Bipolar Disorder may be related to cellular, not blood Vitamin D

Bipolar Disorder = BD = Manic Depression (BD name before 1980)
BD had been just in adults but has increased in children by perhaps 40X since 1980
US appears to have the highest BD rate of any country
BD is partially treated by both Omega-3 and Vitamin D
No data on BD prevention by Vitamin D or Omega-3

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16 articles in the Bipolar category

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See also VitaminDWiki

• Hypothesis: Some Mental Illness could be treated or prevented with vitamin D
• Fewer white spots in MRI brain scans if had more vitamin D – Jan 2014
• Mental health problems cut in half when have adequate level of vitamin D – Jan 2013
  lack of blood flow in brain regions appears to be associated with low vitamin D
• DBP-L is 8 times higher with Bipolar Disorder, but might be invisible to most tests – April 2017
• Bipolar category listing has 16 items along with related searches
• Depression category listing has 267 items along with related searches
• ADHD and Vitamin D Deficiency

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BD recurrence reduced by 6 months of Omega-3 - small RCT Jan 2024

Omega-3 polyunsaturated fatty acids in the prevention of relapse in patients with stable bipolar disorder: A 6-month pilot randomized controlled trial
Psychiatry Research Volume 331 , January 2024, https://doi.org/10.1016/j.psychres.2023.115633
Halliru Zailani a b c. Suet-Kei Wu a b, Kai-Jie Yang a g, Ikbal Andrian Malau a g, Hsien-Feng Liao a. etc.

This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD.

Introduction
Bipolar disorder (BD) is a significant cause of disability and mortality worldwide affecting over 1 % of the global population (Grande et al., 2016). The recurrence rate of BD is high and ranges from 35 to 57 % within 1 year (Shim et al., 2017), necessitating lifelong medications to prevent the disease recurrence. However, suboptimal compliance with these medications due to concerns about their potential adverse effects and toxicity has been reported (Bates et al., 2010; Malhi, 2015), underscoring the need for better-tolerated alternative medications.
Evidence suggests the beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in managing mood disorders with high tolerability (Su et al., 2014; Zailani et al., 2023) and may be good alternatives to BD medications. Notably, n-3 PUFAs deficiency, often accompanied by inflammation characterizes BD (Huang et al., 2022; McNamara and Welge, 2016). Interestingly, n-3 PUFAs have proven abilities to protect neurons and modulate inflammatory pathways, which could partly be responsible for their antidepressant effects.
Findings from previous studies of n-3 PUFAs in BD yielded incoherent results.

• While some studies reported favorable effects of n-3 PUFAs in BD (Frangou et al., 2006; Stoll et al., 1999),
• others reported no benefits (Chiu et al., 2003; Keck et al., 2006; McPhilemy et al., 2021; Murphy et al., 2012).

Of note, previous studies of n-3 PUFAs in BD were limited by

• a relatively short follow-up period,
• the use of DHA-predominant formulations, or a
• lower dose of the n-3 PUFAs.

Thus, this trial aimed to assess the prophylactic effects and tolerability of high-dose n-3 PUFAs in the prevention of relapse of bipolar depression.
Examine.com has a summary of the study

• "The fish oil contained a total of 1,680 mg of eicosapentaenoic acid (EPA) and 880 mg of docosahexaenoic acid (DHA), as well as 8 mg of vitamin E."
• "This was a pilot study, and the findings should be considered preliminary, especially given the small sample size. In total, 8 participants experienced a recurrence of bipolar depression (2 in the omega-3 group, 6 in the placebo group)."

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Omega-3 recommended in the treatment of Bipolar Disorder – 2024

The role of Omega-3 Polyunsaturated Fatty Acids in the treatment of Bipolar Disorder – a narrative review
Med Srod. 2024;27(2):90-94 DOI: https://doi.org/10.26444/ms/187881
Jakub Rogalski 1, Karolina Pokrywka 2, Tomasz Tomczak 3
References (50)

Introduction and objective:
Bipolar Disorder (BD) is a chronic mental condition associated with significant impairment of psychosocial functioning and premature mortality due to somatic comorbidities, as well as high rates of completed suicides. Unfortunately, results of currently available methods of treatment are unsatisfactory. Thus, new therapeutic solutions are sought. Recently, particular attention has been paid to the use of nutraceuticals, especially Omega-3 Polyunsaturated Fatty Acids (n-3 PUFAs), as an adjunctive treatment in various mental disorders. The aim of the review is to show the role of PUFAs in the pathogenesis of BD, and present results of already conducted studies investigating n-3 PUFAs supplementation effects on the BD clinical course.

Materials and Method:
Internet scientific bases were searched throughout January and February 2024 for the relevant to this topic literature from the past 15 years, using keywords: “bipolar disorder”, “cardiovascular risk”, “mental disorders”, “omega-3 fatty acids”, “polyunsaturated fatty acids”, “remission”, “treatment”. Original and review articles were included. Manuscripts in other language than English were excluded from the search. To assess the proper quality of this manuscript, the Scale for the Assessment of Narrative Review Articles were used.

Brief description of the state of knowledge:
There is lack of research assessing the importance of n-3 PUFAs in the treatment of BD. However, it seems that their supplementation may bring significant benefits in the acute phase of depression episode treatment, remission maintenance and reduction in cardiometabolic risk factors.

Summary:
Results of already conducted studies should be treated as a rationale for future research. It is highly recommended to confirm the n-3 PUFAs efficiency in the BD treatment, to justify their widespread use in everyday clinical practice.
 Download the PDF from VitaminDWiki

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Vitamin D Status in Bipolar Disorder (no association found) - Nov 2023

Nutrients 2023, 15(22), 4752; https://doi.org/10.3390/nu15224752
by Zita Späth 1,Adelina Tmava-Berisha 1,*,Frederike T. Fellendorf 1ORCID,Tatjana Stross 1,Alexander Maget 1,Martina Platzer 1,Susanne A. Bengesser 1,Alfred Häussl 1ORCID,Ina Zwigl 1,Armin Birner 1,Robert Queissner 1,Katharina Stix 1ORCID,Linda Wels 1,Melanie Lenger 1,Nina Dalkner 1ORCID,Sieglinde Zelzer 2ORCID,Markus Herrmann 2 andEva Z. Reininghaus 1ORCID

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D, and its principal catabolite 24,25(OH)2D, were measured simultaneously with a validated liquid chromatography–tandem mass spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR = 100×(24,25(OH)2D/25(OH)D). The psychometric assessment comprised: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts.
We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = −0.154, p = 0.040), as well as the Young Mania Rating Scale and the VMR (r = −0.238, p = 0.015).
Based on the small effect size and the predominantly euthymic sample, further exploration in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers and an assessment in different phases of the disease may provide additional insights.
 Download the PDF from VitaminDWiki

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Bipolar Manic Attacks triggered by lower vitamin D - Sept 2023

Does Decreased Vitamin D Level Trigger Bipolar Manic Attacks?
Behav Sci (Basel). 2023 Sep 18;13(9):779. doi: 10.3390/bs13090779.
Okan İmre 1, Mustafa Karaağaç 2, Cuneyt Caglayan 3

Vitamin D levels much lower during mania phase

Background: Bipolar disorder is a chronic psychiatric disorder with depression and manic episodes. It is one of the leading causes of disease-related disability worldwide. Despite the presence of various alternative drug options for bipolar disorder, some patients do not adequately benefit from the treatment. Therefore, possible underlying mechanisms need to be clarified. Recently, studies on the relationship between bipolar disorder and vitamin D (Vit D) have attracted attention. Although many studies have found an association between depression and Vit D deficiency, little is known about the relationship between manic episodes and Vit D. The aim of this study was to compare Vit D and related metabolites of bipolar manic episodes prior to treatment, bipolar remission after treatment, and healthy control groups.

Methods: This case-control study consisted of 34 bipolar manic episode patients and 34 healthy controls. Disease activity was evaluated with the Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS). Firstly, serum 25-hydroxy vitamin D (25-OHD), calcium (Ca) and phosphorus (P) levels of patients in the bipolar manic episode were measured and compared with healthy control. Secondly, serum 25-OHD, Ca and P levels in the euthymic periods of the same patients were measured and compared with healthy control.

Results: Bipolar manic episode Vit D levels were lower when compared to healthy controls; while there was no difference in terms of Ca and P levels. There was no significant difference between the bipolar euthymic period patients and the healthy control group in terms of 25-OHD, Ca and P levels.

Conclusion: Our results demonstrated low serum Vit D concentrations in the acute manic episode of bipolar disorder. Decreased Vit D level may play a role in the onset of the manic episode, or malnutrition and insufficient sunlight during the manic episode may have caused Vit D deficiency. Future studies are needed to exclude potential confounding factors and to compare all mood episodes.
 Download the PDF from VitaminDWiki

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Vitamin D might help bipolar - Jan 2021

The role of vitamin D in bipolar disorder: Epidemiology and influence on disease activity
Journal of Affective Disorders Vol 278, 1 Jan 2021, Pages 209-217 FREE PDF

Background
Although many studies found an association between psychiatric disorders, especially major depressive disorder, and vitamin D deficiency, little is still known about the association between vitamin D and bipolar disorder (BD). Therefore, the present review aims at providing an overview of the available literature exploring the role of vitamin D in BD patients in different phases of the disease.

Methods
From a bibliographic research in PubMed until April 2020, we collected ten original studies that fulfilled our inclusion criteria.

Results
No significant differences in vitamin D levels between BD patients and other psychiatric disorders were found by most of the studies. In the majority of the studies, the average values of vitamin D in BD population were sub-threshold for vitamin D deficiency. Moreover, although an association between vitamin D levels and clinical symptomatology was observed in BD patients, it cannot be considered a specific marker of this disorder but a common characteristic shared with other psychiatric disorders, including schizophrenia and major depressive disorder. Finally, vitamin D supplementation was associated with a reduction in both depressive and manic symptoms.

Limitations
Few studies with small and heterogeneous populations. Methodological heterogeneity in terms of vitamin D measurement and threshold.

Conclusions
The results showed that vitamin D status does not differ between BD and other psychiatric conditions. However, given the correlation between vitamin D levels and depressive or manic symptoms, we could hypothesize that an adequate vitamin D status could positively affect the mood balance thanks to its immunomodulatory activity.

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Bipolar more likely to start a month after low level of UVB - June 2023

Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder

• "Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. "
• "Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production."

 Download the PDF from VitaminDWiki
Note: UVB ==> Vitamin D to brain etc without going thu the gut, liver, kidney, etc.

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Bipolar strongly associated with poor VDR (blood level vit D is a poor indicator) - March 2022

Abnormal pattern of vitamin D receptor-associated genes and lncRNAs in patients with bipolar disorder
BMC Psychiatry volume 22, Article number: 178 (2022) FREE PDF
Reyhane Eghtedarian, Soudeh Ghafouri-Fard, Hamid Bouraghi, Bashdar Mahmud Hussen, Shahram Arsang-Jang & Mohammad Taheri

Background
Bipolar disorder (BD) is a multifactorial condition. Several signaling pathways affect development of this disorder. With the purpose of exploring the role of vitamin D receptor (VDR) signaling in this disorder, we measured expression of selected mRNA coding genes and long non-coding RNAs (lncRNAs) in this pathway in patients versus normal subjects.

Methods
We measured expression of VDR-associated lncRNAs and mRNAs (SNHG6, MALAT1, Linc00511, Linc00346, VDR and CYP27B1) in the peripheral blood of BD patients vs. healthy individuals.

Results
Expression of SNHG6 was significantly higher in cases vs. controls (Posterior beta = 1.29, P value < 0.0001. Subgroup analysis by sex revealed significant results in both subgroups (P value < 0.0001 and P value = 0.023 for males and females, respectively). Expression of CYP27B1 was up-regulated in cases vs. controls (Posterior beta = 0.415, P < 0.0001). Such pattern was also detected among males (P < 0.0001), but not females (P = 0.419). Similarly, MALAT1 and Linc00346 were up-regulated in total cases vs. controls (Posterior beta = 0.694, P < 0.0001 and Posterior beta = 0.4, P = 0.012, respectively) and in male cases compared with male controls (Posterior beta = 0.712, P < 0.0001 and Posterior beta = 0.41, P value = 0.038, respectively). Expression of VDR was up-regulated in total cases compared with controls (Posterior beta = 0.683, P value = 0.001). Finally, expression of Linc00511 was not different between groups. MALAT1, SNHG6, CYP27B1, VDR and Linc00346 had AUC values of 0.95, 0.94, 0.91, 0.85 and 0.83 in differentiation of male patients from controls, respectively.

Conclusion: The current study suggests VDR-associated genes as possible markers for BD.

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More sunlight and higher temperature ==> more bipolar (opposite of Vitamin D association) - Dec 2021

The influence of weather on the course of bipolar disorder: A systematic review
The European J of Psychiatry Vol 35, Issue 4, Dec 2021, Pages 261-273 https://doi.org/10.1016/j.ejpsy.2021.03.002
J.M.Montesa C.Serrano b A.Pascual-Sanchez c

Background and objectives
Several studies have addressed the relationship between bipolar disorder and meteorological variables, but no previous review focusing on the influence of a wide range of meteorological variables on bipolar disorder has been published. The aim of this study is to conduct a systematic review about the influence of weather on the clinical course of bipolar disorder patients.

Methods
Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the main electronic medical databases were searched in February 2020, and studies were screened based on the eligibility criteria. 24 studies were selected for qualitative synthesis. Most of them were observational retrospective studies based in medical records.

Results
The most studied meteorological variables were temperature and sunlight, and the most studied clinical outcomes were hospital admissions. Significant correlations were found between temperature and sunlight and clinical outcomes, although the findings were heterogeneous. Higher temperatures may trigger bipolar disorder relapses that require hospital admission, and higher expositions to sunlight may increase the risk of manic episodes.

Conclusion
Meteorological variables seem to have an influence in the course of bipolar disorder, especially temperature and sunlight, although further studies are needed to clarify this possible relationship.

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Bipolar review of Nutraceuticals (no vitamin D) - Sept 2022

A Systematic Review of Nutraceuticals for the Treatment of Bipolar Disorder
FREE PDF
Studies revealed promising, albeit conflicting, evidence for omega-3 fatty acids and N-acetylcysteine. Isolated positive results were reported for coenzyme Q10.

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BD hypomania reduced by 1 year of Omega-3 - RCT Dec 2020

A 52-week prophylactic randomised control trial of omega-3 polyunsaturated fatty acids in bipolar disorder
Bipolar Disorders Volume23, Issue7. November 2021, PDF behind a paywall
Genevieve McPhilemy, Fintan Byrne, Mairead Waldron, Joseph R. Hibbeln, John Davis, Colm McDonald, Brian Hallahan

OBJECTIVES
Previous work suggests supplementation with omega-3 polyunsaturated fatty acids (PUFAs) may improve mood symptoms in bipolar disorder (BD) although findings remain unclear. In this study, we assess the efficacy of omega-3 PUFA administration for prophylaxis in BD using a clinical trial design over 52-weeks (ClinicalTrials.gov Identifier: NCT04210804).

METHODS
Individuals with BD (n = 80) were randomised to receive placebo (n = 40) or 1 g eicosapentaenoic acid (EPA) plus 1 g docosahexaenoic acid (DHA; n = 40) adjunctively for 52-weeks. The primary outcome measure comprised the number of mood episode relapses including hospital admissions and medication changes experienced. Secondary outcome measures included time to first mood episode relapse and change in psychometric measures of depression and elation (Hamilton Depression Rating Scale and Young Mania Rating Scale).

RESULTS
No significant differences in the number of mood episode relapses (U = 490.00, p = 0.14) or the number of individuals requiring admission to hospital (χ2 = 0.67, p = 0.41) or medication adjustment in the omega-3 PUFA compared to the placebo group were noted. Time to relapse was not significantly different between groups (Log Rank χ2 = 0.41, p = 0.52).
Change in Young Manic Rating Scale (F(3.12, 152.86) = 2.71, p = 0.05) was significantly different between treatment groups over 12-months, with scores at 9-months and 12-months significantly lower than those at 3-months in the omega-3 group and not in the placebo group.
Change in Hamilton Depression Rating Scale, Global Clinical Impression and Global Assessment of Functioning were not different between groups.

CONCLUSIONS
Despite a minor reduction in hypomania scores in the omega-3 PUFA group compared to placebo, we find little evidence that the supplementation of omega-3-PUFAs exhibits prophylactic benefit in BD.

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Less sun more Bipolar Disorder - Oct 2014

Relationship between sunlight and the age of onset of bipolar disorder: An international multisite study
Journal of Affective Disorders, Volume 167, 1 October 2014, Pages 104–111

Background
The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode.

Methods
Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations.

Results: There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California.

Limitations: Recall bias for onset and family history data.

Conclusions: A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.

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Nutritional and Safety Outcomes from an Open-Label Micronutrient Intervention for Pediatric Bipolar Spectrum Disorders Oct 2013

Abstract says the study tried some unspecified amount of vitamin D, which did help.
 Download the PDF from VitaminDWiki

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Mood disorders helped by Vitamin D, Omega-3, etc -Jan 2017

Clinical use of nutraceuticals in the adjunctive treatment of depression in mood disorders.
Australas Psychiatry. 2017 Jan 1:1039856216689533. doi: 10.1177/1039856216689533. [Epub ahead of print]
Sarris J1. Pfessor of Integrative Mental Health, NICM, Western Sydney University, Campbelltown, NSW, and; Principal Research Fellow, The University of Melbourne, Department of Psychiatry, The Melbourne Clinic, Professorial Unit, Melbourne, VIC, Australia.

OBJECTIVES:
The aim of this paper is to detail a summary of the current evidence in this area, to better inform clinical practice. Our recent systematic reviews and meta-analyses of nutrient pharmacotherapies in the treatment unipolar depression revealed primarily positive results for replicated studies testing

• S-adenosyl methionine (SAMe),
• methylfolate,
• omega-3 (EPA or ethyl-EPA), and
• Vitamin D;

with supportive isolated studies found for creatine and an amino acid combination. Mixed results were found for zinc, folic acid, Vitamin C, and tryptophan; and non-significant study results for inositol. In bipolar depression, omega-3 and N-acetyl cysteine (NAC) were found to have supportive evidence, with an isolated study using a chelated mineral formula also displaying efficacy. No major adverse effects were noted in the studies (aside from occasional minor digestive disturbances with omega-3 and NAC).

CONCLUSIONS:
Several clinical considerations are needed when psychiatrists are considering prescribing nutrients, including knowledge of drug interactions, supplement safety and quality issues, individual psychological and biochemical individualities, in addition to cost factors.

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US has the highest lifetime prevalence of bipolar (note: this will tend to ignore youth)

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Bipolar treated by bright light (similar to SAD?) - RCT Oct 2017

Bright light therapy at midday helped patients with bipolar depression

• "Patients were randomly assigned to either a 7,000 lux bright white light or a 50 lux placebo light. The light therapy patients were instructed to place the light box about one foot from their face for 15-minute sessions to start. Every week, they increased their exposure to the light therapy by 15-minute increments until they reached a dose of 60 minutes per day or experienced a significant change in their mood" doi/10.1176/appi.ajp.2017.16101200.

• Seasonal Affective Disorder - treated by both vitamin D and bright light
• Hypothesis – A SAD risk factor is low vitamin D – Nov 2014
• Light Therapy Lamp reviews - for Seasonal Affective Disorder - 2024, 2015

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See also web

• The high prevalence of obstructive sleep apnea among patients with bipolar disorders J Affect Disord. 2013 Oct
  Both are strongly associated with low vitamin D - not mentioned in article. Full text on-line
• Bipolar trends in the US March 2011

has the following chart: 7X increase of bipolar of all ages in a decade (4.3X in 6 years) US

• Bipolar Disorder Symptoms International Mental Health Research Org. has the following graphic

• Woman describing her bipolar life - 4 minute video Oct 2017
• "While ADHD is chronic or ongoing, bipolar disorder is usually episodic, with periods of normal mood interspersed with depression, mania, or hypomania."
• Bipolar Mercola April 2018, Vitamin D not mentioned
• Bipolar increased 40X in children Mercola Oct 2024 vitamin D not mentioned
• The role of vitamin D in bipolar disorder: Epidemiology and influence on disease activity - Sept 2020
  • doi: 10.1016/j.jad.2020.09.039 - behind paywall
  • "Vitamin D status does not differ between Bipolar and other psychiatric conditions"

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