Abstract
Background
Vitamin D supplementation is essential for health, yet its full benefits and optimal use remain incompletely understood, particularly given the global prevalence of deficiency, which affects around 50% of the population, with higher rates in high-latitude regions and among individuals with darker skin. This systematic review synthesizes evidence on the health outcomes of vitamin D supplementation in Africa, addressing gaps in regional and demographic-specific research.
Methods
A comprehensive literature search was conducted using PubMed, Scopus, Epistemonikos, and Google Scholar, limited to English-language publications without date restrictions. Two independent reviewers evaluated study eligibility, data quality, and risk of bias. The findings were reported in accordance with PRISMA guidelines, employing narrative synthesis and meta-analyses to compare the effects of vitamin D supplementation against control groups. Heterogeneity and publication bias were assessed using Egger’s regression and Q statistics.
Results
The review included 14 randomized controlled trials from 9 African countries, involving 11,259 participants. Half of the studies reported health benefits associated with vitamin D supplementation. Meta-analysis of seven studies demonstrated significant increases in serum vitamin D levels (odds ratio = 6.78, p < 0.001) and reduced viral load in patients with human immunodeficiency virus (odds ratio = 1.63, p = 0.033). However, supplementation did not significantly affect weight gain (odds ratio = 1.1, p = 0.18) or mortality rates in patients with tuberculosis and human immunodeficiency virus (odds ratio = 0.971, p = 0.638). Improvements in disease symptoms and biochemical markers were observed (odds ratio = 2.28, p = 0.028), with no significant heterogeneity or publication bias. Subgroup analysis was constrained by the diversity of diseases and insufficient studies.
Conclusions
Vitamin D supplementation showed significant benefits in half of the studies, elevating serum levels and reducing viral load in HIV patients. However, it did not affect weight gain or mortality in TB and HIV patients. While symptom and biomarker improvements were noted, further research is needed to explore subgroup effects and optimize strategies.
Trial registration
PROSPERO registration number CRD42024620729.
Supplementary Information
The online version contains supplementary material available at 10.1186/s40795-025-01046-w.
Keywords: Vitamin D, Supplementation, Health outcomes, Systematic review, Africa
Introduction
Vitamin D supplementation involves taking dietary supplements to address deficiencies and improve health outcomes. This practice is gaining attention for its potential benefits in various health conditions, including diabetes, asthma, and inflammatory diseases [1].
Cholecalciferol is used to prevent and treat vitamin D deficiency, with tablets and capsules making up only 10% of the market in some areas. More common are active forms like calcitriol and alfacalcidiol, often paired with calcium, accounting for 46.5% and 43% of products, respectively [2]. Injectable vitamin D3 provides an alternative to oral supplements, while transdermal film-forming solutions offer a new skin-based absorption method [3].
Vitamin D deficiency is a widespread issues in Africa, especially among vulnerable populations like children and people with chronic disease [4, 5]. Studies have shown that 50.06% of healthy children in Sub-Saharan Africa and 39.36% of sick children are affected by vitamin D deficiency [5]. Among HIV infected African migrants, 92% show a signs of vitamin-deficient disorder, highlighting the link chronic illness and nutrient deficiency [6]. In African countries, vitamin D inadequacy and insufficiency are common among the general population with demonstrated effects on the human body and potential associations with various health consequences [7, 8]. Vitamin D is the active metabolite of vitamin D acting as a hormone that can attach to the vitamin D receptor, found in many human cells, including immune, muscle, and bone cells [9]. The active form of vitamin D has been shown to have immunomodulatory effects by reducting of lymphocyte proliferation and inhibiting of the production of pro-inflammatory cytokines [10].
Epidemiological studies have shown that evidence of vitamin D deficiency levels below 30 nmol/L) [11] and levels between 30 to < 50 nmol/L) are associated with higher mortality from all cause-specific illness like respiratory, cardiovascular, and cancer diseases. While some believe that taking vitamin D supplements is unnecessary [12], Others, argue that, vitamin D is a crucial nutrient with numerous health benefits extending beyond bone health. It plays a vital role in immune function, mental health, and overall well-being, helping to prevent diseases, enhance mood, and improve immune responses against infections. Vitamin D Supplementation has been shown to impact mental disorders like depression and anxiety, as well as neurological conditions such as Alzheimer's [13–16].
Evidence for the effectiveness of vitamin D in reducing mortality and morbidity is mixed, with some studies showing a slight reduction in all-cause mortality but no significant cardiovascular benefits [17]. The evidence supporting clear benefits of vitamin D supplementation is inconsistent, particularly regarding its effects on various health conditions [18].
There are a number of clinical and public health needs that are still inadequately addressed by vitamin D supplementation. Recognizing its significance to bone health and potentially other skeletal benefits but overlooking its wider health importance. This information can lead to fragmented public health program and guidance. Without this information, recommendations and public health strategies may not be properly informed. On the other hand, some argue that focusing on the skeletal benefits justified to due direct public health implication of wide spread problem [19–21]. Therefore, the primary objective of this study was to investigate whether the intake of vitamin D supplements is associated with health outcome or not.
Methods
This systematic review and meta-analysis were guided by the PRISMA 2020 checklist [22]. The systematic review protocol title has been registered on PROSPERO (CRD42024620729).
Eligibility criteria
This synthesized evidence includes all age groups receiving vitamin D tablets and injections of vitamin D3 and vitamin D2 in any of its chemical forms with international standard doses, low or high doses. These assessments include all known studies conducted in Africa assessing the health impacts of vitamin D supplementation. All randomized control trial (RCT) study design conducted in Africa are included for synthesized evidence. Studies comparing Africa with other continents were excluded from this review.
Information sources
Literature search for the study articles was conducted using various leading academic databases and internet websites, such as PubMed (MEDLINE), the Cochrane Library, Scopus, Epistemonikos, and Google Scholar. The sources were selected to include comprehensive and systematic searching of the literature and cover a wide range of biomedical and scientific research studies. The search was completed on December 18, 2024, to capture the most current and relevant studies for review. This multi-source approach aimed to minimize bias and maximize the power of evidence gathered. All review processes and methods were registered with pre-specified protocols that were registered with PROSPERO international register of systematic review (ID = CRD42024620729).
Search strategy
Various search strategies were used to identify relevant articles for this review. A comprehensive search was carried out across multiple databases, including PubMed, Scopus, Epistemonikos, and Google Scholar. The review focused on English-language, peer-reviewed articles and international reports, with emphasis on randomized clinical trials conducted in the African context.
Selection process
The selection process based on pre-established criteria that developed by team of researchers. All articles reported health outcomes due to vitamin D supplementation were exported to EndNote version 20. After duplicates were removed by EndNote version 20, all full text articles were screened for eligibility by two researchers (T.D, Y.M) independently. Any disagreement between reviewers were resolved by a third person (B.D). This review study was structured and written based on the PRISMA 2020 checklist [22].
Data extraction
Data extraction tools were created to gather information about study design and methods, participant demographics and baseline characteristics, sample size, numbers of events or measures of effect, (Hazard ratio, Odds ratio, confidence interval, mean difference, etc. from the included studies. Two individuals independently screened records for inclusion while researchers were blinded during data extraction. Two people separately extracted the data, with a third person arbitrating any discrepancies between their assessments. Study investigators were contacted for unreported data if significant information was missing in documentation. Data was extracted using an Excel sheet.
Data items
collected included all age groups with healthy and disease individuals participating in either experimental or placebo treatment groups. Authors of articles, country of origin, study design used, age group of the population, sex, total sample size (experimental vs Placebo), doses Vitamin D2 or D3 supplemented (Experimental group), route of administration, population health condition, reported health outcomes, final mean and standard deviation (Experimental vs placebo) Groups at end measurement, mean difference, p-value of the population and 95% CI were the main variables extracted from 14 articles for systematic review and meta-analysis. All outcome were measured and reported as positive health effects, no health effects and negative health effect from each finding presented in a summary table. Among the 14 articles, 5 articles that reported end measures (Sample, Mean and Standard deviation) for both experimental and placebo groups were further analyzed in a meta-analysis. Any missing or unclear information was reported in the systematic review report and not included in the meta-analysis.
Study risk of bias assessment
All characteristics, such as study design to assess the outcomes of an intervention (population studied, intervention given, comparator chosen, and outcomes measured) were assessed. Randomization and blinding methods and procedures, baseline characteristics of each study groups, differences between study groups that could affect outcomes, power of calculation, results reported for each outcome in each study group at each follow-up interval, statistical tests used, p-value with 95% confidence interval report and potential source of biased risk were checked. Furthermore, the report of treatment effect, similarity of study participants, study limitation and resource used were assessed based on the Cochrane Risk of Bias tool version 2" (RoB-2) [23]. Two reviewers independently assessed the quality of the 14 articles using the Cochrane Risk of Bias tool version 2" (RoB-2) [23]. Among 14 articles, 13 were rated as high quality and one was rated as medium quality paper based on Critical Appraisal Skills Program [24] assessment checklist: A-D (1–11) criteria for quality assessment for vitamin D supplementation health outcomes articles. The result of quality assessment was represented by (Yes = 1, No = 0). Once reviewer finished the quality assessment of the whole article, all “Yes” and “No” responses added together and rated as (0–5 = Low quality, 6–8 = Medium quality and > = 9 High quality). From the quality assessment of the retrieved articles, 13 were categorized as high-quality, with one article categorized as medium-quality. The grading reflects strict methodological quality standards that informed the appraisal to ensure the majority of included evidence adhered to stringent tests for reliability, validity, and appropriateness. High-quality studies had robust study designs, clear methodology, and stringently documented outcomes, hence having maximum importance to guide evidence-informed conclusions.
Statistical analysis
A meta-analysis was conducted using a random effect model to pool the odds ratio (OR) for health outcomes in both the intervention and control arm. This was achieved by comparing reported differences in means and proportions of various health outcomes between the two groups. Statistical heterogeneity between the studies was evaluated using Cochran’s Q statistic and the I2 statistic. To assess publication bias, funnel plots and Egger's regression tests were utilized. A trim-and-fill analysis was also performed to recalculate the intervention effect, excluding studies that may introduce publication bias. Only studies that reported complete participant data (i.e., those that used intention-to-treat) were included in the main effects. Data from randomized controlled trials (RCTs) were used exclusively to ensure the reliability of the findings. Statistical analysis was conducted using Comprehensive Meta-Analysis software version 4.
Result
Study selection
A total of 20,287 articles and documents were exported to Endnote version 20. Prior to screening, 1,395 articles were removed due to duplication. Following pre-defined eligibility criteria, two authors (TD and YM) independently reviewed 18,892 articles and documents, with 18,833 being excluded based on the title and abstract screening. Any disagreements between reviewers were resolved by BD. A total of 59 articles were sought retrieval, with 55 assessed eligibility and 4 articles not retrieved. The screening and identification process followed the PRISMA 2024 [25] guideline for reporting systematic reviews (Fig. 1).
Fig. 1.
Schematic presentation for assessing health outcomes of Vitamin D supplementation in Africa: Screening and Identification PRISMA flow diagram 2024
Study characteristics
We included a total of 14 articles for systematic and meta-analysis from 9 (nine) different African countries with various geographical locations. These included four articles from South Africa [26–29], two from Egypt [30, 31], Ethiopia [32], Algeria [33], Botswana [34], Tunisia [35] Guinea-Bissau [36], Libya [37] and two from Tanzania [38, 39]. All the studies included in this review were randomized trials, totaling 5,653 experimental groups and 5,606 placebo groups. Participants included, 4126 males and 5972 females, and 1161 individuals whose sex was not specified. Only 14.3% of Vitamin A supplementation was administered intramuscularly, and 93% of the studies considered high-quality based on the RoB-2 assessment checklist [24] (Table 1).
Table 1.
Descriptive summary of 14 studies included in a systematic review and meta-analysis on health outcome of Vitamin D supplementation in Africa, 2025, 2025
| Authors | Year of Publication | Countries | Age groups | Sample size | Sex | Doze | Root of Admission | Study Quality status | Outcomes reported | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Experimental | Placebo | Male | Female | Experimental | |||||||
| Akrour-Aissou, Cherifa, et al | 2020 | Algeria | < 2Years | 125 | 25 | 87 | 63 | 500,000 IU/W | intramuscular | Medium | Serum Vitamin D level |
| Steenhoff, Andrew P., et al | 2015 | Botswana |
5–50.9 Years |
30 | 30 | 30 | 30 | 500,000 IU/W | Oral | High | Serum Vitamin D level, weight gain and Viral suppression |
| Hassan, Rasha Hassan Abdelhalim, et al | 2023 | Egypt |
30–35 years |
10 | 0 | 0 | 10 |
200,000 IU/ day |
Oral | High | Weight gain |
| Gad, Ahmed Ibrahim, et al | 2020 | Egypt | 18–60 years | 40 | 40 | 500,000 IU/W | intramuscular | High | Improve disease status | ||
| Ashenafi, Senait, et al | 2019 | Ethiopia | > 18 Years | 95 | 102 | 40 | 157 | 5000UI/day | Oral | High | Improve disease status and viral suppression |
| Wejse, Christian, et al | 2009 | Guinea-Bissau | > 18 Years | 187 | 178 | 25,000 IU/W | Oral | High | Survival TB and HIV patient | ||
| Sarah Elfituri | 2024 | Libya | > 18 Years | 48 | 20 | 17 | 51 | 500,000 IU/W | Oral | High | Improve disease status, serum vitamin D |
| Middelkoop, Keren, et al | 2024 | South Africa | 6–11 Years | 829 | 853 | 802 | 880 | 10000 IU/W | Oral | High | serum vitamin D, weight gain, other health outcomes |
| Middelkoop, Keren, et al | 2024 | South Africa | 6–11 Years | 228 | 222 | 216 | 234 | 10000 IU/W | Oral | High | serum vitamin D, weight gain, other health outcomes |
| Middelkoop, Keren, et al | 2023 | South Africa | 6–11 Years | 829 | 853 | 802 | 880 | 10,000 IU/W | Oral | High | prevent tuberculosis infection and other health outcomes |
| Middelkoop, Keren, et al | 2024 | South Africa | 6–11 Years | 829 | 853 | 802 | 880 | 10000 IU/W | Oral | High | serum vitamin D, weight gain, other health outcomes |
| Muhihi, Alfa, et al | 2022 | Tanzania | > = 18 Years | 345 | 371 | 5000 IU/W | Oral | High | Viral Suppression, weight gain, HIV survival | ||
| Sudfeld, Christopher R., et al | 2020 | Tanzania | > = 18 Years | 2001 | 1999 | 1265 | 2735 | 50,000 IU/W | Oral | High | TB and HIV survival, serum vitamin D |
| Hela, Abroug, et al | 2023 | Tunisia | > 18 Years | 57 | 60 | 65 | 52 | 200,000 IU* | Oral | High | TB and HIV survival, Improved disease status |
| Total | 5,653 | 5,606 | 4,126 | 5,972 | |||||||
Abbreviation: IU/W international unit per week, IU/day international unit per day, TB Tuberculosis, HIV Human Immune Deficiency virus
Health outcome of vitamin D supplementation
Health outcome 1: positive health outcome
Among 14 studies, 50% reported that vitamin D supplementation elevated serum 25 (OH) D3 concentrations in all age groups [26, 30, 31, 33, 34, 36, 39]. Synthesis of the evidence indicated that vitamin D supplementation improve positive effect on the overall functional state of the body [30]. It was effective in improving laboratory and fibro scan parameters of liver disease in non-alcoholic adult with liver disease patients [31], had a positive impact on rheumatoid arthritis patients [37], positive effect on long jump distance [27] and positive health effect for the prevention of pulmonary tuberculosis [39]. In addition, 14.3% of the studies revealed that vitamin D supplementation had positive health effect for HIV patients [34, 39].
Health Outcome 2: has no health benefit
Vitamin D supplementation had no impact on health effects on HIV viral load, T-cell counts, BMI, or MUAC [32]. It did not improve clinical outcome among patients with TB [29, 36], did not influence growth, body composition, pubertal development or Spiro-metric outcomes [26], had no effect on grip strength [27], no effect on serum concentrations of bone turnover markers [29], did not affect the risk of HIV progression, viral suppression, common morbidities, weight-related indicators, or depression among adults initiating ART [30, 34, 38], had no overall effect on the risk of mortality [39] and had not a beneficial effect on recovery delay among COVID-19 patients [35].
Health outcome 3: Negative health effect
Two studies reported vitamin D supplementation had a negative health impact. Vitamin D supplementation had a negative effect on exercise-induced bronchoconstriction (EIB) (27) and suppressed serum PTH concentrations in HIV-uninfected individuals (29).
Meta-analysis
Improvement in serum vitamin D levels
Seven studies provided data for 6,335 participants; 3,230 received vitamin D supplementation and 3,105 received placebo drug (the control conditions). The vitamin D supplementation dose in the trials ranged from 4,000 IUs to 200,000 IUs. Additionally, the follow-up periods ranged from 2 weeks to 12 months. Individual in the Vitamin D supplementation arm showed significantly higher serum vitamin D levels (OR = 6.78; 95%CI: 5.27–8.23, p < 0.001) than individuals in the control groups (Forest plot 1). There was no statistically significant between studies heterogeneity (Q = 6.9, p = 0.371, I2 = 7.51%) or evidence of publication bias (Egger’s p = 0.346).
Forest plot 1.
Meta-analysis of seven randomized controlled trial vitamin D supplementation studies showing improvement in serum vitamin D levels in Africa, 2025
Viral suppression
Data from four randomized controlled trials (RCTs) were available for 1,338 individuals (657 in the intervention group and 681 in the control group) for the study of the impact of vitamin D supplementation on HIV/AIDS disease progression. HIV/AIDS patients who received vitamin D supplementation achieved significantly lower viral load than those patients in the control arms (OR = 1.63, 95%CI: 1.04 – 2.56, p = 0.033). The observed between studies heterogeneity was not statistically significant (Q = 6.9, p = 0.075, I2 = 56.5%). There was also no evidence of the risk of publication bias (Egger’s p = 0.096) (Forest plot 2).
Forest plot 2.
Meta-analysis of four randomized controlled trial vitamin D supplementation studies showing viral suppression in Africa, 2025
Weight gain in patients
We also examined the effect of vitamin D supplementation on the nutritional status of children and adolescents. Data of 2,823 individuals (1,391 in the intervention and 1,432 in the control arms) was available from four studies. Weight gain among individuals receiving vitamin D supplementation was not statistically different from those in the control arm (OR = 1.1; 95%CI: 0.96–1.26, p = 0.18). We found no evidence for statistically significant between studies heterogeneity (Q = 0.76, p = 0.693, I2 = 0.0%) or risk of publication bias (Egger’s p = 0.821) (Forest plot 3).
Forest plot 3.
Meta-analysis of four randomized controlled trial vitamin D supplementation studies on weight gain in Africa, 2025
Survival in TB and HIV patients
Three RCTs that provided data for 5,081 individuals (2,533 in the intervention and 2,548 in control arms) were used in the study to investigate the effect of vitamin D on survival of TB and HIV/AIDS patients. There was no statistically significant difference in mortality rates between individuals receiving vitamin D supplementation compared to those in the control arms (OR = 0.971, 95%CI: 0.86 – 1.1, p = 0.638). There was no evidence for between study heterogeneity (Q = 1.56, p = 0.459, I2 = 0.0%) or publication bias (Egger’s p = 0.405) (Forest plot 4).
Forest plot 4.
Meta-analysis of three randomized controlled trials vitamin D supplementation studies on survival in TB and HIV Patients in Africa, 2025
Improved disease status
We also assessed the effect of vitamin D on recovery rates or improved prognoses. Four RCTs provided data for 630 individuals (332 in intervention and 298 in control arms) for this study. Vitamin D supplementation was associated with reduction in disease symptoms and biochemical markers (OR = 2.28; 95%CI: 1.09 – 4.76, p = 0.028). A statistically significant heterogeneity was observed between studies (Q = 12, p = 0.01, I2 = 75). There was no evidence for publication bias (Egger’s p-value = 0.734). Given the difference in symptoms for the associated disease (e.g., COVID-19, Rheumatoid Arthritis, and TB) and the limited number of studies for each, subgroup analysis was not possible (Forest plot 5).
Forest plot 5.
Meta-analysis of four randomized controlled trial vitamin D supplementation studies on improved disease status in Africa, 2025
Other health outcomes
There were other health outcomes reported in the studies included. However, due to the limited number of studies for each outcome, pooled effects could not be estimated. Two RCTs that assessed the effect on CD4 cell count change in HIV patents both found no significant differences between HIV patients in the intervention and control arms. The effect of vitamin D supplementation on bone growth was assessed in two RCTs where both found no difference in bone growth between individuals who received vitamin D supplementation compared to those who did not. Similarly, two studies that investigated incidence rates reported no statistically significant difference between individuals in the intervention and control arms.
Risk of publication bias
In this analysis the funnel plot measure of study size indicated on the vertical axis and studies showed distributed symmetrically about the combine log odds ratio and studies evenly distributed on both side of the mean than the other (Fig. 2).
Fig. 2.
Funnel plot of standard error by log odds ratio of vitamin D supplemented and Placebo groups in Africa countries, 202
Discussion
The current systematic review synthesized evidence showed that vitamin-D intake influences health outcomes. Among 14 studies, 50% reported vitamin D supplementation elevated serum vitamin D concentrations in all age groups. This evidence is similar to another study that found vitamin D supplementation significantly increases serum vitamin D levels [40].
In this synthesized evidence vitamin D supplementation had a positive impact on rheumatoid arthritis patients, supported by study conducted in China and Italy. Vitamin D supplementation seemed to be an effective intervention for patients with rheumatoid arthritis with different doses and durations of intervention producing various effects [41–43]. This variability may be due to deficiency status and individual difference in bio-absorption.
The findings of this synthesized evidence are consistent with research from India and Australia, which found a significant correlation between vitamin D levels and the risk of nonalcoholic fatty liver disease. A monthly single intramuscular dose of 200,000 IU of vitamin D supplements was also effective in improving fibro scan [44], Vitamin D supplementation has been associated with improvements in liver function tests [45]. However, in hepatitis C virus cirrhotic patients, while vitamin D levels improved, there was no significant effect on liver function parameters [46].
In the current synthesized evidence vitamin D supplementation had a positive effect on long jump distance and reduce fatigue which in line with study conducted in the USA that found vitamin D supplementation improve mean grip strength, and standing long jump distance [47], The supplementation of vitamin D has also been linked to a reduction in fatigue [48]. Other findings from Europe indicate that maintaining adequate levels of vitamin D can significantly improve physical performance and reduce fatigue, especially among athletes who initially present with insufficient baseline levels of the vitamin [49]. Therefore, the fact that vitamin D has been implicated as a factor in several different autoimmune diseases suggests that vitamin D might be one of the environmental factors that among others normally participates in the control of self-tolerance. The significant role of vitamin D compounds as selective immune suppressants is also illustrated by their ability to either prevent or markedly suppress.
In the current synthesized evidence two studies reported vitamin D supplementation had negative health impact on exercise induced bronchoconstriction. However, these findings have not been supported by other randomized studies, The lung is increasingly recognized as an important target tissue for vitamin D. Observational data link poor vitamin D status with several inflammatory lung diseases or impaired lung function [50, 51].
The current synthesized evidence vitamin D did not have a beneficial effect on recovery among COVID-19 patients. The other finding have compared serum vitamin D concentrations in patients with COVID-19 to individuals without COVID-19 and found a lower level (mean difference of about 12 nmol/l) in patients with COVID-19 [52], at the same time patients receiving calcifediol experienced significantly fewer ICU admissions and lower mortality rates compared to those on standard care alone, suggesting that vitamin D supplementation may enhance recovery and reduce severe outcomes in COVID-19 patients [53]. The variability in outcomes from vitamin D supplementation may stem from differences in baseline vitamin D levels, with deficient individuals showing greater benefits. Dosage, duration, and form of supplementation also influence efficacy, alongside genetic, lifestyle, and comorbidity factors. Additionally, methodological disparities in study design, sample size, and outcome measurements contribute to inconsistent findings, underscoring the need for personalized approaches and further research to establish standardized guidelines.
In the current synthesized evidence vitamin D supplementation, no effect on serum concentrations of bone turnover markers which contradicts previous studies. If vitamin D supplementation have beneficial effects on extra-skeletal health outcomes and major diseases, it is likely to have some effects on mortality, especially in older adults with poor vitamin D status. Large meta-analyses mostly involving women over 70 years old showed a 6–11% reduction in mortality [54, 55]. Research comparing serum and urine biomarkers revealed that while some markers correlated well, others did not. Suggesting that measurement methods may affect the interpretation of bone turnover markers [56]. Several possible reasons exist for this discrepancy with serum 25OHD levels being a highly confounded variable affected by various health behaviors, obesity, socioeconomic status, and education levels.
The synthesized evidence indicated that vitamin D had a positive health effect in preventing pulmonary tuberculosis, consistent with previous research linking low vitamin D levels are increased risk of pulmonary TB mortality and disease progression in HIV-infected individuals. Vitamin D3 supplements are known to be safe and effective in boosting vitamin D status [46, 48, 57, 58]. However, some current studies showed that vitamin D does not improve clinical outcome among patients with TB. Despite vitamin D's ability to strengthen the immune system, research on its effects on TB patients' clinical outcomes has produced conflicting findings. For example, vitamin D supplementation decreased TB scores and alleviated symptoms had no discernible impact on sputum conversion rates or overall treatment effectiveness [56]. The complicated nature of TB treatment, which takes into account a number of variables beyond vitamin D levels, such as illness and the existence of co-morbidities, may explain the lack of significant clinical improvement.
The synthesized evidence from a meta-analysis of seven studies shows that supplementation significantly increased serum vitamin D levels (OR = 6.78; 95% CI: 5.27–8.23, p < 0.001). These findings consistent with global research. including studies from the USA and Europe, which confirm that vitamin D supplementation effectively raises serum levels, especially in individuals with baseline deficiencies [59, 60].
Findings from four randomized controlled trials indicate that vitamin D supplementation significantly reduced viral load in HIV/AIDS patients compared to controls (OR = 1.63, 95% CI: 1.04–2.56, p = 0.033). This suggests that vitamin D may play a beneficial role in slowing HIV/AIDS disease progression, likely due to its immunomodulatory properties. These results are align with previous research emphasizing the potential of vitamin D in enhancing immune response and reducing viral replication in HIV-infected individuals [61, 62]. Vitamin D may reduce viral load through its anti-inflammatory properties and its ability to enhance immune responses [63].
The analysis demonstrates that vitamin D supplementation alone does not significantly improve weight gain in children and adolescents. The lack of significant weight gain (OR = 1.1; 95% CI: 0.96–1.26, p = 0.18) suggests that vitamin D supplementation alone may not be sufficient to influence growth metrics in children and adolescents. This aligns with previous studies showing that while vitamin D deficiency is associated with stunting and undernutrition, supplementation alone does not consistently improve weight gain [62, 64].
Vitamin D plays a critical role in modulating the immune system, which may explain its association with improved recovery rates. It enhances innate immunity by promoting the production of antimicrobial peptides and reducing pro-inflammatory cytokines, which are beneficial in conditions like COVID-19, rheumatoid arthritis (RA), and tuberculosis (TB). The odds ratio (OR = 2.28; 95% CI: 1.09–4.76, p = 0.028) indicates that vitamin D supplementation more than doubles the likelihood of symptom improvement, highlighting its potential as an adjunct therapy [65, 66]. Vitamin D supplementation is associated with improved recovery rates and prognoses across diverse diseases, likely due to its immunomodulatory and anti-inflammatory effects. While the findings are promising, further research is needed to address limitations and optimize supplementation strategies. Clinicians should consider integrating vitamin D into comprehensive treatment plans, particularly for patients with chronic or infectious diseases.
Implication of the synthesized evidence
The synthesized evidence highlights several key policy implications. First, vitamin D supplementation should be prioritized in populations with high prevalence of deficiencies, particularly in HIV/AIDS patients, given its significant impact on reducing viral load and improving biochemical markers. Second, while vitamin D supplementation is beneficial for specific health outcomes, it should not be promoted as a standalone intervention for weight gain in children or mortality reduction in TB and HIV/AIDS patients, as the evidence does not support its efficacy in these areas. Third, public health programs should integrate vitamin D supplementation into broader nutritional and therapeutic strategies to maximize its benefits, particularly in resource-limited settings. Fourth, further research and standardized protocols are needed to address gaps in evidence, such as subgroup analyses and disease-specific effects, to optimize supplementation strategies. Finally, policymakers should consider routine screening for vitamin D deficiency in high-risk populations and ensure access to affordable supplementation as part of comprehensive healthcare interventions.
Strength and Limitation of synthesized evidence
The strength of our synthesized evidence lied incorporating all interventional/RCT studies on vitamin D supplementation indicating support by evidence. The heterogeneity in study designs and populations across the included studies may impact the consistency and comparability of the findings. There is also a potential for language bias, as only English-language studies were included, which may have excluded relevant research published in other languages. Additionally, the generalizability of the results is limited due to the focus on studies conducted within African populations, making the findings potentially less applicable to other regions or contexts.
Conclusion
Vitamin D supplementation demonstrated significant health benefits in 50% of included studies, notably increasing serum vitamin D levels and reducing viral load in HIV/AIDS patients, while showing no significant effects on weight gain or mortality in TB and HIV/AIDS patients. It was associated with improved disease symptoms and biochemical markers, with no evidence of publication bias or significant heterogeneity. Further research is needed to explore subgroup-specific effects.
Registration and protocol
The systematic review and meta-analysis were registered on the PROSPERO database with registration number CRD42024620729. The review protocol can available from the principal authors upon request, and the title was amended from “Health impact of Vitamin D supplementation to reduce morbidity and mortality in developing countries” to “The health outcome of Vitamin D supplementation health outcomes in Africa” For feasibility reasons.
Supplementary Information
Acknowledgements
We extend our sincere gratitude to Dire Dawa University for providing reliable and efficient network services, which have greatly supported our academic and administrative activities. Your commitment to maintaining seamless connectivity has been instrumental in enhancing our productivity and learning experience. We appreciate the continuous efforts of the technical team in ensuring the network's stability and accessibility. Thank you for your invaluable contribution to the university community.
Abbreviations
- CI
Confidence Interval
- CMA
Comprehensive Meta-Analysis
- CASP
Critical Appraisal Skill program
- CVD
Cardio-Vascular Disease
- EIB
Exercise-Induced Bronchoconstriction
- HIV
Human Immune-Deficiency Virus
- NAFLD
Non-alcoholic Fatty Liver Disease
- PTH
Parathyroid Hormone
- RCT
Randomized controlled trials
- TB
Tuberculosis
- USA
United states of America
Authors’ contributions
T.D and Y.M develop search strategies. Y.M, B.D searched the articles through various data bases. T.D, Y.M, B.D and M.Y screened eligible articles. T.D, B.D, Y.M and A.O extract data. M.Y, B.D and T.G Any disagreement raised by reviewers were resolved by third person. T.D and B.D analyzed and interpreted the extracted data. T.D was a major contributor in writing the manuscript. All authors read and approved the final manuscript.
Funding
There is no funding for this research article.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethics approval and consent to participate
Since this is a systematic review and meta-analysis ethical approval and consent to participate is not applicable.
Consent for publication
Are not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
No datasets were generated or analysed during the current study.







