Nutr Hosp. 2015;32(5):2126-2135 ISSN 0212-1611 • CODEN NUHOEQ S.V.R. 318

Original / Alimentos funcionales improves physical fitness in women with fibromyalgia Daniel Collado Mateo1, Francesco Pazzi1, Francisco J. Domínguez Muñoz1, Juan Pedro Martín Martínez1, Pedro R. Olivares2, Narcis Gusi1 and José C. Adsuar1 1Faculty of Sport Science, University of Extremadura, Cáceres, Spain. 2Instituto de Actividad Física y Salud, Universidad Autónoma de Chile, Chile.

Abstract GANODERMA LUCIDUM MEJORA LA CONDICIÓN FÍSICA EN MUJERES CON Introduction: fibromyalgia is a chronic disease charac- FIBROMIALGIA terized by generalized pain, stiffness, poor physical con- ditioning, non-restorative sleep and poor health-related quality of life. Ganoderma lucidum a type of mushroom Resumen that has demonstrated several benefits in different po- Introducción: la fibromialgia es una enfermedad cróni- pulations. Ceratonia siliqua is a natural therapy rich in ca caracterizada por dolor crónico general, rigidez, con- antioxidants with potential benefits on health. dición física pobre, sueño no reparador y mala calidad Objective: to evaluate the effects of 6-week treatment de vida relacionada con la salud. Ganoderma lucidum es of Ganoderma lucidum and Ceratonia siliqua on physical un tipo de hongo que ha demostrado tener diferentes be- fitness in patients suffering from fibromyalgia. neficios en diversas poblaciones. La harina de algarrobo Methods: sixty-four women with fibromyalgia partici- (Ceratonia siliqua) es una fuente natural de antioxidantes pated in the study. They took 6 g of Ganoderma lucidum con potenciales beneficios para la salud. or Ceratonia siliqua per day for 6 weeks. Different fitness Objetivo: evaluar los efectos sobre la condición física tests were selected in order to evaluate functional capa- en mujeres con fibromialgia de un tratamiento de seis se- city. manas con Ganoderma lucidum y compararlos con los de Results: after the 6-week treatment period, Ganoder- un tratamiento con Ceratonia siliqua. ma lucidum significantly improved aerobic endurance, Métodos: sesenta y cuatro mujeres con fibromialgia lower body flexibility, and velocity (p < .05). No signifi- participaron en el estudio. Se hicieron dos grupos, el cant improvement in any physical test was observed in primer grupo tomó 6 g diarios de Ganoderma lucidum, the Ceratonia siliqua group. mientras que el segundo tomó 6 g diarios de Ceratonia Discussion and conclusion: Ganoderma lucidum may siliqua. Se evaluó la condición física mediante diferentes improve physical fitness in women with fibromyalgia, test físicos validados. whereas, Ceratonia siliqua seemed to be ineffective at in- Resultados: después de seis semanas de tratamiento, creasing physical fitness. These results may indicate that Ganoderma lucidum mejoró significativamente la resis- Ganoderma lucidum might be a useful dietary supple- tencia aeróbica, la flexibilidad del miembro inferior y la ment to enhance physical performance of the patients velocidad (p < 0,05). Por otro lado, Ceratonia siliqua no suffering from fibromyalgia. mejoró la condición física. (Nutr Hosp. 2015;32:2126-2135) Discusión y conclusiones: Ganoderma lucidum puede mejorar la condición física en mujeres con fibromialgia, DOI:10.3305/nh.2015.32.5.9601 mientras que Ceratonia siliqua parece no ser efectivo Key words: Chronic pain. Reishi. Ceratonia siliqua. Ga- para este propósito. Estos resultados pueden indicar que noderma lucidum. Nutrition. Endurance. Velocity. 6 g diarios de Ganoderma lucidum podrían ser un suple- mento útil para mejorar la condición física en esta po- blación. (Nutr Hosp. 2015;32:2126-2135) DOI:10.3305/nh.2015.32.5.9601 Palabras clave: Dolor crónico. Reishi. Ceratonia siliqua. Ganoderma lucidum. Nutrición. Resistencia. Velocidad.

Correspondence: Pedro R. Olivares. Instituto de Actividad Física y Salud, Universidad Autónoma de Chile, Chile. E-mail: [email protected] Recibido: 7-VII-2015. Aceptado: 7-VIII-2015.

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031_9601 El Ganoderma lucidum mejora.indd 2126 8/10/15 2:41 Introduction Ceratonia siliqua (CS) is a natural therapy that has been consumed in many Mediterranean countries in Fibromyalgia (FM) is a chronic rheumatic disease culinary preparations of beverages and confectionery. of unknown etiology. It is characterized by generalized It is also called carob tree and it is obtained from the pain, stiffness, and tenderness in at least 11 of 18 spe- fruit of the CS tree. CS flour is rich in polyphenols cific points1. In addition, FM is associated with a range and it acts as an antioxidant in the body25,26. Given its of symptoms, such as muscular stiffness, depression, low prize, CS can be considered a “low cost” source non-refreshing sleep, and cognitive impairments2,3. In of antioxidants. In mice, antidepressant effects were European population, the estimated prevalence of FM also reported in previous studies27. However, to our is around 3% to 5% of the general population4. knowledge, those results have not been studied in hu- Differences in physical fitness between FM and man samples. healthy women were compared in previous studies. Recent studies hypothesized that oxidative stress FM patients showed worse results in upper and lower may have a relevant role in the pathophysiology of limb strength, balance, flexibility, and aerobic endu- FM28. This, along with the effects of oxidative stress in rance5,6. FM is also associated with high prevalence physical condition22, suggests that antioxidant sources of overweight and obesity. In this regard, a recent could improve physical fitness in FM patients. study reported that approximately 72% of women Given the potential effects of GL and CS, not only with fibromyalgia are overweight or obese7. This an- as antioxidant sources (especially the GL, which may thropometric difference could be given because FM have other benefits cited above), the aim of the pre- patients are more prone to physical inactivity than sent study was to evaluate the effects of GL and CS healthy people8. This sedentary tendency may be in- on physical fitness in patients suffering from FM. A creased by FM symptoms like pain, fatigue, stiffness secondary objective was to evaluate the safety of GL or depression, while at the same time some of these and CS treatments. symptoms could be worsened by physical inactivity, i.e. poor physical conditioning or depression9. All of this can lead a reduction in health-related quality of Methods life (HRQoL)10. Recommended therapies in FM include pharmaco- Participants logical and non-pharmacological therapies. Among non-pharmacological treatments, physical therapies All participants were recruited from three FM as- were reported to be effective at increasing well-being sociations. The following inclusion criteria were set: and physical function11. Natural and nutritional the- 1) be diagnosed with FM by a rheumatologist; 2) be rapies are currently being studied in this syndrome able to communicate effectively with study staff; 3) because these could be helpful at improving different be older than 18 years old; 4) Give written-informed symptoms12. consent. On the other hand, exclusion criteria were Among those alternative therapies, Ganoderma lu- the following: 1) be pregnant; 2) change their daily cidum (GL), also known as reishi or linghzi, has been activity during the 6 weeks of treatment; 3) be taking widely used and studied in different populations. It is immunosuppressive; 4) be suffering from diabetes; 5) a type of mushroom that has demonstrated his efficacy be participating in other investigations; 6) be taking C at increasing vital energy, stimulating the immune sys- vitamin supplementation; 7) be taking anticoagulants, tem, and promoting health13. Previous research investi- and 8) have taken GL and/or CS as a treatment be- gated its effect as a treatment of different diseases, like fore. Additionally, an algometer (PainTest™ FPX 25 cancer14, diabetes15, Human Immuno Virus16, or hepa- Algometer. Wagner Instruments, Greenwich, USA) titis17. Different properties and effects were also repor- was used in order to check FM diagnosis. Participants ted, such as anti-inflammatory18, anti-oxidant15, antivi- without acute painful response in at least 11 of 18 spe- ral19, neuroprotective20, and hypotensive21. Effects of cified tender points stimulated with a pressure of 4 kg/ GL on physical conditioning still remain unknown in cm2 were excluded. humans. To our knowledge, only one investigation22 Figure 1 shows the flow diagram of participants. A assessed the effects of GL on physical fitness, and total of 70 subjects were initially recruited. Sixty-se- they concluded that the antioxidant effect of GL could ven of them were women and 3 were men. Five par- protect endurance athletes from overtraining. Effec- ticipants were excluded because they did not meet the tiveness in increasing antioxidant enzymes activities inclusion criteria and 1 declined to participate. A total was also investigated in mice23. This study shown the of 64 women took part in the study. All of them signed evidence that GL possessed protective effects against the informed consent in accordance with the updated a strenuous exercise that could induce oxidative stress. Declaration of Helsinki. Furthermore, relevant effects on physical condition This study was approved by the Biomedical Ethics and fatigue were reported in breast cancer patients24. Committee of the University. The trial was registered However, the mechanism under these improvements in the Australian New Zealand Clinical Trials, register remains unknown. number: ACTRN12614001201662.

Ganoderma lucidum improves physical Nutr Hosp. 2015;32(5):2126-2135 2127 fitness in women with fibromyalgia

031_9601 El Ganoderma lucidum mejora.indd 2127 8/10/15 2:41 Enrollment Assessed for eligibility (n=70)

Excluded (n=6) • Not meeting inclusion criteria (n=5) • Declined to participate (n=1)

Randomized (n=64)

Allocation

Allocated to Ganoderma lucidum Group (n=32) Allocated to Ceratonia Siliqua Group (n=32) • Received allocated intervention (n=32) • Received allocated intervention (n=31) • Did not receive allocated intervention (n=0) • Did not receive allocated intervention (decided not to start treatment) (n=1)

Follow-Up

Lost to follow-up (did not answer the calls) (n=1) Lost to follow-up (did not come the day when Discontinued intervention (did not comply with the physical tests were performed) (n=1) treatment for more than 80% of the dose) (n=5) Discontinued intervention (did not comply with the treatment for more than 80% of the dose) (n=5)

Analysis

Analysed (n=25) Analysed (n=23) • Excluded from analysis (severe back pain) (n=1) • Excluded from analysis (receiving other non usual care therapies) (n=2)

Fig. 1.—Flow Diagram of participants.

Procedures doReishi” provided the substances, and the Chair of Mycology of the University of Valladolid (Spain) was The current study is a randomized, double blind, responsible to analyze GL. clinical trial. Participants were randomly assigned to one of the following two groups: GL group (GLG) or CS group (CSG). Subjects were informed about the Data collection existence of both group, but they did not know which group they were in. Randomization and allocation pro- In order to evaluate functional capacity and physical cesses were conducted by one of the researchers using fitness, the following well-known tests were selected: random code numbers. This researcher was not invol- ved in data acquisition or statistical analysis. Thus, the –– Upper Body Muscular Strength: It was assessed following people were blinded: a) people receiving the using two tests: the handgrip test and the arm treatment; b) people administering the treatment; c) curl test. The handgrip strength was measured people assessing the outcomes; and finally, d) people using a hand dynamometer (Takei TKK 5401 analyzing the results. Digital Handgrip Dynamometer, Tokyo Ja- After initial measurement, participants took GL or pan). Patients had to squeeze the dynamometer CS during a period of 6 weeks. GLG ingested 3g of GL with an optimal grip-span29. The better of two dissolved in warm water twice a day (6g per day). The attempts for each hand was used in the analy- first intake was at breakfast; whereas the second one ses. The second tool was the “Arm curl test”30. was at dinner. CSG took 6 daily grams of CS with the It quantifies the number of repetitions that the same administration indications. The company “Mun- patient is able to lift a hand weight (2.3 kg) in

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031_9601 El Ganoderma lucidum mejora.indd 2128 8/10/15 2:41 30 seconds. One trial with each hand was perfor- • Eyes open on unstable surface. In this test so- med by the patients. matosensory capacity is compromised, thus vi- –– Lower body muscular strength. The 30s-Chair sual and vestibular inputs are measured. stand test was used. Participants started this test • Eyes closed on unstable surface. Only vesti- seated on a chair with their hands over their bular information was estimated by compro- shoulders. They should stand-up and sit-down as mising somatosensory information and visual fast as possible within 30 seconds31. The number feedback. of times they stand-up were recorded. –– Upper Body Flexibility was assessed using the –– Trunk Endurance was evaluated by using the Ito, back scratch test32. In this test, the distance be- Shirado method36. Flexor endurance was assessed tween fingers behind the back is measured and at first. Patients started the test in supine position the overlap is scored positively. and they should raise their lower extremities with –– Lower Body Flexibility: it was measured using 90º flexion of the hip and knees joints. For ex- the chair-sit-and-reach test30. In this test, partici- tensor muscles, participants should be in prone pants were seated on a chair and they had to ex- position while holding their sternum off the floor. tend their legs: first, the right leg, and second, the Subjects must maintain these positions as long as other one. Then, they were instructed to reach the possible in both tests. extended leg with the middle finger of the corres- ponding hand and hold this position. Best score was registered. Statistical analysis –– Balance and agility: the 3 meters version of the Timed-Up-and-Go Test (TUG)33 was used to as- Values of descriptive variables were calculated in sess agility and dynamic balance. Participants order to characterize the two groups. Student’s t test were asked to sit on a chair, placing their back for independent samples was used to compare the cha- against the backrest of the chair. At the signal, racteristics of GLG and CSG at baseline. Distribution they should walk to a line 3 meters away, turn of data was checked using the Kolmogorov-Smirnov around, walk back to the chair and sit-down. Best test with Lilliefors significance. score of two trials was used in the analyses. The analysis of variance (ANOVA) for repeated –– Aerobic Endurance was measured using the measures was used to calculate the effects of the treat- 6-min walking test30. This test aims to determine ment on the physical fitness outcomes. Paired t test the maximum distance that participants were able was calculated in order to estimate the changes of both to walk in 6 minutes. It was performed around a groups comparing from baseline. square measuring 20 meters each side. In addition to the efficacy analysis, which compri- –– Velocity: Participants were asked to walk 20 me- ses the participants who took at least 80% of the do- ters as fast as possible. Mean velocity was calcu- ses and completed the task, an intent-to-treat analysis lated dividing the 20 meters by the time taken to was performed. It comprises the 64 initial participants. complete this 20 meters34. Data of all participants that came to the post-treatment –– Balance: it was measured using Biodex Balance measures were utilized, including data coming from System (Shirley, NY, USA). This device objecti- the people who did not take at least 80% of the do- vely measures the ability of a subject to stabilize ses (n=10). Post-treatment data of the remainder of himself. It also quantifies the tilt about each axis the sample (n=6) was imputed according to the mean during static and dynamic conditions. Clinical change of their group. The level of significance was Test of Sensory Integration of Balance (CTSIB) set at p<.05. Analyses were performed using SPSS sof- protocol was used. This test was performed with tware (version 21). different devices by previous studies35. However, it is the first time, to our knowledge, that this pro- tocol is carried out with Biodex Balance System. Results In all tests, patients maintained their feet on the platform during 30 seconds with a rest of 10 se- Characteristics of participants at baseline are shown conds between each test. The following tests were in table I. No statistically significant difference was performed to quantify postural sway under four observed between GLG and CSG at baseline. different sensory conditions according to the CT- Initially, 64 women were randomly allocated in 2 SIB: equal groups. However, final sample comprised 48 women: 25 belonging to GLG and 23 belonging to • Eyes open on firm surface to measure somato- CSG. Starting from these 64 patients, a total of 5 par- sensory, visual and vestibular sensory inputs. ticipants of each group did not took at least 80% of • Eyes closed on firm surface to estimate somato- the dose and were excluded; 1 subject decided not to sensory and vestibular inputs, since visual input start the treatment after the randomization was per- is not available. formed; another woman did not answer the calls and

Ganoderma lucidum improves physical Nutr Hosp. 2015;32(5):2126-2135 2129 fitness in women with fibromyalgia

031_9601 El Ganoderma lucidum mejora.indd 2129 8/10/15 2:41 Table I Characteristics at baseline of the two groups

GLG (n=25) CSG (n=23) p Age (years) 56.25 (8.05) 53.62 (11.75) .367 Height (cm) 157.16 (4.63) 156.13 (6.16) .514 Weight (kg) 64.21 (9.87) 61.50 (13.50) .429 Muscular mass (%) 62.00 (7.31) 64.76 (8.77) .245 Fat mass (%) 34.80 (7.67) 32.33 (7.92) .285 BMI 26.00 (3.82) 25.20 (4.83) .522 Date when fibromyalgia symptoms started 1993 (12.09) 1992 (12.76) .652 *Values expressed as mean (SD). BMI: Body Mass Index. GLG: Ganoderma lucidum group. CSG: Ceratonia siliqua group.

was lost; 2 women considerably changed their usual researches on the physiological effects of GL in the therapies and were excluded too; 1 woman was not physical condition are needed. able to complete physical fitness tests because she Although the current study is not able to precisely had an acute musculoskeletal injury; 1 woman did not explain how physical condition is improved, the rele- show up when measurements was performed (Fig. 1). vance of our findings is very large. To our knowledge, Finally, 48 women were included in the efficacy this is the first study that investigates the effects of GL analysis (GLG=25; CSG=23), whereas 64 (GLG=32; and/or CS on the physical fitness of a population with CSG=32) were taken in consideration of intent to treat a specific disease. Therefore, this study lays the foun- analysis. dation for future research focused on the GL effects on Effects of GLG and CSG on physical fitness are physical fitness in pathologies characterized by poor represented in table II. After the 6-week treatment physical conditioning. At the same time, findings from period, a statistically significant difference in aerobic the previous study in cyclists are confirmed22. In this endurance was observed between both groups (p<.05). way, the current study is also an important entry point Furthermore, GLG obtained significant improvements for future studies on the effects of GL in sport perfor- (p<.05) in lower body flexibility and velocity in effi- mance. cacy analysis compared with CSG. However, only the The relevance of the physical condition in women improvement in lower body flexibility was significant suffering from FM is widely known. In fact, it is clo- in the intent to treat analysis (Table III). sely related with the satisfaction with life and wellbe- ing40, because it is obviously related with the ability of perform activities of daily living. Furthermore, aerobic Discussion endurance and flexibility are extremely related with HRQoL. The reported treatment effect in velocity is The main finding of the current paper was that 6g/ higher than the minimal real change, which was calcu- day of GL for 6 weeks improved the physical fitness of lated in patients with chronic pain (osteoarthritis) and women suffering from FM. Specifically, we observed it was 0.07 m/s34. improvements on aerobic endurance, walking veloci- Safety of both GL and CS were also demonstrated ty, and lower limb flexibility. On the other hand, CS in the current paper. A total of 10 participants did not seemed to be rather ineffective in improving physical complete the minimum 80% of the treatment. Of the- fitness in FM patients. To our knowledge, this is the se, 5 belonged to the GLG and other 5 to the CSG, first study that assesses the effects of CS and/or GL on which means a 15.63% of the total sample. The most physical condition in FM patients. common complaint in those 10 participants were mild Given the lack of studies about the potential mecha- nausea, diarrhea, discomfort, and nervousness. Some nism of GL and CS in physical fitness, it is difficult participants opined that the reason of those reactions to explain how GL may improve aerobic endurance, were the bad taste. In all cases the reactions were mild velocity, or flexibility. The best explanation based on or moderate and the participants were asked to reduce previous studies is the antioxidant effect37,38. In addi- the dose to 3 grams per day. However, no one of the tion, the oxidative/antioxidative status was suggested patients that reduced the dose were able to continue the to be a critical factor in physical and mental health of treatment and all of them ceased it. This could suggest FM patients28,39. However, both GL and CS are antioxi- that the daily amount of GL and CS is not the cause of dant sources. Therefore, based on our results, there can those complaints. be no assurance that the reported improvements are The current study has several limitations. The most caused by an antioxidant effect. In this context, further important limitation is the lack of previous studies that

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031_9601 El Ganoderma lucidum mejora.indd 2130 8/10/15 2:41 Size 0.112 0.113 0.132 0.021 0.398 0.133 0.887 0.497 0.175 0.625 Effect Effect Global Global 0.07 0.13 0.30 -0.42 -0.34 -1.07 -0.82 -0.25 -4.06 -30.19 (95% CI) Treatment Treatment effect Mean effect Mean (-0.72 to .11) (1.38 to 6.75) (-1.47 to 2.32) (-2.37 to 2.21) (-1.43 to 2.09) (-0.54 to 2.68) (-2.90 to 4.54) (-0.80 to 0.54) (-0.59 to 1.08) (-6.33 to 66.75) b P .656 .946 .705 .188 .659 .045 .561 .706 .004 .040 F 0.201 0.005 0.145 1.784 0.197 4.260 0.343 0.144 9.060 4.491 0.016 0.681 0.058 0.080 0.257 -0.143 -0.877 -0.279 -0.014 -0.059 Effect Size Intra-Group Intra-Group a P .910 .420 .001 .001 .754 .643 .051 .329 .893 .883 CSG -.22 7.00 3.24 -5.86 20.28 19.39 12.91 12.67 10.86 Mean Mean (5.11) (5.68) (3.42) (2.96) (8.35) (2.52) (1.30) (8.98) (0.52) 469.49 (120.45) treatment (SD) after (SD) after

7.31 3.26 -5.36 -0.35 20.36 18.73 10.41 10.09 10.22 (4.09) (3.99) (3.64) (2.99) (8.71) (2.03) (1.10) (9.39) (0.42) 477.73 (79.69) at baseline Mean (SD) Mean (SD)

Table II Table 0.378 0.254 -0.072 -0.131 -0.782 -0.830 -0.029 -0.462 -0.452 -0.301 Effect Size Intra-Group Intra-Group a P .601 .482 .761 .005 .007 .006 .002 <.001 <.001 <.001 GLG 6.85 4.00 3.54 -3.80 11.14 19.92 18.91 13.81 13.36 Mean Mean (4.33) (3.85) (4.40) (4.04) (2.08) (1.02) (9.85) (0.54) 528.97 (10.63) (72.08) treatment (SD) after (SD) after

Effects of 6 weeks of GL vs CS treatment on physical conditioning vs CS treatment Effects of 6 weeks GL 7.29 3.35 -4.12 -0.20 19.58 18.33 10.20 10.48 10.26 (4.11) (4.98) (4.92) (3.55) (1.29) (8.69) (1.71) (0.52) 507.00 (10.99) (73.88) at baseline Mean (SD) Mean (SD) Test CSG (n=23) CSG (n=23) CSG (n=23) CSG (n=23) CSG (n=22) CSG (n=23) CSG (n=22) CSG (n=22) CSG (n=22) CSG (n=23) GLG (n=25) GLG (n=24) GLG (n=25) GLG (n=24) GLG (n=25) GLG (n=25) GLG (n=25) GLG (n=25) GLG (n=25) GLG (n=25) 6 m Walking (m) Walking 6 m Timed-Up-Go (s) Timed-Up-Go Back Scratch (cm) Left Handgrip (kg) Right Handgrip (kg) 20-m walk test (m/s) Arm Curl Left (reps) Arm Curl Right (reps) Chair stand Test (reps) Test Chair stand Chair Sit and Reach (cm) Outcome measure Upper Body Stren - gth Upper Body Flexibility Lower body flexibility Aerobic endurance Balance and agility Lower body strength Velocity

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031_9601 El Ganoderma lucidum mejora.indd 2131 8/10/15 2:41 Size 0.117 0.424 0.329 0.239 0.174 0.205 0.026 0.202 0.242 0.168 Effect Effect Global Global 0.16 0.08 0.28 0.29 -0.54 -0.33 -0.01 -0.10 to 30.87) to 42.92) (95% CI) Treatment Treatment effect Mean effect Mean -6.33 (-18.19 -8.66 (-25.58 (-0.21 to 1.30) (-0.43 to 0.12) (-0.49 to 1.15) (-0.34 to 0.18) (-1.09 to 0.53) (-0.26 to 0.29) (-1.14 to 0.56) (-0.43 to 0.65) b P .157 .271 .422 .558 .490 .931 .497 .693 .605 .612 F 2.066 1.239 0.657 0.348 0.483 0.008 0.469 0.157 0.272 0.261 0.203 0.247 0.245 0.216 0.418 0.106 0.081 -0.243 -0.147 -0.056 Effect Size Intra-Group Intra-Group a P .238 .255 .205 .136 .210 .001 .279 .562 .817 .777 CSG 4.32 0.62 4.20 0.90 4.38 1.05 4.89 2.82 (.99) 41.49 46.41 Mean Mean (2.26) (0.45) (2.06) (0.45) (1.83) (0.37) (2.45) (37.74) (40.75) treatment (SD) after (SD) after

4.72 0.73 4.66 1.01 3.97 1.22 4.57 2.93 39.45 49.73 (1.62) (0.44) (1.66) (0.56) (1.52) (0.44) (1.85) (1.07)

(34.69) (41.22) at baseline Mean (SD) Mean (SD) 0.599 0.083 0.355 0.249 0.000 -0.211 -0.090 -0.078 -0.013 -0.123 Effect Size Table II (cont.) Table Intra-Group Intra-Group a P .478 .021 .591 .080 .635 .218 .933 .997 .321 .666 values of analysis of variance for repeated measures to compare differences between groups after treatment; CI: confidence confidence CI: treatment; groups after between differences compare to measures for repeated of variance of analysis p- values GLG b 4.77 0.51 4.70 0.99 4.14 1.26 4.92 3.22 54.55 59.36 Mean Mean (1.42) (0.24) (1.61) (0.50) (1.41) (0.65) (1.50) (1.24) (39.80) (45.81) treatment (SD) after (SD) after

p of t-test; p of t-test; a Effects of 6 weeks of GL vs CS treatment on physical conditioning vs CS treatment Effects of 6 weeks GL 4.63 0.78 4.83 1.19 4.02 1.42 4.90 3.22 46.18 54.01 (1.68) (0.59) (1.50) (0.62) (1.65) (0.63) (1.37) (0.97) (39.47) (40.84) at baseline Mean (SD) Mean (SD) siliqua group; group; siliqua Test Lumbar (s) Abdominal (s) Swing Index (º) Swing Index (º) Swing Index (º) Swing Index (º) Stability Index (º) Stability Index (º) Stability Index (º) Stability Index (º) ceratonia ceratonia group; CSG: lucidum ganoderma Outcome measure Balance. Eyes Open Firm Surface GLG (n=25) GLG: GLG: interval. CSG (n=23) Balance Eyes Closed Firm Surface GLG (n=25) CSG (n=23) Balance Eyes Open Unstable Surface GLG (n=25) CSG (n=23) Eyes Closed on Unstable Surface GLG (n=25) CSG (n=23) Endurance Trunk GLG (n=25) CSG (n=19)

2132 Nutr Hosp. 2015;32(5):2126-2135 Daniel Collado-Mateo et al.

031_9601 El Ganoderma lucidum mejora.indd 2132 8/10/15 2:41 Size 0.052 0.078 0.160 0.108 0.209 0.313 0.527 0.103 0.486 0.020 0.481 0.218 0.324 0.131 0.141 0.134 Effect Effect Global Global 0.28 0.03 0.56 0.32 0.09 0.14 0.07 0.18 -0.56 -1.74 -2.53 -0.02 -0.15 -0.33 -0.17 -28.84 (95% CI) Treatment Treatment effect Mean effect Mean (0.06 to 4.99) (-1.92 to 1.37) (-0.27 to 0.20) (-2.35 to 1.22) (-1.83 to 1.19) (-0.80 to 1.93) (-1.09 to 4.58) (-0.64 to 0.42) (-0.65 to 0.70) (-0.01 to 0.33) (-0.43 to 1.09) (-0.35 to 0.07) (-0.50 to 0.86) (-0.31 to 0.17) (-0.88 to 0.51) (-1.29 to 58.99) b P .838 .781 .530 .672 .415 .223 .688 .044 .060 .940 .063 .393 .207 .607 .582 .599 F 0.042 0.078 0.399 0.182 0.674 1.514 0.163 4.312 3.661 0.006 3.581 0.740 1.628 0.268 0.306 0.279 0.119 0.346 0.231 0.160 0.096 0.037 0.055 0.219 0.149 0.252 -0.215 -0.909 -0.707 -0.070 -0.275 -0.264 Effect Size Intra-Group Intra-Group a p .571 .029 .117 .147 .000 .000 .282 .288 .397 .478 .003 .808 .726 .087 .330 .029 1.16 7.18 0.43 3.25 4.49 0.68 4.37 0.93 4.35 -6.25 18.51 19.47 12.45 12.65 10.75 Mean Mean (4.16) (0.67) (4.72) (4.08) (3.89) (1.62) (2.81) (0.58) (2.32) (0.58) (1.94) (0.59) (1.74) 474.79 (117.4) CSG (n=32) (10.55) (10.16) treatment (SD) after (SD) after

1.30 9.06 9.92 7.43 3.27 4.60 0.80 4.64 1.08 3.93 -5.00 -0.34 19.98 18.51 10.03 (4.33) (0.53) (4.16) (3.34) (3.83) (1.49) (2.40) (0.47) (1.56) (0.51) (1.65) (0.60) (1.42) 484.46 (11.62) (10.39) (80.52) Mean (SD) Mean (SD) at base line

0.338 0.285 0.322 0.533 0.052 0.388 Table III Table -0.811 -0.084 -0.826 -0.045 -0.398 -0.269 -0.375 -0.282 -0.133 -0.148 Effect Size Intra-Group Intra-Group a P .885 .105 .311 .535 .000 .000 .560 .010 .007 .008 .000 .006 .318 .005 .660 .037 1.25 6.89 3.02 3.51 4.82 0.53 4.84 0.96 4.41 -3.50 11.04 18.17 18.56 12.82 13.65 Mean Mean (4.82) (0.60) (4.37) (3.95) (4.23) (1.05) (2.03) (9.20) (0.56) (1.51) (0.30) (1.77) (0.49) (1.50) 524.76 (10.87) (70.89) GLG (n=32) treatment (SD) after (SD) after

9.76 7.25 3.36 4.60 0.79 4.93 1.19 4.18 1.42 -4.00 -0.28 19.81 18.17 10.36 10.29 (4.87) (4.82) (3.44) (3.87) (1.18) (8.38) (1.72) (0.50) (1.78) (0.62) (1.65) (0.68) (1.59) (0.59) 505.59 (11.02) (71.40) Mean (SD) Mean (SD) at base line Effects of 6 weeks of GL or CS treatments on physical conditioning. Intent-to-treat analysis on physical conditioning. Intent-to-treat or CS treatments Effects of 6 weeks GL (m) Test Swing Index(º) Swing Index(º) Swing Index(º) Stability Index(º) Stability Index(º) Stability Index(º) Timed-Up-Go (s) Timed-Up-Go Back Scratch (cm) Left Handgrip (kg) Left arm curl (reps) Right Handgrip (kg) 20-m walk test (m/s) Right arm curl (reps) Chair stand test (reps) Six minutes walking test Chair Sit and Reach (cm) Outcome measure Upper Body Strength Upper Body Flexibility Lower body flexibility Balance and agility Aerobic endurance Lower Body strength Velocity Balance Eyes Open Firm Surface Balance Eyes Closed Firm Surface Balance Eyes Open Unstable Surface

Ganoderma lucidum improves physical Nutr Hosp. 2015;32(5):2126-2135 2133 fitness in women with fibromyalgia

031_9601 El Ganoderma lucidum mejora.indd 2133 8/10/15 2:41 could explain the mechanisms under the differences

Size observed. In addition, given that the two treatments 0.210 0.029 0.123 0.071 Effect Effect Global Global were antioxidant sources, it is impossible to conclu- de whether the changes are based on the antioxidant effects or not. The second is the lack of knowledge

0.28 about the most adequate dose of both GL and CS in -0.02 to 20.96) to 28.80) (95% CI) Treatment Treatment adult women. Furthermore, the dose and indications of effect Mean effect Mean -4.09 (-12.78 -3.54 (-21.71 (-0.96 to 0.40) (-0.42 to 0.48) both treatments had to be the same in order to keep the

b double-blind. Third, duration of the treatment could be P .413 .910 .630 .780 insufficient to increase some physical fitness variables. Finally, although no statistically significant differences F 0.681 0.013 0.235 0.079 in many physical tests were observed, treatment effects could not be discarded due to the small sample size. Despite all these limitations, it can be concluded that GL may be effective in improving endurance, lower 0.028 -0.119 -0.169 -0.037 body flexibility, and velocity. On the other hand, CS Effect Size Intra-Group Intra-Group seemed to be ineffective in improving physical fitness a

p in women suffering from FM. However, more studies .171 .870 .434 .858 with longer intervention periods and different doses of GL and CS are required. Similarly, further studies focused on the mechanisms under the reported impro- 4.93 2.95 40.62 49.17 Mean Mean (2.18) (1.13) CSG (n=32) (37.16) (41.05) vements are needed. treatment (SD) after (SD) after

Acknowledgments 4.60 2.98 36.36 47.66 (1.68) (1.00)

(34.10) (39.08) The authors acknowledge Juan Andrés Oria de Rue- Mean (SD) Mean (SD) at base line da for the support in the study protocol design. The company “MundoReishi” provided the Ganoderma lu- cidum and Ceratonia siliqua utilized in the study. The 0.000 -0.033 -0.227 -0.121 author DCM was supported by a Predoctoral Fellows- Effect Size Intra-Group Intra-Group

Table III (cont.) Table hip from the “Fundación Tatiana Pérez de Guzmán el

a Bueno”. The authors acknowledge the assistance of P .845 .995 .209 .598 the local associations of Palencia, Salamanca and Chi- piona. values of analysis of variance for repeated measures to compare differences between groups after treatment; CI: confidence confidence CI: treatment; groups after between differences compare to measures for repeated of variance of analysis p- values b 5.02 3.32 53.90 58.86 Mean Mean (1.54) (1.24) (36.98) (44.09) GLG (n=32) treatment (SD) after (SD) after Conflict of Interest

p of t-test; p of t-test; a The authors declare there are not competing finan- cial interests existing. 4.97 3.32 45.55 53.82 (1.48) (1.02) (36.52) (38.69) Mean (SD) Mean (SD) at base line

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Ganoderma lucidum improves physical Nutr Hosp. 2015;32(5):2126-2135 2135 fitness in women with fibromyalgia

031_9601 El Ganoderma lucidum mejora.indd 2135 8/10/15 2:41