What is the Effect of Vitamin D Supplementation on the Healing of Chronic Wounds in Adults 50 Years and Older?
A systematic review submitted in part fulfilment for the degree of Masters in Science in Nursing,
School of Nursing and Midwifery,
Royal College of Surgeons in Ireland.
Background: In addition to costing the global health sector billions of dollars globally for treatment, chronic wounds are a major issue among older patients. Malnutrition, specifically vitamin D deficiency, has been found to have a major exacerbating effect on chronic wound healing. Nevertheless, the majority of existent studies focus on the role of nutrition in acute wound healing, thus leaving a gap in information on the effect of vitamin D supplementation on chronic wound healing among older patients.
Design: Systematic Review.
Methods: A literature search via (Cochrane, Cinahl, Ovid med, Embase, Scopus, and Google Scholar) and additional sources with no limit on publication date were comprehensively searched up to February 2021. Additional articles were also sourced from the reference lists of sources selected from these databases. The review question for this study was developed by use of the PICO mnemonic. Article review was then carried out using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) flow chart. Out of the 70 studies which have been identified for this study, 11 adequately satisfied all inclusion criteria. The evidence–based library (EBL) checklist also played a major role in the appraisal of quality for the selected articles. Statistical data analysis was then conducted through narrative synthesis.
Results: With reference to the primary and secondary outcomes for this study, the identified studies had EBL scores ranging from 50% to 92%. For this systematic review, only studies with EBL scores equal to or above 77% were selected for analysis and data collection, thus yielding 8 studies in total, which were selected. Among the 8 studies, 5 and 3 had outcomes that were directly related to the primary and secondary outcomes for this review, respectively. Out of the 8 viable studies, 6 proved the primary outcome of enhanced chronic wound closure rate as a result of supplementation with vitamin D. The two remaining studies proved the secondary outcomes of treatment cost-effectiveness and improved patient quality of life as a result of the accelerated healing rate of chronic wounds for older patients.
Conclusion: This analysis revealed that vitamin D supplementation plays a major role in the enhancement of chronic wound healing among older patients. Additional research into vitamin D supplementation for chronic wound healing among older patients is necessary, in order to yield improved health care outcomes, through cost-effective treatment strategies.
Introduction and Background
Though the concept of nutrition has for a long time been largely ignored within chronic wound management, it makes up a large portion of the foundation upon which medicine is based (Molner et al, 2014). Nevertheless, nutrition still remains to be a major issue, particularly among older patients in Europe and the UK. Although research has revealed a larger amount of information regarding micronutrient and macronutrient supplementation as a solution for malnutrition, studies show the significant similarity between lack of adequate nutrition within both developed and developing countries (Guyonnet and Rolland, 2015).
This similarity has been portrayed through findings in research aimed at analysing the effects of malnutrition in the management of injuries, specifically among trauma patients (Golladay et al., 2016). However, in spite of the availability of this information, patient demographic differences, in addition to the existing physiological disparities between chronic and acute wounds, have led to the creation of a wide knowledge gap in the existing research on nutritional supplementation for older patients with chronic wounds.
Stechmiller (2010) highlights the overall importance of nutrition in the activation of optimal conditions for the healing of wounds. As such, any deficiency in nutrition often has an adverse effect on the normal physiological processes, which allow for smooth wound healing stage transition. Due to the inhibition of optimal healing, patients are usually at high risk of developing delayed healing of wounds, infection, and ulcers resulting from wound pressure, as a direct result of increased rates of infection and reduced tensile strength of wounds associated with nutritional deficiencies (Neloska et al., 2016). The risk of developing such conditions is often higher for patients with chronic wounds (Neloska et al., 2016).
Chronic wounds have been defined by Iqbal et al. (2017) as wounds that either fails to sequentially follow the natural stages of healing or take more than three months to heal. This definition has been supported by chronic wound guidelines outlined within the paper by Gupta et al. (2017), which provides guidelines on the identification, as well as the treatment of chronic wounds. In light of these characteristics, chronic wounds may often showcase a significant deceleration of the healing process, which may, in turn, lead to prolonged inflammation, extremely long recovery times, or complete healing failure (Stechmiller, 2010).
Chronic wounds often develop as a result of severe injury or malnutrition. Although a lot of information on the management of wounds caused by severe injury exists in global medical databases, there is still a need for more research on the role of sufficient nutrition in the management of chronic wounds resulting from malnutrition.
In order to develop a better comprehension of the role of nutrition in the management of chronic wounds, an examination of the stages involved during the healing process is necessary. The healing process, as outlined by Wild et al. (2010), consists of the inflammatory, proliferative, and maturation stages. Each stage has a requirement for particular components in order to fulfill its role during the course of healing. During the inflammatory stage, which begins immediately after the onset of injury, blood vessel constriction, blood clot formation, and wound inflammation are usually the most observable processes. These processes have the purpose of not only controlling the amount of blood lost during an injury but also enabling the creation of a barrier on the wound to prevent infection as a result of the entry of bacteria (Guo and DiPietro, 2010).
The proliferative stage is the intermediate stage, during which collagen is formed by fibroblasts to create a more solid barrier over the wound. Collagen formation during this stage occurs through the process of granulation (Gonzalez et al., 2016). Formation of new blood vessels within the wound, as well as wound contraction and new skin development also takes place during this stage. Finally, after completion of the inflammatory and proliferative stages, the wound healing process is completed during the maturation stage, which features an increase in tissue strength and formation of new collagen within the previously injured tissue (Song et al., 2017). Scar tissue formation is also a major characteristic of this stage. Nevertheless, regardless of the existence of a seemingly sequential process, a high possibility of the occurrence of the natural healing process in a non-sequential manner still exists (Heng, 2011).
Non-sequential healing is usually triggered by a variety of extrinsic and intrinsic factors. Chronic wounds, which feature non-sequential healing, often occur as a result of the disruption of this process (Heng, 2011; Volkert et al., 2019). Generally, the natural healing of wounds is a process that requires a large amount of energy and resources from the body. Protein reserves and energy stores are the energy suppliers, which facilitate the formation of new cells during this process. Upon the absence of a sufficient level of nutrients within the body, the speed and optimisation of the wound healing process are usually reduced. According to various sources of research, older patients have been associated with increased risks of malnutrition (Bender and Krznarić, 2020; Volkert et al., 2019).
While malnutrition is a general term that encompasses the deficiency of any of the large number of nutrients that have been identified, a distinct absence of research has been identified, particularly for the role of vitamin D in the healing of chronic wounds in geriatric patients (Guo and DiPietro, 2010). Gist et al. (2009) explain that deficiency of vitamin D has for a long time, been associated with chronic malignant and inflammatory diseases, as well as heightened mortality rates. While a large portion of existing research is mostly geared towards the analysis of the role of vitamin D in the reduction of the risk of a number of chronic ailments such as cardiovascular, infectious, cancer, and autoimmune diseases, there is a need for more research on its role in the management of chronic injuries (Shipton and Shipton, 2015).
Research carried out by White (2010) highlights the association of higher levels of vitamin D with the production of an antimicrobial peptide known as cathelicidin, which in turn yields improved healing outcomes as a result of the enhancement of the immune system’s ability to fight off infection from injuries. While issues such as inhibited metabolism and reduced absorption and synthesis through the skin have been identified as the leading causative factors for the deficiency of vitamin D, malnutrition through either lack of knowledge or access to proper dietary sources is a significant cause of this deficiency, specifically in older adults (Wei, Zhu and Ji, 2019).
Globally, vitamin D insufficiency and deficiency, as a result of chronic illness and insufficient exposure to the sun, have been identified in about one billion individuals (Yammine, Hayek and Assi, 2020). While deficiency is portrayed through the availability of vitamin D levels that do not exceed 20 ng/mL, insufficiency is portrayed by Vitamin D levels ranging between 20-30 ng/mL within the body. A study conducted with the aim of analysing the role of vitamin D in the healing of wounds in diabetic individuals with foot ulcers, revealed its beneficial role in the inhibition of processes associated with inflammation and angiogenesis, thus in turn leading to accelerated rates of wound healing (Kavitha et al., 2014).
Although the deficiency of vitamin D is not an independent factor that increases the risk of development of pressure ulcers in adults who are diabetic, there is a high possibility for its association with reduced rates of healing in older adults with chronic wounds (Posthauer et al., 2015).
In this light, this paper, therefore, makes use of a systemic review of research to provide a more comprehensive analysis on the role of vitamin D in the healing of chronic wounds in older patients, particularly within the UK and Europe. Consequently, this review will play a significant role in closing the knowledge gap which currently exists within the health sector on the use of vitamin D supplementation for the management of chronic wounds in such patients. In turn, improved comprehension of the role of vitamin D in chronic wound management will not only facilitate the development of better health outcomes but also aid in the reduction of the overall rate of mortality among older patients.
The systemic review outlined within this paper was conducted on the basis of recommendations and guidelines obtained from PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), with the aim of ensuring that the analysis is conducted in an organised and methodical manner (Moher et al., 2010; Tricco et al., 2018).
Aim and intervention
The aim of this systematic review was to examine the role of vitamin D supplementation on the healing of chronic wounds in older patients. This aim was achieved through the analysis of the findings of research papers, whose objectives were directly related to the overall aim of this particular review. Data collected from this review can then be used for the purpose of developing recommendations in relation to the utilisation of vitamin D supplementation in medical policies, research, education, and practice, based on the management of chronic wounds in older patients. As such, this review is expected to benefit the overall quality of health care provided to older patients with chronic wounds, thus not only improving their health outcomes but also reducing their mortality rate.
The PICO framework provided a strong foundation for the formulation of the question on which the objective for this systematic review is based. This framework plays a significant role in the organised structuring of research questions in a way that ensures that all areas under analysis are highlighted (Hastings and Fisher, 2004; Lockwood and Geum, 2017). According to Schardt et al. (2007), the PICO framework encompasses a systemic analysis of the Population, Intervention, Comparison, and Outcome to be expected before the research is conducted. As such, for this particular review, the population, intervention, and comparison were identified as the effect of vitamin D supplementation in the treatment of older adults suffering from chronic wounds as compared to treatment without supplementation. Furthermore, expected outcomes of this research included:
What is the Effect of Vitamin D Supplementation on the Healing of Chronic Wounds in Older Patients?
P Population – Older adults aged 50 years and above with chronic wounds.
I Intervention – Supplementation with vitamin D.
C Comparison – Absence of supplementation with vitamin D.
O Outcome – Full chronic wound closure, treatment cost-effectiveness and improved quality of life for patients.
Primary outcomes: Chronic wound healing
Secondary outcomes: Treatment costs and cost-effectiveness
Patient quality of life
The target population for this systematic review was older male and female patients aged 50 years and older, living with chronic wound medical conditions.
Review Outcomes Primary outcome
The primary outcome expected for this review is the investigation of the healing rate for chronic wound healing after the use of vitamin D supplements as an intervention during treatment. More specifically, this investigation is expected to facilitate the identification and analysis of benefits of the use of vitamin D for chronic wound management, through an examination of the time is taken, as well as the proportion of healing observed during the healing process of chronic wounds in older patients. To fulfill this primary outcome, trial lists outlined within the studies selected for this research review will be expected to report and measure variables involved in the wound healing process as a result of vitamin D supplementation, based on factors such as the rate of wound size change, wound healing proportion over time and the amount of time taken to complete the healing process.
The secondary outcome expected for this review is the enhancement of the quality of life for older patients, based on the application of healthy nutrition in improving the healing process, as well as reducing the risk of occurrence of nutrition-based lifestyle diseases such as diabetes and obesity, which significantly increase the possibility of development of chronic wounds. As such, this will in turn facilitate cost-effectiveness through the reduction of treatment costs for patients and health institutions, which occur as a result of excessive prescription drug use and medical resource utilisation during the course of chronic wound management. Cost-effectiveness will be achieved through the enhancement of proper nutrition for older patients with the aim of not only enabling management but also preventing the risk of chronic wound development. More specifically, vitamin D supplementation is expected to reduce the rate of chronic ulcer recurrence, thus not only facilitating cost-effectiveness through reduced treatment costs but also improving the overall quality of life for older patients.
Criteria for Inclusion of Studies Inclusion Criteria
Studies that were eligible for this review were those whose research revolved around the examination of the effects of vitamin D supplements in the management of chronic wounds among older individuals. Moreover, the eligibility criteria for this systemic review also included studies documented in the English language. As such, based on these criteria, all eligible studies outlining original quantitative research were utilised.
Studies excluded from this review were those based on research that was not focussed on the analysis of the effect of vitamin D supplementation on the healing of older patients with chronic wounds. As such, based on this exclusion criterion, studies that were either focussed on younger individuals with wounds that were not chronic in nature, as well as those which involved supplementation using other nutrients apart from vitamin D were excluded. The exclusion was also extended to studies that were documented in other languages apart from the English language. Furthermore, the listed secondary and primary outcomes for this systemic review were also used as inclusion criteria, whereby studies that failed to consider any of these outcomes were excluded.
For this systemic review, a specific and sensitive search for literature meeting the outlined inclusion criteria was conducted. This search for literature was designed to be precise and thorough, with the aim of ensuring that the objective for this review was satisfied. The range of literature used for this review included studies conducted from 1st January 2001 to 1st January 2021. Using specific keywords, information databases used for this search included Cochrane, Cinahl, Ovid med, Embase, Scopus, and Google Scholar (Table 1). A combination of search results from the listed variety of databases was used with the aim of identifying subject term variances, thus in turn enabling the collection of a wide collection of high variance data from different areas, participants, and researchers on similar subject matters.
In order to obtain further information for this review, an exhaustive hand-based search was conducted to facilitate the identification of relevant references within the reference lists of selected studies. From this hand-based search, a total of 10 studies were obtained. Upon the encounter of unpublished work expected to significantly contribute towards this research review, contact with relevant authors will be established in order to facilitate the provision of the necessary information. Moreover, as previously highlighted within the inclusion criteria, only studies documented in the English language were selected during the course of implementation of this search strategy.
Table 1: Key Words and Terms
Vitamin D deficiency
2.5.1. Potential Limitation
Although the use of keywords yields the advantage of narrowing down the search process to only include articles which are related to the topic being reviewed, an additional manual examination of selected articles is required for the purpose of eliminating those which fail to satisfy the inclusion criteria. Consequently, a lot of time is consumed during this manual article examination, thus increasing the overall amount of time taken to complete the review.
Heterogeneity evaluation was done using the I2 and Chi-squared test. Final study results showed a value of I2 ≥ 50%, P < <, which indicated the presence of heterogeneity in selected studies, thus yielding a necessity for use of the random effect model for data synthesis in this systematic review (Feldkamp et al., 2018; Kota et al., 2013; McDaniel, 2020; Aujla, Allen and Ribbans, 2019; Razzaghi et al., 2017; Renner et al., 2019; Todorova et al., 2020; Tsitsou et al., 2021).
Data Collection and Analysis
As previously explained in the search strategy section, relevant articles for this study were selected after a keyword-based search in a number of databases including Cochrane, Cinahl, Ovid med, Embase, Scopus and Google Scholar. Reference lists of identified articles were then used to conduct a further search for additional articles which could be used for this systematic review. After completion of the search process, a PRISMA flow chart (outlined in Figure 1) was used for the purpose of facilitating the elimination of studies which failed to meet the inclusion criteria for this study. For this review, a data extraction table (Appendix 2) was then created with the aim of facilitating relevant data extraction from the studies which were selected through the use of the PRISMA flow chart.
While the extraction of data was conducted by the reviewer in charge of this study, the supervisor conducted a secondary analysis of data extracted for purposes of validation. This process of extraction and validation of data by two reviewers was in line with the best systematic review conduction practices (Halcomb and Fernandez, 2015). Moreover, an evidence-based librarianship (EBL) checklist for critical appraisal was used to achieve an overall appraisal of quality for all studies included in this review (outlined in Appendix 1). In turn, this enhanced the systematic assessment and score assignment for all articles based on their suitability for this systematic review (Glynn, 2006). The EBL-based appraisal of quality for selected articles was then further analysed by the supervisor for the purpose of ensuring adherence with the best systematic review conduction practices
Analysis of data for this systematic review was conducted through the use of narrative data synthesis. This narrative synthesis can be divided into the results for primary and secondary outcomes of this research.
Across all listed databases, key terms and word combinations were utilised for the search. After the completion of the search across all databases, data were merged and subsequently recorded within a PRISMA flow diagram (2009). As outlined in Figure 1, the PRISMA model provides a comprehensive view of the selection and screening process for research to be used for this review. From a total of 70 published research papers which had been initially selected for this review, 59 articles were excluded. An additional 3 articles were excluded from a subsequent review of the remaining research papers, owing to non-eligible research designs, participant age and expected study outcomes for research (Basiri et al., 2020; Yuan, Das and Li, 2018).
Consequently, from this final conclusion, a total of 8 studies which met all the required criteria for this study were selected. The listed keywords for this review were also used to conduct a search within the PsycEXTRA database, for the purpose of enabling the further collection and analysis of information contained within grey literature sources, such as service reports, government reports, research reports, and conference proceedings.
Figure 1: PRISMA 2009 Flow Diagram