High-Dose

Summary of High Dose Vitamin D

57 High-Dose items

10 most-visited High-Dose pages

10 High-Dose Interventions using Vitamin D

40-150 ng of Vitamin D need to treat health problems

* Evolution of experiments with patients, often also need co-factors

Vitamin D Life - Diseases treated by high-dose Vitamin D - many studies

Vitamin D mega-doses are safe and effective – review Dec 2021

Safety and effectiveness of vitamin D mega-dose: A systematic review
Clinical Nutrition ESPEN Volume 46, Dec 2021, Pages 115-120 https://doi.org/10.1016/j.clnesp.2021.09.010 PDF behind paywall
Fernanda Lauar Ataide a, Larissa Matos Carvalho Bastos b, Matheus Franklin Vicente Matias b, Thelma Larocca Skare c, Jozélio Freire de Carvalho d

Introduction
Supplementation with high doses of vitamin D, known as mega-dose or “stoss therapy,” refers to administering high doses of vitamin D by oral or intramuscular route in short periods of time. In this sense, conducting a review to organize this knowledge in a single article will generate a helpful instrument for researchers working in this area and for health professionals who use this therapeutic tool.

Objective
To carry out a literature review on safety and efficacy (normalization of serum vitamin D level, and changes in the clinical picture) of vitamin D mega-dose use.

Methodology
This is a systematic review of the literature searching data through the electronic banks of PubMed, Scielo, and LILACS, using the following keywords: “vitamin D,” “mega-dose,” “stoss therapy,” “cholecalciferol,” in different combinations. CONSORT questionnaire was used to assess the quality of the included studies.

Results
Of the 59 articles screened for this review, 10 were included in the review, studying patients with

• rickets,
• osteoporosis, and
• critically ill patients.

Two studies compared the exact dosage of vitamin D by different routes of administration, and three studies compared different doses by the same route. All others studied vitamin D mega-dose versus placebo. Adverse effects were observed through the presence of hypercalcemia/hypercalciuria. Serum vitamin D levels were normalized between 70 and 100% of patients, and adverse effects ranged between 1.9 and 18.5%.

Conclusion
The study demonstrated that vitamin D mega-dose therapy is effective in normalizing serum vitamin levels, and the toxicity assessed through adverse effects was low, with no expressive clinical significance. Despite this, there is still a need for further studies in the area to confirm the results found.

Introduction
Vitamin D deficiency is one of the most common medical conditions worldwide [1] and can lead to growth retardation and deformities in the bone skeleton during childhood. In adults, this deficiency can precipitate or exacerbate osteopenia and osteoporosis, cause osteomalacia and muscle weakness, in addition to increasing the risk of fractures [2,3].

Vitamin D is not only associated with osteo-mineral metabolism; it also takes part in several extra-skeletal conditions participating in the pathophysiology of cancer, infections, hypertension, diabetes, multiple sclerosis, and other chronic diseases [4,5]. Moreover, it is known that vitamin D plays a role in several vital cellular processes [6]; its receptor (VDR) is present in almost all cells and tissues of the human body [7] contributing directly or indirectly to the regulation of about 3% of the human genome [8].

There are three main sources of vitamin D: sun exposure, diet, and supplementation; the most important is sun exposure answering for 80–90% of the total vitamin D pool [9]. Ultraviolet B (UVB) radiation penetrating the deep layers of skin converts the vitamin's precursor, 7-dehydrocholesterol (7-DHC) into pre-vitamin D3 and then to vitamin D3 or cholecalciferol [3,7]. Therefore, any factor that reduces the solar transmission of UVB radiation or any element that interferes with its penetration into the skin will decrease the cutaneous synthesis of vitamin D, leading to deficiency [9].

Some people are at risk for hypovitaminosis D [10]. Elderly individuals, those with gastrointestinal malabsorption [2], with dark skin [6], pregnant and post-menopausal women [3], individuals who live in places with prolonged winters [10] or use some types of clothing such as the burqa [2] are some of them.

Vitamin D supplementation is done orally or through intramuscular injections [11]. The oral route is the most commonly used but adherence may be impaired by gastrointestinal effects and for difficulties in swallowing capsules [12]; the intramuscular route seems to be more efficient [13].

Supplementation with high doses of vitamin D, known as mega-dose or “stoss therapy,” refers to administering high doses of vitamin D by oral or intramuscular route for short periods of time [14]. The dosages vary among the studies; there is no consensus which dose is megadose. In this context a fraction of vitamin D is immediately converted to hydroxi-vitamin D (OH Vit.D), while another part is stored in adipose tissues from which it is slowly released [12]. This type of supplementation offers not only efficacy and safety but also a sustained effect [15]. However, there are no guidelines on how long these doses should be administered and what are the biochemical tests needed to assess its effect and safety [16]. Hypervitaminosis D, inadequate response of some patients and decrease in serum vitamin D levels over time are some of the concerns [13].

Although vitamin D supplementation is relatively safe, poisoning is a potentially severe condition [3,17]. It leads to hypercalciuria and hypercalcemia, and symptoms range from thirst and polyuria to seizures, coma and death [18,19].

The present study aimed to conduct a systematic review of the literature on the safety and efficacy of vitamin D mega-dose use.

Section snippets
Study design
This study followed the Cochrane Handbook recommendations for Systematic Reviews of Interventions for its development and consists of a Systematic Review of the literature. The Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) was used to produce the text. This study was registered on PROSPERO under the number 246048.

Search strategy
A literature search was performed using the following electronic databases: PubMed/MEDLINE, Scielo, and LILACS. The used keywords were: “vitamin D,”…

Methodological quality assessment
To assess the methodological quality of the selected works, the articles were submitted to the CONSORT questionnaire. CONSORT is an acronym for “Consolidated Standards of Reporting Trials,” where there is a minimum set of evidence-based recommendations for reporting controlled clinical trials. Articles that did not reach a score of 70% in this questionnaire were excluded from this study….

Results
The initial search through the descriptors in the electronic databases resulted in ten articles that met all the inclusion criteria, as shown in Fig. 1 (following PRISMA guidelines). The selected articles were published between 2012 and 2021….

The studies came from the following countries: India (n = 3), Australia (n = 2), United States (n = 1), England (n = 1), Austria (n = 1), and Turkey (n = 1). The studied diseases were: rickets (n = 3), critical patients (n = 2), elderly with vitamin D…

Discussion
This review analyses efficacy and safety of vitamin D mega-dose, in different dosages and different administration regimes (oral and intramuscular), in the normalization of serum vitamin D levels and adverse effects such as hypercalcemia and/or hypercalciuria. In general, it has a good efficacy in normalize vitamin D levels with no or minimal side effects.

The included studies can be divided into three main sets. The studies from the first group evaluated vitamin D mega-dose in children with…

References (28)

A. Tellioglu et al. Efficacy and safety of high dose intramuscular or oral cholecalciferol in vitamin D deficient/insufficient elderly Maturitas (2012)
M.F. Holick Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease Am J Clin Nutr (2004)
M.F. Holick et al. Vitamin D deficiency: a worldwide problem with health consequences Am J Clin Nutr (2008)
M.D. Kearns et al. Large, single-dose, oral vitamin d supplementation in adult populations: a systematic review Endocr Pract (2014)
B.R. Shah et al. Single-day therapy for nutritional vitamin D-deficiency rickets: a preferred method J Pediatr (1994)
T.H. Diamond et al. Annual intramuscular injection of a mega-dose of cholecalciferol for treatment of vitamin D deficiency: efficacy and safety data Med J Aust (2005)
M.F. Holick Vitamin D deficiency N Engl J Med (2007)
S. Pilz et al. Vitamin D in preventive medicine Anticancer Res (2015)
C.V. Restorff et al. High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency Bone (2009)
N.J. Schuch et al. Vitamin D and endocrine diseases Arq Bras Endocrinol Metabol (2009)
Optimal vitamin D status at admission appears to improve survival after craniotomy in patients with brain malignancies 2023, Clinical Nutrition ESPEN
Effect of Single High Dose Vitamin D Substitution in Hospitalized COVID-19 Patients with Vitamin D Deficiency on Length of Hospital Stay
2023, Biomedicines
Vitamin D and COVID-19—Revisited
2022, Journal of Internal Medicine
Post-Diagnosis Vitamin D Supplement Use and Survival among Cancer Patients: A Meta-Analysis
2022, Nutrients
Vitamin D Is Associated with Clinical Outcomes in Patients with Primary Biliary Cholangitis
2022, Nutrients
Safety of megadose of vitamin D in patients with nephrolithiasis
Nutrition, Volumes 87–88, 2021, Article 111201
Nutritional and prognostic significance of abdominal wall thickness measured during percutaneous endoscopic gastrostomy in older individuals with dysphagia
Clinical Nutrition ESPEN, Volume 46, 2021, pp. 216-222
Micronutrients for potential therapeutic use against COVID-19; a review
Clinical Nutrition ESPEN, Volume 46, 2021, pp. 9-13
Associations between a composite score of hemoglobin, CRP and albumin and physical performance in older patients undergoing gastrointestinal cancer surgery Clinical Nutrition ESPEN, Volume 46, 2021, pp. 330-335
Vitamin D status is favorably associated with the cardiovascular risk factors in adults with obesity
Clinical Nutrition ESPEN, Volume 46, 2021, pp. 232-239
Effect of parenteral nutrition in oxygen escalation/de-escalation in SARS-CoV-2 infected patients who are pre-intubation: A multicenter, observational study Clinical Nutrition ESPEN, Volume 46, 2021, pp. 206-209

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• Early High-Dose Vitamin D3 for Critically Ill, Vitamin D–Deficient Patients Dec 2019 DOI: 10.1056/NEJMoa1911124 540,000 IU no advantage FREE PDF
• Effectiveness and Safety of a High-Dose Weekly Vitamin D (20,000 IU) Protocol in Older Adults Living in Residential Care - July 2014 https://doi.org/10.1111/jgs.12927 19% still less than 30 ng, 52% > 40 ng - safe, did not notice benefit  PDF from Sci-Hub via VitaminDwiki