The association between micronutrient levels and diabetic foot ulcer: A systematic review with meta-analysis.

Background: Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus (DM). Nutrient deficiencies are among the major risk factors in DFU development and healing. In this context, we aimed to investigate the possible association between micronutrient status and risk of DFU. Methods: A systematic review (Prospero registration: CRD42021259817) of articles, published in PubMed, Web of Science, Scopus, CINAHL Complete, and Embase, that measured the status of micronutrients in DFU patients was performed. Results: Thirty-seven studies were considered, of which thirty were included for meta-analysis. These studies reported levels of 11 micronutrients: vitamins B9, B12, C, D, E, calcium, magnesium, iron, selenium, copper, and zinc. DFU, compared to healthy controls (HC) had significantly lower vitamin D (MD: -10.82 14 ng/ml, 95% CI: -20.47, -1.16), magnesium (MD: -0.45 mg/dL, 95% CI: -0.78, -0.12) and selenium (MD: -0.33 µmol/L, 95% CI: -0.34, -0.32) levels. DFU, compared to DM patients without DFU, had significantly lower vitamin D (MD: -5.41 ng/ml, 95% CI: -8.06, -2.76), and magnesium (MD: -0.20 mg/dL, 95% CI: -0.25, -0.15) levels. The overall analysis showed lower levels of vitamin D [15.55ng/ml (95% CI:13.44, 17.65)], vitamin C [4.99µmol/L (95% CI:3.16, 6.83)], magnesium [1.53mg/dL (95% CI:1.28, 1.78)] and selenium [0.54µmol/L (95% CI:0.45, 0.64)]. Conclusion: This review provides evidence that micronutrient levels significantly differ in DFU patients, suggesting an association between micronutrient status and risk of DFU. Therefore, routine monitoring and supplementations are warranted in DFU patients. We suggest that personalized nutrition therapy may be considered in the DFU management guidelines. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259817, identifier CRD42021259817.

Phytotherapy in Diabetic Foot Ulcers: A Promising Strategy for Effective Wound Healing.

Despite the advancement in wound care, the effective therapy of chronic diabetic ulcers continues to be a challenge. Wound healing is a highly controlled process, which involves a sequence of complex overlapping steps. This healing pathway comprises of hemostasis, inflammation, proliferative, and remodeling phases. Recent evidence suggests that phytomedicines can prevent or repair different kinds of destructive cellular damage, including chronic wounds. Several phytochemicals such as polyphenols, alkaloids, flavonoids, terpenoids, and glycosides have pleiotropic effects, including stimulation of fibroblast proliferation, the main step in wound healing. Besides, the mechanism involves induction of collagen synthesis, migration, and reepithelization and their antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory actions. Similarly, the use of phytochemicals alone or as an adjuvant with standard therapy has demonstrated promising results in managing complications in the diabetic foot. For instance, the extract of Carica papaya has been shown antioxidant, antimicrobial, and anti-inflammatory, and immunomodulatory effects, which, together with proteolytic enzymatic activity, contributes to its wound healing property. It is generally believed that phytotherapy has no or minimal toxicity than synthetic therapeutic agents, favoring its use in diabetic foot ulcer management. The current review highlights the selected phytochemicals and their sources; and potential application in diabetic foot ulcer management.Key teaching points and nutritional relevanceCurrently, phytochemicals have been shown wide potential in disease. management including alleviating clinical manifestations, preventing degenerative disease, and curing illness.Increased evidence of phytochemical as anti-infective and anti-inflammatory suggests its role in the management of diabetic foot ulcer(DFU).Potential benefit along with minimal adverse effect favors its application as adjuvant therapy.Further research is needed to standardize its dose and formulation to enhance its clinical application in DFU management.

Vitamin D attenuates biofilm-associated infections via immunomodulation and cathelicidin expression: a narrative review.

INTRODUCTION: Infections are becoming more difficult to treat, at least partly on account of microbes that produce biofilms. Reports suggest that decreased levels of antimicrobial peptides like cathelicidin, elevated levels of inflammatory cytokines, and biofilm formation are all associated with vitamin D deficiency, making vitamin D - deficient individuals more susceptible to infection. Infections attributable to biofilm-producing microbes can be managed by adjuvant therapy with vitamin D because of its immunomodulatory role, particularly because of the ability of vitamin D-pathway to induce the antimicrobial peptides like cathelicidin and decrease proinflammatory cytokines. AREAS COVERED: This narrative review covers biofilm formation, infections associated with biofilm due to vitamin D deficiency, putative role of vitamin D in host protection and the effect of vitamin D supplementation in biofilm-associated infections. A comprehensive literature search in PubMed and Google Scholar utilizing suitable keywords at multiple time points extracted relevant articles. EXPERT OPINION: Although vitamin D deficiency has been associated with infections by biofilm producing microbes, comprehensive clinical trials in various ethnicities are required to understand the likely relationships between vitamin D receptor gene expression, cathelicidin levels, and infection outcome. Current evidence hypothesizes that maintaining normal vitamin D level can help prevent and treat these infections.

Effect of Vitamin D Supplementation in Type 2 Diabetes Patients with Tuberculosis: A Systematic Review.

BACKGROUND: Diabetes mellitus (DM) and tuberculosis (TB) have been recognized as reemerging epidemics, especially in developing countries. Among all the risk factors, diabetes causes immunosuppression, increasing the risk of active TB three times. Vitamin D has been found as a link between DM-TB co-morbidity. OBJECTIVE: Vitamin D affects the immune response, suppresses Mycobacterium tuberculosis (Mtb) growth, and affects insulin secretion. The present systematic review determines the effect of vitamin D supplementation on clinical and therapeutic outcomes of DM-TB patients. METHOD: A comprehensive literature search was carried out in PubMed, Cochrane, Web of Science, and Scopus database to determine eligible studies from inception to January 2021. Out of the 639 articles retrieved, three randomized controlled trials (RCTs) were included in the systematic review. RESULT: The effect of vitamin D3 or oral cholecalciferol supplementation was assessed on outcomes, such as duration to sputum smear conversion, TB scores improvement, change in glycemic parameters, including HbA1c, FBS, and PLBS, and laboratory parameters, such as Hb, ESR, and CRP. Duration of sputum smear conversion was decreased by two weeks in the vitamin D3 supplemented group in two studies. TB score improvement and changes in glycemic parameters were inclined towards supplemented group; however, they were not significant. CONCLUSION: The overall effect of vitamin D3 supplementation on TB patients with DM was not significant. Further studies are required in the future examining the effect of supplementation on outcomes in this population.

Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects.

Saving lives and flattening the curve are the foremost priorities during the ongoing pandemic spread of SARS-CoV-2. Developing cutting-edge technology and collating available evidence would support frontline health teams. Nutritional adequacy improves general health and immunity to prevent and assuage infections. This review aims to outline the potential role of probiotics in fighting the COVID-19 by covering recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. The high basic reproduction number (R0) of SARS-CoV-2, absence of conclusive remedies, and the pleiotropic effect of probiotics in fighting influenza and other coronaviruses together favour probiotics supplements. However, further support from preclinical and clinical studies and reviews outlining the role of probiotics in COVID-19 are critical. Results are awaited from many ongoing clinical trials investigating the benefits of probiotics in COVID-19.

Vitamin D Supplementation in Diabetic Foot Ulcers: A Current Perspective.

INTRODUCTION: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, as it can physically and emotionally impact the person. Its management can be challenging and expensive, depending on the severity of the wound and the presence of infection. BACKGROUND: The fat-soluble molecule, vitamin D, has gained great importance ever since its pleiotropism has been recognized. Its efficacy could be attributed to the presence of vitamin D receptors in most of the body tissues. Vitamin D plays a significant role in cell proliferation, differentiation, and immune modulation. It modulates the T and B cells resulting in the suppression of the immunoglobulins, autoimmunity, and inflammation. METHODS: We performed a literature search with the objective to highlight the role of vitamin D in peripheral vascular disease and peripheral neuropathy, which are the major risk factors for DFU, as well as evidences of its role in wound healing and management of DFU. RESULTS: Preclinical and clinical studies have shown that vitamin D influences multiple phases of wound healing and thereby accelerates the process. It modulates various cells involved in proliferation and remodelling phases. Vitamin D also enhances the expression of antimicrobial peptides that help to eliminate the microbes, as well as suppress the proinflammatory responses while enhancing the anti-inflammatory responses. CONCLUSION: This review concludes vitamin D to have a protective role in the immune and vascular system, improve glycaemic outcomes, and wound healing. Therefore, vitamin D could be a preferred adjuvant in the management of DFU.

Free radicals and antioxidant therapy in clinical practice: to be or not to be?

Free radicals and antioxidant therapy have attracted a great deal of attention in recent years. Current research reveals the potential applications of antioxidants in prevention or control of disease. However, controversy still exists due to lack of well controlled clinical trials and definitive conclusion on efficacy/safety. This article highlights the debatable issues related to this. Based on the available literature and clinician's experience, recommendation on antioxidant usage is mentioned at the end. There is a need to assimilate the known available information with extensive research to establish a positive role of antioxidant therapy in clinical practice and to use an evidence-based approach for summarizing data, drawing conclusions and making recommendations about antioxidant usage and efficacy. A substantial gap still exists between the claims and the efficacy/safety in this area of research.