EP0706390A1 - Capacite de performance amelioree en economisant le glycogene des muscles grace aux acides gras a chaines moyennes - Google Patents

Capacite de performance amelioree en economisant le glycogene des muscles grace aux acides gras a chaines moyennes

Info

Publication number
EP0706390A1
EP0706390A1 EP94915965A EP94915965A EP0706390A1 EP 0706390 A1 EP0706390 A1 EP 0706390A1 EP 94915965 A EP94915965 A EP 94915965A EP 94915965 A EP94915965 A EP 94915965A EP 0706390 A1 EP0706390 A1 EP 0706390A1
Authority
EP
European Patent Office
Prior art keywords
medium chain
fatty acids
chain fatty
exercise
subject
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP94915965A
Other languages
German (de)
English (en)
Other versions
EP0706390A4 (fr
Inventor
Mark L. Dreher
Ralph A. Jerome
Dondeena G. Bradley
Roger B. Dehnel
Daniel L. Beyer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mars Inc
Original Assignee
Mars Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mars Inc filed Critical Mars Inc
Publication of EP0706390A1 publication Critical patent/EP0706390A1/fr
Publication of EP0706390A4 publication Critical patent/EP0706390A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/225—Polycarboxylic acids

Definitions

  • This invention relates to enhancing physical activity performance capacity.
  • this invention relates to a method of sparing muscle glycogen in a subject by increasing medium chain fatty acids in the subject. More in particular, this invention relates to the use of a triglyceride of medium chain fatty acids to facilitate muscle glycogen sparing during periods of physical activity.
  • Triglycerides are the principal form in which fats are eaten and stored in the body. Triglycerides are composed of two different compounds—fatty acids and glycerol. Three fatty acids are attached to each glycerol molecule as follows:
  • the fatty acid side chain comprises a chain of carbon atoms onto which are bonded hydrogen and oxygen atoms. These chains vary in degree of saturation with hydrogen and length. Fatty acids are classified as saturated, monounsaturated or polyunsaturated depending upon the number of hydrogen atoms. For the purposes of this document, short chain fatty acids are defined as containing fewer than six carbons, medium chain fatty acids contain six to twelve carbons, and long chain fatty acids contain fourteen or more carbons.
  • LCFAs long chain fatty acids
  • LCFAs long chain fatty acids
  • LCFAs long chain fatty acids
  • the LCFAs are then packaged in a fat droplet called a chylomicron. Chylomicrons pass into the lymphatic system and then slowly into the blood stream from which they are subsequently removed by the liver. The chylomicron is then broken down into smaller components called lipoproteins, which are circulated throughout the bloodstream to various tissues, particularly adipose fat storage tissue.
  • LCFAs can be released through further complex processes from the adipose tissue to provide a source of energy to the muscle under certain exercise conditions.
  • MCFAs medium chain fatty acids
  • MCFAs are released from the triglyceride backbone at higher rates than LCFAs by digestive enzymes in the small intestine.
  • MCFAs being more soluble in the blood than LCFAs, are transported and circulated differently throughout the body. MCFAs are absorbed directly through the wall of the small intestine. MCFAs are then released directly into the blood stream that flows to the liver. This is unlike LCFAs which must be packaged into chylomicrons for transport in the body.
  • LCFAs a substance called carnitine is required for transport into the mitochondria. Unlike LCFAs, MCFAs can enter the mitochondria without the help of carnitine due to their shorter chain length. MCFAs are converted within the liver to form ketone bodies. These ketone bodies, uniquely derived from MCFAs, may be transported to the muscle to be used as an additional energy source. Owing to their increased solubility, some MCFAs may bypass the liver and be directly transported to mitochondria located within the muscle as a further source of energy. So, due to these three main differences in metabolism of fatty acids with different chain lengths, MCFAs may provide the muscle with readily available energy.
  • Muscles use energy at a rate proportional to the intensity of physical activity. Energy is produced when the mitochondria contained within muscle cells burn up carbohydrate and fatty acids in the presence of oxygen to make a biochemical compound called ATP. ATP is the substance that actually provides the direct source of energy to the muscles. ATP can also be produced by alternative mechanisms without oxygen, but in this case only carbohydrates and not fats are used.
  • LCFA availability is a limiting factor for the muscle to use fat as an energy source during high intensity exercise.
  • Exercise intensity is defined as the tempo, speed or resistance of an exercise. Intensity can be increased by working faster—doing more work in a given period of time. It is generally measured by evaluating the metabolic response of an individual challenged by exercise of increasing intensity, therefore increasing oxygen consumption (V0 2 ) . A point is reached where, even though the exercise intensity can be increased still further, there is no accompanying increase in oxygen uptake. This is called the maximum oxygen uptake
  • V0 2 max is related to size, age, sex, genetic potential and level of habitual activity of the individual.
  • the relative intensity of the oxygen cost of an activity is expressed as a percentage of V0 2 max.
  • the relative exercise intensity reflects the physiological and psychological demands on an individual more than the absolute values for work loads.
  • Test diets of MCT compared with carbohydrate were ingested 1 hour prior to the exercise ride. 25 grams of MCT in a hot drink flavored with vanilla were ingested 1 hour before the beginning of exercise and compared with the ingestion of a 6% glucose solution. Ingestion of MCT or glucose did not contribute to the reduction of endogenous carbohydrate utilization.
  • This study by Massicotte et al. is unique in contrast to the previously described studies in that glucose and MCTs were labeled with a 13 C tracer to assess more accurately their use for energy throughout the exercise bout. Subjects break down the labeled MCT and glucose as 13 C0 2 which is easily measured in the expired breath. The contribution of MCT and carbohydrate to the total energy expenditure as measured with a 13 C tracer was not statistically significantly different.
  • MCFAs are metabolized differently than LCFAs. MCFAs may provide a readily available source of energy to the muscle when blood flow is constricted during a high intensity exercise.
  • glycogen sparing effect or lowering of the glycogen utilization rates
  • subjects who consumed a product containing a mixture of triglycerides of MCFAs and carbohydrate compared to other products containing triglycerides of LCFAs and carbohydrate or carbohydrate alone.
  • the glycogen utilization rate (amount of muscle carbohydrate used per minute during exercise) for each subject consuming a product containing triglycerides of MCFAs and carbohydrate was significantly reduced in comparison to subjects who consumed products containing either carbohydrate alone or carbohydrate and triglycerides of LCFAs at the same caloric intake. This indicates that subjects who consume triglycerides of MCFAs can use less muscle carbohydrate during physical activity levels which primarily rely on muscle glycogen as a carbohydrate source.
  • the present invention is a method of providing a preferential fuel to enhance performance, particularly a method of sparing muscle glycogen in a subject by increasing medium chain fatty acid for undergoing physical activity at an intensity of greater than 70% of V0 2 max.
  • the concentration of medium chain fatty acid is increased by administering a triglyceride of a least one medium chain fatty acid, particularly by administering a triglyceride of three medium chain fatty acids, to the subject.
  • the medium chain fatty acids are saturated or unsaturated fatty acids having 6 to 12 carbon atoms.
  • the medium chain fatty acids are saturated fatty acids having 6 to 12 carbon atoms, particularly a saturated fatty acid having 10 carbon atoms.
  • the triglyceride is administered in an amount effective for sparing muscle glycogen, preferably 1 to 500 grams, more preferably 4 to 50 grams.
  • the physical exercise intensity is at greater than 70% of V0 2 max, more preferably at least 75% of V0 2 max, still more preferably at least 85% of V0 2 max.
  • the medium chain triglyceride may be administered in a solid or liquid form.
  • the triglyceride is administered by ingestion.
  • the triglyceride may be administered together with a carbohydrate and/or other ingredients.
  • the concentration of medium chain fatty acid is increased before the subject undergoes the physical activity or while the subject undergoes the physical activity.
  • the invention is also a method of sparing muscle glycogen in a subject by increasing medium chain fatty acid in the subject for undergoing physical activity at a level of muscle activity at which glycogen would be metabolized as a source of energy, particularly a method of enhancing physical activity performance capacity of a subject by administering to the subject a triglyceride of medium chain fatty acids for undergoing physical activity at an intensity greater than 70% of V0 2 max.
  • a muscle biopsy of the vastu ⁇ lateralis was taken prior to the exercise bout and after the 30 minute ride. Muscle samples were analyzed for glycogen. MUSCLE GLYCOGEN USE
  • the amount of muscle carbohydrate used per minute during exercise was significantly less for subjects consuming the MCT product versus the LCT product under identical exercise protocols.
  • Glycerol the backbone of the triglycerides of capric acid and of LCFAs, was present at higher levels for the subjects consuming the MCT product versus the LCT product. This indicates that MCFAs were being removed from the glycerol backbone more readily than LCFAs during the exercise protocol.
  • glycogen use rates were compared during similar exercise protocols at 85% of V0 2 max for 30 minutes.
  • test protocol was the same as in Example 1. MUSCLE GLYCOGEN USE
  • the amount of muscle carbohydrate used per minute during exercise was significantly less for subjects consuming the MCT product versus the subjects given carbohydrate alone under identical exercise protocols.
  • Glycerol the backbone of the triglycerides of capric acid, was present at high levels for subjects consuming the MCT product indicating that MCFAs were being removed from the triglyceride backbone during the exercise protocol.
  • glycogen use rates were compared during similar exercise protocols at 100% of V0 2 max for 5 minutes.
  • test protocol was similar to Example 1, however five subjects were tested.
  • Glycerol the backbone of the triglycerides of capric acid, was present at high levels for subjects consuming the MCT product indicating that MCFAs were being removed from the triglyceride backbone during the exercise protocol.
  • glycogen use rates were compared during similar exercise protocols at 65% of V0 2 max for 60 minutes.
  • test protocol was similar to Example 1, however four subjects were tested at 65% of V0 2 max for 60 minutes.
  • MUSCLE GLYCOGEN USE The amount of muscle carbohydrate used per minute during exercise was slightly higher for subjects consuming the MCT product versus the subjects given carbohydrate alone under identical exercise protocols. The results were as follows;
  • glycogen use rates were compared during similar exercise protocols at 50% of V0 2 max for 60 minutes.
  • test protocol was similar to Example 1, however four subjects were tested at 50% of V0 2 max for 60 minutes.
  • performance testing was measured as follows. After the post biopsy, subjects performed one-minute intervals at 115% of V0 2 max with a 1:1 work:rest ratio. Subjects continued until they could not maintain a cadence of greater than 60 RPM or until they completed 10 intervals, whichever came first. The time of the performance test is the total number of seconds of work, not counting rest intervals.
  • Subject 1 227 Subject 2 600
  • Subject 1 176 Subject 2 600

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Procédé consistant à générer un combustible préférentiel afin d'améliorer la performance en économisant le glycogène des muscles d'un sujet exerçant une activité physique très intense, par l'augmentation des acides gras à chaînes moyennes chez le sujet, et notamment par administration d'un triglycéride d'acides gras à chaînes moyennes à ce sujet avant ou pendant l'activité physique.
EP94915965A 1993-04-30 1994-04-29 Capacite de performance amelioree en economisant le glycogene des muscles grace aux acides gras a chaines moyennes Withdrawn EP0706390A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US56035 1987-06-01
US5603593A 1993-04-30 1993-04-30
PCT/US1994/004796 WO1994025019A1 (fr) 1993-04-30 1994-04-29 Capacite de performance amelioree en economisant le glycogene des muscles grace aux acides gras a chaines moyennes

Publications (2)

Publication Number Publication Date
EP0706390A1 true EP0706390A1 (fr) 1996-04-17
EP0706390A4 EP0706390A4 (fr) 2000-08-23

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP94915965A Withdrawn EP0706390A4 (fr) 1993-04-30 1994-04-29 Capacite de performance amelioree en economisant le glycogene des muscles grace aux acides gras a chaines moyennes

Country Status (4)

Country Link
EP (1) EP0706390A4 (fr)
AU (1) AU6779294A (fr)
CA (1) CA2161784A1 (fr)
WO (1) WO1994025019A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005120484A1 (fr) * 2004-06-09 2005-12-22 Kurume University Régulateur pour les fonctions physiologiques de la ghrelin
JP2017531651A (ja) * 2014-10-10 2017-10-26 ネステク ソシエテ アノニム 移動能力又は動作能力を改善するため、あるいはフレイルを治療するための組成物及び方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0481899A1 (fr) * 1990-10-18 1992-04-22 Pernod-Ricard Boisson diététique destinée à permettre de soutenir l'effort
EP0537113A1 (fr) * 1991-10-10 1993-04-14 SANDOZ NUTRITION Ltd. Aliments énergétiques
EP0540462A1 (fr) * 1991-10-10 1993-05-05 Sandoz Nutrition Ltd. L-Glutamine ou un peptide riche en L-glutamine pour la préparation d'une formulation orale pour le traitement d'une diminuation de la concentration sanguine de L-glutamin

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5747446A (en) * 1980-09-05 1982-03-18 Nippon Oil & Fats Co Ltd Nutrious food composition
US4687782A (en) * 1984-12-10 1987-08-18 Nutri-Fuels Systems, Inc. Nutritional composition for enhancing skeletal muscle adaptation to exercise training

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0481899A1 (fr) * 1990-10-18 1992-04-22 Pernod-Ricard Boisson diététique destinée à permettre de soutenir l'effort
EP0537113A1 (fr) * 1991-10-10 1993-04-14 SANDOZ NUTRITION Ltd. Aliments énergétiques
EP0540462A1 (fr) * 1991-10-10 1993-05-05 Sandoz Nutrition Ltd. L-Glutamine ou un peptide riche en L-glutamine pour la préparation d'une formulation orale pour le traitement d'une diminuation de la concentration sanguine de L-glutamin

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Section Ch, Week 198217 Derwent Publications Ltd., London, GB; Class D13, AN 1982-33891E XP002140728 & JP 57 047446 A (NIPPON OILS & FATS CO LTD), 18 March 1982 (1982-03-18) *
See also references of WO9425019A1 *

Also Published As

Publication number Publication date
WO1994025019A1 (fr) 1994-11-10
EP0706390A4 (fr) 2000-08-23
AU6779294A (en) 1994-11-21
CA2161784A1 (fr) 1994-11-10

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