Exercise-Induced Transient Oxidative Stress Is Mitigated in Down Syndrome: Insights About Redox Balance and Muscle Strength.

ABSTRACT: Reis, AL, Deus, LA, Neves, RVP, Corrêa, HL Reis, TL, Aguiar, LS Honorato, FS, Barbosa, JMS, Araújo, TB, Palmeira, TRC, Simões, HG, Prestes, J, Sousa, CV, Ide, BN, and Rosa, TdS. Exercise-induced transient oxidative stress is mitigated in Down syndrome: insights about redox balance and muscle strength. J Strength Cond Res 38(3): e125-e34, 2024-This study aimed to evaluate the acute effects of a session of resistance exercise (RE) performed with elastic tubes on the redox balance and inflammatory profile in individuals with Down syndrome (DS). Subjects ( n = 23) were allocated into 2 groups: individuals with DS (DS; n = 11) and individuals without DS (WDS; n = 12), who performed an acute RE session. Diagnostic assessment included medical history, anthropometric measures (body height, body mass, body mass index, and body composition assessment), biological collections, muscle strength assessments (handgrip and maximal voluntary isometric contraction tests), and exercises. The redox balance and inflammatory profile were assessed in urine and saliva samples before and after an acute RE session. There were no differences between WDS and DS groups for body composition ( p > 0.05). The DS group presented higher values pre and post an acute RE session with elastic tubes for oxidative and proinflammatory markers compared with WDS ( p < 0.05). Uric acid values increased from pre-acute RE session to post-acute RE session for WDS ( p < 0.0001). No differences were identified within groups for the delta analysis ( p > 0.05). Inverse correlations were found between total force and F2-isoprostane, 8OHdG, uric acid, allantoin, IL-6, TNF-α, and the TNF-α:IL-10 ratio. A positive correlation was found between IL-10 and total force. The DS group presented increased peak force in the knee extension and elbow flexion exercises (∼25 and 12%, respectively) but decreases in handgrip strength of ∼7%. The WDS group showed higher peak force values for knee extension, elbow flexion, and handgrip (∼16, 10, and 14%, respectively). The DS group had lower transient elevation of oxidative stress after an acute RE session compared with WDS. Oxidative stress and inflammation responses of DS to an acute RE session with elastic tubes may be insufficient to induce health adaptations for the same relative load compared with WDS.

Impact of cluster set resistance training on strength, functional capacity, metabolic and inflammatory state in older hemodialysis subjects: A randomized controlled clinical trial.

BACKGROUND AND AIMS: Hemodialysis-associated neuromuscular dysfunction appears to be counteracted by resistance training (RT) in older patients with chronic kidney disease (CKD). Thus, the aim of the present study was to evaluate the impact of cluster-set RT protocol on anthropometric parameters, functional capacities, and biochemical variables in older patients with CKD. METHODS AND RESULTS: Seventy-eight older patients (age: 57.55 ± 4.06 years) with CKD undergoing maintenance hemodialysis participated, and were randomly divided into control group (CG, N = 26), traditional RT (RT, N = 26) and cluster-set RT (RT-CS, N = 26) groups. Participants completed 24 weeks of RT three times per week, 1 h and 30 min before the hemodialysis session. Patients from the RT-CS group displayed increased adherence as compared to the RT group (66.35 % versus 61.73 %, p < 0.0001). There was an improvement of all anthropometric variables, handgrip strength, timed up and-go (TUG) and six-minute walking test (6MWT) following both training protocols when compared to control group and pre-intervention values. Fasting blood glucose decreased for both RT and RT-CS groups as compared with pre-intervention, without differences between training protocols and CG. Glycated hemoglobin, inflammatory cytokines, and triglycerides decreased in RT and RT-CS groups as compared with pre-intervention and CG, without differences between them. Furthermore, the RT-CS protocol resulted in a greater number of people who were responsive to training when compared to traditional training. CONCLUSIONS: RT-CS is a clinically valuable tool to improve anthropometric parameters, handgrip strength, TUG, 6MWT, fasting blood glucose, and cytokines in CKD older patients.

The effects of home-based progressive resistance training in chronic kidney disease patients.

INTRODUCTION: Faced with lockdowns, it was mandatory the development of supervised home-based RT protocols to keep patients with chronic kidney disease engaged in programs. Nonetheless, there is a lack of scientific literature regarding its effects on patients. PURPOSE: To investigate the effects of a supervised home-based progressive resistance training program on functional performance, bone mineral density, renal function, endothelial health, inflammation, glycemic homeostasis, metabolism, redox balance, and the modulation of exerkines in patients with CKD in stage 2. METHODS: Patients (n = 31) were randomized and allocated into the control group (CTL; n = 15; 58.07 ± 5.22 yrs) or resistance training group (RT; n = 16; 57.94 ± 2.74 yrs). RT group performed 22 weeks of supervised progressive home-based resistance exercises. Bone mineral density, anthropometric measurements, and functional performance were assessed. Venous blood samples were collected at baseline and after the intervention for the analysis of markers of renal function, endothelial health, inflammation, glycemic homeostasis, metabolism, and redox balance. RESULTS: Twenty-two weeks of home-based RT were effective in improving (P < 0.05) functional performance, bone mineral density, uremic profile, ADMA, inflammatory markers, the Klotho-FGF23 axis, glycemic homeostasis markers, and exerkines. These improvements were accompanied by higher concentrations of exerkines and anti-inflammatory cytokines. RT group displayed a decrease in cases of osteopenia after the intervention (RT: 50 % vs. CTL: 86.7 %; X2 = 4.763; P = 0.029). CONCLUSION: Results provide new evidence that supervised home-based progressive RT may be a relevant intervention to attenuate the progression of CKD and improve functional capacity, bone mineral density, and the immunometabolic profile. These improvements are associated with positive modulation of several exerkines.

Could cardiac autonomic modulation be an objective method to identify hypobaric hypoxia symptoms at 25.000ft among Brazilian military airmen?

Hypobaric hypoxia during a flight can cause accidents, resulting in deaths. Heart rate variability may be more sensitive than self-reported hypoxia symptoms to the effects of HH. The level of physical fitness can contribute to efficient cardiac autonomic modulation. However, no studies have examined the association between fitness, heart rate variability, and the time of onset of hypobaric hypoxia symptoms. To analyze the influence of hypobaric hypoxia on cardiac autonomic function at the time of onset of the first symptoms and its association with physical fitness. Male airmen trained and belonging to the staff of the Brazilian Air Force (n = 23; 30 ± 6.7 years) participated in a flight simulation in a 25.000 ft hypobaric chamber. Heart rate variability was recorded with a Polar® cardiac monitor. Data were analyzed in the time-domain method using Kubios software. We evaluated pulse oximetry with the Mindray PM-60 oximeter. Physical fitness assessment test results were collected from the archive. At moments rest vs. hypoxia revealed a decrease in heart rate variability indices iRR and RMSSD (p < 0.001). The individual analysis of hypoxia-rest variation showed that 100% of the airmen had a negative delta for both iRR and RMSSD indices. The time of onset of hypoxia symptoms was not associated with body composition, physical fitness, oxygen saturation, and HRV indices. Also, we suggest that cardiac autonomic modulation seems to be more sensitive to the effects of hypobaric hypoxia at 25.000 ft than the self-reported subjective perception of symptoms. Further devices that alert to a hypoxic condition during a flight should consider heart rate variability allowing more time and security to reestablish control of the flight.

Phosphate and IL-10 concentration as predictors of long-covid in hemodialysis patients: A Brazilian study.

Background: The global burden of persistent COVID-19 in hemodialysis (HD) patients is a worrisome scenario worth of investigation for the critical care of chronic kidney disease (CKD). We performed an exploratory post-hoc study from the trial U1111-1237-8231 with two specific aims: i) to investigate the prevalence of COVID-19 infection and long COVID symptoms from our Cohort of 178 Brazilians HD patients. ii) to identify whether baseline characteristics should predict long COVID in this sample. Methods: 247 community-dwelling older (>60 years) patients (Men and women) undergoing HD (glomerular filtration rate < 15 mL/min/1.73m2) with arteriovenous fistula volunteered for this study. All patients presented hypertension and diabetes. Patients were divided in two groups: without long-COVID and with long-COVID. Body composition, handgrip strength, functional performance, iron metabolism, phosphate, and inflammatory profile were assessed. Patients were screened for 11-months after COVID-19 infection. Results were considered significant at P < 0.05. Results: We found that more than 85% of the COVID-19 infected patients presented a severe condition during the infection. In our sample, the mortality rate over 11-month follow was relatively low (8.4%) when compared to worldwide (approximately 36%). Long COVID was highly prevalent in COVID-19 survivors representing more than 80% of all cases. Phosphate and IL-10 were higher in the long COVID group, but only phosphate higher than 5.35 mg/dL appears to present an increased prevalence of long COVID, dyspnea, and fatigue. Conclusion: There was a high prevalence of COVID-19 infection and long COVID in HD patients from the Brazilian trial 'U1111-1237-8231'. HD clinics should be aware with phosphate range in HD patients as a possible target for adverse post-COVID events.

A systematic review and meta-analysis demonstrating Klotho as an emerging exerkine.

Klotho is an anti-aging protein with several therapeutic roles in the pathophysiology of different organs, such as the skeletal muscle and kidneys. Available evidence suggests that exercise increases Klotho levels, regardless of the condition or intervention, shedding some light on this anti-aging protein as an emergent and promising exerkine. Development of a systematic review and meta-analysis in order to verify the role of different exercise training protocols on the levels of circulating soluble Klotho (S-Klotho) protein. A systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE through PubMed, EMBASE, CINAHL, CT.gov, and PEDro. Randomized and quasi-randomized controlled trials that investigated effects of exercise training on S-Klotho levels. We included 12 reports in the analysis, comprising 621 participants with age ranging from 30 to 65 years old. Klotho concentration increased significantly after chronic exercise training (minimum of 12 weeks) (Hedge' g [95%CI] 1.3 [0.69-1.90]; P < 0.0001). Moreover, exercise training increases S-Klotho values regardless of the health condition of the individual or the exercise intervention, with the exception of combined aerobic + resistance training. Furthermore, protocol duration and volume seem to influence S-Klotho concentration, since the effect of the meta-analysis changes when subgrouping these variables. Altogether, circulating S-Klotho protein is altered after chronic exercise training and it might be considered an exerkine. However, this effect may be influenced by different training configurations, including protocol duration, volume, and intensity.

Metabolic and hormonal responses to chronic blood-flow restricted resistance training in chronic kidney disease: a randomized trial.

Maintenance of glycemic and lipemic homeostasis can limit the progression of diabetic kidney disease. Resistance training (RT) is effective in controlling glycemia and lipemia in kidney disease; however, the effect of RT with blood flow restriction (RT+BFR) on these metabolic factors has not been investigated. We aimed to verify if chronic (6 months) RT and RT+BFR performed by patients with stage-2 chronic kidney disease (CKD) improves their glycemic homeostasis and immunometabolic profiles. Patients with CKD under conservative treatment (n = 105 (33 females)) from both sexes were randomized into control (n = 35 (11 females); age 57.6 ± 5.2 years), RT (n = 35 (12 females); age 58.0 ± 6.2 years), and RT+BFR (n = 35 (10 females); 58.0 ± 6.4 years) groups. Chronic RT or RT+BFR (6 months) was performed 3 times per week on non-consecutive days with training loading adjusted every 2 months, RT 50%-60%-70% of 1RM, and RT+BFR 30%-40%+50% of 1RM and fixed repetition number. Renal function was estimated with the glomerular filtration rate and serum albumin level. Metabolic, hormonal, and inflammatory assessments were analyzed from blood samples. Six months of RT and RT+BFR were similarly effective in improving glucose homeostasis and hormone mediators of glucose uptake (e.g., irisin, adiponectin, and sirtuin-1), decreasing pro-inflammatory and fibrotic proteins, and attenuating the progression of estimated glomerular filtration rate. Thus, RT+BFR can be considered an additional exercise modality to be included in the treatment of patients with stage 2 chronic kidney disease. Trial registration number: U1111-1237-8231. URL: http://www.ensaiosclinicos.gov.br/rg/RBR-3gpg5w/, no. RBR-3gpg5w. Novelty: Glycemic regulation induced by resistance training prevents the progression of CKD. Chronic RT and RT+BFR promote similar changes in glycemic regulation. RT and RT+BFR can be considered as non-pharmacological tools for the treatment of CKD.

Modulus of Elasticity of Elastic Tubes Used in Neuromuscular Rehabilitation Programs.

CONTEXT: The elastic tubes have been used for clinical rehabilitation programs in which exercises are performed with submaximal intensities due to the difficulty in the measure the applied force. The authors aimed to quantify the elastic constant of elastic tubes used in neuromuscular rehabilitation programs predicting the force related to elastic tube elongation. A force test was performed by stretching the elastic tubes to determine the relationship between force and elongation. Eight elastic tubes with progressive levels of resistance represented by colors (yellow, red, blue, gray, black, grape, purple, and gold-low to higher resistance) were used. DESIGN: Experimental. METHODS: The test and retest were compared using the paired t test. The agreement and reliability between the test versus retest of pooled means colors were analyzed by plotting the Bland-Altman graph and intraclass correlation coefficient and the coefficient of variation. Pearson correlation was used to verify the validity between measurements. RESULTS: The force values generated from the elastic tube elongation increase according to the color and thickness of elastic tubes with a strong and significant association between them (P < .0001). The elastic constant measurements were similar and presented high intraclass correlation coefficient values, low coefficient of variation values, and were reproducible (P < .0001). CONCLUSIONS: The force could be quantified according to elastic tube length variation by the linear regression equation with reproducibility. It gives greater measurement precision and better training load control when using elastic tubes in strength training programs.

Are Resistance Training-Induced BDNF in Hemodialysis Patients Associated with Depressive Symptoms, Quality of Life, Antioxidant Capacity, and Muscle Strength? An Insight for the Muscle-Brain-Renal Axis.

BACKGROUND: Hemodialysis patients are suffering from depressive symptoms. Brain-derived neurotrophic factor (BDNF) levels are negatively associated with depressive symptoms and decrease during a single hemodialysis session. Resistance training (RT) might be an additional non-pharmacological tool to increase BDNF and promote mental health. METHODS: Two randomized groups of hemodialysis patients: control (CTL, n = 76/F36; 66.33 ± 3.88 years) and RT (n = 81/F35; 67.27 ± 3.24 years). RT completed six months of training thrice a week under the supervision of strength and conditioning professional immediately before the dialysis session. Training loads were adjusted using the OMNI rating of perceived exertion. The total antioxidant capacity (TROLOX), glutathione (GSH), thiobarbituric acid reactive substance (TBARS), and BDNF levels were analyzed in serum samples. Quality of life (assessed through Medical Outcomes-SF36), and Beck Depression Inventory was applied. RESULTS: RT improved handgrip strength (21.17 ± 4.38 vs. 27.17 ± 4.34; p = 0.001) but not for CTL (20.09 ± 5.19 vs. 19.75 ± 5.54; p = 0.001). Post-training, RT group had higher values as compared to CTL related to TROLOX (RT,680.8 ± 225.2 vs. CTL,589.5 ± 195.9; p = 0.001) and GSH (RT, 9.33 ± 2.09 vs. CTL,5.00 ± 2.96; p = 0.001). RT group had lower values of TBARS as compared to CTL at post-training (RT, 11.06 ± 2.95 vs. CTL, 13.66 ± 2.62; p = 0.001). BDNF increased for RT (11.66 ± 5.20 vs. 19.60 ± 7.23; p = 0.001), but decreased for CTL (14.40 ± 4.99 vs. 10.84 ± 5.94; p = 0.001). Quality of life and mental health increased (p = 0.001) for RT, but did not change for CTL (p = 0.001). BDNF levels were associated with emotional dimensions of SF36, depressive symptoms, and handgrip (p = 0.001). CONCLUSIONS: RT was effective as a non-pharmacological tool to increased BDNF levels, quality of life, temper the redox balance and decrease depressive symptoms intensity in hemodialysis patients.

Does the Combined Effect of Resistance Training with EPO and Iron Sulfate Improve Iron Metabolism in Older Individuals with End-Stage Renal Disease?

We sought to investigate the effects of resistance training (RT) combined with erythropoietin (EPO) and iron sulfate on the hemoglobin, hepcidin, ferritin, iron status, and inflammatory profile in older individuals with end-stage renal disease (ESRD). ESRD patients (n: 157; age: 66.8 ± 3.6; body mass: 73 ± 15; body mass index: 27 ± 3), were assigned to control (CTL; n: 76) and exercise groups (RT; n: 81). The CTL group was divided according to the iron treatment received: without iron treatment (CTL-none; n = 19), treated only with iron sulfate or EPO (CTL-EPO or IRON; n = 19), and treated with both iron sulfate and EPO (CTL-EPO + IRON; n = 76). The RT group followed the same pattern: (RT-none; n = 20), (RT-EPO or IRON; n = 18), and (RT-EPO + IRON; n = 86). RT consisted of 24 weeks/3 days per week at moderate intensity of full-body resistance exercises prior to the hemodialysis section. The RT group, regardless of the iron treatment, improved iron metabolism in older individuals with ESRD. These results provide some clues on the effects of RT and its combination with EPO and iron sulfate in this population, highlighting RT as an important coadjutant in ESRD-iron deficiency.

Impact of Low Hemoglobin on Body Composition, Strength, and Redox Status of Older Hemodialysis Patients Following Resistance Training.

INTRODUCTION: The purpose of this study was to: (i) investigate the effect of six months of resistance training (RT) on body composition, muscle strength, hematological patterns, and redox profile in maintenance hemodialysis (HD) patients, and; (ii) evaluate the effects of baseline concentrations of hemoglobin on the RT response. METHODS: One hundred fifty-seven subjects with chronic kidney disease (CKD) were randomly allocated into two groups: Control [CTL, (n = 76)] and RT (n = 81). A first visit was required for anamnesis and anthropometric measurements. Venous blood samples were collected at baseline and after twenty-four weeks of training in all patients for the analysis of clinical and redox balance markers. The RT program spanned six months and consisted of three sets of 8-12 repetitions with a rating of perceived exertion between 5 and 8 for three weekly sessions. Each exercise session was performed in twelve resistance exercises and it least for approximately 40 min. RESULTS: The main results demonstrated that RT decreased waist circumference by 3%, and decreased thiobarbituric reactive species (TBARS) by 28%. Moreover, RT increased handgrip strength by 28.4%, fat-free mass by 4.1%, hemoglobin by 5%, iron by 33.4%, glutathione by 121%, and Trolox equivalent antioxidant capacity by 14.2% (p < 0.05). Low hemoglobin concentrations impaired the effect of RT on fat-free mass gain. CONCLUSION: Six months of RT in HD patients improved clinical parameters, such as hemoglobin, iron, body composition, and redox balance, while low hemoglobin concentration impaired exercise-benefits on fat-free mass in patients with CKD. These findings can contribute to a better clinical application of RT in the maintenance of hemodialysis patients.

Improving the prognosis of renal patients: The effects of blood flow-restricted resistance training on redox balance and cardiac autonomic function.

NEW FINDINGS: What is the central question of this study? Can resistance training with and without blood flow restriction improve redox balance and positively impact the autonomic cardiac modulation in chronic kidney disease patients? What is the main finding and its importance? Resistance training with and without blood flow restriction improved antioxidant defence (paraoxonase 1), decreased the pro-oxidative myeloperoxidase, improved cardiac autonomic function and slowed the decrease in renal function. We draw attention to the important clinical implications for the management of redox balance and autonomic cardiac function in chronic kidney disease patients. ABSTRACT: Patients with chronic kidney disease (CKD) are prone to cardiovascular diseases secondary to abnormalities in both autonomic cardiac function and redox balance [myeloperoxidase (MPO) to paraoxonase 1 (PON1) ratio]. Although aerobic training improves both autonomic balance and redox balance in patients with CKD, the cardioprotective effects of resistance training (RT), with and without blood flow restriction (BFR), remain unknown. We aimed to compare the effects of RT and RT+BFR on antioxidant defence (PON1), pro-oxidative status (MPO), cardiac autonomic function (quantified by heart rate variability analysis) and renal function. Conservative CKD (stages 1 to 5 who do not need hemodialysis) patients (n = 105, 33 female) of both sexes were randomized into three groups: control (CTL; 57.6 ± 5.2 years; body mass index, 33.23 ± 1.62 kg/m2 ), RT (58.09 ± 6.26 years; body mass index 33.63 ± 2.05 kg/m2 ) and RT+BFR (58.06 ± 6.47 years; body mass index, 33.32 ± 1.87 kg/m2 ). Patients completed 6 months of RT or RT+BFR on three non-consecutive days per week under the supervision of strength and conditioning professionals. Training loads were adjusted every 2 months. Heart rate variability was recorded with a Polar-RS800 and data were analysed for time and frequency domains using Kubios software. The redox balance markers were PON1 and MPO, which were analysed in plasma samples. Renal function was estimated as estimated glomerular filtration rate. The RT and RT+BFR decreased pro-oxidative MPO (RT, ∼34 ng/ml and RT+BFR, ∼27 ng/ml), improved both antioxidant defence (PON1: RT, ∼23 U/L and RT+BFR, ∼31 U/L) and cardiac autonomic function (R-R interval: RT, ∼120.4 ms and RT+BFR, ∼117.7 ms), and slowed the deterioration of renal function (P < 0.0001). Redox balance markers were inversely correlated with heart rate variability time-domain indices. Our data indicated that both training models were effective as non-pharmacological tools to increase the antioxidant defences, decrease oxidative stress and improve the cardiac autonomic function of CKD patients.

Resistance training improves sleep quality, redox balance and inflammatory profile in maintenance hemodialysis patients: a randomized controlled trial.

Patients in maintenance hemodialisys (HD) present sleep disorders, increased inflammation, unbalanced redox profiles, and elevated biomarkers representing endothelial dysfunction. Resistance training (RT) has shown to mitigate the loss of muscle mass, strength, improve inflammatory profiles, and endothelial function while decreasing oxidative stress for those in HD. However, the relation between those factors and sleep quality are inadequately described. The aim of this study was to verify the effects of 3 months of RT on sleep quality, redox balance, nitric oxide (NO) bioavailability, inflammation profile, and asymmetric dimethylarginine (ADMA) in patients undergoing HD. Our primary goal was to describe the role of RT on sleep quality. Our secondary goal was to evaluate the effect of RT on NO, metabolism markers, and inflammatory and redox profiles as potential mechanisms to explain RT-induced sleep quality changes. Fifty-five men undergoing maintenance hemodialysis were randomized into either a control (CTL, n = 25) and RT group (RTG; n = 30). Participants in the RT group demonstrated an improvement in sleep pattern, redox, inflammatory profiles, and biomarkers of endothelial function (NO2- and ADMA). This group also increased muscle strength (total workload in RT exercises of upper and lower limbs). These findings support that RT may improve the clinical status of HD patients by improving their sleep quality, oxidative and inflammatory parameters.

Eugenia punicifolia (Kunth) DC. as an adjuvant treatment for type-2 diabetes mellitus: a non-controlled, pilot study.

Type-2 diabetes mellitus (DM) is a highly prevalent disease with significant morbidity and mortality around the world. However, there is no universally effective treatment, because response to different treatment regimens can vary widely among patients. In this study, we aimed to investigate whether the use of the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is effective as an adjuvant to the treatment of patients with type-2 DM. Fifteen patients were enrolled in a pilot, non-controlled study, and received E. punicifolia for 3 months. After treatment, we observed a significant decrease in glycosylated hemoglobin, basal insulin, thyroid-stimulating hormone, C-reactive protein, and both systolic and diastolic blood pressure. There were no changes in fasting and postprandial glycemia. The compounds myricetin-3-O-rhamnoside, quercetin-3-O-galactoside, quercetin-3-O-xyloside, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, phytol, gallic acid, and trans-caryophyllene present in the powdered dried leaves of E. punicifolia may be responsible for the therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are promising as an adjuvant in the treatment of type-2 DM and deserve further investigation.

Lippia alba (Mill.) N. E. Brown hydroethanolic extract of the leaves is effective in the treatment of migraine in women.

BACKGROUND: There is no universally accepted and effective prophylaxis of migraine headache episodes. We aimed to investigate the effects of Lippia alba (Mill.) N. E. Brown (chemotype geranial-carvenone) in the treatment of migraine patients. METHODS: Twenty-one women were enrolled in a prospective, phase 2, non-controlled cohort study to orally receive hydroethanolic extract of L. alba leaves. Symptom intensity and impact were assessed using MIDAS and HIT-6 instruments before and after 2 months of treatment. RESULTS: We observed a significant decrease on HIT-6 total score, as well as MIDAS number of missed days, number of headache days, and pain intensity. More than 70% of patients experienced a minimum 50% reduction on pain frequency. CONCLUSIONS: Treatment with L. alba leaves (geranial-carvenone) hydroethanolic extract is a cheap, safe, widely available, highly effective therapy to reduce both the intensity and the frequency of headache episodes of women with migraine. ClinicalTrials.gov Identifier: NCT01259947.