Vitamin D is a Steroid Hormone and Supplementation Should be Cautioned – Overview & Collected Research

Overview of the Evidence for Concern Regarding Vitamin D Supplementation:

Doctors and natural practitioners only test for one storage form of vitamin D (25D), not the physiologically active form (1,25D). We also store 25D in adipose tissue, which is not measured by a blood test.

Despite what is commonly claimed, the human body can synthesize precursors to the active form of vitamin D (1,25) from exposure to UVA wavelengths of light, which are able to be obtained in early morning, at higher latitudes, during winter, or through windows. These precursor forms are not measured by a blood test.

The blood level of 25D which is considered sufficient by medical doctors was raised from 20 ng/mL to 30 ng/mL in 2010. Naturopaths often set a target of 50 – 100 ng/mL for treating symptoms.

Blood levels associated with lowest mortality are between 20 – 24 ng/mL. High levels are associated with increased risk of fractures and calcification.

25D is used to synthesize 1,25D. Magnesium is required to convert 25D to 1,25D. Supplementation of vitamin D3 can deplete magnesium levels.

Low storage (25D) levels do not indicate low active (1,25D) levels. 

Healthy range for the active form (1,25D) is 18 – 78 picograms per milliliter (pg/mL). 25D is measured in nanograms per milliliter (ng/mL). 1 ng = 1,000 pg.

Vitamin D3 (and D2) supplements supply the body with additional storage (25D).

The active form (1,25D) needs to bind to Vitamin D Receptors (VDRs) in order to provide physiological benefits.

Excess storage form (25D) will block the active form (1,25D) from binding to VDRs.

Underlying chronic illness is linked to low vitamin D levels.

A state of chronic illness can allow pathogenic bacteria to proliferate and block VDRs, preventing the active form from binding. To compensate for this, the body increases the rate of conversion of 25D to 1,25D, which can result in low 25D, and high 1,25D.

Underlying illness leads to low vitamin D (25D) levels (12 ng/mL or below), rather than low vitamin D levels leading to chronic illness.

Vitamin D is a steroid hormone. Supplemental vitamin D acts to suppress the adaptive immune system. This can alleviate symptoms via immune system suppression.

The immune system is the cause of inflammation and symptoms. Inflammation is not a root cause, rather it is an immune system response to tissue or cellular damage, often from toxic exposures. Immune system action that attempts to address cellular injury from toxic exposures is an important process for maintaining long term health.

Glucocorticoids, like Prednisone, also act to eliminate symptoms through suppression of the adaptive immune system, via similar mechanisms as Vitamin D3, by impairing dendritic cells.

Despite relief from symptoms short term, immune suppression from vitamin D supplementation leads to worsened internal conditions over the long term.

Aside from magnesium deficiency and calcification, other documented negative effects of excess vitamin D and/or chronic vitamin D supplementation include increased absorption of toxic metals like aluminum, depletion of vitamin B5, kidney stones, kidney damage, proliferation of pathogens in the body, and the development or worsening of chronic conditions.

Vitamin D is necessary but excess levels of 25D can quickly accumulate in the body as a result of vitamin D3 supplementation, due to the long half-life of 25D (2 weeks to 2 months).

While symptom suppression can improve quality of life, it does not correct the underlying root cause of chronic illness. Focusing on other methods to improve health by supporting detoxification and immune system function will allow vitamin D levels to regulate naturally.

The following is a collection of studies and quotes that I gathered over the course of nearly two years diving into the research on vitamin D. It began when I was reading research on aluminum toxicity and stumbled upon a study that stated vitamin D increases the absoprtion of aluminum. I dove in from there. Special thanks to Jim Stephenson Jr for some assistance at the beginning of my journey.

25D VS 1,25D

A Reverse J-Shaped Association of All-Cause Mortality with Serum 25-Hydroxyvitamin D in General Practice: The CopD Study (2012)

“The biomarker used for the determination of vitamin D status is 25(OH)D, rather than the biologically active hormone 1,25-dihydroxyvitamin D.”

Half-life of 25D

“The term vitamin D refers collectively to vitamin D3 and vitamin D2, which is derived from irradiation of the steroid ergosterol in yeast. Biologically active vitamin D is generated via largely hepatic 25-hydroxylation catalyzed by CYP2R1, CYP27A1, and possibly other enzymes to produce 25-hydroxvitamin D (25D) (21, 40, 43, 67, 81), which has a long half-life and is the major circulating vitamin D metabolite.”

“The major circulating metabolite of vitamin D, 25-hydroxyvitamin D (25D) has a half-life of several weeks and varies seasonally with fluctuations in cutaneous vitamin D synthesis.”

“…caution is warranted with dose frequency because there is no conversion required and also because the half-life of 25D is longer (15–18 days) than that of vitamin D (3–7 days), which could result in rapid accumulation to levels above the normal upper range (150 ng/ml).”

“Orally administered vitamin D has access to peripheral tissues from the chylomicron before arriving at the liver for uptake and metabolism. This results in the rapid circulating half-life (4 – 6 h) despite a much longer whole body half-life (2 months) for exogenous vitamin D [20].”

“The freely circulating forms are available for receptor binding, metabolism and excretion. This provides a circulating half-life of 15 days for 25(OH)D3 at concentrations of 25 – 200 nmol/l. At intakes up to approximately 50mg daily, vitamin D3 storage occurs as circulating 25(OH)D3. Adipose tissue is described as a storage site of the vitamin, at higher doses.”

Vitamin D3 increases in abdominal subcutaneous fat tissue after supplementation with vitamin D3 (2015)

“…the subjects in the placebo [no-vitamin D supplementation] group in our study had a median amount of 0.95 mg or 0.04 mill IU fat-stored vitamin D. If this could be mobilized and used at least as efficiently as vitamin D from supplementation, it is equivalent to 90 daily doses of 400 IU.”

HIGH 1,25D

Vitamin D Metabolites as Clinical Markers in Autoimmune and Chronic Disease (2009)

“Results showed a strong positive association between these autoimmune conditions and levels of 1,25-D >110 pmol/L. However, there was little association with vitamin D deficiency or the other inflammatory markers, meaning that the results challenge the assumption that serum levels of 25-D are a sensitive measure of the autoimmune disease state. Rather, These findings support the use of 1,25-D as a clinical marker in autoimmune conditions. High levels of 1,25-D may result when dysregulation of the VDR by bacterial ligands prevents the receptor from expressing enzymes necessary to keep 1,25-D in a normal range.”

Exploring the role of vitamin D in type 1 diabetes, rheumatoid arthritis, and Alzheimer disease: new insights from accurate analysis of 10 forms. (2014)

There are 14 different 25D’s.

Doctors only test for the first two:

  • 25(OH)D2
  • 25(OH)D3
  • 25(OH)D4
  • 25(OH)D2 sulfate 
  • 25(OH)D3 sulfate
  • 25(OH)D4 sulfate
  • Epi-3-25(OH)D2
  • Epi-3-25(OH)D3
  • Epi-3-25(OH)D4
  • Epi-3-25(OH)D2 Sulfate 
  • Epi-3-25(OH)D3 Sulfate 
  • Epi-3-25(OH)D4 Sulfate 
  • 25(OH)D3-Lactone
  • 25(OH)D3 Glucuronide

Sunlight and Vitamin D (2013)

“During exposure to sunlight 7-dehydrocholesterol in the skin absorbs UV B radiation and is converted to previtamin D3 which in turn isomerizes into vitamin D3. Previtamin D3 and vitamin D3 also absorb UV B radiation and are converted into a variety of photoproducts some of which have unique biologic properties.”

“During exposure to sunlight solar radiation with wavelengths of 290–315 nm penetrate into the skin and are absorbed by proteins, DNA and RNA as well as 7-dehydrocholesterol.1,2 Most of this UVB radiation is absorbed in the epidermis and as a result when exposed to sunlight most of the vitamin D3 that is produced in the skin is made in the living cells in the epidermis.”

“When epidermal 7-dehydrocholesterol absorbs solar UVB radiation with energies of 290–315 nm (Fig. 10), it causes an activation of the double bonds causing them to rearrange and open up the B ring to form the seco-steroid (split steroid) previtamin D3.”

“Therefore no matter how much sun a human is exposed to vitamin D intoxication will not occur because any excess previtamin D3 and vitamin D3 is photodegraded into products that have no calcemic activity.”

“Therefore sensible sun exposure to produce previtamin D3, vitamin D3 and its photoproducts may have some additional benefits above and beyond simply taking a vitamin D3 supplement or ingesting vitamin D3 from dietary sources.”

“People who live in the far Northern and Southern hemispheres [with insufficient sunlight exposure in winter] were able to satisfy their vitamin D requirement by eating vitamin D rich foods…”

“Since glass absorbs all UVB radiation, exposure of the skin to sunlight that passes through glass, plexiglass, and plastic will not result in any production of vitamin D3 in the skin…”


“Just recently it has been found that previtamin D can be generated to substantial amounts from tachysterol by irradiation at wavelengths above 315–340 nm. This is in stark contrast to the common belief that vitamin D cannot be produced at wavelengths longer than 320 nm. With respect to the vitamin D deficiency problem, this is an important finding, because this means that even in winter at northern latitudes or in the morning and evening hours of the day, where high energetic UV radiation is not available, previtamin D could be synthesized by Sun exposure. This indicates that Tachy can act as a previtamin D reservoir which is charged under conditions where high energetic UV radiation is present, but can be later used as previtamin D source at longer UV wavelengths.”


Magnesium-dependent rickets (1974)

Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (2013)

“…it is possible that magnesium intake alone or its interaction with vitamin D intake may contribute to vitamin D status.”

Magnesium status and supplementation influence vitamin D status and metabolism (2018)

“…in vitro and in vivo studies indicate that enzymes that synthesize and metabolize vitamin D are magnesium dependent. Recent observational studies found that magnesium intake significantly interacted with vitamin D in relation to vitamin D status and risk of mortality.”

Does magnesium hold the key to vitamin D benefits? (2018)

“Magnesium deficiency shuts down the vitamin D synthesis and metabolism pathway.”

“Treatment with a magnesium supplement led to an increase in vitamin D levels in people who had low levels initially, but it reduced levels of the sunshine vitamin in those with high levels.

This is important because there is an association between too much vitamin D and excess calcium in the blood (hypercalcemia), which can cause serious health complications.”

Excess vitamin D can cause magnesium deficiency.!po=0.295858 (2018)

Role of Magnesium in Vitamin D Activation and Function (2018)

“All of the enzymes that metabolize vitamin D seem to require magnesium, which acts as a cofactor in the enzymatic reactions in the liver and kidneys. Deficiency in either of these nutrients is reported to be associated with various disorders, such as skeletal deformities, cardiovascular diseases, and metabolic syndrome.”

“Magnesium activates more than 600 enzymes and influences extracellular calcium levels. It is essential for the stability of cell function, RNA and DNA synthesis, and cell repair, as well as maintaining the antioxidant status of the cell.”

“Approximately 0.3% of total body magnesium is found in serum; therefore, serum magnesium concentration does not reflect the total amount of body magnesium content and is a poor predictor of intracellular magnesium content. Even when the skeletal or intracellular magnesium content of soft tissue may be depleted, the circulating levels of magnesium could remain within the normal range because of its tight homeostatic control…”

“Vitamin D needs to be converted from its storage or inactive form (25[OH]D) to an active form (1,25[OH]2D) before exerting its biological functions. These various stages of vitamin D conversions are actively dependent on the bioavailability of magnesium.”

“The standard diet in the United States contains about 50% of the recommended daily allowance (RDA) for magnesium, and as much as three-quarters of the total population is estimated to be consuming a magnesium-deficient diet.”

“Magnesium deficiency results in reduced levels of 1,25(OH)2D and impaired parathyroid hormone (PTH) response, and it has been implicated in magnesium-dependent vitamin D–resistant rickets. Magnesium supplementation was shown to markedly reduce the resistance to vitamin D treatment.”

“Also, magnesium plays a significant role in the immunoregulation of the body. It is critical to immunocompetence and in natural and adaptive immunity, partly by influencing the activity of vitamin D metabolites.”

“Consuming the RDA of magnesium may be more effective in preventing bone thinning than vitamin D, as magnesium potentiates vitamin D activities, possibly by increasing its absorption and endogenous activation.”

“Magnesium has been found to be a contributing factor in patients with established osteoporosis with vitamin D deficiency and blunted PTH level. Studies have suggested that magnesium could influence PTH synthesis and determine the number of vitamin D receptors; therefore, a deficiency in magnesium levels may lead to diminished synthesis and secretion of PTH and a reduced number of available vitamin D receptors in the target cells.”

Low 25-Hydroxyvitamin D and Myofascial Pain: Association of Cancer, Colon Polyps, and Tendon Rupture (2017)

“…it is difficult to reliably assess the body’s magnesium reserves, even using current clinical tests such as serum magnesium and red blood cell (RBC) magnesium. Both tests can produce results within the current reference range in individuals who have total body deficiency, because the body works hard to maintain a narrow range of magnesium blood levels.”

“…studies showed that vitamin D3 supplementation and calcium did not reduce the incidence of colorectal adenomas or colon cancer, but magnesium intake through food or water was not addressed. The finding that vitamin D and calcium supplements did not reduce colon adenomas or cancer supports the magnesium hypothesis, because calcium supplementation does not resolve vitamin D deficiency, and supplementing vitamin D3 does not resolve a possible magnesium deficiency.”

Magnesium Supplementation in Vitamin D Deficiency (2019)

“…vitamin D supplementation has become a common practice, but Mg deficiency still remains unaddressed. Screening for chronic magnesium deficiency is difficult because a normal serum level may still be associated with moderate to severe deficiency. To date, there is no simple and accurate laboratory test to determine the total body magnesium status in humans. Mg is essential in the metabolism of vitamin D, and taking large doses of vitamin D can induce severe depletion of Mg.”


Role of Vitamin D Beyond the Skeletal Function: A Review of the Molecular and Clinical Studies (2010)

“Antigen presenting cells (APC) of the innate immune system stimulate the lymphocytes of adaptive immunity through antigen presentation to remove the infectious agents. Dendritic cells (DCs) are the most potent APC and are broadly classified into two subtypes based on their origin including myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). 1,25(OH)2D3 and its analogs are reported to inhibit the maturation, differentiation, and survival of DCs.”

“The overall effect of vitamin D treatment on DC is the decrease in T helper 1 (Th1) cell response.”

Several studies indicated that 1,25(OH)2D3 suppresses T lymphocytes proliferation

1α,25-Dihydroxyvitamin D3 Inhibits Differentiation, Maturation, Activation, and Survival of Dendritic Cells Leading to Impaired Alloreactive T Cell Activation (2000)

“…dendritic cells (DCs) are major targets of 1,25(OH)2D3-induced immunosuppressive activity. 1,25(OH)2D3 prevents the differentiation in immature DCs of human monocytes…”

“This is associated with a reduced capacity of DCs to activate alloreactive T cells…”

“In addition, 1,25(OH)2D3 promotes the spontaneous apoptosis of mature DCs.”

“The inhibition of DC differentiation and maturation as well as modulation of their activation and survival leading to T cell hyporesponsiveness may explain the immunosuppressive activity of 1,25(OH)2D3.”

Dendritic cell modulation by 1α,25 dihydroxyvitamin D3 and its analogs: A vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo (2001)

“Maturation of DCs is inhibited by physiological levels of 1α,25 dihydroxyvitamin D3 [1α,25(OH)2D3] and a related analog, 1α,25(OH)2-16-ene-23-yne-26,27-hexafluoro-19-nor-vitamin D3 (D3 analog). Conditioning of bone marrow cultures with 10−10 M D3 analog resulted in accumulation of immature DCs with reduced IL-12 secretion and without induction of transforming growth factor β1. These DCs retained an immature phenotype after withdrawal of D3 analog and exhibited blunted responses to maturing stimuli…”

“Resistance to maturation depended on the presence of the 1α,25(OH)2D3 receptor (VDR).”

1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes

“1-a,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a steroid hormone known for its ability to regulate calcium metabolism.”

“When monocytes are exposed to 1,25(OH)2D3 during their differentiation into iDCs, the resulting cells are less capable of stimulating T-cell proliferation.”

“Our data are largely in accordance with this picture of 1,25(OH)2 D3 as an immunosuppressive agent for DC development. We confirmed that 1,25(OH)2D3 hampers the differentiation of monocytes into DCs, generating a population of iDCs with a reduced capacity to induce T-cell proliferation. These iDCs generated while exposed to 1,25(OH)2D3 differed in phenotype from classical iDCs.”

“Apparently… 1,25(OH)2D3 skews monocyte differentiation away from [antigen presenting cell] development and towards the direction of mature phagocytosing macrophages. Thus, this hormone probably favours the development of a strong, non-specific, innate immune reaction over that of an antigen-specific immune response.”

Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system (2004)

“On the basis of the ability of 1,25(OH)2D3 to suppress the development of various autoimmune diseases and to prolong allograft survival, 1,25(OH)2D3 has been called an immunosuppressive hormone.”

Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility to Citrobacter rodentium by suppressing mucosal Th17 responses (2012)

“1,25(OH)2D3 treatment of infected mice led to increased pathogen burdens and exaggerated tissue pathology. In association with their increased susceptibility, 1,25(OH)2D3-treated mice showed substantially reduced numbers of Th17 T cells within their infected colons…”

Reversing Bacteria-induced Vitamin D Receptor Dysfunction Is Key to Autoimmune Disease. (2009)

“…vitamin D supplementation, if it achieves high enough levels of the precursor forms (vitamin D and 25-D), actually contributes to VDR blockage and a decrease in the innate immune response.”

“Molecular modeling indicates that at high levels 25-D and 1,25-D can displace the natural ligands from nuclear receptors, such as the thyroid-α- 1, adrenal, and glucocorticoid receptors. This displacement appears to have the potential to disrupt the endocrine system. It could also lead to immunosuppression by reducing the ability of these receptors to induce production of antimicrobial peptides.

Thus, at least two mechanisms exist by which vitamin D supplementation could suppress innate immune system function. This suppression would lead to short-term improvements in patients taking higher levels of vitamin D by slowing bacterial death and subsequent immunopathological reactions. Therefore, studies that evaluate the role of vitamin D supplementation in chronic inflammatory diseases should take into account the potential for short-term symptom reduction as well as exacerbation of the disease process over the long term from pathogen increase.”

Topically Applied 1,25-Dihydroxyvitamin D3 Enhances the Suppressive Activity of CD4+CD25+ Cells in the Draining Lymph Nodes (2007)

“This study demonstrates for the first time that a single topical application of a physiologically relevant amount of 1,25(OH)2D3 to the shaved dorsal skin of mice enhances the suppressive capacity of CD4+CD25+ regulatory T cells in the SDLN.”

Regulatory T cells (TREG) and their roles in immune system with respect to immunopathological disorders. (2010)

“Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress immune response…”

“Chronic feeding of mice with 1,25(OH)2D3 suppressed autoimmune responses in a variety of different mouse models including type 1 diabetes… (8), experimental autoimmune encephalitis(9), arthritis (20 ng 1,25(OH)2 D3 /day, commencing one day before the induction of disease) (10) and asthma (1.6 IU 1,25(OH)2D3/g diet) (11).”


Vitamin D: The alternative hypothesis. (2009)

“Emerging molecular evidence suggests that symptomatic improvements among those administered vitamin D is the result of 25-D’s ability to temper bacterial-induced inflammation by slowing VDR activity. While this results in short-term palliation, persistent pathogens that may influence disease progression, proliferate over the long-term.”

(Reduces inflammation, does not eradicate the bacteria.)

HIGH LEVELS OF 25D DEPLETE VITAMIN B5 (Pantothenic acid) after two years of maintaining 60-80ng/ml blood levels:

Vitamin D deficiency changes the intestinal microbiome reducing B vitamin production in the gut. The resulting lack of pantothenic acid adversely affects the immune system, producing a “pro-inflammatory” state associated with atherosclerosis and autoimmunity (2016)

Vitamin D blood levels of 60-80ng/ml promote normal sleep. The present study was undertaken to explore why this beneficial effect waned after 2 years as arthritic pain increased.”

“In 2012 we reported a successful, uncontrolled trial of vitamin D supplementation (in doses to maintain a blood level of 60–80 ng/ml) as treatment for sleep disorders [1]. This current report documents the continued treatment of the same patient population for another four years. Despite maintaining a vitamin D blood level of 60–80 ng/ml, most patients’ sleep complaints began to return by the end of the second year.”

Improvements in sleep achieved by a vitamin D level of 60–80 ng/ml began to wane at the end of two years, and there were an increasing number of patients with new complaints of pain. References were found linking B5 deficiency to insomnia and pain in the form of a series of 1950s experiments…”

“The addition of B [vitamins] to the vitamin D regimen produced an improvement in both sleep and pain within days, suggesting that a vitamin B deficiency state had somehow been induced by the D supplementation and was now responsible for worsening sleep and pain.”


Vitamin D increases aluminum absorption: (2018)

“In animal studies, calcium deficiency in the diet has been shown to increase the rate and amount of Al absorption. Vitamin D supplementation may increase Al content in the muscles and hearts. Besides, the parathyroid hormone can increase the absorption of Al by stimulating renal synthesis of 1,25-dihydroxyvitamin D3.”

Vitamin D, Essential Minerals, and Toxic Elements: Exploring Interactions between Nutrients and Toxicants in Clinical Medicine (2015)

“Optimal nutritional status, including healthy levels of vitamin D and essential minerals, is requisite for proper physiological function; conversely, accrual of toxic elements has the potential to impair normal physiology. It is evident that vitamin D intake can facilitate the absorption and assimilation of essential inorganic elements (such as calcium, magnesium, copper, zinc, iron, and selenium) but also the uptake of toxic elements (such as lead, arsenic, aluminum, cobalt, and strontium).”


Vitamin D levels determined how human skin color evolved (2013)

“…humans living near the equator developed darker skin tones, while those in northern climates developed lighter hues. High humidity also decreases UVB levels, as marked by the contrast between skin tones of early humans living in dry equatorial Africa and moist equatorial South America.”

Human Skin Pigmentation as an Adaptation to UV Radiation. (2010)

Vitamin D: What’s the “right” level? (2016)

“…from an evolutionary standpoint, it doesn’t make sense that higher vitamin D levels would be beneficial to humans. ‘Vitamin D is actually quite hard to find in naturally occurring food sources,’ he points out. ‘Yes, we can get vitamin D from the sun, but our bodies evolved to create darker skin in the parts of the world that get the most sun. If vitamin D is so critical to humans, why would we evolve in this way, to require something that is hard to come by, and then evolve in such a way as to make it harder to absorb?’”


“No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures. Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration.” (2017)

High-Dose Vitamin D: No Help for Bone Health

— Surprise in randomized trial: a hint of actual adverse effect from supplementation. (2019)

Vitamin D might not be much help for strengthening bones among healthy adults without osteoporosis, Canadian researchers reported, even at doses far higher than recommended daily allowances.

In a clinical trial assessing three levels of daily vitamin D supplementation — 400 IU, 4,000 IU, and 10,000 IU — radial volumetric bone mineral density (BMD) was significantly lower among those (ages 55-70) taking higher doses for 3 years, according to Steven Boyd, PhD, of the University of Calgary in Canada, and colleagues:

No dose of vitamin D supplementation was able to prevent bone loss, as each dose saw a drop in the percentage of radial volumetric BMD over 3 years, they reported in JAMA:

400 IU: -1.2%

4,000 IU: -2.4%

10,000 IU: -3.5%


“…the administration of pharmacological doses of vitamin D sterols can lead to widespread arterial calcification, especially in association with favourable conditions such as atherosclerosis, diabetes and chronic kidney disease (CKD).”

“Literature data suggest that a biphasic dose-response curve exists between vitamin D and vascular calcification, with adverse effects associated with very high and very low vitamin D levels. Negative effects associated with vitamin D excess include hyperphosphataemia, hypercalcaemia, increased matrix metalloproteinase (MMP) levels, medial calcification, arterial stiffness and left ventricular hypertrophy.” (2012)

“…in 15 subjects, hypercalcemia could be directly attributed to vitamin D and serum 25-OH-vitamin D ranged between 164 and 1139 nmol/l [65.6 ng/ml and 455 ng/ml].” (2016)

High Levels of Active 1,25-Dihydroxyvitamin D Despite Low Levels of the 25-Hydroxyvitamin D Precursor-Implications of Dysregulated Vitamin D for Diagnosis and Treatment of Chronic Disease (2006)

“…dysregulated vitamin D conversion can mean that even a moderate intake of vitamin D through ingestion or solar exposure can cause the 1,25D hormone to become high enough to stimulate osteoclastic action, and bone resorption.”


“Select stone formers may be at increased risk for recurrence with vitamin D supplementation, possibly from CYP24A1 gene mutations.” (2020)

“Low 25-hydroxyvitamin D serum levels have been associated with a broad spectrum of diseases, leading to a huge increase in vitamin D prescription in the general population. In parallel, an increased frequency of kidney stone episodes has been observed in prospective studies evaluating vitamin D alone or in association with calcium supplements, and epidemiological studies have identified an association between high 25-hydroxyvitamin D serum levels and kidney stone formation in some groups of patients.” (2018)


Vitamin D overconsumption leaves man with permanent kidney damage. (2019)

“…the man was typically receiving between 8,000 and 12,000 international units (IU) of vitamin D per day [for 2.5 years].”


Elevated Levels of 1,25-Dihydroxyvitamin D in Plasma as a Missing Risk Factor for Celiac Disease (2020)

“First, elevated plasma levels of 1,25(OH)2D are common in CD, especially in the newly diagnosed. Second, nine distinct conditions that increase plasma levels of 1,25(OH)2D are either associated with CD or have indications of such an association in the literature. Third, a retrospective study shows that sustained oral vitamin D supplementation in infancy is associated with increased CD risk, and other studies on comorbid conditions support this association. Fourth, large doses of oral vitamin D upregulate many of the same cytokines, chemokines, and toll-like receptors that are upregulated in CD. Fifth, epidemiological evidence, such as the timing of the inception of a CD “epidemic” in Sweden, the increased prevalence of CD in Finland and the United States in recent decades, the unusually low prevalence of CD in Germany, and the differential in prevalence between Finnish Karelians and Russian Karelians, may all be explained by oral vitamin D exposure increasing CD risk.”

Potential risk factors for celiac disease in childhood: a case-control epidemiological survey (2019)

“This study is the first to find an association between skim milk consumption and CD and vitamin D drop use for greater than 3 months and CD. It also adds to evidence that early life exposure to antibiotics and early life infection, specifically ear infection, are associated with CD.”

Exposure to excessive oral vitamin D in youth: a risk factor for celiac disease in later life? (2015)

“Vitamin D is a prohormone with a number of biochemical functions including immunomodulatory functions in its active form. Supplementation with large doses of vitamin D induces symptoms that are similar to celiac disease in some of the population.”

“A wealth of evidence supports the hypothesis that significant consumption of oral vitamin D among the young is a risk factor for inducing celiac disease. Exposing infants and toddlers to large doses of oral vitamin D has been found to be a risk factor for inducing allergic diseases including atopic dermatitis and asthma both of which have a high comorbidity with celiac.”


Acetaminophen, antibiotics, ear infection, breastfeeding, vitamin D drops, and autism: an epidemiological study!po=0.454545 (2018)

“…the results suggest that postnatal oral vitamin D is weakly associated with increased risk of ASD.”

“…vitamin D drops as well as modeled total oral vitamin D consumed were both weakly associated with ASD in this sample when adjusted for breastfeeding. While none of these results are statistically significant using a 0.05 threshold, analogous results for both vitamin D drops and total vitamin D are statistically significant if gender is not included as a covariate (Table S8). These results seem to support Zhou et al’s work suggesting that excessive nutrient intake may be a risk factor for ASD.25 Specifically, these results suggest that excessive postnatal oral vitamin D exposure may be a risk factor for ASD.”


Vitamin D supplementation worsens Alzheimer’s progression: Animal model and human cohort studies (2022)

“…we first observed that APP/PS1 mice fed a vitamin D‐sufficient diet showed significantly lower levels of serum vitamin D, suggesting its deficiency may be a consequence not a cause of AD. Moreover, supplementation of vitamin D led to increased Aβ deposition and exacerbated AD.”

“Consistently, our population‐based longitudinal study also showed that dementia‐free older adults (n = 14,648) taking vitamin D3 supplements for over 146 days/year were 1.8 times more likely to develop dementia than those not taking the supplements. Among those with pre‐existing dementia (n = 980), those taking vitamin D3 supplements for over 146 days/year had 2.17 times the risk of mortality than those not taking the supplements.”


Studies show that people with the highest levels of vitamin D actually tend to have more bone fractures, fall more frequently, sleep less well, and die sooner than those with lower, but sufficient, levels. If your level is over 20 ng/mL, you probably don’t need a supplement. If your level is above 35 ng/mL, taking a supplement may be doing more harm than good…” (2019)

“…the research results also show higher mortality in people with too high levels of vitamin D in their bloodstream.”

“If the blood contains less than 10 nanomol (nmol) of vitamin per liter of serum [ 4 ng/mL ], mortality is 2.31 times higher. However, if the blood contains more than 140 nmol of vitamin per liter of serum [ 56 ng/mL ], mortality is higher by a factor of 1.42. Both values are compared to 50 nmol of vitamin per liter of serum [ 20 ng/mL ], where the scientists see the lowest mortality rate.” (2012)

“…low and high levels of 25(OH)D were associated with cardiovascular disease, stroke, and acute myocardial mortality.” (2015)

The lowest mortality risk was at 50–60 nmol/liter [20-24ng/ml].” (2012)


“Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.” (2014)

“The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders.” (2013)

Controversies and consensus regarding vitamin D deficiency in 2015: whom to test and whom to treat? (2015)

“To minimise the impact of reverse causation, a recent systematic review examining the relationship between 25(OH)D concentration and ill health analysed prospective and nested case–control studies where the disorder of interest was not previously diagnosed and only studies that measured 25(OH)D concentrations, rather than predicted vitamin D status according to sunlight exposure or dietary intake, were included, to limit classification bias. The authors confirmed that most prospective observational studies showed an inverse association between 25(OH)D concentrations and a number of diverse health outcomes. However, to minimise residual confounding and determine causality, analysis of the randomised trials of vitamin D supplementation was also undertaken. This showed, almost universally, that vitamin D supplementation had little or no effect on the occurrence, severity and clinical course of these illnesses — even after subgroup analyses of subjects with vitamin D deficiency who received adequate dose supplementation. The discrepancy between the observational and interventional trial findings suggests that low 25(OH)D may be a marker, rather than a cause, of ill health — perhaps reflecting the effects of inflammation and the negative acute phase response of vitamin D-binding protein.”

Low blood levels of vitamin D have long been associated with disease, and the assumption has been that vitamin D supplements may protect against disease. However, this new research demonstrates that ingested vitamin D is immunosuppressive and that low blood levels of vitamin D may be actually a result of the disease process. Supplementation may make the disease worse.”


Inflammation and vitamin D: the infection connection (2014)

“Some authorities now believe that low 25(OH)D is a consequence of chronic inflammation rather than the cause. Research points to a bacterial etiology pathogenesis for an inflammatory disease process which results in high 1,25(OH)2D [active] and low 25(OH)D [storage]. Immunotherapy, directed at eradicating persistent intracellular pathogens, corrects dysregulated vitamin D metabolism and resolves inflammatory symptoms.”

Reversing Bacteria-induced Vitamin D Receptor Dysfunction Is Key to Autoimmune Disease (2009)

“The conventional view of autoimmune disease is that it results from the adaptive immune system “gone awry,” leading to inflammation and destruction of human tissue. Consequently, immunosuppressive agents are frequently used to curb what is considered to be inappropriate immune activation. One of the agents proposed for this purpose is vitamin D. 

The use of vitamin D in various forms has had particular appeal because of a lower level of the precursor form 25-hydroxyvitamin D (25-D) often being associated with autoimmune disease. This inverse association has fostered the view that adding vitamin D is correcting a deficiency.

The new model discussed here is based on a different view of vitamin D and the pathogenesis of autoimmune disease. Vitamin D is a secosteroid with a close resemblance in structure to immunosuppressive steroids. The levels of each of the vitamin D metabolites are affected by a complex network of feedback mechanisms involving multiple enzymes and receptors, indicating vitamin D is regulated more like a steroid than a nutrient. A low level of serum 25-D is seen as the result of downregulation rather than a causal factor leading to illness.”

High Levels of Active 1,25-Dihydroxyvitamin D Despite Low Levels of the 25-Hydroxyvitamin D Precursor-Implications of Dysregulated Vitamin D for Diagnosis and Treatment of Chronic Disease (2006)

“The active secosteroid hormone 1,25-dihydroxyvitamin-D (1,25D) often reaches excessive levels in normocalcemic patients suffering from chronic Th1 inflammatory illnesses, including sarcoidosis and rheumatoid arthritis. This is due to unregulated production of 1,25D in the mitochondria of activated macrophages. [Some] forms of bacteria drive this dysfunction of vitamin D metabolism. The paracrine levels of 1,25D rise and the level of substrate 25-D falls. If studies measure only the 25D precursor, a low 25D may be misinterpreted as indicating the patient requires vitamin D supplementation.”

Reversing bacteria-induced vitamin D receptor dysfunction is key to autoimmune disease (2009)


“The aim of the present review was to explore major evidence regarding the potential scavenger capacity of vitamin D in high-evidence human studies. Studies considered by the present review suggest that the potential role of vitamin D as an antioxidant could not be confirmed.”

“…there is need of further and high-quality studies testing the antioxidant effect of vitamin D supplementation.”

The controversial role of vitamin D as an antioxidant: results from randomised controlled trials (2019)


Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: A longitudinal, nested case-control study in the Nordic countries (2003)

“We studied serum 25(OH)-vitamin D levels of 622 prostate cancer cases and 1,451 matched controls and found that both low (≤19 nmol/l [7.6ng/mL]) and high (≥80 nmol/l [32ng/mL]) 25(OH)-vitamin D serum concentrations are associated with higher prostate cancer risk. The normal average serum concentration of 25(OH)-vitamin D (40–60 nmol/l [16-20 mg/mL]) comprises the lowest risk of prostate cancer.”

Mechanistic Effects of Calcitriol in Cancer Biology (2015)

“In in vitro and in vivo animal models, calcitriol [1,25D] has been shown to have anti-proliferative, pro-differentiative and pro-apoptotic actions in cancer cells. In this manner, vitamin D could limit cancer progression or prevent it. A large number of observational studies have shown that low circulating levels of cholecalciferol [25D], which are related to geographical location, diet and activity, are associated with a higher risk of cancer and cancer-specific worse prognostic. 

However, data regarding the role of vitamin D in cancer risk, incidence and mortality is still controversial. Some studies suggest a positive correlation between circulating [25D] concentrations in patients with a diagnostic of cancer, although several epidemiologic studies including colorectal, breast, and hepatocellular carcinoma have demonstrated an inverse association between serum [25D] levels and the risk to develop these pathologies. It has not yet been clearly elucidated if low serum [25D] levels are causative of associative parameters of cancer.”

“It remains unclear whether hypovitaminosis D is a causality or effect of breast cancer development…”

Monthly High-Dose Vitamin D Supplementation and Cancer Risk. (2018)

“The primary outcome of cancer comprised 328 total cases of cancer … and occurred in 165 of 2558 participants (6.5%) in the vitamin D group and 163 of 2550 (6.4%) in the placebo group…”

Exploring vitamin D metabolism and function in cancer (2018)

“It is now well-accepted that chronic inflammation is one of the main contributors to the initiation of tumorigenesis. Accumulating data suggest that vitamin D exerts anti-inflammatory effects via at least four mechanisms.”

“Because the numerous epidemiological and experimental data indicate the beneficial role of vitamin D in the prevention and treatment of several types of cancers, clinical use of calcitriol or vitamin D analogs has been investigated. However, hypercalcemia, the major toxic effect of vitamin D, has strongly limited its clinical applications. Moreover, accumulating data suggest that cancer cells employ several mechanisms that reduce cellular calcitriol levels, as well as diminish its function to protect themselves from the antitumorigenic effects of vitamin D.”

“…vitamin D metabolism and function are dysregulated in cancer to promote resistance to the antitumorigenic effect of vitamin D.”

“Although CYP24A1 expression is induced by calcitriol–VDR activation via negative feedback regulation, the high level of CYP24A1 expression observed in cancer cells is unlikely to be mediated by VDR activation because, as mentioned above, VDR expression and activity are downregulated in most cancer.”

***The immune system may be down-regulating vitamin D synthesis as a defense mechanism. Cancer itself is a defense mechanism and inflammation is not the root cause, it is a symptom of a root cause. While D is absolutely necessary for the body to function correctly, it is a steroid, and studies show a positive and negative correlation with various cancers. ***

Vitamin D, magnesium, calcium, and their interaction in relation to colorectal cancer recurrence and all-cause mortality (2020)

“Serum 25(OH)D3 concentrations seemed to be associated with all-cause mortality. An inverse association between magnesium intake… but not calcium intake, and all-cause mortality was observed.” [High magnesium intake = low mortality / low magnesium = high mortality.]

“When investigating the interaction between 25(OH)D3 and magnesium, we observed the lowest risk of all-cause mortality in patients with sufficient vitamin D concentrations (≥50 nmol/L [20 ng/mL]) and a high magnesium intake…”

Topical hydrocortisone, clobetasol propionate, and calcipotriol do not increase photocarcinogenesis induced by simulated solar irradiation in hairless mice (2010)

“Topical corticosteroids such as hydrocortisone-17-butyrate (HCB) and clobetasol-17-propionate (CP) and vitamin D3 derivatives such as calcipotriol (CAL) are widely used to treat psoriasis. The immunosuppressive effects of corticosteroids make their topical use a concern for skin carcinogenicity. Few studies have assessed the effect of topical corticosteroids and topical vitamin D3 derivatives on photocarcinogenesis induced by ultraviolet radiation. We investigated whether HCB, CP, or CAL can accelerate photocarcinogenesis using simulated solar radiation (SSR).”

standard erythema doses (SED)

“CAL-2SED decreased the time to onset of the first tumor but not of the second and third tumor.”


“Hypercalcemia of malignancy is a common finding typically in patients with advanced stage cancers. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and patients are therefore usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy, including PTHrP-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25-dihydroxyvitamin D mediated-hypercalcemia, and PTH-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers.”


The pathophysiology of hypercalcemia of malignancy is mainly through three mechanisms: excessive secretion of parathyroid hormone-related protein (PTHrP), bony metastasis with the release of osteoclast activating factors, and production of 1,25-dihydroxy vitamin D (calcitriol). 

Almost all cases of Hodgkin lymphoma and about one-third of non-Hodgkin lymphoma cases and granulomatous diseases like sarcoidosis and tuberculosis cause hypercalcemia by increasing 1,25-dihydroxy vitamin D production.

Lymphoma and granulomatous diseases are suspected when 1,25-dihydroxy vitamin D levels are elevated.


Vitamin D deficiency in community-acquired pneumonia: low levels of 1,25(OH)2 D are associated with disease severity (2014)

“No common definition exists for adequate vitamin D status measured as 25-OH serum concentrations. A recent guideline has been suggested that vitamin D deficiency be defined as 25-OH below 20 ng/ml, insufficiency as 21–29 ng/ml, and sufficiency as 30–100 ng/ml [2]. According to this guideline, serum 1,25-OH2 does not reflect vitamin D reserves and is frequently either normal or even elevated in those with vitamin D deficiency [2].”

“Because vitamin D skews the immune system towards a more tolerogenic state, some authors have hypothesized that a high vitamin D serum levels might result in a lower antibody response to influenza infection and vaccination [10–12].” 

*** Immunosuppression ***

“In our study, low 1,25-OH was significantly associated with renal co-morbidity but not hepatic co-morbidity, whereas low D 25-OH levels were significantly associated with hepatic and pulmonary but not renal-comorbidity. All these statistically significant associations can be explained by the vitamin D metabolism: the 25-hydroxylation occurs in the liver and the consecutive 1-hydroxylation in the kidney. Obviously, low 25-OH levels can be compensated for by increased renal hydroxylation. Vice versa, sufficient 25-OH levels do not necessarily translate into sufficient 1,25-OH2 levels.”

“Therefore, to measure only the reservoir form (25-OH) -as recommended by guidelines to determine the vitamin D “status”- may be insufficient. Effects of vitamin D are primarily conferred by the active form (1,25-OH2) and there is no linear relationship between the serum levels of these 2 metabolites. In line with our approach, Powe et al. stressed the importance of studying not only 25-OH but also 1,25-OH2 to understand the complex effects of vitamin D metabolism in a recent study published in the New England Journal of Medicine [17, 18].”

Vitamin D: What’s the “right” level? (2016)

“…several of the leading epidemiologists and endocrinologists who were on the original IOM committee argue for a lowering of the currently accepted cutoff level of 20, stating that the level they estimated as acceptable was never intended to be used to define vitamin D deficiency. They feel that we are over-screening for vitamin D deficiency, and unnecessarily treating individuals…”

“Based on their analysis, a more appropriate cutoff for vitamin D deficiency would be much lower, 12.5 ng/mL.”

“‘For perimenopausal women or other groups of people with higher fracture risk, certainly a level of 20 or above is ideal,’ and he adds: ‘For the vast majority of healthy individuals, levels much lower, 15, maybe 10, are probably perfectly fine…’”

“Vitamin D requirements may vary by individual; thus, no one serum vitamin D level cutpoint defines deficiency, and no consensus exists regarding the precise serum levels of vitamin D that represent optimal health or sufficiency.”

“Depending on the serum threshold used to define deficiency, the prevalence of vitamin D deficiency is 2 to 10 times higher in non-Hispanic Black persons than in non-Hispanic White persons, likely related to differences in skin pigmentation.7-9,14 However, these prevalence estimates are based on total 25(OH)D levels, and controversy remains about whether this is the best measure of vitamin D status among different racial and ethnic groups.” (2021)