October 25, 2023
A recently published meta-analysis compared the treatment of ADHD with multi-nutrient supplements versus placebo.
Children received either placebo or Daily Essential Nutrients(Vit A 384 IU, Vit C 40 mg, Vit D 200 IU, Vit E 24 IU, Vit K 8 μg, B1 4 mg, B21.2 mg, B3 6 mg, B6 4.67 mg, B9 50 μg, B12 60 μg, B7 72 μg, B5 2 mg, Ca 88 mg, Fe 0.92 mg, P 56 mg, I 13.6 μg, Mg 40 mg, Zn 3.2 mg, Se 13.6 μg, Cu 0.48 mg, Mn0.64 mg, Cr 41.6 μg, Mo 9.6 μg, P 16 mg. Proprietary blend: Choline bitartrate, Alpha-lipoic acid, Inositol, Acety-l-carnitine (as acetyl-L-carnitine hydrochloride), Grape seed extract, Ginkgo biloba leaf extract, Methionine (asL-methionine hydrochloride), Cysteine (as N-acetyl-L-cysteine), Germanium sesquioxide (as chelate), Boron, Vanadium, Lithium orotate, Nickel. Other ingredients: Cellulose glycine 45 mg, Citric acid 26.814 mg, Magnesium stearate24 mg, Silicon dioxide 20 mg).
Adults received either placebo or EMP+ (Vit A 5760IU, Vit C 600 mg, Vit D 1440 IU, Vit E 360 IU, B1 18 mg, B2 13.5 mg, B3 90 mg,B5 21.6 mg, B6 36 mg, B9 1440 μg, B12 900 μg, Biotin 1080 μg, Pantothenic acid21.6 mg, Ca 1320 mg, Fe 13.74 mg, P 840mg, I 204 μg, Mg 600 mg, Zn 48 mg, Se204 μg, Cu 7.2 mg, Mn 9.6 mg, Cr 624 μg, Mo 144 μg, K 240 mg, Germaniumsesquioxide 20.7 mg, B 2400 μg, V 1194 μg, Ni 29.4 μg, Choline bitartrate 540mg, DL-phenylalanine 360 mg, Citrus bioflavonoids 240 mg, Inositol 180 mg,Glutamine 180 mg, L-methionine 60 mg, Gingko biloba 36 mg, grape seed extract45 mg).
Using the Global Assessment of Functioning (GAF) scale for adults, and the Children's Global Assessment Scale (CGAS) for children, the study team reported moderate improvements in overall functioning from the use of the supplements. GAF and CGAF are used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of an individual.
Yet no significant improvements were found for either clinician-rated or observer-rated ADHD Change Scores.
Moreover, the positive finding was compromised by a series of methodological shortcomings:
· It was just barely a meta-analysis, involving only two studies.
· The combined number of participants in the two studies was small, 173, consisting of 93 children in one study and 80 adults in the other.
· Both studies had the same lead author, Julia J. Rucklidge, who was also a member of the meta-analysis team.
With only two studies, there was no way to evaluate publication bias.
Jeanette M. Johnstone, Andrew Hughes, Joshua Z. Goldenberg, Amy R. Romijn, and Julia J. Rucklidge, "Multinutrients for the Treatment of Psychiatric Symptoms in Clinical Samples: A Systematic Review and Meta-Analysis of Randomized Controlled Trials," Nutrients (2020) 12, 3394, https://doi:10.3390/nu12113394.
The Background:
Caffeine and its primary breakdown compounds – paraxanthine, theophylline, and theobromine (also the primary alkaloid in chocolate) – readily cross the placenta and tend to linger due to the underdevelopment of fetal caffeine metabolizing enzymes.
Could accumulating caffeine metabolites harm the developing fetal brain? Studies to date have come to contradictory conclusions, some finding an association, others finding none.
Norway has a national single-payer health insurance system with a national health registry comprehensively tracking virtually all residents.
The Methods:
An international study team used Norways’s registry, and its Mother, Father, and Child Cohort Study (MoBa) to explore the relationship between maternal and paternal coffee consumption and offspring neurodevelopmental difficulties (ND), including symptoms of ADHD as determined from validated rating scales, using 58,964 mother-child pairs and 22,576 father-child pairs, covering the decade 1999-2008.
Unadjusted results indicated a strong association between maternal coffee consumption before and during pregnancy with offspring ADHD, but none with paternal coffee consumption. Superficially, that might seem like compelling evidence.
Yet after adjusting for education, income, smoking, and alcohol, “previously significant effects attenuated towards zero and some associations switched from being positive to negative.”
Then, after further adjusting for genetic confounding, ADHD symptoms at 1.5 years, 3 years, 5 years (on both of two different rating scales), and 8 years (including separate measures of inattention and hyperactivity symptoms) all became indistinguishable between offspring from mothers consuming coffee during pregnancy and offspring of mothers abstaining from coffee during pregnancy.
Conclusion:
The team concluded, “This study applied several conventional and genetic epidemiological approaches to investigate the potential relationship between maternal coffee consumption during pregnancy and offspring NDs [neurodevelopmental difficulties]. When considering the results of the conventional and genetic epidemiological analyses, as well as the broader literature, we conclude that there is little evidence that maternal coffee consumption during pregnancy is strongly causally related to offspring NDs.”
More specifically, the team found no evidence of any causal relationship with offspring ADHD.
There has been consistent evidence of an association between ADHD and subjectively reported sleep problems even in patients not medicated for the disorder. There have also been studies using wrist-worn actigraphy (a wrist watch-like device that measures gross motor activity) and sleep lab-based polysomnography that measure objective sleep parameters.
What has been missing are large population-based cohort studies to explore the prevalence rates of different sleep disorders and medical prescriptions in ADHD.
Methods Used:
Sweden has a single-payer health insurance system and a series of national population registers that track virtually its entire population. Using the Swedish Total Population Register, a local research team created a cohort of all 6,470,658 persons born between 1945 and 2008. They linked this to the Swedish National Patient Register, which includes inpatient hospitalizations from 1975 to 2013, and outpatient specialist diagnoses from 2001 to 2013, to identify diagnoses of sleep disorders. They also linked to the Prescribed Drug Register, covering 2005 to 2013, to identify prescriptions for sleep medications.
Summary of Findings:
Overall, persons with ADHD were eight times more likely to be diagnosed with any sleep disorder relative to normally developing peers. Broken down by age, adolescents with ADHD were 16 times more likely to receive such diagnoses, young adults (18-30) twelve times more likely, children and mid-age adults (31-45) eight times more likely, and older adults six times more likely.
Broken down by specific sleep disorder diagnoses, relative to normally developing peers, persons with ADHD were:
As for sleep medication, relative to normally developing peers, persons with ADHD were:
Conclusion:
The team concluded, “Our findings also suggest that greater clinical attention should be directed towards addressing sleep problems in individuals with ADHD. This entails implementing proactive measures through sleep education programmes and providing both pharmacological and non-pharmacological approaches such as cognitive behavioural therapy and parental sleep training.”
Congenital cleft lip and palate (CCLP) are birth defects associated with genetic and environmental factors. The latter include heavy maternal consumption of alcohol and fetal exposure to retinoid drugs derived from vitamin A.
Methods:
Taiwan has an island-wide single-payer health insurance system that reaches over 99% of the population. To explore the relationship between CCLP and various psychiatric disorders including ADHD, a Taiwanese study team used the island’s National Health Insurance Research Database to identify all 1,158 children and adolescents with CCLP during a ten-year period. They matched them ten-to-one with 11,580 age and sex-paired controls without CCLP.
Summary of Results:
Further adjusting for demographic data (income, residence) and family history of major psychiatric disorders, children and adolescents with CCLP were more than seven times more likely to be diagnosed with ADHD during the follow-up period than controls. Patients with both cleft palate and cleft lip were more than nine times more likely to be subsequently diagnosed with ADHD than controls.
Patients with CCLP were also six times more likely to be diagnosed with autism spectrum disorder and more than seven times as likely to be diagnosed with schizophrenia as non-CCLP controls. They were also more likely to be diagnosed with bipolar disorder or major depressive disorder, but these results did not reach statistical significance.
Conclusion:
This study highlights a significant association between congenital cleft lip and palate (CCLP) and an increased risk of developing ADHD, with CCLP patients being more than seven times as likely to be diagnosed with the disorder. Additionally, CCLP was linked to a higher prevalence of other psychiatric conditions, including autism spectrum disorder and schizophrenia. These findings underscore the importance of monitoring mental health in individuals with CCLP and call for further research into the risk factors connecting these birth defects with psychiatric disorders.
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