Patent Application
20220023327
The present invention relates to mangiferin-containing herbal formulations which improve performance by an athlete, sports person, or exerciser during exertion, by increasing peak power output by the athlete, sports person, or exerciser; mean power output by the athlete, sports person, or exerciser; tissue oxygenation in the athlete, sports person, or exerciser, or peak oxygen consumption by the athlete, sports person, or exerciser.
Fatigue is a complex process which may originate in any structure intervening in the production and control of muscle contractions. Performance-enhancing compounds may exert their effects by facilitating energy supply and utilization, easing central command and motor control and reducing the negative effects caused by energy depletion, shortage of O2, metabolite accumulation, and reactive oxygen and nitrogen species (RONS) on force generation, muscle contraction activation and afferent feedback. Polyphenols are believed to have sports performance-enhancing properties. Polyphenols may act as antioxidants, signaling molecules, or hold anti-inflammatory, anti-aging, neuromodulatory or neuroprotective properties, which may confer their ergogenic potential. Most of these effects have only been demonstrated in cell culture or high-dose animal models.
Reactive oxygen and nitrogen radicals form during sprint exercise, with iron-catalyzed formation of hydroxyl radicals being accelerated by acidification from high glycolytic rates attained during sprints. Acidosis accelerates hydroxyl radical production and reduces the activities of antioxidant enzymes. Compounds which mitigate formation of hydroxyl radicals may improve performance during exercise.
The ergogenic potential of the polyphenols luteolin and mangiferin remains unknown, and the effects of quercetin on performance during repeated all-out prolonged sprints is yet to be studied in humans. Mangiferin (2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a non-flavonoid polyphenol, present in mango leaves and other plants. Mangiferin protects against free radical production due to its iron-chelating properties. Mangiferin can traverse the blood-brain barrier and modulate neurotransmission. It remains unknown whether mangiferin attenuates the effects of ischemia/reperfusion in humans.
Quercetin is a flavonoid polyphenol found in several fruits and vegetables, including mangoes. Although quercetin has a low bioavailability due to its poor intestinal absorption, this may be improved by an oleaginous vehicle, such as tiger nut extract, which is rich in glyceryl esters of fatty acids. Quercetin, like mangiferin, is a phytoestrogen, capable of activating estrogen receptors.
Luteolin (30, 40, 50, 70-tetrahydroxyflavone) is a flavone and, like mangiferin and quercetin, is a potent antioxidant and inhibitor of xanthine oxidase. Luteolin is also a NADPH (nicotinamide adenine dinucleotide phosphate) oxidase inhibitor.
No study to date has determined the efficacy of natural polyphenols in mitigating the deterioration of skeletal muscle contractile function after short ischemia/reperfusion in humans. An object disclosed herein relates to use of mangiferin, administered with quercetin, tiger nut extract, and/or luteolin, to provide a performance-enhancing effect in men and women during exercise or physical exertion. An object disclosed herein relates to use of herbal formulations comprising mangiferin to mitigate ischemia/reperfusion injuries to muscle tissue during exertion.
The objects are illustrative of those that can be achieved by various embodiments disclosed herein, and are not intended to be limit the possible advantages which can be realized. Thus, these and other objects and advantages of the various exemplary embodiments will be apparent from the description herein or can be learned from practicing the disclosed embodiments, both as described herein or as modified in view of any variation that may be apparent to those skilled in the art. Accordingly, the present invention resides in the novel methods, arrangements, combinations, and improvements herein shown and described.
In light of the present need for safe methods of improving athletic performance, a brief summary of various exemplary embodiments is presented. Some simplifications and omissions may be made in the following summary, which is intended to highlight and introduce some aspects of the various exemplary embodiments, but not to limit the scope of the invention. Detailed descriptions of a preferred exemplary embodiment adequate to allow those of ordinary skill in the art to make and use the inventive concepts will follow in later sections.
Various embodiments disclosed herein relate to a formulation for increasing sports performance, comprising at least one herbal ingredient. In various embodiments, the formulation comprises from 25 mg to 5,000 mg, from 25 mg to 3,000 mg, from 25 mg to 2,000 mg, from 35 mg to 1,500 mg, from 55 mg to 1,000 mg, from 65 mg to 500 mg, from 75 mg to 250 mg, or from 84 mg to 140 mg of mangiferin. The mangiferin may be administered as substantially pure mangiferin, where substantially pure mangiferin is pharmaceutically acceptable and contains >80% by weight mangiferin; >90% by weight mangiferin; >95% by weight mangiferin; or >99% by weight mangiferin. The mangiferin may be administered as a component of a plant extract, wherein the plant extract comprises from 10% to 90% by weight mangiferin; from 20% to 85% by weight mangiferin; from 40% to 75% by weight mangiferin; or from 50% to 70% by weight mangiferin, or about 60% by weight mangiferin. In various embodiments, the mangiferin is administered as a component of a mango leaf extract. The mangiferin may be a component of an extract obtained by extraction of mango leaves with water, a polar protic solvent, or a polar aprotic solvent. The extract may be obtained by extraction of mango leaves with water or a lower alcohol.
According to various embodiments disclosed herein, mangiferin may be administered in combination with a second herbal active ingredient. This second herbal active ingredient may be luteolin in an amount of between 10 mg and 5,000 mg, between 20 mg and 4,000 mg, between 30 mg and 2,000 mg, between 45 mg to 1,000 mg, or between 50 mg to 500 mg per day. In various embodiments, the luteolin is administered as a component of an Arachis hypogeae or Perilla frutescens extract. The luteolin may be a component of an extract obtained by extraction of Arachis hypogeae or Perilla frutescens with water, a polar protic solvent, a polar aprotic solvent, a nonpolar solvent, or mixtures thereof. The extract may be obtained by extraction of Arachis hypogeae or Perilla frutescens with a lower alcohol, ethyl acetate, a hydrocarbon solvent, or a halogenated hydrocarbon solvent.
In some embodiments disclosed herein, mangiferin may be administered in combination with quercetin. Quercetin may be administered in an amount of between 50 mg and 10,000 mg, between 100 mg and 8,000 mg, between 150 mg and 6,000 mg, between 300 mg and 4,000 mg, or between 500 mg and 2,000 mg per day. In various embodiments, the quercetin is administered as a component of a Sophora japonica extract. The quercetin may be a component of an extract obtained by extraction of Sophora japonica with water, a polar protic solvent, a polar aprotic solvent, or mixtures thereof. The extract may be obtained by extraction of Sophora japonica with water, a lower alcohol, a mixture of water and a C1-C4 alcohol, or ethyl acetate.
In further embodiments, mangiferin may be administered in combination with a high potency fraction of Cyperus esculentus tubers. The high potency fraction of Cyperus esculentus tubers is obtained by extraction with ethyl acetate to obtain an organic solvent soluble fraction. The high potency fraction comprises:
from 70% to 95% by weight oleic acid glyceryl esters, from 80% to 94% by weight oleic acid glyceryl esters, from 85% to 93% by weight oleic acid glyceryl esters, from 90% to 92% by weight oleic acid glyceryl esters, or about 91% by weight oleic acid glyceryl esters;
from 1% to 15% by weight linoleic acid glyceryl esters, from 3% to 14% by weight linoleic acid glyceryl esters, from 5% to 12% by weight linoleic acid glyceryl esters, from 6% to 9% by weight linoleic acid glyceryl esters, or about 7% by weight linoleic acid glyceryl esters; phytosterols, such as stigmasterol, in an amount of 0.2% by weight or more; and
flavonoids, such as myricetin, in an amount of 0.2% by weight or more.
The high potency fraction of Cyperus esculentus tubers is administered in an amount of between 5 mg and 5,000 mg per day; between 10 mg and 500 mg per day; or between 15 mg and 350 mg per day.
Various embodiments disclosed herein relate to a formulation for increasing sports performance, comprising mangiferin and at least one of luteolin in an amount of between 10 mg and 5,000 mg, quercetin in an amount of between 50 mg and 10,000 mg; and a high potency fraction of Cyperus esculentus tubers in an amount of between 5 mg and 5,000 mg per day from 100 mg to 10 g quercetin; from 50 mg to 5,000 mg of an ethyl acetate extract of Cyperus esculentus tubers; and mixtures thereof. In various embodiments, the formulation comprises from 50 mg to 5,000 mg of mangiferin and from 10 mg to 5,000 mg of luteolin. In some embodiments, the formulation comprises from 50 mg to 5,000 mg of mangiferin; from 100 mg to 10 g quercetin; and from 50 mg to 5,000 mg of an ethyl acetate extract of Cyperus esculentus tubers.
In various embodiments disclosed herein, the mangiferin formulation comprises a single dosage form for once-daily administration. In certain embodiments, the formulation comprises multiple dosage forms, wherein each dosage form has similar contents, allowing a desired daily dosage to be administered in multiple divided doses. In some embodiments, the formulation comprises a first dosage form comprising mangiferin; and a second dosage form comprising luteolin, quercetin, an ethyl acetate extract of Cyperus esculentus tubers, or a mixture thereof.
Various embodiments disclosed herein relate to methods for increasing performance by a person engaged in physical activity, e.g., physical exercise, an individual sport, or a team sport. Such a person, here referred to as an athlete, a sports person, or an exerciser, may be administered from 50 mg to 5,000 mg of mangiferin. The mangiferin may be administered as a sole component, or the mangiferin may be administered in combination with at least one active ingredient selected from the group consisting of luteolin; quercetin; and an ethyl acetate extract of Cyperus esculentus tubers; and mixtures thereof. The formulation increases sports performance in a male or female athlete by increasing peak power output by the athlete during physical exertion, e.g., running, cycling, or swimming; by increasing mean power output by the male or female athlete during physical exertion; by increasing brain frontal lobe oxygenation by a female athlete during physical exertion; and/or by increasing peak oxygen consumption by the female athlete.
Certain embodiments disclosed herein relate to methods for increasing sports performance by increasing power output during physical exertion by a male or female athlete, by administering a combination of mangiferin and luteolin to the athlete. The combination is administered in a single daily dosage, or from two to five divided doses per day. The total daily dosage is:
from 25 mg to 5,000 mg, from 25 mg to 3,000 mg, from 25 mg to 2,000 mg, from 35 mg to 1,500 mg, from 55 mg to 1,000 mg, from 65 mg to 500 mg, from 75 mg to 250 mg, or from 84 mg to 140 mg of mangiferin per day; and from 10 mg and 5,000 mg, from 20 mg and 4,000 mg, from 30 mg and 2,000 mg, from 45 mg to 1,000 mg, or from 50 mg to 500 mg luteolin per day.
Certain embodiments disclosed herein relate to methods for increasing sports performance by increasing power output during physical exertion by a male or female athlete, by administering a combination of mangiferin, quercetin, and an ethyl acetate extract of Cyperus esculentus tubers to the athlete. The combination is administered in a single daily dosage, or from two to five divided doses per day. The total daily dosage is:
from 25 mg to 5,000 mg, from 25 mg to 3,000 mg, from 25 mg to 2,000 mg, from 35 mg to 1,500 mg, from 55 mg to 1,000 mg, from 65 mg to 500 mg, from 75 mg to 250 mg, or from 84 mg to 140 mg of mangiferin per day;
between 50 mg and 10,000 mg, between 100 mg and 8,000 mg, between 150 mg and 6,000 mg, between 300 mg and 4,000 mg, or between 500 mg and 2,000 mg of quercetin per day; and between 5 mg and 5,000 mg; between 10 mg and 500 mg per day; or between 15 mg and 350 mg per day of a high potency fraction of Cyperus esculentus tubers.
Various embodiments described herein relate to methods for increasing sports performance by increasing brain oxygenation, preventing fatigue, and/or increasing peak oxygen consumption during physical exertion by a female athlete, by administering a mangiferin composition to the athlete. The combination is administered in a single daily dosage, or from two to five divided doses per day. The total daily dosage is:
from 25 mg to 5,000 mg, from 25 mg to 3,000 mg, from 25 mg to 2,000 mg, from 35 mg to 1,500 mg, from 55 mg to 1,000 mg, from 65 mg to 500 mg, from 75 mg to 250 mg, or from 84 mg to 140 mg of mangiferin per day; and at least one of
from 10 mg and 5,000 mg, from 20 mg and 4,000 mg, from 30 mg and 2,000 mg, from 45 mg to 1,000 mg, or from 50 mg to 500 mg luteolin per day;
between 50 mg and 10,000 mg, between 100 mg and 8,000 mg, between 150 mg and 6,000 mg, between 300 mg and 4,000 mg, or between 500 mg and 2,000 mg of quercetin per day; and
between 5 mg and 5,000 mg; between 10 mg and 500 mg per day; or
between 15 mg and 350 mg per day of a high potency fraction of Cyperus esculentus tubers.
The term “athlete,” as used herein, generally relates to any person engaged in physical exercise, performing in an individual sport, or participating in a team sport. The terms “athlete,” “sports person,” and “exerciser,” unless otherwise specified, should be understood to be synonymous for the purpose of this disclosure.
Various embodiments disclosed herein relate to supplements containing a mango leaf extract rich in mangiferin. These supplements enhance performance in humans during high intensity exercise. In various embodiments, the supplements comprise a first component from 25 mg to 5,000 mg, from 25 mg to 3,000 mg, from 25 mg to 2,000 mg, from 35 mg to 1,500 mg, from 55 mg to 1,000 mg, from 65 mg to 500 mg, from 75 mg to 250 mg, or from 84 mg to 140 mg of mangiferin, administered per day in a single dose or multiple divided doses. The mangiferin may be administered as substantially pure mangiferin; or as a component of a plant extract, wherein the plant extract comprises from 10% to 90% by weight mangiferin; from 20% to 85% by weight mangiferin; from 40% to 75% by weight mangiferin; or from 50% to 70% by weight mangiferin, or about 60% by weight mangiferin. In various embodiments, the mangiferin is administered as a component of a mango leaf extract comprising 60% or more of mangiferin; up to 2.5% of isomangiferin; trace levels of isomangiferin; and up to 10% of sugars, based on weight %.
According to various embodiments disclosed herein, mangiferin may be administered in combination with a second herbal active ingredient. This second herbal active ingredient may comprise luteolin in an amount of between 10 mg and 5,000 mg, between 20 mg and 4,000 mg, between 30 mg and 2,000 mg, between 45 mg to 1,000 mg, or between 50 mg to 500 mg per day. In various embodiments, the second herbal active ingredient is an extract of Arachis hypogeae shells or Perilla frutescens herb, comprising at least 90% by weight luteolin. Alternatively, the second herbal active ingredient may comprise quercetin. Quercetin may be administered in an amount of between 50 mg and 10,000 mg, between 100 mg and 8,000 mg, between 150 mg and 6,000 mg, between 300 mg and 4,000 mg, or between 500 mg and 2,000 mg per day. In various embodiments, the second herbal active ingredient is a Sophora japonica extract, comprising at least 90% by weight quercetin. In further embodiments, mangiferin may be administered in combination with a high potency fraction of Cyperus esculentus tubers as a second herbal active ingredient. The high potency fraction of Cyperus esculentus tubers is obtained by extraction with ethyl acetate to obtain an organic solvent soluble fraction.
The high potency fraction comprises:
from 70% to 95% by weight oleic acid glyceryl esters, from 80% to 94% by weight oleic acid glyceryl esters, from 85% to 93% by weight oleic acid glyceryl esters, from 90% to 92% by weight oleic acid glyceryl esters, or about 91% by weight oleic acid glyceryl esters;
from 1% to 15% by weight linoleic acid glyceryl esters, from 3% to 14% by weight linoleic acid glyceryl esters, from 5% to 12% by weight linoleic acid glyceryl esters, from 6% to 9% by weight linoleic acid glyceryl esters, or about 7% by weight linoleic acid glyceryl esters; phytosterols, such as stigmasterol, in an amount of 0.2% by weight or more; and
flavonoids, such as myricetin, in an amount of 0.2% by weight or more. Various embodiments disclosed herein relate to supplements comprising from 25 mg to 5,000 mg, from 25 mg to 3,000 mg, from 25 mg to 2,000 mg, from 35 mg to 1,500 mg, from 55 mg to 1,000 mg, from 65 mg to 500 mg, from 75 mg to 250 mg, or from 84 mg to 140 mg of mangiferin; and between 10 mg and 5,000 mg, 20 mg and 4,000 mg, 30 mg and 2,000 mg, 45 mg to 1,000 mg, 50 mg to 500 mg luteolin, or 50 mg to 150 mg luteolin, in a single dosage form or multiple divided dosage forms. In various embodiments, the supplements comprise from 65 mg to 500 mg, from 75 mg to 250 mg, or about 140 mg of mango leaf extract comprising 60% mangiferin; and from 50 mg to 150 mg luteolin, in a single dosage form or in divided doses.
In various embodiments, the present disclosure describes supplements comprising:
In various embodiments, supplements comprising mangiferin in combination with luteolin or a mixture of quercetin and a high potency ethyl acetate extract of Cyperus esculentus increase peak power output after ischemia of a skeletal muscle, followed by reperfusion. This effect is seen in both men and women. In women, mangiferin supplements improve brain oxygenation at rest and during exercise, and increased peak VO2 during high-intensity exercise. Mangiferin extracts enhance performance during physical exertion, without leading to significant increases in consumption of oxygen. Moreover, a trend for better muscular extraction of O2 was observed during physical exertion performed after ischemia/reperfusion when the subjects had taken the combined MLE/quercetin/tiger.
Two supplements containing MLE had positive effects on performance during physical exertion. However, mangiferin/quercetin/tiger nut extract combinations are superior to mangiferin/luteolin combinations, particularly regarding the effects on power output during exercise following ischemia and reperfusion of skeletal muscles. While luteolin attenuates the ischemia/reperfusion injury in several tissues, it remains unknown whether luteolin prevents ischemia/reperfusion injury in skeletal muscle. Quercetin may protect skeletal muscle from ischemia/reperfusion injury in rodents submitted to ischemia. However, quercetin supplementation for 1 week in 30 m running sprints has been reported to reduce athletic performance. The present data show that an increase in performance, measured in terms of mean and peak power output during physical activity, was observed when mangiferin was administered, suggesting that mangiferin may be responsible for the effect on power output.
In various embodiments disclosed herein, administration of mangiferin in combination with luteolin or quercetin does not increase blood lactate responses or carbohydrate oxidation during submaximal exercise or other physical exertion. Although mangiferin activates pyruvate dehydrogenase (PDH) in cell cultures, resulting in reduced lactate production and increase carbohydrate oxidation, changes in lactate and carbohydrate levels during exercise were not observed when mangiferin was combined with luteolin or quercetin.
Muscle energy efficiency is reduced during high intensity exercise by several mechanisms which include, among others, increased recruitment of less efficient type II muscle fibers, lactic acidosis, electrolyte alterations, and the generation of reactive oxygen and nitrogen species (RONS). During high intensity exercise, RONS are produced due to both the high mitochondrial respiratory rate and the activation of the anaerobic metabolism. RONS may contribute to muscle fatigue by reducing calcium sensitivity, and reducing calcium release from sarcoplasmic reticulum. Mangiferin supplements may enhances myofilament Ca2+ sensitivity, which may result in greater force production if the required energy is available.
Excessive RONS production could reduce mitochondrial phosphate/oxygen ratio, or P/O ratio, while antioxidants in mangiferin supplements may favorably influence mitochondrial increase the P/O ratio. Moreover, the ingestion of antioxidants before physical exertion reduces the level of protein carbonyls in muscle and plasma, and lowers the glycolytic rate without a detrimental effect on performance.
Various embodiments disclosed herein relate to use of the polyphenols mangiferin, luteolin, quercetin, and combinations thereof for quenching free radicals generated during exercise or physical exertion. The three polyphenols discussed herein also inhibit xanthine oxidase. The present disclosure shows for the first time that antioxidants are capable of enhancing peak power output and mean power output during the fatigued state induced by repeated prolonged sprint exercise. These compounds thus enhance performance during sports activity or manual labor.
The antioxidant properties of the polyphenol supplements described herein may contribute to enhanced physical performance. However, a wide variety of antioxidants have previously failed to enhance peak power output in humans, and none have shown these properties in the fatigued state. To boost performance in a fatigued muscle, greater calcium release is needed to enhance the number of cross-bridges of muscle filaments that can be established, but also a faster calcium reuptake is required to shorten the relaxation phase. Caffeine can enhance force in fatigued muscle by boosting Ca2+ release, but the dose needed to cause a significant change in performance would be lethal for humans. Mangiferin, a major component of mango leaf extract, shares some common intracellular mechanisms of action with caffeine, which may facilitate calcium release in the fatigued state (i.e., when Ca2+ release is depressed). Like caffeine and beta-agonists, mangiferin increases cyclic AMP (cAMP) levels, and can, through the activation of protein kinase A (PKA), stimulate slow-twitch skeletal muscle isoform (SERCA) activity. However, at tolerable doses, caffeine does not alter skeletal muscle metabolism. The main mechanism of the ergogenic action of caffeine is its effect on the central nervous system, by enhancing muscle activation.
Although caffeine may enhance performance during prolonged exercise and team-sport activities, caffeine is unlikely to enhance power and strength under normal use. Moreover, there is no evidence supporting an ergogenic effect of caffeine during episodes of ischemia/reperfusion in sport disciplines. Unlike caffeine, which may cause hypokalemia in athletes, mangiferin/luteolin and mangiferin/quercetin extracts cause no significant changes during physical exertion on plasma calcium, potassium, sodium, and chloride levels.
Reduction in brain oxygenation is associated with fatigue. Moreover, at exhaustion during exercise improving the oxygenation of the brain and upper body by increasing oxygen intake while maintaining the lower extremities in a deoxygenated state by occluding circulation, was associated with improved performance. This supports a mechanistic link between brain oxygenation and fatigue during sprint exercise in a fatigued state. In various embodiments disclosed herein, mangiferin-containing supplements consumed before sprint exercise may counteract fatigue in female athletes by improving brain oxygenation.
The present disclosure describes the protective effects of a polyphenol combination including mango leaf extract (MLE), quercetin, and tiger nut extract on functional deterioration induced by an inadequate blood supply to muscle tissue (ischemia), followed by reperfusion of blood into the muscle tissue.
The results presented herein show that mangiferin-containing MLE has a remarkable ergogenic effect increasing muscle power in fatigued subjects, without increasing oxygen consumption, submaximal exercise efficiency, or submaximal and maximal blood lactate concentrations. This is expected for a compound acting on the central nervous system. MLE, when combined with quercetin and tiger nut extract, assists in maintaining skeletal muscle function during ischemia/reperfusion, strongly suggesting that this combination is also acting directly on the skeletal muscles.
The terms “effective amount” or “dose” as used herein are interchangeable and may refer to the amount of an active ingredient or agent or composition that elicits a biological response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, or any combination thereof. A biological or response may include, for example, the following: (1) increasing sports performance.
In the context of the present invention the term “part” in relation with the formulation refers to the amount and/or ratio in mass of each of the ingredients of said formulation.
In the context of the present invention the expression “acute phase” refers to the phase of about 48 hours of supplementation.
In the context of the present invention the expression “chronic phase” to the phase of about two weeks hours of supplementation.
In the context of the present invention the expression “carrier” refers to forms to which substances are incorporated to improve the delivery and the effectiveness of formulations or drugs. Carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions (U.S. National Library of Medicine. National Institutes of Health). Adjuvant is a substance added to a drug product formulation that affects the action of the active ingredient in a predictable way. Vehicle is an excipient or a substance, preferably without therapeutic action, used as a medium to give bulk for the administration of medicines (Stedman's Medical Spellchecker, © 2006 Lippincott Williams & Wilkins). Such pharmaceutical carriers, adjuvants or vehicles can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like, excipients, disgregants, wetting agents or diluents. Suitable pharmaceutical carriers are described in “Remington's Pharmaceutical Sciences” by E. W. Martin. The selection of these excipients and the amounts to be used will depend on the form of application of the pharmaceutical composition.
The present invention will now be described by way of examples which serve to illustrate the construction and testing of illustrative embodiments. However, it is understood that the present invention is not limited in any way to the examples below.
A. Subjects
Data on the effect of mangiferin-containing compositions was obtained from 17 men and 13 women. Subjects were requested to avoid strenuous exercise 48 h before the laboratory test and not to drink beverages containing caffeine or taurine during the 24 h preceding the test.
Body composition of the subjects was determined by dual-energy x-ray absorptiometry (Lunar iDXA, GE Healthcare, Wisconsin; USA). Subjects were tested to determine peak oxygen consumption (VO2peak), maximal heart rate (HRmax) and maximal power output (Wmax) in normoxia (F1O2: 0.21, P1O2: 143 mmHg) with an incremental exercise test to exhaustion with verification. The test started with 3 min at 20 W, followed by 15 and 20 W increases every 3 min in women and men, respectively, until the respiratory exchange ratio (RER) was >1.0.
After completion of the intensity with an RER ≤1.0, the intensity was increased by 10 and 15 W/min increase (women and men, respectively) until exhaustion. The intensity attained at exhaustion was taken at the maximal power output of the incremental exercise test (Wmax). At exhaustion, the ergometer was unloaded and subjects remained seated on the cycle ergometer pedaling at a slow speed (30-40 rpm) for 3 min. Thereafter, the verification test started at Wmax+5 W for 1 min, followed by 4 and 5 W increase (women and men, respectively) every 20 s until exhaustion. Between 1 and 2 weeks later, subjects reported to the laboratory on two occasions separated by at least 1 week, to carry out a constant-intensity supramaximal exercise to exhaustion at 120% of VO2max. This test was used to determine the anaerobic capacity. The constant-intensity supramaximal exercise test with longer endurance time to exhaustion was retained as representative for each subject. Data on the test subjects is presented in Table 2.
B. Power Output, Oxygen Uptake, and Supramaximal Exercise O2 Demand and Deficit
Power output during the sprint was reported as instantaneous peak power output (Wpeak) and mean power output (Wmean) throughout the duration of the sprints. Oxygen uptake was measured with a metabolic cart, calibrated according with high-grade certified gases. Respiratory variables were analyzed breath-by-breath and averaged every 20 s during the incremental exercise tests and during the repeated sprints. The highest 20 s averaged VO2 recorded during the incremental test (i.e., including the verification phase) was taken as VO2peak. The O2 demand during the sprints was calculated from the linear relationship between the last 20 s averaged VO2 of each load, from 80 W up to 80-90% of VO2max, while subjects were pedaling at 80 rpm. The accumulated oxygen deficit (AOD), representing the difference between O2 demand and VO2, was determined.
The volunteers were randomly assigned to three treatments, following a double-blind design. Treatment A was a placebo treatment (500 mg of maltodextrin per day); treatment B consisted in 140 mg of mango leaf extract (MLE; 60% mangiferin) and 50 mg of luteolin per day; and treatment C contained 140 mg of MLE (60% mangiferin), 600 mg of quercetin and 350 mg of tiger nut extract per day. The three treatments were divided in three daily doses administered every 8 h in methylcellulose capsules of identical appearance. The active ingredients in the extracts used in the test compositions is presented in Table 2.
Magnifera indica L. extract
Arachis hypogaea extract
Sophora japonica extract
Cyperus esculentus extract
uercetin (≥90%)
(≥0.2%)
≤7%
Mangifera i. extract (100%)
Arachis h. extract (100%)
Sophora j. extract (100%)
Cyperus e. Extract (≥50%)
aHigh Activity Fraction (HAF): Fraction in ethyl acetate.
bRelative to the amount of the HAF.
indicates data missing or illegible when filed
Subjects started supplement intake 48 h before the main experimental days. On the day of the experiment, subjects reported to the laboratory after a 10 h overnight fast, and 60 min before the start of the experiment ingested an additional dose of the supplement (i.e., ⅓ of the daily dose). Subjects were seated on cycle ergometers and performed two warming-up 8 s sprints in isokinetic mode at 80 rpm, separated by a 2 min interval (recovery phase 1) during which they pedaled with the cycle ergometer unloaded, as shown in
Blood samples were obtained from a heated hand vein at rest, 3 min after the second 30 s Wingate test, 1 min after the last sprint, and 5 and 10 min into the recovery period. The samples were analyzed for hemoglobin concentration, blood gases, electrolytes and acid-base balance.
B. Cerebral Oxygenation
Cerebral oxygenation was assessed at rest and during exercise using near-infrared spectroscopy, employing spatial resolved spectroscopy to obtain the tissue oxygenation index (TOI) using a path-length factor of 5.92. The NIRS optodes were placed on the right frontoparietal region at 3 cm from the midline and 2-3 cm above the supraorbital crest, to avoid the sagittal and frontal sinus areas. Using this optode placement the tissue oxygenation of the superficial frontal cerebral cortex was recorded. An additional optode was placed in the lateral aspect of the thigh at middle length between the patella and the anterosuperior iliac crest, over the middle portion of the Musculus vastus lateralis. The rate of muscle deoxygenation upon occlusion was calculated by determining the maximal slope of the linear decay of TOI over time. For this purpose, data were averaged every second and the slope TOI/time was calculated from the start of the occlusion to the end of occlusion, with a minimum interval of 4 s and a maximum of 20 s. Since the best linear fit was obtained with a 4 s interval, this was applied to all the occlusions.
C. Middle Cerebral Artery Blood Velocity
The mean blood velocity in the middle cerebral artery (MCAvmean) was determined as an estimate of cerebral blood flow. Two Doppler 2 MHz transducers were applied bilaterally over the middle transtemporal window, and the readings from the transducers were averaged. A head harness was used to minimize potential movement artifacts. Resting cerebral oxygenation and MCAvmean was calculated as the average of a 2 min collection period, while during exercise 5 s averages were generated and the average for the whole sprint reported.
D. Power Output
All pre-tests were performed on the same cycle ergometer, which maintains constant exercise intensity despite variations in pedaling rate. During all tests subjects were requested to maintain a pedaling rate close to 80 rpm. An isokinetic ergometer was used to determine power output. The ergometer was operated in a rpm-independent constant load during the warm-up and recovery phases, and switched to an isokinetic mode during the sprints, with the speed set at 80 rpm. During the isokinetic sprints, the subjects pedaled as fast and hard as possible, exerting as much force on the pedals as they could at each pedal stroke from the start to the end of the sprint. The servo-control brake system adjusted the braking force continuously to maintain a pedaling rate of 80 rpm during the entire sprint. Exhaustion was defined by the incapacity of the subject to maintain a pedaling rate above 50 rpm for 5 s, or by a sudden stop in pedaling.
D. Oxygen Demand and Deficit
The O2 demand during the supramaximal exercise bouts was estimated from the linear relationship between the last min averaged VO2 of each load, from 20 to 40 W to the highest intensity with an RER<1.00 in the incremental exercise test. The accumulated oxygen deficit (AOD), representing the difference between O2 demand and VO2, was determined.
E. Assessment of Pain and Effectiveness of Concealment
Subjects were requested to rate the level of pain felt during the occlusion from 0 to 10, 10 being the highest muscle pain ever suffered during or after exercise in their life. At the end of the experiment subjects were asked about the kind of supplement they suspected they had received to check on the effectiveness of concealment. After placebo administration, 7 out of 30 subjects guessed correctly that they had placebo. Following B supplementation, 11 subjects out of 30 guessed correctly that they had polyphenols, and after supplement C, 16 out of 30 guessed correctly that they had polyphenols. Subjects generally guessed that they had taken polyphenols when they felt better during the whole experiment.
F. Results
In this study, men and women had comparable levels of fitness. Men had a 15% greater VO2max per kg of body mass than women, but the between-sex difference disappeared when the VO2max was expressed per kg of lean mass of the lower extremities. Men had 41% greater anaerobic capacity than women per kg of body mass, but this difference was reduced to 23% when expressed in relation to the lean mass of the lower extremities. No significant between-sex differences were observed in the Wingate test when the values were normalized to the lean mass of the lower extremities.
1. Effects on Performance
Supplements B (mangiferin+luteolin) and C (mangiferin+quercetin+tiger nut extract) enhanced performance during Sprint 3 (the 60-second sprint), relative to a placebo. Additionally, supplement C enhanced performance during Sprint 3 and Sprint 4 (the first 15-second sprint), relative to a placebo, and during Sprint 4, relative to Supplement B. The peak power output (Wpeak) observed during the sprints of
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Also as seen in Table 3, Wpeak during Sprint 4 (the first 15-second sprint) from patients administered placebo was 288.0 W, while Wmean during Sprint 4 was 165.4 W. In patients administered Supplement B, Wpeak increased to 311.9 W and Wmean increased to 172.5 W; however, these increases were not significant, relative to placebo. In patients administered Supplement C, Wpeak increased to 343.9 W and Wmean increased to 183.9 W. The increases in power output in patients administered Supplement C during Sprint 4 were determined to be significant, relative to placebo (p<0.05). Also, the differences in both peak and mean power output between patients administered Supplement B and patients administered Supplement C were determined to be significant (p<0.05). During Sprint 5, patients administered Supplement C also showed a statistically significant increase in peak power output relative to patients administered placebo (p<0.05). During the 60 s long sprint, supplements B and C increased Wpeak by 12.5 and 10.8%, respectively. In Sprint 4, performed after ischemia, supplement C increased Wpeak by 19.4% compared to placebo (p<0.001) and by 10.2% compared to supplement B (p<0.05). The total amount of work performed was 2.4% higher following the ingestion of supplements B and C, compared with placebo in women (34.1±4.3, 34.9±4.1, and 34.9±4.0 kJ, for placebo and supplements B and C, respectively, p<0.05). The corresponding values in men were 51.7±6.7, 52.1±7.3, and 52.3±5.8 kJ, respectively (p>0.3). During the sprint performed after ischemia (Sprint 4), supplement C enhanced Wmean by 11.2% (p<0.001) compared with the placebo trial and 6.7% compared with supplement B (p=0.012). As seen in
2. Pulmonary Gas Exchange
In women, the peak VO2 reached during the repeated sprints was 5.8% greater after the administration of supplements (mean of both trials) compared with the placebo trial (2,189±334 and 2,316±403 mL/min, for placebo and supplements, respectively, P=0.012). No such effect was observed in men (3,265±406 and 3,318±422 mL/min, placebo and supplements, respectively, P=0.42). The O2 deficit incurred was 2.7-fold greater after the ingestion of supplement C than after placebo in men (P=0.001), while it remained at the same level in women.
Neither the accumulated VO2 nor the O2 deficit observed during the sprints were significantly altered by any of the treatments, when all sprints were analyzed conjointly. Nevertheless, during the 15 s sprint performed after ischemia (Sprint 4), the vastus lateralis oxygenation index tended to be a slightly lower value after the administration of supplement C, compared with placebo (P=0.056), as shown in
3. Brain Oxygenation
Resting brain oxygenation was lower in women than in men (P<0.001). This was associated with lower PETCO2 (end tidal CO2 concentration, mm Hg) in women than in men (30.7±2.6 and 34.2±2.1 mm Hg in women and men, respectively, P<0.001). In women, both supplements increased frontal lobe oxygenation at rest (59.4±5.7, 64.9±3 0.8, and 64.9±6.4%, for placebo, Supplement B, and Supplement C, respectively, P<0.05, for the comparisons of supplement B and C against placebo). In men, brain oxygenation remained substantially unchanged (69.3±5.4, 69.1±4.2, and 68.0±4.4%, for placebo, Supplement B, and Supplement C, respectively, P>0.50, for the comparisons of supplement B and C against placebo).
In women, brain oxygenation during the sprints was greater after the ingestion of supplements B and C than placebo (
A. Subjects
Twelve healthy male physical education students (age=21.3±2.1 yr, height=176.6±5.8 cm, body mass=75.7±9.9 kg, body fat=20.3±5.3%, VO2max: 3.69±0.47 L/min and 49.4±8.2 mL/(Kg·min)) agreed to participate in this investigation (Table 1). Before volunteering, subjects received full oral and written information about the experiments and possible risks associated with participation. Written consent was obtained from each subject. The study was performed by the Helsinki Declaration and approved by the Ethical Committee of the University of Las Palmas de Gran Canaria (CEIH-2016-02). The sample size required to allow detecting a 5% improvement of performance with a statistical power of 0.8 (α=0.05), assuming a coefficient of variation for the ergometric test below 5%, was eight subjects. To account for potential dropouts twelve subjects were finally recruited.
The inclusion criteria for participation in the study were: age from 18 to 35 years old; male without chronic diseases or recent surgery; non-smoker; normal resting electrocardiogram; body mass index below 30 and above 18; no history of disease requiring medical treatments lasting more than 15 days during the preceding 6 months; no medical contraindications to exercise testing; and lack of allergies to peanuts or mango fruit. All volunteers applying met the inclusion criteria.
After inclusion, a medical history, resting electrocardiogram, a blood analysis including the assessment of a basic hemogram and general biochemistry, and a basic urine analysis were carried out to verify the health status of participants. Then subjects were assigned to a control placebo trial or to a treatment trial with a double-blind crossover design. Six subjects were randomly allocated to a placebo (P) and another six to a treatment group (T). The placebo received microcrystalline cellulose capsules containing 500 mg of maltodextrin, while the treatment group received similar capsules containing luteolin and mangiferin. The daily doses were for three subjects (50 mg of luteolin and 100 mg Mangiferin; low dose treatment group; LT) and for the other three (100 mg of luteolin and 300 mg Mangiferin; low dose treatment group; LT). Subjects ingested the supplements every three hours during fifteen days, then after 4-6 weeks, treatment groups received placebo, and the placebo group was again split into low and a high dose treatment groups, also for 15 days.
Forty-eight hours after the start of the supplementation subjects reported to the laboratory early in the morning under fasting conditions and received an extra dose of the assigned supplements. After that, their body composition was determined using dual-energy x-ray absorptiometry (Lunar iDXA, General Electric, Wisconsin, USA), followed by the assessment of their resting metabolic rate (BMR). Then near-infrared spectroscopy (NIRS) optodes were placed on the frontal lobe and vastus lateralis as previously reported (Curtelin D, Morales-Alamo et al. J Cereb Blood Flow Metab 271678X17691986, 2017). With the subjects resting supine a 10 cm wide cuff connected to a fast compressor (SCD10, Hokanson, Bellevue, USA) was placed around the right thigh, as proximal as possible and the leg elevated for 3 min. At the end of the three min, the circulation was occluded for 8 min, and the cuff was released and the hyperemic response measured during the next two minutes. After that, a forearm vein was catheterized and a resting blood sample obtained before the start of the exercise protocol.
The exercise protocol started with an 8 s isokinetic sprint on a cycle ergometer (Excalibur Sport 925900, Lode, Groningen, The Netherlands) (
This exercise protocol was repeated after 15 days of supplementation, to determine potential effects due to chronic supplementation. After 4-6 weeks, the acute and chronic phase was repeated following the crossover design described above.
Power output during the sprint is reported as instantaneous peak power (Wpeak-i), and as the mean power output achieved during the full duration of the sprints (Wmean-8 and Wmean 30). Oxygen uptake was measured with a calibrated metabolic cart (Vyntus; Carefusion-BD, Madrid, Hospital Hispania). Respiratory variables were analyzed breath-by-breath and averaged every 5 s during the sprints. During maximal exercise 15 breath rolling average was generated starting from 120 s before the end of exercise and highest 15-breath averaged value was taken as the VO2max.
Cerebral Oxygenation and Musculus vastus lateralis Oxygenation
Cerebral oxygenation was assessed using near-infrared spectroscopy (NIRS, NIRO-200, Hamamatsu, Japan) employing spatial resolved spectroscopy to obtain the tissue oxygenation index (TOI) using a pathlength factor of 5.92 (Van der Zee P et al. Adv Exp Med Biol 316: 143-153, 1992.). The NIRS optodes were placed on the right frontoparietal region at 3 cm from the midline and 2-3 cm above the supraorbital crest, to avoid the sagittal and frontal sinus areas. With this optode placement, the tissue oxygenation of the superficial frontal cerebral cortex is recorded. This region is irrigated by the anterior cerebral artery, which, like the MCA, receives its flow from the internal carotid artery. Both MCA and anterior cerebral arteries communicate through the circle of Willis. An additional optode was placed in the lateral aspect of the thigh at middle length between the patella and the anterosuperior iliac crest, over the middle portion of the m. vastus lateralis.
This test was performed in the same cycler ergometer started at 20 W, and the load was increased by 20 W every 3 min (1, 69). The arm cranking MFO test began at 10 W for 5 min followed by a 10-W increase every 3 min. The leg MFO test started at 30 W for 5 min, followed by a 30-W increment every 3 min. At the end of the 3-min period during which the subject exhibited an RER>1.0, the exercise was stopped.
The O2 demand during the sprints was calculated from the linear relationship between the last 60-s averaged VO2 of each load, measured during the MFO. The accumulated oxygen deficit (AOD), representing the difference between O2 demand and VO2, was determined as previously reported (Calbet J A, Chavarren J, and Dorado C. Eur J Appl Physiol 76: 308-313, 1997., Dorado C, Sanchis-Moysi J, and Calbet J A Can J. Appl Physiol 29: 227-244, 2004). The energy efficiency of exercise was determined as previously reported (Chavarren J, and Calbet J A. Eur J Appl Physiol 80: 555-563, 1999), using the data collected during the MFO tests.
Dietary information was collected from all subjects before the start of the supplementation, and after one week into each supplementation period using dietary logs including four days. For this purpose, subjects were provided with a dietary diary and a kitchen scale (1 g precision from 0 to 5000 g, calibrated in our laboratory with Class M1 calibration weight, Schenk) and instructions to report in grams all food and drinks ingested. The information recorded was later analyzed with specific software for the Spanish diet (Dial, Alce Ingenieria, Madrid, Spain (Ortega R M. et al. Eur J Clin Nutr 61: 77-82, 2007).
Ten mL blood samples were obtained at each sampling point and processed to obtain serum and plasma, and immediately frozen at −80° C. Further analysis will be carried out on this samples including the concentration of carbonylated proteins as a marker for oxidative stress using the“OxyBlot” protein oxidation kit (Intergen Company, Purchase, N.Y.) as previously described (Morales-Alamo D et al. J Appl Physiol 113: 917-928, 2012, Romagnoli M et al. Free Radic Biol Med 49: 171-177, 2010).
Statistics
Variables were checked for normal distribution by using the Shapiro-Wilks test. When necessary, the analysis was carried out on logarithmically transformed data. A double repeated-measures ANOVA test with time (two levels: acute and chronic) and treatment with another two levels (Placebo vs. treatment) was first applied. Pairwise comparisons were carried using the least significant post hoc test (LSD). A comparison between high and low dose was also carried out using a repeated measures analysis with dose levels as between-subjects factor with two levels (low and high). The relationship between variables was determined using linear regression analysis. Values are reported as the mean±standard error of the mean (unless otherwise stated). P 0.05 was considered significant. Statistical analysis was performed using SPSS v.15.0 for Windows (SPSS Inc., Chicago, Ill.).
Polyphenols had no significant effects on the hemogram and blood biochemistry clinical tests. The diet was not significantly altered by the treatment regarding total energy, macronutrients, vitamins, dietary fiber and plant sterols intakes. Likewise, no significant alterations were observed in resting blood lactate concentration, resting metabolic rate or the body composition. Nevertheless, the resting breathing frequency and the resting PETCO2 were slightly increased and decreased, respectively from the first to the second assessment (Table 1). The resting blood pressure, blood lactate concentration and heart rate were not altered by the intervention.
All respiratory variables responded similarly to the placebo and the polyphenol treatment. Indices of maximality of tests were also similar, indicating that the subjects exercised to a similar extent in all tests. Neither the VO2max nor the load reached at exhaustion (Wmax) were affected by the treatment. There was a small 2 mmHg improvement in PETO2 in second test which was also accompanied by a small reduction in PETCO2 (˜2 mmHg).
Lactate responses to submaximal exercise were almost identical. Although, blood lactate concentration at 200 W was 11% lower after the polyphenol treatment, this effect did not reach statistical significance (P=0.11). Delta efficiency was transiently improved 48 h after the start of polyphenols in the group receiving the lower dose (P=0.002, compared to placebo; Treatment×time×dose interaction P=0.001) (Table 1). This effect evanished following 15 days of supplementation (P=0.87 compared to placebo). Polyphenols supplementation did not alter the MFO (Table 1) nor peak HR.
Sprint Exercise after Ischemia/Reperfusion
The PPOi was not altered by the acute administration of polyphenols (
In the sprints post ischemia performed with polyphenols, the mean power output developed during the first 5 s was increased by 23% from 48 h (272.5±63.8 W) to 15 days (333.8±93.2 W) (P=0.01). In contrast, no significant changes were observed form 48 h to 15 days in the placebo conditions (
(
Compared to placebo, polyphenol intake resulted in 4.0% greater MPO (acute and chronic assessments combined, P=0.017; ANOVA Wingate×time×treatment P=0.027). Acutely, compared to placebo, polyphenol administration enhanced MPO by 5% in the second Wingate test (P=0.009) (
The last sprint was performed after a time trial to exhaustion followed by a 60 s ischemia, in a situation of extreme fatigue and exhaustion of the energy resources. After 48 h of supplementation, MPO was 15% higher in the group receiving polyphenols than in the placebo group (P=0.04). No significant differences were observed neither in brain oxygenation index during the last Wingate test (65.8±8.6 and 68.5±7.2%, for the placebo and polyphenols trials, respectively, P=0.38) nor in quadriceps muscle oxygenation index (57.1±6.7 and 55.8±9.0%, for the placebo and polyphenols trials, respectively, P=0.22).
No significant differences were observed in the mean lactate responses after incremental exercise and the three Wingate tests (10.3±2.4 and 11.1±2.3 mM, for the placebo and polyphenols trials, respectively, P=0.15).
No significant effects were observed in the total work performed during the final time trial (101.3±56.6±103.5±61.6 Kj, for the placebo and polyphenol trial, respectively P=0.85). Neither brain oxygenation index (64.6±6.5 and 68.0±6.0%, for the placebo and polyphenol trial, respectively P=0.18) nor quadriceps muscle oxygenation index (61.3±6.3 and 60.6±8.5%, for the placebo and polyphenol trial, respectively P=0.34).
During the first five seconds of the occlusion quadriceps muscle oxygenation index was reduced to lower levels after the ingestion of polyphenols (P=0.04,
This example shows that the combination of a mango leaves extract rich in mangiferin with luteolin enhances exercise performance during sprint exercise and facilitates muscle oxygen extraction in the fatigued state. In addition, this polyphenolic combination improves muscle performance after ischemia/reperfusion by two main mechanisms. Firstly, it facilitates muscle oxygen extraction as demonstrated by the greatest reduction of the muscle oxygenation index during the first five seconds of total occlusion of the circulation. Secondly, it may facilitate the production of ATP through an additional recruitment of the glycolysis, as indicated by the greater levels of blood lactate concentration observed in the sprints performed after ischemia/reperfusion. Importantly, MLE and luteolin enhanced mean power output during prolonged sprints (30 s Wingate test) carried out after 30 min of recovery. This improvement in prolonged sprint performance was accompanied by better brain oxygenation and larger muscle oxygen extraction during the sprints.
A mango leaves extract combined with luteolin improves muscle O2 extraction. In the present example we have shown that MLE+Luteolin supplementation allows the skeletal muscle to reach lower levels of tissue oxygenation. This effect could be explained by a reduction of skeletal muscle O2 delivery, better microvascular distribution of perfusion (prioritizing the active skeletal muscle fibers) and enhanced mitochondrial O2 extraction. Since the effect of MLE+Luteolin was greater during the second Wingate test, i.e., when skeletal muscle blood flow is expected to increase quicker a to a higher level, a reduction in O2 delivery to exercising muscles is unlikely. Moreover, the fact that the HR response was not different with supplementation also argues against a different cardiovascular regulation between conditions. The matching between perfusion and VO2 at the microvascular level second explanation cannot be tested with current technology during whole body exercise in humans. Thus, the most plausible mechanism by which polyphenol supplementation could have enhanced O2 extraction is by improving mitochondrial respiration, which could be impaired by the high levels of reactive oxygen and nitrogen species (RONS) produced during repeated sprint exercise.
A mango leaves extract combined with luteolin enhances sprint performance after ischemia/reperfusion. Sprint performance after ischemia reperfusion was improved, particularly after the first ischemia, which was followed immediately by a sprint, while the effect was less marked during the second 15 s sprint, which was preceded by 30 s of ischemia and 10 s of active recovery with reoxygenation. In the present investigation the inhibitory action of MLE+luteolin on XO might have been beneficial during high intensity-exercise, ischemia and ischemia/reperfusion by reducing superoxide and secondary RONS production and attenuating NO production from nitrite and, hence, the inhibition of mitochondrial respiration. Consequently, MLE+luteolin could have facilitated mitochondrial respiration and aerobic energy production during the sprints and ischemia periods, as actually shown by the lower levels of muscle oxygenation observed in this investigation when the experiments were preceded by the ingestion polyphenols.
Mangiferin administration combined with Luteolin increases frontal lobe oxygenation during repeated sprint exercise.
Better frontal lobe oxygenation was observed during the prolonged sprints performed after the ingestion of MLE+luteolin. These effects may be related to a better distribution of blood flow between tissues or enhanced cerebral vasodilation facilitated by the polyphenols.
In summary, supplementation with mango leaves extract combined with luteolin enhances exercise sprint performance, likely by improving brain oxygenation and enhancing muscle oxygen extraction.
Although the various exemplary embodiments have been described in detail with particular reference to certain exemplary aspects thereof, it should be understood that the invention is capable of other embodiments and its details are capable of modifications in various obvious respects. As is readily apparent to those skilled in the art, variations and modifications can be affected while remaining within the spirit and scope of the invention. Accordingly, the foregoing disclosure, description, and figures are for illustrative purposes only and do not in any way limit the invention, which is defined only by the claims.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2018/084023 | 12/7/2018 | WO | 00 |
