a composition for treating tinnitus includes components that may function through different biological mechanisms to provide an additive effect that is equal to or greater than a sum of the effect of the individual components . the composition is typically used for treating tinnitus that may result from trauma to an inner ear of a mammal or may have no known cause . the trauma may be further defined as mechanically - induced metabolic trauma , mechanical / metabolic trauma , stress trauma , stress - induced damage , or environmental stress . however , it is also possible that the composition may also be used to treat or prevent other types of tinnitus , including , for example , age - related tinnitus , antibiotic - induced tinnitus , and chemotherapeutic - induced tinnitus . the composition may further be used to prevent tinnitus during restoration surgery performed on the inner ear . a method in accordance with the instant disclosure includes the step of administering a composition to a mammal that includes components that function through different biological mechanisms . in the method , the composition is typically used for treating tinnitus resulting from trauma to the inner ear of a mammal . in various embodiments , the trauma may be further defined as high intensity noise . high intensity noise can cause damage to micromechanical properties of sensory transducers in the ear , can cause changes in blood flow in the ear , can cause modification in intracellular ion transport properties , can cause depletion of sensory cell transmitter substances ( e . g . glutamate ), can cause changes in post synaptic membrane transmitter receptors ( e . g . glur ) on afferent nerve fibers , can cause modification of dispersion and uptake properties of transmitters in extracellular , synaptic spaces , and / or can cause changes in postsynaptic membrane biophysical properties that may affect space - and time - constant properties modifying depolarization . in addition , high intensity noise can cause changes of an excitotoxic nature in postsynaptic membranes causing destruction of afferent neural tissues . any one of these changes can result in modification of spontaneous activity in individual or small populations of afferent nerve fibers , which can result in the perception of tinnitus . while a number of factors may influence these changes , intercellular redox properties of cells , blood flow to the inner ear and calcium uptake by postsynaptic afferent nerve fiber membranes may be of particular importance in causing these changes . it has been found that one result of noise trauma , or other stressors such as age and drugs , is that free radicals form in association with metabolic trauma . the free radicals damage sensitive structures , such as hair cells , within the ear and can initiate processes that can lead to tinnitus . vasoconstriction also occurs as a result of the noise , which leads to decreased blood flow to the inner ear and causes cell death that results in tinnitus . it has been found that the underlying cause of vasoconstriction is noise - induced free radical formation . specifically , one of the molecules formed in the inner ear as a result of the presence of free radicals is 8 - isoprostane - 2f alpha , which is a bioactive agent . the bioactive agent induces a constriction of blood vessels in the inner ear , which causes a reduction in blood flow . in order to counteract the free radical formation and the vasoconstriction , the composition of the subject disclosure typically includes at least one scavenger of singlet oxygen , a donor antioxidant , a third antioxidant , and a vasodilator . unexpectedly , it was found that the composition including the at least one scavenger of singlet oxygen , the donor antioxidant , the third antioxidant , and the vasodilator produce an additive effect that is not only greater than the effect of any one of those components alone , but at least equal to or greater than a sum of the effects of each of the components . many genetic hearing disorders are dependent upon a defect in a single gene leading to hearing impairment or deafness ; many reflect defects in more that one gene , and may be associated with other , non hearing , clinical disorder . tinnitus may be associated with either class of genetic hearing disorders and thus associated with one ( non - syndromic ) mutation or with mutations in more than one gene ( e . g . syndromic ) and may be associated with other inherited clinical disorders tinnitus may reflect a defect in a gene resulting in flawed gene copies which mis - instructs production of a protein important for homeostasis and transduction processes in the inner ear . this could lead to disruption of micromechanical properties of hair cells , depolarization defects , inadequate production and or assembly of transmitter substances , and / or compromised synaptic activity . this may also result in disruption of ion metabolism , e . g . potassium , their distribution and movement in the inner ear and particularly in the lateral wall and sensory cells , and a disruption of cellular homeostasis in these cells , frequently leading to cell death . since potassium homeostasis in the inner ear is important for normal function of the sensory cells of the inner ear ( hair cells ), any disruption tends to result in hearing impairment and may induce tinnitus . knockout mouse models of genetic hearing impairment may show early widespread degeneration of both inner and outer hair cells , presumably secondary to defects that upregulate apoptotic cell death pathways . in humans , hearing impairment may begin sometime following birth and progress until profound deafness occurs . however , gene defects may be expressed as mild to moderate hearing impairment . more specifically , one or more genetic defects may lead to disruption of potassium homeostasis in an inner ear of a mammal . potassium homeostasis may regulate apoptosis such that stress - driven disruption of inner ear potassium homeostasis may lead to increase production of free radicals by mitochondria directly leading to upregulation of apoptotic cell death pathways as well as support direct potassium induced cytochrome c release and apoptosis . potassium channels kv1 . 3 , mitochondrial ca 2 + regulated potassium channel , mitobkca , and mitochondrial atp - regulated potassium channel — mitokatp have been demonstrated in mitochondrial membranes . mitochondrial potassium channels effect energy production by the mitochondrion . in addition , there may be a direct dependence of free radical formation on potassium channel function during the respiratory chain in mitochondrial function . moreover , increased mitochondrial k + influx may result in release of cytochrome c and caspase - 3 followed by apoptosis . these events could be blocked by bcl - 2 , which upregulated the mitochondrial k / h - exchanger , leading to increased removal of k . in addition , bcl - 2 and tbid proteins may counter - regulate mitochondrial potassium transport . by removing / eliminating excess free radicals antioxidants may restore mitochondrial function . antioxidants act through a variety of mechanisms . the at least one scavenger of singlet oxygen and the donor antioxidant are two different classes of antioxidants that act through different mechanisms . the third antioxidant , while typically a scavenger of singlet oxygen , may be a different antioxidant that acts through a different mechanism . scavengers of singlet oxygen reduce free radicals that contribute to inner ear pathology and thus to tinnitus . these free radicals may also cause side effects of antibiotic treatment such as kidney damage and loss of balance . more specifically , by reducing free radicals , the scavengers of singlet oxygen prevent , among other damaging effects , the singlet oxygen from reacting with lipids to form lipid hydroperoxides . lipid hydroperoxides may play a role in causing tinnitus . even within the class of scavengers of singlet oxygen , it is believed that various antioxidants react at different sites within the body , and in particular , within cells to attenuate free radical formation . for example , one of the scavengers of singlet oxygen is typically vitamin a . in various non - limiting embodiments described herein , the terminology vitamin a and beta - carotene may be used interchangeably . however , these embodiments in no way limit this disclosure . vitamin a is a generic term that captures a number of molecules with a biological activity of retinol or carotenoids . primary dietary forms of vitamin a / retinol include retinol esters and beta - carotene . the beta - carotene is made up of a polyene chain of 11 conjugated double bonds with methyl branches spaced along the polyene chain , capped at both ends by cyclohexenyl rings with 1 , 1 , 5 - trimethyl substitution . other forms of vitamin a include xanxthophylls , astaxanthin , canthxanxin , lutein , and zeaxanthin , which include a backbone of beta - carotene with hydroxyl and / or carbonyl substitution on one or more of the cyclohexenyl rings . for purposes of the subject disclosure , the vitamin a is typically present as beta - carotene . beta - carotene is a powerful scavenger of singlet oxygen , as well as nitric oxide and peroxynitrite , and may also scavenge lipid peroxyl radicals within a lipophilic compartment of a mitochondrial membrane . beta - carotene is an excellent scavenger of free radicals under normal physiological conditions present in most tissues . in addition to vitamin a , other scavengers of singlet oxygen may also be present in the composition of the subject disclosure . for example , another scavenger of singlet oxygen that may be present is resveratrol . resveratrol is more efficient at scavenging hydroxyl radicals than vitamin c , and the addition of resveratrol to the vitamins a may have additive effects . the at least one scavenger of singlet oxygen may be present in the composition in a biologically effective amount . for purposes of the subject disclosure , the biologically effective amount may be further defined as an amount that is sufficient to produce an additive effect in a reduction in stress induced threshold shift or tinnitus when used in combination with other antioxidants and the magnesium . additive effect , as used herein , refers to an effect that is equal to or greater than a sum of the effects of the individual components . in order to produce additive effect and the reduction in threshold shift or tinnitus , the at least one scavenger of singlet oxygen is typically present in the composition in a total amount of at least 830 international units ( iu ), more typically from 830 to 120 , 000 iu , most typically from about 2 , 100 to 70 , 000 iu for an adult dosage . the amount of the vitamin a present in the composition is dependent upon the form of vitamin a that is used . for example , in one embodiment , vitamin a is present as retinol in an amount of at least 830 iu , more typically from 830 to 10 , 000 iu , more typically from 2 , 100 to 10 , 000 iu , most typically from 2 , 100 to 8 , 000 iu . as known in the art , a conversion of iu to weight for vitamin a ( as retinol ) is 3 . 33 iu / μg . thus , at least 830 international units ( iu ) of vitamin a ( as retinol ) is equivalent to at least 0 . 25 mg of vitamin a , from 830 to 10 , 000 iu of vitamin a ( as retinol ) is equivalent to from 0 . 25 to 3 mg of vitamin a , and from 2 , 100 to 8 , 000 iu of vitamin a ( as retinol ) is equivalent to from 0 . 63 to 2 . 4 mg vitamin a . alternatively , the vitamin a may be present in the composition as beta - carotene , as opposed to retinol . the retinol activity equivalents ( rae ) for retinol conversion to beta - carotene , which is a pro - vitamin a carotenoid , is 1 mg to 12 mg . in terms of conversion of the amounts set forth above for the vitamin a present in the composition as retinol to the vitamin a present in the composition as beta - carotene , in one example , a total amount of at least 3 . 0 mg or at least 830 international units ( iu ) of vitamin a as beta - carotene , more typically from 3 . 0 to 180 mg or 830 to 50 , 000 iu vitamin a as beta - carotene , most typically from about 7 . 2 to 108 mg or 2000 to 30 , 000 iu of vitamin a as beta - carotene is typically present for an adult dosage . in another example , a total amount of at least 3 . 0 mg or at least 10 , 000 international units ( iu ) of vitamin a as beta - carotene , more typically from 3 . 0 to 36 mg or 10 , 000 to 120 , 000 iu vitamin a as beta - carotene , most typically from about 7 . 5 to 21 mg or 25 , 000 to 70 , 000 iu of vitamin a as beta - carotene is typically present for an adult dosage . specific amounts of the vitamin a present in the composition may be dependent on the body weight of the mammal . in one specific example , the amount of vitamin a present as retinol in the composition is about 0 . 0178 mg / kg body weight . thus , for an average human weighing about 70 kg , the amount of vitamin a present as retinol in the composition may be about 1 . 25 mg . if the vitamin a is in the form of beta - carotene , in one example , the beta carotene in the composition is about 0 . 257 mg / kg body weight may be present in an amount of about 18 mg . in another example , the beta - carotene in the composition may be about in an amount of about 15 mg . it is to be appreciated that , when additional scavengers of singlet oxygen such as resveratrol are present in the composition in addition to vitamin a , the total amount of scavengers of singlet oxygen may be greater than the ranges set forth above for the at least one scavenger of singlet oxygen , so long as at least one scavenger of singlet oxygen is present in the amounts set forth above . in addition , other scavengers of singlet oxygen may be used in place of vitamin a , so long as the amount of the at least one scavenger of singlet oxygen is present within the amounts set forth above . when present , the resveratrol is typically included in the composition in an amount of at least 1 mg , more typically in an amount of from 10 mg to 1500 mg , most typically in an amount of from 15 mg to 1000 mg . whereas the at least one scavenger of singlet oxygen tends to prevent the initial formation of lipid peroxides , the donor antioxidant tends to reduce peroxyl radicals and inhibits propagation of lipid peroxidation that contributes to inner ear pathology and tinnitus . more specifically , the donor antioxidant reacts with and reduces peroxyl radicals and thus serves a chain - breaking function to inhibit propagation of lipid peroxidation . as is evident from the chain - breaking function of the donor antioxidant in lipid peroxidation , the donor antioxidant functions within cell membranes . a specific donor antioxidant that is contemplated for use in the composition of the subject disclosure is vitamin e . vitamin e is a generic term for all tocols and tocotrienol derivatives with a biological activity of alpha - tocopherol . primary dietary forms of vitamin e include vitamin e itself and alpha - tocopherol . trolox ®, a water - soluble analogue of alpha - tocopheral commercially available from hoffman - laroche , ltd . of basel , switzerland , is a research agent that is typically used as a source of vitamin e . the donor antioxidant is typically present in the composition , for example , in an amount of at least 75 iu , more typically from 75 iu to 2 , 000 iu , more typically from 150 to 1 , 500 iu , most typically from 150 iu to 800 iu . in another example , the donor antioxidant is present in the composition in an amount of at least 75 iu , more typically from 75 iu to 1 , 500 iu , most typically from 150 iu to 800 iu . as known in the art , a conversion of iu to weight for synthetic vitamin e is 0 . 66 mg / iu and for natural vitamin e is 0 . 45 mg / iu . thus , when the donor antioxidant is synthetic vitamin e , in on example , at least 75 iu of vitamin e is equivalent to at least 50 mg of vitamin e , from 75 to 2 , 000 iu of synthetic vitamin e is equivalent to from 50 to 1 , 320 mg of vitamin e , from 150 to 1 , 500 iu of synthetic vitamin e is equivalent to from 100 to 1 , 000 mg of vitamin e , and from 150 to 800 iu of synthetic vitamin e is equivalent to from 100 to 536 mg of vitamin e . in another example , when the donor antioxidant is vitamin e , at least 75 iu of vitamin e is equivalent to at least 50 mg of vitamin e , from 75 to 1500 iu of vitamin e is equivalent to from 50 to 1000 mg of vitamin e , and from 150 to 800 iu of vitamin e is equivalent to from 150 to 600 mg of vitamin e . as with the amount and type of vitamin a , specific amounts of the vitamin e present in the composition may be dependent on the body weight of the mammal . in one specific example , the amount of synthetic vitamin e present in the composition is about 3 . 8 mg / kg body weight . thus , for an average human weighing about 70 kg , the amount of vitamin e present in the composition may be about 266 mg . in another specific example , the amount of synthetic or natural vitamin e present in the composition is about 2 . 6 mg / kg body weight . thus , for an average human weighing about 70 kg , the amount of vitamin e present in the composition may be about 182 mg . in addition to the at least one scavenger of singlet oxygen and the donor antioxidant , the composition further includes the third antioxidant . while the third antioxidant may be a scavenger of singlet oxygen , the third antioxidant may also be an antioxidant that functions through a different mechanism . when the third antioxidant is a scavenger of singlet oxygen , the at least one scavenger of singlet oxygen is still present in the composition as a separate component from the third antioxidant , and is still present in the composition in the amounts set forth above for the at least one scavenger of singlet oxygen . as a result of the third antioxidant being another scavenger of singlet oxygen , the resulting composition would have at least two scavengers of singlet oxygen . the third antioxidant is typically vitamin c , which is a scavenger of singlet oxygen and reactive nitrogen species . it is to be appreciated that , although the third antioxidant is typically vitamin c , other antioxidants may be used in place of the vitamin c , and the other antioxidants may function through different mechanisms than vitamin c . the term vitamin c applies to substances that possess antiscorbutic activity and includes two compounds and their salts : l - ascorbic acid ( commonly called ascorbic acid ) and l - dehydroascorbic acid . in addition to being known as ascorbic acid and l - ascorbic acid , vitamin c is also known as 2 , 3 - didehydro - l - threo - hexano - 1 , 4 - lactone , 3 - oxo - l - gulofuranolactone , l - threo - hex - 2 - enonic acid gamma - lactone , l - 3 - keto - threo - hexuronic acid lactone , l - xylo - ascorbic acid and antiscorbutic vitamin . vitamin c is known to scavenge both reactive oxygen species and reactive nitrogen species . it can be oxidized by most reactive oxygen and nitrogen species , including superoxide , hydroxyl , peroxyl and nitroxide radicals , as well as such non - radical reactive species as singlet oxygen , peroxynitrite and hypochlorite . vitamin c thus inhibits lipid peroxidation , oxidative dna damage , and oxidative protein damage . in contrast to vitamin a , which functions best under conditions present in most tissues , water - soluble vitamin c is an excellent free radical scavenger in an aqueous phase to thus reduce free radicals at a site different from that of vitamin a . more specifically , ascorbic acid functions to reduce free radicals in fluid , such as in cytoplasmic fluid and / or blood , before the free radicals reach cell membranes . the third antioxidant is typically present , for example , in an amount of at least 4 , 000 iu , more typically from 4 , 000 to 60 , 000 , more typically from 8 , 000 to 40 , 000 iu , most typically from 8 , 000 to 20 , 000 iu . in another example , the third antioxidant is typically present in an amount of at least 4 , 000 iu , more typically from 6 , 000 to 40 , 000 iu , and most typically from 8 , 000 to 20 , 000 iu . using vitamin c as an example for converting iu to weight units for the third antioxidant , as known in the art , a conversion of iu to weight for vitamin c is 0 . 05 mg / iu . thus , at least 4 , 000 iu of vitamin c is equivalent to at least 200 mg of vitamin c , from 6 , 000 to 60 , 000 iu of vitamin c is equivalent to from 300 to 3 , 000 mg vitamin c , from 6 , 000 to 40 , 000 iu of vitamin c is equivalent to from 300 to 2 , 000 mg , from 8 , 000 to 40 , 000 iu of vitamin c is equivalent to from 400 to 2 , 000 mg vitamin c , and from 8 , 000 to 20 , 000 iu vitamin c is equivalent to from 400 to 1 , 000 mg vitamin c . as with vitamins a and e , specific amounts of the vitamin c or other third antioxidant present in the composition may be dependent on the body weight of the mammal . in one specific example , the amount of vitamin c present in the composition is about 7 . 14 mg / kg body weight . thus , for an average human weighing about 70 kg , the amount of vitamin c present in the composition may be about 500 mg . as set forth above , the composition further includes a vasodilator . typically , the vasodilator includes magnesium ; however , the vasodilator , for purposes of the subject disclosure , may include other vasodilators in place of or in addition to magnesium , in place of or in addition to those including magnesium , or may include only magnesium or only magnesium - containing compounds . vasodilators can be used for treating tinnitus . vasodilators including magnesium prevent decreases in cochlear blood flow and oxygenation via biochemical mechanisms involving changes in calcium concentration and prostaglandins . deficient cochlear blood flow and lack of oxygenation can contribute to tinnitus by causing metabolic changes in lateral wall tissues important for maintaining normal homeostasis of the inner ear , e . g . endocochlear potential , and normal transduction ; and may cause cell death in sensitive hair cells within a cochlea of the ear . vasodilators including magnesium have also been found to improve the efficacy of immunosuppressant therapy or carbogen inhalation therapy in recovery from sudden tinnitus . furthermore , it has been found that magnesium deficiency leads to increased calcium channel permeability and greater influx of calcium into cochlear hair cells and afferent nerve endings , increased glutamate release , and auditory nerve excitotoxicity , each of which play a role in health of the inner ear . although the vasodilators are known in the art for treating tinnitus , the vasodilators , especially those including magnesium , exhibit an unexpected additive effect when combined with the biologically effective amounts of the at least one scavenger of singlet oxygen , the donor antioxidant , and the third antioxidant , especially when the at least one scavenger of singlet oxygen is vitamin a , the donor antioxidant is vitamin e , and the third antioxidant is vitamin c for purposes of treating noise - induced tinnitus . the additive effect referred to above is greater than not only the most efficacious of the components for treating inner ear pathology that causes tinnitus , but typically greater than the sum of the effects of each of the components for treating tinnitus . while vasodilators other than those including magnesium are envisioned for purposes of the present disclosure , additive effects are not observed with all vasodilators . for example , betahistine , which is another known vasodilator , does not exhibit an additive effect . the vasodilator including magnesium typically includes a magnesium salt or magnesium salt complex and , more specifically , magnesium sulfate or magnesium citrate . other vasodilators including magnesium that may be suitable for purposes of the subject disclosure include ; magnesium acetate , magnesium aspartate , magnesium carbonate , magnesium chloride , magnesium fumarate , magnesium gluconate , magnesium glycinate , magnesium hydroxide , magnesium lactate , magnesium oxide , magnesium salicylate , magnesium stearate , and magnesium sulfate . other representative salts include but are not limited to ; hydrobromide , hydrochloride , bisulfate , nitrate , arginate , ascorbate , oxalate , valerate , oleate , palmitate , laurate , borate , benzoate , phosphate , tosylate , maleate , fumarate , succinate , taurate , tartrate , naphthylate , mesylate , glucoheptonate , lactobionate and laurylsulphonate salts . typically , the vasodilator is present in the composition in an amount of at least 50 mg . for example , when the vasodilator is magnesium , the magnesium is typically present in an amount of from 50 to 450 mg , most typically from 100 to 350 mg . as with vitamins a , c , and e , specific amounts of the vasodilator present in the composition may be dependent on the body weight of the mammal . in one specific example , the amount of the vasodilator including magnesium present in the composition is about 4 . 46 mg / kg body weight . thus , for an average human weighing about 70 kg , the amount of the vasodilator including magnesium present in the composition may be about 312 mg . in another example , the amount of the vasodilator including magnesium present in the composition is about 2 . 14 mg / kg body weight . thus , for an average human weighing about 70 kg , the amount of the vasodilator including magnesium present in the composition may be about 150 mg . non - limiting examples of amounts of the typical components included in the composition , along with more and most typical amounts , are summarized in table 1 below . with respect to table 1 , the amounts specified for the antioxidants and the vasodilator correlate , in terms of biological effectiveness , to amounts used for humans . furthermore , it is to be appreciated that the biologically effective amounts of the antioxidants and vasodilator may be lower within the above ranges for children than for the average human , based on lower us recommended daily allowances and maximum intake levels for children . this is evident based on the typical dosages in table 1 based on mg / kg . other non - limiting examples of amounts of the typical components included in the composition , along with more and most typical amounts , are summarized in table 2 below . with respect to table 2 , the amounts specified for the antioxidants and the vasodilator correlate , in terms of biological effectiveness , to amounts used in animal studies on guinea pigs . furthermore , it is to be appreciated that the biologically effective amounts of the antioxidants and vasodilator may be lower within the above ranges for children than for the average human , based on lower u . s . recommended daily allowances and maximum intake levels for children . this is evident based on the typical dosages in table 2 based on mg / kg . in addition to the antioxidants and vasodilator , other components may also be present in the composition for treating tinnitus . these components may be used for treating the side effects of the antibiotic treatment also . for example , in one embodiment , the composition further includes a withanolide . withanolides have been suggested for use in anti - inflammatory , anti - tumor , cytotoxic , and immunological applications . one example of a specific withanolide that may be included in the composition of the subject disclosure is the withanolide extracted from day lily plants . the extract is a powerful natural antioxidant which may be effective in preventing cell death in the inner ear by interrupting the cell - death pathway initiated by deafferentation of the auditory nerve . when included in the composition , the withanolide may be present in an amount of at least 10 ppm , more typically from 10 to 1000 ppm . additional components , besides withanolides , can also be included . typically , the composition is free of components that interfere with the biological mechanisms through which the at least one scavenger of singlet oxygen , the donor antioxidant , the third antioxidant , and the vasodilator function . the composition is also typically free of additional components that could degrade or neutralize the at least one scavenger of singlet oxygen , the donor antioxidant , the third antioxidant , and the vasodilator function when mixed therewith prior to internally administering the composition to the mammal . those of skill in the art can readily identify such components in view of the mechanisms by which the individual components in the composition function as set forth above ( e . g ., components that cause vasoconstriction , various oxidizing agents , etc .). it is also to be appreciated that , even if additional components are present in the composition that could interfere with the mechanisms by which the at least one scavenger of singlet oxygen , the donor antioxidant , the third antioxidant , and the vasodilator function , the composition described above is may still be effective for purposes of treating side effects of the antibiotic treatment . as one example , and as described in further detail below , the composition including the at least one scavenger of singlet oxygen , the donor antioxidant , the third antioxidant , and the vasodilator may be effective for treating tinnitus and other side effects of antibiotic treatment when administered in conjunction with aminoglycoside antibiotics . this is true even though aminoglycoside antibiotics , themselves , are responsible for causing tinnitus and other side effects such as kidney damage and loss of balance through free radical formation . in view of the fact that components as detrimental as aminoglycosides can be administered in conjunction with the composition described above , it is clear that additional components that are less detrimental to the specific mechanisms by which the at least one scavenger of singlet oxygen , the donor antioxidant , the third antioxidant , and the vasodilator function can also be present in the composition with an expectation that the composition maintains effectiveness for purposes of treating side effects of antibiotic treatment such as antibiotic - induced tinnitus . examples of some additional components that may be included in the composition include , but are not limited to , excipients , flavoring agents , fillers , binders , and additional vitamins or minerals not specifically mentioned herein . as alluded to above , the method of treating tinnitus and the method of treating side effects from antibiotic treatment of the instant disclosure includes the step of internally administering the composition of the subject disclosure to a mammal . the composition may be orally administered to the mammal , such as in the form of a tablet , liquid , gel , etc . alternatively , the composition may be intravenously administered to the mammal through an iv or an injection of the composition . when specifically used to treat antibiotic - induced tinnitus , the composition may also be locally administered via the round window membrane of the cochlea . as a specific example , the vitamins a , c , and e , the vasodilator including magnesium , and the optional components may be first combined to form the composition , with the composition then administered to the mammal . alternatively , the vitamins a , c , and e , the vasodilator including magnesium , and the other optional components may be separately administered , in which case the composition forms within the mammal . for purposes of the subject disclosure , tinnitus is typically associated with stress ( noise , antibiotic , genetic )- induced hearing loss as objectively measured in terms of differences in threshold shift , or through measurement of a percentage of hair cell loss . in guinea pig studies , tinnitus , as objectively measured as a change in gap - detection , is observed in the majority of animals , either transiently or prolonged , following exposure to noise . reduction in tinnitus reflecting the efficacy of the composition for treating noise - induced tinnitus may be measured as an average difference in threshold shift from baseline threshold sensitivity at 4 , 8 , and 16 khz , as compared to an untreated control , after exposure to high indensity octave band noise centered at 4 khz for three hours . small differences in threshold shift may be associated with less tinnitus and greater efficacy of the composition for treating the antibiotic - induced tinnitus . for purposes of the subject disclosure , tinnitus may be objectively measured in terms of differences in threshold shift , or through measurement of a percentage of hair cell loss . in guinea pig studies , tinnitus and the efficacy of the composition for treating antibiotic - induced tinnitus may be measured as an average difference in threshold shift from baseline threshold sensitivity at 4 , 8 , and 16 khz , as compared to an untreated control , after exposure to 120 decibel spl octave band noise centered at 4 khz for five hours . larger differences in threshold shift correlate to less tinnitus and greater efficacy of the composition for treating the antibiotic - induced tinnitus . it is has been shown that hair cell loss correlates to threshold shift . for example , in guinea pig ears that recover from temporary threshold shift , morphological damage is limited to tips of stereocilia in a third row of outer hair cells ( ohcs ) whereas ears from animals with permanent threshold shift have damage to all three rows of ohcs and , in some cases , the inner hair cells ( ihcs ), with damage throughout the length of the stereocilia as well as the to the body of the hair cell . in one embodiment , the composition of the present disclosure is administered to the mammal within three days of trauma to the inner ear of the mammal in order to alleviate permanent threshold shift . it is to be appreciated that by administering the composition within three days of trauma , treatment prior to trauma is also contemplated through the method of the present disclosure . data from animal studies indicate that temporary threshold shift measured 24 hours post - trauma is well - correlated with permanent threshold shift . given the relationship between temporary threshold shift and permanent threshold shift , it is clinically beneficial to reduce temporary threshold shift . as such , the composition is typically administered within one day of trauma to the inner ear of the mammal . even so , it is expected that treatment within three days with the composition of the present disclosure is substantially as effective in minimizing permanent threshold shift as treatment within one day . treatment within three days is most appropriate when the mammal has sustained trauma to the inner ear through unexpected loud noise or other trauma . ideally , the composition is administered to the mammal prior to trauma to the inner ear . treatment prior to trauma is most feasible when the mammal is preparing for sustaining trauma to the inner ear . for example , the composition may be administered prior to restoration surgery performed on the inner ear . as another example , if a person will be firing a weapon or attending an event such as a rock concert , the person may begin treatment prior to sustaining the trauma to the inner ear to attain the best results . after initial administration of the composition , the composition is typically administered to the mammal each day for at least five days following the trauma to the inner ear of the mammal . although excellent results have been achieved through such treatment , it is to be appreciated that other treatment regimens may also prove efficacious for purposes of the present disclosure . for the method of treating side effects of antibiotic treatment , the composition is internally administered to the mammal in conjunction with administration of the antibiotic . in this regard , the method also includes the step of internally administering the antibiotic , which antibiotic is capable of inducing tinnitus in the mammal . it is to be appreciated that , even though the antibiotic with which the composition is administered is capable of inducing tinnitus , the method of the instant disclosure is not strictly limited to treatment of tinnitus that is induced by the antibiotics . more specifically , the method of the instant disclosure proscribes the step of administering the subject composition in conjunction with administration of the antibiotic for any purpose including for treating any side effect of the antibiotics including not only antibiotic - induced tinnitus , but also kidney damage , loss of balance , among other side effects . non - limiting examples of antibiotics that are thought to potentially contribute to inducing tinnitus in mammals include aminoglycoside antibiotics such as amikacin , arbekacin , gentamicin , kanamycin , neomycin , netilmicin , paromomycin , rhodostreptomycin , streptomycin , tobramycin , and apramycin ; and glycopeptide antibiotics such as vancomycin , teicoplanin , telavancin , bleomycin , ramoplanin , and decaplanin . the treatment is particularly effective against aminoglycoside - induced side effects . in one specific embodiment , the antibiotic is gentamicin , which is commonly used in developing countries due to low cost and effectiveness against certain drug - resistant diseases . the dosages of the antibiotic that are administered to the mammal may vary within the medically - accepted ranges for therapeutic treatment , as may the number of days over which the antibiotic is administered . the antibiotic is typically administered daily . for purposes of objectively establishing the effectiveness of the treatment described herein , a dosage of 140 g of gentamicin was administered to guinea pigs for a period of 16 days . however , it is to be appreciated that the specific dosages and days over which the antibiotic is administered are not material for purposes of establishing the viability of the treatment described herein so long as the composition described herein is administered in conjunction with administration of the antibiotic ( although the effectiveness of the treatment described herein may vary based upon dosages and days over which the antibiotics are administered ). for purposes of the instant disclosure , administration of the composition described herein “ in conjunction with ” administration of the antibiotic refers to a connection in the administration of the composition and the antibiotic during the course of antibiotic treatment . to maximize effectiveness of the treatment described herein , it is desirable to establish stable serum levels of the at least one scavenger of singlet oxygen , the donor antioxidant , the third antioxidant , and the vasodilator at the time that the antibiotics reach serum levels within the mammal that may cause material side effects such as tinnitus . typically , the composition is internally administered to the mammal no longer than three days after administration of a first dosage of the antibiotic , which is sufficient to achieve the stable serum levels of the at least one scavenger of singlet oxygen , the donor antioxidant , the third antioxidant , and the vasodilator before the antibiotics begin to materially cause the side effects such as tinnitus . in one embodiment , the composition is internally administered prior to administration of the first dosage of the antibiotic . in this embodiment , the composition may be administered at least five days , alternatively at least ten days , prior to administration of the first dosage of the antibiotic for purposes of maximizing the effectiveness of the treatment for side effects of antibiotic treatment described herein . once administration of the composition has begun , the composition is typically administered each day the antibiotic is administered to maintain adequate serum levels of the at least one scavenger of singlet oxygen , the donor antioxidant , the third antioxidant , and the vasodilator . additionally , the composition is typically administered for at least 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , or 21 days following cessation of administration of the antibiotic . this is typically performed for purposes of ensuring that adequate serum levels of the at least one scavenger of singlet oxygen , the donor antioxidant , the third antioxidant , and the vasodilator are maintained until the serum levels of the antibiotic decrease , and typically until all of the additional free radicals formed secondary to the antibiotic treatment are eliminated . in varying embodiments , an average difference in threshold shift in mammals from baseline threshold sensitivity at 4 , 8 , and 16 khz , as compared to an untreated control , is at least 25 decibels after exposure to 120 decibel spl octave band noise centered at 4 khz for five hours . more specifically , the threshold shift in mammals treated with the composition of the present disclosure is expected to be at least 25 decibels lower than the threshold shift in mammals that are treated with a control saline solution . to obtain those results , the composition is orally administered one hour prior to exposure to the noise and administered again each day for five days subsequent to the exposure to the noise . the threshold shift is measured 10 days after exposure to the noise using auditory brainstem response ( abr ) testing . similar results would be anticipated using other alternative measures of auditory or sensory cell function , such as psychophysical tests or otoacoustic emission measures . while effectiveness of treatment in accordance with the method of the instant disclosure is related to measurement and mitigation of shifts in threshold , which is routinely associated with tinnitus , it is to be appreciated that the method is not strictly limited to treatment of noise - tinnitus alone . in addition , outer hair cell loss and inner hair cell loss is measured both in the whole cochlea and in a trauma region of the cochlea . after treatment according to the method of the present disclosure , outer hair cell loss in the whole cochlea is typically less than 10 %, and inner hair cell loss in the whole cochlea is typically less than 5 %. outer cell hair loss in the trauma region is typically less than 20 %, while inner hair cell loss in the trauma region is typically less than 10 %. for the method of treatment in accordance with the present disclosure , outer hair cell loss in the whole cochlea is typically less than 50 %, while inner hair cell loss in the whole cochlea is typically less than 5 %. to obtain those results , the composition is orally administered to guinea pigs for 10 to 16 days prior to first administration of the antibiotic , and the composition and antibiotic are administered again each day for forty days . the guinea pigs are then euthanized and the hair cells counted . conversely , when the antibiotic is administered for forty days without administering the composition described herein in conjunction with the antibiotic , outer hair cell loss approaches 80 %, while inner hair cell loss is about 8 %. one or more of the values described above may vary by − 5 %, − 10 %, − 15 %, − 20 %, − 25 %, etc . so long as the variance remains within the scope of the disclosure . unexpected results may be obtained from each member of a markush group independent from all other members . each member may be relied upon individually and or in combination and provides adequate support for specific embodiments within the scope of the appended claims . the subject matter of all combinations of independent and dependent claims is herein expressly contemplated . the disclosure is illustrative including words of description rather than of limitation . many modifications and variations of the present disclosure are possible in light of the above teachings , and the disclosure may be practiced otherwise than as specifically described herein . in additional non - limiting embodiments , all values and ranges of values within any aforementioned range of numbers are hereby expressly contemplated .
a method of treating tinnitus includes the step administering a composition to the mammal , wherein the composition consists essentially of a biologically effective amount of vitamin a , vitamin e , vitamin c , a vasodilator comprising magnesium , and , optionally , a withanolide , and / or resveratrol .