05 Jul Kids Health & Vitamin D
- Feeling seen, heard and supported during times of struggle has been shown to enhance patient immune function (p<0.001). In a meta-analysis and systematic review of 56 randomised-controlled clinical trials, psychological support provided to 4,060 patients (e.g. cognitive-behavioural counselling) led to a 14.7% improvement in systemic immune function.1 Such clinical outcomes were evidenced with higher immune cell counts (CD+4 lymphocytes), as well as an 18% decrease in pro-inflammatory cytokines (interleukin-6) associated with weakened immune function. These results persisted for six months following treatment, evidencing the therapeutic value of interpersonal support to promote healthy immune function.
- In obese patients, reducing body mass index (BMI) has been shown to enhance the adaptive immune response involved in fighting infection.2 In a randomised-controlled clinical study, subjects underwent a weight-loss program involving 135 minutes of aerobic exercise weekly combined with a calorie-restricted diet (i.e. 1,200 kcal/d) for 12 weeks. Compared to the control group (who received no intervention), the treatment group achieved a four-point reduction in BMI (31.73 ± 2.68 reduced to 27.86 ± 2.24), which was associated with enhanced levels of cluster of differentiation 4 (CD+4) and CD+8 lymphocytes (p<0.05). Such evidence supports the importance of addressing metabolic disease with diet and lifestyle interventions to promote a more effective immune response.
- A poor sense of smell is common amongst older people, and now, research has found it may have broader implications for immune health. In a prospective cohort study, 2,494 participants aged 71 to 82 years were tested for olfactory function and monitored over 13 years. Outcomes of the study indicated that patients with poor sense of smell were 37% more likely to develop pneumonia compared to patients with good olfaction scores (p<0.019).3 These findings provide evidence that poor sense of smell is associated with a long-term risk of pneumonia, however further research is required to understand its implications in clinical practice.
Fortifying the Immune Response on All Sides: A review of Vitamin D in ActionFollowing its endogenous synthesis or supplementation, vitamin D binds to vitamin D receptors (VDRs), which activate several genes and transcription proteins involved in modulating immune cell activity,6 including: • Cluster of differentiation 14 (CD14) glycoproteins; • Thymocyte selection associated family member 2 (THEMIS2) genes; • Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4) genes; and, • Leucine-rich repeat-containing protein 25 (LRRC25).
Checks and Balances: How Vitamin D Moderates the Immune Response to Manage InfectionsBeyond stimulating immune activity, vitamin D plays a key role in immune modulation, which is fundamental to managing infectious disease. Vitamin D-sensitive LILRB4 genes promote differentiation of T regulatory cells (Tregs),11 which are key modulators of the immune response.12,13 Notably, Tregs downregulate excessive inflammatory responses triggered by viral disease, subsequently reducing infection-associated tissue damage.14Comparably, LRRC25 activation in monocytes, dendritic cells and T lymphocytes regulates cytokine production to supress inflammation,15 thereby limiting the degree of inflammatory damage to the body. As such, sufficient levels of vitamin D are required to coordinate several events that enhance and modulate immune function.
Tried and True: Clinical Research Supports Vitamin D for Minimising Infectious RiskWhen it comes to human clinical trials, positive effects on immunity have been observed following vitamin D supplementation in both healthy and immunocompromised patients.16,17 For example, in a systematic review and meta-analysis, 11,321 infants, children and adults with and without pre-existing illness were prescribed supplemental vitamin D (between 800 IU/d and 2,000 IU/d). Outcomes of the study revealed a reduction in acute respiratory tract infection risk (p<0.001).18 Interestingly, greater protective effects were seen in individuals with baseline vitamin D deficiency (<25 nmol/L; p<0.006), emphasising Vitamin D’s ability to support a protective immune response in deficient populations susceptible to illness. Similar findings have also been observed in immunocompromised patients with inflammatory bowel disease and insufficient vitamin D (i.e. <50 nmol/l); highlighting the importance of optimising vitamin D status to offset infectious risk.19 Research further supports the immune-enhancing effects of vitamin D in seriously ill patients without vitamin D insufficiency (i.e. >50 nmol/L). As an example, in 208 paediatric patients with invasive Candida albicans infection, 300 IU/d of vitamin D significantly lowered growth of candida, measured in blood and urine samples, as well as reducing patient ICU admission time.20 This demonstrates the clinical value of prescribing vitamin D to enhance immunity and minimise infectious load, subsequently reducing hospitalisation length and illness severity.
Vitamin D: A Key Player in the Fight Against COVID-19To date, research has yielded promising results for the role of vitamin D in management of COVID-19. In one randomised clinical trial looking at the effects of high-dose vitamin D3 in 50 hospitalised COVID-19 patients, only 2% of cases required intensive care unit (ICU) admission compared to 50% in the non-supplemented group (p<0.001).21 Clinical data has also revealed that vitamin D insufficiency (<50 nmol/L) is associated with raised inflammatory markers+ and longer COVID-19 hospitalisation time. Additionally, these presentations were more prevalent in individuals with hypertension and cardiovascular disease; complicating COVID-19 recovery outcomes in these patients.22 Collectively, these findings suggest that vitamin D improves COVID-19 outcomes, while insufficient levels of vitamin D can compromise immune function, particularly in patients with comorbid diseases, increasing infection severity.
Set Your Patients’ Immune Function up for SuccessWhen acute and chronic infections present clinically, vitamin D may be the key to shifting patient immunity in the right direction, paving the way forward for a stronger immune system. Vitamin D’s ability to enhance and modulate the immune response has been demonstrated in numerous population studies and clinical trials, highlighting its capacity to prevent infectious onset and severity. As such, Practitioners should consider vitamin D supplementations as a core treatment strategy to support immune function, particularly for infection and in immunocompromised individuals.
1 Shields GS, Spahr CM, Slavich GM. Psychosocial interventions and immune system function: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry. 2020 Oct 1;77(10):1031-1043. doi: 10.1001/jamapsychiatry.2020.0431. 2 Al-Sharif FM, Abd El-Kader SM, Neamatallah ZA, AlKhateeb AM. Weight reduction improves immune system and inflammatory cytokines in obese asthmatic patients. Afr Health Sci. 2020 Jun;20(2):897-902. doi: 10.4314/ahs.v20i2.44. 3 Yuan Y, Luo Z, Li C, Pinto J, Shiroma E, Simonsick E, et al. Poor olfaction and pneumonia hospitalization among community-dwelling older adults: a cohort study. Lancet Healthy Longev. 2021 May 1;2(5):275-282.doi: 10.1016/S2666-7568(21)00083-0 4 Koivisto O, Hanel A, Carlberg C. Key Vitamin d target genes with functions in the immune system. Nutrients. 2020 Apr 19;12(4):1140. doi: 10.3390/nu12041140. 5 Pereira M, Dantas Damascena A, Galvão Azevedo LM, de Almeida Oliveira T, da Mota Santana J. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2020 Nov 4:1-9. doi: 10.1080/10408398.2020.1841090. 6 Koivisto O, Hanel A, Carlberg C. Key Vitamin d target genes with functions in the immune system. Nutrients. 2020 Apr 19;12(4):1140. doi: 10.3390/nu12041140. 7 Koivisto O, Hanel A, Carlberg C. Key Vitamin d target genes with functions in the immune system. Nutrients. 2020 Apr 19;12(4):1140. doi: 10.3390/nu12041140. 8 Zhu Y, Yao S, Chen L. Cell surface signaling molecules in the control of immune responses: a tide model. Immunity. 2011 Apr 22;34(4):466-78. doi: 10.1016/j.immuni.2011.04.008. 9 Zhu Y, Yao S, Chen L. Cell surface signaling molecules in the control of immune responses: a tide model. Immunity. 2011 Apr 22;34(4):466-78. doi: 10.1016/j.immuni.2011.04.008. 10 Koivisto O, Hanel A, Carlberg C. Key Vitamin d target genes with functions in the immune system. Nutrients. 2020 Apr 19;12(4):1140. doi: 10.3390/nu12041140. 11 Koivisto O, Hanel A, Carlberg C. Key Vitamin d target genes with functions in the immune system. Nutrients. 2020 Apr 19;12(4):1140. doi: 10.3390/nu12041140. 12 Fisher SA, Rahimzadeh M, Brierley C, Gration B, Doree C, Kimber CE, et al. The role of vitamin D in increasing circulating T regulatory cell numbers and modulating T regulatory cell phenotypes in patients with inflammatory disease or in healthy volunteers: A systematic review. PLoS One. 2019 Sep 24;14(9):e0222313. doi: 10.1371/journal.pone.0222313. 13 Mocanu V, Oboroceanu T, Zugun-Eloae F. Current status in vitamin D and regulatory T cells–immunological implications. Rev Med Chir Soc Med Nat Iasi. 2013 Oct-Dec;117(4):965-73. PMID: 24502077. 14 Veiga-Parga T, Sehrawat S, Rouse BT. Role of regulatory T cells during virus infection. Immunol Rev. 2013 Sep;255(1):182-96. doi: 10.1111/imr.12085. 15 Koivisto O, Hanel A, Carlberg C. Key Vitamin d target genes with functions in the immune system. Nutrients. 2020 Apr 19;12(4):1140. doi: 10.3390/nu12041140. 16 Arihiro S, Nakashima A, Matsuoka M, Suto S, Uchiyama K, Kato T, et al. Randomized trial of vitamin d supplementation to prevent seasonal influenza and upper respiratory infection in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2019 May 4;25(6):1088-1095. doi: 10.1093/ibd/izy346. 17 Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15;356:i6583. doi: 10.1136/bmj.i6583. 18 Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15;356:i6583. doi: 10.1136/bmj.i6583. 19 Arihiro S, Nakashima A, Matsuoka M, Suto S, Uchiyama K, Kato T, et al. Randomized trial of vitamin d supplementation to prevent seasonal influenza and upper respiratory infection in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2019 May 4;25(6):1088-1095. doi: 10.1093/ibd/izy346. 20 Xie J, Zhu L, Zhu T, Jian Y, Ding Y, Zhou M, et al. Vitamin D-supplemented yogurt drink reduces Candida infections in a paediatric intensive care unit: a randomised, placebo-controlled clinical trial. J Hum Nutr Diet. 2019 Aug;32(4):512-517. doi: 10.1111/jhn.12634. 21 Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, Alcalá Díaz JF, López Miranda J, Bouillon R, at al. Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. J Steroid Biochem Mol Biol. 2020 Oct;203:105751. doi: 10.1016/j.jsbmb.2020.105751. 22 Hernández JL, Nan D, Fernandez-Ayala M, García-Unzueta M, Hernández-Hernández MA, López-Hoyos M, et al. Vitamin D status in hospitalized patients with SARS-CoV-2 infection. J Clin Endocrinol Metab. 2021 Mar 8;106(3):e1343-e1353. doi: 10.1210/clinem/dgaa733.