[Nutrition in the prevention and healing of chronic wounds. Importance in improving the diabetic foot]. / La nutrición en la prevención y curación de heridas crónicas. Importancia en la mejora del pie diabético.

INTRODUCTION: Nutrition plays an essential role in chronic wound healing as extra nutrients are needed for tissue repair and to restore losses through wound exudate. Insufficient intake of energy, protein, antioxidants (vitamin C, A, and zinc) and vitamin D are common in patients with chronic wounds and have been linked to delayed wound healing and dehiscence. Other risk factors such as obesity, diabetes, advanced age, corticosteroid use, and dehydration can also reduce or impede the healing process, and nutritional screening is important to identify patients with malnutrition. Proteins, amino acids (arginine, glutamine and methionine), vitamins C and A, and zinc have been used as pharmacological nutrients in pressure ulcer healing; however, omega-3 fatty acids, although they appear to slow progression, do not show improved healing rates. In patients with diabetic foot, supplementation with vitamins D, C, A, and E, magnesium, zinc, omega-3 fatty acids, and probiotics reduces ulcer size and improves glycemic control, although they have not been associated with complete healing; however, supplementation with arginine, glutamine, and ß-hydroxy-ß-methylbutyrate does show wound healing, although further evidence is needed to confirm these results.

INTRODUCCIÓN: La nutrición tiene un papel esencial en la cicatrización de las heridas crónicas ya que se necesita un aporte extra de nutrientes en la reparación tisular y para restablecer las pérdidas originadas a través del exudado de la herida. El aporte insuficiente de energía, proteínas, antioxidantes (vitamina C, vitamina A y zinc) y vitamina D es frecuente en los pacientes con heridas crónicas y se ha relacionado con retrasos en la curación y dehiscencia de la herida. También otros factores de riesgo como la obesidad, la diabetes, la edad avanzada, el consumo de glucocorticoides y la deshidratación pueden disminuir o impedir el proceso de la cicatrización, siendo importante la realización de un cribado nutricional para identificar a los pacientes con desnutrición. Las proteínas, los aminoácidos (arginina, glutamina y metionina), las vitaminas C y A, y el zinc se han utilizado como nutrientes farmacológicos para la cicatrización de las úlceras por presión; sin embargo, los ácidos grasos omega-3, aunque parecen disminuir su progresión, no muestran mejores tasas de curación. En los pacientes con pie diabético, la suplementación con vitaminas D, C, A y E, magnesio, zinc y ácidos grasos omega-3, así como la administración de probióticos, reduce el tamaño de la úlcera y mejora el control glucémico, aunque no se han relacionado con una cicatrización completa; sin embargo, la suplementación con arginina, glutamina y ß-hidroxi-ß-metilbutirato logra la curación de la herida, aunque es necesaria una mayor evidencia que confirme estos resultados.

La nutrición en la prevención y curación de heridas crónicas. Importancia en la mejora del pie diabético / Nutrition in the prevention and healing of chronic wounds. Importance in improving the diabetic foot

La nutrición tiene un papel esencial en la cicatrización de las heridas crónicas ya que se necesita un aporte extra de nutrientes en la reparación tisular y para restablecer las pérdidas originadas a través del exudado de la herida. El aporte insuficiente de energía, proteínas, antioxidantes (vitamina C, vitamina A y zinc) y vitamina D es frecuente en los pacientes con heridas crónicas y se ha relacionado con retrasos en la curación y dehiscencia de la herida. También otros factores de riesgo como la obesidad, la diabetes, la edad avanzada, el consumo de glucocorticoides y la deshidratación pueden disminuir o impedir el proceso de la cicatrización, siendo importante la realización de un cribado nutricional para identificar a los pacientes con desnutrición. Las proteínas, los aminoácidos (arginina, glutamina y metionina), las vitaminas C y A, y el zinc se han utilizado como nutrientes farmacológicos para la cicatrización de las úlceras por presión; sin embargo, los ácidos grasos omega-3, aunque parecen disminuir su progresión, no muestran mejores tasas de curación. En los pacientes con pie diabético, la suplementación con vitaminas D, C, A y E, magnesio, zinc y ácidos grasos omega-3, así como la administración de probióticos, reduce el tamaño de la úlcera y mejora el control glucémico, aunque no se han relacionado con una cicatrización completa; sin embargo, la suplementación con arginina, glutamina y β-hidroxi-β-metilbutirato logra la curación de la herida, aunque es necesaria una mayor evidencia que confirme estos resultados. (AU)

Nutrition plays an essential role in chronic wound healing as extra nutrients are needed for tissue repair and to restore losses through wound exudate. Insufficient intake of energy, protein, antioxidants (vitamin C, A, and zinc) and vitamin D are common in patients with chronic wounds and have been linked to delayed wound healing and dehiscence. Other risk factors such as obesity, diabetes, advanced age, corticosteroid use, and dehydration can also reduce or impede the healing process, and nutritional screening is important to identify patients with malnutrition. Proteins, amino acids (arginine, glutamine and methionine), vitamins C and A, and zinc have been used as pharmacological nutrients in pressure ulcer healing; however, omega-3 fatty acids, although they appear to slow progression, do not show improved healing rates. In patients with diabetic foot, supplementation with vitamins D, C, A, and E, magnesium, zinc, omega-3 fatty acids, and probiotics reduces ulcer size and improves glycemic control, although they have not been associated with complete healing; however, supplementation with arginine, glutamine, and β-hydroxy-β-methylbutyrate does show wound healing, although further evidence is needed to confirm these results. (AU)

Nutritional interventions for treating foot ulcers in people with diabetes.

BACKGROUND: Foot ulcers in people with diabetes are non-healing, or poorly healing, partial, or full-thickness wounds below the ankle. These ulcers are common, expensive to manage and cause significant morbidity and mortality. The presence of a wound has an impact on nutritional status because of the metabolic cost of repairing tissue damage, in addition to the nutrient losses via wound fluid. Nutritional interventions may improve wound healing of foot ulcers in people with diabetes. OBJECTIVES: To evaluate the effects of nutritional interventions on the healing of foot ulcers in people with diabetes. SEARCH METHODS: In March 2020 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated the effect of nutritional interventions on the healing of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS: Two review authors, working independently, assessed included RCTs for their risk of bias and rated the certainty of evidence using GRADE methodology, using pre-determined inclusion and quality criteria. MAIN RESULTS: We identified nine RCTs (629 participants). Studies explored oral nutritional interventions as follows: a protein (20 g protein per 200 mL bottle), 1 kcal/mL ready-to-drink, nutritional supplement with added vitamins, minerals and trace elements; arginine, glutamine and ß-hydroxy-ß-methylbutyrate supplement; 220 mg zinc sulphate supplements; 250 mg magnesium oxide supplements; 1000 mg/day omega-3 fatty acid from flaxseed oil; 150,000 IU of vitamin D, versus 300,000 IU of vitamin D; 250 mg magnesium oxide plus 400 IU vitamin E and 50,000 IU vitamin D supplements. The comparator in eight studies was placebo, and in one study a different dose of vitamin D. Eight studies reported the primary outcome measure of ulcer healing; only two studies reported a measure of complete healing. Six further studies reported measures of change in ulcer dimension, these studies reported only individual parameters of ulcer dimensions (i.e. length, width and depth) and not change in ulcer volume. All of the evidence identified was very low certainty. We downgraded it for risks of bias, indirectness and imprecision. It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, increases the proportion of ulcers healed at six months more than placebo (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.42 to 1.53). It is also uncertain whether arginine, glutamine and ß-hydroxy-ß-methylbutyrate supplement increases the proportion of ulcers healed at 16 weeks compared with placebo (RR 1.09, 95% CI 0.85 to 1.40). It is uncertain whether the following interventions change parameters of ulcer dimensions over time when compared with placebo; 220 mg zinc sulphate supplement containing 50 mg elemental zinc, 250 mg magnesium oxide supplement, 1000 mg/day omega-3 fatty acid from flaxseed oil supplement, magnesium and vitamin E co-supplementation and vitamin D supplementation. It is also uncertain whether 150,000 IU of vitamin D, impacts ulcer dimensions when compared with 300,000 IU of vitamin D. Two studies explored some of the secondary outcomes of interest for this review. It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, reduces the number of deaths (RR 0.96, 95% CI 0.06 to 14.60) or amputations (RR 4.82, 95% CI 0.24 to 95.88) more than placebo. It is uncertain whether arginine, glutamine and ß-hydroxy-ß-methylbutyrate supplement increases health-related quality of life at 16 weeks more than placebo (MD -0.03, 95% CI -0.09 to 0.03). It is also uncertain whether arginine, glutamine and ß-hydroxy-ß-methylbutyrate supplement reduces the numbers of new ulcers (RR 1.04, 95% CI 0.71 to 1.51), or amputations (RR 0.66, 95% CI 0.16 to 2.69) more than placebo. None of the included studies reported the secondary outcomes cost of intervention, acceptability of the intervention (or satisfaction) with respect to patient comfort, length of patient hospital stay, surgical interventions, or osteomyelitis incidence. One study exploring the impact of arginine, glutamine and ß-hydroxy-ß-methylbutyrate supplement versus placebo did not report on any relevant outcomes. AUTHORS' CONCLUSIONS: Evidence for the impact of nutritional interventions on the healing of foot ulcers in people with diabetes compared with no nutritional supplementation, or compared with a different dose of nutritional supplementation, remains uncertain, with eight studies showing no clear benefit or harm. It is also uncertain whether there is a difference in rates of adverse events, amputation rate, development of new foot ulcers, or quality of life, between nutritional interventions and placebo. More research is needed to clarify the impact of nutritional interventions on the healing of foot ulcers in people with diabetes.

Nutritional Supplementation for Diabetic Foot Ulcers: The Big Challenge.

Diabetic foot ulcers remain difficult to heal and nutritional supplementation may be an important complementary therapeutic measure. However, we need to clarify many issues before such supplementation is more widely used. Indeed, improvements are needed in the following areas: evaluation of nutritional inadequacy, completion of randomized controlled trials, understanding of patient and ulcer characteristics that favor response to nutritional supplementation, optimal duration of supplementation therapy, and evaluation of patient adherence. The challenge is now to acquire more knowledge in the aforementioned areas.

Nutrition and Lower Extremity Ulcers: Causality and/or Treatment.

The association between malnutrition, impaired wound healing, and the presence of chronic wounds has been recognized for a long time. It is widely believed that the lack of adequate nutrition increases the risk of developing wounds which have a great likelihood of progressing to chronicity due to lack of appropriate healing responses. This risk is particularly high in the aging population. For the individual patient, as well as patient populations, the diagnosis of malnutrition has been in dispute; further, there is lack of agreement of when and how to intervene nutritionally in those with wounds or healing deficits. This article examines the relationship of nutritional status with the presence and clinical evolution of leg ulcers in humans, focusing on diabetic and venous leg ulcers; we will further review the effect of nutritional therapy on the outcome of these ulcers.

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.

BACKGROUND: Data on the effects of flaxseed oil omega-3 fatty acids supplementation on wound healing and metabolic status in subjects with diabetic foot ulcer (DFU) are scarce. OBJECTIVE: This study was conducted to evaluate the effects of flaxseed oil omega-3 fatty acids supplementation on wound healing and metabolic status in subjects with DFU. METHODS: The current randomized, double-blind, placebo-controlled trial was conducted among 60 subjects (aged 40-85years old) with grade 3 DFU. Subjects were randomly allocated into two groups (30 subjects each group) to receive either 1000mg omega-3 fatty acids from flaxseed oil supplements or placebo twice a day for 12weeks. RESULTS: After the 12-week intervention, compared with the placebo, omega-3 fatty acids supplementation resulted in significant decreases in ulcer length (-2.0±2.3 vs. -1.0±1.1cm, P=0.03), width (-1.8±1.7 vs. -1.0±1.0cm, P=0.02) and depth (-0.8±0.6 vs. -0.5±0.5cm, P=0.01). Additionally, significant reductions in serum insulin concentrations (-4.4±5.5 vs. +1.4±8.3 µIU/mL, P=0.002), homeostasis model of assessment-estimated insulin resistance (-2.1±3.0 vs. +1.0±5.0, P=0.005) and HbA1c (-0.9±1.5 vs. -0.1±0.4%, P=0.01), and a significant rise in the quantitative insulin sensitivity check index (+0.01±0.01 vs. -0.005±0.02, P=0.002) were seen following supplementation with omega-3 fatty acids compared with the placebo. In addition, omega-3 fatty acids supplementation significantly decreased serum high sensitivity C-reactive protein (hs-CRP) (-25.5±31.5 vs. -8.2±18.9µg/mL, P=0.01), and significantly increased plasma total antioxidant capacity (TAC) (+83.5±111.7 vs. -73.4±195.5mmol/L, P<0.001) and glutathione (GSH) concentrations (+60.7±140.2 vs. -15.5±129.7µmol/L, P=0.03) compared with the placebo. CONCLUSIONS: Overall, omega-3 fatty acids supplementation for 12weeks among subjects with DFU had beneficial effects on parameters of ulcer size, markers of insulin metabolism, serum hs-CRP, plasma TAC and GSH levels. In addition, flaxseed oil omega-3 fatty acids may have played an indirect role in wound healing due to its effects on improved metabolic profiles.

Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial.

AIMS: Among people with diabetes, 10-25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and ß-hydroxy-ß-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes. METHODS: Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and ß-hydroxy-ß-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle-brachial index, and supplementation on healing was investigated. RESULTS: Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle-brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and ß-hydroxy-ß-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38) times more likely to heal. CONCLUSIONS: While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and ß-hydroxy-ß-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and ß-hydroxy-ß-methylbutyrate in these high-risk subgroups might prove clinically valuable.

Diet and paraoxonase 1 enzymatic activity in diabetic foot patients from Romania and Belgium: favorable association of high flavonoid dietary intake with arylesterase activity.

BACKGROUND/AIMS: The antiatherosclerotic enzyme paraoxonase (PON1) is affected by disease and lifestyle. We investigated the impact of diet in diabetic foot patients from 2 European countries. METHODS: Dietary intake and serum PON1 activity, using as substrate paraoxon (paraoxonase) or phenylacetate (arylesterase), were assessed in patients from Bucharest (n = 40) and Antwerp (n = 30) and in 34 healthy controls. RESULTS: The diabetic patients had lower paraoxonase and arylesterase activities than the controls. Arylesterase was lowest in the Bucharest patients, 116 +/- 42 U/ml, versus 141 +/- 43 and 184 +/- 49 U/ml in the Antwerp patients and controls, respectively (p < 0.0005). The Bucharest patients had worse glycemic control, higher blood pressure, lower HDL cholesterol and a diet richer in cholesterol and poorer in monounsaturated fats and fish. In contrast, their median intake of vitamins E and C, folic acid and flavonoids was higher, 82 mg (range: 4-259 mg), versus 28 mg (range: 5-169 mg) aglycone units in Antwerp (p = 0.005). Flavonoid intake predicted arylesterase independently of HDL cholesterol, region and sex (beta = 0.27; p = 0.03), and patients with high intake achieved normal levels of arylesterase (30.1 +/- 10.0 U/micromol in the highest versus 21.0 +/- 8.2 U/micromol total cholesterol in the lowest tertile; p = 0.02). CONCLUSION: A flavonoid-rich diet is positively associated with PON1 arylesterase activity in diabetic foot patients.

Nutritional supplementation for diabetic foot ulcers: the first RCT.

OBJECTIVE: To determine if oral nutritional supplementation improved wound healing in malnourished patients with diabetic foot ulcers when compared with a placebo. METHOD: This prospective randomised controlled double-blind trial involved patients aged over 60 with diabetes mellitus and a Wagner grade I-II foot ulcer of over four weeks' duration. Patients received either 400 ml (400 kcal) oral nutritional supplementation (n = 26) or 400 ml placebo (n = 27) daily for six months. Patients were followed monthly for six months and after one and two years. RESULTS: A third of the patients were classified as having protein-energy malnutrition at inclusion, with no difference between the two groups. Critical leg ischaemia was more common in the intervention group than in the placebo group (p = 0.008). Nine patients in the intervention group (35%) and four in the placebo group (15%) dropped out of the study (not significant). Of those who completed the study, the wound had healed at six months in eight out of 23 patients (41%) (placebo) and in seven out of 17 (35%) (intervention) (not significant). Twenty-four per cent of patients with protein-energy malnutrition at inclusion had healed at six months compared with 50% of those without it (not significant). CONCLUSION: This is the first study to evaluate the possible benefits of nutritional supplementation on diabetic foot ulcers. A third of patients were malnourished. We encountered several methodological problems and were unable to demonstrate an improved wound healing rate in these patients.