A Case Study of Vitamin D Supplementation Therapy and Acute Respiratory Tract Infection

Abstract

Background

Low serum concentrations of 25-hydroxyvitamin D correlate with higher susceptibility to acute respiratory tract infections (ARTIs). The case study presented here aims at sheding light on the correlation between vitamin D levels, the vitamin D supplement dose, and the incidence of ARTIs.

Case Report

A 23-year-old female patient with a vitamin D insufficiency was able to successfully increase her vitamin D levels from 45.60 nmol/l to 85.91 nmol/l (reference ranges 75-200 nmol/l) through the use of supplements. However, it was surprising to observe a decrease in vitamin D levels even though the patient continued taking supplements. Further examination indicated that the patient was experiencing common symptoms of an acute respiratory tract infection (ARTI). This case highlights the intricate connection between ARTIs and vitamin D intake.

Conclusion

This case study clearly demonstrates the intricate connection between vitamin D levels, supplement treatment, and ARTIs. The observed decrease in vitamin D levels during the course of supplementation, while the patient was suffering from an ARTI, suggests that respiratory infections may affect vitamin D metabolism.

Acute respiratory tract infections (ARTIs) are a significant threat to children under the age of five worldwide, accounting for roughly 10% of emergency department visits in the USA (1-3). Studies have found that low levels of 25-hydroxyvitamin D, which is the storage form of vitamin D in the body (4,5), are associated with an increased risk of developing ARTIs. This is because 25-hydroxyvitamin D helps produce antimicrobial peptides that combat viruses and bacteria (5-7), and vitamin D metabolites have been shown to activate innate antimicrobial mediator mechanisms like autophagy and the production of radical oxygen and nitrogen intermediates (8). While some studies have suggested that vitamin D supplements can prevent ARTIs (9,10), results have been inconsistent (11-13). Supplementation may be more beneficial for patients with chronic respiratory conditions and low initial vitamin D levels, though the response to treatment may be influenced by age and body mass index. It’s important to note that high doses of vitamin D have been shown to reduce treatment effectiveness (9) and, in some cases, increase the risk of adverse outcomes (14).

An individual participant data (IPD) meta-analysis is the sole means to examine impact modifiers at the individual level, such as baseline vitamin D status. By conducting an IPD meta-analysis, we can thoroughly examine how participant covariates and baseline vitamin D levels impact the effects of vitamin D supplementation on therapeutic outcomes for patients with ARTIs. Our case report highlights the importance of understanding the relationship between vitamin D and inflammatory processes and infections, specifically ARTIs. It is critical to comprehend how ARTIs impact vitamin D levels by affecting its synthesis or metabolism to improve patient outcomes and optimize treatment plans. This knowledge is crucial in developing targeted therapies and improving treatment regimens that address vitamin D insufficiency in conjunction with an ARTI. By identifying the variables that affect vitamin D levels, we can identify individuals who may benefit from supplementation and personalized treatment methods. This will provide valuable insight into individual-level variations and lead to a better understanding of the relationship between vitamin D and therapeutic outcomes.

Case Report

The participant in this case study was a 23-year-old female medical student. The patient characteristics are shown in Table I. In March 2023, the medical student took part in a healthcare event organized by the University Hospital in Pilsen. The event aimed to determine the level of [25(OH)D)] in the serum following the winter season, using the chemiluminescent assay Access 25(OH) Vitamin D Total (Beckman Coulter, Brea, CA, USA). The initial concentration of serum [25(OH)D)] measured was 45.6 nmol/l, indicating a deficiency in vitamin D, and vitamin D supplementation was recommended.

Table I. Participant characteristics.

To address the deficiency, the student began taking 4,000 IU of vitamin D3 for the first 14 days, followed by 2,000 IU for an additional 14 days. The goal was to reach the lower end of the reference range (75 nmol/l) for the European population (15), using an over-the-counter (OTC) vitamin D3 oral solution that contained 25 µg (1,000 IU) per drop. After one month, the level of [25(OH)D)] was 85.91 nmol/l, indicating successful supplementation.

Given the potential benefits of higher serum levels of vitamin D (16-19), and the fact that indigenous populations such as the Maasai have levels in the range of 100-150 nmol/l (20), it was decided to increase the student’s supplementation. The student, a well-informed medical student, agreed to further supplementation, with the goal of reaching a serum level of 120 nmol/l.

To achieve this goal, we used the loading dose methodology (21), previously used successfully in our practice. The dosage was calculated as follows:

IU=40 × (target value in nmol/l – measured start concentration in nmol/l) × patient weight (kg).

The total loading dose of 84,543 IU was given gradually with a weekly dose of 25,000 IU. The regimen involved taking 5,000 IU per day from Monday to Friday, with a break on Saturday and Sunday. After three weeks, a serum level of [25(OH)D)] was conducted, and we were expecting a measurement of approximately 120 nmol/l. However, the actual result was only 70.04 nmol/l which was surprising given the doubled dosage. We immediately reached out to our participant to verify if she had followed the supplementation instructions, which she confirmed. However, she had contracted a viral respiratory infection ten days after initiating the higher dosage of vitamin D, with typical symptoms of sore throat, fatigue, headache, cough, and rhinitis, but no fever. Based on the symptoms presented, it seems likely that the individual was experiencing an acute respiratory tract infection (ARTI).

There were no signs of significant breathing difficulties or complications. According to the Department of Microbiology at University Hospital in Pilsen, adenoviruses are the primary culprits for acute respiratory tract infections (ARTIs) in our region. Based on the patient’s clinical presentation, it’s likely that they suffered from an adenovirus infection. The patient practiced self-care by resting, drinking more fluids, and taking over-the-counter painkillers. After thoroughly discussing the case, the patient was advised to keep monitoring their symptoms and seek medical attention if they worsen or new ones arise. A follow-up assessment was suggested to track any changes in vitamin D levels. The patient continued taking 5,000 IU supplements daily for four weeks, and the final measurement of her [25(OH)D)] serum level was 132 nmol/l. The patient’s ARTI symptoms gradually improved over a few weeks, eventually leading to a full recovery.

Discussion

The present case study raises important questions regarding the relationship between vitamin D levels and acute respiratory tract infections (ARTIs). Research indicates that insufficient vitamin D is linked to a greater likelihood of respiratory infections, including ARTIs. However, the correlation between ARTIs and vitamin D levels is an ongoing area of debate and investigation.

A recommendation was made for this participant to take a vitamin D supplement to address her insufficient vitamin D levels. The primary goal was to achieve a level of 75 nmol/l, with a secondary target of 120 nmol/l within two months of starting the supplement. However, during the course of treatment, her vitamin D levels unexpectedly decreased. This decline was noted on the seventh day of an ongoing ARTI, suggesting a potential connection between ARTIs and vitamin D metabolism.

There are various factors that can impact the levels of vitamin D in the body when someone experiences an ARTI. During an ARTI, the immune system releases inflammatory cytokines and mediators, such as TNF-alpha and IL-6. These substances can interfere with the 25-hydroxylase (CYP2R1), 1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1) that are responsible for the synthesis and metabolism of vitamin D. This disruption may result in reduced vitamin D levels (22,23).

Research has furthermore demonstrated that the attachment of pro-inflammatory cytokines to specific cells triggers the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. This activation has been found to impede the expression of the vitamin D receptor (VDR), which is crucial for the physiological effects of vitamin D. Consequently, a decrease in VDR expression may impair the cellular response and diminish the immunomodulatory effects of vitamin D (24-26).

It is also possible that the reduced breakdown of vitamin D during immune activation is caused by the heightened production of reactive oxygen and nitrogen species within immune cells during ARTIs (27,28).

Other studies claim that the body uses [25(OH)D] in an effort to heal itself, thus lowering [25(OH)D] levels by converting it to [1,25(OH)2D)] to modulate the inflammation. Regarding the argument that vitamin D reduces inflammation, some in vitro studies indicate that [1,25(OH)2D)] has anti-inflammatory effects (29-31). The mechanisms by which [1,25(OH)2D)] reduces inflammation are multiple. Overall, there is a shift from a more inflammatory T-helper 1 (Th1)/Th17 response to a less inflammatory Th2/Treg response (32). This effect lowers the release of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukins IL-2 and IL-12, but elevates the production of anti-inflammatory cytokines such as IL-10 (33).

Recent research suggests that adequate levels of vitamin D can enhance the genetic expression of antimicrobial peptides in various cells, including human monocytes and neutrophils. Furthermore, individuals with higher vitamin D levels tend to exhibit better lung function when compared to those with lower levels of the vitamin (28,34).

The conclusions drawn from this case study are in line with current research that underscores the intricate connection between respiratory infections and vitamin D levels. Previous studies investigating the correlation between vitamin D levels and ARTIs have yielded conflicting results. While certain studies indicate an inverse relationship between vitamin D levels and the frequency or severity of respiratory infections, other studies have not consistently established this association. In their recent investigation, Bradley et al. analyzed the link between vitamin D levels and ARTIs in infants (35). They found that vitamin D insufficiency increased the risk of ARTIs and recommended vitamin D supplementation as a preventive measure. Their study did not, however, explore the impact of ARTIs on vitamin D levels.

A recent research study conducted by Saeed et al. , thoroughly reviewed and analyzed the impact of vitamin D supplementation on respiratory tract infections. The findings revealed that individuals who were vitamin D deficient and took vitamin D supplements had a reduced likelihood of developing ARTIs (36). However, the study did not investigate how ARTIs affect vitamin D levels. Another systematic evaluation, conducted by Xiao et al. in 2015 (12), further delved into this topic and concluded that vitamin D supplementation therapy was ineffective in preventing pediatric ARTIs. Studies conducted by Martineau et al. (37) and Pham et al. (38) have shown that keeping serum levels of [25(OH)D] high can aid in preventing ARTIs. In addition, micronutrients, such as vitamin D, vitamin C, and zinc, as noted by Abioye et al. (39), may decrease the occurrence and intensity of ARTIs. While the trial conducted by Jolliffe et al. (40) exhibited significant heterogeneity, it did indicate that vitamin D supplementation may slightly reduce the risk of ARTIs in comparison to the control group.

Study limitations. First, we exclusively relied on clinical symptoms for identification of the virus in the participant’s blood, without utilizing antibody testing or sequencing. While we acknowledge that this may be a potential limitation, the symptoms were evident and widespread during the study period, providing adequate evidence of an ongoing ARTI. Second, we recognize that our measurement timing may have influenced the evaluation of vitamin D serum levels at the end of the second month of supplementation. Our standard protocol is to conclude supplementation studies in April to avoid any potential impact from the body’s natural production of vitamin D in the skin. However, in this particular case, we made an exception to verify the effectiveness of supplementation during the ARTI’s fading period.

It’s worth noting that the participant spent time in Pilsen, West Bohemia, where vitamin D production in the skin is approximately 50% lower in May than during the summer season. Moreover, the participant was in the final stages of preparing for an upcoming examination period commencing in June, and spent most of her time indoors studying with limited opportunity to venture outdoors. Therefore, we can confidently dismiss the possibility of elevated vitamin D levels originating from exposure to direct sunlight. Considering the participant’s lifestyle, any increase in vitamin D can only be marginally associated with any direct contact with sunlight, if at all.

Conclusion

This research holds significance as it reveals a decline in serum vitamin D levels in a medically compliant individual who was under regulated vitamin D supplement intake and observation. The participant, a cooperative medical student, exhibited a clear correlation between the decrease in vitamin D levels and the occurrence of ARTI.

However, due to the study’s constraints, it is not feasible to accurately pinpoint the exact cause of the decline or extrapolate the outcomes to the broader population based on a single observation.

Nonetheless, this discovery emphasizes the importance of focusing on ARTIs in future vitamin D supplementation research, which is scheduled to continue over the next two years during the winter season.

Conflicts of Interest

The Authors declare no conflicts of interest in relation to this study.

Authors’ Contributions

Conceptualization, V.Š; methodology, R.K, E.D; investigation, E.D; writing original draft preparation, E.D, M.K, R.K; writing, review, and editing, O.T, R.K, V.Š; supervision, V.Š. All Authors have read and agreed to the published version of the manuscript.

Acknowledgements

The Authors gratefully acknowledge the participant for her help and assistance at every stage of this research.

Funding

This study was supported by the Ministry of Health, Czech Republic-conceptual development of research organization (Faculty Hospital in Pilsen-FNPl, 00669806), BBMRI-CZ: Biobank net-work – a versatile platform for the research of the etiopathogenesis of diseases CZ.02.1.01/0.0/0.0/16_013/000167 and LM2015089, and by the “Cooperatio” Program, research area Pharmaceutical Sciences.