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2,000 IU of Vitamin D is safe and somewhat effective for all adults – Jan 2024


Vitamin D Supplementation: A Review of the Evidence Arguing for a Daily Dose of 2000 International Units (50 ug) of Vitamin D for Adults in the General Population

Nutrients 2024, 16,391. https://doi.org/10.3390/ nu16030391
Pawel Pludowski 1 William B. Grant 2 , Spyridon N. Karras 3 , Armin Zittermann 4 and Stefan Pilz 5 stefan.pilz at medunigraz.at

  1. Department of Clinical Biochemistry, The Children's Memorial Health Institute, 04-730 Warsaw, Poland; p.pludowski at ipczd.pl
  2. Sunlight, Nutrition, and Health Research Center, P.O. Box 641603, San Francisco, CA 94164-1603, USA; wbgrant at infionline.net
  3. Laboratory of Biological Chemistry, Medical School, Aristotle University, 54636 Thessaloniki, Greece; karraspiros at yahoo.gr
  4. Clinic for Thoracic and Cardiovascular Surgery, Herz- und Diabeteszentrum Nordrhein-Westfalen (NRW), Ruhr University Bochum, 32545 Bad Oeynhausen, Germany; azittermann at hdz-nrw.de
  5. Dept. of Internal Medicine, Division of Endocrinology and Diabetology, Medical U. of Graz, Auenbruggerplatz 15, 8036 Graz, Austria

Vitamin D deficiency is considered a public health problem due to its worldwide high prevalence and adverse clinical consequences regarding musculoskeletal health. In addition, vitamin D may also be crucial for the prevention of certain extraskeletal diseases. Despite decades of intensive scientific research, several knowledge gaps remain regarding the precise definition of vitamin D deficiency and sufficiency, the health benefits of improving vitamin D status, and the required vitamin D intakes. Consequently, various societies and expert groups have released heterogeneous recommendations on the dosages for vitamin D supplementation. In this brief narrative review, we outline and discuss recent advances regarding the scientific evidence arguing for a daily vitamin D supplementation with 2000 international units (IU) (50 ug) of vitamin D3 to prevent and treat vitamin D deficiency. According to data from randomized controlled trials (RCTs), such a dose may improve some health outcomes and is sufficient to raise and maintain serum 25(OH)D concentrations above 50 nmol/L (20 ng/mL) and above 75 nmol/L (30 ng/mL) in >99% and >90% of the general adult population, respectively. According to large vitamin D RCTs, there are no significant safety concerns in supplementing such a dose for several years, even in individuals with an already sufficient vitamin D status at baseline. A daily vitamin D supplementation with 2000 IU (50 ug) may be considered a simple, effective, and safe dosage to prevent and treat vitamin D deficiency in the adult general population.
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Introduction

Vitamin D deficiency can be regarded as a public health problem because it has a high prevalence and contributes to skeletal diseases, including rickets and osteomalacia, but may also play a role in certain extraskeletal diseases [1,2]. The main source of vitamin D for humans is ultraviolet-B (UV-B) (sunlight) induced vitamin D synthesis from its precursor 7-dehydrocholesterol in the skin, whereas natural food sources of vitamin D (e.g., fish or mushrooms) play only a minor role in overall vitamin D supply. Limited sunlight exposure of the skin, obesity with deposition of vitamin D metabolites in the adipose tissue, and poor nutrition contribute, amongst others, to the high prevalence of vitamin D deficiency [3,4]. Laboratory detection of vitamin D deficiency is based on the measurement of serum concentrations of 25-hydroxyvitamin D (25(OH)D), the vitamin D metabolite that best reflects the overall supply from all different vitamin D sources, and that is the accepted parameter of vitamin D status. Vitamin D itself is considered biologically inactive and is converted to 25(OH)D by enzymes that are mainly located in the liver.
The clinical role of vitamin D is historically based on the fact that vitamin D was discovered as a substance that is capable of preventing and curing rickets, a bone disease with low serum calcium and low serum phosphate, and the widening and delaying of mineralization of growth plates, leading to bone deformation and muscle weakness in children [5,6]. Further investigations established the role of vitamin D as a regulator of calcium (mineral) and bone metabolism. The discovery of vitamin D receptors (VDR) in almost all human tissues and the fact that VDR activation regulates gene expression like classic steroid hormones, including hundreds of vitamin D-regulated genes, provides a sound scientific basis to postulate a potential role of vitamin D not only for skeletal diseases but also for many extraskeletal chronic diseases, including cancer, autoimmune, or infectious diseases [1,7-9]. Although there is evidence from meta-analyses of RCTs supporting the notion that vitamin D supplementation may prevent certain extraskeletal outcomes, great controversy remains regarding the precise role of vitamin D in the context of overall human health [1,2,5,10-16]. In this context, we wish to underscore the efficacy of vitamin D supplementation for some selected clinically relevant outcomes beyond bone health, with a focus on high-quality and up-to-date meta-analyses. Meta-analyses on vitamin D supplementation and all-cause mortality reported inconsistent results with either a moderate, yet statistically significant, reduction of all-cause mortality by vitamin D or no significant effect [14,17,18]. In this context, a recently published meta-analysis of 80 vitamin D RCTs, including 82,210 participants, documented that vitamin D supplemen­tation reduced the risk of all-cause mortality with an odds ratio (OR) (95% confidence interval (CI)) of 0.95 (0.91-0.99) comparing the vitamin D versus the placebo group [18]. A meta-analysis of 14 RCTs with 104,727 participants reported a relative risk (RR) (95% CI) for vitamin D versus placebo regarding cancer mortality of 0.94 (0.86-1.02) that became significant when restricting the analysis to trials with a daily dosing schedule (RR: 0.88; 95% CI: 0.78-0.98) [19]. In a meta-analysis of 46 RCTs with 75,541 participants, the OR (95% CI) for acute respiratory infections in the vitamin D compared to the placebo group was statistically significant with 0.92 (0.86-0.99) [20]. Regarding exacerbations of chronic obstructive pulmonary disease and asthma control, the evidence from recent meta-analyses of RCTs has largely failed to confirm the significant vitamin D effects reported in older publications [15,21-23]. Meta-analyses of RCTs do not document any beneficial effect of vitamin D supplementation on cardiovascular outcomes [24,25]. Regarding pregnancy out­comes, the evidence is inconsistent, but it should be noted that a Cochrane article published in 2019 in 22 RCTs in 3725 pregnant women concluded that vitamin D probably reduces the risk of gestational diabetes, pre-eclampsia, low birth weight, and postpartum hemorrhage, but more high-quality trials and an update of this analysis are required [26]. As a complete summary of vitamin D RCTs on non-skeletal health outcomes is beyond the scope of this narrative review, we refer the reader to some other publications on this issue [2,27,28].
In this brief narrative review, we critically appraise current vitamin D guidelines in the context of recently published evidence from large vitamin D RCTs that may, in our opinion, support re-considerations of vitamin D guidelines towards higher dosage recommendations, i.e., 2000 international units (IU) (50ug) of vitamin D per day, in the general adult population also covering individuals suffering from chronic diseases. For this aim, we start with a comprehensive outline of current vitamin D guidelines and then describe how the results of recent large vitamin D RCTs have provided important new safety data on vitamin D that may alter previous risk-benefit considerations. We then discuss evidence arguing for higher 25(OH)D target levels compared to the rather conservative threshold levels supported by most nutritional vitamin D guidelines.
As we are well aware of the limitations of a narrative review, we considered the Scale for the Assessment of Narrative Review Articles (SANRA) to improve the methodological quality of our work [29]. Regarding the first two topics of SANRA, i.e., “Justification of the article's importance for the readership" and “Statement of concrete aims or formulations of questions," we refer to the paragraph above, noting that recent large vitamin D RCTs with 2000IU (50ug) of vitamin D have to be critically appraised in the context of current guidelines, as they may have an impact on future guidelines and daily clinical practice. Regarding the third SANRA topic, i.e., “Description of the literature search," we performed a PubMed search with the following search terms: “(Vitamin D) AND ( (RCT) OR (ran­domized) ) AND ( (2000 IU) OR (2000 international units) OR (50ug) )" to find relevant articles for our topic and retrieved 750 publications by this search. We addressed the fourth SANRA topic, i.e., “Referencing," by supporting our key statements with the respective publications (references). The fifth SANRA topic, i.e., “Scientific reasoning," is considered by our focus on RCTs and meta-analysis data in this work. The sixth SANRA topic, i.e., “Appropriate presentation of data," is addressed by presenting data of clinically relevant endpoints and including effect sizes for some major findings [29].

Current Vitamin D Guidelines

Current guidelines for vitamin D intakes are mainly based on the role of vitamin D in musculoskeletal health, particularly regarding the prevention of rickets and osteoma­lacia [30,31]. The general framework of vitamin D guidelines is to first establish target serum 25(OH)D concentrations that meet the vitamin D requirements and then to calculate the vitamin D intake doses that are needed to achieve these serum 25(OH)D ranges under conditions of minimal to no sunlight-induced vitamin D synthesis (i.e., during winter) and by assuming that intakes of other nutrients are adequate [30,32]. There exists wide agreement that serum 25(OH)D concentrations below 25 to 30 nmol/L (10 to 12 ng/mL) indicate vitamin D deficiency and should be prevented and treated by vitamin D intake. For serum 25(OH)D concentrations from 25-30 nmol/L (10-12 ng/mL) up to 75 nmol/L (30 ng/mL), there is controversy on the threshold for sufficiency with the main scientific debate on whether concentrations > 50 nmol/L (20 ng/mL) or >75 nmol/L (30 ng/mL) should be the target 25(OH)D level for vitamin D sufficiency [5,31,33,34]. As a consequence of this debate and owing to the different approaches and uncertainties regarding the dose- response relationship of vitamin D supplementation and its resulting increase in serum 25(OH)D concentrations, there are numerous vitamin D guidelines and expert recommen­dations published with a wide range of different recommended vitamin D doses [34-36]. Nutritional vitamin D guidelines are usually based on vitamin D intake recommendations under conditions of minimal to no sunshine exposure and cover vitamin D supply from all sources, including diet and supplements. In contrast, we refer in the further text, if not otherwise stated, to vitamin D supplement doses and do not consider additional dietary intakes that are usually very low (i.e., below 200 IU (5ug) for the vast majority of the population).
Regarding the required vitamin D intakes to achieve serum 25(OH)D concentrations of >25-30 nmol/L (10-12 ng/mL) and >50 nmol/L (20 ng/mL) in 97.5% of the population, it can be assumed that a daily vitamin D supplement with 400 IU (10ug) and 800 IU (20ug) of vitamin D, respectively, is sufficient [30,37,38]. Such vitamin D doses ranging from 400 to 800 IU (5 to 10ug) of vitamin D per day are generally recommended by nutritional vitamin D guidelines [31]. These recommendations were, however, mainly based on White individuals, whereas recent investigations suggest that there may be much higher intakes required in individuals from other ethnicities, and vitamin D requirements may also vary considerably between different regions or continents, suggesting that some populations may require higher doses than previously estimated [4,39-41]. For example, one individual participant data (IPD) meta-analysis of vitamin D RCTs in dark-skinned persons (Black or South Asian descent) residing at higher latitudes (i.e., >40° N), estimated vitamin D intakes to achieve serum 25(OH)D levels of >50 nmol/L (20 ng/mL) in 90%, 95% and 97.5% of the population at 2008, 2364, and 2672 IU (50.2, 59.1 and 66.8ug), respectively [40]. These data require considerations in updated dosing recommendations for vitamin D and stand in contrast to previous statements that conservative doses of, e.g., 800 IU (20ug) (or even less) of vitamin D per day meet the vitamin D requirements for almost everyone [31,42]. It should also be stressed that vitamin D RCTs on dose-response relationships of vitamin D intakes and serum 25(OH)D may probably be prone to healthy volunteer bias and not always well resemble the general population that frequently suffers from conditions with a diminished dose-response curve such as obesity [38]. It has also been revealed that relying on summary statistics (e.g., using conventional meta-analyses) usually underestimates vitamin D requirements as opposed to IPD (meta-)analyses that capture the full between-individual variability in the dose-response curve [30,38]. Of note, achieving serum 25(OH)D concentrations of >75 nmol/L (30 ng/mL) in the vast majority of the population may require a daily vitamin D supplementation of about 2000 IU (50ug) [33,35,43].
In this whole discussion on vitamin D dosage recommendations, one major scientific debate is whether serum 25(OH)D > 50 nmol/L (20 ng/mL) or >75nmol/L (30 ng/mL) should be the target and whether a general vitamin D supplementation with doses aiming to achieve >75 nmol/L (30 ng/mL), i.e., about 2000 IU (50ug), is safe for the general adult population [33,42,44]. Given that general recommendations for a vitamin D supplementa­tion with 2000 IU (50ug) per day would shift the whole 25(OH)D distribution of a given population to higher levels and thus increase the risk of harm by vitamin D overdosing for those at the higher end of this distribution, it was argued that there may be a safety concern with such doses [42,45]. In view of recent publications from large vitamin D RCTs supporting the high safety of such doses, we aim to discuss the evidence arguing for the safety of 2000 IU (50ug) of vitamin D per day and for the target range of >75 nmol/L (30 ng/mL) in this work.

Safety of a Daily Vitamin D Supplementation with 2000 IU (50 ug)

The safety of vitamin D supplementation is discussed in the context of establishing serum 25(OH)D concentrations above which there is a risk of potential harm from vitamin D overdosing. A classic sign of vitamin D toxicity is hypercalcemia, which does usually not occur until serum 25(OH)D concentrations exceed 150 ng/mL (375 nmol/L) and that requires daily vitamin D intakes over long time periods of more than 20,000 IU (500ug) [45]. The concept of vitamin D toxicity is also based on potential adverse vitamin D effects that may occur well below the threshold for hypercalcemia. Observational studies indicate a U- or J-shaped association of serum 25(OH)D and various health outcomes [42]. In detail, some, but not all, investigations suggested adverse clinical outcomes for individuals with serum 25(OH)D above 125 to 150 nmol/L (50 to 60 ng/mL), which can be achieved by relatively moderate vitamin D doses [42]. When assuming that a general vitamin D supplementation is shifting the whole 25(OH)D distribution of a population to higher levels, there may be a relatively high risk of vitamin D overdosing in those individuals at the higher end of the 25(OH)D distribution at baseline. As a consequence, caution was stressed for vitamin D doses that may well be below the no adverse observed effect level (NOAEL) of 10,000 IU (250ug) and even below the respective tolerable upper intake level of 4000 IU (100ug) (calculated as the NOAEL with a safety margin of 2.5 times), but that may potentially lead to serum 25(OH)D concentrations above 125 nmol/L (50 ng/mL) in a few percent of the population [42,45]. Recent RCTs have significantly contributed to more safety data on this issue and have particularly documented the safety of a dose of 2000 IU (50ug) of vitamin D per day when administered for long periods in relatively unselected general adult populations [43,46,47]. In particular, the VITamin D and OmegA-3 Trial (VITAL), an RCT of 2000 IU (50ug) of vitamin D in 25,871 older men and women from the US with an intervention period of 5.3 years showed no significant signs of vitamin D toxicity in the intervention group. However, they had relatively high serum 25(OH)D at baseline and were allowed to take vitamin D supplements up to 800 IU (20ug) per day in addition to the study medication [46]. In detail, after one year of the VITAL trial, participants allocated to vitamin D achieved serum 25(OH)D concentrations of >50 nmol/L (20 ng/mL), >75 nmol/L (30 ng/mL), and >100 nmol/L (40 ng/mL) at 99.4%, 91.9%, and 53%, respectively [43]. Such high serum 25(OH)D concentrations and missing safety concerns in this well-examined cohort strongly support the safety of a daily vitamin D dose of 2000 IU (50ug). These data must also be interpreted in light of relatively high serum 25(OH)D levels of the study population at baseline, systematic vitamin D food fortification in the US, and vitamin D supplement use in addition to the study medication by almost half of the study population, all contributing to a higher vitamin D status. Therefore, recommendations of 2000 IU (50ug) of vitamin D per day in other countries/populations may likewise result in a less significant, and thus even safer, vitamin D exposure. In line with this, one meta-analysis in 15 vitamin D RCTs (3150 participants) supplementing >2800 IU (70ug) for at least one year showed no increase in overall total adverse events (RR: 1.05; (95% CI): 0.88-1.24; 1731 participants from 10 trials) nor kidney stones (RR: 1.26; (95% CI): 0.35-4.58; 1336 participants from 5 trials) when comparing the vitamin D versus the placebo group [48]. This later meta-analysis included RCTs in different populations, including, amongst others, patients with heart failure, epilepsy, multiple sclerosis, chronic obstructive pulmonary disease, or lung transplantation [48]. However, a more recent meta­analysis in 22 RCTs including 12,952 participants with a daily vitamin D supplementation of 3200 to 4000 IU (80 to 100ug) lasting at least 6 months, revealed a RR (95% CI) for hypercalcemia of 2.21 (1.26-3.87), for falls of 1.25 (1.01-1.55), and for hospitalizations of 1.16 (1.01-1.33), when comparing the vitamin D versus the control group, whereas there was no risk difference for hypercalciuria, kidney stones and mortality [49]. Importantly, vitamin D supplementation versus placebo did not increase the risk of hypercalcemia in a meta-analysis of 11 RCTs in 906 chronic kidney disease patients (RR 0.68; 95% CI: 0.39-1.19) [50]. Apart from this, it should be stressed that the high safety and efficacy of vitamin D supplementation has also been documented by RCTs in pregnant and lactating women [26,51-54].
Despite outlining the high safety of 2000 IU (50ug) of vitamin D per day, we want to express some words of caution as vitamin D supplementation does indeed have an undeniable potential for adverse effects depending on the dose, the dosing schedule (with increasing risk with intermittent high dose approaches), and for certain groups [49,55-58]. One major finding in terms of the safety and efficacy of vitamin D is that daily vitamin D supplementation may be superior compared to intermittent bolus dosing of vitamin D [9,59-62]. Another important safety issue is that some evidence argues that older and diseased individuals may be more prone to adverse effects of vitamin D overdosing. This suggests that considerations regarding vitamin D supplementation doses should also consider the age of the person [49,62]. It should also be mentioned that there exist inher­ited pathogenic mutations of CYP24A1 (24-hydroxylase) that lead to impaired vitamin D catabolism and, therefore, predispose to hypercalcemia in individuals who are supple­mented with vitamin D [58]. These pathogenic mutations of CYP24A1 are very rare but should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. It should also be considered that a dose of 2000 IU (50ug) of vitamin D is only about 10% of the 20,000 IU (500ug) of vitamin D that a human body can produce under optimal circumstances due to sunlight-induced vitamin D synthesis in the human skin, an endogenous vitamin D production that is superior in light versus dark-skinned individuals [34,63]. Interestingly, during our evolution, a high vitamin D responsiveness was probably essential for surviving dark winters as it reduced the adverse consequences of vitamin D deficiency [63].

Evidence Arguing for a Target Serum 25(OH)D Concentration of 75 nmol/L (30 ng/mL)

Numerous observational studies have evaluated the risk of adverse health outcomes according to serum 25(OH)D concentrations. Large epidemiological surveys and meta­analyses of observational studies indicate that the lowest mortality risk is present at serum 25(OH)D concentrations slightly above 75 nmol/L (30 ng/mL) [64,65]. When relating serum 25(OH)D to various other health outcomes, it has been documented that for most chronic diseases, optimal serum 25(OH)D concentrations with the lowest risk are above 75 nmol/L (30 ng/mL) [64-69] . In detail, one meta-analysis of European cohort studies showed that the lowest mortality risk was detected for serum 25(OH)D concentrations of approximately 78 nmol/L (31ng/mL((see Figure 1 ) [64].

Image
Figure 1. Dose-response; trend of hazard ratios of death from all causes lay standardized 25- hydroxyvitamin D. Dose-response trend of hazard ratios of all-cause morta lity by standardized 25-hydroxyvitamin D were adjusted for age, sex, BMI, and season of blood drawing concentra­tions. Hazard ratios (blue line with 95% confidence interval as the dotted blue lines) refer to the 25-hydroxyvitamin D concentration of 83.4 nmol/L (i.e., tire median 25-hydroxyvitamin D concentra­tion for the group with 25 -hydroxyvitamin D concentrations from 75 to 99.99 nmol/L). Reproduced from Ref. [64] under the terms of the CC0 1.0 Universal (CC0 1.0) Public Domain Dedication.

While we cannot definitely claim causality for vitamin D and various extraskeletal diseases, the overall conclusion on the relationship between serum 25(OH)D and various health outcomes based on observational studies is that serum 25(OH)D concentrations above 75 nmol/L (30 ng/mL) are superior to concentrations from 50 to 75 nmol/L (20 to 30 ng/mL) for most c(inical endpoints [65]. The exception for this is vitamin D requirements for the prevention of rickets and osteomalacia that are met at lower 25(OH)D concentra­tions with conservative estimates of about 30 nmol/L (12 ng/mL), although there is also controversy on whether higher levels may be required [5,10]. Thus, the optimal serum 25(OH)D concentration may vary depending on the outcome studied and the population. Some evidence suggests that particularly high 25(OH)D levels may be ideal for certain health outcomes [65,70]. For example, data from the Vitamin D and Type 2 Diabetes (D2d) RCT suggest that based on intra-trial 25(OH)D concentrations, levels of >100 nmol/L (40 ng/mL) may be optimal to reduce the risk of diabetes in persons with prediabetes [71].
Serum 25(OH)D concentrations of >40 ng/mL (100 nmol/L) or even higher might also be optimal for other health outcomes such as cancer [72,73].
The scientific debate on optimal target concentrations for serum 25(OH)D is, of course, based on risk-benefit considerations, but the argument to not target 75 nmol/L (30 ng/mL) due to safety concerns is, in our opinion, no longer as justified, as it was, and has been acknowledged in previously published vitamin D guidelines [31,42]. Consequently, more weight and attention in this discussion should be paid to the potential extraskeletal health effects of vitamin D, which may require higher 25(OH)D levels than those established for skeletal health. Apart from the above-described epidemiological data that are in line with target concentrations for 25(OH)D of at least 75 nmol/L (30 ng/mL), there are also some findings from RCTs that support relatively high vitamin D doses [19,20,26,27,74-78]. However, regarding vitamin D RCTs, it must be stressed that one of the major limitations of large vitamin D trials was the inclusion of mainly vitamin D-sufficient individuals who were allowed to take vitamin D supplements in addition to the study medication [60,79,80]. Nevertheless, we wish to emphasize that there are several data from RCTs, observational, and molecular studies supporting a beneficial role of vitamin D for various extraskeletal diseases such as cancer, respiratory infections, autoimmune/inflammatory diseases, or diabetes mellitus requiring relatively high vitamin D doses [71,75,76,81,82]. In this context, we are well aware that the high number of RCTs and their post-hoc analyses may probably increase the "false positive" findings, i.e., formally statistically significant results indicating beneficial vitamin D effects; therefore, we must be cautious with the interpretation of such findings [83,84].
An additional argument for a target 25(OH)D level of at least 75 nmol/L (30 ng/mL) is that there is substantial variation regarding the precision of laboratory methods quan­tifying serum 25(OH)D [85,86]. Targeting a serum concentration of at least 75 nmol/L (30 ng/mL) would, therefore, guarantee that almost all individuals have a 25(OH)D level above 50 nmol/L (20 ng/mL), even if test procedures are used, which overestimate cir­culating 25(OH)D. The huge individual differences in the response to vitamin D supple­mentation, evidenced by the molecular effects on vitamin D target genes, could also be considered as supporting higher vitamin D doses to meet the vitamin D requirements of all individuals [87-90].
We reiterate that in clinical routine, particular attention should be paid to obese individ­uals who require higher vitamin D doses to increase their serum 25(OH)D concentrations as compared to lean persons and to patients with malabsorption syndromes, such as, e.g., patients suffering from inflammatory bowel diseases, who may also require much higher vitamin D dosages to achieve their serum 25(OH)D target concentrations [91,92]. For exam­ple, after two years of supplementing 2000IU (50ug) of vitamin D per day in the VITAL trial, the multivariable-adjusted mean serum 25(OH)D concentrations in individuals with a body mass index of <25.0,25.0-29.9,30.0-34.9, and >35.0 kg/m2 were 110,103, 98, and 92 nmol/L (44.0,41.2, 39.4 and 37.0 ng/mL), respectively, indicating a highly significant treatment effect interaction by body mass index (p < 0.001) [93]. In a meta-analysis of RCTs evaluating the effect of body weight on increases in serum 25(OH)D, the vitamin D dose per body weight explained 34.5% of the variation in 25(OH)D [94]. Patients with inflammatory bowel disease have significantly lower serum 25(OH)D levels compared to matched controls (e.g., 47 versus 62 nmol/L (18.9 versus 25 ng/mL) in one study), in particular during episodes with high disease activity [95,96]. In one vitamin D RCT in 143 patients with inflammatory bowel diseases treated with 25,000 IU (625ug) once weekly (corresponding to 3571 IU (89ug) per day), the mean serum 25(OH)D concentrations after 26 weeks was only 81 nmol/L (32.5 ng/mL) in the intervention group [97]. Medications such as antiepileptic drugs that may interfere with vitamin D metabolism may also alter vitamin D status, with one meta-analysis documenting that serum 25(OH)D concentrations were 10 nmol/L (4 ng/mL) lower in patients taking carbamazepine versus controls [98].
Although it is beyond the scope of this present review, there is accumulating evidence and ongoing research on other forms of vitamin D treatment (e.g., calcifediol) or other administration routes (e.g., intramuscularly) that may be useful for certain individuals as reviewed elsewhere [99,100]. Regarding the form of vitamin D that is used for supplemen­tation, we recommend vitamin D3 (cholecalciferol) rather than vitamin D2 (ergocalciferol), as the evidence for treatment efficacy is superior for vitamin D3 and it is also more efficient in increasing serum 25(OH)D concentrations [101,102].

Practical and Pragmatic Considerations

There are also some practical and pragmatic considerations underpinning the notion that a daily vitamin D supplemental dose of 2000 IU (50 ug) is a reasonable approach to prevent and treat vitamin D deficiency Using conventional vitamin D doses such as 600 to 800 IU (15 to 20 ug) may, for many individuals, not even be sufficient to achieve the conser­vative target concentration of at least 50 nmol/L (20 ng/mL) when considering the wide inter-individual dose response according to IPD meta-regression analyses and when taking into account the multiple clinical factors such as obesity, malabsorption syndromes (that may not always be already diagnosed), or medications that impair vitamin D metabolism (e.g., antiepileptic drugs) that all require higher vitamin D doses [35,93,98,103,104]. Clin­icians who strictly adhere to nutritional vitamin D guidelines may thus not sufficiently treat their patients with vitamin D supplements when always adhering to conservative dosing regimens not exceeding 800 IU (20 ug) of vitamin D per day [31]. We suggest that clinicians treat vitamin D deficiency of their patients with a supplemental dose that can be either 2000 IU (50 ug) per day as a one-size-fits-all dose or, if they prefer this, that they can tailor the vitamin D dosage according to the patient needs and characteristics as a means of personalized treatment with a dosing range from 800 to 2000 IU (20 to 50 ug). Such an approach may also better meet the preferences of physicians, as we learned from personal unpublished communications from many colleagues. In our own experience, many clini­cians have argued that conservative doses such as 800 IU (20 ug) per day were not sufficient to achieve 25(OH)D target levels, and they have thus occasionally proceeded with much higher and potentially harmful vitamin D doses (e.g., >4000 IU (>100 ug) per day) [49,105]. Setting a sufficiently high but not overwhelming vitamin D dosing recommendation with 2000 IU (50 ug) per day may, therefore, also provide helpful guidance in this regard and potentially reduce overdosing of vitamin D.
The seasonal variation in vitamin D status with higher 25(OH)D levels in summer and lower levels in winter is significantly mitigated by the storage and release of vitamin D metabolites from tissues like the musculature and adipose tissue [3,106-108]. Because the large vitamin D RCTs addressing clinical endpoints did not adjust their dose according to season and given that the seasonal variability in serum 25(OH)D may also have a huge interindividual variability with some individuals having almost no seasonal changes in 25(OH)D, we recommend a consistent (identical) vitamin D dose throughout the year [109].
We are well aware that there exist differences between nutritional guidelines to estab­lish dietary nutrient intakes and clinical guidelines that aim to inform physicians. However, without diving into discussions on guideline frameworks and their applications, we wish to stress that accumulating evidence on the safety and efficacy of vitamin D has to be con­sidered in what we, as physicians, but also well-informed non-healthcare experts should be “allowed" to recommend and take as a means to prevent and treat vitamin D deficiency, i.e., 2000 IU (50 ug) of vitamin D per day, without being blamed for deviating from health authority guidelines [33,34,110].
We agree that the best way to achieve a sufficient vitamin D status is a healthy lifestyle, including an optimal diet combined with normal body weight, sufficient physical activity (that may per se mobilize vitamin D metabolites from its body stores), and moderate sunlight exposure [111-113]. Improving and optimizing vitamin D status using such an approach should always be prioritized and incorporated into any recommendation. However, we must accept the very high prevalence of vitamin D deficiency and offer simple, safe, and effective approaches to addressing this vitamin D pandemic, i.e., vitamin D supplementation with effective and safe dosages. Apart from this, we are also strong proponents of systematic vitamin D food fortification, but this has not yet been introduced in the majority of countries and may not completely erase vitamin D deficiency [45].

Conclusions

In this brief narrative review, we have outlined and discussed the evidence arguing for a vitamin D supplementation dose of 2000IU (50ug) per day as an efficient and safe approach to prevent and treat vitamin D deficiency (see Table 1).
Table 1. Main arguments supporting a vitamin D supplement dose of 2000 IU (50 ug) per day for the prevention and treatment of vitamin D deficiency.

  • Previous publications and guidelines may have partially underestimated the vitamin D requirements to achieve certain target serum 25(OH)D concentrations.
  • The high safety of a daily vitamin D supplementation dose of 2000 IU (50ug) has been well established by recent RCT data documenting this over several years of treatment.
  • Clinical studies support a serum 25(OH)D concentration of 75 nmol/L (30 ng/mL) and higher as the optimal level.
  • Some RCT data support clinical extraskeletal benefits of vitamin D supplementation with 2000 (IU) (50ug) per day.
    • IU = international units;   25(OH)D = 25-hydroxyvitamin D;  RCT = randomized controlled trial

Considering the evidence outlined and discussed in this brief review, it appears reasonable to consider recommending a daily vitamin D supplement dose of 2000 IU (50 ug) to prevent and treat vitamin D deficiency in the general adult population [39-41,43,65]. Such a recommendation is supported by the Endocrine Society clinical practice guideline for evaluating, treating, and preventing vitamin D deficiency, and newer evidence is now reinforcing these older clinical practice recommendations [33]. As we have the impression that the evidence underpinning recommendations for 2000 IU (50 ug) per day is not (yet) well recognized in the scientific literature and the currently published vitamin D guidelines, we drafted this review with the aim that it may serve as a basis for considerations regarding future national health authority guidelines for vitamin D. We are well aware that our work is only a narrative expert review lacking a pre-registered systematic review. We, therefore, have to acknowledge this as a limitation.
Finally, we emphasize that the worldwide prevalence of serum 25(OH)D below 25/30 nmol/L (10/12 ng/mL) and below 50 nmol/L (20 ng/mL) ranges from about 5 to 18% and 24 to 49%, respectively, thereby underscoring the need for actions that aim to reduce the burden of vitamin D deficiency [114]. There exists no "one size fits all" approach for vitamin D supplementation, but as long as individualized approaches, including base­line and follow-up measurements of serum 25(OH)D, are not feasible and cost-effective, we believe that it appears reasonable to recommend a daily dose of vitamin D with 2000 IU (50ug) when someone asks for advice regarding an effective and safe vitamin D dosage that prevents and treats vitamin D deficiency. A more conservative and personalized approach may suggest a daily vitamin D dose in the range of 800 to 2000 IU (20 to 50ug) according to the individual needs with characteristics such as very low serum 25(OH)D, obesity, or malabsorption syndromes arguing for the higher end of this dosing range and vice versa.

114 References
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  88. Seuter, S.; Virtanen, J.K.; Nurmi, T.; Pihlajamaki, J.; Mursu, J.; Voutilainen, S.; Tuomainen, T.P.; Neme, A.; Carlberg, C. Molecular evaluation of vitamin D responsiveness of healthy young adults. J. Steroid Biochem. Mol. Biol. 2017, 174, 314-321. [CrossRef] [PubMed]
  89. Vukic, M.; Neme, A.; Seuter, S.; Saksa, N.; de Mello, V.D.; Nurmi, T.; Uusitupa, M.; Tuomainen, T.P.; Virtanen, J.K.; Carlberg, C. Relevance of vitamin D receptor target genes for monitoring the vitamin D responsiveness of primary human cells. PLoS ONE 2015,10, e0124339. [CrossRef] [PubMed]
  90. Gospodarska, E.; Ghosh Dastidar, R.; Carlberg, C. Intervention Approaches in Studying the Response to Vitamin D(3) Supple­mentation. Nutrients 2023,15, 3382. [CrossRef]
  91. Nikolova, M.G.; Boyanov, M.A.; Tsakova, A.D. Correlations of Serum Vitamin D with Metabolic Parameters in Adult Outpatients with Different Degrees of Overweight / Obesity Coming from an Urban Community. Acta Endocrinol. 2018,14, 375-383. [CrossRef]
  92. Bilezikian, J.P.; Formenti, A.M.; Adler, R.A.; Binkley, N.; Bouillon, R.; Lazaretti-Castro, M.; Marcocci, C.; Napoli, N.; Rizzoli, R.; Giustina, A. Vitamin D: Dosing, levels, form, and route of administration: Does one approach fit all? Rev. Endocr. Metab. Disord. 2021, 22,1201-1218. [CrossRef]
  93. Tobias, D.K.; Luttmann-Gibson, H.; Mora, S.; Danik, J.; Bubes, V.; Copeland, T.; LeBoff, M.S.; Cook, N.R.; Lee, I.M.; Buring, J.E.; et al. Association of Body Weight With Response to Vitamin D Supplementation and Metabolism. JAMA Netw. Open 2023, 6, e2250681. [CrossRef]
  94. Zittermann, A.; Ernst, J.B.; Gummert, J.F.; Borgermann, J. Vitamin D supplementation, body weight and human serum 25- hydroxyvitamin D response: A systematic review. Eur. J. Nutr. 2014, 53, 367-374. [CrossRef]
  95. Burrelli Scotti, G.; Afferri, M.T.; De Carolis, A.; Vaiarello, V.; Fassino, V.; Ferrone, F.; Minisola, S.; Nieddu, L.; Vernia, P. Factors affecting vitamin D deficiency in active inflammatory bowel diseases. Dig. Liver Dis. 2019, 51, 657-662. [CrossRef] [PubMed]
  96. Nielsen, O.H.; Hansen, T.I.; Gubatan, J.M.; Jensen, K.B.; Rejnmark, L. Managing vitamin D deficiency in inflammatory bowel disease. Frontline Gastroenterol. 2019,10, 394-400. [CrossRef] [PubMed]
  97. de Bruyn, J.R.; Bossuyt, P.; Ferrante, M.; West, R.L.; Dijkstra, G.; Witteman, B.J.; Wildenberg, M.; Hoentjen, F.; Franchimont, D.; Clasquin, E.; et al. High-Dose Vitamin D Does Not Prevent Postoperative Recurrence of Crohn's Disease in a Randomized Placebo-Controlled Trial. Clin. Gastroenterol. Hepatol. 2021,19,1573-1582. [CrossRef]
  98. LoPinto-Khoury, C.; Brennan, L.; Mintzer, S. Impact of carbamazepine on vitamin D levels: A meta-analysis. Epilepsy Res. 2021, 178,106829. [CrossRef] [PubMed]
  99. Quesada-Gomez, J.M.; Bouillon, R. Is calcifediol better than cholecalciferol for vitamin D supplementation? Osteoporos. Int. 2018, 29,1697-1711. [CrossRef] [PubMed]
  100. Wylon, K.; Drozdenko, G.; Krannich, A.; Heine, G.; Dolle, S.; Worm, M. Pharmacokinetic Evaluation of a Single Intramuscular High Dose versus an Oral Long-Term Supplementation of Cholecalciferol. PLoS ONE 2017,12, e0169620. [CrossRef]
  101. Tripkovic, L.; Lambert, H.; Hart, K.; Smith, C.P.; Bucca, G.; Penson, S.; Chope, G.; Hypponen, E.; Berry, J.; Vieth, R.; et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: A systematic review and meta-analysis. Am. J. Clin. Nutr. 2012, 95,1357-1364. [CrossRef] [PubMed]
  102. van den Heuvel, E.G.; Lips, P.; Schoonmade, L.J.; Lanham-New, S.A.; van Schoor, N.M. Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis. Adv. Nutr. 2023,15,100133. [CrossRef] [PubMed]
  103. Gallagher, J.C.; Yalamanchili, V.; Smith, L.M. The effect of vitamin D supplementation on serum 25(OH)D in thin and obese women. J. Steroid Biochem. Mol. Biol. 2013,136,195-200. [CrossRef] [PubMed]
  104. Drincic, A.; Fuller, E.; Heaney, R.P.; Armas, L.A. 25-Hydroxyvitamin D response to graded vitamin D(3) supplementation among obese adults. J. Clin. Endocrinol. Meta. 2013, 98, 4845-4851. [CrossRef] [PubMed]
  105. Rooney, M.R.; Harnack, L.; Michos, E.D.; Ogilvie, R.P.; Sempos, C.T.; Lutsey, P.L. Trends in Use of High-Dose Vitamin D Supplements Exceeding 1000 or 4000 International Units Daily, 1999-2014. JAMA 2017, 317, 2448-2450. [CrossRef]
  106. Rybchyn, M.S.; Abboud, M.; Puglisi, D.A.; Gordon-Thomson, C.; Brennan-Speranza, T.C.; Mason, R.S.; Fraser, D.R. Skeletal Muscle and the Maintenance of Vitamin D Status. Nutrients 2020,12, 3270. [CrossRef]
  107. Kroll, M.H.; Bi, C.; Garber, C.C.; Kaufman, H.W.; Liu, D.; Caston-Balderrama, A.; Zhang, K.; Clarke, N.; Xie, M.; Reitz, R.E.; et al. Temporal relationship between vitamin D status and parathyroid hormone in the United States. PLoS ONE 2015, 10, e0118108. [CrossRef]
  108. Mason, R.S.; Rybchyn, M.S.; Abboud, M.; Brennan-Speranza, T.C.; Fraser, D.R. The Role of Skeletal Muscle in Maintaining Vitamin D Status in Winter. Curr. Dev. Nutr. 2019, 3, nzz087. [CrossRef]
  109. Levis, S.; Gomez, A.; Jimenez, C.; Veras, L.; Ma, F.; Lai, S.; Hollis, B.; Roos, B.A. Vitamin d deficiency and seasonal variation in an adult South Florida population. J. Clin. Endocrinol. Metab. 2005, 90,1557-1562. [CrossRef]
  110. Holick, M.F.; Binkley, N.C.; Bischoff-Ferrari, H.A.; Gordon, C.M.; Hanley, D.A.; Heaney, R.P.; Murad, M.H.; Weaver, C.M. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J. Clin. Endocrinol. Metab. 2012, 97, 1153-1158. [CrossRef]
  111. Sun, X.; Cao, Z.B.; Tanisawa, K.; Taniguchi, H.; Kubo, T.; Higuchi, M. Effects of chronic endurance exercise training on serum 25(OH)D concentrations in elderly Japanese men. Endocrine 2018, 59, 330-337. [CrossRef] [PubMed]
  112. Sun, X.; Cao, Z.B.; Taniguchi, H.; Tanisawa, K.; Higuchi, M. Effect of an Acute Bout of Endurance Exercise on Serum 25(OH)D Concentrations in Young Adults. J. Clin. Endocrinol. Metab. 2017,102, 3937-3944. [CrossRef]
  113. Dzik, K.P.; Grzywacz, T.; Luszczyk, M.; Kujach, S.; Flis, D.J.; Kaczor, J.J. Single bout of exercise triggers the increase of vitamin D blood concentration in adolescent trained boys: A pilot study. Sci. Rep. 2022,12,1825. [CrossRef] [PubMed]
  114. Cashman, K.D. Global differences in vitamin D status and dietary intake: A review of the data. Endocr. Connect. 2021,11, e210282. [CrossRef]

VitaminDWiki – Consensus Vitamin D category contains:

68 Vitamin D consensus publications

VitaminDWiki – Optimum category contains

The RDA is barely enough for the bones to survive.
   Need an optimal level for the body to thrive

98 items in Optimum Vitamin D category

Example pages

Image


The amount and type of Vitamin D needed varies a lot


VitaminDWiki – 8 Items in both categories Genetics and Predict Vitamin D

Also in genetics


Overview Gut and vitamin D contains the following gut-friendly alternatives

Gut-friendly, Sublingual, injection, topical, UV, sunshine

Getting Vitamin D into your body has the following chart
Image

Getting Vitamin D into your body also has the following
If poorly functioning gut
Bio-D-Mulsion Forte – especially made for those with poorly functioning guts, or perhaps lacking gallbladder
Sublingual – goes directly into the bloodstream
   you can make your own sublingual by dissolving Vitamin D in water or use nano form
Oil: 1 drop typically contains 400 IU, 1,000 IU, or 4,000 IU, typically not taste good
Topical – goes directly into the bloodstream. Put oil on your skin, Use Aloe vera cream with Vitamin D, or make your own
Vaginal – goes directly into the bloodstream. Prescription-only?
Bio-Tech might be usefulit is also water-soluble
Vitamin D sprayed inside cheeks (buccal spray) - several studies
    and, those people with malabsorption problems had a larger response to spray
Inject Vitamin D quarterly into muscle, into vein, or perhaps into body cavity if quickly needed
Nanoparticles could be used to increase vitamin D getting to the gut – Oct 2015
Poor guts need different forms of vitamin D has the following
Guesses of Vitamin D response if poor gut

Bio FormSpeedDuration
10Injection ($$$)
or Calcidiol or Calcitriol
D - Slow
C -Fast
Long
10 Sun/UVBSlowLong
10Topical
(skin patch/cream, vagina)
Slow
Fast nano
Normal
9Nanoemulsion -mucosal
perhaps activates VDR
FastNormal
9?Inhaled (future)FastNormal
8Bio-D-Mulsion ForteNormalNormal
6Water soluble (Bio-Tech)NormalNormal
4Sublingual/spray
(some goes into gut)
FastNormal
3Coconut oil basedSlowNormal
2Food (salmon etc.)SlowNormal
2Olive oil based (majority)SlowNormal

10= best bioavailable, 0 = worst, guesses have a range of +-2
Speed: Fast ~2-6 hours, Slow ~10-30 hours
Duration: Long ~3-6 months, Normal = ~2 months


VitaminDWiki – Predict Vitamin D shows how much effort is needed to make fuzzy predictions

It is very difficult to predict the response to supplementation of Vitamin D, or additional sun/UV
There are a huge number of factors involved.
 
This page also has studies predicting deficiency without Vitamin D tests

77 Predict Vitamin D articles examples:

Image Image


VitaminDWiki – Response to 2,000 IU can take 6 months

http://vitamindwiki.com/tiki-index.php?page_id=8096


69+ VitaminDWiki pages have "2000 IU" in the title

This list is automatically updated

Items found: 69
Title Modified
Cancers reduced after 2 years of 2000 IU Vitamin D daily (2nd RCT) – RCT Aug 03 Nov, 2023
Cancers reduced after 2 years of 2000 IU Vitamin D daily (2nd RCT) – RCT Aug 03 Nov, 2023
A common recurrent childhood fever (PFAPA) was reduced by half by 2000 IU of daily vitamin D – Oct 2023 23 Oct, 2023
Cancer mortality reduced 40 pcnt by 2000 IU Vitamin D daily if normal weight – Meta-analysis June 2022 03 Jul, 2022
Myth for 50 years: 2000 IU of vitamin D is toxic - still taught as fact in 2010 20 Mar, 2021
Vitamin D Not Reduce Short-Term All-Cause Mortality (if less than 2000 IU, etc.) Sept 2019 11 Sep, 2019
Children need 2000 IU of Vitamin D (India) - RCT May 2019 19 May, 2019
Vitamin D 2000-5,000 IU and Vitamin K2 320 microgram – June 2018 01 Dec, 2018
2000 IU of vitamin D should improve toddlers health in winter – RCT almost completed Feb 2014 03 Oct, 2017
30 percent of vitamin D sold now has more than 2000 IU - Dec 2012 27 Feb, 2017
Crohn's disease treated by 2000 IU Vitamin D - RCT June 2015 31 Jan, 2017
291 genes improved expression by 2000 IU of vitamin D – RCT March 2013 21 Jan, 2017
Indoor bicycling and 2000 IU of vitamin D lowers heart rate by 6 percent – RCT Dec 2016 13 Dec, 2016
2000 IU vitamin D not enough to get most Chinese to 20 ng level – RCT Feb 2015 10 Nov, 2016
2000 IU of vitamin D for just 2 weeks helped in many ways – RCT June 2016 20 Aug, 2016
2000 IU vitamin D during pregnancy and 800 IU to infant resulted in less use of antibiotics – RCT April 2014 17 Apr, 2016
800 IU vitamin D for infant and 2000 IU for mother is good, not great – RCT Dec 2013 04 Apr, 2016
2000 IU of vitamin D during pregnancy got most infants to more than 12 ng (need more) – RCT Aug 2015 21 Oct, 2015
2000 IU of vitamin D- doctors trained that it was too much, but it is often too little 30 Sep, 2015
2000 IU of vitamin D - too much or to little 29 Sep, 2015
2000 IU of vitamin D reduced fatigue of advanced cancer – RCT May 2012 03 Sep, 2015
39% fewer falls with 2000 IU than 800 IU – RCT June 2010 17 Aug, 2015
Good news: Australian clinical trial for vitamin D, bad news: used a max of 2000 IU– Oct 2012 07 Aug, 2015
Multiple Sclerosis web survey: 82 percent take vitamin D (2000-5000 IU), strong association with latitude - Aug 2015 05 Aug, 2015
Breast-feeding mothers need 2000 IU of vitamin D to get infants to even 12 ng – July 2015 14 Jul, 2015
Telomeres improved when obese blacks took 2000 IU of vitamin D daily – Oct 2011 25 Mar, 2015
Many doctors still belief (incorrectly) that more than 800 or 2000 IU of vitamin D is toxic - Oct 2014 10 Nov, 2014
Viral infection reduced 90 percent with 2000 IU of vitamin D – Dec 2010 18 Oct, 2014
Respiratory Tract Infection visits 2.5 less likely with vitamin D: Pregnancy 2000 IU, Infant 800 IU – RCT Oct 2014 04 Oct, 2014
2000 IU daily raised vitamin D levels by 5 nanograms while on submarine patrol – July 2014 22 Jul, 2014
2000 IU of vitamin D should improve health in winter – RCT almost completed Feb 2014 12 Feb, 2014
Sun-cured hay often has 2000 IU of vitamin D per kilogram 08 Jan, 2014
People with no UV for 6 months in the winter need at least 2000 IU of vitamin D – April 2011 17 Dec, 2013
2000 IU vitamin D3 was not enough for children with chronic kidney disease – Feb 2013 10 Dec, 2013
2000 to 3000 IU required to start to help with osteoporos – June 2010 11 Oct, 2013
Review of Vitamin D3 and depression in older adults (take 1000-2000 IU) – Sept 2013 08 Oct, 2013
2000 IU vitamin D raised virtually all Lebanese youths above 20 ng – RCT Oct 2013 05 Oct, 2013
Probably need 1500-2000 IU of vitamin D, high risk groups need more – Sept 2013 08 Sep, 2013
Pathways that vitamin D prevents and treats colon cancer discovered, 2000 IU needed – Dec 2012 25 Jan, 2013
2000 IU of vitamin D for just 5 days did not treat severe pneumonia – RCT June 2012 19 Jan, 2013
2000 IU of vitamin D helped Type 2 diabetic women, but was not enough – July 2012 19 Dec, 2012
RCT confirms that Australians need at least 2000 IU vitamin D – Dec 2012 06 Dec, 2012
2000 IU raised vitamin D levels of thin teens by 10 ng, obese teens by 6 ng – Oct 2012 07 Nov, 2012
Vitamin D repletion = 2000 IU daily for adults and 5000 IU daily for seniors May 2010 13 Oct, 2012
BC elderly median 400 IU only only 3 percent exceed 2000 IU vitamin D – June 2010 03 Sep, 2012
Finland max 2000 IU vitamin D since cannot get more from food - 2011 03 Sep, 2012
400 IU vitamin D for infants and 2000 IU during pregnancy if high risk – June 2010 25 Jun, 2012
To increase vitamin D levels in children need 1000 or 2000 IU – June 2010 25 Jun, 2012
2000 IU daily dose of vitamin D would save Germany 37 billion euros – Aug 2010 23 Jun, 2012
Vitamin D for elderly 800 to 2000 IU - Osteoporosis Canada - Sept 2010 23 Jun, 2012
2000 IU of vitamin D is a step in the right direction for Canada– Nov 2010 23 Jun, 2012
40 ng response plateau to 2000 to 4,000 IU of vitamin D – June 2012 19 Jun, 2012
2000 IU vitamin D was safe and helped elderly – Feb 2011 06 Feb, 2012
Vitamin D 2000 IU Linus Pauling - July 2011 10 Dec, 2011
Improved blood flow in blacks with just 2000 IU of vitamin D – Feb 2011 22 Nov, 2011
200 to 2000 IU vitamin D daily did not improve child bone density – BMJ Jan 2011 01 Feb, 2011
Large Healthcare Org: 1500-2000 IU vitamin D to reduce cancer - Dec 2009 28 Nov, 2010
Vitamin D researchers are taking 2000 to 10000 IU – July 2010 25 Nov, 2010
2000 IU raised black teens vitamin D level to 34 ng and they lost fat – Oct 2010 20 Nov, 2010
56 suppliers of 10000 IU vitamin D – yet 2000 IU toxicity claim persists Oct 2010 29 Oct, 2010
Vitamin D reporting – scientists take 2000 and 3000 IU June 2010 28 Sep, 2010
Scientists call for vitamin D action 2000 IU and more than 40 ng – 2008 30 Aug, 2010
Vitamin D supplementation in a nursing home population – min 2000 IU Aug 2010 30 Aug, 2010
Europe vitamin D Upper Limit 1000 IU and 2000 IU - 2002 28 Aug, 2010
Influenza not reduced by 2000 IU of vitamin D in health adults – Aug 2010 17 Aug, 2010
Upper Limit 2000 IU - July 2010 03 Aug, 2010
Aortas of 16 year old blacks helped by 2000 IU of vitamin D – July 2010 28 Jul, 2010
Average of less than 2000 IU of vitamin D2 did not help bone health – July 2010 18 Jul, 2010
Seniors needed 2000 to 3000 IU of vitamin D to increase serum levels – June 2010 18 Jun, 2010

74+ VitaminDWiki pages have "2,000 IU" in the title

This list is automatically updated

Items found: 73
Title Modified
2,000 IU of Vitamin D is safe and somewhat effective for all adults – Jan 2024 07 Feb, 2024
2,000 IU of Vitamin D per kg of food – best growth, bone strength, etc. (pig trial) – Dec 2022 24 Dec, 2023
Infections in children reduced a bit by 2,000 IU of vitamin D - meta-analysis July 2023 08 Oct, 2023
Senior Cognition not improved by 2,000 IU Vitamin D avg.- RCT Aug 2023 26 Aug, 2023
Knee Osteoarthritis treated by vitamin D if use more than 2,000 IU daily or non-daily high dose – meta-analysis Aug 2023 21 Aug, 2023
Schizophrenia severity reduced somewhat by daily 2,000 IU of Vitamin D – RCT Aug 2023 07 Aug, 2023
Response to infant 2,000 IU Vitamin D daily was in 194 ng, monthly dosing was 20% less – RCT May 2023 17 May, 2023
Vitamiin D Does Not Reduce Fractues in seniors (VITAL 2,000 IU D, no Calcium) - Dec 2022 16 Dec, 2022
Depression is treated by 2,000 IU of Vitamin D – 2 meta-analyses July 2022 30 Oct, 2022
IBD treated in children by Vitamin D, especially if use more than 2,000 IU daily for 12 weeks – meta-analysis – Sept 2022 14 Sep, 2022
Hypertension (both systolic and diastolic) reduced with 2,000 IU of vitamin D – RCT June 2014 23 Jun, 2022
HIV not helped by 2,000 IU of Vitamin D (no surprise) – RCT April 2022 25 Apr, 2022
Responses by healthy individuals to 2,000 IU vitamin D daily – Feb 2022 03 Feb, 2022
Many doctors continue to believe 2,000 IU of vitamin D is max (Hungary in this case)– Dec 2021 07 Dec, 2021
Need more than 2,000 IU daily to get obese people to 30 ng level of vitamin D (not a surprise) – review Jan 2022 07 Dec, 2021
Less cognitive decline in older blacks getting 2,000 IU of vitamin D daily for years (VITAL, etc. post analysis) – RCT Dec 2021 02 Dec, 2021
Post-stroke depression not reduced by 2,000 IU of vitamin D (not a surprise) – Nov 2021 12 Nov, 2021
TB not prevented by a small amount of Vitamin D (2,000 IU daily average, Mongolia) – RCT July 2020 26 Sep, 2021
NAFLD somewhat treated in children with 2,000 IU Vitamin D daily – RCT Aug 2021 30 Aug, 2021
Dark-skinned hunter-gatherers may generate 2,000 IU of vitamin D daily - June 2016 23 Jul, 2021
Digestive Tract Cancer survival increased 3X if 2,000 IU of vitamin D and have high level of PD-L1 – RCT June 2021 29 Jun, 2021
2,000 IU of Vitamin D daily to German Seniors would save 30,000 lives a year – March 2021 08 Mar, 2021
2,000 IU of vitamin D daily helped 80 percent of adolescents – Dec 2020 07 Jan, 2021
2,000 IU of vitamin D and Omega-3 reduced Cancer death rate bv 40% (normal weight) – VITAL RCT Nov 2020 03 Dec, 2020
Swine flu not prevented by 2,000 IU of vitamin D daily (the upper limit at the time) – RCT 2014 30 Aug, 2020
2,000 IU vitamin D is the smallest dose in Saudi Arabia (GCC statement) – March 2020 04 Mar, 2020
Stroke not prevented by just 2,000 IU of vitamin D plus 840 mg Omega-3 (VITAL) – Feb 2020 16 Feb, 2020
2 X better survival of digestive cancer if 2,000 IU of Vitamin D plus good VDBP gene – RCT Feb 2020 04 Feb, 2020
Arterial stiffness reduced if use at least 2,000 IU of Vitamin D for 4 months – meta-analysis Dec 2019 06 Dec, 2019
Digestive track Cancer (poorly differentiated) death 4X less likely if 2,000 IU of vitamin D – RCT Oct 2019 29 Oct, 2019
Poland sets the Vitamin D upper limit to 2,000 IU (wrong) - Aug 2019 28 Aug, 2019
Stroke patients need more than 2,000 IU of vitamin D (found this time in Japan) – RCT June 2019 09 Jul, 2019
Gut genes related to important disease changed in Obese with 2,000 IU for 12 weeks – May 2019 01 Jul, 2019
2,000 IU Vitamin D if healthy. More if overweight or elderly - Dr. Greger April 2019 26 Apr, 2019
Following hip fracture 2,000 IU of vitamin D daily improved quality of life – Feb 2019 23 Mar, 2019
All preteen aged girls in India taking 2,000 IU of vitamin D got levels above 20 ng – RCT Nov 2018 08 Mar, 2019
2,000 IU of Vitamin D raised all girls to above 20 ng (India) – RCT Nov 2018 28 Dec, 2018
Vitamin D 2000-5,000 IU and Vitamin K2 320 microgram – June 2018 01 Dec, 2018
2,000 IU of Vitamin D is not enough to maintain levels above 30 ng – RCT Aug 2018 22 Sep, 2018
Knee replacement not helped by 2,000 IU of vitamin D (both too late and too little) – RCT July 2018 11 Jul, 2018
Diabetes treated and prevented by more than 2,000 IU of vitamin D (need more and gut-friendly) - meta-analyses 2018 08 May, 2018
Much more than 2,000 IU of vitamin D is needed daily (Middle East studies agree) – meta-analysis Nov 2016 10 Apr, 2018
Bottles containing 2,000 IU capsules of Vitamin D seized in Canada (not on authorized list) - March 2018 05 Mar, 2018
Bipolar Spectrum Disorder decreased with 2,000 IU of vitamin D - June 2015 13 Jan, 2018
Russian children need 2,000-4,000 IU of Vitamin D to get most above 40 ng - Dec 2017 26 Dec, 2017
Response to a large dose of vitamin D (80,000 IU) typically varied by 2 X – June 2016 14 Nov, 2017
Can burn pain be relieved by 4 g of Omega-3 and 2,000 IU of vitamin D – RCT due 2021 18 Oct, 2017
Time in sun (in Spain) to get 4,000 IU of vitamin D: half hour in July , 2 hours in October – Sept 2016 08 Jun, 2017
Asthma not helped by less than 2,000 IU of vitamin D - meta-analysis Aug 2015 08 Jan, 2017
Perinatal depression greatly decreased with just a few weeks of 2,000 IU of vitamin D – RCT Aug 2016 09 Dec, 2016
Trial starting for Vitamin D with US soldiers – 2,000 and 5,000 IU for 3 months – Nov 2016 03 Nov, 2016
Obese teens need more than 2,000 IU of vitamin D for 3 months– RCT Feb 2015 02 Nov, 2016
Cancer risk in older women reduced 32 percent by 2,000 IU of Vitamin D plus Calcium – 4 year RCT Oct 2016 12 Oct, 2016
Bacterial vaginosis reduced 3X by 2,000 IU of vitamin D – RCT June 2015 19 Apr, 2016
Dark-skinned hunter-gatherers appear to generate 2,000 IU of vitamin D daily - March 2016 03 Apr, 2016
Staph infections with eczema reduced with 2,000 IU of vitamin D – RCT Oct 2015 13 Feb, 2016
5X fewer school days missed due to asthma if take 2,000 IU vitamin D daily – RCT Feb 2016 05 Feb, 2016
More calcium in bones in those teenage girls getting 2,000 IUs daily – RCT Jan 2016 04 Feb, 2016
Improved births with 2,000 IU vitamin D during pregnancy in India - RCT Feb 2015 12 Nov, 2015
2,000 IU of vitamin D during pregnancy got infants to just above 12 ng – RCT July 2015 21 Oct, 2015
Pregnancy supplemented with 2,000 IU vitamin D got most infants to more than 12 nanograms – Aug 2015 21 Oct, 2015
2,000 IU vitamin D recommended for pediatric rheumatology – May 2015 29 Sep, 2015
Pediatric rheumatologists – recommend 2,000 IU vitamin D supplementation – May 2015 29 Sep, 2015
2,000 IU of vitamin D reduced schizophrenia chance by 77 percent (male infants) - 2004 01 Jun, 2015
2,000,000 IU Vitamin D was not a problem - Sept 2014 01 Apr, 2015
Diabetes in Saudi women improved with just 2,000 IU of vitamin D – July 2012 16 Mar, 2015
Lupus flareups cut in half by just 2,000 IU of vitamin D – RCT Dec 2012 17 Sep, 2014
Influenza A: 5X reduction in first month (only) with 2,000 IU of vitamin D– RCT July 2014 14 Jul, 2014
Fewer injuries and higher ballet jumps with 2,000 IU of vitamin D – April 2013 13 Dec, 2013
Mayo clinic starting Cancer RCT using grossly inadequate 2,000 IU of vitamin D – Sept 2013 04 Dec, 2013
Chronic Heart Failure helped with 2,000 IU of vitamin D (PRA reduced) – RCT June 2013 30 Jun, 2013
Spinal Cord Injury patients normalized by 2,000 IU of vitamin D for 3 months – Sept 2011 04 Jun, 2013
40,000 IU vitamin D2 22 Mar, 2010

Short URL = https://is.gd/2000iu

Attached files

ID Name Comment Uploaded Size Downloads
20771 Mortality.png admin 08 Feb, 2024 151.03 Kb 41
20765 2,000 IU Grant_CompressPdf.pdf admin 07 Feb, 2024 244.21 Kb 9