and men and 1200 mg per day for postmenopausal women.

Calcium can be found in food sources or dietary supplements.

Monitoring:

In adults being treated for vitamin D deficiency, a blood test is recommended to monitor blood levels of 25(OH)D three months after beginning treatment. The dose of vitamin D may need to be adjusted based on these results and subsequent blood levels of 25(OH)D obtained to assure that normal levels result from the adjusted dose.

Side effects:

Side effects of vitamin D are uncommon unless the 25(OH)D level becomes very elevated (>100 ng/mL or 250 mmol/L) and the person is taking high-dose calcium supplements. However, it is important to follow dosing instructions closely and to avoid taking multiple products that contain vitamin D (eg, multivitamin and vitamin D).

If 25(OH)D levels do become very elevated, complications such as high blood calcium levels or kidney stones can develop.

Potential complications of a vitamin D deficiency:

The most serious complications of vitamin D deficiency are low blood calcium (hypocalcemia), low blood phosphate (hypophosphatemia), rickets (softening of the bones during childhood), and osteomalacia (softening of the bones in adults). However, these complications have become less common over time because many foods and drinks have added vitamin D.

"Subclinical" vitamin D deficiency or vitamin D insufficiency is common and is defined as a lower than normal vitamin D level that has no visible signs or symptoms. However, vitamin D insufficiency is often associated with reduced gastrointestinal calcium absorption, decreased bone density (osteopenia or osteoporosis), and, in some cases, a mild decrease of the blood calcium level, elevated parathyroid hormone (which accelerates bone resorption), an increased risk of falls, and possibly fractures, all of which can seriously affect a person's quality of life.

Thus, identifying and treating vitamin D insufficiency or deficiency is important to maintain bone strength. Treatment may even improve the health of other body systems, such as the immune, muscular, and cardiovascular systems, although more research is needed in these areas.

Additional note: Catching the sun’s rays in a sunny office or driving in a car unfortunately will not help to obtain vitamin D as window glass completely blocks UVB ultraviolet light.

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