Nguyen-Hoang A and Dhadra M. Factors affecting vitamin D absorption efficiency in infants and children: implications for supplementation. HPHR. 2023;52. DOI: https://doi.org/10.54111/0001/OO10
Around one billion individuals, including children, worldwide suffer from a deficiency of Vitamin D. Insufficient levels of this vitamin are linked to conditions such as rickets, asthma, sleep disorders, respiratory infections in children, and the development of chronic diseases later in life. While sunlight exposure remains the primary means of acquiring Vitamin D, it poses a significant risk to the delicate skin and eyes of babies and children, making sun protection a crucial concern during childhood. Consequently, this can impede their ability to produce Vitamin D naturally through the skin. Additionally, the dietary intake of Vitamin D is typically minimal. For these reasons, the importance of using Vitamin D supplements as an alternative source for this population has been well reported, but the absorption efficiency of the source is nascent. This narrative review aims to explore the various factors that impact the absorption efficiency of Vitamin D supplementation in infants and children.
Vitamin D deficiency in infancy or childhood can result in rickets, a condition that impacted over 80% of children in the US and Europe in the 20th century.1 Despite efforts to curb the prevalence of rickets, recent reports indicate a resurgence of hospitalizations related to this condition in both developed and developing countries.2-3 Vitamin D deficiency remains a major public health concern globally, with an estimated one billion people worldwide being deficient in this important nutrient.4 The role of Vitamin D in maintaining bone health and supporting the immune system makes it a nutrient of concern. Vitamin D is required for the proper absorption of calcium and phosphate in the small intestine and the deposition of these minerals in bones. A deficiency of Vitamin D leads to decreased absorption efficiency of calcium by up to 3 times.5 Recent meta-analyses and systematic reviews have linked Vitamin D deficiency to an increased risk of asthma, sleep disorders, and respiratory infections in children.6-9 Inadequate serum Vitamin D levels in early childhood have also been linked to an increased risk of metabolic disorders such as heart disease and diabetes in adulthood.10
There is currently no global consensus on the definition of Vitamin D deficiency and sufficiency. Different health organizations and societies have proposed different definitions, with some considering serum levels of 25(OH)D below 50 nmol/L as deficient and others considering levels above 50 nmol/L as sufficient.11 Studies conducted in multiple countries, including the United States, the United Kingdom, New Zealand, China, India, and Europe, have reported that more than 35% of the pediatric population is deficient in Vitamin D.12-14 The prevalence of Vitamin D deficiency in children is unexpectedly high in sunny locations, such as Southeast Asian countries, where up to 58% of children under 5 years old in Vietnam15 and nearly 36% of healthy children aged 7-12 in Malaysia have deficient levels of serum Vitamin D.16
The primary source of Vitamin D is sunlight, which triggers the natural production of Vitamin D3 in the skin through exposure to UV-B rays. However, Maurya and Aggarwal17 argued that sun exposure alone does not meet the Recommended Dietary Allowance (RDA) for Vitamin D. This discrepancy is influenced by a range of factors, including atmospheric components, clothing choices, skin pigmentation, age, obesity, latitude, season, and time of day, highlighting the complex nature of achieving adequate Vitamin D levels through sunlight exposure. Moreover, prolonged sun exposure is not recommended for young children and babies, as they are more susceptible to skin and eye damage from UV radiation than adults.18-19 To protect against the sun, the American Academy of Dermatology suggests using a sunscreen with an SPF of 30 or higher for all children, regardless of age and skin tone.20 Other sun protection measures such as seeking shade, wearing a hat, clothing, and sunglasses are also recommended. However, sun protection methods can obstruct the synthesis of Vitamin D in the skin of babies and children, so the American Academy of Pediatrics suggests using Vitamin D supplements and Vitamin D-fortified foods to maintain a healthy Vitamin D level for this age group.19
Studies suggest it is difficult for children to get adequate amounts of Vitamin D from their diet alone. On average, children only receive 288 IU of Vitamin D from food per day, and even an 8-ounce glass of milk only provides 100 IU.21 There are two forms of Vitamin D in food: Vitamin D2 found in plants and mushrooms, and Vitamin D3 found in small amounts in animal-based foods like oily fish, cheese, milk, and egg yolks. Although breast milk is a nutritious option, it has a low amount of Vitamin D, less than 50 IU/l.22-23 This highlights the importance of alternative sources of Vitamin D, such as supplements, for children’s health. This narrative review investigates the factors affecting the absorption efficiency of this source in children.
Various systematic reviews have found that oral Vitamin D supplementation could effectively correct insufficient levels of serum 25(OH)D for children.24-25 Oral Vitamin D supplementation is the most effective source of Vitamin D for babies and young children. Numerous international health bodies and societies have agreed the oral administration of 400 IU/day is safe and effective to prevent rickets and ensure adequate Vitamin D status.26-30 Most of these health societies, including WHO emphasized Vitamin D supplements should be administered at birth.23 Regarding the preferred form of Vitamin D for supplementation, the National Institute for Health and Care Excellence guideline recommended Vitamin D drops in infants and young children.31
Vitamin D absorption efficiency varies considerately, from 55% to 99%, in healthy individuals.32 The oral supplementation of Vitamin D is challenging due to its fat-soluble nature, which leads to low solubility in water-rich digestive fluids, resulting in limited bioavailability. Additionally, Vitamin D is vulnerable to degradation when exposed to light, temperature, oxygen, and humidity.33 To improve the solubility and absorption of Vitamin D, various delivery systems have been explored. One of them is micellar delivery (MD) which has shown promise in increasing the solubility and stability of fat-soluble vitamins like Vitamin D3.34-35 In this method, the active compound (Vitamin D3) is surrounded by micelles, small spherical structures made up of surfactant molecules. The micelles have a hydrophobic interior and hydrophilic exterior, which allows them to easily diffuse across biological membranes and into cells, enhancing the absorption of the active compound.
Emuldrop, a patented MD system, is used in Smartbibi to improve the bioavailability of lipophilic actives including poorly soluble vitamins like Vitamin D3 and K2 in children. This system uses a micellar solution in glycerol to enhance the absorption of vitamins. The lipid shell of the micelle in this system protects the vitamins from degradation and improves their solubility, allowing them to be better absorbed by the body. Fratter et al36conducted a comparative study examining the enteric bio-accessibility of Vitamin D3 in two distinct formulations: an oily non-formulated form and a novel micellar liquid system featuring finely dispersed Vitamin D3. The findings demonstrated a significant enhancement in the bio-accessibility of Vitamin D3 by the water-based micellar system, showing a 16-fold increase compared to the unformulated oil form (70.9 ± 14.8 IU/mL vs. 4.2 ± 0.8 IU/mL). Furthermore, the study revealed that the micellar system exhibited a significantly higher recovery of Vitamin D3 at the end of the digestive process compared to the unformulated oil form, with recovery rates of 102.0 ± 6.4% and 6.6 ± 0.6%, respectively.
These findings emphasize the potential of the micellar liquid system as a promising vehicle for enhancing the bioavailability of Vitamin D3 in the enteric system. Similarly, another laboratory study shows that the bioavailability of micellar Vitamin D3 is significantly higher compared to standard oil preparations.35 To date, only one clinical trial on healthy children has been conducted to examine the effectiveness of the micellar delivery system. The trial showed that the levels of serum 25(OH) D in healthy children are significantly higher after taking Vitamin D3 in micelles compared to traditional Vitamin D3 forms, although the trial was open-labeled and non-randomized.37 Further randomized controlled trials are needed in this population. Micellar Vitamin D has also been reported to be more stable against factors such as light, degradation, and oxidation.35,38.
Vitamin D deficiency is widespread among children and can lead to various health problems like rickets and infections, as well as an increased risk of future issues like heart disease and diabetes. To address these issues, ensuring adequate Vitamin D intake in infants and children is crucial. Supplementation with Vitamin D has been identified as an effective approach to boost and rectify low levels of serum 25(OH)D in children. Vitamin D3 in liquid form is the recommended form of supplementation, starting at birth with a daily dose of 400 IU. This has been shown to be safe and effective in preventing rickets and ensuring adequate Vitamin D status for children of all ages. It is important to consider that the absorption of Vitamin D can vary significantly, and the micellar delivery system has demonstrated improved bioavailability of Vitamin D in healthy children, though additional randomized controlled trials are needed to confirm these results.
Anh Nguyen-Hoang is an alumnus of Harvard Medical School, a Registered Nutrition Practitioner (UK) and Consultant in Genomic Medicine (UK). He has been recognized as a Fellow of the British Association for Nutrition and Lifestyle Medicine. His work focuses on patient-oriented research projects on precision nutrition and genomics. He is also known for the efforts to explain profound concepts in personalized nutrition and lifestyle medicine between European and Asian children. Additionally, he has been elected as an Ambassadorial Scholar to the Genetics Society, one of the oldest learned societies in the UK dedicated to genetics. In this role, he actively promotes education and research on nutritional genomics for healthcare professionals in both the UK and Asia.
With a strong interest in teaching and academic service, he serves as the guest faculty of the European Lifestyle Medicine Organization’s lifestyle medicine certificate program for medical doctors across Europe. As Guest Speaker at The Economist, he has participated in workshop series on nutrition, health, genomics, and mindfulness for policymakers, healthcare CEOs, and thought leaders across the globe. He has also performed as panel speaker at the Asia Summit Global Health 2021 on public health issues in Asia, organized by The Hong Kong Trade Development Council.
Mona Dhadra, a full-qualified nutritional therapy practitioner and a registered Five-Element acupuncturist in Birmingham, United Kingdom. As a member of the British Acupuncture Council, all her treatments adhere to the highest standards of safety and competency. She has a keen interest in natural health. She qualified as a nutritional therapist from the University of Worcester and has since gone on to receive her degree equivalent qualification in Traditional Chinese medicine and five element acupuncture from The Acupuncture Academy. Mona operates a clinic in Oldbury, England, where she specializes in providing acupuncture treatments. Her practice interests are mental health and chronic pain.