CLA and vitamin D -
In some embodiments, the CLA is administered before the Vitamin D is administered to the subject. In some embodiments, the CLA is administered after the Vitamin D is administered to the subject.
In some embodiments, the CLA and Vitamin D are administered to the subject concurrently. In some embodiments, the method comprises reducing or preventing loss of muscle mass and function in a subject in need thereof.
In some embodiments, the method comprises increasing muscle protein synthesis in a subject in need thereof. In some embodiments, at least one of the one or more isomers of CLA is in triglyceride form, free fatty acid form, or ester form.
In some embodiments, at least one of the one or more isomers of CLA is cis-9, cis octadecadienoic acid, cis-9, trans- octadecadienoic acid, trans-9, cisoctadecadienoic acid, trans-9, trans- 11 -octadecadienoic acid, cis, cisoctadecadienoic acid, cis, trans- octadecadienoic acid, trans- 10, cisoctadecadienoic acid, trans- 10, trans- octadecadienoic acid, or any combination thereof.
The mixture can, for example, comprise cis-9, trans- 11 -octadecadienoic acid CLA, trans- 10, cis- octadecadienoic acid, or any mixture thereof. In some embodiments, the mixture comprises cis-9, trans octadecadienoic acid CLA and trans- 10, cis- octadecadienoic acid in a ratio.
The tocopherol can be, or comprise, δ- tocopherol, γ-tocopherol, a-tocopherol, or any combination thereof. In some embodiments, the vitamin D comprises vitamin D3, vitamin D 2 , their biologically active metabolites and precursors, or any mixture thereof.
In some embodiments, at least one of the one or more Group A agents is an omega-3 fatty acid, amino acid, vitamin, or any mixture thereof. In some embodiments, at least one of the one or more Group A agents is aniline or Vitamin E.
In some embodiments, the omega-3 fatty acid can be, or comprise, alpha-linolenic acid, stearidonic acid, eicosapentanoic acid, docosahexanoic acid, or any mixture thereof. The method can, for example, comprise administrating one or more Group B agents that positively impacts the muscle stimulating mechanism.
In some embodiments, at least one of the one or more Group B agents is, or comprise, a vitamin D other than Vitamin D3, Vitamin D 2 , citrulline, creatine, leucine, whey protein, or a mixture thereof.
In some embodiments, the method comprises administrating at least one Group A agent and at least one Group B agent to the subject. In some embodiments, the method comprises administrating at least two Group A agents and at least two Group B agents to the subject.
For example, the CLA can be administered in an amount from about 2. In some embodiments, the CLA is administered in an amount from about 3. In some embodiments, the CLA is administered in an amount of about 4 g per day and the vitamin D is administered in an amount of about IU per day.
In some embodiments, the dose is administered in a single unit dosage form. In some embodiments, the dose is administered in two or more unit dosage forms. In some embodiments, the administration of one or more of the CLA, vitamin D, Group A agent s and Group B agent s is repeated more than one time per day.
In some embodiments, the administration of one or more of the CLA, Vitamin D, Group A agent s and Group B agent s is oral, intravenous, intraperitoneal, intragastric, or intravascular administration.
In some embodiments, the administration of one or more of the CLA, Vitamin D, Group A agent s and Group B agent s is oral administration. For example, the subject can be an adult. The subject can be a male or a female.
In some embodiments, the subject is a middle-aged adult. In some embodiments, the subject is an elderly adult. In some embodiments, the subject is human is a person of the age of 40 years or more.
In some embodiments, the subject is human is a person of the age of 60 years or more. In some embodiments, the subject is with an active lifestyle. In some embodiments, the subject is with a sedentary lifestyle.
In some embodiments, the subject has sarcopenia or is at risk of developing sarcopenia. In some embodiments, the method comprises determining muscle weight, muscle circumference, lean muscle, body weight, fat mass, lean mass, brain water content, locomotor activity, protein synthesis rate, or any combination thereof of the subject.
In some embodiments, at least one symptom of the condition of muscle loss is skeletal muscle loss, or muscle mass loss. In some embodiments, the condition of muscle loss is caused by aging, disease, injury, inactivity, or any combination thereof.
In some embodiments, the condition of muscle loss is sarcopenia, muscle atrophy, cachexia, muscular dystrophy, or any combination thereof. The increased muscle protein synthesis can comprise, for example, increased muscle fractional synthesis rate FSR. In some embodiments, the administration of a combination of the CLA and vitamin D has a synergistic effect.
The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here.
It will be readily understood that the aspects of the present disclosure, as generally described herein, can be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and make part of this disclosure.
Doctor of Allopathic medicine or Doctor of Osteopathic medicine or a Doctor of Veterinary Medicine, to attempt to cure, or at least ameliorate the effects of, a particular disease or disorder or to prevent the disease or disorder from occurring in the first place.
The dosages of a pharmaceutically active ingredient which are useful in treatment are therapeutically effective amounts. For example, a therapeutic effect may be observed by a reduction of the subjective discomfort that is communicated by a subject e.
The term "prophylactic treatment" refers to treating a subject who does not yet exhibit symptoms of a disease or condition, but who is susceptible to, or otherwise at risk of, a particular disease or condition, whereby the treatment reduces the likelihood that the patient will develop the disease or condition.
The term "therapeutic treatment" refers to administering treatment to a subject already suffering from a disease or condition. This term is used to distinguish effects on muscle mass and function in a subject where a change in that subject's lifestyle materially contributes to an impact on muscle mass and function.
The effect can be any of the measurable effects described herein. Non-limiting symptoms of muscle loss can be loss or reduction of muscle mass, loss or reduction of lean muscle, loss or reduction of muscle weight, loss or reduction of muscle circumference, loss or reduction of fat mass, loss or reduction of lean mass, loss or reduction of muscle function, loss or reduction of muscle strength, loss or reduction of mobility, weight loss, reduction in muscle protein fractional synthesis rate FSR , or any combination thereof.
In some embodiments, at least one symptom of the condition of muscle loss is muscle mass loss or skeletal muscle loss. In some embodiment, at least one symptom of the condition of muscle loss is weight loss.
In some embodiment, at least one symptom of the condition of muscle loss is loss or reduction in lean mass, loss or reduction of muscle circumference, or reduction in FSR. There are a variety of causes for muscle loss.
For example, the muscle loss can be caused by aging, disease for example cancer and liver diseases , inactivity, injury for example liver transplantation , or any combination thereof.
In some embodiments, the condition of muscle loss is sarcopenia, muscle atrophy, cachexia, muscular dystrophy, muscle wasting, or any combination thereof.
In patients having sarcopenia, the patients display a deterioration of muscle quantity and quality, leads to a decrease in functional capacity, adversely affecting survival, and quality of life. In some embodiments, muscle loss can be measured by tracking the lean body mass LBM of a subject over time.
Sarcopenia is characterized by a loss of muscle mass, strength and function occurring during aging. Exercise, increased protein intake, and amino acid supplements have been proposed to improve outcomes of elderly muscle loss and sarcopenia. Several factors contribute to muscle protein synthesis, among which the most important are the availability of amino acids serving as building blocks for the newly synthesized proteins and the activation signals generated by anabolic amino acids or anabolic amino acid derivatives e.
citrulline, leucine, essential amino acids EAA , and creatine. However, protein intake is typically decreased in elderly, which leads to inadequate postprandial availability of amino acids.
Furthermore, aging is characterized by decreased muscle sensitivity to the anabolic effect of essential amino acids, especially leucine. This reduced responsiveness to leucine is associated with a decrease in the activation of intracellular pathways controlling muscle protein synthesis.
Hence, to counteract the deleterious effect of aging on muscle protein synthesis, it been proposed to simultaneously target the bioavailability of amino acids, especially essential amino acids, by increasing the intake of high-quality protein rich in essential amino acids, especially leucine , and the muscle response to anabolic amino acids by improving muscle sensitivity to these amino acids.
Elderly muscle fractional synthetic rate response to protein intake is deficient, however. Currently recommended supplements target stimulus of muscle growth but do not target inflammatory oxidative mechanism with respect to sarcopenia. Current recommendations typically require the administration of more than 8 g amino acids or more than 15 g protein.
Such amounts can be too large to be applicable to the dietary supplement formats of pills or soft gels. Hence, current supplemental regimens are delivered by meal replacement beverages or powdered beverages which may increase adiposity and calorie consumption and therefore may be counterproductive in those overweight or trying to watch weight while simultaneously maintaining muscle mass.
Current supplemental regimens such as creatine require the combination with resistance exercise; however, a large portion of US population is sedentary. Thus, additional approaches for reducing and preventing loss of muscle mass and function in sedentary populations are needed.
CLA is a collective name for a class of positional and structural isomers of linoleic acid that contain conjugated double bonds. CLA are a family of at least 28 isomers of linoleic acid found mostly in the meat and dairy products derived from ruminants. CLAs can be either cis- or trans-fats and the double bonds of CLAs are conjugated and separated by a single bond between them.
In , the United States Food and Drug Administration categorized CLA as generally recognized as safe GRAS. Supplementation with CLA for 24 months has been found to be well tolerated and reduce body fat mass in healthy, overweight humans. CLA supplementation studies in younger populations have found a reduction of muscle breakdown markers after resistance exercise.
It is intended that this term encompass and indicate all positional and geometric isomers of linoleic acid with two conjugated carbon-carbon double bonds any place in the molecule. CLA differs from ordinary linoleic acid in that ordinary linoleic acid has double bonds at carbon atoms 9 and In some embodiments, CLA can comprise one or more of free fatty acid s of CLA, physiologically acceptable salts of CLA, and esters with physiologically acceptable, preferably naturally occurring, alcohols e.
As used herein, the term conjugated linoleic acid or CLA is intended to include "esters" of CLA which term includes any CLA isomer bound through an ester linkage to an alcohol or any other chemical group.
If a positional isomer of CLA is designated without a "c" or a "t", then that designation includes all four possible isomers. For example, 10,12 octadecadienoic acid encompasses cl0,tl2; tl0,cl2; tl0,tl2; and cl0,cl2 octadecadienoic acid.
In some embodiments, the CLA administered to patients is or comprises an octadecadienoic acid isomer selected from the group of cis-9, trans; cis-9, cis; trans-9, cis; trans-9, trans; cis, cis, trans; trans, cis; trans, trans octadecadienoic acid and mixtures thereof. In some embodiments, the minor isomer is cl l,tl3; tl l,cl3; tl l,tl3; or cl l,cl3 octadecadienoic acid.
In some embodiments, the CLA comprises an ester or triglyceride. In some embodiments, eight possible geometric isomers of 9,11 and 10,12 octadecadienoic acid i. Therefore, in some embodiments, these isomers can be used in a purified form or a substantially purified form, or in CLA compositions containing high ratios of these isomers.
In some embodiments, isomers in the CLA mixtures include 9,octadecadienonic acid, 10,octadecadienoic acid, most preferably the c9,tl l and tl0,cl2 isomers. It is contemplated that in some embodiments, supplementation of the CLA mixture derived from isomerization of linoleic acid with purified or synthesized tl0,cl2 isomer may be necessary to achieve these percentages.
As used herein, the term "CLA" also refers to such derivatives. For example, CLA can be free or bound through ester linkages or provided in the form of an oil comprising CLA triglycerides.
In these embodiments, the triglycerides may be partially or wholly comprised of CLA attached to a glycerol backbone. The CLA can, in some embodiments, be provided as a methylester or ethylester.
In some embodiments, the CLA is in the form of a non-toxic salt, such as a potassium or sodium salt e. The non-toxic salts of the free acids may be made by reacting the free acids with a non-toxic base. The CLA can be heat stable and can be used as is, or dried and powdered.
The CLA can be readily converted into a non-toxic salt, such as the sodium or potassium salt, by reacting chemically equivalent amounts of the free acid with an alkali hydroxide at a pH of about 8 to 9. In still further embodiments, the one or more isomers of CLA is selected from the group comprising cis-9, cis -octadecadienoic acid, cis-9, trans octadecadienoic acid, trans-9, cisoctadecadienoic acid, trans-9, trans- octadecadienoic acid, cis, cisoctadecadienoic acid, cis, trans- octadecadienoic acid, trans- 10, cis- octadecadienoic acid, and trans- 10, trans- octadecadienoic acid.
In some embodiments, the CLA comprises cis-9, trans- 11 -octadecadienoic acid CLA and trans, cis octadecadienoic acid at about a to In some embodiments, the one or more tocopherols is selected from the group consisting of consisting of δ-tocopherol, γ-tocopherol, a-tocopherol, and combinations thereof.
These are known collectively as calciferol. Vitamin D without a subscript refers to all forms of vitamin D including vitamin Di, D 2 , D3, D 4 , and D5 , in particular D 2 and D3, or any mixture thereof.
When ingested, vitamin D is hydroxylated in the liver endoplasmic reticulum to hydroxycholecalciferol 25 OH D , also known as calcidiol, by the enzyme 25 -hydroxylase, produced by hepatocytes. Once made, the product is stored in the hepatocytes until it is needed and can be released into the plasma where it will be bound to an a-globulin.
The enzyme la-hydroxylase which is activated by parathyroid hormone and additionally by low calcium or phosphate forms the main biologically active vitamin D hormone with a CI hydroxylation forming 1,dihydroxy cholecalciferol l,25 OH 2 D, also known as calcitriol.
A separate enzyme hydroxylates the C24 atom forming 24R,25 OH 2 D3 when la-hydroxylase is not active, this inactivates the molecule from any biological activity. In some embodiments, the Vitamin D can be provided in an active l,25 OH 2 D or inactive Vitamin D3 or D 2 form.
Deficiency of vitamin D, which has hormonal effects on muscle mass and strength, has been described as a risk factor in falls and bone fractures in the elderly. Loss of muscle strength has been correlated with a loss of vitamin D receptors VDR in muscle cells. Supplemental vitamin D of at least IU per day may result in a clinically significant increase in VDR in muscle cells, and this may be in part be the mechanism whereby other studies have shown improvement in body-sway, muscle strength and falling risk were seen with vitamin D supplementation at this level.
Muscle contains VDRs for l,H 2 -VitD 3 , found in both the nucleus and at the cell membrane, and these are also involved in non-specific binding H-VitD 3 as well. It has been shown that feeding D 3 to vitamin D deficient rats 7 hours prior to measurement increased protein synthesis as measured by H-leucine incorporation into muscle cell proteins.
However, when the muscles were removed from the vitamin D deficient rats and studied, it was found that only OH VitD 3 acts directly in the muscles.
Vitamin D receptors were discovered in muscle tissue, thus providing direct evidence of vitamin D's effect on muscle function.
Muscle biopsies in adults with vitamin D deficiency exhibit mainly type II muscle fiber atrophy. Type II fibers are important because they are the first initiated to prevent a fall.
A recent randomized controlled study found that daily supplementation of 1, IU of vitamin D 2 in elderly stroke survivors resulted in an increase in mean type II fiber diameter and in percentage of type II fibers.
There was also a correlation between serum H-VitD 3 level and type II fiber diameter. VDR is expressed in particular stages of differentiation from myoblast to myotubes.
Two different VDRs have been described. One is located at the nucleus and acts as a nuclear receptor and the other is located at the cell membrane and acts as a cellular receptor. VDR knockout mice are characterized by a reduction in body weight and size, as well as impaired motor coordination.
The nuclear VDR is a ligand-dependent nuclear transcription factor that belongs to the steroid-thyroid hormone receptor gene superfamily. It has been reported that the first in situ detection of VDR in human muscle tissue with significant associated intranuclear staining for VDR. Once l,H 2 -VitD3 binds to its nuclear receptor, it causes changes in mRNA transcription and subsequent protein synthesis.
The genomic pathway has been known to influence muscle calcium uptake, phosphate transport across the cell membrane, phospholipid metabolism, and muscle cell proliferation and differentiation.
Recent data indicate that l,H-VitD3 has a fast activation of mitogen-activated protein kinase MAPK signaling pathways, which in turn forward signals to their intracellular targets that effect the initiation of myogenesis, cell proliferation, differentiation, or apoptosis.
Studies that shown that vitamin D regulates the expression of VDR and the neural growth factor NGF in Schwann cells. Recent studies have also shown that vitamin D enhances glial cell line-derived neurotrophic factor GDNF in rats and that this may have beneficial effects in neurodegenerative disease.
Therefore, vitamin D can act through several mechanisms of cellular function and neural interaction to improve overall muscle strength and function. Hence, 1, IU is the biological equivalent of 25 μg. In some embodiments, vitamin D is used in an amount of IU or more per daily dosage in combination with CLA, such as, for instance 1,, 2,, 3,, 4,, 5,, 6,, 7,, 8,, 9, or 10, IU, or any value between any of two of said values or over, but not so high that it causes toxicity in the subject to which it is administered.
In some embodiments, vitamin D is used in an amount of 20 μg or more per daily dosage in combination with CLA, such as, for instance 25, 50, 75, , , , , , or μg per daily dosage, or any value in between any of two of said values or over. CLA and Vitamin D Supplementation for Muscle Maintenance.
Studies suggest that vitamin D metabolite calcefidiol slows muscle loss in elderly populations optionally with vitamin D3 cholecalciferol. Another study demonstrated the short term use of high concentrated omega-3 fatty acids 4g for 2 months stimulates muscle synthesis in an elderly population.
This was followed by another study that demonstrated impact of long term intake of omega-3 fatty acids 6 months on skeletal muscle mass and functions in elderly populations. These dosages, however, are too high in view of FDA recommendations in the United States market. Further, while CLA in combination with creatine has been tested in the elderly, this combination intervention was not compared to each intervention alone, and the combination was not shown to be superior to prior results observed with creatine.
CLA has been shown to have an impact on muscle in younger and post-menopausal populations but has not been tested in older populations losing muscle. CLA feeding studies also show improvement in muscle status and muscle markers in older mice.
CLA supplementation in older mice shows an improvement in oxidative and mitochondrial markers, which are markers that are affected by elderly muscle loss. Due to CLA's impact on muscle metabolism it has been termed an exercise mimetic.
Individual studies of vitamin D supplementation in randomized controlled trials showed improvements in muscle function in older populations e.
Vitamin D supplementation interacts with muscle via the receptor VDR, which hypothesized to affect downstream regulation of insulin-like growth factor signaling pathway. Studies have also found that adequate vitamin D is necessary for proper performance of muscle growth ingredient HMB in restoring muscle function in elderly persons.
CLA is hypothesized to activate mechanisms similar to resistance exercise and impact mitochondrial energy production in muscle, deficiency in which due to systemic inflammation and resultant oxidative stress is a key mechanism in muscle loss in the elderly.
Without being bound by any particular theory, it is believed that CLA can impact the utilization of fat as an energy source in muscle. Also without being bound by any particular theory, it is believed that Vitamin D can impact muscle growth stimulatory mechanisms, and has been shown to impact falls in the elderly a measure of elderly muscle strength.
Low serum OH D concentrations are associated with an increased risk of sarcopenia in elderly. Also provided, in some embodiments, are compositions comprising CLA and vitamin D, and methods of co-administering CLA and vitamin D, to improve muscle synthetic rate, breakdown rate, mass, strength, or function.
In some embodiments, stimulating muscle protein synthesis results in the treatment or prevention of a condition of muscle loss. In some embodiments, increasing muscle mass results in the treatment or prevention of a condition of muscle loss.
In some embodiments, increasing muscle function results in the treatment or prevention of the condition of muscle loss. In some embodiments, increasing the rate of muscle synthesis results in the treatment or prevention of a condition of muscle loss.
In some embodiments, decreasing the rate of muscle breakdown results in the treatment or prevention of the condition of muscle loss. In some embodiments, increasing the rate of muscle protein synthesis results in the reduction or prevention of age-related loss of muscle mass or function.
In some embodiments, increasing the rate of muscle protein synthesis results in the treatment or prevention of a condition of muscle loss. In some embodiments, increasing the rate of muscle protein synthesis results in the reduction or prevention of sarcopenia. In some embodiments, co-administering CLA and vitamin D to a subject in need thereof treats or prevents a condition of muscle loss by reducing or preventing age- related loss of muscle mass and function.
Some such embodiments include therapeutic treatment, and some embodiments include prophylactic treatment. In some embodiments, the agents are administered simultaneously. In some embodiments, administration in combination is accomplished by combining the agents in a single dosage form.
In some embodiments, the agents are administered sequentially. In some embodiments, the agents for example CLA and Vitamin D are administered through the same route, such as orally. In some embodiments, the agents for example CLA and Vitamin D are administered through different routes, such as one being administered orally and another being administered i.
The subject may have, or may not have, symptoms of sarcopenia. In some embodiments, the subject does not have sarcopenia. In some embodiments, the subject has sarcopenia. The age for the subject in need thereof can vary. For example, the subject can be an adult, for example a middle-aged adult, or an elderly adult.
In some embodiments, the subject is of the age of 40, 45, 50, 55, 60, 65, 70, 75, or more. For example, the subject can be a person at least 40 years old, or the subject can be a person at least 60 years old.
The gender of the subject in need thereof can vary. In some embodiments, the subject is a female. In some embodiments, the subject is a male. Some embodiments can include identifying a subject as having or at risk for developing a condition of muscle loss e. The regulation or maintenance of the subject's rate of muscle protein synthesis can allow for a subject to experience a number of beneficial effects.
The subject may or may not engage in exercise. In some embodiments, exercising in conjunction with the co-administration of CLA and vitamin D results in an even greater improvement in muscle mass and function, but exercise is not necessary to improve muscle mass and function.
The amount of CLA and vitamin D administered that are effective for increasing the animal's muscle mass can be determined in accordance with methods known in the art. In some embodiments, the effective amount of CLA administered may be from about 1 g to about 6 g and the effective amount of vitamin D administered may be from may be from about IU to about IU per 24 hour period.
For example, the methods and composition may prevent muscle mass loss including but not limited to loss of lean muscle mass from occurring. As another example, the methods and composition may reduce the final muscle mass loss including but not limited to final loss in lean muscle mass.
For example, the methods and composition may prevent muscle function loss including but not limited to loss of lean muscle function from occurring.
As another example, the methods and composition may reduce the final muscle function loss including but not limited to final loss in lean muscle function. For example, the methods and composition may prevent muscle weight loss from occurring.
As another example, the methods and composition may reduce the final muscle weight loss. For example, the methods and composition may prevent muscle circumference loss from occurring.
As another example, the methods and composition may reduce the final muscle circumference loss. For example, the methods and composition may prevent muscle strength loss from occurring. As another example, the methods and composition may reduce the final muscle strength loss.
For example, the methods and composition may prevent mobility loss from occurring. As another example, the methods and composition may reduce the final mobility loss. For example, the methods and composition may prevent the reduction in muscle protein FSR from occurring.
This co-administration can be used on all age groups seeking enhancement in overall muscle mass, function and strength. The methods described herein, in some embodiments, yield increased overall muscle mass, function and strength even in non- exercising subjects.
In some embodiments, CLA and vitamin D are co-administered in elderly subjects. Current estimates place a large portion of the older population at risk for falls with potential significant associated morbidities. In some embodiments, the coadministration of CLA and vitamin D specifically targets muscle mass, strength and function and consequently may produce significant improvement in health, quality of life, and in particular, decreased falls and injury in this group.
The younger population also benefits from the co-administration of CLA and vitamin D in still further embodiments, in part due to the widespread occurrence of vitamin D deficiency. Women also benefit from the coadministration of CLA and vitamin D in some embodiments, as women are prone to vitamin D deficiency.
Synergistic Effects of Co-administration of CLA and Vitamin D. These synergistic effects can be such that the one or more effects of the combination compositions are greater than the one or more effects of each component alone at a comparable dosing level, or they can be greater than the predicted sum of the effects of all of the components at a comparable dosing level, assuming that each component acts independently.
The composition comprising a plurality of components can be such that the synergistic effect is an enhancement in FSR and that FSR is increased to a greater degree as compared to the sum of the effects of administering each component, determined as if each component exerted its effect independently, also referred to as the predicted additive effect herein.
In some embodiments, the synergistic effect can be at least about 0. Furthermore, the synergistic effect can allow for results that are not achievable through any other treatments. Therefore, proper identification, specification, and use of combination compositions can allow for significant improvements in the reduction and prevention of age-related loss of muscle mass and function.
The compositions include the combination compositions described herein, such as combination compositions comprising CLA and vitamin D. In general, an amount of CLA and vitamin D in the levels sufficient to improve muscle strength, function, and mass is administered for an effective period of time.
A subject can receive dosing for a period of about, less than about, or greater than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,. I I, 12, 13, 14, or more days, weeks or months. A unit dose can be chosen such that the subject is administered about or greater than about mg of CLA e.
about or more than about mg, 1 mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, or more and about or greater than about IU of vitamin D e.
The vitamin D can comprise Vitamin D3. A unit dose can be a fraction of the daily dose, such as the daily dose divided by the number of unit doses to be administered per day. A unit dose can be a fraction of the daily dose that is the daily dose divided by the number of unit doses to be administered per day and further divided by the number of unit doses e.
tablets per administration. The number of unit doses per administration may be about, less than about, or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more. The number of doses per day may be about, less than about, or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more.
The number of unit doses per day may be determined by dividing the daily dose by the unit dose, and may be about, less than about, or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 6, 17, 18, 19, 20, or more unit doses per day.
A unit dose can be about one- third of the daily amount and administered to the subject three times daily. A unit dose can be about one- half of the daily amount and administered to the subject twice daily. A unit dose can be about one-fourth of the daily amount with two unit doses administered to the subject twice daily.
For example, a unit dose can have about, less than about, or more than about mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, mg, or more of CLA and about, less than about, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, IU, or more of vitamin D.
The specified ratio can provide for effective stimulation of muscle protein synthesis. Such beneficial effects can result from, in part, an increase in mitochondrial biogenesis, changes in mitochondrial oxidative stress-reductive pathways, changes in inflammation and inflammatory pathways, or a variety of other changes in cellular metabolism or the energy metabolism pathway.
The ratio of CLA to vitamin D can be a mass ratio, a molar ratio, or a volume ratio. In some embodiments, the mass ratio of CLA to vitamin D is about, greater than about, or less than about 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, , , , , , , , , , , , , or more. In some embodiments, the molar ratio of CLA to vitamin D co-administered is about, greater than about, or less than about 90, 95, 90, 95, , , , , , , , , , , , , or more.
In some embodiments, the measurement of FSR can be for a test group as compared to a control group. For example, the compositions can be administered one, two, three, four times a day, or even more frequent.
The subject can be administered every 1 , 2, 3, 4, 5, 6, or 7 days. In some embodiments, the compositions are administered three times daily. The administration can be concurrent with meal time of a subject. The period of treatment or diet supplementation can be for about 1 , 2, 3, 4, 5, 6, 7, 8, or 9 days, 2 weeks, 1 months, or 1 year, 2 years, 5 years, or even longer.
In some embodiments disclosed herein, the dosages that are administered to a subject can change or remain constant over the period of treatment. For example, the daily dosing amounts can increase or decrease over the period of administration. The period of time can be one, two, three, four or more weeks.
In some embodiments, the period of time can be one, two, three, four, five, six or more months. For example, dosing levels can be increased for subjects that show reduced effects in FSR or circulating levels of CLA or vitamin D below desired target levels.
For example, the ratio of CLA to vitamin D or the particular components in a combination composition can be adjusted. For example, separate capsules, pills, mixtures, etc.
of vitamin D and of CLA may be administered to a subject to carry out the claimed methods. The administration of CLA and vitamin D may be at the same time or at different times provided that effective concentrations of both CLA and vitamin D are both found in the subject at the same time.
In some embodiments, administration of both CLA and vitamin D is at the same time, preferably in a single composition, in order to facilitate the compliance of the subject to adhere to a schedule of administration.
In some embodiments, it is contemplated that individuals beginning treatment will be given a 2. The dosing regimen of the compositions disclosed herein can be administered three times a day, twice a day, daily, every other day, three times a week, every other week, three times per month, once monthly, substantially continuously or continuously.
Typically, the dose range of the composition administered to the patient can be from about 0. The dosage may be a single one or a series of two or more given in the course of one or more days, as is needed by the patient.
In instances where human dosages for the compositions have been established for at least some condition, the present disclosure will use those same dosages, or dosages that are between about 0. Where no human dosage is established, as will be the case for newly-discovered pharmaceutical compounds, a suitable human dosage can be inferred from ED 50 or ID 50 values, or other appropriate values derived from in vitro or in vivo studies, as qualified by toxicity studies and efficacy studies in animals.
Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response were not adequate precluding toxicity. The magnitude of an administrated dose in the management of the disorder of interest will vary with the severity of the condition to be treated and to the route of administration.
The severity of the condition may, for example, be evaluated, in part, by standard prognostic evaluation methods. Further, the dose and perhaps dose frequency, will also vary according to the age, body weight, and response of the individual patient.
A program comparable to that discussed above may be used in veterinary medicine. In cases of administration of a pharmaceutically acceptable salt, dosages may be calculated as the free base.
In some embodiments, the composition is administered 1 to 4 times per day. In some embodiments, the compositions of the compositions disclosed herein can be administered by continuous intravenous infusion, preferably at a dose of each active ingredient up to g per day.
As will be understood by those of skill in the art, in certain situations it may be necessary to administer the compositions disclosed herein in amounts that exceed, or even far exceed, the above-stated, preferred dosage range in order to effectively and aggressively treat particularly aggressive diseases or infections.
In some embodiments, the compositions disclosed herein are administered for a period of continuous therapy, for example for a week or more, or for months or years. Group A Agents and Group B Agents.
In some embodiments, the Group A agent is selected from the group comprising omega-3 fatty acid-containing substances e. alanine , and vitamins e. In some embodiments, the omega-3 fatty acid is selected from the group consisting of alpha-linolenic acid, stearidonic acid, eicosapentanoic acid, docosahexanoic acid, and mixtures thereof.
In some embodiments, the Group B agent is selected from the group comprising another vitamin D other than D3, creatine, leucine, and whey protein. Leucine may be used as a free amino acid, or in a bound form, such as a dipeptide, an oligopeptide, a polypeptide or a protein.
Common protein sources of leucine are dairy proteins such as whey, casein, micellar casein, caseinate, and glycomacroprotein GMP , and vegetable proteins such as wheat, rice, pea, lupine and soy proteins.
Said sources of protein may provide intact proteins, hydrolysates or mixtures thereof, hereafter further called proteinaceous matter. Leucine is known as a potent activator of muscle protein synthesis. Citrulline is an a- amino acid.
Citrulline, in the form of citrulline malate, is sold as a performance-enhancing athletic dietary supplement was been suggested to promote aerobic energy production and to increase athletic performance and decreasing muscle soreness.
In the human body, citrulline is produced from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from arginine in the body as a by-product of the reaction catalyzed by NOS family.
Citrulline is also capable of promoting muscle protein synthesis and has been described in human and animal studies. Creatine is a nitrogenous organic acid that is produced in vertebrates, in particular the human body from L-arginine, glycine, and L- methionine and helps to supply energy to muscles.
In some embodiments, such daily dosage is administered as a single serving. In the context of this application, with "free form" is meant a peptide comprising 1 to 5 amino acids, preferably 1 to 3 amino acids, more preferably 1 amino acid.
Preferably, leucine is a free amino acid, either as a base, a salt or a chelate. In some embodiments, citrulline is provided in a daily dosage of 0. In some embodiments, creatine is provided in a daily dosage of 0.
In some embodiments, any combination of leucine, citrulline, and creatine is provided in a daily dosage of 0. Any combination is a combination selected from the group of leucine and citrulline; leucine and creatine; citrulline and creatine; and leucine, citrulline and creatine.
The whey protein may be an intact whey protein, a hydrolysed whey protein, a microparticular whey protein, a nanoparticular whey protein, a micellar whey protein, and the like. Preferably, the whey protein is an intact whey protein, i.
a whey protein in its intact form, such as present in fresh milk. whey obtained by any process for the preparation of whey known in the art, as well as whey protein fractions prepared thereof, or the proteins that constitute the bulk of the whey proteins being β-lactoglobulin, ct- lactalbumin and serum albumin, such as liquid whey, or whey in powder form, such as whey protein isolate WPI or whey protein concentrate WPC.
Whey protein concentrate is rich in whey proteins, but also contains other components such as fat, lactose and glycomacroprotein GMP , a casein-related non-globular protein.
Typically, whey protein concentrate is produced by membrane filtration. On the other hand, whey protein isolate consists primarily of whey proteins with minimal amounts of fat and lactose.
Whey protein isolate usually requires a more rigorous separation process such as a combination of microfiltration and ultra-filtration or ion exchange chromatography.
In particular, sweet whey, obtained as a by-product in the manufacturing of cheese, acid whey, obtained as a by-product in the manufacturing of acid casein, native whey, obtained by milk microfiltration or rennet whey, obtained as a byproduct in the manufacturing of rennet casein, may be used as a source of whey proteins.
In some embodiments, the at least one other ingredient is provided in amounts sufficient to elicit noticeable effects which can be measured as described herein. The compositions can be administered to a subject orally or by any other methods.
Methods of oral administration include, in some embodiments, administering the composition as a liquid, a solid, or a semisolid that can be taken in the form of a dietary supplement or a foodstuff. The CLA and vitamin D may be formulated together with suitable carriers such as starch, sucrose or lactose in tablets, pills, dragees, capsules, solutions, liquids, slurries, suspensions and emulsions.
The vitamin D and CLA may be administered separately or together, provided that the total amount of CLA and vitamin D is an effective amount in combination per day to have a substantial impact on the rate of muscle protein synthesis. For example, the food composition can be, or comprise, a nutritional complete formula, a dairy product, a chilled or shelf stable beverage, a powdered beverage, a mineral or purified water, a liquid drink, a soup, a dietary supplement, a meal replacement, a nutritional bar, a confectionery, a milk, a fermented milk product, a yoghurt, a milk based powder, an enteral nutrition product, an infant formula, an infant nutritional product, a cereal product or a fermented cereal-based product, an ice cream, a chocolate, coffee, a culinary product such as mayonnaise, tomato puree, salad dressings, a pet food, or any combination thereof.
They are formulated by means of the usual methods for producing sugar-coated tablets, pills, pastes, gums, gelatin capsules, gels, emulsions, tablets, capsules or drinkable solutions or emulsions, which can then be taken directly with water or by any other known means.
This supplement may also include a sweetener, a stabilizer, an additive, a flavoring or a colorant. A supplement for cosmetic purpose can additionally comprises a compound active with respect to the skin.
Methods for preparing them are common knowledge. The composition may also contain synthetic or natural bioactive ingredients such as amino acids, fatty acids, vitamins, minerals, carotenoids, polyphenols, etc.
According to some embodiments, the composition disclosed herein can be used cosmetically. In therapeutic applications, compositions are administered to a patient already suffering from a disease, as described herein under, in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications.
An amount adequate to accomplish this is defined as "a therapeutically effective dose". Amounts effective for this will depend on the severity of the disease and the weight and general state of the patient.
In prophylactic applications, compositions disclosed herein are administered to a patient susceptible to or otherwise at risk of a particular disease. Such an amount is defined to be "a prophylactic effective dose". In this use, the precise amounts again depend on the patient's state of health and weight.
The desired formulation can be made using a variety of excipients including, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, magnesium carbonate. This composition may be a tablet, a capsule, a pill, a solution, a suspension, a syrup, a dried oral supplement, a wet oral supplement.
For administration via intravenous infusion, the composition is preferably in a water-soluble non-toxic form. Intravenous administration is particularly suitable for hospitalized patients that are undergoing intravenous IV therapy.
For example, the composition can be dissolved in an IV solution e. The amounts of the composition to be administered intravenously can be similar to levels used in oral administration. Intravenous infusion may be more controlled and accurate than oral administration.
In some embodiments, the combination of CLA and vitamin D are formulated for administration with a pharmaceutically acceptable carrier or diluent. The exact nature of the formulation will depend upon several factors including the desired route of administration.
Typically, combination of CLA and vitamin D are formulated for oral, intravenous, intragastric, intravascular or intraperitoneal administration. Standard pharmaceutical formulation techniques may be used, such as those disclosed in Remington's The Science and Practice of Pharmacy, 21st Ed.
The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated.
In addition, various adjuvants such as are commonly used in the art may be included. Considerations for the inclusion of various components in pharmaceutical compositions are described, e. As used herein, a "unit dosage form" is a composition that is suitable for administration to an animal, preferably mammal subject, in a single dose, according to good medical practice.
The preparation of a single or unit dosage form however, does not imply that the dosage form is administered once per day or once per course of therapy.
Such dosage forms are contemplated to be administered once, twice, thrice or more per day and may be administered as infusion over a period of time e.
The skilled artisan will recognize that the formulation does not specifically contemplate the entire course of therapy and such decisions are left for those skilled in the art of treatment rather than formulation.
The skilled artisan will appreciate that oral and nasal compositions include compositions that are administered by inhalation, and made using available methodologies. Depending upon the particular route of administration desired, a variety of pharmaceutically-acceptable carriers well-known in the art may be used.
Pharmaceutically-acceptable carriers include, for example, solid or liquid fillers, diluents, hydrotropies, surface-active agents, and encapsulating substances.
Optional pharmaceutically-active materials may be included, which do not substantially interfere with the inhibitory activity of the composition. The amount of carrier employed in conjunction with the composition is sufficient to provide a practical quantity of material for administration per unit dose of the composition.
Techniques and compositions for making dosage forms useful in the methods described herein are described in the following references, all incorporated by reference herein: Modern Pharmaceutics, 4th Ed. Tablets can be compressed, tablet triturates, enteric-coated, sugar-coated, film-coated, or multiple-compressed, containing suitable binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, flow-inducing agents, and melting agents.
Tablets typically comprise conventional pharmaceutically-compatible adjuvants as inert diluents, such as calcium carbonate, sodium carbonate, mannitol, lactose and cellulose; binders such as starch, gelatin and sucrose; disintegrants such as starch, alginic acid and croscarmelose; lubricants such as magnesium stearate, stearic acid and talc.
Glidants such as silicon dioxide can be used to improve flow characteristics of the powder mixture. Sweeteners and flavoring agents, such as aspartame, saccharin, menthol, peppermint, and fruit flavors, are useful adjuvants for chewable tablets.
Capsules typically comprise one or more solid diluents disclosed above. But with so many online vitamin stores, why should you purchase supplements from Bronson?
In short, our company is time proven, offering the purest, high quality vitamins backed by science. Trust Bronson to provide the very best natural health products for you and your family. As a dietary supplement for adults, take 2 softgels twice daily with meals, or as directed by a health professional.
Directions: As a dietary supplement for adults, take 2 softgels twice daily with meals, or as directed by a health professional. Other Ingredients: Gelatin, glycerin, purified water, caramel color. WARNING: Consult a healthcare professional before taking this product if you are pregnant or nursing.
Do not use if seal under cap is broken or missing. Store at room temperature. Keep out of reach of children. Your complete satisfaction is our highest priority. Simply return the unused portion within one year of purchase for a refund less shipping. Checkmark Icon Item added to your cart.
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Background: Aging ans associated with annd muscle anabolic resistance i. Vitxmin results from Mindfulness and digestion conducted in cell culture systems and animals suggest that both vitamin Vitanin and conjugated linoleic acids CLAs vifamin muscle protein Antifungal remedies for oral thrush. Objectives: To Herbal weight loss shakes a randomized, CLA and vitamin D, placebo-controlled clinical trial to determine the independent and combined effects of dietary vitamin D and CLA supplementation on myofibrillar protein synthesis rates in sedentary older adults. Myofibrillar protein synthesis rates were evaluated by using intravenous [ring-2H5]phenylalanine infusion in conjunction with muscle biopsies during basal, postabsorptive conditions and during combined amino acid and insulin infusion before and after the supplementation period. Results: Before the intervention, basal myofibrillar protein synthesis rates were not different among groups Placebo: 0. The study was registered at clinicaltrials. Cart vitajin. Search Home Sales Clearance Free Zone Promotion Monthly Specials Vtamin Packs Vitamins CAL A Overall vitality enhancement B Vitamin C Vitanin D Vitamin E Vitamin CLA and vitamin D Multi Natural pest-resistant seed options Herbal weight loss shakes Viamin Astragalus Root Bilberry Black Ad CLA and vitamin D Thistle Blueberry Boswellia Cayenne Cinnamon Coconut Cranberry Dandelion Vitamn Claw Echinacea Ginkgo Biloba Vitajin Grape Seed CLA and vitamin D Tea Horny Goat Vitamij Medicinal Mushroom Milk Thistle Nettle Nutrition Tea Peppermint Resveratrol Rhodiola Richline Silica Horsetail Extract St. John's Wort Turmeric Specialty Health Allergies Anti-aging and Skincare Antioxidants Anti-viral Children's Health Cleansing and Detox Colds and Flu Diabetic Diet Energy Glucose Management Gout Hair Care Heart Health and Cardio Support Immune Support Inflammation Joint, Muscle and Bone Support Memory Enhancement Men's Health Organic Pet Products Probiotics and Digestives Protein Senior Care Sleep Sports Nutrition Stress and Emotional Well-being Super Foods Vegan Friendly Vision Care Weight Loss Women's Health Minerals and Supplements Amino Acid Bee Products Calcium Chromium CLA Enzymes Greens Iron Lutein Lycopene Magnesium Probiotics Selenium Spirulina Vanadium Zinc Oils Essential Oils Evening Primrose Oil Fish Oil Flaxseed Oil Krill Oil Lecithin Oil of Oregano Omega 3.
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