25-Hydroxy Vitamin D3

Vitamin D3, also known as cholecalciferol, is a crucial nutrient synthesized in the skin through sunlight exposure and found in certain animal-based foods. It is one of the two primary forms of Vitamin D, the other being plant-derived Vitamin D2. 

Once in the body, Vitamin D3 is hydroxylated in the liver to form 25-hydroxyvitamin D3 (25(OH)D3), a prohormone and major circulating form of vitamin D. 

This is further processed in the kidneys to produce 1,25-dihydroxyvitamin D3, the biologically active form of the vitamin, playing a vital role in regulating calcium and phosphate balance, essential for bone, muscle, and nerve health. 

Additionally, it supports immune function and has potential implications in mood regulation and cardiovascular health. 

The measurement of serum 25(OH)D levels, which includes contributions from both Vitamin D2 and D3, remains the most accurate indicator of vitamin D status in the body. This article explores the sources, functions, and health benefits of Vitamin D3, as well as guidelines for its intake and supplementation.

Understanding 25-OH Vitamin D3

What is Vitamin D3?

Vitamin D3 is one of the two main forms of Vitamin D, the other being Vitamin D2 (ergocalciferol). Unlike Vitamin D2, which primarily comes from plant sources and fortified foods, Vitamin D3 is synthesized in the human skin in response to sunlight exposure and is also found in certain animal-based foods.

1,25-dihydroxyvitamin D3 is the active form of vitamin D3 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 D3 is synthesized in the kidneys through a series of enzymatic reactions from calcidiol, or 25(OH) vitamin D, which is considered a prohormone.  

Together with 1,25-dihydroxyvitamin D2, 1,25-dihydroxyvitamin D3 makes up the body’s available pool of active vitamin D, calcitriol.  [11., 18.] 

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 D3?  [8., 22., 23., 24.]

25-hydroxyvitamin D3 (25(OH)D3), also known as calcidiol, is a prohormone and the major circulating form of vitamin D in the body.  It is produced in the liver by hydroxylation of vitamin D3 (cholecalciferol) by the enzyme 25-hydroxylase (CYP2R1).

As a prohormone, 25(OH)D3 is biologically inactive and must undergo further hydroxylation in the kidneys by the enzyme 1α-hydroxylase (CYP27B1) to form the biologically active form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), also known as calcitriol.

This active form is responsible for maintaining calcium and phosphate homeostasis, as well as regulating various other physiological processes.

The total serum level of 25(OH)D, which includes both 25(OH)D3 and 25(OH)D2 (derived from vitamin D2), is considered the best indicator of vitamin D status in the body.  This is because 25(OH)D has a longer half-life of approximately 2-3 weeks, compared to the shorter half-life of vitamin D3 and 1,25(OH)2D3.

Measuring serum 25(OH)D levels is crucial for diagnosing vitamin D deficiency, insufficiency, or toxicity, as well as monitoring the efficacy of vitamin D supplementation.

Natural Sources of Vitamin D3

• Sunlight: the body produces Vitamin D3 from cholesterol precursors when the skin is exposed to UVB rays from the sun.
• Dietary Sources: foods such as fatty fish (e.g. salmon, mackerel, and tuna), fish liver oils, egg yolks, and fortified products like milk and cereal provide Vitamin D3.

Functions and Health Benefits of Vitamin D3

What is Vitamin D3 Good For?

The functions of active vitamin D3 are the same as the active form of vitamin D.  These include:  [1., 2., 9., 13., 18., 20.]

• Bone Health: 

• 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.  It also helps enhance the body’s natural defense against infections.  

• 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.  Adequate levels of Vitamin D3 are important for muscle strength and coordination, potentially reducing the risk of falls and muscle weakness, especially in older adults.

• 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 D3 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:  [9., 15.]

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 D3 Supplementation

Vitamin D3 is used to treat or prevent deficiencies, especially in populations with limited sun exposure or dietary restrictions.

Deficiency Symptoms 

Vitamin D3 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., 6., 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.  [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 D3 supplementation.

Other Benefits of Vitamin D3 Supplementation

Supplementing with Vitamin D3 can benefit health and wellness in the following contexts:

• Enhancing Bone Health: to prevent or treat bone-related diseases.
• Boosting Immune Function: especially in individuals with lower exposure to sunlight or during winter months.
• Mood Regulation: supplementation may help improve mood, especially in cases of Seasonal Affective Disorder (SAD).  [12.]

Factors to Consider in Supplementation

• Form of vitamin D in supplements: vitamin D3 is often recommended due to its higher potency compared to Vitamin D2.  It is important to discuss the ideal form of vitamin D with your healthcare provider.
• Source and quality of supplements: choosing high-quality supplements and consulting with healthcare providers for personalized advice.
• Monitoring and adjustment: regular monitoring of Vitamin D levels via appropriate lab testing is crucial, especially for those on high-dose supplements, to avoid the risk of toxicity.

Testing Options for Vitamin D3 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 a 25-OH Vitamin D3 Normal Range?

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.  [9.]

Serum analysis of 25(OH) vitamin D comprises 25(OH) vitamin D2 and 25(OH) vitamin D3.  [9.]

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.  [19.]  

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.  [11.]

Optimal Ranges for Vitamin D in the Blood

Typical optimal ranges for the total 25-OH vitamin D, measured in ng/mL, is 25-80 ng/mL.  [16.]

Results may also be reported as nmol/L, which has a reference range of 75-125 nmol/L.  [10.]

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:  [10.]

• 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)  [22.]

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.

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

Dietary Sources of Vitamin D  [15.]

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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