Vitamin D: A review of systematic reviews
Includes important updates to original posting
It should be obvious that our health is intimately linked to the Sun, however, just what does current scientific evidence have to say about Vitamin D?
In the health-related professions, systematic reviews are considered the most reliable sources of evidence to guide clinical practice. The purpose of a systematic review is to deliver a meticulous summary of all the available primary research (all the randomized controlled trials, or all the cohort studies) that focus on answering a specific question. Systematic reviews are one of the most reliable types of study. The level of evidence for the systematic review is 1 which is to say they appear at the top of the hierarchy of evidence.
Meta-analysis is the statistical procedure for combining data from multiple studies included in the systematic review and analyzed as if they were one study. When the treatment effect (or effect size) is consistent from one study to the next, meta-analysis can be used to identify the common effects.
Here you’ll find documented 68 systematic reviews and meta-analyses which evaluate the links between Vitamin D and our most common illnesses and medical conditions.
METABOLIC DISORDERS
METABOLIC SYNDROME
Dose-response meta-analysis demonstrated that a 10-ng/mL increase in the serum vitamin D concentration was associated with 20% and 15% lower risks of Metabolic Syndrome in cross-sectional studies and cohort studies, respectively. https://pubmed.ncbi.nlm.nih.gov/34093974/
Four out of the five observational studies we reviewed support that Vitamin D level is significantly associated with the following components of Metabolic Syndrome: obesity and BMI, dyslipidemia, Blood Pressure, and insulin and glucose metabolism https://pubmed.ncbi.nlm.nih.gov/34589329/
METABOLIC SYNDROME IN CHILDREN
This meta-analysis revealed that circulating vitamin D concentration was inversely associated with odds of Metabolic Syndrome in children, in a dose-response fashion. https://pubmed.ncbi.nlm.nih.gov/34231300/
CARDIOMETABOLIC DISORDERS
High levels of vitamin D among middle-age and elderly populations are associated with a substantial decrease in cardiovascular disease, type 2 diabetes and metabolic syndrome. If the relationship proves to be causal, interventions targeting vitamin D deficiency in adult populations could potentially slow the current epidemics of cardiometabolic disorders. https://pubmed.ncbi.nlm.nih.gov/20031348/
OBESITY
the prevalence of vitamin D deficiency was more elevated in obese subjects. https://pubmed.ncbi.nlm.nih.gov/25688659/
TYPE 2 DIABETES
Vitamin D status at baseline in apparently healthy adults is inversely associated with future risks of T2D and Metabolic Syndrome. Interventions aimed at maintaining adequate levels of vitamin D in addition to preventing deficiency may be a useful preventive measure for metabolic diseases. https://pubmed.ncbi.nlm.nih.gov/23107484/
GUT MICROBIOTA
appropriate dose of vitamin D can alter the gut microbiota with increase in Bacteroidetes and decrease in Firmicutes. At genera level, vitamin D may connect to some genera of Lachnospiaceaefamily (e.g., Blautia, Rosburia, Dorea, and Coprococcus). Therefore, maintaining the appropriate amount of vitamin D in the body seems to have beneficial effects on the composition of the gut microbiota. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331286/
NON-ALCOHOLIC FATTY LIVER DISEASE
The present study provides substantial evidence that supplemental vitamin D has favorable effects on glycemic control and insulin sensitivity in NAFLD patients. Vitamin D could be as an adjuvant pharmacotherapy of NAFLD. https://pubmed.ncbi.nlm.nih.gov/32966467/
GLYCEMIC CONTROL
This meta-analysis indicates that Vitamin D fortification improves indices of glycemic control. Hence, food fortified with Vitamin D may be of potential therapeutic value in diabetic patients, as an adjuvant therapy. https://pubmed.ncbi.nlm.nih.gov/32350957/
LIVER FIBROSIS
Low vitamin D status is common in chronic Hepatitis C patients and is associated with advanced liver fibrosis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316848/
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AUTOIMMUNE DISEASES
ALZHEIMER’S
Alzheimer’s Disease cases had lower serum vitamin D concentrations than matched controls. This reinforces the conceptualization of vitamin D as a 'neurosteroid hormone' and as a potential biomarker of Alzheimer’s Disease https://pubmed.ncbi.nlm.nih.gov/23042216/
SYSTEMIC LUPUS ERYTHEMATOSUS
Inadequate levels of serum vitamin D is significantly high in patients with SLE compared to healthy subjects, therefore, vitamin D supplementation with regular monitoring should be considered as part of their health management plans. https://pubmed.ncbi.nlm.nih.gov/31520805/
TYPE 1 DIABETES
vitamin D intake during early life may be associated with a reduced risk of type 1 diabetes. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798920/
GRAVE’S DISEASE and HOSHIMOTO THYROIDITIS
we have demonstrated that vitamin D deficiency is prevalent in Autoimmune Thyroid Disease subjects and that these subjects have lower levels of Vit D, suggesting that lower serum vitamin D is related to Autoimmune Thyroid Disease and the deficiency in vitamin D may plays a role in the development of the disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425156/
MULTIPLE SCLEROSIS
findings suggest that vitamin D supplementation may have a therapeutic role in the treatment of MS. https://pubmed.ncbi.nlm.nih.gov/30284038/
Sufficient levels of vitamin D during pregnancy may be protective against offspring's development of multiple sclerosis later in life. https://pubmed.ncbi.nlm.nih.gov/32014337/
Our meta-analysis showed a significant negative correlation between 25 (OH) vitamin D level and disability of MS patients so that the disability reduces with increasing the 25 (OH) vitamin D level. https://pubmed.ncbi.nlm.nih.gov/33709027/
CHRON’S DISEASE
We found that patients with Crohn's disease had lower serum 25(OH)D concentrations compared with their healthy counterparts, and more than half of them have hypovitaminosis D. Moreover, there was an inverse correlation between circulating 25(OH)D concentrations and severity of Crohn's disease. https://pubmed.ncbi.nlm.nih.gov/26837598/
IRRITABLE BOWEL SYNDROME
Vitamin D supplementation significantly improved IBS symptom severity scale scores https://pubmed.ncbi.nlm.nih.gov/35396764/
INFLAMMATORY BOWEL DISEASE
IBD is significantly associated with having higher odds of vitamin D deficiency. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615394/
ASTHMA
Vitamin D supplementation reduced the rate of asthma exacerbations requiring treatment with systemic corticosteroids overall. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693329/
ALLERGIC RHINITIS
lower vitamin D levels were associated with a higher AR prevalence only in children https://pubmed.ncbi.nlm.nih.gov/27188226/
ULCERATIVE COLITIS
Compared with placebo control interventions, vitamin D supplementation seemed to be an effective intervention for patients with ulcerative colitis https://pubmed.ncbi.nlm.nih.gov/34075433/
ATOPIC DERMATITIS (ECZEMA)
Vitamin D has a potentially significant role for improving the symptoms of Atopic Dermatitis. The results from this study suggest that vitamin D supplementation may help ameliorate the severity of AD, and can be considered as a safe and tolerable therapy.
https://pubmed.ncbi.nlm.nih.gov/
RHEUMATOID ARTHRITIS
Compared with placebo control interventions, vitamin D supplementation seemed to be an effective intervention for patients with rheumatoid arthritis. Different doses of vitamin D and durations of intervention produce different effects. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661491/
PARKINSON’S DISEASE
this systematic review indicates that Parkinson’s Disease is associated with lower serum vitamin D levels. Secondly, higher vitamin D levels are associated with better balance, and vitamin D supplementation appears to have a positive effect on Parkinson’s Disease motor symptoms. Finally, results from rodent models suggest that vitamin D may also have a neuroprotective effect https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927872/
FIBROMYALGIA
Vitamin D supplementation may be an effective fibromyalgia therapeutic approach. https://www.tandfonline.com/doi/abs/10.1080/17512433.2022.2081151?journalCode=ierj20
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CANCER
General
Vit D deficiency was directly related to breast cancer while total vitamin D and supplemental vitamin D intakes had an inverse relationship (increased Vitamin D, decreased breast cancer) with this outcome. https://pubmed.ncbi.nlm.nih.gov/30904218/
Vitamin D supplementation significantly reduced total cancer mortality https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821324/
Vitamin D supplementation reduced the risk of cancer death by 16% https://pubmed.ncbi.nlm.nih.gov/31405892/
COLORECTAL CANCER
This meta-analysis demonstrates that vitamin D not only has a positive impact on the incidence of Colorectal Cancer from either the dietary or supplemental sources but also benefits clinical outcomes and improves the long-term survival of Colorectal Cancer patients https://pubmed.ncbi.nlm.nih.gov/33598751/
NON-HODGKIN LYMPHOMA
While risk estimates varied by different measures of vitamin D status, a protective effect of sunlight/UVR exposure on NHL incidence was verified, across most of the tested subtypes as well as exposure categories. https://pubmed.ncbi.nlm.nih.gov/31034511/
PEDIATRIC CANCERS
There is a possibility of a high prevalence of vitamin D inadequacy in pediatric cancer patients, especially older children urging the need for high-quality population-based longitudinal studies using standard definitions. https://pubmed.ncbi.nlm.nih.gov/25638403/
GASTRIC CANCER
Vitamin D levels are negatively correlated with the occurrence of gastric cancer. Vitamin D levels are significantly correlated with different clinical stages, degrees of differentiation and lymph node metastasis, suggesting that low vitamin D levels may be a predictor of poor prognosis in gastric cancer. https://www.researchgate.net/publication/356238140_Vitamin_D_and_gastric_cancer_A_systematic_review_and_meta-analysis
BLADDER CANCER
Ensuring sufficient serum 25-hydroxyvitamin D concentrations might play an important role in decreasing the risk of bladder cancer. The serum 25-hydroxyvitamin D concentration ≥74 nmol/L was associated with a 60% lower risk of bladder cancer incidence. https://pubmed.ncbi.nlm.nih.gov/26822497/
LIVER CANCER
The results of this meta-analysis indicate that vitamin D deficiency is associated with increased risk of liver cancer. The 25(OH)D3 levels are lower in HCC patients than those in health controls. Maintenance of sufficient serum vitamin D levels would be beneficial for prevention of liver cancer. https://pubmed.ncbi.nlm.nih.gov/33906289/
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INFECTIOUS DISEASE
COVID-19
Low serum vitamin D levels are statistically significantly associated with the risk of COVID-19 infection. Supplementation of vitamin D especially in the deficiency risk groups is indicated. https://pubmed.ncbi.nlm.nih.gov/34308537/
For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes…We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. https://pubmed.ncbi.nlm.nih.gov/35793346/
Conclusively, COVID-19 patients supplemented with vitamin D are more likely to demonstrate fewer rates of ICU admission, mortality events, and RT-PCR positivity. https://pubmed.ncbi.nlm.nih.gov/35086394/
TUBERCULOSIS
Low serum vitamin D levels are associated with higher risk of active tuberculosis. Although more prospectively designed studies are needed to firmly establish the direction of this association, it is more likely that low body vitamin D levels increase the risk of active tuberculosis https://pubmed.ncbi.nlm.nih.gov/18245055/
INFLUENZA
The meta-analysis produced a corroboration that vitamin D supplement has a preventive effect on influenza. Strategies for preventing influenza can be optimized by vitamin D supplementation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777486/
NEONATAL RESPIRATORY DISTRESS SYNDROME
This systematic review and meta-analysis study suggests that vitamin D deficiency is very likely to be a high-risk factor of NRDS, and reasonable vitamin D supplementation during pregnancy and after birth is of great significance. https://pubmed.ncbi.nlm.nih.gov/35127597/
OTHER RESPIRATORY TRACT INFECTIONS
Vitamin D supplementation decreases the events related to respiratory tract infections. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543548/
LOWER URINARY TRACT INFECTIONS
Consistent results indicated that vitamin D insufficiency was a crucial risk factor for lower urinary tract symptoms and that vitamin D supplementation showed promising effects on these symptoms. It would be of great guiding significance to consider vitamin D status when treating lower urinary tract symptoms. https://pubmed.ncbi.nlm.nih.gov/33207134/
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MENTAL/NEURODEVELOPMENTAL DISORDERS
DEPRESSION
The effect size for Vitamin D in depression demonstrated in this meta-analysis is comparable with the effect of anti-depressant medication, an accepted treatment for depression. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011048/
Our results support the hypothesis that vitamin D supplementation can reduce negative emotions. Patients with major depressive disorder and individuals with vitamin D deficiency are most likely to benefit from supplementation. https://pubmed.ncbi.nlm.nih.gov/32365423/
SCHIZOPHRENIA
Patients with schizophrenia have significantly lower levels of vitamin D than controls. Also, subjects with schizophrenia were more likely to have vitamin D deficiency or insufficiency compared to controls. In conclusion, our analyses are consistent with the hypothesis that vitamin D deficiency is associated with schizophrenia. https://pubmed.ncbi.nlm.nih.gov/32335466/
DEMENTIA
The results of this systematic review show that low vitamin D levels might contribute to the development of dementia. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237198/
ADHD
Children and adolescents with ADHD have lower mean concentrations of serum Vitamin D than do healthy controls. The studies also showed a significant association between lower vitamin D status and the likelihood of ADHD. Furthermore, the meta-analysis of prospective studies indicated that perinatal vitamin D status is significantly associated with risk of ADHD in childhood or adolescence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333940/
OTHER PSYCHIATRIC DISORDERS
Overall, the current meta-analysis demonstrated that taking vitamin D supplements among patients with psychiatric disorders had beneficial effects, improved mental health and reduced inflammatory markers https://www.sciencedirect.com/science/article/abs/pii/S0278584619302258
COGNITION
Our meta-analyses support the relationship between low vitamin D, poor cognition and cognitive decline in observational studies https://pubmed.ncbi.nlm.nih.gov/28758188/
MEMORY AND LEARNING
despite the nonsignificance of the relationship between serum levels of vitamin D and memory, learning, and cognitive and executive function, increased serum levels of vitamin D and the cases cited in the reviewed studies were positively associated. https://www.alliedacademies.org/articles/vitamin-d-and-its-association-with-memory-and-learning-a-systematic-review-and-metaanalysis.pdf
BRAIN VOLUME
this systematic review and meta-analysis provides evidence that participants with vitamin D depletion have smaller brain volume and enlarged lateral ventricles than participants without vitamin D depletion. Mechanisms implicated could be based on reduced bioavailability of neurotrophic agents and on the loss of the neuroprotective effects of vitamin D, making the central nervous system less resistant and/or more sensitive to any stress. https://www.sciencedirect.com/science/article/abs/pii/S0378512214000644
AUTISM SPECTRUM DISORDER
Vitamin D plays a significant role in brain homeostasis, neurodevelopment, and immunological modulation, and its deficiency has been reported in children with ASD. The polymorphism of Vitamin D Receptor was associated with an increased risk of ASD https://www.nature.com/articles/s41398-022-02009-6
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REPRODUCTIVE DISORDERS
MISCARRIAGE
Vitamin D deficiency and insufficiency are associated with miscarriage. https://www.sciencedirect.com/science/article/pii/S0015028222002588
RECURRENT SPONTANEOUS ABORTION
Patients with Recurrent Spontaneous Abortion had lower serum vitamin D levels than normal pregnant women, and pregnant women with Vitamin D Deficiency might be at higher risk for RSA. https://onlinelibrary.wiley.com/doi/10.1111/aji.13582?af=R
PRE TERM BIRTH
vitamin D deficiency in middle pregnancy is likely to have an important effect on Pre Term Births. Vitamin D levels should be measured in the second trimester of pregnancy, and vitamin D supplements should be provided if necessary. https://journals.lww.com/md-journal/fulltext/2021/06180/systematic_review_and_meta_analysis_of_vitamin_d.26.aspx
ENDOMETRIOSIS
Women with endometriosis had lower vitamin D status when compared with controls, and a negative relationship between vitamin D levels and severity of endometriosis was observed. In addition, hypovitaminosis D was a potential risk factor for endometriosis. https://pubmed.ncbi.nlm.nih.gov/32430755/
OTHER REPRODUCTIVE DISORDERS
Vitamin D influences the functioning of the reproductive system in women and has been associated with PCOS, uterine leiomyomas, endometriosis and in vitro fertilization (IVF) outcome. https://pubmed.ncbi.nlm.nih.gov/28030942/
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CARDIOVASCULAR DISEASE
GENERAL
Data from prospective investigations suggest an inverse association between Vit D level and cardiovascular risk (increasing Vit D, decreasing CVD). https://www.sciencedirect.com/science/article/abs/pii/S0091743510002409
MAJOR ADVERSE CARDIOVASCULAR EVENTS
low blood levels of vitamin D are associated with MACE, but no such difference in all-cause mortality, myocardial infarction or heart failure was observed. Appropriate supplementation of vitamin D in selected populations might be cardioprotective in nature and warrants extensive trials. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019228/
STROKE
Our analysis indicated that lower circulating level of vitamin D was associated with an elevated risk of stroke https://pubmed.ncbi.nlm.nih.gov/34325429/
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline serum Vitamin D levels <25 nmol/L (deficiency) but not in those with higher levels. https://pubmed.ncbi.nlm.nih.gov/34325429/
HYPERTENSION
this meta-analysis of epidemiologic studies disclosed that serum vitamin D concentration was inversely associated with risk of hypertension in adults, in a dose–response manner in both cohort and cross-sectional studies. The same association was found for pre-hypertension. https://pubmed.ncbi.nlm.nih.gov/35360696/
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SLEEP DISORDERS
vitamin D deficiency is associated with a higher risk of sleep disorders. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213953/
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VERTIGO
The available evidence suggests that Benign Paroxysmal Positional Vertigo is associated with decreased levels of serum Vitamin D, and vitamin D deficiency was an independent risk factor for BPPV. https://pubmed.ncbi.nlm.nih.gov/31630244/
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DENTAL CARIES
The analysis of controlled clinical trials data identified vitamin D as a promising caries-preventive agent, leading to a low-certainty conclusion that vitamin D may reduce the incidence of caries. https://pubmed.ncbi.nlm.nih.gov/23356636/
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MYOPIA (NEARSIGHTEDNESS)
Lower serum Vitamin D is associated with increased risk of myopia https://pubmed.ncbi.nlm.nih.gov/30018147/
SIGHT THREATENING DIABETIC RETINOPATHY
Vitamin D deficiency is significantly associated with Sight Threatening Diabetic Retinopathy. Given the well-reported associations between vitamin D deficiency and other unfavourable outcomes, it is important that vitamin D deficiency is managed appropriately and in a timely manner to reduce the risk of blindness in people with diabetes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167360/
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Despite the mountain of research, current medical standards still do not recommend serum Vitamin D as a diagnostic in clinical practice for most people. Similarly, the silence regarding Vitamin D from public health officials is deafening. Make of that what you will.
The take home message here is
Know where you stand by having your Vitamin D level routinely tested
Take the appropriate steps to optimize your levels if necessary
Attempt to uncover and resolve or mitigate your underlying causes of suboptimal Vitamin D levels
For a compilation of the best practical steps specifically regarding Vitamin D optimization see here: Optimize Your Vitamin D Levels
Finally, read part 2 of this article found below which explores the primary causative link to Vitamin D dysregulation and the chronic illnesses listed above.
Spoiler Alert: Glyphosate/Roundup is exposed as Public Enemy #1!
I hope you find this “cheat sheet” useful and, with further exploration, are able to integrate these ideas into your personal, integrated wellness routine.
Thank you for reading and I welcome your comments below!
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