Associations between Nutrients and Foot Ulceration in Diabetes: A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
- (i)
- Cochrane Library (searched 17 September 2020)
- (ii)
- Ovid Embase (searched 17 September 2020)
- (iii)
- Ovid MEDLINE (searched 17 September 2020)
- (iv)
- PubMed (searched 17 September 2020)
Inclusion and Exclusion Criteria
3. Results
3.1. Study Selection
3.2. Included Studies
3.3. Demographic Data
- (i)
- (ii)
- (iii)
- One RCT included participants grade 1–2 DFU [23];
- (iv)
- The remaining RCT included participants with diabetes who had at least one University of Texas grade 1A foot ulcer [22];
- (v)
- (vi)
- (vii)
- The other case-control study included participants with diabetes and foot ulceration, and a control group without diabetes or foot ulceration [26];
- (viii)
- The remaining prospective cohort study included any participants with foot ulceration; 90% of whom had diabetes [30].
3.3.1. Vitamin C
3.3.2. Vitamin D
3.3.3. Vitamins B12 and Folic Acid
3.3.4. Vitamin E
3.3.5. Omega-3 Polyunsaturated Fatty Acids
3.3.6. Minerals (Magnesium, Selenium, Zinc, Copper)
3.3.7. Probiotics
3.3.8. Amino Acids
3.3.9. Protein-Energy Supplementation
4. Discussion
Strengths and Limitations
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
- Boulton, A. The diabetic foot: A global view. Diabetes Metab. Res. Rev. 2000, 16, S2–S5. [Google Scholar] [CrossRef]
- Reardon, R.; Simring, D.; Kim, B.; Mortensen, J.; Williams, D.; Leslie, A. The diabetic foot ulcer. Aust. J. Gen. Pract. 2020, 49, 250–255. [Google Scholar] [CrossRef] [PubMed]
- ACSQHC. Australian Atlas of Healthcare Variation Series: Australian Government. 2016. Available online: http://www.safetyandquality.gov.au/atlas/ (accessed on 24 July 2020).
- Davis, W.; Norman, P.E.; Bruce, D.; Davis, T. Predictors, consequences and costs of diabetes-related lower extremity amputation complicating type 2 diabetes: The Fremantle Diabetes Study. Diabetology 2006, 49, 2634–2641. [Google Scholar] [CrossRef]
- Cheng, Q.; A Lazzarini, P.; Gibb, M.; Derhy, P.H.; Kinnear, E.M.; Burn, E.; Graves, N.; E Norman, R. A cost-effectiveness analysis of optimal care for diabetic foot ulcers in Australia. Int. Wound J. 2016, 14, 616–628. [Google Scholar] [CrossRef]
- Bakker, K.; Apelqvist, J.; Schaper, N.; International Working Group on the Diabetic Foot Editorial Board. Practical guidelines on the management and prevention of the diabetic foot 2011. Diabetes Metab. Res. Rev. 2012, 28, 225–231. [Google Scholar] [CrossRef] [PubMed]
- Collins, N. Nutrition 411: Revisiting vitamin C and wound healing. Ostomy Wound Manag. 2013, 59, 12. [Google Scholar]
- Christie-David, D.J.; Gunton, J.E. Vitamin C deficiency and diabetes mellitus—Easily missed? Diabet. Med. 2017, 34, 294–296. [Google Scholar] [CrossRef] [Green Version]
- Anderson, B. Nutrition and wound healing: The necessity of assessment. Br. J. Nurs. 2005, 14, S30–S38. [Google Scholar] [CrossRef]
- Polcz, M.E.; Barbul, A. The Role of Vitamin A in Wound Healing. Nutr. Clin. Pract. 2019, 34, 695–700. [Google Scholar] [CrossRef]
- Zinder, R.; Cooley, R.; Vlad, L.G.; Molnar, J.A. Vitamin A and Wound Healing. Nutr. Clin. Pract. 2019, 34, 839–849. [Google Scholar] [CrossRef]
- Zubair, M.; Malik, A.; Meerza, D.; Ahmad, J. 25-Hydroxyvitamin D [25(OH)D] levels and diabetic foot ulcer: Is there any relationship? Diabetes Metab. Syndr. Clin. Res. Rev. 2013, 7, 148–153. [Google Scholar] [CrossRef]
- Dai, J.; Jiang, C.; Chen, H.; Chai, Y. Vitamin D and diabetic foot ulcer: A systematic review and meta-analysis. Nutr. Diabetes 2019, 9, 1–6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oda, Y.; Tu, C.-L.; Menendez, A.; Nguyen, T.; Bikle, D.D. Vitamin D and calcium regulation of epidermal wound healing. J. Steroid Biochem. Mol. Biol. 2016, 164, 379–385. [Google Scholar] [CrossRef] [Green Version]
- Quain, A.M.; Khardori, N.M. Nutrition in Wound Care Management: A Comprehensive Overview. Wounds 2015, 27, 327–335. [Google Scholar] [PubMed]
- ODS. Selenium USA: USA Government. 2020; [updated 11 March 2020]. Available online: https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/ (accessed on 24 July 2020).
- Afzali, H.; Kashi, A.H.J.; Momen-Heravi, M.; Razzaghi, R.; Amirani, E.; Bahmani, F.; Gilasi, H.R.; Asemi, Z. The effects of magnesium and vitamin E co-supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. Wound Repair Regen. 2019, 27, 277–284. [Google Scholar] [CrossRef] [PubMed]
- Kamble, A.; Ambad, R.; Padamwar, M.; Kakade, A.; Yeola, M. To study the effect of oral vitamin D supplements on wound healing in patient with diabetic foot ulcer and its effect on lipid metabolism. Int. J. Res. Pharm. Sci. 2020, 11, 2701–2706. [Google Scholar] [CrossRef]
- Razzaghi, R.; Pourbagheri, H.; Momen-Heravi, M.; Bahmani, F.; Shadi, J.; Soleimani, Z.; Asemi, Z. The effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. J. Diabetes Its Complicat. 2017, 31, 766–772. [Google Scholar] [CrossRef]
- Soleimani, Z.; Hashemdokht, F.; Bahmani, F.; Taghizadeh, M.; Memarzadeh, M.R.; Asemi, Z. Clinical and metabolic response to flaxseed oil omega-3 fatty acids supplementation in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. J. Diabetes Its Complicat. 2017, 31, 1394–1400. [Google Scholar] [CrossRef]
- Razzaghi, R.; Pidar, F.; Momen-Heravi, M.; Bahmani, F.; Akbari, H.; Asemi, Z. Magnesium Supplementation and the Effects on Wound Healing and Metabolic Status in Patients with Diabetic Foot Ulcer: A Randomized, Double-Blind, Placebo-Controlled Trial. Biol. Trace Element Res. 2017, 181, 207–215. [Google Scholar] [CrossRef]
- Armstrong, D.G.; Hanft, J.R.; Driver, V.R.; Smith, A.P.S.; Martinez, J.L.L.; Reyzelman, A.M.; Furst, G.J.; Vayser, D.J.; Cervantes, H.L.; Snyder, R.J.; et al. Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: A prospective randomized controlled trial. Diabet. Med. 2014, 31, 1069–1077. [Google Scholar] [CrossRef]
- Eneroth, M.; Larsson, J.; Oscarsson, C.; Apelqvist, J. Nutritional supplementation for diabetic foot ulcers: The first RCT. J. Wound Care 2004, 13, 230–234. [Google Scholar] [CrossRef]
- Mohseni, S.; Bayani, M.; Bahmani, F.; Tajabadi-Ebrahimi, M.; Bayani, M.A.; Jafari, P.; Asemi, Z. The beneficial effects of probiotic administration on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. Diabetes/Metab. Res. Rev. 2018, 34, e2970. [Google Scholar] [CrossRef]
- Momen-Heravi, M.; Barahimi, E.; Razzaghi, R.; Bahmani, F.; Gilasi, H.R.; Asemi, Z. The effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. Wound Repair Regen. 2017, 25, 512–520. [Google Scholar] [CrossRef] [PubMed]
- Bolajoko, E.B.; Akinosun, O.M.; Anetor, J.; Mossanda, K.S. Relationship between selected micronutrient deficiencies and oxidative stress biomarkers in diabetes mellitus patients with foot ulcers in Ibadan, Nigeria. Turk. J. Med Sci. 2017, 47, 1117–1123. [Google Scholar] [CrossRef] [PubMed]
- Badedi, M.; Darraj, H.; Hummadi, A.; Solan, Y.; Zakri, I.; Khawaji, A.; Daghreeri, M.; Budaydi, A. Vitamin B12 Deficiency and Foot Ulcers in Type 2 Diabetes Mellitus: A Case–Control Study. Diabetes Metab. Syndr. Obes. Targets Ther. 2019, 12, 2589–2596. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Boykin, J.V.; Hoke, G.D.; Driscoll, C.R.; Dharmaraj, B.S. High-dose folic acid and its effect on early stage diabetic foot ulcer wound healing. Wound Repair Regen. 2020, 28, 517–525. [Google Scholar] [CrossRef]
- Pena, G.; Kuang, B.; Cowled, P.; Howell, S.; Dawson, J.; Philpot, R.; Fitridge, R. Micronutrient Status in Diabetic Patients with Foot Ulcers. Adv. Wound Care 2020, 9, 9–15. [Google Scholar] [CrossRef]
- Smart, H.; AlGhareeb, A.M.; Smart, S.-A. 25-Hydroxyvitamin D Deficiency: Impacting Deep-Wound Infection and Poor Healing Outcomes in Patients With Diabetes. Adv. Ski. Wound Care 2019, 32, 321–328. [Google Scholar] [CrossRef]
- Armstrong, D.G.; Mills, J.L. Juggling risk to reduce amputations: The three-ring circus of infection, ischemia and tissue loss-dominant conditions. Wound Med. 2013, 1, 13–14. [Google Scholar] [CrossRef]
- Kyaw, A. A simple colorimetric method for ascorbic acid determination in blood plasma. Clin. Chim. Acta 1978, 86, 153–157. [Google Scholar] [CrossRef]
- de Jager, J.; Kooy, A.; Lehert, P.; Wulffelé, M.; van der Kolk, J.; Bets, D.; Verburg, J.; Donker, J.M.; Stehouwer, D.A. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: Randomised placebo controlled trial. BMJ 2010, 340. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hartweg, J.; Perera, R.; Montori, V.; Dinneen, S.; Neil, A.H.; Farmer, A.J. Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus. Cochrane Database Syst. Rev. 2008, CD003205. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.; Yu, X.; Shao, S. Effects of Omega-3 Fatty Acid Supplementation on Glucose Control and Lipid Levels in Type 2 Diabetes: A Meta-Analysis. PLoS ONE 2015, 10, e0139565. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moore, Z.; Corcoran, M.; Patton, D. Nutritional interventions for treating foot ulcers in people with diabetes (review). Cochrane Database Syst. Rev. 2020, 7. [Google Scholar] [CrossRef]
- Gunton, J.E.; Girgis, C.M.; Lau, T.; Vicaretti, M.; Begg, L.; Flood, V. Vitamin C Improves Healing of Foot Ulcers; A Randomised, Double-Blind, Placebo-Controlled Trial. Br. J. Nutr. 2020, 2020, 1–21. [Google Scholar] [CrossRef]
Reference, Country | Study Design and Sample Sizes | Age (Years) | Gender (M:F) | BMI (kg/m2) | HbA1c (%) | Nutrient(s) or Supplement Studied | Baseline Tested (Y/N) |
---|---|---|---|---|---|---|---|
Afzali et al. Iran | RCT control, N = 28 | 55.5 ± 4.9 | 22:6 | 29.7 ± 3.9 | 7.6 ± 0.6 | Magnesium (Mg) and Vitamin E | Y Mg (mg/dL) only, 1.51 ± 0.15 in controls and 1.55 ± 0.18 in intervention |
RCT intervention, N = 29 | 57.2 ± 11.0 | 23:6 | 30.3 ± 3.9 | 7.4 ± 0.8 | |||
Armstrong et al. USA | RCT control, N = 141 | 59 ^ | 111:30 | 31.6 ± 7.1 | 8.0 ± 1.5 | Arginine, glutamine, and beta-hydroxy-beta-methylbutyrate | N |
RCT intervention, N = 129 | 58 ^ | 93:36 | 33.1 ± 7.3 | 8.0 ± 1.7 | |||
Badedi et al. Saudi Arabia | Case-control. Control N = 215 | 54 ± 9.8 | 126:89 | 28.8 ± 4.3 | 8.5 ± 2.1 | Vit B12 | Y Deficiency in 32.1% of controls and 59.2% of cases (p = 0.001) |
Cases, N = 108 | 56.9 ± 12.2 | 66:42 | 28.9 ± 5.3 | 10.5 ± 2.0 | |||
Bolajoko et al. Nigeria | Case-control. Control, N = 50 | 51.6 ± 1.03 | NR | 22.9 ± 0.2 | 4.1 ± 0.1 | Cu, Se, Zn, Vit C and E | Y Significantly lower Vit C (p = 0.003), Se and Vit E between case and controls (p < 0.001) |
Cases, N = 70 | 51.6 ± 1.07 | NR | 26.1 ± 0.3 | 8.6 ± 0.2 | |||
Boykin et al. USA | No controls | - | - | - | - | Folic acid | N |
Retrospective cohort, N = 9 | 67.7 ± 10.2 | 9:0 | NR | 8.1 ± 1.4 | |||
Eneroth et al. Sweden | RCT control, N = 27 | 75 ^ | 21:6 | NR | 7.0 ± 5.2 ^ | 400kcal liquid oral supplementation (20 g protein per 200 mL plus other unspecified micronutrients) | Y Protein-energy malnutrition, 44% in placebo group and 19% in intervention |
RCT intervention, N = 26 | 74 ^ | 19:7 | NR | 7.1 ± 5.4 ^ | |||
Kamble et al. India | RCT control, N = 30 | 59.7 ± 8.4 | 23:7 | 25.9 ± 3.8 | 9.8 ± 3.5 | Vitamin D | Y Vit D (ng/mL) 20.5 ± 9.3 in controls, 18.5 ± 11.6 in intervention |
RCT intervention, N = 30 | 60.2 ± 9.3 | 25:5 | 26.4 ± 4.2 | 9.1 ± 2.1 | |||
Mohseni et al. Iran | RCT control, N = 30 | 58.5 ± 11.0 | 20:10 | 25.3 ± 3.7 | 7.9 ± 0.7 | Probiotic | N |
RCT intervention, N = 30 | 62.6 ± 9.7 | 20:10 | 26.4 ± 3.0 | 8.0 ± 0.9 | |||
Momen-Heravi et al. Iran | RCT control, N = 30 | 60.0 ± 10.0 | 21:9 | 25.8 ± 3.1 | 7.9 ± 0.7 | Zn | Y Zn (mg/dL) 77.6 ± 12.9 in controls, 76.4 ± 4.5 in intervention |
RCT intervention, N = 30 | 58.3 ± 8.6 | 21:9 | 25.8 ± 3.0 | 7.8 ± 0.9 | |||
Pena et al. Australia | No control group | - | - | - | - | Vit A, C, D; and E, Cu, and Zn | Y Vit A deficiency in 10.9% of patients, Vit D 55.7%, Zn 26.9%. Suboptimal Vit C in 22.2% and deficiency in 50.8% |
Prosp cohort, N= 131 | 66.3 ± 13.1 | 104:27 | 29.4 ± 6.1 | 8.8 ± 4.4 | |||
Razzaghi et al. (2017) Iran | RCT control, N = 30 | 58.6 ± 8.6 | 22:8 | 26.2 ±3.8 | 7.8 ± 0.7 | Vitamin D | Y Vit D (ng/mL) 20.2 ± 15.6 in controls, 15.2 ± 9.9 in intervention |
RCT intervention, N = 30 | 59.6 ± 8.2 | 22:8 | 26.0 ± 4.4 | 8.3 ± 1.0 | |||
Razzaghi et al. (2018) Iran | RCT control, N = 35 | 59.0 ± 10.1 | 24:11 | 26.2 ± 4.1 | 7.8 ± 0.6 | Magnesium | Y Mg (mg/dL) 2.0 ± 0.2 in controls and 2.1 ± 0.3 in intervention |
RCT intervention, N = 35 | 60.1 ± 11.1 | 22:13 | 28.2 ± 5.2 | 8.3 ± 1.9 | |||
Smart et al. Bahrain | No control group | - | - | - | Vitamin D | Y Vit D deficiency 85% of cohort, plus insufficient in 15% | |
Prosp cohort, N = 80 | 55.8 ± 15.9 | 57:23 | NR | 8.2 ± 2.2 (n = 72) | |||
Soleimani et al. Iran | RCT control, N = 30 | 59.9 ± 9.2 | 23:7 | 26.9 ± 2.7 | 7.9 ± 0.7 | Omega-3 PUFA from flaxseed oil | N No significant differences in baseline dietary omega-3 intake |
RCT intervention, N = 30 | 58.8 ± 11.2 | 23:7 | 27.0 ± 4.5 | 7.5 ± 1.5 | |||
Zubair et al. India | Prosp cohort control, N = 162 | 47.1 ± 12.1 | 102:58 | 24.0 ± 4.2 | 7.9 ± 0.9 | Vitamin D | Y Vit D (ng/mL) 29.8 in controls and 8.4 in cases (p < 0.005) |
Prosp cohort cases, N = 162 | 46.3 ± 13.2 | 103:59 | 24.8 ± 4.5 | 9.6 ± 2.0 |
Stage/Grade | |
---|---|
0 | No open lesions; may have deformity or cellulitis |
1 | Superficial diabetic ulcer (partial or full thickness) |
2 | Ulcer extension to ligament, tendon, joint capsule, or deep fascia without abscess or osteomyelitis |
3 | Deep ulcer with abscess, osteomyelitis, or joint sepsis |
4 | Gangrene localized to portion of forefoot or heel |
5 | Extensive gangrenous involvement of the entire foot |
Stage/Grade | 0 | 1 | 2 | 3 |
---|---|---|---|---|
A | Pre or post ulcerative lesion completely epithelialised | Superficial wound. Not involving tendon, capsule, or bone | Wound penetrating to tendon or capsule | Wound penetrating to bone or joint |
B | With infection | With infection | With infection | With infection |
C | With ischemia | With ischemia | With ischemia | With ischemia |
D | With infection and ischemia | With infection and ischemia | With infection and ischemia | With infection and ischemia |
Author | Study Design | Primary Measure | Exclusion Criteria | Results | Micronutrients (Basal→Final) | Limitations |
---|---|---|---|---|---|---|
Armstrong et al. | RCT | Arginine, glutamine and beta-hydroxy-beta-methylbutyrate | Pregnancy, <6 weeks post-partum, breastfeeding, <18 years old, ulceration on lesser digits that was diabetic or neuropathic in aetiology, ulcer <30 days or > 12 months duration, ulcer surface area <1 cm2 or >10 cm2, ankle-brachial index <0.7 or >1.2, change in medication during the trial period, any dietary supplements or alternative therapies, not agreeable to wear offloading device | No difference in wound closure or time to wound healing in non-ischemic patients or those with normal baseline albumin. Post-hoc analysis of those in the intervention group with baseline low albumin levels showed improved healing at 16 weeks vs. placebo (p = 0.03). Those with ABI <1.0 had increased healing rates when compared to placebo (p = 0.008). | N/A | Study limited to those with University of Texas ulcer classification 1A. Study period of 16 weeks which may not be long enough to identify overall benefit in larger population group |
Badedi et al. | Case-control | Vit B12 | Anyone taking B12 supplementation | B12 deficiency was significantly associated with DFU (odds ratio 3.1), indicating patients with vitamin B12 deficiency were 3 times more likely to develop a foot ulcer | N/A | Diabetes duration was significantly longer in DFU group, and higher rate of neuropathy and arterial disease. The study design cannot prove causation. |
Bolajoko et al. | Case-control | Vit C and E, Cu, Se and Zn | Pregnancy, healthy controls with fasting glucose >5.6 mmol/L, peripheral arterial disease, osteomyelitis at ulcer site, those with renal or liver disease | Significantly lower vitamin C (p = 0.003), selenium and vitamin E in those with DFU vs. controls (p < 0.001). No significant change in copper or zinc | N/A | Control group was not diabetic. Ulcer size was not correlated with vitamin levels |
Boykin et al. | Retro cohort | 5 mg folic acid, 4 mg cyanocobalamin (B12), and 50 mg pyridoxine (B6) | If NPWT had been used previously, any change in medication within 1 month of folic acid treatment, or the wound had reduced in size by 50% 4 weeks prior to starting folic acid | Significant improvements in wound areas for 4-week periods before and after high dose folic acid treatment (p < 0.05) | N/A | Small sample size, blood tests not completed prior to treatment with high dose folic acid, no control group |
Eneroth et al. | RCT | 400 kcal liquid oral supplementation (20 g protein per 200 mL plus other unspecified micronutrients) | Active chronic inflammatory intestinal disease, immunosuppressive treatment, malignancy, decreased kidney function, severe heart disease, psychiatric or addictive illness | At 6 months wound healing achieved in 8 out of 23 patients (41%) in the placebo group, and in 7 out of 17 (35%) in the intervention group. 24% of patients with protein energy malnutrition had healed at 6 months when compared with 50% of those without it. Neither of these results were significant. | Y Protein-energy malnutrition, 44%→52% of those in placebo group and 19%→27% in the intervention | Small sample size, did not assess a specific nutrient, regular food and fluid intake was not assessed after the intervention, not known if the supplement led to a decrease in normal food or fluid intake |
Kamble et al. | RCT | 60,000 IU Vit D weekly | Non diabetic foot ulcer, chronic kidney disease, liver disease, taking immunosuppressant’s or calcium supplements | Decrease in HbA1c (p = 0.008) and total cholesterol (p = 0.05) vs. controls. Decrease in wound surface area (p = 0.0001) | Y Baseline Vit D 20.5→20.1 ng/mL in controls and 18.5→31.0 (p = 0.0001) in D group | Small sample size, wound area was measured by calculation of greatest length and width, not using digital photography or wound analysis software |
Pena et al. | Prosp cohort | Vit A, C, D; and E, Cu and Zn | Nondiabetic, under 18 years of age | Increased severity of DFU associated with lower vitamin C concentrations (p = 0.02). 1 in 5 patients had non-measurable vitamin C | N/A | Clinical correlation not assessed with healing outcomes. Further research needed to identify clinical implications of deficiencies and effect on healing |
Smart et al. | Prosp cohort | Vit D | Anyone under 18 years of age | Poor wound healing associated with older age and higher HbA1c (p < 0.0001). Exposed bone, or temperature difference over 3°F were linked to poor healing (p < 0.006). Lower 25(OH)D levels correlated with poor healing | N/A | No control group. Only a cross-sectional study and a RCT follow up to assess causal link between vitamin D and wound healing outcomes |
Zubair et al. | Prosp cohort | Vit D | Patients with inflammatory, infectious, autoimmune, rheumatic diseases, cancer, or severe renal or liver failure. Those taking anti-inflammatory drugs. Those with recent VTE | Higher vitamin D inadequacy (97.1%) in DFU patients vs. diabetic controls. HbA1c, triglycerides, neuropathy, retinopathy, hypertension, smoking and nephropathy were all linked to DFU development | Diabetic subjects with and without foot disease included. Unclear whether vitamin D is directly related to delayed wound healing or a secondary effect |
First Author, City, Year | Nutrient(s) Tested | Sample Size Initial→Final | Age (y) | M:F | BMI (kg/m2) | Ins Rx | W-M Grade | HbA1c Basal→Final (%) | Length Basal→Final (cm) | Width Basal→Final (cm) | Depth Basal→Final (cm) | Micro-Nutrients Basal→Final | Allocation and Notes |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Afzali ## Kashan 2019 | 250 mg Mg oxide + 400 IU Vit E | 30 placebo→28 | 55.5 ± 4.9 | 22:6 | 29.7 ± 3.9 | NR | 3 | 7.6→7.4 | 3.1→2.3 | 2.5→1.8 | 1.1→0.9 | 1.51→1.50 | Block randomised, 2 tablets from different makers for active group, unclear if same number of tablets for placebo group (third manufacturer). |
30 active→29 | 57.2 ± 11.0 | 23:6 | 30.3 ± 3.9 | NR | 3 | 7.4→6.8 ** | 2.8→1.6 * | 2.1→1.2 * | 0.9→0.4 * | 1.55→1.83 (p < 0.001) | |||
Mohseni ## Babol 2018 | Probiotic 2 × 109 CFU/g each | 30 placebo→28 | 58.5 ± 11.0 | 20:10 | 25.3 ± 3.7 | 100% | 3 | 7.9→7.7 | 3.2→2.4 | 2.6→1.9 | 1.1→0.8 | N/A | Randomised by clinic staff. 1 placebo subject lost to follow-up but paper states 30 people analysed. Not clear where data has fewer subjects. |
30 active→30 | 62.6 ± 9.7 | 20:10 | 26.4 ± 3.0 | 100% | 3 | 8.0→7.4 ** | 3.2→1.9 * | 2.4→1.3 * | 1.2→0.7 * | ||||
Momen-Heravi ## Kashan 2017 | 220 mg zinc sulphate | 30 placebo→28 | 60.0 ± 10.0 | 21:9 | 25.8 ± 3.1 | 100% | 3 | 7.9→7.8 | 3.1→2.2 | 2.7→1.9 | 1.3→1.0 | 77.6→74.0 | Randomised by clinic staff. 2 placebo subjects lost to follow-up and 30 people analysed. Not clear where data has fewer subjects. |
30 active | 58.3 ± 8.6 | 21:9 | 25.8 ± 3.0 | 100% | 3 | 7.8→7.3 ** | 3.1→1.6 * | 2.9→1.5 * | 1.3→0.8 * | 76.4→89.1 (p < 0.001) | |||
Razzaghi ^^ Kashan 2017 | 50,000 IU Vit D | 30 placebo→28 | 58.6 ± 8.6 | 22:8 | 26.2 ± 3.8 | 100% | 3 | 7.8→7.7 | NR. −1.1 cm | NR −1.1 cm | NR −0.5 cm | 20.2→18.4 | Randomisation by clinic staff. 2 placebo subjects lost to follow-up and 30 people analysed. Unclear where data has lower N. Ulcer size in 1cm increments. |
30 active | 59.6 ± 8.2 | 22:8 | 26.0 ± 4.4 | 100% | 3 | 8.3→7.7 ** | NR −2.1 cm * | NR −2.0 cm * | NR −1.0 cm * | 15.2→28.1 (p < 0.001) | |||
Razzaghi ~~ Kashan 2018 | 250 mg Mg oxide | 35 placebo→31 | 59.0 ± 10.1 | 24:11 | 26.2 ± 4.1 | 100% | 3 | 7.8→7.7 | 3.6→2.7 | 2.9→2.1 | 1.3→0.9 | 2.0→1.9 | Randomised by clinic staff. 9 lost to follow-up but reported as 70 people analysed. Not clear where data has fewer subjects. |
35 active→30 | 60.1 ± 11.1 | 22:13 | 28.2 ± 5.2 | 100% | 3 | 8.3→7.6 ** | 3.6→1.8 * | 3.3→1.7 * | 1.7→0.9 * | 2.1→2.3 (p < 0.001) | |||
Soleimani ^^ Kashan 2017 | 1000mg omega-3 PUFA from flaxseed bd | 30 placebo→28 | 59.9 ± 9.2 | 23:7 | 26.9 ± 2.7 | 100% | 3 | 7.9→7.8 | 3.4→2.4 | 2.9→1.9 | 1.3→0.8 | N/A | Randomised by clinic staff. 5 lost to follow-up, reported as 60 analysed. Unclear where N is lower. |
30 active→27 | 58.8 ± 11.2 | 23:7 | 27.0 ± 4.5 | 100% | 3 | 7.5→6.6 ** | 3.5→1.4 | 2.9→1.1 | 1.4→0.5 |
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Bechara, N.; Gunton, J.E.; Flood, V.; Hng, T.-M.; McGloin, C. Associations between Nutrients and Foot Ulceration in Diabetes: A Systematic Review. Nutrients 2021, 13, 2576. https://doi.org/10.3390/nu13082576
Bechara N, Gunton JE, Flood V, Hng T-M, McGloin C. Associations between Nutrients and Foot Ulceration in Diabetes: A Systematic Review. Nutrients. 2021; 13(8):2576. https://doi.org/10.3390/nu13082576
Chicago/Turabian StyleBechara, Nada, Jenny E. Gunton, Victoria Flood, Tien-Ming Hng, and Clare McGloin. 2021. "Associations between Nutrients and Foot Ulceration in Diabetes: A Systematic Review" Nutrients 13, no. 8: 2576. https://doi.org/10.3390/nu13082576