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Extremely high-dose Vitamin D not a problem for pregnant mice (60M IU injection, 0.6 M IU oral) – Sept 2024


Supplementation of high doses of vitamin D during the gestational period do not cause reproductive, teratogenic and genotoxic damage in mice

Food and Chemical Toxicology Sept 2024, https://doi.org/10.1016/j.fct.2024.115007

Vitamin D deficiency during pregnancy may have adverse effects on embryo-fetal and postnatal development. Indeed, vitamin D supplementation has been indicated for pregnant women. However, there are no studies that indicate the safe dose of this supplementation during the gestational period. Therefore, the present study assessed the effects of high doses of vitamin D and vitamin D combined with calcium on reproductive performance, embryo-fetal development, and DNA integrity in Swiss mice.
A total of 140 pregnant female mice treated with vitamin D and vitamin D combined with calcium were analyzed in two experiments.

  • In one experiment, mice received intramuscular supplementation at doses of 600,000, 6,000,000, or 60,000,000 IU of vitamin D.
    • These same doses were also associated with the dose of 8.56 mg/kg of calcium.
  • In the other experiment, mice received a single oral dose of 6,000, 60,000, or 600,000 IU of vitamin D.

These same doses were also associated with the dose of 8.56 mg/kg of calcium. The treatments were always carried out in the 10th gestational day. The results show that neither intramuscularly nor orally administered vitamin D and vitamin D combined with calcium affected reproductive performance, embryo-fetal development, or DNA integrity at the different doses tested. These pioneering results confirm the safety of using this type of high doses of supplementation, including during pregnancy.

Introduction
Low vitamin D levels during pregnancy may cause adverse effects on embryo-fetal and postnatal development and result in premature birth [1]. Moreover, low serum levels of vitamin D have been correlated with an increased risk for infectious diseases, changes in tooth development [1], schizophrenia [2], type 1 diabetes [3] and asthma [4] in humans. Furthermore, postnatal changes, such as rickets and delayed bone mineralization persisting until nine years of age [5], [6], have also been reported in the literature. These facts show the necessity of vitamin D for embryofetal health and fetal programming [7], [8], [9].
Notably, vitamin D deficiency/insufficiency is associated with the development of metabolic syndrome and obesity [10], [11], [12], [13], two important current public health issues [10], [11], [12], [13], [14], [15], [16]. The literature is still discordant in stating whether metabolic syndrome results in obesity or whether it is obesity that causes metabolic syndrome. However, the association between these is well described [17]. Metabolic syndrome is characterized by the presence of obesity (especially abdominal), high blood pressure, altered lipid and glucose metabolism, elevated fasting glycemia, increased serum triglyceride levels and reduced HDL-c [18], [19], [20]. Furthermore, it is very common to observe atherogenic diseases and insulin resistance [21]. To make the diagnosis, at least three of these changes must be associated [22]. According to Castro et al. [23], obesity is important for the development of metabolic syndrome and in this context low serum levels of Vitamin D and its components are observed [24], [25], [26]. Thus, it is believed that the reduction of Vitiman D in obese patients and/or patients with metabolic syndrome occurs because Vitamin D is sequestered by adipocytes due to the high affinity of Vitamin D and the lipids accumulated in these cells. Continuing, the sequestration of Vitamin D determines the reduction of the stimulus of cascades of hypothalamic reactions. Thus, the individual will have an increased feeling of hunger and a decrease in energy expenditure. These two factors may favor an increase in the degree of obesity and an increasing reduction in bioavailable Vitamin D [20], [27], [28], [29].

Women during pregnancy gain weight due to the development of the fetus, fluid retention and above all due to the increase in fat reserves [30]. However, some women gain more weight than others and most pregnant women do not easily return to their usual weight after delivery [31], [32], [33], that is, they have difficulty losing the weight gained during pregnancy.

It should also note that many pregnant women have obesity and metabolic syndrome [34], [35], [36]. These facts show the necessity of vitamin D for the maintenance of maternal weight during pregnancy and after birth. Therefore, vitamin D supplementation is necessary, especially because exposure to sunlight and dietary intake does not provide sufficient amounts of this vitamin [8], [9], [37]. These facts are preponderant causes for the epidemic of Vitamin D deficiency/insufficiency globally [38], that is, this condition is present in both developed and underdeveloped countries [39], [40]. It is also noteworthy that this is also found in tropical/equatorial regions (where there is a lot of sunshine) [12] and in temperate countries (where there is low sunshine) [41]. It is also observed that even in populations that use the Mediterranean diet (rich in Vitamin D) deficiency/insufficiency of this vitamin still occurs [42].
Facts that prove this need for supplementation is the study by Cui et al. [43] who reported found that globally, 15.7% (95% Crl 13.7-17.8), 47.9% (95% Crl 44.9-50.9), and 76·6% (95% Crl 74.0-79.1) of participants had serum 25- hydroxyvitamin D levels less than 30, 50, and 75 nmol/L, respectively. That same study reports that the prevalence slightly decreased from 2000-2010 to 2011-2022, but it was still at a high level; people living in high latitude areas had a higher prevalence; the prevalence in winter-spring was 1.7 (95% Crl 1.4-2.0) times that in summer-autumn; the Eastern Mediterranean region and Lower-middle-income countries had a higher prevalence; females were vulnerable to vitamin D deficiency.
Weekly supplementation with 50,000 IU vitamin D for eight weeks or 6,000 IU vitamin D per day until reaching serum levels of 25(OH)D higher than 30 ng/mL is also suggested for adults deficient in vitamin D.
After normalization, normal vitamin D levels are maintained with supplementation ranging from 1,500 to 2,000 IU per day [44]. The vitamin D levels of women considering pregnancy or who are pregnant should be monitored every three months, and these women should be treated with at least 4,400 IU per day, if necessary [45], [46]. Conversely, lactating women require 6,400 IU per day to ensure that breast milk is a rich source of vitamin D [47]. In cases of severe vitamin D deficiency, single intramuscular doses of up to 600,000 IU are reported as therapeutic doses in the literature [48], [49] and this prescription even includes pregnant women. However, the safety of this supplementation during the gestational period has not yet been demonstrated, and higher doses may be required to treat patients with autoimmune conditions because they poorly metabolize vitamin D [50].
Calcium is an element necessary for bone mineralization [51], a process that also affects vitamin D. Therefore, when the calcium levels are reduced there is an increase in the active form of vitamin D that raises intestinal absorption [52]. In pregnant women, there is a necessity of the highest number of calcium intake (which can be done by ingesting chelated calcium), especially, in the third trimester of pregnancy when the fetal bone reaches the highest peak of growth. Consequently, there is a corresponding increase in the absorption of this element in the intestinal mucosa of the mother. These physiologic processes lead to an increase in activated vitamin D 1,25 (OH) 2D synthesis [52], [53], [54].
In view of the above, the present study aimed to investigate the effects of high doses of vitamin D supplementation and its combination with calcium on reproductive performance, embryo-fetal development, and DNA integrity in pregnant Swiss mice.

Section snippets
Chemical agents
Vitamin D, cholecalciferol 25(OH)2D, (Lot 1408221) and Chelated calcium was provided by the Compounding Pharmacy Formédica Ltd. (National Registry of Legal Entities (Cadastro Nacional da Pessoa Jurídica – CNPJ) 82.342.403/0001-83), whose managing pharmacist is Sandra Kuniyoshi.
Vitamin D: doses, routes and period of administration
Two double-blind experiments were conducted: In one experiment, mice received intramuscular supplementation at a dose corresponding to 600,000 IU in a 70-kg patient [48], whereas in the other experiment, the mice received…

Biometric parameters
The animals were randomly assigned to different lots and experimental groups. Animals receiving the two highest intramuscularly doses of vitamin D combined with calcium exhibited weight reductions compared with the control group, whereas orally vitamin D did not significantly impact body weight (p>0.05). The final weight, weight gain, uterine weight, and net weight gain did not differ (p>0.05) between any groups in (Table S1).
The absolute and relative organ weight did not differ between groups,…

Discussion
The assessment of biometric parameters showed no signs of maternal toxicity. The only significant variation identified as the relative spleen weight of the animals treated with the lowest dose of vitamin D in combination with calcium. This difference is an isolated incidence. The absence of variations in biometric parameters along with the absence of clinical signs of intoxication (opacity of eyes and hair, mucosal dryness, hair bristling, behavioral changes, changes in walking, i.e., locomotor…
Conclusion
Based on the above considerations, infer that vitamin D and vitamin D are associated with calcium, at intramuscular doses of 600,000IU, 6,000,000IU and 60,000,000IU and at orally doses of 6,000IU, 60,000IU and 600,000IU, tested in pregnant Swiss mice is not maternal-toxic, not genotoxic and do not change the reproductive performance and embryofetal development, what suggest safety of use also during the gestational period.


81+ VitaminDWiki pages have HIGH DOSE in the title

The list is automatically updated

Items found: 82
Title Modified
Cofactors are needed when taking high-dose vitamin D - video Nov 2024 07 Nov, 2024
Extremely high-dose Vitamin D not a problem for pregnant mice (60M IU injection, 0.6 M IU oral) – Sept 2024 28 Sep, 2024
3X reduced mortality in one metabolic cluster of ICU patients by high-dose Vitamin D – Nov 2024 21 Sep, 2024
High-Doses (50,000 IU weekly, etc.) if at high risk of Vitamin D deficiency - Aug 2024 12 Aug, 2024
High Dose Vitamin D reduces skin problems during Cancer Treatment - May 2024 20 May, 2024
High-dose Vitamin D reduced inflammation and insulin resistance (obese children) - Dec 2023 02 Jan, 2024
High dose vitamin D (20,000 IU per kg of feed) safe for pigs – Aug 2015 24 Dec, 2023
Coimbra high-dose vitamin D protocol - many studies 10 Nov, 2023
Multiple Sclerosis prevention with high-dose vitamin D (in rats in this case) - July 2023 19 Sep, 2023
Knee Osteoarthritis treated by vitamin D if use more than 2,000 IU daily or non-daily high dose – meta-analysis Aug 2023 21 Aug, 2023
Doctor got MS and was later cured by high-dose Vitamin D - Aug 2023 10 Aug, 2023
Cluster headaches virtually eliminated in 7,000 people with high-dose vitamin D and cofactors - Feb 2022 16 Jul, 2023
Rheumatoid Arthritis pain is reduced by Vitamin D, high doses also reduced inflammation (CRP) – Meta-analysis July 2023 13 Jul, 2023
COVID predicted to be a pandemic that could be stopped by high dose vitamin D - Feb 2020 25 Mar, 2023
Muscular Dystrophy probably treated by high-dose Vitamin D plus muscle rehab 23 Mar, 2023
Fracture 4X less likely following kidney transplant if high-dose Vitamin D (100,000 every 2 weeks) – RCT Jan 2023 25 Jan, 2023
High-Dose 18 Jan, 2023
Some pathogens and health problems restrict Vitamin D from being used – Coimbra high-dose protocol – April 2021 18 Jan, 2023
Diseases treated by high-dose Vitamin D - many studies 18 Jan, 2023
50,000 IU and other high dose vitamin studies 15 Jan, 2023
Coimbra protocol using high-dose Vitamin D is safe – April 2022 22 Dec, 2022
High dose vitamin D fights Folate gene changes by COVID, autoimmune, CVD, ALZ – Oct 2022 06 Oct, 2022
Treat COVID with early high-dose Vitamin D (20th as of June 2022) 16 Jun, 2022
High-Dose Vitamin D puts surplus calories into muscles instead of fat (mice) – May 2022 20 May, 2022
Comparing High-dose vitamin D therapies 04 May, 2022
High-dose Vitamin D safe for children (10,000 IU daily, 600,000 IU bolus) – meta-analysis April 2022 15 Apr, 2022
Several rheumatic diseases treated by high-dose vitamin D, but made worse if Calcium was added – April 2022 28 Mar, 2022
Cluster Headaches treated by high-dose Vitamin D, etc. (interview and transcript) - Feb 2022 23 Feb, 2022
Beyond vitamin D - book of testimonials on high-dose Coimbra Protocol - Aug, 2021 16 Feb, 2022
High-Dose Vitamin D Therapy – book July 2018 11 Feb, 2022
High-dose Vitamin D is safe and effective – review of 10 studies – Sept 2021 08 Feb, 2022
HIV treatment augmented by high-dose vitamin D, daily or weekly – Dec 2021 30 Jan, 2022
High-dose Omega-3 fought COVID in 2 hospital trials (6x reduction in ICU, reduced time) – Masterjohn Oct 2021 14 Oct, 2021
Multiple Sclerosis treated by Vitamin D, recommends investigating high dose Coimbra - Oct 2021 07 Oct, 2021
Those getting high dose vitamin D were 7 X less likely to die of COVID-19 - Dec 11, 2020 30 Sep, 2021
Vitamin D3 better than D2, especially if non-daily or high dose - meta-analysis Sept 2021 23 Sep, 2021
High-dose vitamin D improves health (presentation) - Aug 30, 2021 30 Aug, 2021
High dose vitamin D for Autoimmune diseases - Portuguese - 2019 01 Jul, 2021
High Dose Vitamin D for autoimmune diseases -blog June 13, 2021 20 Jun, 2021
Kidney patients who happened to be getting high-dose Calcitriol were 9X less likely to die of COVID-19 - April 6, 2021 13 Apr, 2021
Autoimmune and high-dose vitamin D (Dr. Coimbra) - Dr. Mahtani video and transcript - Nov 2020 11 Apr, 2021
Vitamin D Resistance hypothesis confirmed by Coimbra high-dose vitamin D protocol – April 2021 11 Apr, 2021
Crohn’s Disease reduced for a year by 7 weeks of high dose Vitamin D – RCT March 2021 26 Mar, 2021
COVID-19 and high-dose Vitamin D - Video interview of Dr. Coimbra - May 2020 09 Aug, 2020
High doses vitamin D may prevent or treat COVID-19 - June 2020 31 Jul, 2020
Many doctors believe that high dose vitamin D can fight COVID-19 – BMJ April 2020 14 Apr, 2020
Lowering Calcium Risk when having High Dose Vitamin D3 – Cawley Dec 2019 18 Dec, 2019
The use of high dose Vitamin D (Coimbra Protocol) for multiple sclerosis in Germany – 2019 26 Nov, 2019
Cystic Fibrosis is safely treated by high-dose Vitamin D – Sept 2019 26 Nov, 2019
Rheumatoid Arthritis sometimes helped by very high dose vitamin D2 – 1935 29 Oct, 2019
High-dose Vitamin D for Multiple Sclerosis is OK while pregnant – Sept 2019 10 Sep, 2019
Cardiovascular Prevention with Omega-3 (finally using high doses) – Sept 2019 09 Sep, 2019
Treat autoimmune diseases with high-dose vitamin D – Germany online Aug 24, 25 2019 17 Aug, 2019
Successful high dose vitamin D (Coimbra Protocol) should be evaluated – June 2019 09 Jun, 2019
Hypertension gene expression reduced by high-dose vitamin D (hypertensive rats) – March 2019 27 Mar, 2019
High-dose vitamin D forum – for Multiple Sclerosis and many other diseases – Jan 2019 05 Jan, 2019
Vitamin D nanoemulsion corrected deficiency and improved bones in 1 week (high dose in rats) – Jan 2019 05 Jan, 2019
Multiple Sclerosis - Coimbra Protocol (high-dose Vitamin D) - by one of the 120 doctors of 20,000 patients - Dec 2018 08 Dec, 2018
Problem with vitamin C if high dose Vitamin D for MS and have gene problem – Sept 2018 10 Oct, 2018
Replies to doctor’s comments about high dose Vitamin D for Multiple Sclerosis– Nov 2016 27 Jun, 2018
Guide for patients on high doses of Vitamin D – Coimbra 2017 21 Jun, 2018
Multiple Sclerosis treated when use high doses of vitamin D – meta-analysis May 2018 16 May, 2018
Liver cancer nicely treated by high dose vitamin D for 16 weeks (early stage, in rats) – April 2018 23 Apr, 2018
Gene activation by high dose vitamin D - both quick and long term - April 2015 27 Jun, 2017
ICU cost reduced by at least 27,000 dollars if get high dose vitamin D in first week - April 2017 02 May, 2017
High dose vitamin D to treat Multiple Sclerosis etc. – protocol April 2017 27 Apr, 2017
High dose Omega-3 probably reduces heart problems – American Heart Association – March 2017 18 Mar, 2017
Video by Dr. Coimbra – 95 percent of auto-immune cured with vitamin D in high doses - April 2014 15 Jan, 2017
Caution When Prescribing High Dose Vitamin D (100,000 IU D2 daily for is too much after 4 years) – Nov 2016 26 Nov, 2016
Hospital ICU added high dose vitamin D - malpractice lawsuit costs dropped from 26 million dollars to ZERO - Oct 2016 20 Nov, 2016
70 percent of people with IBS had symptoms relieved with high dose vitamin D – 2012 04 Nov, 2016
Pediatric trials of high dose vitamin D -163 are in a single online database – Feb 2016 07 Aug, 2016
Kidney disease helped by active or high dose Vitamin D - Feb 2014 28 Apr, 2016
Dr. Coimbra explains his treatment with high dose vitamin D for multiple sclerosis – Feb 2015 27 Apr, 2016
High dose vitamin reduced pain of fibromyalgia, osteoarthritis, and rheumatoid arthritis - July 2015 11 Jul, 2015
Brazillian petition to permit high vitamin D doses for autoimune diseases – Aug 2014 08 Feb, 2015
Update on Treating Multiple Sclerosis with high dose vitamin D - Sept 2013 08 Feb, 2015
Video by Dr. Coimbra – auto-immune cures with high-dose vitamin D in Brazil - April 2014 19 Apr, 2014
Response to high dose vitamin D is limited by vitamin A - July 2013 13 Apr, 2014
Liverpool is starting universal supplementation and needs high dose vitamin D – March 2014 26 Feb, 2014
4 clinical trials not find change in disease risk markers with high dose vitamin D – March 2013 13 Apr, 2013
Is High Dose Vitamin D Harmful – Dec 2012 20 Dec, 2012

VitaminDWiki – Overview Toxicity of vitamin D dosing chart

Graph of dose vs week
600,000 IU daily for a week MIGHT be toxic


VitaminDWiki – Injection contains:

68 items in Vitamin D Injection category

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Very strange: 50% of mice should be killed by 34,000 IU (20 gram mouse)

The oral LD50 (lethal dose for 50% of the population) of cholecalciferol in rats/mice is 43.6 mg/kg