What is Vitamin D?

Vitamin D is a vital compound responsible for increasing the intestinal absorption of calcium, magnesium, and phosphate. It is part of the group of fat-soluble secosteroids which includes Vitamin D3, also known as cholecalciferol, and Vitamin D2, also known as ergocalciferol. Both of these are the two major forms of Vitamin D. They are collectively termed as Calciferol.

Vitamin D has several important functions. The most important functions of Vitamin D are regulating the absorption of calcium and phosphorus, and aiding in the normal immune system function. More recently, it has become clear that receptors for vitamin D are present in different cells of the human body, and that this hormone has a wide range of biologic effects which extend far beyond control of mineral metabolism. Specifically, Vitamin D assists in promoting healthy bones and teeth, supporting immune, brain, and nervous system health, influencing insulin levels and helping in diabetes management, promoting lung function and cardiovascular health, and controlling the expression of genes involved in cancer development.

Formation, Absorption, and Mechanism of Action of Vitamin D in the Body

As stated above, the Vitamin D3, also known as cholecalciferol, is one of the major forms of Vitamin D. It is produced in the skin of animals and humans when light energy from the Sun is absorbed by a precursor molecule termed as 7-dehydrocholesterol. The other major form of Vitamin D, Vitamin D2 or Ergocalciferol, is the form found in plants. Studies show that natural diets typically do not contain enough amount of Vitamin D. Hence, it is important that exposure to sunlight or consumption of food rich with Vitamin D must be done in order to reduce the risk of having Vitamin D Deficiency. 

Molecular structures of both Vitamin D2 and D3 are shown below: 

Vitamin D2 structure

Vitamin D2 structure. (Image lifted from: https://upload.wikimedia.org/wikipedia/commons/5/5f/Ergocalciferol.svg)

Vitamin D3 structure

Vitamin D3 structure. (Image lifted from: https://upload.wikimedia.org/wikipedia/commons/7/79/Cholecalciferol.svg)

Both major forms of Vitamin D do not have significant biology activity. Hence, it must be metabolized in the body to an active form which is 1,25-dihydroxycholecalciferol. This process of transforming to this hormonally active form is depicted below:

hormonally active form

(Image lifted from: http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/vitamind.html#:~:text=The%20Vitamin%20D%20Receptor%20and,binding%20and%20DNA%2Dbinding%20domains.)

This process involves two main organs of the human body: Liver and Kidney. In the liver, cholecalciferol is hydroxylated to 25-hydroxycholecalciferol by the enzyme 25-hydroxylase. This 25-hydroxycholecalciferol has a halflife of several weeks. In the Kidney, 25-hydroxycholecalciferol serves as a substrate for 1-alpha-hydroxylase, yielding 1,25-dihydroxycholecalciferol which is the biologically active form of the prohormone Vitamin D. This active form has a halflife of only a few hours. In addition to that, it is good to note that Vitamin D binding protein is the major carrier of the prohormone in the blood, and hence responsible for transporting the prohormone in order for the whole process to occur. 

Liver synthesis of 25-hydroxycholecalciferol, which is a vital step in order to produce the active form, is not as tightly regulated like that of in the Kidney. The level of 25-hydroxycholecalciferol in the blood is directly proportional to its production when measured. In contrast to the Liver synthesis, the Kidney has a more regulated process in the production of the active form of Vitamin D. Specifically, the enzyme 1-alpha-hydroxylase found in the kidney serves as the major control point in the production of the active hormone. This enzyme is induced by parathyroid hormone and low blood levels of phosphate. Hence, people with low dietary intake of phosphate or people with parathyroid gland dysfunction have increased 1-alpha-hydroxylase activity.

The active form of Vitamin D binds to the intracellular receptors in order to modulate gene expression. The Vitamin D receptor has both hormone-binding and DNA-binding domains just like the receptors for thyroid and steroid hormones. The receptor forms a complex with a retinoid-x receptor, and this combination binds to the DNA. This binding causes either activation or suppression of transcription. The vitamin D receptor binds different forms of cholecalciferol. However, its affinity for 1,25-dihydroxycholecalciferol is approximately 1000 times more than that for 25-hydroxycholecalciferol. This explains why 1,25-dihydroxycholecalciferol has more potent biological activity compared to other forms. 

Recommended Dose or Adequate levels of Vitamin D in the Body

The 25-hydroxy Vitamin D blood test is the most accurate way to measure how much Vitamin D is present in your body. A level of 20 nanograms/milliliter to 50 ng/mL is considered an adequate level for healthy people. A level less than 12 ng/mL indicates Vitamin D Deficiency. Hence, it warrants for further investigation and/or treatment to reduce the risk of complications with the deficiency of the vitamin. 

Deficiency of Vitamin D

As stated above, A level less than 12 ng/mL indicates Vitamin D Deficiency and warrants for further investigation. There are different manifestations for adults and children with Vitamin D Deficiency. Children with vitamin D Deficiency suffer from a condition called Rickets, while Adults suffer from a disease called Osteomalacia. 

Symptoms of vitamin D deficiency may include regular sickness or infection, fatigue, bone and back pain, low mood, impaired wound healing, hair loss, and muscle pain. If Vitamin D deficiency continues for long periods, it may result in complications, such as, cardiovascular conditions, autoimmune problems, neurological diseases, infections, pregnancy complications, and certain cancers, especially breast, prostate, and colon.

  • Osteomalacia
Osteomalacia

   (Image lifted from: https://nurse-books.blogspot.com/2013/12/nursing-care-plan-for-osteomalacia.html)

Osteomalacia is a disease in adults caused by deficiency of Vitamin D. The Characteristics of this disease includes softening of the bones, leading to bending of the spine, bowing of the legs, proximal muscle weakness, bone fragility, and increased risk for fractures. There is an increase for bone fractures due to the reduction in calcium absorption and increased loss of calcium from bones. This disease usually manifests if the levels of 25-hydroxyvitamin D are less than 10 ng/mL. Some patients also suffer from chronic musculoskeletal pain. However, more studies should still be conducted in order to prove the link between chronic pain and vitamin D deficiency. It has also been observed that Vitamin D supplementation has no effect on controlling the symptom of chronic pain.

  • Rickets
Rickets

(Image lifted from: https://www.123rf.com/stock-photo/rickets.html?sti=mytbdut64wi5z2fbjw|)

Rickets is a childhood disease characterized by impeded growth and soft, weak, deformed long bones that bend and bow under their weight as children start to walk. It usually appears between 3 and 18 months of age of the newborn. The most important clinical symptom of this disease is bow legs which can be caused by vitamin D, calcium, or phosphorus deficiency. There are also isolated cases of genetic disorders producing the same symptoms such as pseudovitamin D deficiency rickets. This disease occurs because there is significant disruption in the regulation  of calcium, magnesium, and phosphate metabolism which in exchange cause for the underdevelopment of the bone. This also causes the weakening and softening of bones which leads to deformity of the long bones. 

It must be noted that maternal vitamin D deficiency may have a significant impact on development of bone disease from before birth and impairment of bone quality after birth. However, there are other factors such as dietary risk factors such as having darker skin plus having a diet deviated from a western omnivore pattern characterized by high intakes of meat, fish, and eggs, and low intakes of high-extraction cereals. Abstaining from animal foods is also a risk factor for developing the disease. 

In addition, because breast milk is low in vitamin D and social customs and climatic conditions can prevent adequate sun exposure, Vitamin D deficiency remains the main cause of rickets among young infants in most countries.However, recent statistics show that an increase in the proportion of animal protein in the modern diet coupled with increased consumption of milk formulated with relatively small quantities of vitamin D has caused for a significant decrease in the number of rickets cases. Moreover, in countries like the United States and Canada, there are vitamin D-fortified milk, infant vitamin supplements, and vitamin supplements that have helped in eradicating the majority of cases of rickets for children with fat malabsorption conditions.

Newborn and Vitamin D 

Due to increased risk for rickets and decreased sunlight exposure, the American Academy of Pediatrics recommends that all newborn babies receive routine vitamin D supplementation with a recommended dose of 400 IU per day.

As stated above, newborns who have insufficient exposure to sunlight are highly recommended for intake of vitamin D supplementation. To explain further who needs the vitamin D supplementation, here are the factors that put your breastfed baby at increased risk for vitamin D deficiency (Rickets):

  • The newborn has minimal exposure to sunlight. This occurs when you live up north in the map, if you live in an urban area where pollution or tall buildings can block the sunlight, if your newborn is always covered and kept out of the sun, or if the baby is always inside the house during the day, or if you are fond of applying high-SPF sunscreen to your newborn. These factors can significantly affect the sunlight exposure, increasing the risk for rickets development. 
  • The darker the skin pigmentation, the greater the amount of sun exposure needed in order to transform precursor to active form of vitamin D. Hence, both mothers and newborns who have darker skin need more time to be outside in order to produce adequate amounts of vitamin D. With that, vitamin D supplementation is recommended in order to make sure that even in short sun exposure, enough vitamin D still circulates in the body. 
  • Vitamin D deficient mothers. The amount of vitamin D in breast milk depends on the vitamin D status of the mother. So even if the newborn gets enough sun exposure but the mother’s vitamin D status is low, then studies show that the newborn will still likely develop rickets. Breast milk is an important contributor of Vitamin D to newborns. So if newborns do not get enough vitamin D from sun exposure, then they must get it from the breast milk. So it is important that mothers get enough sunlight exposure and consume enough foods rich in vitamin D, or they intake vitamin D supplements in order to make sure that she is not vitamin D deficient to have enough levels of the vitamins in her breast milk.

Sun exposure is the traditional and natural way of getting vitamin D. However, as stated above, there are certainly several factors that affect sun exposure to both mothers and newborns. Many factors influence vitamin D synthesis, such as skin pigmentation, latitude, and amount of skin exposed, making it difficult to assess how much vitamin D will be converted from sunlight exposure. Infants and children who have darker pigmentation require five to 10 times the length of sunlight exposure to reach the same levels of 25-hydroxyvitamin D when compared with children who have lighter pigmentation. These factors have significant effects on the vitamin D production. More than that, it is hard to determine how much time outside and how long you should be exposed to sunlight in order to consider that you have already gotten the adequate levels of vitamin D. However, some studies suggest that as little as 10 to 15 minutes of direct sunlight can generate 10,000 to 20,000 IU of vitamin D. In addition to that, the American Academy of Pediatrics recommends that infants younger than six months be kept out of direct sunlight. Although the goal of limiting sunlight exposure is to minimize the risk of skin cancer, it may also predispose children to vitamin D deficiency. Because the safe level of sunlight exposure needed for vitamin D conversion is unknown, increasing vitamin D supplementation is a reasonable alternative. 

More importantly, a mother’s vitamin D status during pregnancy directly affects the newborn’s vitamin D stores at birth, especially during the first 2 to 3 months of life. Hence, it is very important that pregnant women take vitamin D supplementation during pregnancy. Other than that, adding a vitamin D supplement to a mother’s diet and/or exposure to sunlight will significantly increase the amount of vitamin D in her breast milk. However, it must be noted that only a portion of this vitamin D will be utilized by newborns. Hence, newborns should still undergo sun exposure to increase vitamin D.  It is also good to note that a study in 2015 by Hollis et al. has concluded that a dose of 6400 IU/day of vitamin D supplementation to mothers safely provides breast milk with adequate vitamin D that can satisfy the nursing infant’s requirement and offers an alternate strategy to direct infant supplementation. Moreover, a study conducted in 2004 by Hollis and Wagner concluded that a dose of 2000-4000 IU of vitamin D per day significantly increased both the mother’s and the newborn’s vitamin D status. It also achieved substantial progress in bone development and reduced the risk for bone disease. With these data on hand, vitamin D supplementation is indeed helpful in maintaining bone health and decreasing risks for disease, and thus newborns and mothers should really intake the recommended dose per day of vitamin D. 

Benefits of Vitamin D Supplementation to Newborns

Other than reducing the risk for rickets or bone disease as what have been stated above, there are other benefits of Vitamin D supplementation to newborns and children. This may include, but not limited to, cardiovascular health, immune system, allergic manifestation, and mental health. To be more specific here is a list of benefits vitamin D offers:  

  1. Promotes better cardiovascular health

Vitamin D deficiency has been proven to have links to high blood pressure in children. A study by Skrzypczyk et al. in 2018 suggested that low vitamin D levels may promote hypertension. The aim of the study was to assess vitamin D status in children and adolescents with arterial hypertension and to find the relation between vitamin D and clinical and biochemical parameters of hypertension. This study proved the relation between vitamin D status and ambulatory arterial stiffness index, suggesting a negative influence of vitamin D on arterial walls. It also highly recommended that vitamin D deficiency should be suspected especially in Autumn-Winter period and among obese and short children. 

  1. Reduces the risk of developing flu

A 2018 review by Gruber-Bzura has suggested that some studies have found that vitamin D had a protective effect against the influenza virus which may be linked to the many extraskeletal effects due to the vitamin D receptor which is present in most tissues throughout the body. It may also be linked to the significant role of vitamin D on the innate and adaptive immune responses. Hence, the study recommends assessing vitamin D status and maintaining optimal serum levels in children. Vitamin D should be considered as a micronutrient that is part of essential factors that improve overall health conditions and improve the body’s guard against disease. However, further research should still be conducted in order to confirm this protective effect. 

  1. Reduces allergic sensitization

Studies show that there is a link between increased risk for allergic sensitization and low serum vitamin D in children and adults and food allergy in infants. The American Academy of Allergy, Asthma, and Immunology has found out that people living further away from the equator, thus having lower sun exposure, have been shown to have higher rates of childhood food allergy-related hospital admissions, epinephrine auto injector prescriptions, and peanut allergy. There is a relatively 6 times more risk than those living closer to the equator and thus having adequate sunlight exposure. Newborns born in autumn or winter when there is less sunlight exposure have also been associated with higher risk of anaphylaxis and food allergy. In addition to that, there is also a link between late introduction of egg, which is one of the few common dietary sources of vitamin D in the infant diet, and food allergy. Those who were introduced earlier had significantly less food allergy. To be specific, the children who started eating eggs after 6 months were more likely to develop food allergies than children who started between 4–6 months of age. Hence, there is a link between allergy and low vitamin D. There is increased risk for developing multiple allergies to infants with low vitamin D compared to infants with normal vitamin D levels. Lastly, vitamin D has potential use as a supportive therapy for people with steroid resistant asthma because studies have found out that it may enhance the anti-inflammatory effects of glucocorticoids. 

  1. Reduces the risk for depression

Research has shown that vitamin D has a significant role in regulating mood and thus reducing the risk of developing depression in adult life. In adults, research has found out that patients with depression who receive vitamin D supplements noticed relative improvement in their symptoms. Furthermore, in patients with fibromyalgia, vitamin D deficiency was more common in those who experience anxiety and depression. Hence, it is usually recommended for children to have vitamin D supplementation in order to reduce the risk of developing anxiety disorders and depression. Further research must still be conducted in order to prove the direct link between hormonal control of mental disorders and vitamin D levels. 

Vitamin D supplementation 

In most developed and developing countries, few foods are an abundant source of vitamin D. These foods that provide vitamin D include fatty fish, like tuna, mackerel, and salmon; foods fortified with vitamin D, like some dairy products, orange juice, soy milk, and cereals; beef liver; cheese; and egg yolks. However, achieving recommended intake of vitamin D is unlikely to occur through diet alone, unless there is fortification of key food groups. Especially in the context of newborns, they must need some other source of vitamin D in order to ensure adequate levels that reduces the risk of developing rickets or other bone disease. 

Guidelines for Vitamin D supplementation 

Studies show that vitamin D deficiency can occur early in life and that serum 25-hydroxyvitamin D concentration tends to be lower in breastfed infants. Hence, a recommended dose of 400 IU of vitamin D supplementation in newborns or infants should be followed in order to maintain higher concentrations of 25-hydroxyvitamin D and increase bone density. More specifically, the clinical recommendation are the following:

  • Infants ingesting less than 1 L (33.8 fl oz) of formula per day, as well as all breastfed or partially breastfed infants, should receive 400 IU of supplemental vitamin D daily.
  • Children and adolescents consuming less than 1 L of vitamin D–fortified milk per day should receive 400 IU of supplemental vitamin D daily.
  • Children at increased risk of vitamin D deficiency may require higher doses of supplemental vitamin D.

Supplementation Options

Vitamin D3, also known as cholecalciferol, is the preferred form of vitamin D for supplementation. However, children with certain conditions, such as fat malabsorption, and those who require long-term use of seizure medications may need higher doses of vitamin D because of increased risk of deficiency growing up. It should also be noted that monitoring 25-hydroxyvitamin D levels every three months, and parathyroid hormone levels and bone-mineral status every six months, is recommended for these children.

Available formulations preferable for infants are 400, 1,000, and 2,000 IU per Vitamin D3 drops. However, it must be noted that there are varying amounts of vitamin D3 available within formulations of the same brand. Infants or newborns usually just 1 drop or 1 mL in order to provide the total daily requirement for the vitamin. On the other hand, for older children, chewable and gummy vitamins contain 200 or 400 IU of vitamin D, but may vary by formulation from the same manufacturer. Older children usually need one tablet for children four years and older or 1/2 tablet for children two and three years of age for vitamin D supplementation with 400 IU in its preparation, or Two gummies for children two years and older for those preparation with 200 IU of vitamin D per serving. Hence, physicians may prefer to recommend one brand and formulation for each age group to ensure that patients reach a daily dosage of 400 IU 

How to choose the right supplement for Infants?

Other than knowing all of the benefits stated above, it is also important to know how to choose the right supplements for your infant for safety purposes and to know if you are getting the most out of the vitamin D supplementation. To help you, here are some things to remember when choosing the vitamin D supplement. 

  1. Choose Vitamin D3

As stated above, there are two major forms of supplemental vitamin D – D2 and D3. It is recommended that you choose the vitamin D3, since it is the type of vitamin D that is produced naturally by the human skin and hence slightly easier for the body to absorb and process. Hence, this type of vitamin D3 should be labeled in your infant’s vitamin D supplementation. It is also easier for infants to absorb this form of vitamin D. 

  1. Always check the dose per serving

Always check the dose per serving in the bottle’s or manufacturer’s label. In this way, you would know that you will not underdose or overdose your infant with the Vitamin D supplementation. As stated above, a recommended dose of 400 IU per day should be given to infants. Hence, you should be buying a vitamin D supplementation around this dose. Too much vitamin D can be harmful to infants. It can cause vitamin D toxicity. Beware of the signs of this toxicity such as nausea, vomiting, and weakness of infants. Hence, for safety, always check the label. 

  1. Opt for Liquid Drops

For the obvious reason that infants and young children cannot or have difficulty in ingesting caps, liquids or drops should be opted for vitamin D supplementation. Moreover, liquid drops have higher bioavailability compared to solid vitamin D supplementation. Hence, making sure that the per serving dose will be delivered properly through the body. Moreover, this is easier to administer to infants and young children. There are different doses per serving depending on the manufacturer of the vitamin D drops. Hence, some may need only 1 drop to cover the 400 IU daily recommended dose, while others need more drops. All these things are provided in the label or information sheet and thus must be read thoroughly before administration. 

  1. Look for third-party certification

Some supplements contain more than what their labels state, which can increase the risk for toxicity.  Hence, it is highly recommended for people to check vitamin D bottles for a USP verification seal, which indicates the supplement went through voluntary independent quality testing. These liquid drops listed their amounts most accurately. 

Indeed, vitamin D, a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone,  has  significant effects on infant health. It has a wide range of benefits on cardiovascular health, immune system, allergic manifestation, and mental health. More importantly, Vitamin D is important in order to prevent infants from developing rickets. 

Vitamin D3 can be harvested from many different foods however, achieving recommended intake of vitamin D3 is unlikely to occur through diet alone especially breastfed newborns. They must need some other source of vitamin D in order to ensure adequate levels of the vitamin in the body. 

Hence, a recommended dose of 400 IU of vitamin D3 supplementation in newborns or infants should be followed in order to maintain higher concentrations of 25-hydroxyvitamin D. This protects infants from developing rickets and also promoting other health benefits. With that, choosing the right Vitamin D supplementation must also be highlighted in order to make sure that no toxicity would occur. With these in mind, your infant will surely benefit with proper vitamin D supplementation. 

References:

  1. American Academy of Allergy, Asthma & Immunology. 2018. Vitamin D and Food Allergy. Retrieved from: https://www.aaaai.org/conditions-and-treatments/library/allergy-library/vitamin-d-food-allergy. Retrieved on 8 June 2020.
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  9. Skrzypczyk, P; Dziedzic-Jankowska, K.; Ofiara, A.; Szyszka, M.2; Panczyk-Tomaszewska, M. 2018. Vitamin D And Blood Pressure Parameters In Children And Adolescents With Arterial Hypertension. J. Htn. (36):250.
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