How does long-term high-dose vitamin D supplementation affect 25(OH)D levels. Is daily intake of up to 60,000 IU vitamin D3 safe for adults. What are the potential benefits and risks of high-dose vitamin D therapy.

Historical Use of High-Dose Vitamin D Therapy

In the 1930s and 1940s, vitamin D was used as a treatment for various conditions, including asthma, psoriasis, rheumatoid arthritis, rickets, and tuberculosis. Remarkably high doses were administered:

• 60,000 to 300,000 IU daily for asthma
• 200,000 to 600,000 IU daily for rheumatoid arthritis

These supraphysiologic doses led to toxicity from hypercalcemia after prolonged use. At the time, blood assays for vitamin D were unavailable, making it impossible to determine the levels associated with hypercalcemia.

Modern Understanding of Vitamin D Toxicity

A 2011 report shed new light on vitamin D toxicity. It revealed that hypercalcemia resolved when 25-hydroxyvitamin D (25OHD) blood levels dropped below 400 ng/ml in patients who had accidentally ingested massive doses of vitamin D. These patients had initially presented with 25OHD levels ranging from 645 ng/ml to 1220 ng/ml.

We now know that the human body can naturally produce up to 25,000 IU of vitamin D daily through skin exposure to UVB radiation. However, there is limited data on the safety and effects of prolonged daily intake of vitamin D in this range.

Case Study: Long-Term High-Dose Vitamin D3 Supplementation

This report presents a case study of three adult males who took high doses of vitamin D3 for extended periods. Their experiences provide valuable insights into the safety and effects of long-term, high-dose vitamin D supplementation.

Subject 1: Escalating Doses Over 6 Years

The first subject followed an increasing dosage regimen over six years, starting in April 2009:

1. 6,500 IU daily for 6 months
2. 10,000 IU daily for 13 months
3. 20,000 IU daily for 24 months
4. 40,000 IU daily for 12 months
5. 50,000 IU daily for 10 months
6. 60,000 IU daily since October 2014

The subject’s 25OHD blood levels were monitored throughout the study, showing values of 28, 81, 204, 216, 225, 166, and 218 ng/ml at various points.

Subject 2: Moderate Dose Escalation

The second subject began with a more moderate dosing regimen:

• 10,000 IU daily from November 2011
• Increased to 20,000 IU in February 2014
• 25,000 IU in June 2014
• 30,000 IU in October 2014
• Decreased to 20,000 IU in June 2015

This subject’s 25OHD blood levels were 96.6, 161.1, and 106.9 ng/ml at different points during the study. Notably, he reported significant improvement in his asthma symptoms.

Subject 3: Gradual Increase to Moderate Dose

The third subject followed a more conservative approach:

• Started with 10,000 IU daily in September 2013
• Increased to 20,000 IU in November 2013

This subject’s 25OHD blood levels were measured at 31.4, 102, 164, 148, and 143 ng/ml throughout the study period.

Safety and Tolerability of High-Dose Vitamin D3

The most significant finding from this case series is that prolonged daily dosing of vitamin D3, ranging from 10,000 to 60,000 IU, was safely tolerated by all three subjects. None of the participants developed hypercalcemia or experienced any adverse events during the study period.

This observation challenges the conventional wisdom regarding the upper limits of vitamin D supplementation and suggests that higher doses may be safe for some individuals under proper medical supervision.

Potential Benefits of High-Dose Vitamin D Therapy

While this case study primarily focused on safety, it also hinted at potential benefits of high-dose vitamin D supplementation. Subject 2 reported marked clinical improvement in his asthma symptoms, which aligns with historical use of vitamin D for respiratory conditions.

Are there other potential benefits of high-dose vitamin D therapy? Research suggests that optimal vitamin D levels may support:

• Bone health and calcium metabolism
• Immune system function
• Cardiovascular health
• Mood regulation
• Cognitive function

However, more research is needed to fully understand the effects of long-term, high-dose supplementation on these and other health outcomes.

Comparing Modern Approaches to Historical High-Dose Therapy

The doses used in this case study, while high by modern standards, are significantly lower than those used in the 1930s and 1940s. Can we draw any conclusions from this comparison?

The historical doses of 60,000 to 300,000 IU daily for asthma and 200,000 to 600,000 IU daily for rheumatoid arthritis were associated with toxicity from hypercalcemia. In contrast, the doses used in this modern case study (up to 60,000 IU daily) did not result in hypercalcemia or other adverse events.

This difference may be attributed to:

• Better understanding of vitamin D metabolism
• Improved monitoring capabilities (25OHD blood level testing)
• More gradual dose escalation
• Individual variability in vitamin D metabolism and tolerance

Implications for Vitamin D Supplementation Guidelines

The findings from this case study raise important questions about current vitamin D supplementation guidelines. Do these results suggest that current recommended upper limits for vitamin D intake are overly conservative?

Current guidelines from various health organizations typically recommend:

• 600-800 IU daily for adults under normal circumstances
• Up to 4,000 IU daily as the upper limit for safe supplementation

However, this case study demonstrates that some individuals can tolerate much higher doses without adverse effects. This suggests that a more personalized approach to vitamin D supplementation may be warranted, taking into account factors such as:

• Baseline vitamin D status
• Individual health conditions
• Genetic factors affecting vitamin D metabolism
• Sunlight exposure and geographical location
• Dietary intake of vitamin D

Monitoring and Safety Considerations for High-Dose Vitamin D Therapy

While this case study shows promising results for the safety of high-dose vitamin D supplementation, it’s crucial to emphasize the importance of proper monitoring and medical supervision. What precautions should be taken when considering high-dose vitamin D therapy?

• Regular monitoring of 25OHD blood levels
• Periodic assessment of serum calcium levels
• Evaluation of kidney function
• Consideration of individual risk factors for vitamin D toxicity
• Gradual dose escalation rather than immediate high dosing

Healthcare providers should also be aware of potential interactions between high-dose vitamin D and certain medications or health conditions.

Signs and Symptoms of Vitamin D Toxicity

Although no adverse events were reported in this case study, it’s important to be aware of the potential signs of vitamin D toxicity, which can include:

• Hypercalcemia (elevated blood calcium levels)
• Nausea and vomiting
• Weakness and fatigue
• Confusion and disorientation
• Kidney problems, including kidney stones

Any individual considering high-dose vitamin D supplementation should be educated about these potential symptoms and instructed to seek medical attention if they occur.

Future Research Directions in High-Dose Vitamin D Therapy

This case study provides valuable insights into the safety and potential benefits of high-dose vitamin D supplementation, but it also raises numerous questions for future research. What areas should be prioritized for further investigation?

• Larger, controlled studies on the long-term safety of high-dose vitamin D supplementation
• Investigation of optimal dosing strategies for different health conditions and populations
• Exploration of the relationship between high-dose vitamin D supplementation and specific health outcomes
• Examination of genetic factors influencing individual responses to high-dose vitamin D
• Development of personalized vitamin D supplementation protocols based on individual factors

Additionally, research into the potential synergistic effects of high-dose vitamin D with other nutrients, such as vitamin K2, magnesium, and omega-3 fatty acids, could provide valuable insights into optimizing supplementation strategies.

Potential Applications in Clinical Practice

As research in this area progresses, it may lead to new applications of high-dose vitamin D therapy in clinical practice. Some potential areas of exploration include:

• Treatment of severe vitamin D deficiency
• Management of autoimmune conditions
• Support for patients with compromised immune function
• Adjunct therapy for mood disorders
• Bone health optimization in high-risk populations

However, it’s crucial to emphasize that any clinical applications of high-dose vitamin D therapy should be based on robust scientific evidence and implemented under close medical supervision.

Conclusion: Balancing Potential Benefits and Risks

The case study presented here offers intriguing evidence for the safety of long-term, high-dose vitamin D3 supplementation in adult males. With doses ranging from 10,000 to 60,000 IU daily, the subjects maintained high 25OHD blood levels without developing hypercalcemia or experiencing adverse events.

These findings challenge current guidelines on upper limits for vitamin D supplementation and suggest that some individuals may safely tolerate and potentially benefit from higher doses. However, it’s crucial to interpret these results cautiously, as they represent a small case series rather than a large-scale clinical trial.

The potential benefits of optimizing vitamin D status are numerous, ranging from improved bone health to enhanced immune function. However, these must be weighed against the risks of excessive supplementation, including the possibility of vitamin D toxicity.

As research in this area continues to evolve, healthcare providers and individuals interested in vitamin D supplementation should stay informed about the latest findings. A personalized approach, taking into account individual factors and employing proper monitoring, may be the key to maximizing the benefits of vitamin D while minimizing risks.

Ultimately, while this case study provides valuable insights, it also underscores the need for further research to fully understand the long-term effects, optimal dosing strategies, and potential applications of high-dose vitamin D therapy.

Results of daily oral dosing with up to 60,000 international units (iu) of vitamin D3 for 2 to 6 years in 3 adult males

In the 1930’s and 1940’s, vitamin D was reported to be an effective treatment for a number of diseases, including asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. High doses were used, 60,000 to 300,000 IU a day for asthma, and 200,000 to 600,000 IU a day for rheumatoid arthritis. Toxicity from hypercalcemia occurred after prolonged oral dosing with these supraphysiologic doses. Assays for measuring vitamin D in the blood were not available, and blood levels of vitamin D associated with hypercalcemia were unknown. A 2011 report on vitamin D toxicity showed that hypercalcemia resolved when 25-hydroxyvitamin D (25OHD) blood levels dropped below 400ng/ml in 2 patients with blood levels ranging from 645ng/ml to 1220ng/ml after accidental ingestion of massive doses of vitamin D. We now know that vitamin D is made in the skin in amounts ranging up to 25,000 IU a day with exposure to UVB radiation. There is little data on the safety and blood levels of 25OHD and calcium after prolonged daily intake of amounts of vitamin D in this range. In this report, one subject took increasing daily doses of vitamin D3 for 6 years starting in April 2009: 6500 IU for 6 months; increasing to 10,000 IU for 13 months; 20,000 IU for 24 months; 40,000 IU for 12 months; 50,000 IU for 10 months, and 60,000 IU since October 2014. 25OHD blood levels were 28, 81, 204, 216, 225, 166, and 218ng/ml. Subject 2 began 10,000 IU in Nov 2011, increased to 20,000 IU in Feb 2014, 25,000 IU in June 2014, and 30,000 IU in Oct 2014, and then decreased to 20,000 IU in June 2015. 25OHD blood levels were 96.6, 161.1 and 106.9ng/ml. He reported marked clinical improvement in his asthma. Subject 3 started on daily 10,000 IU in Sept 2013, increasing to 20,000 IU on Nov 2013. 25OHD blood levels were 31.4, 102, 164, 148, and 143ng/ml. No one developed hypercalcemia or any adverse events. The major finding of this case series is prolonged daily dosing of vitamin D3 with doses of 10,000 to 60,000 IU was safely tolerated.

Keywords:

10,000 IU; 20,000 IU; 25OHD blood levels; 60,000 IU; Oral dosing; Safety; Vitamin D.

A Randomised, Double-Blinded, Placebo-Controlled, Parallel Study of Vitamin D3 Supplementation with Different Schemes Based on Multiples of 25,000 IU Doses

Vitamin D (VTD) treatment is recommended in patients presenting different causes of diseases. To treat these patients, physicians rely on the different available pharmaceutical forms present in their country. Unfortunately, even in a given country, there is no consensus on the best way to treat the patients. In Belgium, VTD is mostly prescribed as ampoules containing 25,000 IU of VTD. In this randomised controlled study, we evaluated whether four therapeutic schemes using multiples of 25,000 IU of VTD according to basal vitamin D concentration were able to increase or maintain the 25(OH)D serum level above 30 ng/mL. We randomized 175 subjects who received the drug () or placebo (). Total duration of the study was 12 weeks. Doses ranged from 4167 to 1667 IU/day. Blood sampling was performed at baseline and each 4 visits. In the treated (placebo) subjects, mean 25(OH)D serum concentration was 18.7 (19.1) ng/mL at baseline and 31.5 (20.7) ng/mL at w-12. At the end of the study, 57.1% of the subjects treated with VTD presented 25(OH)D serum concentration ≥30 ng/mL, whereas 94.3% were ≥20 ng/mL. In conclusion, the doses administered were safe and increased or maintained the 25(OH)D concentration ≥20 ng/mL. However, concentrations ≥30 ng/mL were only achieved in 57.1% of the subjects.

1. Introduction

Vitamin D deficiency has recently been identified as a worldwide problem [1]. Indeed, the dietary sources of vitamin D are scarce, the only really significant ones being marine fatty fish, although egg yolk and some mushrooms could be additional sources [2]. Thus, in humans, the major source of vitamin D comes from the exposure of the skin to sunlight. While, in tropical zones, UVB radiation is sufficient throughout the year, it is absent for a significant part of the year in more northern (or southern) latitudes. In Belgium (around 51° North), the UVB ray will be insufficient to allow the skin synthesis of vitamin D during approximately 6 months of the year. Hence, while all experts agree that the 25-hydroxy vitamin D (25(OH)D) level is the correct indicator of vitamin D status, they do not agree on the 25(OH)D level that should be used to define vitamin D sufficiency. Indeed, the expert panels from the Endocrine Society [3] or the Institute of Medicine (IOM) [4] have recently released divergent recommendations on the use of vitamin D. The recent report by the IOM indicates that a 25(OH)D level of 20 ng/mL is largely sufficient and the RDIs set forth should be sufficient for 97.5% of the population to achieve that level whereas the Endocrine Society group considers that the optimal 25(OH)D level for musculoskeletal health should be 30 ng/mL and more in individual patients. It should be considered that the IOM cutoff is intended for public health recommendations while the Endocrine Society group targets its recommendations on patient care and considers that vitamin D deficiency (what should be avoided in any patient) corresponds to 25(OH)D levels <20 ng/mL and insufficiency (what may be deleterious for a significant proportion of patients) to levels of 20 to 30 ng/mL. Now, considering a threshold of 30 ng/mL, but even with the more conservative IOM cutoff of 20 ng/mL, insufficient vitamin D status is highly frequent. This can easily be understood if one considers that the usual daily intakes of vitamin D are not higher than 200 IU (and often much lower) [5, 6] whereas the most conservative recommendations of the IOM are of 600 IU for adults up to 70 years and 800 IU for those older. Taking that into consideration, one might consider that a moderate supplementation without prior evaluation of vitamin D status is necessary at the population level to fulfil this recommendation. Now, there are some groups of patients for whom many experts consider that a certain reasonably evidence-based range of 25(OH)D concentration should be targeted for optimal effects of vitamin D. In these patients, we [7], like many others [3, 8] consider that 25(OH)D should be measured, and vitamin D supplementation should be prescribed according to the measured serum level (higher dosages in those with lower 25(OH)D concentrations). This mostly apply to musculoskeletal effects of vitamin D and concern patients with, or at risk of, osteoporosis, chronic kidney disease, primary hyperparathyroidism, intestinal malabsorption, and so on… for whom we use to target concentrations of 30–60 ng/mL. Daily dosages (600 to 4000 IU/day for example) may be preferred as they are theoretically more physiologic, but they usually suffer from poor compliance. Although it has become usual practice to avoid very large spaced out doses such as 500,000 IU vitamin D3 once a year due to the results of a recent RCT [9], many physicians and patients prefer intermediate doses given at intervals between one week and one to two months. In Belgium, one of the major source of pharmaceutical vitamin D supplementation is the D-Cure (SMB Laboratories, Belgium), an oily solution containing 25,000 IU of cholecalciferol per ampoule. This drug is largely prescribed to correct vitamin D deficiency, but there is actually no validated treatment scheme. Several protocols using doses of 50,000 IU vitamin D2 or D3 [1, 8] or 100,000 IU vitamin D3 [10] have been tested, but to our knowledge, only one paper has reported the results of supplementation with doses of 25,000 IU vitamin D3 [11]. In this randomised, parallel, double-blinded, placebo-controlled study, we aimed to evaluate whether four therapeutic schemes that used different doses of D-Cure according to basal vitamin D concentration were able to increase or maintain (depending on the baseline level) the 25(OH)D serum level above 30 ng/mL.

2. Methods

2.1. Methodology

The study took place between the 23rd of January and the 22nd of July, 2011. More than two hundred subjects were screened within 14 days prior to starting the study. Those who met all inclusion and none of the exclusion criteria were randomized to one of the four strata based on their baseline 25(OH)D serum concentration. The subjects took the study medication under the supervision of the study personnel at Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), and Visit 5 (week 8). The total duration of the study was 12 weeks with an 8-week period of supplementation followed by a 4-week period without supplementation. Blood samples for measurement of 25(OH)D concentration, calcium, phosphorus, and albumin were collected at each visit after an overnight fast and before next the vitamin D dose. We included Caucasian (defined as European and North African) male or female subjects over 50 years old with a body mass index between 18 kg/m² and 35 kg/m² who were able to comply with all study procedures. They gave written, informed consent to participate in this trial. The exclusion criteria were past or current history of any immunological, neoplasic, endocrine, haematological, hepatic, renal, gastrointestinal, neurological, or psychiatric abnormalities or medical disease. Subjects who used UV light solarium 2 weeks before the screening visit or planned to travel outside European countries during the study were excluded. We also excluded patients under treatment with drugs that may interfere with vitamin D metabolism (e.g., phenobarbital, phenytoin, and glucocorticoids) and those with past or current history of granulomatosis, especially sarcoidosis, urinary lithiasis, and osteomalacia. Finally, patients who presented a 25(OH)D concentration >60 ng/mL, serum creatinine >150 μmol/L and albumin corrected serum calcium >2.65 mmol/L (corresponding to 10.6 mg/dL) at screening were also excluded, as well as those with any sensitivity or allergy to any of the products used in the study or a history of drug and/or alcohol abuse.

2.1.1. Randomisation

At the baseline/randomisation visit (Visit 2), after confirmation that the patients met all eligibility criteria for the study, they were randomized and assigned a randomisation number by an interactive web response System (IWRS). A central, electronic, balanced, permuted blocks randomisation were used. Patients were assigned at random to placebo or vitamin D treatments of the 4 possible groups. The IWRS will randomize a subject to either test or placebo according to a 4 : 1 ratio. It was a block randomization (blocks size of 5) stratified by subgroup.

The objective of this randomization was to obtain 50 patients in each group (40 to D-CURE treatment and 10 to placebo). When the objective was attained in a group, no more inclusion was accepted in that group. Finally, only the objective in group with 25(OH)D level >30 ng/mL was not attained. In fact, only 20 patients were randomized to receive vitamin D and 5 to placebo in that group, due to the fact that the patients with 25(OH) level >30 ng/mL are rare in the Belgium population. In total, 175 patients have been enrolled (140 in treatment group and 35 in the placebo group). The reasons of screening failures were BMI > 35 (exclusion criteria; 1 subject), patient consent withdrawn (1 subject), HCV positive (1 subject), and hypothyroidism (1 subject).

2.1.2. Treatment Scheme

At the end of the screening phase, 175 subjects were selected. 140 were assigned to receive the D-Cure and 35, the placebo according to this scheme received.Group 1. Subjects with baseline serum concentrations of 25(OH)D ≤ 10 ng/mL. Intake: 3 ampoules taken at week 0 and 2 followed by 2 ampoules at week 4 and 8 (total intake: 250,000 IU; ) or placebo ().Group 2. Subjects with baseline serum concentrations of 25(OH)D > 10 ng/mL and ≤20 ng/mL. Intake: 3 ampoules taken at week 0 followed by 2 ampoules at week 2 and 1 ampoule at week 4 and 8 (total intake: 175,000 IU; ) or placebo ().Group 3. Subjects with baseline serum concentrations of 25(OH)D > 20 ng/mL and ≤30 ng/mL. Intake: 2 ampoules taken at week 0 followed by 1 ampoule at week 2, 4, and 8 (total intake: 125,000 IU; ) or placebo ().Group 4. Subjects with baseline serum concentrations of 25(OH)D > 30 ng/mL and ≤60 ng/mL. Intake: 1 ampoule taken at week 0, 2, 4, and 8 (total intake: 100,000 IU; ) or placebo ().

The treatment schemes are summarized in Table 1. These schemes were chosen on the basis of the relationship between a received daily dose of vitamin D3 and the subsequent increase in the 25(OH)D serum level that had been published previously. As, according to a rule of thumb, a daily dose of 1,000 IU vitamin D3 was considered to increase the 25(OH)D level by approximately 7 to 10 ng/mL [12], we decided to give cumulative doses over the 8-week period of supplementations (60 days) that were approximately equivalent to 4,000, 3,000, and 2,000 IU/day in those with a baseline 25(OH)D concentration <10 ng/mL, between 10 and 20 ng/mL, and between 20 and 30 ng/mL, respectively. As we were using 25,000 IU doses, this translated in practice into 250,000 IU over the 8-week period, corresponding to 4167 IU/day in group 1 subjects, 175,000 IU corresponding to 2917 IU/day in group 2, and 125,000 IU corresponding to 2083 IU/day in group 3. For group 4 subjects, we arbitrarily decided to give one ampoule every other week corresponding to 1667 IU/day. For practical reasons, the number of takings of vitamin D3 ampoules was limited to four, so that the study personnel was able to be present at each taking, ensuring an optimal compliance.

We used the DiaSorin Liaison (Stillwater, MN, USA) for 25(OH)D determination. In our lab, intra-, and interassay coefficient of variation are <5% and <10%, respectively. The functional detection limit is 8 ng/mL serum calcium; phosphorus and albumin concentrations were evaluated with the Roche Modular instrument (Mannheim, Germany).

2.2. Statistical Methods

We used the raw SAS Version 9.1 or higher software to compute the results. All statistical tests were performed two sided, and a value less than 5% was considered as statistically significant. Mean changes from baseline to week 12 was calculated with ANOVA. The percentages of subjects reaching 25-hydroxyvitamin D serum concentrations ≥20 ng/mL and ≥30 ng/mL at the end of the study were analysed by means of a chi-square test comparing D-CURE and placebo. For the main continuous baseline characteristics age, and BMI, an ANOVA was performed, and for the binomial baseline variable sex, we used a Cochran-Mantel-Haenszel Test. All safety data obtained in this study was tabulated with descriptive statistics. Comparisons between treatment groups were based on descriptive statistics.

This trial was approved by the relevant Independent Ethics Committee (IEC) and the Competent Authority prior to the start of the study and conducted in compliance with the protocol, with the ICH Harmonized Tripartite Guideline, Guideline for Good Clinical Practice, Step 5 (CPMP/ICH/135/95), the applicable regulatory requirements based on EU Directive 2001/20/EC and EU GCP Directive (2005/28/EC), and the Declaration of Helsinki (World Medical Association) in its revised edition.

3. Results

One hundred and seventy-five subjects completed the study. Their demographics are shown in Table 2. As treatment was taken under the supervision of the study personnel, observance was of 100%.

Vitamin D treatment group Placebo group P value   Group 1 () Group 2 () Group 3 () Group 4 () Subtotal () Group 1 () Group 2 () Group 3 () Group 4 () Subtotal () Age (years) Mean ± SD Min–max 51–89 50–84 51–88 52–87 50–89 50–90 50–85 51–71 50–81 50–90 Subject gender Male: n (%) 14 (35. 0) 15 (37.5) 17 (42.5) 5 (25.0) 51 (36.4) 5 (50.0) 5 (50.0) 4 (40.0) 1 (20.0) 15 (42.9) 0.473 Female: n (%) 26 (65.0) 25 (62.5) 23 (57.5) 15 (75.0) 89 (63.6) 5 (50.0) 5 (50.0) 6 (60.0) 4 (80.0) 20 (57.1) BMI (kg/m²) Mean ± SD Min–max 19–35 20–34 19–34 19–37 19–37 22–32 20–35 19–30 24–31 19–35

In the treated subjects, the mean 25(OH)D serum concentration was 18. 7 ng/mL at baseline and 31.5 ng/mL at week 12, with a mean change to baseline of  ng/mL. In the placebo group, the mean 25(OH)D serum concentration was 19.1 ng/mL at baseline and 20.7 ng/mL at week 12; the mean change to baseline was  ng/mL. The mean 25(OH)D serum concentration at all timepoints is shown in Table 3 for each group. There was a significant increase in 25(OH)D levels at week 12 for all treated groups compared to baseline (, , , and  ng/mL for the Group 1, 2, 3, and, 4, resp.). During the study there was a significant difference between the vitamin D and placebo groups in the 25(OH)D concentrations at week 2, 4, 8, and 12 ( for the global group analysis).

Visit 1 (week 2) Visit 2 (week 0) Visit 3 (week 2) Visit 4 (week 4) Visit 5 (week 8) Visit 6 (week 12) Group 1 25(OH)D Mean ± SD (min–max) 7. 62 ± 2.11 (4.0–12.0) 9.08 ± 3.37 (4.0–19.0) 21.00 ± 5.97 (11.0–46.0) 26.93 ± 7.54 (14.0–45.0) 28.25 ± 8.31 (10.0–45.0) 28.63 ± 8.08 (13.0–49.0) n (%) with 25(OH)D ≤ 20 ng/mL 40 (100) 38 (95) 21 (52) 9 (22) 6 (15) 6 (15) n (%) with 25(OH)D ≤ 30 ng/mL 40 (100) 40 (100) 37 (92) 27 (67) 26 (65) 25 (62) Group 2 25(OH)D Mean ± SD (min–max) 13.72 ± 2.63 (8.0–20.0) 15.30 ± 3.38 (7.0–23.0) 25. 55 ± 5.89 (12.0–41.0) 31.65 ± 7.60 (18.0–50.0) 28.15 ± 7.69 (14.0–46.0) 30.10 ± 8.15 (13.0–50.0) n (%) with 25(OH)D ≤ 20 ng/mL 40 (100) 35 (87) 8 (20) 1 (2) 7 (17) 3 (7) n (%) with 25(OH)D ≤ 30 ng/mL 40 (100) 40 (100) 35 (87) 20 (50) 27 (67) 24 (60) Group 3 25(OH)D Mean ± SD (min–max) 24.88 ± 2.75 (21.0–30.0) 24.38 ± 5.31 (12.0–38.0) 32.88 ± 5.63 (20.0–51.0) 33.90 ± 8.24 (24.0–62. 0) 35.25 ± 7.22 (23.0–54.0) 33.90 ± 8.21 (5.0–50.0) n (%) with 25(OH)D ≤ 20 ng/mL 0 (0) 10 (25) 1 (2) 0 (0) 0 (0) 1 (2) n (%) with 25(OH)D ≤ 30 ng/mL 40 (100) 36 (90) 14 (35) 14 (35) 12 (30) 10 (25) Group 4 25(OH)D Mean ± SD (min–max) 38.21 ± 6.11 (31.0–51.0) 32.70 ± 10.01 (11.0–53.0) 34.85 ± 8.25 (21.0–56.0) 35.65 ± 10.49 (17.0–55.0) 36.25 ± 11.90 (20.0–67.0) 35. 15 ± 13.37 (11.0–68.0) n (%) with 25(OH)D ≤ 20 ng/mL 0 (0) 3 (15) 0 (0) 2 (10) 1 (5) 1 (5) n (%) with 25(OH)D ≤ 30 ng/mL 0 (0) 6 (30) 7 (35) 2 (10) 8 (40) 9 (45) Placebo group (group 5 + 6 + 7 + 8) 25(OH)D Mean ± SD (min–max) 18.83 ± 10.89 (6.0–50.0) 19.09 ± 9.43 (5.0–42.0) 18.57 ± 8.48 (6.0–43.0) 19.06 ± 9.34 (6.0–39.0) 19.17 ± 9.41 (4.0–38.0) 20.74 ± 9.48 (4.0–39.0) n (%) with 25(OH)D ≤ 20 ng/mL 20 (57) 19 (54) 21 (60) 21 (60) 21 (60) 19 (54) n (%) with 25(OH)D ≤ 30 ng/mL 30 (86) 31 (89) 33 (94) 29 (83) 30 (86) 30 (86)

The highest serum 25(OH)D concentration (68 ng/mL) was observed at week 12 in one subject of the group 4, whose basal level was of 48 ng/mL.

At the end of the study, (week 12) 57.1% () of subjects in the vitamin D group had a 25(OH)D serum concentration ≥30 ng/mL, and 94.3% (), a concentration ≥20 ng/mL. In the placebo group, 20.0% () had a 25(OH)D serum concentration ≥30 ng/mL and 54.3% () ≥20 ng/mL. The number of subjects that did not reach 25(OH)D levels of 30 ng/mL or 20 ng/mL at each timepoint is shown in Table 3 and Figure 1 for each treated and placebo group separately. The lower number of subjects that did not reach 25(OH)D serum concentrations of ≥30 ng/mL at week 12 was seen in group 3 subjects (25%, ). There were 25/40 (62%) subjects and 24/40 (60%) subjects who did not reach serum concentrations of 25(OH) vitamin D ≥30 ng/mL at week 12 in the groups 1 and 2, respectively.

Altogether 106 of the 140 subjects of the vitamin D group (75.71%) and 11 of the 35 subjects treated with placebo (31.43%) had a serum 25(OH)D concentration of ≥30 ng/mL at one or more time points during the study. The highest number of subjects was in subgroup 3. In this group, 97.5% of the subjects achieved a serum 25(OH)D concentration of ≥30 ng/mL in one or more visit, but only 77.5% of them had a serum 25(OH)D concentration of ≥30 ng/mL at the end of the study.

There were no significant changes to baseline seen in the mean plasma phosphorus and calcium concentrations during the study. The mean change to baseline at week 12 for plasma phosphorus was −0.29 mg/dL (±1.960) in subjects treated with SMB D-CURE and −0.26 mg/dL (±0.584) in the placebo group. The mean change to baseline at week 12 for plasma calcium was 0.00 mg/dL ± 0.378 in subjects treated with SMB D-CURE and 0.02 mg/dL ± 0.259 in the placebo group. We did neither observe hypercalcemia nor kidney stone during the study.

4. Discussion

We performed a trial to test several schemes of supplementation with ampoules containing 25,000 IU vitamin D3 in subjects 50 years of age and older, based on their baseline serum concentration of 25(OH)D. The main strengths of this study are its double-blinded, placebo-controlled nature, allowing to control for possible confounders such as season-, or diet-related changes in the 25(OH)D level, and the supervision by the study staff of the administration of all vitamin D3 doses allowing for a compliance of 100%.

The concentration of 25(OH)D in serum was significantly increased after treatment with D-CURE compared to placebo for the total analysis. As this study took place during a part of spring, it is important to note that we did not observe any significant increase in the placebo group, suggesting that these increases in the treated group are only due to the treatment.

At week 12 of the study, that is one month after a 60-day supplementation period with doses of vitamin D3 corresponding to 1667 to 4167 IU/day, the mean change from baseline in the different subgroups ranged from +2.5 to +19.7 ng/mL. This was somewhat lower than the expected increase of 7 to 10 ng/mL in the 25(OH)D level for every 1,000 IU vitamin D3 per day, according to Heaney [12]. The 25(OH)D increase in our study was also lower than what could have been predicted from a more recent meta-analysis where the average increase during different RCT or open trials was 0.78 ng/mL per 40 IU of vitamin D3 supplement per day in Caucasian subjects over 50 yr old, albeit with a great variability [13]. In this meta-analyse, the authors underlined different sources of between-trial variability. Poor adherence to supplementation, often due to coadministration of calcium supplements, use of vitamin D2 instead of vitamin D3, and high proportion of overweight subjects included in the trial were identified as potential causes for a weak increase in the 25(OH)D serum level. These reasons do not apply to the present study in which compliance was 100%, calcium supplements were not provided, vitamin D3 was used, and the mean BMI was close to 26 kg/m² with very few obese (BMI > 30) subjects. Another potential cause of variability in the 25(OH)D response to vitamin D supplementation among studies is the use of various 25(OH)D assays. In the present study, we used the DiaSorin Liaison assay, an automated assay widely used worldwide and for which the results of the external proficiency testing DEQAS samples in our laboratory are very close of the all laboratory trimmed mean (ALTM).

While most of the vitamin D-treated subjects reached a 25(OH)D serum concentration of 20 ng/mL or more, only 42. 5% of those with baseline concentrations below 10 ng/mL, 47.5% of those with baseline concentrations of 10 to ≤20 ng/mL, and 77.5% of those with a baseline level of 20 to ≤30 ng/mL achieved a 25(OH)D concentration of ≥30 ng/mL at week 12. Furthermore, only 65.0% of those who had concentrations of ≥30 ng/mL at week 0 had still such a value at week 12 after treatment. Overall, this suggests that the doses of vitamin D3 administered in the present study were insufficient to achieve or maintain the 30 ng/mL target in a significant proportion of the included subjects. It must be underlined that the dose administered to the subjects with a baseline serum level ≤10 ng/mL was already very close (slightly above in fact) to the upper safety limit (UL) of 4,000 IU/day defined by the IOM [4]. Thus, if a 25(OH)D level of 30 ng/mL or more is targeted in future studies, higher doses than the IOM UL should be used.

At week 12, change from baseline in the 25(OH)D concentration of the placebo groups ranged from −8. 20 to +4.30 ng/mL. The negative change was observed in the subgroup with baseline 25(OH)D > 30 ng/mL and confirms that even if this target level is reached, a maintenance dose is usually required to sustain the serum 25(OH)D above 30 ng/mL.

The maximum serum 25(OH)-vitamin D concentration (68 ng/mL) was observed at week 12 and is far from 150 ng/mL, generally considered as the potentially “toxic” limit. We did not observe clinically significant change in the plasma calcium and phosphorus concentrations.

In conclusion, this study explored the change in serum 25(OH)D concentrations in subjects with different baseline concentrations of 25(OH)D who received different doses of vitamin D. The current doses administered were safe and produced a significant change compared to placebo, increasing or maintaining (depending on the baseline level) the 25(OH)D concentration ≥20 ng/mL. However, serum concentrations of 25(OH)D ≥ 30 ng/mL were only achieved in 57.1% of the subjects receiving the vitamin D, indicating that the doses may need to be increased in subsequent studies where this concentration will be targeted.

Acknowledgment

The study was financed by SMB Laboratories (Brussels, Belgium).

What is the correct dosing for Vitamin D?

Dr. Kenneth Madden (biography and disclosures)

What I did before

Every year, one-third of older adults (age greater than 65) experience one or more falls.¹  One therapy with the potential to reduce both falling and fractures is vitamin D supplementation, possibly due to a direct stimulation of vitamin D receptors on muscle tissue.²  Often the patients that would most benefit from vitamin D (frail older adults with frequent falls) have swallowing issues that make swallowing large vitamin pills difficult.  Since “there is no correct dose” and it is “only a vitamin” I often administered larger doses (such as yearly courses of 50 000 IU cholecalciferol once per week X 8 weeks) to make administration easier for patients with swallowing issues.

What changed my practice

Unfortunately, a closer look at the issue revealed the appropriate dose of vitamin D necessary to safely reduce fall and fracture risk remains controversial.   A recent meta-analysis of all studies done to date³ demonstrated that “high dose” vitamin D reduced falls by 23 percent (RR 0.77, 95% confidence interval 0.71 to 0.92) when “high dose” was defined as 700 to 1000 IU per day.  Lower doses (less than 700 IU) had no effect on fall risk.  The effects of doses higher than 1000 IU had not been examined previously to the publication of this meta-analysis.  It is also important to remember that large doses of vitamins are not necessarily benign; the increase in mortality with high-dosage vitamin E⁴ should serve as a cautionary example.

After the publication of the above meta-analysis, a randomized, controlled, double blind study⁵ examined the effect of a massive yearly doses of vitamin D on falls and fractures.  The investigators recruited a large number of older adult women (median age of 76 years, n=2258) that were at high risk for falls (defined as the subject being a self-reported faller, having a previous fracture, or having a family history of maternal hip fracture).  The study intervention was 500 000 IU cholecalciferol given as 10 tablets taken on a single day.  Unfortunately, the large-dose vitamin D group both fell and had more fractures than the placebo group.  In fact, there was approximately one more fracture per 100 person-years in the vitamin D group as compared to the placebo group. Of even more concern, fracture rates in the treatment group were highest in the first 3 months following the large dose of vitamin D, suggesting a direct toxic effect.

What I do now

There is support for using vitamin D to prevent falls in older adults, but only in a dose ranging from 700 IU to 1000 IU per day.  I no longer give patients larger doses of vitamin D at less frequent intervals; in fact this practice might have been causing harm. There is no literature to determine what the impact of a more temperate but larger dose of vitamin D will have on fall and fracture rates.  Like any other medication, large doses of vitamins can be harmful.

References: (Note: Article requests require a login ID with CPSBC or UBC)

1. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988;319:1701-7. (View article with CPSBC or UBC)
2. Bischoff-Ferrari HA, Borchers M, Gudat F, Durmuller U, Stahelin HB, Dick W. Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 2004;19:265-9. (View article with CPSBC or UBC)
3. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 2009;339:b3692. (View article with CPSBC or UBC)
4. Miller ER, 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:37-46. (View article with CPSBC or UBC)
5. Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 2010;303:1815-22. (View article with CPSBC or UBC)

Notes from the BC Guidelines

http://www.bcguidelines.ca/guideline_vitamind.html

There is good evidence that supplementation with at least 800 international units (IU) of vitamin D₃ per day, combined with calcium, is required to reduce the risk of fragility fractures, therefore 800 – 1000 IU daily is recommended (although the optimum daily requirement of vitamin D₃ is not known).^4,5,6 Weekly dosing (one week’s adult dose of vitamin D₃ taken as a single weekly dose, i.e. 7000 IU) or monthly dosing (one month’s adult dose of vitamin D₃ taken once a month, i.e. 30,000 IU) may be more convenient for some patients and has been shown to be safe.^1,4,7 At this time, high doses of vitamin D₃ once a year is not recommended as recent evidence has shown possible increased fracture risk.⁸

Population at Risk

The BC population is at risk of low vitamin D levels from autumn to spring. There is no clinical utility in performing vitamin D tests on patients who are thought to be at risk for sub-optimal vitamin D levels and who would benefit from vitamin D supplementation.

Vitamin D Supplementation without Testing

Because vitamin D supplementation in the general adult population is safe, it is reasonable to advise supplementation without testing. Routine testing of vitamin D levels [25-hydroxyvitamin D or 25(OH)D] is not medically necessary prior to or after starting vitamin D supplementation.

Utilization and Cost of Serum Vitamin D Testing in BC

Utilization of vitamin D testing [as 25(OH)D] in BC has increased ten-fold in the past five years. Medical Service Plan expenditures are approximately $3 million annually for outpatient vitamin D testing with a cost per test of $93.63 in 2009.

Please indicate how this article will change your practice:

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Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience

Vitamin D3 is a secosteroid hormone produced in the skin in amounts estimated up to 25,000 international units (IUs) a day by the action of UVB radiation on 7-dehydrocholesterol. Vitamin D deficiency is common due to both lack of adequate sun exposure to the skin, and because vitamin D is present in very few food sources. Deficiency is strongly linked to increased risk for a multitude of diseases, several of which have historically been shown to improve dramatically with either adequate UVB exposure to the skin, or to oral or topical supplementation with vitamin D. These diseases include asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. All patients in our hospital have been routinely screened on admission for vitamin D deficiency since July 2011, and offered supplementation to either correct or prevent deficiency. During this time, we have admitted over 4700 patients, the vast majority of whom agreed to supplementation with either 5000 or 10,000 IUs/day. Due to disease concerns, a few agreed to larger amounts, ranging from 20,000 to 50,000 IUs/day. There have been no cases of vitamin D3 induced hypercalcemia or any adverse events attributable to vitamin D3 supplementation in any patient. Three patients with psoriasis showed marked clinical improvement in their skin using 20,000 to 50,000 IUs/day. Analysis of 777 recently tested patients (new and long-term) not on D3 revealed 28.7% with 25-hydroxyvitaminD3 (25OHD3) blood levels < 20 ng/ml, 64.1% < 30 ng/ml, a mean 25OHD3 level of 27.1 ng/ml, with a range from 4.9 to 74.8 ng/ml. Analysis of 418 inpatients on D3 long enough to develop 25OHD3 blood levels > 74.4 ng/ml showed a mean 25OHD3 level of 118.9 ng/ml, with a range from 74.4 to 384.8 ng/ml. The average serum calcium level in these 2 groups was 9.5 (no D3) vs 9.6 (D3), with ranges of 8.4 to 10.7 (no D3) vs 8.6 to 10.7 mg/dl (D3), after excluding patients with other causes of hypercalcemia. The average intact parathyroid hormone levels were 24.2 pg/ml (D3) vs. 30.2 pg/ml (no D3). In summary, long-term supplementation with vitamin D3 in doses ranging from 5000 to 50,000 IUs/day appears to be safe.

Vitamin D: A rapid review of the evidence for treatment or prevention in COVID-19

May 1, 2020

Joseph Lee, Oliver van Hecke, Nia Roberts

On behalf of the Oxford COVID-19 Evidence Service Team
Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences
University of Oxford

Correspondence to [email protected]

VERDICT
We found no clinical evidence on vitamin D in COVID-19. There was no evidence related to vitamin D deficiency predisposing to COVID-19, nor were there studies of supplementation for preventing or treating COVID-19 (Search date upto 4th of April 2020, clinicaltrials.gov searched upto on 23rd April).

There is some evidence that daily vitamin D3 supplementation over weeks to months may prevent other acute respiratory infections, particularly in people with low or very low vitamin D status. This evidence has limitations, including heterogeneity in study populations, interventions, and definitions of respiratory infections that include upper and lower respiratory tract involvement.

The current advice is that the whole population of the UK should take vitamin D supplements to prevent vitamin D deficiency. This advice applies irrespective of any possible link with respiratory infection.

Clinicians should treat patients with vitamin D deficiency irrespective of any link with respiratory infection.

Policymakers should attend to public health measures to ensure the population has adequate vitamin D intake.

BACKGROUND
Vitamin D
Vitamin D is the name given to a group of vitamins (see box 1). Vitamin D2 (ergocalciferol, found in plants) and vitamin D3 (cholecalciferol, found in animal tissues) are pharmacologically inactive and we convert them to active compounds by hydroxylation in the liver and then kidneys (Figure 1).[1] The liver converts vitamin D3 to 25-hydroxycholecalciferol, which is weakly active. The kidneys then convert this to either 24,25-dihydroxycholecalciferol, which is also weakly active, or to 1α,25-dihydroxycholecalciferol, the most active form of vitamin D (Box 1).[1] Vitamin D is important for bone metabolism, and regulates calcium concentrations in the blood. Vitamin D increases absorption of calcium from the gut and reduces the amount lost by the kidneys. Many tissues have vitamin D receptors, and vitamin D may have other roles.[2]

Figure 1: Metabolic pathways of vitamin D, reproduced with permission from The Oxford Textbook of Clinical Pharmacology and Drug Therapy

Sources of vitamin D
We get vitamin D predominantly by synthesizing D3 in our skin using ultraviolet B (UVB) light, with small quantities obtained from food sources. In countries at high latitudes, the UVB in winter isn’t sufficient to synthesize enough vitamin D, so oral intake becomes more important. Dietary sources include animal products like oily fish, red meat, liver, and egg yolks, and fortified foods like infant formula milk, breakfast cereals and margarines (Box 2). Some mushrooms can provide vitamin D if grown under ultraviolet light.[3] The UK government’s Scientific Advisory Committee on Nutrition (SACN) advises a daily intake of 10 µg (micrograms) (400 International Units/day)* for everyone over the age of four years living in the UK in order to ensure musculoskeletal health.[4] They estimate that this will meet the needs of 97.5% of the population, but note that it is difficult to achieve this intake with diet alone and recommend supplements.[4] In adults the standard dose for prevention of vitamin D deficiency is 10 µg (400 IU) daily.[5] For young children SACN defined safe intake levels rather than reference intake values; for those less than one year of age 8.5 to 10 µg (340 to 400 IU) per day, and for children aged one to four 10 µg (400 IU) daily.[4]

Vitamin D deficiency
Vitamin D is usually measured in blood serum in the relatively stable 25-hydroxycholecaliferol form (25(OH)D3). In the UK, 25 nmol/L (10ng/ml) is used as the cut off for deficiency, but there is no universally agreed definition so clinical studies have used different values to define vitamin D deficiency.[4]

Vitamin D deficiency is very common, particularly in winter. In January to March in the UK, 30% of people aged 65 years and over and 40% of people aged 19–64 years had serum vitamin D concentrations below 25 nmol/L.[6]

The UK government’s SACN report identifies people at high risk of deficiency [4]:

• Infants and children aged under four years old;
• Pregnant and breastfeeding women, particularly teenagers and young women;
• People over 65;
• People who have low or no exposure to the sun, for example those who cover their skin for cultural reasons and those who are housebound or confined indoors for long periods;
• People with darker skin, for example people of African, African-Caribbean, or South Asian family origin.

In vitro evidence for vitamin D’s role in immunity and infection

There is in vitro evidence that vitamin D is involved in immune cell responses to some viral and bacterial respiratory pathogens. Vitamin D appears to upregulate genes involved in responses in immune cells that are exposed to Streptococcus pneumoniae.[7] There are laboratory studies showing that respiratory epithelial cells can convert vitamin D to its active form, and that vitamin D metabolites increase cytokines involved in immunity in response to respiratory viruses. However, vitamin D metabolites do not seem to prevent viral replication in cell cultures.[2, 8]

Why consider vitamin D in COVID-19?

Some have speculated that people with low serum vitamin D might be at higher risk of infection with COVID-19, or do worse if infected.[9] There is an overlap between groups at high risk of vitamin D deficiency and groups at high risk of severe COVID-19. Examples include people with chronic disease, older age, and people of black and minority ethnic (BAME) heritage. However, infants and children are at risk of vitamin D deficiency, but are not considered high-risk for severe COVID-19.[10]

Media coverage has highlighted the high burden of COVID-19 in BAME populations.[11] On 10 April 2020 the UK’s Intensive Care National Audit and Research Centre (ICNARC) reported that 31% (310/993) of patients requiring advanced respiratory support defined their ethnicity in a non-white category, compared with 24% of patients (99/408) receiving basic respiratory support.[12] These data are intriguing, but we need to be cautious about over-interpreting them. These audits did not set out to examine the risk of vitamin D deficiency as a risk factor for COVID-19 infection, and many factors that might explain this apparent association have not been accounted for.

If vitamin D does have a role in preventing or mitigating the effects of COVID-19 infection, supplementation would be a cheap and low risk intervention. We therefore aimed to review the clinical evidence that vitamin D has a role in preventing or treating COVID-19.

CLINICAL EVIDENCE IN COVID-19
We searched PubMed and Google Scholar for studies that included terms for vitamin D and COVID-19. We found no trials of vitamin D in COVID-19 that have reported results. We did find several studies that are registered, but have not yet reported. None seemed to be masked comparisons to placebo.

A trial of vitamin D3 plus zinc versus usual care is planned in an open-label randomised controlled trial (RCT) in adults over the age of 60 years who are ‘institutionalized’ but asymptomatic.[13] The dose of vitamin D3 is 2000 IU (50 µg) plus 30 mg of zinc gluconate per day for two months. The primary outcome measure is mortality; the incidence of COVID-19 infection is a secondary outcome.

One trial is testing whether a single oral dose of 25,000 IU (625 µg) of vitamin D (form not specified) will improve mortality in patients who are infected with SARS-CoV-2 but do not have severe symptoms, compared with usual care.[14] The rationale draws on veterinary findings that reduced levels of vitamin D in calves were associated with bovine coronavirus infection.

Another RCT will compare single doses of vitamin D3, 50,000 IU to 200,000 IU (1250 Vs 5000 µg) in people with COVID-19 pneumonia who are over 75 years of age, or over 70 with low oxygen saturations; the primary outcome measure is mortality at 14 days.[15]

Single group studies:
A single group open-label study is using a combination of hydroxychloroquine, vitamins C and D (form not specified), and zinc as prophylaxis in healthy healthcare workers who are at risk of COVID-19 through exposure to infected patients.[16] The same investigator has registered another study, that will give all participants hydroxychloroquine, vitamins C and D (form not specified), and zinc plus azithromycin, with the aim of determining if this combination can effectively treat COVID-19.[17] It is unclear how these studies will meet their stated aims without comparison groups.

VITAMIN D TO PREVENT OTHER ACUTE RESPIRATORY TRACT INFECTIONS
As our searches returned no relevant results, we widened the criteria to include other acute respiratory tract infections (ARTI). ARTIs were defined by most of the studies as a broad group comprising both upper and lower respiratory infections.

Observational evidence suggests that low, particularly very low serum vitamin D concentrations are associated with a higher incidence of ARTIs. A recent meta-analysis of observational studies showed a significantly greater risk of ARTI in patients with the lowest 25(OH)D3 categories compared with the highest categories (odds ratio (OR) 1.83; 95% CI 1.42 to 2.37; I² = 78.8%,14 studies, n=78,217 adults).[18] They pooled vitamin D categories as defined by the included studies (which varied a great deal), and included diverse ARTIs from upper respiratory tract infections to pneumonia. They looked for a dose response relationship and found a non-linear association between infections and serum vitamin D (highest risk in <37.5nmol/L but risk detectable at <60nmol/L in data from 5 studies of 37,902 participants). Patients were at higher risk of a composite outcome of severe infection or dying in the lowest vitamin D categories compared with the highest (OR 2.46, 95% CI 1.65 to 3.66; I² = 49.8, 5 studies, n=1495) and also at higher risk of dying (OR 2.46; 95% CI 1.65 to3.66; I² = 49.8%; 4 studies, n=1422). The authors raised some important concerns about the data, including evidence of publication bias and a high degree of heterogeneity in the results.

Reviews and meta-analyses of RCTs have found a protective effect of vitamin D3 supplementation taken over weeks to months. This was more pronounced in patients with the lowest baseline concentrations of vitamin D (though definitions of deficiency varied).[19, 20] One review of RCTs showed that vitamin D supplementation was associated with reduced ARTIs (OR for combined upper and lower RTI 0.64; 95% CI 0.49 to 0.84; p = 0.0014, I² = 72%; 11 studies, n = 5389, NNTs over 3 months 9 to 33).[19] They also examined whether other factors might explain this effect, such as infrequent versus daily dosing of vitamin D3, baseline vitamin D status, adults versus children, sex, or healthy participants versus patients. The only significant association was the dosing interval: when vitamin D3 was administered daily it was associated with a significant reduction in ARTIs (OR, 0.51; 95% CI, 0.39 to 0.67), while vitamin D3 had no effect when administered in large doses once per month or less often (OR 0.86; 95% CI, 0.62 to 1.20).

A large meta-analysis of individual patient data from RCTs showed similar findings.[20] Vitamin D3 supplementation resulted in a significant reduction in the proportion of patients experiencing at least one ARTI (adjusted OR 0.88, 95% CI 0.81 to 0.96, P=0.003; NNT=33 [20 to 101], n=10,933). The effect of supplementation was greatest in patients with serum concentrations below 25 nmol/L (adjusted OR 0.58, 95% CI 0.40 to 0.82, NNT = 8 [5 to 21], n=538). Daily or weekly dosing seemed to be protective, even when baseline concentrations were above 25 nmol/L, but intermittent larger doses were not effective, even in patients with vitamin D deficiency. Subgroup analyses did not show significant effects when upper and lower respiratory tract infections were analysed separately.

Lastly, an overview of systematic reviews of vitamin D for all non-skeletal conditions suggests that vitamin D2 or D3 supplementation has no important clinical effect on most conditions, including chronic inflammation, strengthening the hypothesis that low vitamin D status is a consequence of ill health, rather than its cause.[21]

CONCLUSIONS
We found no clinical evidence that vitamin D supplements are beneficial in preventing or treating COVID-19. We would need evidence from well-masked randomized trials to determine if there are effects, before recommending vitamin D3 supplements for treating or preventing COVID-19 infection.

There is some evidence that vitamin D may have a role in preventing other respiratory infections, particularly for people with low or very low vitamin D status. Whilst this evidence comes from systematic reviews of randomised trials, it has many limitations, including heterogeneous definitions of respiratory infections, study populations, interventions and definitions of vitamin D deficiency.

People at risk of vitamin D deficiency should in any case take supplements in line with current guidance. Currently the whole UK population is advised to take supplements. Similarly, clinicians should continue to treat people with vitamin D deficiency – but not because of any possible association with respiratory infection. Policymakers should attend to the recommendations of the SACN, including developing food-based strategies for the general population to achieve adequate vitamin D intake.

Disclaimer:  This article has not been peer-reviewed; it should not replace individual clinical judgement and the sources cited should be checked. The views expressed in this commentary represent the views of the authors and not necessarily those of the host institution, the NHS, the NIHR, or the Department of Health. The views are not a substitute for professional medical advice.

Acknowledgements:  We would like to thank Professor Susan Jebb and Dr Jeffrey Aronson for their helpful comments, and Dr Aronson for permission to reproduce material from The Oxford Textbook of Clinical Pharmacology and Drug Therapy.

AUTHORS
Joseph Jonathan Lee is a General Practitioner and doctoral researcher based at the Nuffield Department of Primary Care Health Sciences, University of Oxford.
Oliver van Hecke is a General Practitioner and NIHR Academic Clinical Lecturer based at the Nuffield Department of Primary Care Health Sciences, University of Oxford.
Nia Wyn Roberts is an Information Specialist based at the Nuffield Department of Primary Care Health Sciences, University of Oxford.

*1 International Unit (IU) is the biological equivalent of 25 nanograms of cholecalciferol or ergocalciferol; i.e. 40 IU = 1 microgram of vitamin D. It is defined as the total amount of vitamin D that will produce a narrow line of calcium deposit in the rachitic metaphyses of the distal ends of the radii and ulnae of standard rachitic rats within 10 days.[1]

SEARCH TERMS
We searched Pubmed, Google Scholar and medRxiv on 4 April 2020 for evidence for a number of reviews of substances in COVID-19, including vitamin D. For vitamin D we included the search terms: Vitamin D* OR vit d* OR colecalciferol, AND coronavirus, SARS-Cov-2, 2019-NCov, and COVID-19; and broader search terms Vitamin D* OR vit d* OR colecalciferol AND bronchitis OR common cold OR influenza OR pneumonia OR SARS OR MERS OR severe respiratory infections OR acute respiratory infections OR “Respiratory Tract Infections”[Mesh]. We also searched clinicaltrials.gov for registered trials of vitamin D in COVID-19 on 23/04/2020. In addition, we included reviews of the existing literature on this topic. We provide a narrative summary of the current literature.

REFERENCES

1. Grahame-Smith DG, Aronson JK. The Oxford Textbook of Clinical Pharmacology and Drug Therapy. Oxford: Oxford University Press; 2002.
2. Hansdottir S, Monick M, Hinde S, Lovan N, Look D, Hunninglake G. Respiratory Epithelial Cells Convert Inactive Vitamin D to its Active Form. J. Immunol. 2008; 181: 7090–7099.
3. Cardwell G, Bornman JF, James AP, Black LJ. A review of mushrooms as a potential source of dietary vitamin D. Nutrients 2018; 10: 1–11.
4. Public Health England. Vitamin D and Health 2016 [Internet]. Sci. Advis. Comm. Nutr. 2016 Available from: https://www.gov.uk/government/publications/sacn-vitamin-d-and-health-report.
5. Joint Formulary Comittee. British National Formulary [Internet]. London: BMJ Group and Pharmaceutical Press; 2019.Available from: https://bnf.nice.org.uk/drug/colecalciferol.html#indicationsAndDoses.
6. Bates B, Lennox A, Prentice A, Bates C, Page P, Nicholson S, Swan G. National Diet and Nutrition Survey Results from Years 1, 2, 3 and 4 (combined) of the Rolling Programme. London; 2008.
7. Olliver M, Spelmink L, Hiew J, Meyer-Hoffert U, Henriques-Normark B, Bergman P. Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae. J. Infect. Dis. 2013; 208: 1474–1481.
8. Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients 2015; 7: 4240–4270.
9. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, Bhattoa HP. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 2020; 12: 988.
10. Coronavirus (COVID-19): Shielded patients list [Internet]. Available from: https://digital.nhs.uk/coronavirus/shielded-patient-list.
11. Croxford R (BBC). Coronavirus: Ethnic minorities “are a third” of patients [Internet]. 2020.Available from: https://www.bbc.co.uk/news/uk-52255863.
12. ICNARC. ICNARC report on COVID-19 in critical care. 2020; : 1–9.
13. Seguy D. Impact of Zinc and Vitamin D3 Supplementation on the Survival of Aged Patients Infected With COVID-19 (ZnD3-CoVici) [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT04351490.
14. Castillo MJ. Vitamin D on Prevention and Treatment of COVID-19 (COVITD-19) [Internet]. NCT04334005 2020.Available from: https://clinicaltrials.gov/ct2/show/NCT04334005.
15. Annweiler C. COvid-19 and Vitamin D Supplementation: a Multicenter Randomized Controlled Trial of High Dose Versus Standard Dose Vitamin D3 in High-risk COVID-19 Patients (CoVitTrial) [Internet]. 2020.Available from: https://clinicaltrials.gov/ct2/show/record/NCT04344041.
16. Haza S. A Study of Hydroxychloroquine, Vitamin C, Vitamin D, and Zinc for the Prevention of COVID-19 Infection (HELPCOVID-19) [Internet]. 2020.Available from: https://clinicaltrials.gov/ct2/show/record/NCT04335084.
17. Haza S. A Study of Quintuple Therapy to Treat COVID-19 Infection (HAZDpaC) [Internet]. 2020.Available from: https://clinicaltrials.gov/ct2/show/NCT04334512.
18. Pham H, Rahman A, Majidi A, Waterhouse M, Neale RE. Acute respiratory tract infection and 25-hydroxyvitamin D concentration: A systematic review and meta-analysis. Int. J. Environ. Res. Public Health 2019; 16.
19. Bergman P, Lindh ÅU, Björkhem-Bergman L, Lindh JD. Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS One 2013; 8.
20. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S, Stelmach I, Kumar GT, Urashima M, Camargo CA. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ 2017; 356.
21. Autier P, Mullie P, Macacu A, Dragomir M, Boniol M, Coppens K, Pizot C, Boniol M. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017; 5: 986–1004.
22. Stamets P. Growing Gourmet and Medicinal Mushrooms. 3rd ed. Berkely, California: Ten Speed Press; 2000.

FURTHER REVIEWS: 
NICE published a rapid review of the evidence for Vitamin D for COVID-19 on the 29th of June 2020. It can be found here.
SACN published an update to their review of vitamin D and acute respiratory tract infections on 11th June 2020. It can be found here.

Vitamin D: A Rapid Review

Dosage of Vitamin D Needed To Achieve 35 to 40 ng/ml (90-100 nmol/L)

Historically, 400 IU (10 ug) of vitamin D was recommended for better health because it closely approximated the amount of vitamin D in a teaspoonful of cod liver oil. However, 800 to 1,000 IU is the dose that may have a better chance of giving a patient a normal vitamin D level. In some countries, vitamin D is listed in micrograms, and the relationship is as follows:

It is much easier to access the patient’s need after a vitamin D blood test. Few individuals would allow their clinician to simply guess an individual’s cholesterol level before placing him/her on some type of medication. Clinicians have access to an accurate lipid test that provides guidance. The same is true for vitamin D levels. Clinicians should not suggest high intakes of vitamin D (5,000 IU for example) before recommending the 25-OH vitamin D test.

Health care professionals need to keep in mind that in general, 100 IU (2.5 mcg) of vitamin D per day can raise the vitamin D blood test only 1 ng/ml or just 2.5 nmol/L after 2 to 3 months. How much vitamin D is needed per day to obtain a normal vitamin D blood level? The following examples include:

• 100 IU (2.5 mcg) per day increases vitamin D blood levels 1 ng/ml (2.5 nmol/L).

• 200 IU (5 mcg) per day increases vitamin D blood levels 2 ng/ml (5 nmol/L).

• 400 IU (10 mcg) per day increases vitamin D blood levels 4 ng/ml (10 nmol/L).

• 500 IU (12.5 mcg) per day increases vitamin D blood levels 5 ng/ml (12.5 nmol/L).

• 800 IU (20 mcg) per day increases vitamin D blood levels 8 ng/ml (20 nmol/L).

• 1000 IU (25 mcg) per day increases vitamin D blood levels 10 ng/ml (25 nmol/L).

• 2000 IU (50 mcg) per day increases vitamin D blood levels 20 ng/ml (50 nmol/L).

If the vitamin D blood test was 30 ng/ml (75 nmol/L) and a 40 ng/ml (100 nmol/L) level was desired, 1,000 IU (25 mcg) of vitamin D per day over several months should be taken to achieve a normal blood level or 40 ng/ml (100 nmol/L). Upon reaching the goal, most individuals need to supplement with 800 to 1,000 IU per day to maintain this level. Only working closely with a clinician over time can provide the most accurate answer. However, issues of insurance and health care access suggest that 800 to 1,000 IU is ample for many individuals who are not able to have their blood tested.

Vitamin D-3, 25,000 IU 60 capsules by Metabolic Maintenance

Vitamin D-3, 25,000 IU is a dietary supplement containing 25,000 IU of Vitamin D to support normal blood levels plus Vitamin K-2 for normal bone support.

What Vitamin D-3, 25,000 IU is Best For

Vitamin D-3, 25,000 IU is recommended for people wishing to increase their intake of vitamin D.

Vitamin D-3, 25,000 IU may be used for the following:

• Supports normal blood levels
• Supports normal bone function
• Supports normal skin function

How Vitamin D-3, 25,000 IU Works

Vitamin D-3 25,000 IU is from the Metabolic Maintenance Vitamins / Minerals product line.

25,000 IU of Vitamin D is recommended for those whose 25(OH)D3 levels are extremely low, and is helpful for those who have difficulty complying with a daily dose. One capsule two or three times per week may be recommended for a short time to increase blood levels to a normal range.

Monitoring serum calcium and 25(OH)D3 levels is strongly recommended to prevent toxicity.

This formula also contains Vitamin K-2, which research has shown to be an essential nutrient for supporting normal bone density and proper bone nutrition.

Vitamin D-3, 25,000 IU Serving Size

As a dietary supplement, take 1 capsule daily, or as recommended by a healthcare practitioner.

Vitamin D-3, 25,000 IU Ingredients

Serving Size 1 capsule

Servings per container 60

Vitamin D-3 25000 IU

(as Cholecalciferol)

Vitamin K-2 45 mcg (as K-2 M7)

Other ingredients: Vegetarian cellulose capsule, L-leucine.

Vitamin D-3, 25,000 IU Side Effects

Consult your healthcare provider.

Vitamin D-3, 25,000 IU Where to Buy

Vitamin D-3, 25,000 IU product is available only from licensed healthcare professionals. Buy Vitamin D-3, 25,000 IU Online here at AcuAtlanta.net or our clinic.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Ultra-D Vitamin D3 25 μg (1000 IU) instructions for use: indications, contraindications, side effects – description Ultra-D Vitamin D3 25 mkg (1000 IU) Chewable tablets (45455)

Places of sale are determined by the national legislation of the member states of the Eurasian Economic Union.

References:

1. Lesnyak OM, et al., Prevention, diagnosis and treatment of vitamin D and calcium deficiency in the adult population of Russia and patients with osteoporosis (based on the prepared clinical guidelines).Scientific and practical rheumatology. 2015; 53 (4): 403-408.

2. I.E. Zazerskaya, Vitamin D and reproductive health of women, Eco Vector St. Petersburg 2017.

3. Holick MF, Vitamin D Deficiency. The New England Journal of medicine, July 19, 2007.

4. Lerchbaum E et al. Vitamin D and fertility: a systematic review. Eur J Endocrinol. 2012 May; 166 (5): 765-78.

5. Garbedian K et al. Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization, CMAJ Open.2013 May-Jul; 1 (2): E77 – E82.

6. E.L. Heyden, S.J. Wimalawansa. Vitamin D: Effects on human reproduction, pregnancy, and fetal well-being. Journal of Steroid Biochemistry and Molecular Biology 180 (2018) 41-50.

7. Russian Association of Endocrinologists. Clinical guidelines. Vitamin D deficiency in adults: diagnosis, treatment and prevention. Ministry of Health of the Russian Federation 2015.

8. L.I. Maltseva et al. Vitamin D provision and correction of its deficiency during pregnancy. Practical Medicine 5 (106) September 2017

9. Cristina de Angelis, et al. The role of vitamin D in male fertility: A focus on the testis. Rev Endocr Metab Disord (2017) 18: 285-305.

10. Gromova OA, et al. On the role of vitamin D in the prevention and treatment of male infertility. Quality Clinical Practice # 3 2017.

11. Schlogl M, Holick MF. Vitamin D and neurocognitive function Clinical Interventions in Aging 2014: 9.

12. N.V. Rylova et al. The role of vitamin D in the regulation of the immune system. Practical Medicine 5 (106) September 2017

13. Jafari T, et al. Effects of vitamin D on serum lipid profile in patients with type 2 diabetes: A meta-analysis of randomized controlled trials. Clinical Nutrition. 35 (2016), 1259-1268.

14. Dusso AS. Update on the Biologic Role of the Vitamin D Endocrine System Current Vascular Pharmacology Volume 12, Issue 2, 2014.

15. Torshin I.Yu., Gromova O.A. Pharmacokinetic analysis of oral vitamin D preparations. Pharmacokinetics and pharmacodynamics, No. 3 2018.

16. Vaibhav Kumar Maurya. Factors influencing the absorption of vitamin D in GIT: an overview. J Food Sci Technol (November 2017) 54 (12): 3753-3765.

17. E.V. Shikh et al. “Experience in the use of various dosage regimens for cholecalciferol to achieve an adequate level in patients with impaired reproductive function”, Obstetrics and Gynecology No. 2, 2019.

18. Pre-gravid preparation. Clinical protocol. Approved by Protocol No. 4P-16 of the Presidium of the Board of the Interdisciplinary Association of Reproductive Medicine Professionals (MARS) dated 28.06.2016.

19. Roth DE. Vitamin D supplementation during pregnancy: safety considerations in the design and interpretation of clinical trials. J Perinatol. 2011 Jul; 31 (7): 449-59.

20. Guidelines for the prescribing of vitamin D in adults. NHS.2013 (https://slidex.tips/download/guidelines-for-theprescribing-of-vitamin-d-in-adults).

90,000 Vitamin D-25,000, Vitamin D, Thorne Research, 60 capsules, 14666

• Nutritional Supplement
• Hypoallergenic Products
• For those looking for a fast acting, concentrated Vitamin D supplement
• Thorne Vitamin D is pure Vitamin D, with no hidden ingredients such as lactose, BHT, BGA, sodium benzoate and sorbic acid, which can have a negative effect on people with hypersensitivity.
• Supports cardiovascular health, immunity and bone health
• Vitamin D Information

It is very important to maintain adequate vitamin D levels throughout life, from fetal development to old age. Vitamin D helps protect many important bodily functions. The RDA for Vitamin D, 200-600 IU, is based on the minimum amount needed to prevent bone disease. However, in light of recent research, it is planned to amend the FDA regulations to increase this amount.Current research suggests that vitamin D levels should be in the 50-80 ng / ml 25-hydroxyvitamin D (25 (OH) D) range. While the sun is a great source of vitamin D, many people don’t get enough due to changing seasons, latitudes, or lifestyles. Therefore, vitamin D supplementation can save the day.

Vitamin D deficiency is common, especially among the elderly. For example, a study conducted at the Glasgow Clinic, Scotland, found nearly widespread vitamin D deficiency in a group of 548 older adults.Individuals with vitamin D deficiency need to take 5,000-1,000 IU of vitamin D for tissue repair. Those requiring a high concentration of vitamin D include those who are obese (the more a person weighs, the more vitamin D they need), those with chronic illnesses, dark-skinned people, and people with digestion problems.

Some respond well to 25,000-50,000 IU over a few days or a week, after which a reduced dosage is taken to maintain the effect.With these people in mind, we created Thorne D-25,000, which contains 25,000 IU of vitamin D3 in each vegetable capsule. Concentrated vitamin D for short-term intake (2-3 days) may also support immunity.

Composition

Microcrystalline cellulose, hypromellose (derived from cellulose) capsule, vitamin E (mixed tocopherols), leucine, silicon dioxide.

Does not contain preservatives.

Warnings

First Opening Control: Use only if the bottle is sealed.

If pregnant, consult a physician before use.

Store tightly closed in a cool dry place.

Vitamin D – the mechanism of action and whether it is necessary to take supplements

Vitamin D is often mentioned in the modern literature on maintaining a healthy lifestyle and its prolongation. In some works it is recommended to regularly check its level and drink maintenance doses, while other works claim that it is unclear whether there is any benefit from this.

In our article we will understand what vitamin D is, how it works, what it affects, and if you have come to the conclusion that you want to take it to improve health and prolong life, then how to do it correctly.

A little history and general description

Vitamin D was discovered in 1922 and was originally considered as a common vitamin. However, now it is considered a provitamin, that is, it must go through several stages of biochemical transformations for activation.

The uniqueness of vitamin D lies in the fact that it enters our body not only with food, but is also produced by the body when exposed to sunlight. This makes it difficult to develop recommendations for taking it as a supplement.
However, for us geeks, as a rule, you can discard the sun factor, such are our life habits.

The common name for vitamin D (also calciferol) includes several secosteroids of which the most important forms are D2 and D3.

We get D2 only with food, and D3 is produced when ultraviolet radiation + from food gets on the skin. They are the same in their effect, which can be seen in the picture above. However, research is still underway on what is more beneficial in the long term.So far there is no definite answer and we can accept that it is not important and buy the most suitable form D2 or D3.

In some countries, for example, the USA, Canada, India, milk and other products fortified with vitamin D are sold. In 2016, the FDA (the US state drug agency) approved an increase in vitamin D standards in milk and milk replacement drinks (soy milk, etc.). p.), up to 84 IU (or IU) per 100 grams of product. This may indirectly indicate that the lack of vitamin D is officially recognized.

For the measurement of soluble vitamins, doses are usually measured in IU (International Unit) or IU (International Unit). Each vitamin has its own correspondence to direct weight. One microgram (one millionth gram) of vitamin D = 40IU (400IU = 10mcg or µg).

Why vitamin D is important for our health

For the purposes of prolonging life and a healthy brain, maintaining normal vitamin D levels is very important and therefore we started our series of articles on vitamins with it.

Initially, the main role of this vitamin was considered to maintain calcium and bone homeostasis.In other words, with a lack of it, rickets in children or osteoporosis in adults can develop. It was during the study of rickets that vitamin D was discovered.

For a more complete list of possible diseases from vitamin deficiency (for example, weakness, bone pain, muscle pain, etc.) and for a complete study of the evidence base on it, you can look at Pubmed for a very complete systemic review with a recommendation to introduce screening in USA + a second review on the deficiency of this vitamin in adults.

And although only problems with bones and muscles are enough to start maintaining the level of this vitamin normal, but, in addition to this, in recent decades it was found that vitamin D is involved in many more important body processes: 90 140 ( below are links to the Telegram channel, which translated excerpts from Pabmed’s research, the title of the article is a link to the original on Pubmed)

(a picture from the journal Nature about participation in the immune system)

Here we give only points that are important for us if you search for vitamin D at https: // scholar.google.ru, in the last year alone we will receive 53,000 results. In general, it is clear that if we have a deficiency of this vitamin, then it is advisable to take a supplement to maintain it at a normal level.

Of course, all this information does not mean that some kind of panacea has been found and we will now live forever. But this vitamin, according to a lot of modern research, is quite important to maintain at normal levels for long-term health. Moreover, the price of the issue is not at all high.

More information.

Also in books and articles it is often written that vitamin D prevents cancer and cardiovascular disease. However, there is a possibility that he does not prevent them, but accompanies them. In other words, taking supplements and raising blood levels will not prevent these diseases. A huge placebo-controlled study was conducted in New Zealand to clarify this issue.

It lasted 4 years and was attended by 5100 people, about half took a placebo, others took 100,000 IU of vitamin D monthly.

Based on the results of this study, it was found that this did not reduce the likelihood of these diseases. BUT! The researchers themselves noted that in New Zealand, most of the subjects undergoing the study had a blood level of 32.8 ng / mL (placebo also), and about 75% of the US population has a level below 30 ng / mL, and about 30% below 20 ng / mL. (Note Lifext – and in Russia, where there is even less sun than in the USA and where milk is not fortified with vitamin D – it can be assumed that it is even lower)

Therefore, as the authors note, additional research is required.(Study 1, Study 2)

What are the normal levels and what doses to drink?

For vitamin D, we can determine our norm by taking a blood test for its content. The indicator 25 (OH) D (the main metabolite of vitamin D present in the blood) is measured and it is considered that the level of 30-100 ng / ml is normal (see source)

In some books about the extension of life and brain health, the following parameters are indicated to which the authors recommend striving for

1. “The norm is between 30 and 100 ng / ml, but this does not mean that one can stop at the indicator 31.The optimal vitamin D level is around 80 ng / ml. This is the middle of the so-called normal zone. Ask your GP to help you adjust your dosage to achieve the optimal dosage level. Thereafter, 2,000 IU is usually sufficient to maintain healthy levels. However, be sure to consult your doctor. ” (Christine Loberg David Perlmutter Food and the Brain.)
2. “Your level must be at least 50 ng / ml” (Ray Kurzweil, Terry Grossman Transcend: Nine Steps Towards Eternal Life)

Condition for choosing your dose

• 25 (OH) D level <20 ng / ml - take 5000 IU of vitamin D per day (see.source)
• 21
• 31 (all recommendations are for adults only)

IMPORTANT! If ​​you drink a dose of 2000 IU per day or more, then the vitamin level must be measured once every three months.

It is quite safe to drink a dose of 1000 IU every day, while measuring the level of vitamin 1 once a year and, if it is below 30ng / ml, then increase it according to the scheme above and make a new measurement in three months.

So, if you are too lazy to measure the level and you do not work in the sun for an hour or more a day (which, by the way, is more harmful than useful), then you can safely start drinking vitamin D at a dosage of 1000 IU (IU) per day.

In a couple of months we will come to a full set of tests for the long life of the geek’s body and brain and where to go with them and try to get us discounts on this, but for now you can wait or do it in any laboratory.

Purchase advice

Below I provide links to the purchase of three vitamins that are recommended for everyone, especially in early spring.

At this point, you have read the full study on vitamin D. only.

Drinking daily with breakfast or with another meal will reduce the stress on your digestive system. We accept everything in 1 piece, except for fish oil – there are 2 of them.

• Vitamin D3 1000 IU
• If measured the level, then one of two options
  dosage 5000 IU or 2000 IU
• Fish Oil – 2 capsules with breakfast

In conclusion, I want to remind you that the meaning is not so much in supplements and vitamins, but in attention to our lifestyle and the direction of a meager part of mental strength on how we will live, for example, at 60, 80, 90 years (if we live, of course).If we do not improve the lifestyle and all sorts of nuances that arise, then supplements will not help much.

Recommended complex for daily intake

Fish oil and vitamin D are very important for the brain and body, minerals and protein are important for the long-term health of the body. It is advisable to take for those over 30 years old.

After 35-40 years, you can also start taking a couple of supplements for youthful skin and tissues and health of joints:

90 140

Vitamins D: which is better, hair loss, the norm, where it is contained, reviews

Fact: Everyone reading this article is vitamin D deficient – unless you are already taking it on purpose.Why is this bad, what are the reasons and how to deal with the deficit?

I have been struggling with hair loss for several years now. One of the reasons aggravating the situation is a deficiency of vitamin D. Until I faced the problem, I did not even suspect that I had so little vitamin D – and then it turned out that not only me, but almost the entire population of Russia …

Vladislav Tkachev

Almost no one checks this indicator on purpose, doctors are also rarely aware of this deficit – and the opinion prevails in society that if you at least sometimes walk on the street, then you should be all right with D.We drink multivitamins to correct a non-existent vitamin deficiency, but we do not suspect a real deficiency of a particular vitamin.

My doctor, a leading trichologist of the DSD de Luxe brand, a dermatologist, candidate of medical sciences, vice-president of Scientific -practical society of trichology, head of the course of medical trichology of the RUDN University Vladislav Tkachev.

Why are we all vitamin D deficient?

– How is it that people all over the world are deficient in vitamin D? Even Dubai has it!

– Lifestyle has changed.A hundred years ago, people spent a lot of time outdoors, worked on the street, walked more, children played in yards … Now we are constantly indoors. In Dubai, for example, there is a lot of sun, but people are always at home, or in a store, or in an office, under air conditioning. As a result, little substance is synthesized in the skin – the precursor of vitamin D.

– How does this affect our health?

– Vitamin D affects many functions, activates over 2000 genes. More than 200 diseases have been proven to be linked to vitamin D.And this is not only rickets, but also many types of oncology, diabetes, obesity, osteoporosis, Alzheimer’s disease, multiple sclerosis, and other autoimmune diseases.

Vitamin D also affects the condition of the hair. Hair follicles have receptors for vitamin D. And as a result of their inactivation (shutdown), both humans and mice develop alopecia, a study by Kong J. et al. Vitamin D may be a protective factor against – including – alopecia areata. ((1), see end of article) D-deficiency may exacerbate diffuse hair loss, especially in women, and be a significant factor in scarring alopecia.

– How long does it take to walk on the street to synthesize enough of it?

– To get the daily dosage of vitamin D, you need to spend three hours a day under the bright sun (subject to wearing open clothing). If you are sunbathing in a swimsuit and without SPF, 30 minutes is enough. But, for example, even six hours of walking on a sunny day will not help compensate for the existing deficit.

And you need to remember that ultraviolet light is dangerous, increasing the risk of developing melanoma – and this risk is significant if you have a vitamin D deficiency and you sunbathe illiterately, leading to burns.But the paradox is that it is vitamin D that protects the skin from melanoma (2). If you do not have a deficiency and you tan competently, without burns, then the risks of ultraviolet radiation are significantly reduced and its positive health effects begin to prevail.

We can get about 10% of vitamin D from food. But now, neither meat, nor eggs, nor milk, even farmed fish contain the amount of vitamin D that should be. After all, animals no longer graze in the open air anymore.

– Is this deficit about the same for everyone?

– There are population groups that need even more vitamin D. These are pregnant and lactating women, people with chronic diseases. With surgical interventions, injuries – as well. In old people, the skin synthesizes vitamin D poorly, even if they sit under the sun, therefore, their need is increased.

The only way out in the current situation is to take additional vitamin D for everyone.

Why is vitamin D deficiency bad?

– What exactly is vitamin D?

– In fact, it is not a vitamin, but a hormone.The skin produces forms of vitamin D2 and D3 – ergocalciferol and cholecalciferol (and also comes with food). Further, in the liver, these precursors of steroid hormones are converted into calcidol, and then in the kidneys an active hormone, calcitriol, is synthesized from it. And this is no longer just a hormone, but a whole “hormonal conductor” – it can influence the synthesis of other hormones or act in synergy with them. In my patients, I have repeatedly noticed that vitamin D supplementation normalized levels of other hormones, including androgens.

– Do we need androgens?

– Of course they are. What is testosterone or dehydroepiandrosterone deficiency? This is the path to obesity, depression and neurasthenia, decreased libido, low muscle mass – sarcopenia, osteoporosis, numerous metabolic disorders. And one of the factors affecting their synthesis or metabolism is a lack of vitamin D.

– What else does vitamin D deficiency affect?

– Please note – the further we move from south to north, the more often autoimmune diseases, such as multiple sclerosis, occur in the population.The frequency grows hundreds of times (3). And here a likely role belongs to both dietary habits, genetic predisposition, and the amount of solar radiation.

If you have adequate vitamin D levels, the risks of malignant and other neoplasms are reduced by 75%, and the risks of type 2 diabetes, obesity, multiple sclerosis – 50 to 80% (4). The risks of cardiovascular diseases are reduced, phosphorus-calcium metabolism improves, and immunity is regulated.

Vitamin D can also help with diseases that are extremely difficult to treat. An interesting study was conducted in Brazil on psoriasis and vitiligo. It was possible to achieve stable remission in these conditions on monotherapy with high doses of vitamin D (under medical supervision, patients took 35,000 IU of vitamin D daily for 6 months) (5). ( But self-administration of such dosages is unacceptable!)

For idiopathic itching, a number of dermatoses, treatment with only vitamin D (at a dose of 50,000 IU per week, i.e.that is, about 7000 IU per day) in 70% of cases allowed to achieve remission of (6).

– And from the point of view of the beauty of a healthy person – hair, skin?

– We will age faster with a deficiency of hormone D. There will be pale, tired, dry, wrinkled skin. Taking vitamin D helps to improve beauty, if only because it is an active steroid, the synthesis and absorption of which decreases with age, like other hormones. Only here it is worth remembering photoaging – and in the pursuit of the “sunny” vitamin, do not forget to cover your face and hair.

– Will normalizing vitamin D levels affect the well-being of a healthy person?

– A conditionally healthy person (conditionally, because, being deficient in vitamin D, it is hardly possible to be healthy), there is an “energy boost”, general well-being improves, tone increases, vigor appears, even the time it takes to get enough sleep decreases. Many patients note that pain in the area of ​​muscles, joints and ligaments decreases, pain manifestations of osteochondrosis, osteoporosis, muscle-tonic syndromes, and fibromyalgia decrease.

– Do children need vitamin D? What are the doses?

– Needed, and right from birth. Even while breastfeeding – if the mother is deficient, where does the vitamin D in milk come from? Even rickets has recently become more frequent again.

How to check your vitamin D level?

– When I tell my acquaintances that we all have a deficit, people ask which doctor to go to check it?

– You need to take a blood test for 25-OH vitamin D.The number in the analyzes should be at least 30 ng / ml. However, this figure is only a compromise. Recently, many laboratories are switching to another standard, when the lower limit of the norm is considered to be 40 ng / ml. But the optimal range is from 50 to 100 ng / ml.

Please note that units and rates may differ from laboratory to laboratory, depending on the method used. Preferably, vitamin D levels are measured by LC-MS (liquid chromatography-mass spectrometry).

A doctor of any specialty should send a patient to check vitamin D, in an amicable way, because this hormone is involved in the regulation of the vast majority of organs and systems. Traditionally, endocrinologists are engaged in this. But even among endocrinologists, there are those who do not actively delve into this topic. Basically, they remember him when they see violations of the parathyroid glands and kidneys, with obvious violations of calcium-phosphorus metabolism. And we would not get to these violations.

– But the analysis can be taken independently and without a doctor.And then what to do with the results?

– Start taking it. As for the dosage, the safety range is considered to be from 400 to 4000 IU per day. With rare exceptions, for those who have a problem with the parathyroid glands, excess calcium and phosphate, kidney stones, sarcoidosis – you need to be careful.

There are such international recommendations for dosages, depending on age:

Institute of Medicine, Food and Nutrition Board.Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010

– It turns out that finding a doctor who would prescribe an adequate dose is still more difficult than going to get tested and start taking a prophylactic dose?

– So far, unfortunately, this is exactly the situation. Most doctors prefer to recommend low dosages, 400-800 IU. But even a dose of 4000 IU is, in fact, prophylactic for our region, and when taken, the level of vitamin D only reaches the lower limit of the norm.And in conditions of deficiency, the therapeutic dose should be even higher.

– Total: How many times a year does each person need to be tested for vitamin D?

– Personally, I already know that if I take 10,000 IU of micro-lingual vitamin D, my level will be 100, this is the highest limit of the norm. If I take 5000, the level will be 50 (this is the average value of the norm). Therefore, I no longer need analyzes.

But patients need tests – to understand that there is a serious deficiency, to understand that changes are taking place, to find out when vitamin D has already returned to normal levels.And when it is reached, you can not do the tests, the main thing is to constantly take your dose.

Norms for vitamin D

– What level of vitamin D should you aim for?

– The upper limit of the norm is 100 ng / ml. In principle, when there are no disorders in the functioning of the kidneys and parathyroid glands, a person can easily tolerate even larger numbers in the tests, but walking on a razor’s edge is not worth it (the level of calcium in the blood may rise excessively, which adversely affects many organs, especially the kidneys).Blood values ​​of 60-70 ng / ml are optimal. But a typical analysis of a Muscovite in winter is 12-14 ng / ml. Summer – about 20.

– Will 4000 IU be enough to get to level 40?

– All modern studies say that you need at least 4000 IU per day (this is 8 drops of “Vigantol”). Nevertheless, we still use the old norms, 400-500 IU are indicated there. If the doctor offers you 400 IU, do not hope that this will help – I have already redid thousands of tests for this vitamin, such dosages do not work.4000 IU is the minimum dose with which you can get the lower limit of the norm.

– So everyone should take 4000 IU every day?

– Yes. Except for the days when he actually spends three hours in the sun. That is, for a vacation in the south – we take a break.

But 4000 IU is the minimum, in fact a compromise. And the official recommendations are so far that this is the maximum prophylactic dosage for adults, and I cannot indiscriminately recommend to everyone even these 8 drops without taking into account individual characteristics and contraindications.Although I sometimes recommend to my patients and much higher therapeutic doses.

Which Vitamin D Should I Take?

– Is there a difference between vitamin D, which was synthesized in the body itself, and which we took in the form of a supplement?

– In principle – no, everything is converted into the same substance.

– What is Vitamin D Supplement Made of?

– The starting material is the substance ergosterol, which is extracted from phytoplankton, brown and green algae; as well as some types of yeasts and molds.The resulting ergosterol is irradiated with ultraviolet light. So synthetic vitamin D isn’t all that synthetic. And its synthesis was established long ago, back in the Soviet Union.

– And the norms are so low, too, have remained from the Soviet times?

– The rates are changing upwards, but very slowly. Although in recent years, progress with the study of the properties of vitamin D has been quite active. Now no one treats him only as a vitamin for rickets.

The fear of vitamin D poisoning remains.Where did it come from at all? It used to be in the form of an alcohol solution. The bottle with it could not be closed completely, the alcohol evaporated, vitamin D became very concentrated – and the dose could be ten times more than it was written. There have been cases of poisoning when people took an oil solution of vitamin D not in drops, but in spoons, mistaking it for vegetable oil.

– What exactly to take today? Vigantol? “Aquadetrim”? There are also complexes with calcium, such as “Calcium-D3-Nikomeda”.

– “Vigantol”, “Aquadetrim” can be taken. But the complexes are not worth it. In complexes, the dose of vitamin D is too small, you will not get rid of the deficiency with it. And when a person is already saturated with vitamin D, he does not need additional calcium, he will already have enough calcium. Even with high doses of vitamin D – from 4000 IU – we ask patients to follow a low-calcium diet.

– Is there a difference between the absorption of different vitamin D preparations?

– Both “Vigantol” and “Aquadetrim” are normally absorbed, although in our experience in some batches of vitamin D they sometimes have less than the declared amount and patients go to the lower limit of the norm longer.

I am taking the sublingual (sublingual) version of the drug. In my opinion, it works more reliably. But these drugs are no longer medicinal, they belong to dietary supplements, they are not sold in pharmacies in Russia and therefore cannot be officially recommended.

Is there a danger of vitamin D overdose?

– How easy is it to get poisoned with vitamin D?

– There are studies that doses up to 10,000 IU per day do not give side effects (provided there are no contraindications, which we have already discussed) (7)

– And in the West, patients are given an injection with a much higher dosage in order to increase vitamin D faster, and then they are prescribed a small dose for prevention.

– That’s right. It is necessary to raise, and then maintain with a smaller dose. We do not have such injections, they are not legally sold.

– That is, if you get 50,000 IU from the injection once, there will be no poisoning?

– No. If it is a weekly, and even more so, a monthly dosage. That is, if 50,000 IU is injected once a month, the dose will be the same as when taking 1660 IU per day.

Hypervitaminosis develops at doses above 40,000 – 100,000 IU daily, for more than a month – but we are far from these doses.

But even if you took 100,000 IU once (and then did not take it), after about two months, vitamin D will reach the bottom, and then there will be a deficiency. ”

Julia:

“My vitamin D level recently reached 89. My gynecologist-endocrinologist and I didn’t dance a jig when we got the test results -). The hair is still with me, although I do not do much for this – it means that the correction of deficiency conditions still works.

(From funny – I used to have a slight crazy-mania – I really liked to eat calcium gluconate tablets. With the normalization of vitamin D levels, this mania disappeared without a trace -)). ”

Mentioned studies:

1. The Role of Vitamin D Receptor Mutations in the Development of Alopecia. Peter J. Malloy and David Feldman. Molecular and Cellular Endocrinology
2. Protective actions of vitamin D in UVB induced skin cancer. Photochem Photobiol Sci.2012 Sep 18. Bikle DD. Departments of Medicine and Dermatology, San Francisco VA Medical Center and University of California, San Francisco, CA, USA
3. Campbell T. M. 2nd, Campbell T. C. The breadth of evidence favoring a whole foods, plant-based diet
4. Holick, Michael F., PhD., M.D., Boston University School of Medicine, textbook – Physiology, Molecular Biology, and Clinical Applications
5. A pilot study assessing the effect of the prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis.Danilo C Finamor, ¹ Rita Sinigaglia-Coimbra et al. Dermatoendocrinol. 2013 Jan 1; 5 (1): 222-234.
6. W V Med J. 2011 Jan-Feb; 107 (1): 14-20. Idiopathic itch, rash, and urticaria / angioedema merit serum vitamin D evaluation: a descriptive case series. Goetz DW .; Exemplar Allergy & Asthma, Morgantown, WV, USA
7. J Bone Miner Res. 2007 Dec; 22 Suppl 2: V64-8. doi: 10.1359 / jbmr.07s221. Vitamin D toxicity, policy, and science. Vieth R.

Do you know your vitamin D level? Follow him?

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