25-Hydroxy Vitamin D2

Vitamin D2, or ergocalciferol, is a plant-derived form of vitamin D.  In contrast, vitamin D3 is synthesized in the skin through sunlight exposure and found in animal-based foods. 

Once ingested or supplemented, Vitamin D2 is metabolized in the liver into 25-hydroxyvitamin D2 (25(OH)D2), a prohormone and one of the primary indicators of vitamin D status in the body. 

Despite structural differences from Vitamin D3, such as a unique double bond and methyl group placements, both forms convert into the active hormone, calcitriol, in the body.  

However, studies suggest that Vitamin D3 might be more effective at elevating and maintaining serum levels of 25-hydroxyvitamin D, though this remains a topic of ongoing scientific inquiry. 

The assessment of 25(OH)D2 levels is crucial for determining vitamin D sufficiency and plays a significant role in managing health, particularly when Vitamin D2 is the primary supplementation choice.

Understanding 25-OH 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.]

What is 25-OH Vitamin D2? [6., 7., 18.]

25(OH) vitamin D is also called calcidiol, which is considered a prohormone.

25-hydroxyvitamin D2 (25(OH)D2) is a metabolite of vitamin D2 (ergocalciferol) that is formed in the liver after ingestion or supplementation with vitamin D2.  It is one of the two major circulating forms of vitamin D, along with 25-hydroxyvitamin D3 (25(OH)D3), which is derived from vitamin D3 (cholecalciferol).

25(OH)D2 has a longer half-life of around 15 days compared to the parent vitamin D2, making it a better indicator of vitamin D status.

However, studies have shown that vitamin D2 is less effective than vitamin D3 in raising and maintaining serum 25(OH)D levels, with vitamin D2 being approximately 30-50% as effective as vitamin D3.  [6.]

When vitamin D2 and vitamin D3 are given together, the rise in total 25(OH)D levels is comparable to giving either form alone, suggesting that vitamin D2 does not interfere with the metabolism of vitamin D3.  [6.]

The total serum 25(OH)D level, which includes both 25(OH)D2 and 25(OH)D3, is considered the best indicator of vitamin D status.

While 25(OH)D2 is less potent than 25(OH)D3, it still plays a role in maintaining vitamin D levels in the body, especially when vitamin D2 is the primary source of supplementation.

Clinical Importance of 25-OH Vitamin D2

25-OH Vitamin D2, or calcidiol, is not physiologically active in the body, so it is considered a prohormone.  However, because it is one of the two major circulating forms of vitamin D (along with 25-OH vitamin D3) it is considered the standard assessment for vitamin D levels in the body.  

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., 9., 12., 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:  [7., 8., 9., 11., 14.]

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., 9.]

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., 7., 9.]

Cardiovascular Health

Adequate Vitamin D levels may be associated with a reduced risk of heart disease, possibly by influencing blood pressure and vascular health.  [7.]

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.

Why Do Doctors Prescribe Vitamin D2 Instead of Vitamin D3? 

Doctors may prescribe vitamin D2 (ergocalciferol) instead of vitamin D3 (cholecalciferol) in certain situations based on patient-specific factors and clinical considerations. 

For example, the decision to prescribe vitamin D2 could be due to its availability in different formulations, such as vegetarian or vegan-friendly options, making it suitable for individuals with dietary restrictions or preferences. 

Additionally, some patients may have medical conditions or allergies that preclude the use of vitamin D3 sourced from animal products. 

Furthermore, cost considerations or insurance coverage may influence the choice of vitamin D formulation, as vitamin D2 may be more affordable or covered by insurance plans. 

However, it's essential to note that while vitamin D2 and D3 are both effective at raising serum vitamin D levels, there is ongoing debate regarding their comparative efficacy and bioavailability.  In the absence of contraindications, many experts recommend vitamin D3 supplementation.   [9.]

The decision to prescribe vitamin D2 over D3 should be based on individual patient needs, preferences, and clinical judgment.

Testing Options for 25-Hydroxyvitamin 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 calcitriol levels typically involve obtaining blood samples through venipuncture.  It is a relatively simple and easy sample collection, although some people find blood draws unpleasant.  

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 a Normal Range of 25-OH Vitamin D2?

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.  [7.]

Serum analysis of 25(OH) vitamin D comprises 25(OH) vitamin D2 and 25(OH) vitamin D3.  [7.]

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.  

When calcitriol  levels are run, this often includes 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 levels.  [15.]  

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.  [9.]

Optimal Level 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.  [12.]

Results may also be reported as nmol/L, which has a reference range of 75-125 nmol/L.  [8.]

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:  [8.]

• 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)  [18.]

Diet and Lifestyle Factors to Support 25-OH Vitamin D2 in the Body

Dietary Sources of Vitamin D  [11.]

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.  In contrast, vitamin D2 is available in plant sources and is synthesized and added to supplements.  

• 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.  [5.]

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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