Vitamin D

Among the biomarkers important in assessing an individual’s health status and predisposition to disease, Vitamin D stands out due to its unique role in various physiological processes. It plays a crucial role in various physiological processes, including calcium metabolism, parathyroid hormone secretion, bone health, and immune function. 

Vitamin D, synthesized in our skin in response to sunlight and also obtained from dietary sources, is essential for maintaining overall health and is increasingly recognized as significant in preventive healthcare.

Vitamin D obtained from the diet or synthesized in the skin is converted to its active form, calcitriol, in the kidneys from calcidiol.  Active vitamin D, calcitriol, is considered a hormone, and due to its importance in human physiology, is also administered as a medication.  

Given its expansive influence on health, understanding VItamin D’s role and monitoring Vitamin D levels through lab testing is vital. This is particularly crucial since Vitamin D deficiency is a global health issue that is often overlooked due to its subtle and nonspecific symptoms.

Understanding Vitamin D

Active vitamin D is a hormone with complex roles in the body's health and functioning. 

What is Vitamin D?

Vitamin D refers to a group of fat-soluble secosteroids responsible for enhancing intestinal absorption of calcium, magnesium, and phosphate, and multiple other biological effects. 

It's unique among vitamins because in addition to being available in the diet it can also be synthesized by the body from sunlight, specifically UVB radiation. The two primary forms of Vitamin D are:

• Vitamin D2 (Ergocalciferol): Found in some plants, fungi, and yeasts.
• Vitamin D3 (Cholecalciferol): Synthesized by the skin when exposed to sunlight and found in animal-based foods.

Vitamin D2 and Vitamin D3 are also available as supplements.  They are activated to calcitriol, the active form of vitamin D, in the kidneys.  The total pool of calcitriol in the body consists of the sum of the active forms of vitamin D2, 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin vitamin D3.

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.

Functions of Vitamin D: What Does Vitamin D Do?  [2., 3., 8., 12., 17., 18.]

Vitamin D plays several vital roles in the body:

• 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 signalling.
• 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.]

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., 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.

Sources of Vitamin D: What Foods Contain Vitamin D?

Dietary Sources of Vitamin D  [14.]

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.]

Vitamin D Forms and Supplement Indications

Vitamin D is available in the diet as vitamin D2, ergocalciferol, and vitamin D3, cholecalciferol.  Cholecalciferol is also synthesized in the skin when exposed to sunlight.  

Vitamin D2 and vitamin D3 are also available in supplements.  

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.   [10.]

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

Supplement Indications for Vitamin D: What is Vitamin D Good For?  

Deficiency Symptoms 

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.  [3., 8., 14.]

Association with Chronic Conditions 

Deficient levels of Vitamin D have been associated with various chronic conditions such as autoimmune diseases including type 1 diabetes, osteoporosis, neurodegenerative and mood conditions, rickets in children and may be associated with cardiovascular problems.  [1., 2., 3., 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.  [4.]

Testing Vitamin D 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 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, known as 1,25-dihydroxyvitamin D (1,25(OH)2D), 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.

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.  [15.]

Results may also be reported as nmol/L, which has a reference range of 75-125 nmol/L.  [13.]

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:  [13.]

• Severe deficiency: a serum 25-hydroxyvitamin D (25(OH)D) level below 12 ng/mL (30 nmol/L) which requires intervention through diet changes or supplements
• Deficiency: a serum 25-hydroxyvitamin D (25(OH)D) level between 12-20 ng/mL (30-50 nmol/L), suggesting a need for increased sun exposure, dietary intake, or supplementation.
• 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.]

Factors Affecting Vitamin D Levels

Various factors can influence the accuracy of Vitamin D testing:

• Geographical Location and Sun Exposure: Less sun exposure can lead to lower Vitamin D synthesis in the skin.
• Dietary Habits: Limited intake of Vitamin D-rich foods can affect levels.
• Age and Skin Pigmentation: Older individuals and those with darker skin synthesize less Vitamin D from sunlight.

The Clinical Relevance of Vitamin D Testing

Regular testing of Vitamin D levels is important for:

• Diagnosing Deficiencies: Early detection of low Vitamin D levels can prevent complications like bone diseases.
• Guiding Treatment Decisions: Test results help in determining the need for and dosage of Vitamin D supplements.
• Monitoring Health in At-Risk Populations: Certain groups, like the elderly, individuals with limited sun exposure, and those with certain medical conditions, might require regular monitoring.

Understanding Vitamin D Needs: How Much Vitamin D Should I Take?

Understanding an individual’s vitamin D needs requires a personalized healthcare approach.  The decision to supplement vitamin D, and how much, depends on various clinical factors including the individual’s age, current level of vitamin D in blood, dietary intake and geographical location, personal and family health history, and other factors.  

Additionally, some functional medicine practitioners consider a person’s genetics when building a vitamin D supplement plan.  

It is important to consult a healthcare professional to determine the amount of vitamin D necessary for an individual’s healthcare outcomes.  

Related Biomarkers and Their Testing

Understanding Vitamin D levels in isolation isn’t enough; it’s important to consider other related biomarkers. This section focuses on additional tests that are often performed alongside Vitamin D testing to provide a more comprehensive view of health.

Calcium - A Key Biomarker in Relation to Vitamin D

Vitamin D plays a significant role in calcium absorption and bone health. Hence, assessing calcium levels is crucial:

• Blood Calcium Test: Measures the amount of calcium in the blood.
• Interpreting Results: High or low levels of calcium can indicate various health issues, including bone disorders, kidney disease, and parathyroid problems.

Parathyroid Hormone (PTH) and Its Interplay with Vitamin D

PTH helps regulate calcium levels in the body, and its function is closely related to Vitamin D:

• PTH Test: Measures the level of parathyroid hormone in the blood.
• Understanding Results: Abnormal PTH levels, along with Vitamin D data, can help diagnose parathyroid disorders and other related conditions.

Phosphate Levels

Phosphate balance is another health aspect influenced by Vitamin D:

• Serum Phosphate Test: Determines the amount of phosphate in the blood.
• Relevance: Abnormal phosphate levels, in conjunction with Vitamin D data, can indicate issues like bone and kidney diseases.

Other Biomarkers to Consider

Depending on individual health conditions, additional biomarkers might be tested alongside Vitamin D:

• Kidney Function Tests: As kidney health impacts Vitamin D metabolism.
• Magnesium Levels: Important for bone health and Vitamin D metabolism.
• 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.  [11.]

The Comprehensive Approach in Biomarker Testing

Testing for these related biomarkers provides a more holistic view of an individual’s health status, especially when investigating bone health, hormonal imbalances, or nutrient deficiencies.

• Integrated Analysis: Understanding how these biomarkers interact is key to diagnosing and managing various health conditions.
• Personalized Health Assessment: These tests can guide personalized health plans and interventions.

Diet and Lifestyle Factors to Support Calcitriol Function in the Body

Dietary Sources of Vitamin D  [14.]

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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