Vitamin A

Vitamin A is a vital nutrient essential for various physiological functions in the human body, ranging from vision and immune function to growth and development.  Because of its many important roles in human health, identifying a deficiency or toxicity is clinically relevant in many settings.  

This article provides a comprehensive exploration of vitamin A, covering its chemical structure, activation into its active form (retinoic acid), different forms such as retinol and provitamin A carotenoids, and its diverse roles in the body. 

Additionally, the article examines symptoms and risks associated with vitamin A overdose, testing options, interpretation of results, and natural ways to boost vitamin A levels through diet. 

By delving into these key aspects, the article aims to enhance awareness and knowledge regarding the importance of vitamin A in promoting overall health and well-being.

Structure and Activation of Vitamin A

Description of Vitamin A: What is Vitamin A?

Vitamin A, a fat-soluble vitamin, exists in various forms; retinol is the most common active form in dietary sources. 

The main forms of vitamin A include:

Retinol: The most common form of vitamin A found in animal-based foods and supplements, serving as the primary storage and transport form in the body.  Retinol and carotenoids are two dietary forms of vitamin A that must be converted to retinal or retinoic acid in the tissues to support biological function.

Retinal: An intermediate form of vitamin A involved in the visual cycle, converting light signals into electrical signals in the retina.

Retinoic Acid: The biologically active form of vitamin A, playing a crucial role in gene expression regulation and various cellular processes, including cell differentiation and growth.

Provitamin A Carotenoids: Precursors of vitamin A found in plant-based foods, such as beta-carotene, alpha-carotene, and beta-cryptoxanthin, which can be converted into retinol in the body as needed.

Along with retinol, carotenoids must be converted to retinal or retinoic acid in the tissues to support biological function.

Understanding the Main Forms of Vitamin A

Retinol, Retinal, and Retinoic Acid

All three of the following forms of vitamin A are considered active.  They can also be stored in the body in the form of long chain fatty esters of vitamin A, such as retinyl palmitate, oleate, myristate, stearate and linoleate.  [9.]

Retinol 

Retinol is the preformed, active form of vitamin A found in animal-based foods and dietary supplements.  Retinol and retinyl esters are the two primary forms of preformed vitamin A in the diet.  Retinol is known to have antioxidant effects.  [9.]  

In contrast, the carotenoids are provitamin A, meaning that they are precursors that are converted to vitamin A in the body.  

In the liver, retinol is converted to retinyl ester and stored in the liver’s stellate cells.  These are released as necessary and then converted to retinal and retinoic acid in the tissues, where they exert effects on various physiological functions including vision, immune function, and skin health. 

Retinol travels in the bloodstream bound to retinol-binding protein (RBP).  [9.]

Retinal

Retinal, also known as retinaldehyde, is an intermediate form of vitamin A that plays a central role in the visual cycle. It is essential for the conversion of light signals into electrical signals in the retina, enabling visual perception.  

Retinal is mainly active in the retina, so it is found in very low concentrations in other parts of the body, where conversion to retinol or retinoic acid is favored.  [9.] 

Retinoic Acid

Retinoic acid, the biologically active form of vitamin A, regulates gene expression by binding to nuclear receptors known as retinoic acid receptors (RARs) and retinoid X receptors (RXRs). 

This activation process modulates cellular processes such as normal cell differentiation, growth, and development, as well as immune regulation.  Retinoic acid forms heterodimers with vitamin D and thyroid hormones.  [9.] 

An appropriate level, neither too much nor too little, is important for embryological development.  [13.]  Retinoic acid may also have antioxidant properties.  [10.]

Retinoic can travel in the bloodstream bound to albumin.  [9.] 

Provitamin A Carotenoids

Provitamin A carotenoids such as beta-carotene, alpha-carotene, and beta-cryptoxanthin, are plant-derived pigments that serve as precursors to vitamin A in the body.  While there are over 600 carotenoids, only about 50 have provitamin A activity, and one of the most famous is beta-carotene.  [9.] 

These carotenoids are found abundantly in fruits and vegetables, particularly those with vibrant orange, red, and yellow colors. Upon ingestion, provitamin A carotenoids are enzymatically converted into retinol by the body, primarily in the intestinal mucosa and liver.  The conversion rate of beta-carotene to retinol varies widely and often falls between 3.6–28:1 by weight.  [11.]

Beta-carotene is the most well-known and studied provitamin A carotenoid, with potent antioxidant properties and potential health benefits outside of its relationship to vitamin A.  [2.]

Functions of Vitamin A in the Human Body  [6.]

Vitamin A serves crucial biological functions, encompassing roles in embryonic development, immune system maturation, maintenance of epithelial integrity, and support for learning, memory, and neurogenesis in the adult brain, alongside its pivotal role in vision.

Role in Vision and Eye Health

Vitamin A plays a pivotal role in vision and overall eye health, particularly through its involvement in the visual cycle. 

In the retina, retinal, an active form of vitamin A, combines with opsin proteins to form visual pigments known as rhodopsin and iodopsin, which are essential for light perception. Rhodopsin allows for vision in low-light conditions (night vision), while iodopsin facilitates color vision in bright light. 

Vitamin A also supports health of the cornea and other ocular tissues, contributing to clear vision and preventing conditions such as night blindness and dry eyes.

Importance in Immune Function and Skin Health

Vitamin A is crucial for immune function, as it supports the maturation and activation of various immune cells, including T cells, B cells, and macrophages, helping the body effectively combat infections and pathogens. 

Furthermore, vitamin A plays a vital role in maintaining the integrity of the skin and mucous membranes, acting as a barrier against pathogens and environmental toxins. It promotes the proliferation and differentiation of keratinocytes, the primary cells in the epidermis, aiding in wound healing and reducing the risk of skin infections. 

Deficiencies in vitamin A can compromise immune function and skin health, increasing susceptibility to infections and dermatological conditions.

Contribution to Growth and Development

Vitamin A is essential for proper growth and development, particularly during embryonic and fetal stages. It is critical for the development of various organ systems, including the nervous system, respiratory system, and skeletal system.

 Vitamin A regulates gene expression involved in cell differentiation, proliferation, and tissue formation, ensuring the proper development of organs and structures. 

In childhood and adolescence, vitamin A continues to support growth and development, promoting bone health, muscle growth, and overall physical maturation. Adequate intake of vitamin A is essential throughout all stages of life to support optimal growth, development, and overall health.

Symptoms and Risks of Vitamin A Overdose [6.]

Vitamin A toxicity may be associated with acute or chronic overdose.  

Acute Vitamin A Toxicity Symptoms

• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Lethargy
• Drowsiness
• Increased intracranial pressure
• Skin changes such as erythema, pruritus, or desquamation

Chronic Vitamin A Toxicity Symptoms

• Low-grade fever
• Headache
• Fatigue
• Anorexia
• Intestinal disturbances
• Hepatosplenomegaly
• Anemia
• Hypercalcemia
• Subcutaneous swelling
• Nocturia
• Joint and bone pain
• Skin changes like yellowing, dryness, alopecia, and photosensitivity

Risks Associated with Excessive Vitamin A Intake

• Increased risk of birth defects if consumed in excess during pregnancysome text
  • Excessive vitamin A during pregnancy can cause serious birth defects. It affects fetal development and may cause facial, heart, and brain abnormalities. Pregnant women should avoid vitamin A supplements unless they have a vitamin A deficiency, and even then, they should not take more than 10,000 IU daily.  [6.] 
• Potential for bone abnormalities and fractures due to interference with bone remodeling  [4.]
• Liver toxicity and damage, especially with chronic overconsumption of vitamin A supplements  [5.] 
• Increased risk of hypertriglyceridemia  [8.]

Testing Options for Vitamin A

Laboratory Testing Methods

Laboratory testing for vitamin A typically involves measuring levels of retinol or retinyl esters in blood serum.  Blood samples are commonly collected by venipuncture, although the test is also available via dried blood spot.    

Preparation for Testing

Prior to vitamin A testing, individuals are typically advised to fast overnight and to avoid alcohol for at least 24 hours to ensure accurate results, as vitamin A levels can be affected by recent dietary intake. 

Interpretation of Test Results

Interpretation of vitamin A test results depends on the reference ranges established by the laboratory conducting the analysis.  Interpretation should also consider individual factors such as age, sex, dietary intake, and underlying health conditions. 

Typical reference ranges are given in micrograms per deciliter (mcg/dL) and include:  [1.]

0-30 days: not established

1 month-5 years: 14.4-42.6

6-11 years: 18.2-45.7

12-19 years:  18.8-54.9

20-39 years: 18.9-57.3

40-59 years:  20.1-62.0

> 59 years: 22.0-69.5

Clinicians should also be aware that serum retinol levels may not always accurately reflect vitamin A status, as they can be influenced by factors such as inflammation, liver function, and lipid levels. Thus, clinical correlation and consideration of other indicators of vitamin A status are essential for accurate interpretation of test results.

Recommended Daily Intake and Safe Limits

Recommended Daily Allowance for Vitamin A  [3.]

The Recommended Dietary Allowance (RDA) for vitamin A varies depending on age, sex, and life stage. 

For adult males, the RDA is typically around 900 micrograms of retinol activity equivalents (RAE) per day, while for adult females, it is around 700 micrograms RAE per day. 

Pregnant and lactating women may require higher amounts of vitamin A to support fetal development and breastfeeding, with RDAs set at 770 micrograms RAE per day.  

Establishing Safe Upper Limits for Vitamin A Intake

The Tolerable Upper Intake Level (UL) for vitamin A represents the maximum daily intake unlikely to cause adverse health effects in most individuals. For adults, the UL is typically set at 3000 micrograms RAE per day, with higher levels posing an increased risk of toxicity.  [3.]

Pregnant women should be cautious, as excessive vitamin A intake during pregnancy can increase the risk of birth defects. Therefore, it is essential to avoid exceeding the UL and to consult with healthcare professionals before taking high-dose vitamin A supplements, especially during pregnancy.

Natural Ways to Boost Vitamin A Levels

Dietary Sources Rich in Vitamin A  [7.]

Liver: feef liver, chicken liver, and fish liver oils are exceptionally rich sources of vitamin A.

Animal Products: egg yolks, whole milk, butter, and cheese contain moderate amounts of vitamin A.

Orange and Yellow Vegetables: carrots, sweet potatoes, pumpkin, and winter squash are high in provitamin A carotenoids like beta-carotene.

Leafy Greens: Spinach, kale, and collard greens provide beta-carotene and other carotenoids.

Fruits: Apricots, cantaloupe, mangoes, and papayas are rich in provitamin A carotenoids.

Testing Options for Vitamin A

Click here to view a list of tests that assess for nutrient levels including vitamin A.