coenzyme - q10 ( coq - h2 ) , n - acetylcysteine , vitamin c and vitamin e amongst others have been identified as nutritional ingredients necessary for dm management . this identifies the effects of antioxidants in the management of oxidative damage in dm . to prevent or slow down the progression of diabetes and its complications , dieticians evaluate the patient 's diet and determine necessary changes . clinical algorithms have been suggested to guide the use of dietary therapy using laboratory measures . thus , the crucial factor of oxidative stress ( os ) and the basic principle that physiological systems are regulated by metabolic processes is being overlooked . the inherent and ongoing danger is that the efficacy of medical nutrition therapy is still sub - optimal and the validity still a subject of debate . for instance , while there has been acknowledgement that vitamins c and e can nullify oxidative stress and prevent diabetic cardiovascular complications , there are contrary reports of the risk of hypertension and mortality associated with vitamin e in dm patients . the dangerous debate surrounding antioxidant vitamins was hallmarked by the guideline of the american heart association ( aha ) that listed antioxidant vitamin supplements as not recommended for cvd prevention in diabetes , because of risk of harm . furthermore , the recently published executive summary of revised recommendations from canada does not contain any statement regarding antioxidant vitamins . this raises the need to clarify how the different antioxidants act in dm , how the widely reported toxicity arises and how the toxicity can be avoided in dietary treatment of diabetes . the objective of this commentary is to offer insights that put in perspective how to optimize outcomes of medical nutrition therapies in diabetes management through laboratory monitoring . to achieve the set objective , ( i ) how are the choices and outcomes of antioxidant vitamins nutrition determined in research ? ( ii ) how are the choices and outcomes of antioxidant vitamins nutrition determined in clinical practice ? ( iii ) what does the medical nutrition therapy guidelines recommend ? review 1 : how are the choices and outcomes of antioxidant vitamins nutrition determined in research ? the literatures available on ovid , pubmed , science - direct and wiley interscience databases were reviewed similar to the method of witte , clarke and cleland . this review was with particular interest on the antioxidant vitamins and co - antioxidants that were determined in diabetes study . therefore vitamins c and e as well as diabetes , coq - h2 , and reduced glutathione ( gsh ) were used as search terms . the result , which was presented at an international conference , shows that none of the opponents or proponents of vitamin e nutrition has evaluated all of the endogenous co - antioxidants that are necessary for optimal efficacy ( table 1 ) . a random review of some of the research protocols showed that every study acknowledged the importance of co - antioxidants interactions , but omitted the laboratory assessment of at least one co - antioxidant component . review 2 : how are the choices and outcomes of antioxidant vitamins nutrition determined in clinical practice ? first , a one year ( january to december 2007 ) archived results were reviewed to ascertain whether the antioxidant tests that were performed in our laboratory are appropriately in perspective . secondly , the  evidence - based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications  was reviewed . as reported in a conference , table 2 presents data of antioxidant vitamins tests that were performed in 2007 . a total of 115 vitamin e and 32 vitamin c tests were performed . coq - h2 and gsh levels are not being determined ( table 2 ) . furthermore , it is interesting to note that these tests were not requested by nutrition and dietetic practitioners or for the purpose of nutrition evaluation in dm management . number of antioxidant assessed in 2007 at a reference clinical laboratory in another reported review , laboratory records of all diabetes patients who were followed up for diabetes control in 2008 were audited . it was observed that none of the 10,342 glycaemic index ( hba1c ) requests received in the year was requested for any antioxidant vitamin . the guidelines indicate amongst others that if deficiencies of antioxidant vitamins are identified , supplementation can be beneficial , but that this is difficult to ascertain . canadian diabetes association 2008 clinical practice guidelines for the prevention and management of diabetes in canada was also reviewed . this shows that choices of antioxidant nutrition are not based on any laboratory evaluation of levels of the micronutrients ; because the guidelines are silent and/or contain that it is difficult to ascertain . this is evidence of either lack of awareness or a system oversight that requires addressing . to achieve the set objective , the following three questions were briefly addressed by brief reviews . ( i ) how are the choices and outcomes of antioxidant vitamins nutrition determined in research ? ( ii ) how are the choices and outcomes of antioxidant vitamins nutrition determined in clinical practice ? ( iii ) what does the medical nutrition therapy guidelines recommend ? review 1 : how are the choices and outcomes of antioxidant vitamins nutrition determined in research ? the literatures available on ovid , pubmed , science - direct and wiley interscience databases were reviewed similar to the method of witte , clarke and cleland . this review was with particular interest on the antioxidant vitamins and co - antioxidants that were determined in diabetes study . therefore vitamins c and e as well as diabetes , coq - h2 , and reduced glutathione ( gsh ) were used as search terms . the result , which was presented at an international conference , shows that none of the opponents or proponents of vitamin e nutrition has evaluated all of the endogenous co - antioxidants that are necessary for optimal efficacy ( table 1 ) . a random review of some of the research protocols showed that every study acknowledged the importance of co - antioxidants interactions , but omitted the laboratory assessment of at least one co - antioxidant component . review 2 : how are the choices and outcomes of antioxidant vitamins nutrition determined in clinical practice ? first , a one year ( january to december 2007 ) archived results were reviewed to ascertain whether the antioxidant tests that were performed in our laboratory are appropriately in perspective . secondly , the  evidence - based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications  was reviewed . as reported in a conference , table 2 presents data of antioxidant vitamins tests that were performed in 2007 . a total of 115 vitamin e and 32 vitamin c tests were performed . coq - h2 and gsh levels are not being determined ( table 2 ) . furthermore , it is interesting to note that these tests were not requested by nutrition and dietetic practitioners or for the purpose of nutrition evaluation in dm management . number of antioxidant assessed in 2007 at a reference clinical laboratory in another reported review , laboratory records of all diabetes patients who were followed up for diabetes control in 2008 were audited . it was observed that none of the 10,342 glycaemic index ( hba1c ) requests received in the year was requested for any antioxidant vitamin . the guidelines indicate amongst others that if deficiencies of antioxidant vitamins are identified , supplementation can be beneficial , but that this is difficult to ascertain . canadian diabetes association 2008 clinical practice guidelines for the prevention and management of diabetes in canada was also reviewed . this shows that choices of antioxidant nutrition are not based on any laboratory evaluation of levels of the micronutrients ; because the guidelines are silent and/or contain that it is difficult to ascertain . this is evidence of either lack of awareness or a system oversight that requires addressing . antioxidant activities in diabetes pathology : to correct the possible oversight , it is pertinent to have an overview of antioxidant activities and limitations . this is one of a complex interactions involving feedback and feedforward effect of biochemical processes . the activity of one antioxidant triggers the action of one or more co - antioxidant , but all constitute a kind of closed circuit network ( fig . keys : 1 - 6 = eq1  eq6 respectively ; aa = ascorbic acid ; daa = dehydro - ascorbic acid ; gr = glutathione reductase ; gsh = reduced glutathione ; gssg = oxidized glutathione ; looh = lipid peroxide ; loo = lipid peroxyl radical ; rc = mitochondrial respiratory chain ; toh = tocopherol ( vitamin e ) ; to = tocopheroxyl radical . importance and limit of reduced glutathione ( gsh ) : in dm , the frontline cellular antioxidant is gsh , which is involved in recycling both vitamins c and e. when there is inadequate level of gsh , both vitamins e and c are inadequately regenerated . a pathophysiological effect is that un - regenerated radicals of the vitamins will exercise their pro - oxidant activity and exacerbate os ( fig . therefore , when vitamin e supplementation is prescribed without assessment of gsh level , two sources of error are inherent . firstly , evidence is not established whether the person 's actual need is vitamin e. it could be that the frontline antioxidant is what is lacking . secondly , the adequacy of the antioxidant that will regenerate vitamins c and e from their pro - oxidant states is being undermined . this is the basis of support for n - acetylcysteine in diabetes management , to supplement of gsh . vitamin e activity : the antioxidation reaction of vitamin e ( tocopherol - oh ) involves loss of electron via donation of a hydrogen atom ( h ) . it then becomes a pro - oxidant molecule ( tocopherol - o ) that is capable of initiating os by a process of tocopherol - mediated peroxidation . tocopherol - mediated peroxidation is prevented by complex feedback activities of coq - h2 , gsh and vitamin c. when there is deficiency in one or more of these co - antioxidants ( fig . 1 ) , the feedforward os that occurs explains the reported toxicity of vitamin e. importance and limit of vitamin c : vitamin c ( ascorbic acid ) fundamentally acts in the regeneration of vitamin e. therefore , its therapeutic use as an antioxidant is only necessary if there is either evidence of inadequate recycling of vitamin e , or foreseeable need to backup for intended vitamin e supplementation . ascorbic acid acts first by donating one electron and thereafter becomes dehydroascorbic acid , which has a pro - oxidant property . 1 ) . otherwise , the pro - oxidant activity of dehydroascorbic acid causes os , which explains the reports of toxicity and casts doubt on the validity of vitamin c therapy . importance and limit of coq - h2 : a reduced rate of regeneration of vitamin e by gsh and/or vitamin c is accompanied by a deficiency of vitamin e to scavenge the lipid peroxide . as a feedback mechanism , the coq - h2 activity will tend to increase . this triggers a feedback whereby coq - h2 tends to increase its rate of scavenging for the accumulating lipid peroxides ( fig . 1 ) . although coq - h2 may be indispensable as a mitochondrial antioxidant and is useful for the regeneration of vitamin e ( fig . 1 ) , its rate of reaction shifts during vitamin e deficiency and cause its sub - optimal activities in the mitochondria . meanwhile , there is the paradox of increased ros production in the respiratory chain , which contributes to oxidative mitochondrial damage , thereby exacerbating dm complications . in summary , antioxidant interactions constitute a complex factor that determines whether a therapeutic dietary recommendation yields a positive or negative outcome . it is a vital precaution that no single component is arbitrarily assumed to be predominant in disease conditions . this draws attention to the notion that giving vitamins c and e supplements at the onset of diabetes is preventive . the fallacy or omission in this belief is that the limitation of vitamin c in regenerating vitamin e is overlooked . if any of the other co - antioxidants is deficient , it is impossible for vitamin c and/or e to be very effective . instead , administration of even a normal daily dose of the antioxidant vitamin will yield pro - oxidants that may not be regenerated well enough . the net effect is increased os , which is negative and unwanted . thereby casting doubt about the validity of the antioxidant supplement or dietary regimen . insights to optimize medical nutritional therapies with laboratory assessment : firstly , the impression that identification of deficiencies of antioxidant vitamin level is difficult to ascertain needs to be corrected . validated methods for in vitro diagnostic use exist for vitamins c and e ( table 1 ) . in australia , the tests can be done at no cost to the patient , because they are listed for bulk billing . the other strongly related co - antioxidants , coq - h2 and gsh , are available in some research laboratories , but still require standardization for in vitro diagnostic use . for the mean time , the available vitamins c and e tests can be used to ascertain the levels of antioxidant vitamins , which the current guideline acknowledges to be important but did not recommend . secondly , it is pertinent to note the following points on how to interpret and optimize the laboratory tests . if laboratory result indicates normal level of vitamin c and/or e , it provides evidence base not to recommend the antioxidant vitamin nutrition / supplement.if laboratory result flags low level of vitamin c and/or e , one of two scenarios is probable . the antioxidant vitamin may be in abundance , but existing in its pro - oxidant form and requires to be recycled . imagine that a person who was tested for vitamin c showed a low level result . if there is deficient gsh , any recommended nutritional or supplementary vitamin c would be converted to additional dha without being recycled . thus , follow up laboratory tests result will flag low level.the antioxidant may be truly deficient and requires supplementation . if there is sufficient gsh , the recommended nutritional or supplementary vitamin c would be converted to dha , but adequately recycled in a feedback response . thus , follow up laboratory tests result will indicate improved or normal level . 
 assess the levels of both vitamins c and e. the data presented shows that in the month of may 2007 , three persons were tested for vitamin e ; none of whom was tested for vitamin c ( table 2 ) . if the test were requested for medical nutrition purposes , it would benefit to determine whether a deficiency of vitamin e is concomitant with deficiency of vitamin c. such determination will form evidence base to take one of three decisions 
 start with an initial supplementation of vitamin c and evaluate how much of vitamin e has been recycled ( from its pro - oxidant state ) . during follow up , non - improvement in vitamin e levels with improvement in vitamin c should be affirmation of deficiency of the former . however , improvement in vitamin e levels with no improvement in vitamin c should suggest deficient recycling of the latter , which in turn suggest a requirement for n - acetylcysteine nutrient to boost gsh synthesis.vitamins c and e nutrients and/or supplements could be given with follow up tests to evaluate improvement in levels . a repeat observation of low level results would be clear indication of failed regeneration system ( fig . , it will be indirect indication of deficient levels of other co - antioxidants , which will then form evidence base for the need of nutritional therapies other than vitamins c or e.concomitant deficiencies of vitamins c and e being probable indication of failed regeneration system can be attended to . in this case , it has to be noted that the vitamins may be much in the pro - oxidant forms and requiring regeneration . therefore , a discrete combination of food that contains coq - h2 and n - acetylcysteine may be what is required to improve recycling . if the probability is true , the follow up evaluation tests should present improved levels of vitamins c and e. 

  if laboratory result indicates normal level of vitamin c and/or e , it provides evidence base not to recommend the antioxidant vitamin nutrition / supplement . if laboratory result flags low level of vitamin c and/or e , one of two scenarios is probable . the antioxidant vitamin may be in abundance , but existing in its pro - oxidant form and requires to be recycled . imagine that a person who was tested for vitamin c showed a low level result . if there is deficient gsh , any recommended nutritional or supplementary vitamin c would be converted to additional dha without being recycled . thus , follow up laboratory tests result will flag low level.the antioxidant may be truly deficient and requires supplementation . if there is sufficient gsh , the recommended nutritional or supplementary vitamin c would be converted to dha , but adequately recycled in a feedback response . . 
  the antioxidant vitamin may be in abundance , but existing in its pro - oxidant form and requires to be recycled . imagine that a person who was tested for vitamin c showed a low level result . if there is deficient gsh , any recommended nutritional or supplementary vitamin c would be converted to additional dha without being recycled . if there is sufficient gsh , the recommended nutritional or supplementary vitamin c would be converted to dha , but adequately recycled in a feedback response . assess the levels of both vitamins c and e. the data presented shows that in the month of may 2007 , three persons were tested for vitamin e ; none of whom was tested for vitamin c ( table 2 ) . if the test were requested for medical nutrition purposes , it would benefit to determine whether a deficiency of vitamin e is concomitant with deficiency of vitamin c. such determination will form evidence base to take one of three decisions 
 start with an initial supplementation of vitamin c and evaluate how much of vitamin e has been recycled ( from its pro - oxidant state ) . during follow up , non - improvement in vitamin e levels with improvement in vitamin c should be affirmation of deficiency of the former . however , improvement in vitamin e levels with no improvement in vitamin c should suggest deficient recycling of the latter , which in turn suggest a requirement for n - acetylcysteine nutrient to boost gsh synthesis.vitamins c and e nutrients and/or supplements could be given with follow up tests to evaluate improvement in levels . a repeat observation of low level results would be clear indication of failed regeneration system ( fig . , it will be indirect indication of deficient levels of other co - antioxidants , which will then form evidence base for the need of nutritional therapies other than vitamins c or e.concomitant deficiencies of vitamins c and e being probable indication of failed regeneration system can be attended to . in this case , it has to be noted that the vitamins may be much in the pro - oxidant forms and requiring regeneration . therefore , a discrete combination of food that contains coq - h2 and n - acetylcysteine may be what is required to improve recycling . if the probability is true , the follow up evaluation tests should present improved levels of vitamins c and e. 
  start with an initial supplementation of vitamin c and evaluate how much of vitamin e has been recycled ( from its pro - oxidant state ) . during follow up , non - improvement in vitamin e levels with improvement in vitamin c should be affirmation of deficiency of the former . however , improvement in vitamin e levels with no improvement in vitamin c should suggest deficient recycling of the latter , which in turn suggest a requirement for n - acetylcysteine nutrient to boost gsh synthesis . vitamins c and e nutrients and/or supplements could be given with follow up tests to evaluate improvement in levels . a repeat observation of low level results would be clear indication of failed regeneration system ( fig . , it will be indirect indication of deficient levels of other co - antioxidants , which will then form evidence base for the need of nutritional therapies other than vitamins c or e. concomitant deficiencies of vitamins c and e being probable indication of failed regeneration system can be attended to . in this case , it has to be noted that the vitamins may be much in the pro - oxidant forms and requiring regeneration . therefore , a discrete combination of food that contains coq - h2 and n - acetylcysteine may be what is required to improve recycling . if the probability is true , the follow up evaluation tests should present improved levels of vitamins c and e. these are suggestions of how and when clinical laboratory monitoring can optimize the outcomes of dietary evaluations . the summary insight is that in an occasion where the laboratory results of vitamin c and/or e flags low , any recommended nutritional therapy should necessarily be monitored with follow - up laboratory evaluations . dietitians have played and are still playing crucial roles in diabetes and diabetic complications programs . clinical algorithms have been proposed to guide the use of medical nutrition therapy using validated laboratory measures of glycaemic control , insulin sensitivity , and beta - cell reserve . hence , patients are often given incorrect and inappropriate dietary advice by their health consultants . what this article contributes is that the process of dietary evaluation for patients will benefit from laboratory assessment of the patient 's need for specific nutritional antioxidants . while the effect of dietary therapy in diabetes management is not in doubt , the outcome of dietary evaluation and therapy can be in doubt when the limitations of the antioxidant nutrients are undermined . performing laboratory test of antioxidant status of patients during dietician 's assessment would be invaluable protocol to optimize outcomes .
medical nutrition therapy ( mnt ) guidelines acknowledge the need to identify deficiencies of antioxidant vitamins . 
 however , the guidelines contain that such identification is difficult . 
 thus , there is evidence that available clinical laboratory tests for antioxidant vitamins c and e are not in perspective in clinical practice . 
 coenzyme - q10 and glutathione tests are also available in research laboratories . 
 these indices are invaluable tools for discrete recommendation and monitoring of antioxidant nutrition therapies . 
 this commentary addresses biomarker insight to what the mnt guidelines consider difficult . 
 the importance and limits of the various dietary antioxidants is overviewed . 
 it puts in perspective how clinical laboratory monitoring of vitamins c and e levels can be used to optimize the outcomes of dietary evaluations for diabetes management . insight to how to interpret the laboratory results is presented . 
 the importance of this commentary is hinged on the premise that the outcome of dietary therapy can be counter - productive when laboratory evaluation or limitations of the antioxidant nutrients are undermined .