approximately 26% of american adults are suffering from a diagnosable mental disease , and nearly half ( 45% ) of them meet criteria for two or more disorders strongly related to comorbidity .
major depressive disorder ( mdd ) , one of the most common mental disorders , affects almost 15 million american adults ( about 7% of the population ) , and women report more depressive symptoms than men . furthermore , mdd is the leading cause of disability in the united states for persons between the ages of 15 and 44 , resulting in almost half of all lost productivity that translates into a cost burden of $ 44 billion per year .
in addition , the world health organization 's global burden of disease study measured lost years of healthy life in the developed world , regardless of whether they were lost to premature death or disability for various diseases , concluding that disability burden caused by mdd ranks second only to cardiovascular disease . while 3545% of depressed patients receiving fda - approved antidepressants experience complete relief from their symptoms , 5565% have inadequate response and/or side effects , such as sexual dysfunction , insomnia , weight gain , restlessness , and memory lapses , among others .
moreover , antidepressants have also been found to have serious side effects , such as suicide , violence , psychosis , and abnormal bleeding [ 7 , 8 ] .
thus , many patients end up on revolving medication trials , switching repeatedly from one drug to another or combining drugs to maximize their effects .
in addition , a literature review found that among patients with mdd placebo was as effective as antidepressants .
interestingly , according to several studies , modifiable factors , such as optimizing nutritional status , may help to improve the symptoms of depression . in one study ,
12  g / day of inositol resulted in positive therapeutic improvements similar to common antidepressant drugs , but without untoward side effects .
ernst found that ginkgo biloba was effective at improving depressed mood , anxiety , memory , concentration , and fatigue .
s - adenosyl methionine ( same ) was compared to oral doses of imipramine in a double - blind study for 14 days .
significant improvements were observed with same by the end of the first week , and at the end of the protocol 66% of the same patients had a clinically significant improvement in depressive symptoms compared to 22% of the imipramine patients .
another study that included 23 elderly patients with type 2 diabetes and hypomagnesemia showed that magnesium chloride was as effective as 50  mg / day of imipramine in improving depressive symptoms .
given these positive findings , a low - cost , safe alternative to medication can be considered for persons suffering from mdd .
thus , our study will extend the evaluative process of a vitamin b complex supplement 's efficacy and safety in improving depression , anxiety , and quality of life in a sample of adults diagnosed with depression through a randomized , double - blind , placebo - controlled clinical trial . with the overall high prevalence of dietary supplement use , the multifaceted problems associated with depression , including the untoward effects of standard treatment , and the growing number of readily available alternative and complementary remedies in the united states , the efficacy and safety of these substances demand more randomized clinical studies .
therefore , only scientifically valid results from well - controlled trials can help to evaluate and support claims of effectiveness of all treatments , including natural products .
the study was conducted with the approval of the university of miami institutional review board for human subjects research , and each subject signed informed consent and hipaa forms before enrolling in the study .
potential participants ( n = 120 ) were identified through referrals from clinical offices and centers at the university of miami miller school of medicine and from local community centers from miami - dade county from march 2010 to october 2011 .
thirty - six participants failed the screening inclusion / exclusion criteria , 24 participants were eligible for the study , but never enrolled , and 60 eligible participants were enrolled in the study at baseline .
potential study candidates were identified as individuals who expressed an interest in a study assessing the efficacy of a dietary supplement on depression , anxiety , and quality of life .
subjects were enrolled if they were ( a ) 18 years of age and older ; ( b ) currently diagnosed with mdd or a related depressive disorder as classified by the dsm - iv - tr ; ( c ) english speaking ; ( d ) had an elevated level of homocysteine ( > 10  mol / l ) at screening as a marker of inflammation ; ( e ) interested in participating in a novel nutritional supplement program ; and ( f ) willing to follow recommendations , including discontinuing all dietary supplements ( e.g. , multivitamin and mineral formula and vitamin b complex ) for depression 2 weeks before starting and during the entire intervention period .
exclusion criteria consisted of ( a ) current enrollment in another research trial for depression treatment ; ( b ) inability to consent to the study ; or ( c ) pregnancy in women .
potential study subjects were prescreened for the inclusion and exclusion criteria and given a brief introduction to the nature and purpose of the study .
all otherwise eligible subjects had a sample of venous blood drawn to measure homocysteine , a sulfurated amino acid derived from methionine , with higher levels directly related to depression .
the blood sample was collected in an edta tube and delivered to the laboratory for processing within 2 hours of collection .
following completion of the baseline assessment , participants were randomly assigned to one of two conditions ( a ) max stress b ( a whole - food dietary supplement ) or ( b ) placebo .
assignment of subjects into one of the two treatment groups was accomplished with a computer - generated table of random permutations , designed to balance the number of subjects in each group .
the table was arranged in advance , and the predetermined list of treatments served to prepare the numbered supplement containers ( used in order ) and the envelopes to be opened in the case of emergency . all subjects and investigators were blind to the treatment condition . only the staff at premier research labs ( the manufacturer of max stress b ) knew the assignment of treatment condition .
each participant completed a basic sociodemographics and medical history questionnaire , including current medications , at baseline .
they were also asked to note any changes in type or amount of medications during the course of the study .
criteria used to select the assessment instruments included ( a ) appropriateness for the population ; ( b ) ease of administration and scoring ; ( c ) experience administering these measures ; and ( d ) employment of measures involving a multimethod ( i.e. , self - report and physical measures ) approach to enhance the validity of the overall assessment .
the beck depression inventory - ii ( bdi )   and beck anxiety inventory ( bai )   were administered at baseline and 30- and 60-day followups to assess changes in depressive and anxiety symptoms , respectively , over the course of the intervention .
both the bdi and bai consist of 21 items and are scored 0 to 63 , where higher levels indicate progressive levels of depression ( 09 : minimal , 1018 : mild , 1929 : moderate , and 3063 : severe ) and anxiety ( 07 : minimal , 815 : mild , 1625 : moderate , and 2663 : severe ) .
the secondary outcome , administered at baseline and 30- and 60-day followups , included change in general health - related quality of life according to the medical outcomes study short form 36 ( sf-36 ) .
the sf-36 provides psychometrically based physical and mental health summary measures and as such is sensitive to subtle changes in relatively healthy persons , including those due to illness or injury .
in addition , the sf-36 is reliable , valid , and provides a t score for each scale or domain ranging from 0 to 100 with higher scores representing better perceived quality of life . as a control variable ,
physical activity was assessed at baseline and 30- and 60-day followups by the stanford 7-day physical activity recall .
this instrument has been validated for use in community - based settings , and it assesses the amount ( number of hours ) of moderate , physically challenging , and very physically challenging activities over the past 7 days .
this assessment tool provides useful estimates of habitual physical activity for research and highly correlates with daily self - report of physical activity [ 20 , 21 ] . for the 60-day intervention period ,
participants who enrolled in the study received ( a ) max stress b ( a whole nutrient natural source extract from probiotic colonies that contains vitamins b1 , b2 , b3 , b5 , b6 , and b12 , and folate , paba , biotin , inositol , purified water , and certified organic alcohol ) or ( b ) placebo ( an oil / water emulsion with food coloring similar to the test product ) .
subjects were instructed to consume 1 vial ( equivalent to 1/2 teaspoon ) of product in at least 12 ounces of water over the course of each day .
they were not advised to modify eating or physical activity habits or nondepression prescription medication use .
subjects were also instructed not to consume other nutritional supplements containing any of the vitamin b complex nutrients , same , inositol , paba , or folate for two weeks prior to having the baseline assessment and until the conclusion of the 60-day intervention period .
analysis of variance and chi - square were utilized to determine the presence of differences in background contextual variables by study arm assignment .
we utilized linear mixed modeling ( lmm ) to assess the fixed effect of time by randomization ( max stress b versus placebo ) on changes in our outcome variables from baseline to 60-day followup . if the type iii test of the fixed effect of time by randomization was significant , then we used pairwise comparisons to determine the unique differences in effects over time by study arm between baseline and followup at 30 and 60 days for depression , anxiety , and quality of life variables .
lmm with heterogeneous compound symmetry covariance allowed us to account for subject attrition , intercorrelated responses between time points , and nonconstant variability .
during the entire study period , no subjects reported adverse events or complications from the test products . 

table 1 presents the sociodemographic variables by study arm assignment for age , gender , race / ethnicity , education , and marital status . the sample ( n = 60 ) comprised of 68% males ( n = 41 ) and 32% females ( n = 19 ) with a mean age of 51 years ( sd = 7.8 ;  r = 22,68 ) .
the racial / ethnic distributions of the subjects were as follows : 63% black , non - hispanic ( n = 38 )
, 20% hispanic ( n = 12 ) , and 16.7% white , non - hispanic ( n = 10 ) .   table 2 shows the most commonly prevalent history of diseases and disorders among this sample , including hypertension , arthritis , hepatitis , low back pain / herniated disc , and sleep apnea .
table 3 displays the most prevalent current prescription medications and over - the - counter remedies , including antianxiety , antidepressant , antiviral , antihypertensive , and insomnia and aspirin , tylenol , and vitamin / mineral dietary supplements .
no proportions were significantly different between the study groups . regarding physical activity , study groups were statistically similar on the number of times exercised at strenuous , moderate , and mild exertion levels in the previous 7 days at each assessment . 

figure 1 shows the mean values for the bdi and bai over the course of the intervention for both study groups . for the bdi , the fixed effects for time ( f[2,83.3 ] = 21.7 , p < 0.01 ) and randomization ( f[1,57.6 ] = 4.0 , p = 0.05 )
post hoc comparisons revealed that the bdi significantly decreased from baseline to 30 days ( mean difference = 6.8 ; se = 1.2 ; 95% ci : 3.8 , 9.7 ; p < 0.01 ) and 60 days ( mean difference = 7.7 ;  se = 1.3 ;  95% ci :  4.5 , 10.9 ; p < 0.01 ) for the total sample .
for the max stress b group , the bdi significantly decreased from baseline to 30 days ( mean difference = 5.8 ; se = 1.7 ; 95% ci : 1.7 , 10.0 ; p < 0.01 ) and 60 days ( mean difference = 7.5 ; se = 1.8 ; 95% ci : 3.1 , 12.0 ; p < 0.001 ) . for the placebo group ,
the bdi significantly decreased from baseline to 30 days ( mean difference = 7.7 ; se = 1.7 ; 95% ci : 3.4 , 11.9 ; p < 0.001 ) and 60 days ( mean difference = 7.9 ; se = 1.9 ; 95% ci : 3.2 , 12.5 ; p < 0.001 ) . for the bai ,
the fixed effect for time ( f[2,93.4 ] = 3.8 , p < 0.05 ) was significant , but the effects for randomization and time by randomization were nonsignificant .
post hoc comparisons revealed that the bai significantly decreased from baseline to 60 days ( mean difference = 3.8 ; se = 1.4 ; 95% ci : 0.4 , 7.2 ; p < 0.05 ) for the total sample .
the bai showed a positive trend , but was statistically not significant , from baseline to 60 days ( mean difference = 4.2 ; se = 1.9 ; 95% ci : 0.5 , 8.8 ; p = 0.10 ) for the max stress b group , whereas the placebo group 's score stayed flat over the course of the intervention ( mean difference = 3.4 ; se = 2.0 ; 95% ci : 1.4 , 8.3 ; p = 0.25 ) . 
 table 4 shows the descriptive values for the sf-36 , including the scores for physical functioning , role - physical , general health , vitality , social functioning , role - emotional , mental health , and bodily pain . for role - physical , general health , and bodily pain the fixed effects for time , randomization , and time by randomization were nonsignificant . for physical functioning ,
the time by randomization effect was not significant ( f[2,87.9 ] = 3.0 , p = 0.06 ) , and post hoc comparisons revealed that the 60-day score was significantly higher than the baseline ( mean difference = 11.6 ; se = 4.6 ; 95% ci : 0.3 , 22.9 ; p < 0.05 ) for the placebo group . for vitality , the fixed effect for time ( f[2,78.9 ] = 5.6 ,  p < 0.01 ) was significant , but the effects for randomization and time by randomization were nonsignificant .
post hoc comparisons revealed that the score significantly increased from baseline to 30 days ( mean difference = 6.3 ; se = 2.5 ; 95% ci : 0.3 , 12.3 ; p < 0.05 ) and 60 days ( mean difference = 8.3 ; se = 2.7 ; 95% ci : 1.7 , 14.8 ; p < 0.01 ) for the total sample . for social functioning , the fixed effect for time by randomization ( f[2,85.1 ] = 2.5 , 
p = 0.09 ) was not significant , and the effect for time ( f[2,85.1 ] = 5.9 ,  p < 0.01 ) was significant , but the effect for randomization was nonsignificant .
post hoc comparisons revealed that the placebo group score was significantly higher than the max stress b group ( mean difference = 16.6 ; se = 6.6 ; 95% ci : 3.3 , 29.9 ; p < 0.05 ) at 30 days .
for the placebo group , the score at 30 days ( mean difference = 14.8 ; se = 4.5 ; 95% ci : 3.9 , 25.7 ; p < 0.01 ) and 60 days ( mean difference = 11.3 ; se = 4.7 ; 95% ci : 0.1 , 22.8 ; p = 0.05 ) significantly improved compared to baseline . for
role - emotional , the fixed effect for time ( f[2,77.4 ] = 5.3 , p < 0.01 ) was significant , but the effects for randomization and time by randomization were nonsignificant .
post hoc comparisons revealed that the score significantly increased from baseline to 30 days ( mean difference = 10.3 ; se = 3.6 ; 95% ci : 1.4 , 19.2 ; p < 0.05 ) and 60 days ( mean difference = 10.3 ; se = 3.9 ; 95% ci : 0.7 , 19.8 ; p < 0.05 ) for the total sample . for mental health ,
the fixed effects for time by randomization ( f[2,92.1 ] = 3.6 ,  p < 0.05 ) and time ( f[2,92.1 ] = 13.6 ,  p < 0.01 ) were significant , but the effect for randomization was nonsignificant .
post hoc comparisons revealed that the placebo group score was significantly higher than the max stress b group ( mean difference = 13.9 ; se = 6.2 ; 95% ci : 1.5 , 26.2 ; p < 0.05 ) at 30 days .
for the max stress b group , the scores at 30 days ( mean difference = 9.5 ; se = 3.5 ; 95% ci : 0.9 , 18.2 ; p < 0.05 ) and 60 days ( mean difference = 15.8 ; se = 3.4 ; 95% ci : 7.6 , 24.0 ; p < 0.01 ) were significantly improved compared to baseline . for the placebo group , the score at 30 days ( mean difference = 13.0
; se = 3.6 ; 95% ci : 4.2 , 21.8 ; p < 0.01 ) significantly improved , but not at 60 days .
in the current study , we have demonstrated moderate short - term ( 60 days ) improvements in depression , anxiety , and overall mental health with the max stress b product , which contains several whole - food nutrients .
globally , the bdi and bai are valid and reliable assessments used to detect many symptoms of depression and anxiety , respectively [ 17 , 18 ] , and both study groups demonstrated improved scores from baseline on both assessment tools .
the max stress b group showed greater improvement on the bai , while the placebo group demonstrated greater improvement on the bdi ( 25% versus 22% and 34% versus 39% , respectively ) .
however , the max stress b group achieved a more continuous decrease throughout the protocol , while the placebo group had less or no improvement from 30 to 60 days . considering the positive trend demonstrated by the max stress b group , our study
thus , our findings are modestly similar to those of others showing that dietary supplements have the ability to improve certain aspects of mood [ 1115 ] .
in addition to some mood benefits , the max stress b arm showed positive effects on the mental health scale according to the sf-36 .
our findings are consistent with another study that showed improvements in mood ( depression and anxiety ) along with memory , concentration , and fatigue in response to consuming ginkgo biloba .
another recent study found that ginkgo biloba was beneficial on scores of neuropsychiatric impairment , including apathy and depression / dysphoria , compared to placebo in a sample of adults with dementia
. an additional study showed some improvement in ratings of depression and cognition after taking ginkgo biloba in a sample of adults who had alzheimer 's .
thus , our findings appear to support other research that max stress b , similar to other nutrients , has the ability to improve subjective ratings of mental health . in summary
, we have showed that max stress b offers utility for improving the overall mental health quality of life of adults with mdd or another depressive disorder with no side effects .
furthermore , future trials should include longer interventions to more firmly determine the effect of max stress b on mental health and mood of adults suffering from depressive disorders .
we enrolled english speaking individuals only , so our results may not be generalizable to non - english speaking persons of different racial / ethnic backgrounds .
our findings may be restricted by the length of the intervention , given that mood disorder symptom changes may take longer than 60 days to occur .
we did not assess dietary intake ; thus , we were not able to control for possible influences that variable may have had on our final results
. however , we did assess physical activity levels , which were found to be unrelated to the outcome variables .
furthermore , we did not restrict or change the use of medications by our participants , such as the use of steroids , antidepressants , or anti - inflammatory agents , given the ethical considerations associated with such decision .
the findings of our study are also potentially limited by a small sample size in each study arm
. a larger sample size could result in even more significant findings for mood symptoms and quality of life .
assessing the changes in homocysteine and depression and anxiety scores could have provided useful information and would be of interest in future trials .
depression is a significant problem that is increasing in prevalence . in fact , approximately 15 million adults have mdd , and the prevalence of mdd and its associated financial costs are a significant drain on an already overburdened united states health system and are getting worse .
this disease shows signs of spiraling out of control , as options for prevention or treatment are limited .
thus , any safe intervention that demonstrates promise for either sustaining mood or improving the condition of persons with mdd or another depressive disorder is urgently needed . the formula used in the current study
the max stress b formula showed modest improvements in mood and mental health according to the bdi , bai , and sf-36 , making our findings consistent with the prior studies .
thus , our study shows that a high quality , whole - food dietary supplement may offer an opportunity for adults with depression to improve mood symptoms and quality of life .
 depression , the most common type of mental illness , is the second leading cause of disability and is increasing among americans . 
 the effect of improved nutrition , particularly with dietary supplements , on depression may provide an alternative to standard medical treatment . 
 some studies have shown that certain nutrients ( e.g. , inositol and s - adenosyl methionine ) are effective at improving depressed mood , although the results are not unequivocal . 
 the current study was a randomized , double - blind , placebo - controlled trial to evaluate the efficacy of a vitamin b complex nutritional supplement ( max stress b ) for improving depressive and anxiety symptoms according to the beck depression and anxiety inventories ( bdi and bai ) in 60 adults diagnosed with major depression or other forms of depressive disorders . 
 secondary outcomes included quality of life according to the sf-36 . 
 participants were assessed at baseline and 30- and 60-day followups . 
 
 max stress b showed significant and more continuous improvements in depressive and anxiety symptoms , compared to placebo . 
 additionally , max stress b showed significant improvement on the mental health scale of the sf-36 compared to placebo . 
 thus , we showed modest utility of max stress b to improve mood symptoms and mental health quality of life in adults with depression . 
1. Introduction
2. Methods
3. Results
4. Discussion
5. Conclusions