Effects of zinc, vitamin D, and their co-supplementation on mood, serum cortisol, and brain-derived neurotrophic factor in patients with obesity and mild to moderate depressive symptoms: A phase II, 12-wk, 2 × 2 factorial design, double-blind, randomized, placebo-controlled trial

Probably not a substantial claim: may not pass S3 (load-bearing).

Supplementation with 400 IU of vitamin D combined with 1,000 mg of elemental calcium on measures of depression in a randomized, double-blinded US trial comprising 36,282 postmenopausal women did not affect depression symptoms.

“Supplementation with 400 IU of vitamin D combined with 1,000 mg of elemental calcium on measures of depression in a randomized, double-blinded US trial comprising 36,282 postmenopausal women did not affect depression symptoms (56).”

• cites [56] Al-Dujaili, 2016, Effect of vitamin D supplementation on cardiovascular disease risk factors and exercise performance in healthy participants: a randomized placebo-controlled preliminary study, Ther Adv Endocrinol Metab sourceDisputed

  The Study design section (page unavailable) describes a single-blinded trial of 15 participants given 2,000 IU of vitamin D or placebo for two weeks—not a double-blinded trial of 36,282 postmenopausal women given vitamin D and calcium. The Abstract lists cardiovascular, cortisol, and exercise outcomes, not depression symptoms. (LLM, conf=0.87)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

Evidence suggests that zinc homeostasis and function may be increased following vitamin D supplementation, and that the control of zinc in systemic levels is regulated by vitamin D.

“there is evidence to suggest that zinc homeostasis and function may be increased following vitamin D supplementation, and that the control of zinc in systemic levels is regulated by vitamin D (47).”

• cites [47] Sepehrmanesh, 2015, Vitamin D supplementation affects the Beck Depression Inventory, insulin resistance, and biomarkers of oxidative stress in patients with major depressive disorder: a randomized, controlled clinical trial, 2, J Nutr sourceCould not verify

  The Introduction discusses calcium homeostasis, and the Results table reports calcium and metabolic measures, but neither addresses zinc. Searches of our copy for “zinc,” “zinc homeostasis and function,” and systemic zinc regulation found no passage supporting the attributed claim. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Some work has reported no evidence for a significant association between zinc and depression.

“some work has reported that there is no evidence for the significant association between zinc and depression (34).”

• cites [34] Vieth, 2004, Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients, Nutr J sourceCould not verify

  The Methods (Questionnaire) and Conclusions discuss vitamin D supplementation, wellbeing, and depressive symptoms, not zinc. A search of our full-text copy for “zinc” and “zinc depression association” found no passage addressing whether zinc is significantly associated with depression. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Zongyao Li noted a significant inverse association between dietary zinc intake and risk of depression.

“Similarly, Zongyao Li noted a significant inverse association between dietary zinc intake and risk of depression (44).”

• cites [44] Ghassemzadeh, 2005, Psychometric properties of a Persian‐language version of the Beck Depression Inventory‐Second edition: BDI‐II‐PERSIAN, Depress Anxiety sourceCould not verify

  The Concurrent Validity and Factor Structure sections examine correlations between depression measures and the properties of the BDI-II-Persian. Searches for dietary zinc intake, depression risk, and Zongyao Li found no passage addressing the claimed inverse association. (LLM, conf=0.77)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Several biological mechanisms for the beneficial effects of zinc and vitamin D on depression have been proposed.

“Several biological mechanisms for the beneficial effects of zinc and vitamin D on depression have been proposed (44,60).”

• cites [44] Ghassemzadeh, 2005, Psychometric properties of a Persian‐language version of the Beck Depression Inventory‐Second edition: BDI‐II‐PERSIAN, Depress Anxiety sourceCould not verify

  The Introduction and Factor Structure sections discuss the Beck Depression Inventory and its psychometric properties, not biological mechanisms of depression. Searches for zinc, vitamin D, and their proposed beneficial mechanisms found no relevant passage in our copy; page numbers were not provided. (LLM, conf=0.77)

  Experimental — accuracy not yet measured
• cites [60]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

In Ranjbar et al, it was reported that serum levels of BDNF in depressed patients receiving zinc supplement did not increase.

“In Ranjbar et al, it was reported that serum levels of BDNF in depressed patients receiving zinc supplement did not increase (51).”

• cites [51] Bertone-Johnson, 2009, Vitamin D and the occurrence of depression: causal association or circumstantial evidence?, Nutr Rev sourceCould not verify

  The section on a randomized trial of vitamin D supplementation reports changes in depression scores, not serum BDNF after zinc supplementation. Searches for Ranjbar, zinc supplementation, and brain-derived neurotrophic factor found no passage in our copy addressing the claimed result. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The trial used the validated Persian version of the Beck Depression Inventory-II (BDI-II).

“The trial used the validated Persian version of Beck depression inventory-II (BDI-II) (50)”

• cites [50] Shaffer, 2014, Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials, Psychosom Med sourceCould not verify

  The Results (Trial Characteristics; page unavailable) say the reviewed trials used varying instruments to assess depressive symptoms, but do not identify a validated Persian BDI-II. Searches for “Persian” and “BDI-II” found no passage establishing that the trial used that version. (LLM, conf=0.75)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The baseline mean of the BDI-II score was 19.21±7.34 for the whole population.

“The baseline mean of the BDI-II score was 19.21±7.34,for the whole population.”

May combine two claims.

There were significant differences in serum zinc (p<0.001), vitamin D (p<0.001), cortisol (p=0.049) and BDNF (p=0.004) between the study groups at baseline.

“We found significant differences in serum zinc (p<0.001),vitamin D (table 3) (p<0.001),cortisol (p=0.049) and BDNF (p=0.004)(table 2) between the study groups at baseline.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In total, 15 patients declined to complete the intervention and were excluded from subsequent analysis.

“In total, 15 patients declined to complete the intervention, and were therefore excluded from subsequent analysis (diagram 1).”

May combine two claims.

The trial was conducted among 140 overweight/obese adult subjects aged >20 years with BDI-II≥10.

“was conducted among 140 overweight/obese (BMI> 27 kg/m 2 ) adult subjects aged > 20 years with BDI-II≥10.”

May combine two claims.

From baseline to 12 weeks, mean serum cortisol changed by -1.37 in the zinc group, -1.66 in the vitamin D group, -0.82 in the zinc-vitamin D group, and -1.19 in the placebo group, with no significant between-group difference (P=0.974).

“Cortisol | -1.37 (-3.43, 0.67) | -1.66 (-3.71, 0.38) | -0.82 (-3.52. 1.88) | -1.19 (-3.29, 0.90) | 0.974 | 0.056”

May combine two claims.

In the present study, after 12 weeks of treatment with zinc, serum levels of BDNF dropped significantly compared to baseline, but were not statistically different as compared to the placebo group.

“in the present study, after 12 weeks of treatment with zinc, serum levels of BDNF dropped significantly compared to baseline, but were not statistically different as compared to the placebo group.”

May combine two claims.

From baseline to 12 weeks, mean BDI-II score decreased by 7.02 points in the zinc group, 3.87 in the vitamin D group, 7.62 in the zinc-vitamin D group, and 0.76 in the placebo group.

“BDI-II score | -7.02 (-9.13, -4.74) | -3.87 (-6.15, -1.59) | -7.62 (-10.63, -4.61) | -0.76 (-3.05, 1.52) | 0.0001 * | 0.969”

May combine two claims.

From baseline to 12 weeks, mean serum BDNF changed by -0.19 in the zinc group, -0.11 in the vitamin D group, 0.19 in the zinc-vitamin D group, and -0.17 in the placebo group, with no significant between-group difference (P=0.08).

“BDNF | -0.19 (-0.36, -0.02) | -0.11 (-0.28, 0.05) | 0.19 (-0.02, 0.41) | -0.17 (-0.34, -0.003) | 0.08 | 0.589”

Classified as probably not a substantial claim.

Nutritional intervention can be considered an effective alternative or adjunct, preventive or treatment strategy to pharmacotherapy in depression.

“nutritional intervention can be considered as an effective alternative or adjunct, preventive or treatment strategy to pharmacotherapy in depression (19).”

• cites [19] Jorde, 2008, Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial, J Intern Med sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Mood disorders, particularly depression, are among the most prevalent mental health symptoms in patients with obesity.

“Mood disorders, particularly depression, are one of the most prevalent mental health symptoms in patients with obesity (1)(2)(3).”

• cites (1)(2)(3)Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Patients with obesity can suffer from major depression.

“Several studies have reported that patients with obesity can suffer with major depression (4)(5)(6).”

• cites (4)(5)(6)Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Clinically depressed patients have abnormalities in the hypothalamic-pituitary-adrenal axis, particularly in cortisol regulation, which is related to obesity.

“A growing evidence base indicates that there are abnormalities in the hypothalamic-pituitary-adrenal axis, particularly in the regulation of cortisol, in clinically depressed patients, which is, in turn, related to obesity (10)(11)(12).”

• cites (10)(11)(12)Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Zinc deficiency can induce depressive-like behavior, and the symptom can be effectively reversed by zinc supplementation.

“Zinc deficiency can induce depressive-like behavior, and in this instance, the symptom can be effectively reversed by zinc supplementation (24,25).”

• cites [24] Nowak, 2003, Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study, Pol J PharmacolNot checked — no full text of the source
• cites [25] Siwek, 2009, Zinc supplementation augments efficacy of imipramine in treatment resistant patients: a double blind, placebo-controlled study, J Affect Disord sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Analyses were performed based on a per-protocol approach.

“The analyses were performed based on a perprotocol approach.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The trial was performed according to the principles of Declaration of Helsinki, and the study protocol was approved by the institutional ethics committee of Iran University of Medical Sciences.

“This trial was performed according to the principles of the Declaration of Helsinki, and the study protocol was approved by the institutional ethics committee of Iran University of Medical Sciences (IR.IUMS.REC 1395.9221324205).”

Classified as probably not a substantial claim.

ANCOVA was adjusted by baseline serum zinc, vitamin D, cortisol, BDNF and Beck depression score.

“applied analysis of co-variance (ANCOVA; adjusted by baseline serum zinc, vitamin D, cortisol, BDNF and beck depression score).”

Classified as probably not a substantial claim.

Previous studies have shown that vitamin D or zinc supplementation, individually, may improve depression severity.

“Previous studies have shown that vitamin D or zinc supplementation, individually, may improve depression severity (13,23)”

• cites [13] Rush, 2006, Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report, Am J Psychiatry sourceNot checked — no full text of the source
• cites [23] Szewczyk, 2011, The role of zinc in neurodegenerative inflammatory pathways in depression, Prog Neuropsychopharmacol Biol Psychiatry sourceNot checked — no full text of the source

May combine two claims.

Only one randomized control trial has examined the effects of zinc monotherapy on BDI-II score in obese patients, and it resulted in a decreased BDI-II score.

“only one randomized control trial has examined the effects of zinc monotherapy on BDI-II score in obese patients, which resulted in a decreased BDI-II score (13).”

• cites [13] Rush, 2006, Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report, Am J Psychiatry sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Serum cortisol was measured by ELISA with inter- and intra-assay coefficients of variation of 11% and 5.1%.

“ELISA methods were used to measure serum cortisol (diametra, Italy).The inter-and intra-assay coefficients of variation of this method were 11% and 5.1%.respectively.”

Classified as probably not a substantial claim.

The placebo was indistinguishable in color, shape, size, packaging, and taste from vitamin D and zinc tablets.

“The appearance of the placebo was indistinguishable in color, shape, size, packaging, and taste from vitamin D and zinc tablets.”

Probably not a substantial claim: may not pass S3 (load-bearing).

This has been disputed in some empirical work.

“although this has been disputed in some empirical work (34)(35)(36).”

• cites (34)(35)(36)Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The trial was registered in the Iranian Web site for registration of clinical trials.

“This trial was registered in the Iranian Web site (www.irct.ir)for registration of clinical trials (http://www.irct.ir:IRCT201601252394N31-31-10-2016).”

May combine two claims.

Only one study has examined the effects of vitamin D monotherapy on BDI-II in obese patients with pre-existing depressive symptoms, and it suggested that high doses of vitamin D can ameliorate depression symptoms.

“only one study has examined the effects of vitamin D monotherapy on BDI-II in obese patients with pre-existing depressive symptoms, where the authors suggested that supplementation of high doses of vitamin D can ameliorate depression symptoms (23).”

• cites [23] Szewczyk, 2011, The role of zinc in neurodegenerative inflammatory pathways in depression, Prog Neuropsychopharmacol Biol Psychiatry sourceNot checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

Depression status was evaluated by BDI-II questionnaire, and those with BDI-II score greater than 10 were considered eligible.

“The depression status was evaluated by Beck Depression Inventory-II (BDI-II) questionnaire, and those who had a BDI-II score greater than 10 points were considered as eligible for current the trial.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Randomized assignment was performed using balanced block randomization method.

“Randomized assignment was performed using balanced the block randomization method.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Serum BDNF was quantified using ELISA with inter- and intra-assay coefficients of variation of 10% and 8%.

“Serum BDNF was quantified using the ELISA method (crystalday, china).The inter-and intra-assay coefficients of variation of this method were 10% and 8% respectively.”

Classified as probably not a substantial claim. May combine two claims.

Meta-analyses have concluded that although there is evidence supporting the use of zinc/vitamin D for depression, available research needs to be confirmed by larger RCT and prospective cohort studies.

“Several meta-analyses have evaluated effect of zinc/vitamin D on depression (40)(41)(42)(43) , concluding that, although there is evidence supporting their use, available research needs to be confirmed by larger RCT and prospective cohort studies (44)(45)(46).”

• cites (40)(41)(42)(43)Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites (44)(45)(46)Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Compliance was assessed by fortnightly tablet count.

“a tablet count was performed fortnightly by the investigator to assess compliance.”

Classified as probably not a substantial claim.

Participants were randomized to four groups in a 1:1:1:1 ratio.

“assigned to one of the four groups via the balanced block randomization method (in a 1:1:1:1 ratio)”

Probably not a substantial claim: may not pass S3 (load-bearing).

In cases of minor imbalances, adjustment for these variables was made in analyses.

“In cases of minor imbalances, adjustment for these variables will be made our analyses.”

Classified as probably not a substantial claim.

The present study was a 12-week 2 × 2 factorial design randomized double-blind placebo-controlled trial.

“The present study was a 12-week 2 × 2 factorial design randomized double-blind placebo controlled trial”

Classified as probably not a substantial claim.

All research staff including investigators and laboratory technicians, as well as participants, were blinded to the random allocation.

“All research staff including investigators and laboratory technicians, as well as participants, were blinded to the random allocation.”

May combine two claims.

Sample size was calculated using standard formula for factorial design, with type I error 0.05 and type II error 0.20, based on previous study (13), using SD 5.698 and mean difference 2.92 in BDI-II score, requiring 33 persons per group.

“To calculate sample size, we used the standard formula suggested for factorial design, clinical trials by considering type I error (a) of 0.05 and type II error (b) of 0.20.Based on a previous study (13), we used 5.698 as the standard deviation and 2.92 as the mean difference in BDI-II score as a variable primary outcome.Based on this, we required 33 persons in each group.”

• cites [13] Rush, 2006, Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report, Am J Psychiatry sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

To ensure baseline characteristics balance was achieved by randomization, analyses were conducted for baseline characteristics (zinc, vitamin D, age, sex, BMI, weight, height).

“To ensure that baseline characteristics balance was achieved by the randomization, analyses was conducted for baseline characteristics (zinc, vitamin D, age, sex, BMI, weight, height).”

Probably not a substantial claim: may not pass S3 (load-bearing).

In a double-blinded, placebo controlled prospective trial, involving 489 postmenopausal elderly women, there was no effect of hormone therapy and calcitriol, either individually or in combination, on depression.

“In a double-blinded, placebo controlled prospective trial, involving 489 postmenopausal elderly women, there was no effect of hormone therapy and calcitriol, either individually or in combination, on depression (55).”

• cites [55] Swardfager, 2013, Potential roles of zinc in the pathophysiology and treatment of major depressive disorder, Neurosci Biobehav Rev sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

Participants in our study were obese individuals with MDD, who might have an increased need to vitamin D.

“Participants in our study were obese individuals with MDD, who might have an increased need to vitamin D.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The drop in BDNF in the zinc group may be related to a placebo effect, because the placebo group had a significant reduction in levels of BDNF, while no concurrent reduction in depression was noted.

“This may conceivably be related to a placebo effect, because the placebo group had a significant reduction in levels of BDNF, while no concurrent reduction in depression was noted.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The neurotrophin hypothesis of depression, mainly based on the inverse association between stress and BDNF levels, is one of the most popular hypotheses in the pathophysiology of depression.

“'Neurotrophin hypothesis of depression', mainly based on the inverse association between stress and brain-derived neurotrophic factor (BDNF) levels, is one of the most popular hypotheses in the pathophysiology of depression (61).”

• cites [61]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Other mechanisms have been proposed to mediate the effects of zinc and vitamin D on depression, including modulation of the HPA axis.

“Other mechanisms have been proposed to mediate the effects of zinc and vitamin D on depression, including modulation of the hypothalamus-pituitary-adrenal (HPA) axis (63).”

• cites [63]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Normal status in zinc at baseline and continuity of vitamin D deficiency at study cessation in the zinc-vitamin D group could explain this finding.

“normal status in zinc at baseline and continuity of vitamin D deficiency at study cessation in the zinc-vitamin D group could explain this finding.”

May combine two claims.

A large randomized trial in older women assessed the effect of a single annual dose of 500 kIU vitamin D for 3-5 y, and did not find any effect of vitamin D supplementation on depression symptom.

“A large randomized trial in older women assessed the effect of a single annual dose of 500 kIU vitamin D for 3-5 y, and did not find any effect of vitamin D supplementation on depression symptom (35);”

• cites [35] Li, 2014, Efficacy of vitamin D supplementation in depression in adults: a systematic review, J Clin Endocrinol Metab sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In Solati et al., zinc supplementation resulted in increased serum BDNF levels.

“In Solati, et al., zinc supplementation resulted in increased serum BDNF levels (13).”

• cites [13] Rush, 2006, Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report, Am J Psychiatry sourceNot checked — no full text of the source

May combine two claims.

The current trial suggests a causal association between zinc status and depression in obese/overweight subjects, and that greater depression improvement is manifest in zinc, compared to vitamin D, supplementation.

“The current trial suggests a causal association between zinc status and depression in obese/overweight subjects, and that greater depression improvement is manifest in zinc, compared to vitamin D, supplementation.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Some studies have reported a beneficial effect of vitamin D supplementation on depression.

“some studies have reported a beneficial effect of vitamin D supplementation on depression (23).”

• cites [23] Szewczyk, 2011, The role of zinc in neurodegenerative inflammatory pathways in depression, Prog Neuropsychopharmacol Biol Psychiatry sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Expression of BDNF has been reported to be down-regulated in depressed patients, compared to non-depressed matched controls.

“Expression of BDNF has been reported to be down-regulated in depressed patients, compared to non-depressed matched controls (62),”

• cites [62]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

A trial conducted in elderly patients with MDD showed that a single 300-kIU dose of vitamin D results in a decreased score of depression.

“a trial conducted in elderly patients with MDD showed that a single 300-kIU dose of vitamin D results in a decreased score of depression (57);”

• cites [57] Marreiro, 2002, Zinc nutritional status in obese children and adolescents, Biol Trace Elem Res sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

A recent meta-analysis, which included nine trials with a total of 4923 participants, concluded that no significant reduction in depression was seen after vitamin D supplementation.

“A recent meta-analysis, which included nine trials with a total of 4923 participants, concluded that no significant reduction in depression was seen after vitamin D supplementation (45).”

• cites [45] Ranjbar, 2014, Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression, Nutr Neurosci sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Daily physiological and behavioral rhythms, including sleep and body temperature, can significantly influence cortisol concentration, and these were not controlled in the present study.

“Furthermore, daily physiological and behavioral rhythms including sleep, and body temperature can significantly influence cortisol concentration, which we could not control in the present study.”

Probably not a substantial claim: may not pass S3 (load-bearing).

BDNF is shown to increase after chronic antidepressant administration.

“however, it is shown to increase after chronic antidepressant administration (62).”

• cites [62]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Supplementation with zinc, vitamin D, or joint zinc-vitamin D can improve BDI-II score in obese patients with depressive symptoms.

“Supplementation with zinc, vitamin D or joint zinc-vitamin D can improve BDI-II score in obese patients with depressive symptoms.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Weekly supplementation with 40000 IU vitamin D for 6 months had no significant effect on depressive symptom scores, when compared with placebo.

“further work reported that weekly supplementation with 40000 IU vitamin D for 6 months had no significant effect on depressive symptom scores, when compared with placebo (54).”

• cites [54] Dallman, 2006, Glucocorticoids, chronic stress, and obesity, Prog Brain Res sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In a study of 441 obese subjects, supplementation with 20.000 or 40.000 IU vitamin D per week for 1 year ameliorates depression symptoms.

“in a study of 441 obese subjects, it was indicated that supplementation with 20.000 or 40.000IU vitamin D per week for 1 year ameliorates depression symptoms (23).”

• cites [23] Szewczyk, 2011, The role of zinc in neurodegenerative inflammatory pathways in depression, Prog Neuropsychopharmacol Biol Psychiatry sourceNot checked — no full text of the source

May combine two claims.

The sample size calculation was based on the variability in depression score and may not have been adequate for the analysis of serum cortisol as a secondary outcome.

“Second, our sample size calculation was based on the variability in depression score, and may not have been adequate for the analysis of serum cortisol as a secondary outcome.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The regression to mean phenomenon may be considered as an alternative explanation for the changes in BDNF in the zinc and placebo groups.

“the regression to mean phenomenon, where if a variable is extreme on its first measurement, it will tend to be closer to the average on its second measurement-and if it is extreme on its second measurement, it will tend to have been closer to the average on its first, may be considered as an alternative explanation for the changes in BDNF in the zinc and placebo groups.”

May combine two claims.

Despite randomization, serum zinc and vitamin D levels at baseline were unequal, but these variables were adjusted for in the applied analysis.

“Finally, in the current trial, despite the randomization, serum zinc and vitamin D level at baseline were unequal, however, these variables were adjusted accordingly in the applied analysis.”