1: Zinc and Antidepressant Therapy
Polish Journal of Pharmacology Pol. J. Pharmacol., 2003, 55, 1143–1147 ISSN 1230-6002
Effect of Zinc Suppldmentation on Antidepressant Therapy in Unipolar Depression: A Priliminary Placebo-Controlled Study
Gabriel Nowak1,3,#, Marcin Siwek2, Dominika Dudek2, Andrzej Ziêba2,
A growing body of evidence implicates a derangement of zinc homeostasis in mood disorders. In general, unipolar depression is connected with low blood zinc levels that are increased by effective antidepressant therapy. A placebo-controlled, double blind pilot study of zinc supplementation in antidepressant therapy was conducted in patients who fulfilled DSM IV criteria for major (unipolar) depression. Patients received zinc supplementation (6 patients; 25 mg of Zn2+ once daily) or placebo (8 patients) and were treated with standard antidepressant therapy (tricyclic antidepressants, selective serotonin reuptake inhibitors). Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) were used to assess efficacy of antidepressant therapy, and patients’ status was evaluated before the treatment and 2, 6 and 12 weeks after its commencement. Antidepressant treatment significantly reduced HDRS scores by the 2nd week of treatment in both groups, and lowered BDI scores at the 6th week in zinc-treated group. Zinc supplementation significantly reduced scores in both measures after 6- and 12-week supplementation when compared with placebo treatment. This preliminary study is the first demonstration of the benefit of zinc supplementation in antidepressant therapy. The mechanism(s) may be related to modulation of glutamatergic or immune systems by zinc ion.
2: The Effect of Zinc on Immune Cells
Mol Med. 2008 May-Jun; 14(5-6): 353–357.
Published online 2008 Apr 3. doi: 10.2119/2008-00033.Prasad
Zinc in Human Health: Effect of Zinc on Immune Cells
Ananda S Prasad
Although the essentiality of zinc for plants and animals has been known for many decades, the essentiality of zinc for humans was recognized only 40 years ago in the Middle East. The zinc-deficient patients had severe immune dysfunctions, inasmuch as they died of intercurrent infections by the time they were 25 years of age. In our studies in an experimental human model of zinc deficiency, we documented decreased serum testosterone level, oligospermia, severe immune dysfunctions mainly affecting T helper cells, hyperammonemia, neurosensory disorders, and decreased lean body mass. It appears that zinc deficiency is prevalent in the developing world and as many as two billion subjects may be growth retarded due to zinc deficiency. Besides growth retardation and immune dysfunctions, cognitive impairment due to zinc deficiency also has been reported recently. Our studies in the cell culture models showed that the activation of many zinc-dependent enzymes and transcription factors were adversely affected due to zinc deficiency. In HUT-78 (T helper 0 [Th(0)] cell line), we showed that a decrease in gene expression of interleukin-2 (IL-2) and IL-2 receptor alpha(IL-2Ralpha) were due to decreased activation of nuclear factor-kappaB (NF-kappaB) in zinc deficient cells. Decreased NF-kappaB activation in HUT-78 due to zinc deficiency was due to decreased binding of NF-kappaB to DNA, decreased level of NF-kappaB p105 (the precursor of NF-kappaB p50) mRNA, decreased kappaB inhibitory protein (IkappaB) phosphorylation, and decreased Ikappa kappa. These effects of zinc were cell specific. Zinc also is an antioxidant and has anti-inflammatory actions. The therapeutic roles of zinc in acute infantile diarrhea, acrodermatitis enteropathica, prevention of blindness in patients with age-related macular degeneration, and treatment of common cold with zinc have been reported. In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8. We have reported recently that in both young adults and elderly subjects, zinc supplementation decreased oxidative stress markers and generation of inflammatory cytokines.
3: Clinical Study Reviews:
Zinc for treating the common cold: review of all clinical trials since 1984:
All eight publications since 1984 that have reported a total of 10 clinical studies of the treatment of common colds with zinc are reviewed. The reasons for the puzzling mix of diametrically opposite results in these studies are elucidated and related to independent in vitro investigations. A theoretical framework is put forth that explains the beneficial effects of zinc and that has a solid foundation based on the known molecular structures of the surface of human rhinovirus and intercellular adhesion molecule-1, the docking point for human rhinovirus present on the surfaces of cells of the nasal epithelium. The results of clinical investigations and theory suggest that consistently beneficial therapeutic effects can be expected of zinc ions from zinc gluconate with glycine in lozenges prepared according to homeopathic principles and procedures. The latest study published used an "intent to treat" statistical model, and the highly beneficial effects of zinc found in that study could not be compared directly with results from any earlier studies. Raw data from that study were therefore reanalyzed on the basis of assessable patients, and the results show an even better effect and can be compared directly with earlier findings. No side effects or adverse experiences due to zinc that were serious, disturbing, or persistent were found in any of the 10 studies.
4: Zinc and Insomnia
Journal of the American Geriatric Society: 2011 Jan;59(1): 82-90
The effect of melatonin, magnesium, and zinc on primary insomnia in long-term care facility residents in Italy: a double-blind, placebo-controlled clinical trial.
OBJECTIVES: To determine whether nightly administration of melatonin, magnesium, and zinc improves primary insomnia in long-term care facility residents.
DESIGN: Double-blind, placebo-controlled clinical trial.
SETTING: One long-term care facility in Pavia, Italy.
PARTICIPANTS: Forty-three participants with primary insomnia (22 in the supplemented group, 21 in the placebo group) aged 78.3 ± 3.9.
INTERVENTION: Participants took a food supplement (5 mg melatonin, 225 mg magnesium, and 11.25 mg zinc, mixed with 100 g of pear pulp) or placebo (100 g pear pulp) every day for 8 weeks, 1 hour before bedtime.
MEASUREMENTS: The primary goal was to evaluate sleep quality using the Pittsburgh Sleep Quality Index. The Epworth Sleepiness Scale, the Leeds Sleep Evaluation Questionnaire (LSEQ), the Short Insomnia Questionnaire (SDQ), and a validated quality-of-life instrument (Medical Outcomes Study 36-item Short Form Survey (SF-36)) were administered as secondary end points. Total sleep time was evaluated using a wearable armband-shaped sensor. All measures were performed at baseline and after 60 days.
RESULTS: The food supplement resulted in considerably better overall PSQI scores than placebo (difference between groups in change from baseline PSQI score=6.8; 95% confidence interval=5.4-8.3, P<.001). Moreover, the significant improvements in all four domains of the LSEQ (ease of getting to sleep, P<.001; quality of sleep, P<.001; hangover on awakening from sleep, P=.005; alertness and behavioral integrity the following morning, P=.001), in SDQ score (P<.001), in total sleep time (P<.001), and in SF-36 physical score (P=.006) suggest that treatment had a beneficial effect on the restorative value of sleep.
CONCLUSION: The administration of nightly melatonin, magnesium, and zinc appears to improve the quality of sleep and the quality of life in long-term care facility residents with primary insomnia.
© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society