Broad-spectrum Micronutrients Research Articles

Novel and complementary treatment approaches in attention-deficit/hyperactivity disorder.

To provide an updated review of novel and complementary treatment approaches for children and adolescents with attention-deficit/hyperactivity disorder. The evidence for complementary attention-deficit/hyperactivity disorder treatments is often promising, but limited to small, unblinded studies. Recent evidence from larger, more rigorous studies reveals that most of these treatments have modest efficacy. Omega-3 polyunsaturated fatty acids, saffron, broad spectrum micronutrients, and physical exercise have potential benefits that seem to outweigh known risks. However, neurofeedback, cognitive training, and trigeminal nerve stimulation need further research to determine whether specific sub-groups of children/adolescents with attention-deficit/hyperactivity disorder would benefit long-term with their associated tolerable risks. There is not sufficient evidence for complementary treatments to be recommended as substitutes for first-line pharmacological and psychosocial treatment options. Nonetheless, some adjuvant therapies to currently recommended attention-deficit/hyperactivity disorder treatments can be safe. Physicians should be familiar with existing and emerging complementary treatments to help guide families.

Efficacy and safety of a mineral and vitamin treatment on symptoms of antenatal depression: 12-week fully blinded randomised placebo-controlled trial (NUTRIMUM).

Broad-spectrum micronutrients (minerals and vitamins) have shown benefit for treatment of depressive symptoms. To determine whether additional micronutrients reduce symptoms of antenatal depression. Eighty-eight medication-free pregnant women at 12-24 weeks gestation, who scored ≥13 on the Edinburgh Postnatal Depression Scale (EPDS), were randomised 1:1 to micronutrients or active placebo (containing iodine and riboflavin), for 12 weeks. Micronutrient doses were generally between recommended dietary allowance and tolerable upper level. Primary outcomes (EPDS and Clinical Global Impression - Improvement Scale (CGI-I)) were analysed with constrained longitudinal data analysis. Seventeen (19%) women dropped out, with no group differences, and four (4.5%) gave birth before trial completion. Both groups improved on the EPDS, with no group differences (P = 0.1018); 77.3% taking micronutrients and 72.7% taking placebos were considered recovered. However, the micronutrient group demonstrated significantly greater improvement, based on CGI-I clinician ratings, over time (P = 0.0196). The micronutrient group had significantly greater improvement on sleep and global assessment of functioning, and were more likely to identify themselves as 'much' to 'very much' improved (68.8%) compared with placebo (38.5%) (odds ratio 3.52, P = 0.011; number needed to treat: 3). There were no significant group differences on treatment-emergent adverse events, including suicidal ideation. Homocysteine decreased significantly more in the micronutrient group. Presence of personality difficulties, history of psychiatric medication use and higher social support tended to increase micronutrient response compared with placebo. This study highlights the benefits of active monitoring on antenatal depression, with added efficacy for overall functioning when taking micronutrients, with no evidence of harm. Trial replication with larger samples and clinically diagnosed depression are needed.

Problems most concerning to parents of children with ADHD and emotional dysregulation in a randomized controlled trial of multinutrients: MADDY secondary analysis.

With dual focus on structured, objective quantification of parent observations of child's behavior and identifying behaviors most amenable to change, this report examines Parent Target Problems (PTP) as a secondary outcome in a randomized clinical trial (RCT) of children with attention-deficit/ hyperactivity disorder (ADHD) in which one primary outcome, Clinical Global Impression-Improvement, showed a significant advantage of multinutrients over placebo and the other, Likert-type parent ratings, showed significant improvement in both groups, without significant difference between them. In a multisite 8-week RCT of broad-spectrum micronutrients ("multinutrients"), parents of children ages 6-12 (N = 126, 73% male, 88% white) with ADHD and emotional dysregulation nominated their child's most concerning problem(s) at baseline and quantified them by frequency, duration, impairment, and consequences. At subsequent visits, parents re-quantified the problem(s). Blinded child psychiatrists independently reviewed the PTPs and rated change at two timepoints compared to baseline. PTPs were grouped into 9 categories. Mean ratings were compared between active and placebo groups and explored by category. By week 8, a significant separation favored multinutrients: 38% of the multinutrient group were "definitely improved" or better, compared to 25% of the placebo group, and ratings of "no change" or "worse" occurred in 35% with placebo versus 23% with multinutrients (p = 0.04). Inattention (72.2%) and emotional dysregulation (69.1%) were the most frequently reported PTP categories. Inattention and internalizing symptoms improved more with multinutrients than placebo (p = 0.01, d = 0.55; p = 0.03, d = 0.80, respectively). The multinutrient advantage was not significant for 7 other symptoms, including hyperactivity/impulsivity, aggression, autistic symptoms, or emotional dysregulation/irritable oppositionality. This secondary analysis found that the multinutrients, compared to placebo, were associated with improvements in parental concerns overall, and in two domains specifically: inattention and internalizing symptoms (anxiety/depression), but not in seven domains: hyperactivity/impulsivity, aggression, autistic symptoms or physiological symptoms, peer relationships or emotional dysregulation/irritable oppositionality.

Broad spectrum micronutrients: a potential key player to address emotional dysregulation

Psychiatric conditions are inherently multifactorial and must be understood and addressed within a multidimensional framework. Adequate nutritional intake is necessary for optimal mental health and is thus an essential component of any psychiatric treatment plan; this is especially true as many patients have a diet high in ultra-processed foods. However, due to a variety of factors such as individual biological and behavioral contributors, modern farming practices, and climate change, implementing a healthy diet alone may not be sufficient to satisfy nutritional requirements. Research studies on three formulations of broad-spectrum micronutrients (BSMs) have demonstrated significant efficacy in treating a range of mental health disorders. In particular, outcomes associated with emotional regulation via BSMs across a variety of psychiatric illnesses (ADHD, autism, trauma, mood disorders, nicotine dependence, and psychosis) to date have been positive.

Diet and Anxiety: A Scoping Review.

Anxiety disorders are the most common group of mental disorders. There is mounting evidence demonstrating the importance of nutrition in the development and progression of mental disorders such as depression; however, less is known about the role of nutrition in anxiety disorders. This scoping review sought to systematically map the existing literature on anxiety disorders and nutrition in order to identify associations between dietary factors and anxiety symptoms or disorder prevalence as well as identify gaps and opportunities for further research. The review followed established methodological approaches for scoping reviews. Due to the large volume of results, an online program (Abstrackr) with artificial intelligence features was used. Studies reporting an association between a dietary constituent and anxiety symptoms or disorders were counted and presented in figures. A total of 55,914 unique results were identified. After a full-text review, 1541 articles met criteria for inclusion. Analysis revealed an association between less anxiety and more fruits and vegetables, omega-3 fatty acids, “healthy” dietary patterns, caloric restriction, breakfast consumption, ketogenic diet, broad-spectrum micronutrient supplementation, zinc, magnesium and selenium, probiotics, and a range of phytochemicals. Analysis revealed an association between higher levels of anxiety and high-fat diet, inadequate tryptophan and dietary protein, high intake of sugar and refined carbohydrates, and “unhealthy” dietary patterns. Results are limited by a large percentage of animal and observational studies. Only 10% of intervention studies involved participants with anxiety disorders, limiting the applicability of the findings. High quality intervention studies involving participants with anxiety disorders are warranted.

A Pilot Randomized Treatment-Controlled Trial Comparing Vitamin B6 with Broad-Spectrum Micronutrients for Premenstrual Syndrome.

Objective: Premenstrual syndrome (PMS) affects 20%-30% of women but current medical treatments are limited in their efficacy. The objective of this study was to compare efficacy of a broad-spectrum micronutrient formula (consisting mainly of minerals and vitamins) to a single vitamin (B6) for treatment of PMS, for which B6 has already been shown to be efficacious. Methods: This double-blind, randomized, treatment-controlled trial allocated 78 (72 completed) regularly menstruating women with PMS to consume micronutrients or vitamin B6 (80 mg/day) daily following a two-cycle baseline period, for three menstrual cycles. The primary outcome measure, Daily Record of Severity of Problems (DRSP), established PMS as well as tracked change in five PMS symptoms: psychological, somatic, total symptoms, impact ratings, and worst day ratings. Results: Linear-mixed model analyses indicated both treatments produced comparable reduction in PMS symptoms with medium effect sizes (ES) across all PMS variables as measured by the DRSP (micronutrient ES = 0.50-0.56; B6 ES = 0.43-0.56), with 72% of the micronutrient and 60% of the vitamin B6 group identified as in full remission in PMS symptoms after three cycles. The micronutrient-treated participants showed greater improvement than the B6 group (between group d = 0.51, p < 0.05) in health-related quality of life. For those women (n = 28) who met criteria for premenstrual dysphoric disorder (PMDD), the DRSP ES were larger for those who had been in the micronutrient condition (ES = 1.28-1.67) as compared with those on B6 (ES = 0.50-0.75), although the group differences were not statistically reliable. There were no group differences in side effects, nor any serious adverse effects reported. Conclusions: Both treatments provided similar benefit for reducing PMS symptoms, with greater effect of micronutrients on quality of life as well as potential clinical benefit of micronutrients for PMDD. This study provides further efficacy data on B6 and also identifies the nutritionally broader spectrum intervention as possibly having specific advantages for those whose symptoms are more severe. As this is the first study to investigate these treatments for PMDD, systematic replication is required.

Do Changes in Blood Nutrient Levels Mediate Treatment Response in Children and Adults With ADHD Consuming a Vitamin–Mineral Supplement?

Objective: We investigated whether changes in serum nutrient levels mediate clinical response to a micronutrient intervention for ADHD. Method: Data were compiled from two ADHD trials (8-10 weeks), one in adults (n = 53) and one in children (n = 38). Seven outcomes included change in ADHD symptoms, mood, overall functioning (all clinician-rated) as well as response status. Change in serum/plasma nutrient levels (vitamins B12 and D, folate, ferritin, iron, zinc, and copper) were considered putative mediators. Results: A decrease in ferritin and an increase in copper were weakly associated with greater likelihood of being identified as an ADHD responder; none of the other nutrient biomarkers served as mediators. Conclusion: Further research looking at nutrients more broadly from other tissues are required to confirm these initial observations of the limited value of nutrient levels in deciphering mechanism of action. Monitoring these biomarkers on their own is unlikely helpful in understanding clinical response to a broad-spectrum micronutrient approach.

Rationale and design of an international randomized placebo-controlled trial of a 36-ingredient micronutrient supplement for children with ADHD and irritable mood: the Micronutrients for ADHD in Youth (MADDY) Study

BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) is a chronic neurodevelopmental disorder affecting up to 9% of children and substantial numbers of adults. Existing pharmacologic treatments often improve symptoms, but concerns exist over side effects, stigma, potential long-term health effects, and residual irritability, often treated with adjunctive antipsychotics. To address public and clinician demand for non-pharmacologic evidence-based treatments, this study will examine efficacy of a 36-ingredient micronutrient (vitamin/mineral) supplement as treatment for children with ADHD and irritability. MethodsAn international team of experts in ADHD, mood dysregulation, nutrition, epidemiology, and clinical trials conferred to develop/refine a protocol powered to detect a medium effect. The study will employ a fully-blind randomized controlled trial (RCT) design, comparing the micronutrient supplement to matched placebo in 135 children aged 6-12 with ADHD symptoms and irritability, based on the parent-rated Child and Adolescent Symptom Inventory-5 (CASI-5). Irritability measured by at least one symptom of oppositional defiant disorder (ODD) or disruptive mood dysregulation disorder (DMDD). Based on research suggesting an irritable ADHD subtype, the primary outcome will be a composite score comprised of the CASI-5 subscales: ADHD, ODD, DMDD, and the Peer Conflict Scale, which assesses anger and aggression perpetrated towards peers. Participants will provide biological samples (blood, urine, saliva, hair and stool) to explore the micronutrients’ mechanisms of action. DiscussionThis study is the first adequately powered RCT in North America to examine both behavioral responses to, and biological mechanisms of, micronutrients for ADHD and irritability in children. If found efficacious, broad-spectrum micronutrients, given at therapeutic doses, may provide an evidence-based alternative to prescription medications for ADHD and associated irritability. Trial registrationNCT03252522. Registered 26 July 2017;

Mineral-Vitamin Treatment Associated with Remission in Attention-Deficit/Hyperactivity Disorder Symptoms and Related Problems: 1-Year Naturalistic Outcomes of a 10-Week Randomized Placebo-Controlled Trial.

Objective: This article presents 1-year follow-up of a randomized placebo-controlled trial with open-label extension evaluating the efficacy of a broad-spectrum micronutrient (vitamins and minerals) intervention. The object was to determine if dominant treatment at follow-up was associated with differential psychological outcomes. Methods: Ninety percent of the original sample of 93 children with attention-deficit/hyperactivity disorder (ADHD) were followed 52 weeks postbaseline. Assessments included measures of ADHD, mood, anxiety, and general function based on parent/clinician report. Outcome was considered based on dominant therapy at 52 weeks (trial micronutrients [n = 19], medications [n = 21], and no treatment [n = 35]). Nine children were not categorized due to inconsistent therapies. Results: Based on dominant treatment, more of those who stayed on trial micronutrients (84%) were identified as "Much" or "Very Much" improved overall relative to baseline functioning, compared to 50% of those who switched to psychiatric medications and only 21% of those who discontinued treatment [χ2(2) = 19.476, p < 0.001]. Fifteen (79%) of those still taking micronutrients, 8 (42%) of those using medications, and 7 (23%) of those who discontinued treatment were considered remitters based on parent-reported ADHD [χ2(2) = 15.3, p < 0.001]. Those who stayed on micronutrients were more likely to have failed medication treatment in the past. The micronutrient group also displayed better outcomes on measures of parent-rated hyperactivity and anxiety, and clinician-rated general function and mood, with moderate to large between-group effect sizes (micronutrients vs. medication: ES = 0.73-1.01; micronutrients vs. no treatment: ES = 0.54-1.01). Most common reasons for stopping trial micronutrients were cost and number of pills to swallow. No continued side effects were associated with micronutrients. Conclusions: Children who benefitted from micronutrients in the short term maintained changes at follow-up, without side effects. While both those who continued micronutrients and those who switched to medication showed improved ADHD symptoms, psychiatric medication use was associated with deterioration in mood and anxiety. Inherent selection bias limits generalizability.

Human gut microbiome changes during a 10 week Randomised Control Trial for micronutrient supplementation in children with attention deficit hyperactivity disorder

It has been widely hypothesized that both diet and the microbiome play a role in the regulation of attention-deficit/hyperactivity disorder (ADHD) behaviour. However, there has been very limited scientific investigation into the potential biological connection. We performed a 10-week pilot study investigating the effects of a broad spectrum micronutrient administration on faecal microbiome content, using 16S rRNA gene sequencing. The study consisted of 17 children (seven in the placebo and ten in the treatment group) between the ages of seven and 12 years, who were diagnosed with ADHD. We found that micronutrient treatment did not drive large-scale changes in composition or structure of the microbiome. However, observed OTUs significantly increased in the treatment group, and showed no mean change in the placebo group. The differential abundance and relative frequency of Actinobacteria significantly decreased post- micronutrient treatment, and this was largely attributed to species from the genus Bifidobacterium. This was compensated by an increase in the relative frequency of species from the genus Collinsella. Further research is required to establish the role that Bifidobacterium contribute towards neuropsychiatric disorders; however, these findings suggest that micronutrient administration could be used as a safe, therapeutic method to modulate Bifidobacterium abundance, which could have potential implications for modulating and regulating ADHD behaviour. Our pilot study provides an initial observation into this area of research, and highlights an interesting avenue for further investigation in a larger cohort. Furthermore, these novel results provide a basis for future research on the biological connection between ADHD, diet and the microbiome.

Broad spectrum micronutrient supplementation for irritability, inattention and post-disaster stress

Broad spectrum micronutrient supplementation for irritability, inattention and post-disaster stress

Dietary and Micronutrient Treatments for Children with Neurodevelopment Disorders

There is an increased use of dietary and nutritional treatments among families of children with attention-deficit/hyperactivity disorder, autism spectrum disorder, and other neurodevelopmental disorders. With unclear and sometimes contradictory information regarding the effectiveness and safety of such treatments, this review critically reviews available research. This review identified treatments with promising and increasing levels of evidence including the few foods diet, PUFAs, probiotic treatments, and broad spectrum micronutrients; treatments with inconclusive or inconsistent findings such as gluten-free or additive-free diets, and those treatments with little evidence for effectiveness such as a sugar-free diet. There is reasonably robust evidence for the use of some dietary and nutritional approaches such as reduction of food dyes and supplementing with essential fatty acids and broad spectrum micronutrients. Additionally, the literature reviewed provided theoretical mechanisms for these treatments. Many methodological challenges (such as sample size, length of intervention, and difficulties with researcher blinding) were reviewed, demonstrating the need for a well-designed, well-controlled replications studies to provide further guidance and reassurance to families and health professionals.

Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial.

Evaluation of broad-spectrum micronutrient (vitamins and minerals) treatment for childhood ADHD has been limited to open-label studies that highlight beneficial effects across many aspects of psychological functioning. This is the first fully blinded randomized controlled trial of medication-free children (n=93) with ADHD (7-12years) assigned to either micronutrients (n=47) or placebo (n=46) in a 1:1 ratio, for 10weeks. All children received standardized ADHD assessments. Data were collected from clinicians, parents, participants and teachers across a range of measures assessing ADHD symptoms, general functioning and impairment, mood, aggression and emotional regulation. Intent-to-treat analyses showed significant between-group differences favouring micronutrient treatment on the Clinical Global Impression-Improvement (ES=0.46), with 47% of those on micronutrients identified as 'much' to 'very much' improved versus 28% on placebo. No group differences were identified on clinician, parent and teacher ratings of overall ADHD symptoms (ES ranged 0.03-0.17). However, according to clinicians, 32% of those on micronutrients versus 9% of those on placebo showed a clinically meaningful improvement on inattentive (OR=4.9; 95% CI: 1.5-16.3), but no group differences on improvement in hyperactive-impulsive symptoms (OR=1.0; 95% CI: 0.4-2.5). Based on clinician, parent and teacher report, those on micronutrients showed greater improvements in emotional regulation, aggression and general functioning compared to placebo (ES ranged 0.35-0.66). There were two dropouts per group, no group differences in adverse events and no serious adverse events identified. Blinding was successful with guessing no better than chance. Micronutrients improved overall function, reduced impairment and improved inattention, emotional regulation and aggression, but not hyperactive/impulsive symptoms, in this sample of children with ADHD. Although direct benefit for core ADHD symptoms was modest, with mixed findings across raters, the low rate of adverse effects and the benefits reported across multiple areas of functioning indicate micronutrients may be a favourable option for some children, particularly those with both ADHD and emotional dysregulation. Trial registered with the Australian New Zealand Clinical Trials Registry ACTRN12613000896774.

Hospitalization cost of conventional psychiatric care compared to broad-spectrum micronutrient treatment: literature review and case study of adult psychosis

BackgroundHealthcare costs are skyrocketing, with mental health treatment amongst the most expensive, especially when hospitalization is involved. According to the Mental Health Commission of Canada, one in five Canadians is living with a mental disorder in any given year, at an annual cost of $50 billion. In light of this societal burden, alternative approaches are being evaluated, such as brief psychotherapy by phone, peer support, and, as part of the emerging field of nutritional mental health, treatment with micronutrients (minerals and vitamins). Effectiveness of micronutrients has been demonstrated for many types of psychiatric symptoms, in about 45 studies of formulas that are either multinutrient (e.g., several B vitamins) or broad-spectrum (usually over 20 minerals and vitamins). Although this literature demonstrates therapeutic benefits, the potential economic impact of micronutrient treatment has been evaluated in only one case study of childhood psychosis.MethodsThe current case study was initiated to evaluate mental health-related hospitalization costs from 1997 to 2003 for a female adult diagnosed with various mood and psychotic symptoms. She was treated for the first 5 years with conventional methods and then subsequently with a broad-spectrum micronutrient formula.ResultsThe patient’s annual mental health hospitalization costs during conventional treatment averaged $59,864 across 5 years (1997–2001), with a peak annual cost of about $140,000. Since transitioning to broad-spectrum micronutrients, she has incurred no provincial hospitalization costs for mental health care, though her self-funded costs are currently $720/year for the micronutrients.ConclusionFurther exploration of the treatment of mental health problems with broad-spectrum micronutrient formulas has the potential to make two significant contributions: improved mental health, and decreased costs for governments.

Effect of Micronutrients on Insomnia in Adults

Insomnia is a debilitating condition causing psychological distress and frequently comorbid with other mental health conditions. This study examined the effect of 8 weeks of treatment by broad spectrum micronutrients (vitamins and minerals) on insomnia using a multiple-baseline-across-participants open-label trial design. Seventeen adults were randomized to 1-, 2-, or 3-week baseline periods (14 completed). Self-report measures were the Consensus Sleep Diary–Morning (CSD-M), the Pittsburgh Insomnia Rating Scale (PIRS), and the Depression, Anxiety, Stress Scale (DASS). Baselines were generally stable. Treatment completers reported reliable and clinically significant change in insomnia severity (PIRS), in depression, stress, and anxiety (DASS), and on at least two aspects of sleep measured by the CDS-M. All completers were treatment-compliant, and side effects were minimal. Nutritional supplementation is shown to be a novel, beneficial treatment for insomnia in adults. Follow-up research using placebo-controlled designs as well as comparisons to cognitive-behavioral and other treatments is recommended.

Multiple micronutrient supplementation and birth outcomes: The potential importance of selenium

A healthy diet and lifestyle is a pre requisite to a healthy pregnancy, however this is often not the case. Many pregnant women are overweight or clinically obese and this has been shown to increase their risk of major complications of pregnancy such a preeclampsia, intrauterine growth retardation, preterm birth and gestational diabetes. An adequate and balanced diet is important, as is the balance between macronutrients such as carbohydrates, fats and protein and the vitamins and essential trace elements needed to support metabolism. In this review, we look at the use of micronutrient supplements during pregnancy and examine the recommendations currently in place to guide the use of these products. We also present evidence that broad-spectrum micronutrients may have a beneficial effect in pregnancy and lower the incidence of preeclampsia and preterm labour, especially in overweight and obese women. Finally we focus on the essential trace element Selenium and present a strong case for its importance in maintaining mitochondrial function during oxidative stress which is generated in the placentae of women experiencing these complications of pregnancy. It can no longer be assumed that women are consuming an adequate and well balanced diet during pregnancy and the use of micronutrient supplements may potentially have positive effects on a healthy start to life. Globally, millions of women are currently taking these products each year and an opportunity exists to systematically determine their beneficial effect.

Clinically Significant Symptom Reduction in Children with Attention-Deficit/Hyperactivity Disorder Treated with Micronutrients: An Open-Label Reversal Design Study.

The purpose of this study was to investigate the clinical effect and safety of a broad spectrum, 36 ingredient micronutrient (vitamins and minerals) in treating children with attention-deficit/hyperactivity disorder (ADHD). This open-label, on-off-on-off (reversal design) study followed 14 participants (8-12 years of age) with ADHD, diagnosed using standardized instruments, for 6 months with no dropouts. Following baseline assessment, including hematology and biochemistry screening, participants began an 8 week treatment phase with micronutrients titrated up to maximum dose (15 capsules/day). Treatment was withdrawn for 4 weeks, reinstated for a further 8 weeks, and then withdrawn for 4 weeks. Primary outcomes included the Conners' Parent Rating Scale, the Clinical Global Impressions Scale (CGI), and the Strengths and Difficulties Questionnaire - Parent version (SDQ). Secondary outcomes were mood and global functioning. Modified Brinley plots revealed a reduction in ADHD symptoms, improved mood, and improved overall functioning during intervention phases, and deterioration in ADHD symptoms, mood, and overall functioning during the withdrawal phases. Reliable change analyses, Cohen's d and percent superiority effect sizes, 95% confidence intervals and t tests confirmed clinically and statistically significant change between the intervention and withdrawal phases, with large effect sizes observed pre- to post-exposure of micronutrients (d = 1.2-2.2) on ADHD symptoms during intervention phases. Seventy-one percent of participants showed at least a 30% decrease in ADHD symptoms by the end of the second treatment phase, and 79% were identified as "much improved" or "very much improved" at the end of the second phase (5 months) based on the clinician-rated CGI when considering functioning generally. The SDQ showed that these benefits occurred across other areas of functioning including emotional symptoms, conduct problems, and prosocial behaviours. The children's self-reports confirmed the improvements. Excellent adherence to treatment occurred throughout, side effects were mild and transitory, and no safety issues were identified through blood analyses. This study demonstrates the clinical benefit, feasibility, and safety of broad-spectrum micronutrients in the treatment of childhood ADHD. Replications utilizing double-blind placebo-controlled studies are warranted. Trial is registered with the Australia and New Zealand Clinical Trial Registry: ACTRN12612000645853.

Broad-spectrum micronutrient treatment for attention-deficit/hyperactivity disorder: rationale and evidence to date.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric illness, which often co-occurs with other common psychiatric problems. Although empirical evidence supports the short-term efficacy of pharmacological and behavioural treatments, families often search for alternative treatment methods because of concerns about side effects and safety, cost and access, as well as fears about long-term exposure to psychotropic medications. This review presents the published evidence on use of broad-spectrum micronutrients to treat ADHD symptoms. This approach makes physiological sense in that nutrients are required for many critical biochemical reactions to occur, ranging from manufacturing neurotransmitters, to providing the mitochondria with essential nutrients for energy production, to assisting the gut to heal from inflammation. Multi-nutrient treatment approaches are an intriguing yet under-researched area; all but one of the trials conducted in the last decade have shown benefit for the treatment of ADHD symptoms, and the one negative trial likely used doses too low to effect change. However, the methodologies have varied widely from case-controlled studies to open-label trials to one randomized controlled trial. Sample sizes have typically been modest, although the effect sizes have tended to be medium to large. What is required now is replication, as well as investigation into the optimal ingredient range and optimal doses of nutrients. We discuss the proven and potential benefits of the broad-spectrum nutrient approach, considering the heterogeneous nature of ADHD.

Micronutrient Supplementation Increases CD4 Count in HIV-Infected Individuals on Highly Active Antiretroviral Therapy

To examine the immunologic, metabolic, and clinical effects of broad spectrum micronutrient supplementation in HIV-infected patients taking highly active antiretroviral therapy (HAART). A prospective, randomized, double-blinded, placebo-controlled trial. Forty HIV-infected patients taking a stavudine and/or didanosine-based HAART regimen were prospectively randomized to receive micronutrients or placebo twice daily for 12 weeks. Data were collected at 4-week intervals including immunologic, metabolic, and clinical measurements. The study examined the effect of micronutrient supplementation on immunologic parameters as the primary end point. The secondary end points were metabolic and clinical effects and distal symmetrical polyneuropathy. The mean absolute CD4 count increased by an average of 65 cells in the micronutrient group versus a 6-cell decline in the placebo group at 12 weeks (P = 0.029). The absolute CD4 count increased by an average of 24% in the micronutrient group versus a 0% change in the placebo group (P = 0.01). The mean HIV-1 RNA decreased in the micronutrient supplementation group, although not significantly. Neuropathy scores improved in the micronutrient group by 42% compared with a 33% improvement in the placebo arm. This difference did not reach statistical significance. Fasting serum glucose, insulin, and lipids were not adversely affected in the patients taking the micronutrients. Micronutrient supplementation can significantly improve CD4 cell count reconstitution in HIV-infected patients taking HAART. The micronutrient supplement tested was well tolerated and may hold promise as an adjuvant therapy in the treatment of HIV. Further investigation is warranted.

Failure of HIV-1 to Infect Human Oocytes Directly

In this study, the susceptibility of mature human oocytes to HIV-1 infection has been investigated. We exposed in vitro human oocytes of healthy women using inocula of cell-free HIV-1. We also tested for the presence of HIV-1-specific receptor molecules on the surface of these cells. By applying polymerase chain reaction (PCR) analysis, transmission electron microscopy (TEM), and immunocytochemistry at both light and electron microscopic levels, we did not obtain evidence for HIV DNA production nor for oocyte-associated HIV particles. Experiments of immunostaining for CD4, CCR5, and GalAAG (putative receptor for HIV in sperm), as well as reverse transcriptase (RT)-PCR for CD4, CCR5, and CXCR4, which all suggested the absence of the mentioned receptors in mature oocytes and in follicular cells. This study fills an important gap concerning the information available on the direct HIV infection of human gametes, adds to our basic understanding of HIV infection in human oocytes, provides different results from those obtained with human spermatozoa using comparable methods, and provides a basic contribution to the investigation on HIV infection in human oocytes.