Vitamin D2

Vitamin D, recognized for its essential role in human health, encompasses various forms crucial for physiological functions such as bone health, immune system regulation, and cellular growth. 

Vitamin D2, or ergocalciferol, is one of the two major forms of Vitamin D.  Vitamin D is vital for numerous bodily functions, especially bone health and immune system regulation. Unlike its counterpart, Vitamin D3, Vitamin D2 is primarily obtained from plant sources and fortified foods.

This informational article provides an in-depth exploration of vitamin D2, covering its definition and function, as well as its clinical uses and indications. Additionally, it discusses the mechanism of action in the body and examines the available testing options for assessing vitamin D.   

Understanding Vitamin D2

What is Vitamin D2?

Vitamin D2, or ergocalciferol  is one of the two main forms of Vitamin D. Unlike Vitamin D3 (cholecalciferol), which is produced by the skin when exposed to sunlight and found in animal-based foods, Vitamin D2 is derived from plant sources and certain fungi. 

It is also available through vitamin D2-fortified foods or supplements.

Structurally, vitamin D2 has a double bond between carbons 22 and 23, while vitamin D3 has an additional methyl group at carbon 24. Despite these structural differences, both forms undergo similar metabolic processes in the body, ultimately being converted into the active form of vitamin D, calcitriol. 

While both forms are effective at raising serum 25-hydroxyvitamin D levels, some studies suggest that vitamin D3 may be more potent and bioavailable than vitamin D2. However, the clinical significance of this difference remains a topic of ongoing research and debate.  [3., 4.]

1,25-dihydroxyvitamin D2 is the active form of vitamin D2 in the human body.  It plays a vital role in regulating calcium and phosphate levels which are essential for bone health, muscle function, and nerve transmission.  It also is important in immune function.  

1,25-dihydroxyvitamin D2 is synthesized in the kidneys through a series of enzymatic reactions from calcidiol, or 25(OH) vitamin D, which is considered a prohormone.  

Learn more about the active form of vitamin D, calcitriol, here.

Learn more about the active form of vitamin D2, 1,25-dihydroxyvitamin D2, here.  

Learn more about the active form of vitamin D3, 1,25-dihydroxyvitamin D3, here.

Sources of Vitamin D2

• Fortified Foods: Common sources include fortified milk and cereals
• Mushrooms: some types of mushrooms exposed to ultraviolet light contain ergocalciferol
• Supplements: Vitamin D2 is available in dietary supplements, often used to prevent or treat deficiencies.

Functions of Vitamin D2: What is Vitamin D2 Good for?

The functions of active vitamin D2 are the same as the active form of vitamin D.  These include:  [1., 2., 8., 11., 16., 18.]

• Bone Health: some text
  • Calcium Absorption: It's crucial for calcium absorption in the gut, which is necessary for maintaining healthy bones and teeth. This is particularly important in preventing conditions like rickets in children and osteoporosis in adults.  Adequate calcium in the blood is also essential for muscle and nerve function.
  • Phosphate Absorption: vitamin D also regulates calcium absorption in the GI tract
  • Balances bone resorption and remodeling for healthy growth and bone preservation in adulthood
• Immune System Function: Vitamin D modulates the immune system.  Specifically, vitamin D promotes a healthy immune balance, prioritizing TH1 cellular immunity and the generation of CD4+CD25+ regulatory T cells (Tregs), essential in immune regulation and mitigating autoimmune conditions. 
• Mood Regulation and Brain Health: There's growing evidence linking Vitamin D levels to mood regulation and a reduced risk of depression. It's also thought to play a key role in brain health and cognitive function.
• Muscle and Nerve Function: Adequate Vitamin D levels are important for muscle strength, coordination, and proper nerve signaling.
• Cardiovascular Health: Emerging research suggests Vitamin D might play a role in heart health, although more research is needed to confirm this association and understand optimal vitamin D levels.  [6.]

Recommended Vitamin D2 Intake and Supplementation

RDA of Vitamin D

The recommended dietary allowance (RDA) of Vitamin D varies depending on age, gender, and other factors. Generally, these guidelines are:  [8., 13.]

Infants (0-12 months): 400 IU (10 mcg) per day.

Children and Teenagers (1-18 years): 600 IU (15 mcg) per day.

Adults (19-70 years): 600 IU (15 mcg) per day.

Older Adults (over 70 years): 800 IU (20 mcg) per day.

Pregnant and Breastfeeding Women: 600 IU (15 mcg) per day.

Indications for Vitamin D2 Supplementation

Vitamin D2 is specifically used to treat or prevent deficiencies, especially in populations with limited sun exposure or dietary restrictions.

Deficiency Symptoms 

Vitamin D2 supplements are prescribed to elevate and maintain adequate Vitamin D levels in the body. Vitamin D deficiency can lead to bone pain, muscle weakness, and increased risk of bone fractures. In severe cases, it can cause rickets in children and osteomalacia or osteoporosis in adults.  [2., 8.]

Association with Chronic Conditions 

Deficient levels of Vitamin D have been associated with various chronic conditions such as autoimmune diseases, osteoporosis, neurodegenerative and mood conditions, rickets in children and may be associated with cardiovascular problems.  [1., 2., 6., 8.]

Cardiovascular Health

Adequate Vitamin D levels may be associated with a reduced risk of heart disease, possibly by influencing blood pressure and vascular health.  [6.]

Cancer Prevention 

Some studies suggest a link between adequate Vitamin D levels and a reduced risk of development of certain cancers, particularly of advanced or fatal cancers.  This benefit may be more apparent in non obese people.  [5.]

Prevention in At-risk Groups 

People who are at risk of Vitamin D deficiency, such as those living in areas with limited sunlight, those following strict vegan diets, and the elderly, may benefit from Vitamin D2 supplementation.

High-Dose Vitamin D2 Supplementation: What is Vitamin D2 50,000 Units Used For?

High-dose Vitamin D2, such as 50,000 IU capsules, is often prescribed for the treatment of significant Vitamin D deficiencies where rapid correction is necessary.

Additionally, conditions such as osteoporosis, rickets, or particular bone disorders might require such high doses for effective treatment.

This treatment is typically short-term and closely monitored.  High doses require careful monitoring by healthcare providers to avoid the risk of toxicity and ensure optimal treatment outcomes.

Supplementation Considerations

When considering Vitamin D supplementation, it’s important to take the following into account:

• Individual Needs: Factors like dietary habits, sun exposure, skin type, and geographic location influence the need for supplementation.
• Form of Vitamin D in Supplements: While Vitamin D2 is effective, Vitamin D3 is often preferred due to its higher potency and longer duration in the body.
• Combination with Other Nutrients: Vitamin D's effectiveness can be enhanced when taken with other nutrients like calcium and magnesium.

The Importance of Testing for Vitamin D2

Testing for Vitamin D2 is particularly important in certain scenarios:

• Supplementation Monitoring: For individuals taking Vitamin D2 supplements, especially high doses, monitoring levels is crucial to avoid toxicity.
• Differential Diagnosis of Deficiency: In cases of Vitamin D deficiency, distinguishing between D2 and D3 levels can help determine the source of deficiency and guide appropriate supplementation.  [10.]

Testing Options for Vitamin D2 Levels

Laboratory Testing Methods

Vitamin D measurements are typically done via serum, although they may also be done via plasma or blood spot analysis.  Fasting or other special preparation is not typically required for a vitamin D test, but patients should consult their healthcare provider to confirm.  

Sample Collection and Preparation

Sample collection and preparation for testing vitamin D levels typically involve obtaining blood samples through venipuncture. 

Alternatively, blood spot testing for vitamin D involves collecting a small sample of blood from a finger prick onto filter paper. This method offers convenience for both patients and healthcare providers and can provide accurate measurements of vitamin D levels, making it useful for screening and monitoring vitamin D status.  A blood spot sample can be taken from the comfort of a patient’s home.  

Interpretation of Vitamin D Blood Tests

What is Measured in a Vitamin D Blood Test?

Vitamin D blood testing measures the concentration of specific forms of vitamin D in the blood. 

This typically includes the measurement of 25-hydroxyvitamin D (25(OH)D), which is the major circulating form of vitamin D and is considered the best indicator of overall vitamin D status as it reflects dietary intake and skin synthesis.  [8.]

Serum analysis of 25(OH) vitamin D comprises 25(OH) vitamin D2 and 25(OH) vitamin D3.  [8.]

Some labs may also measure the active form of vitamin D [1,25-dihydroxyvitamin D (1,25(OH)2D) or calcitriol] although this is less commonly done as it has a shorter half-life and may not reflect long-term vitamin D status as accurately as 25(OH)D, calcidiol.  

When calcitriol  levels are run, this often includes 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 levels.  [17.]  

Some labs offer the option to test for levels of vitamin D2 and vitamin D3 as separate fractions, which may be clinically useful to monitor treatment progress.  [10.]

Reference Ranges for Vitamin D in the Blood

Typical reference ranges for the total 25-OH vitamin D, measured in ng/mL, is 25-80 ng/mL.  [14.]

Results may also be reported as nmol/L, which has a reference range of 75-125 nmol/L.  [9.]

Many experts define vitamin D deficiency according to the following levels, although it is important to note that there is some discrepancy regarding vitamin D insufficiency:  [9.]

• Severe deficiency: a serum 25-hydroxyvitamin D (25(OH)D) level below 12 ng/mL (30 nmol/L)
• Deficiency:  a serum 25-hydroxyvitamin D (25(OH)D) level between 12-20 ng/mL (30-50 nmol/L)
• Vitamin D sufficiency:  a serum 25-hydroxyvitamin D (25(OH)D) level above 30 ng/mL (75 nmol/L)
• Vitamin D toxicity: serum 25(OH)D levels greater than 150 ng/mL (374 nmol/L)  [20.]

Why Do Doctors Prescribe Vitamin D2 Instead of D3?

There are several reasons why Vitamin D2 may be prescribed over D3 in certain scenarios:

• Availability and Cost: Vitamin D2 is often more readily available in higher doses and can be more cost-effective or more fully covered by insurance than D3 supplements.
• Dietary Preferences: For individuals following a strict vegan diet, Vitamin D2, being plant-derived, is often the preferred choice.
• Specific Clinical Protocols: Certain treatment protocols or medical guidelines may specify the use of Vitamin D2 based on the nature of the condition being treated.

• Individual Response: The effectiveness of Vitamin D2 can vary from person to person, and doctors often consider individual factors when prescribing it.

Related Biomarkers and Their Testing

In addition to Vitamin D2 levels, testing may involve other related biomarkers for a comprehensive assessment:

• Calcium and Phosphorus: As Vitamin D is crucial for calcium and phosphorus metabolism, testing these minerals can provide additional insights.
• Parathyroid Hormone (PTH): PTH levels can help understand the body's response to changes in Vitamin D and calcium levels.
• Vitamin D3 Levels: Testing for Vitamin D3 alongside D2 may provide a complete picture of the body’s Vitamin D status.
• Genetic factors influencing vitamin D function and status: genetic factors such as GC, CYP2R1, VDR, and CYP24A1 SNPs may carry clinical relevance for some people.  [9.]  This may be done as a blood test or via cheek swab.

Diet and Lifestyle Factors to Support Vitamin D Function in the Body

Dietary Sources of Vitamin D  [13.]

Vitamin D3 is synthesized in the skin in humans, and it can also be obtained through the consumption of animal-based foods in the diet.

• Fatty fish such as salmon, mackerel, and tuna are rich dietary sources of vitamin D.
• Egg yolks and fortified foods such as fortified milk, orange juice, and cereals also contribute to dietary intake of vitamin D.
• Some mushrooms, particularly those exposed to ultraviolet light, contain small amounts of vitamin D.  Mushrooms contain a compound called ergosterol that is converted to vitamin D2, ergocalciferol, in the presence of UV light.  [7.]

Sun Exposure and Vitamin D Synthesis

Exposure of the skin to sunlight triggers vitamin D synthesis: Vitamin D3 (cholecalciferol) is produced in human skin from 7-dehydrocholesterol upon exposure to sunlight.  

Sun exposure is most effective when the sun is high in the sky, typically between 10 a.m. and 3 p.m.  Other factors such as latitude, season, cloud cover, sunscreen use, and skin pigmentation influence the amount of vitamin D synthesized through sun exposure.

Lifestyle Habits for Optimal Bone Health

• Regular weight-bearing and muscle-strengthening exercises, such as walking, jogging, weightlifting, and resistance training, promote bone health by stimulating bone formation and density.
• Adequate intake of calcium and vitamin D through diet or supplements supports bone health by providing essential nutrients for bone formation and maintenance.
• Avoiding smoking and excessive alcohol consumption helps maintain optimal bone health, as smoking and alcohol can negatively impact bone density and increase the risk of fractures.

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