Large dose Vitamin D before surgery was found to help by 35 studies

This small study would probably have gotten statistically significant results if they have given the 300,000 IU of Vitamin D 3 days BEFORE the surgery. It takes several days for oral vitamin D to get to the cells (injection is slower, nanoemulsion is faster)

Optimal vitamin D status at admission appears to improve survival after craniotomy in patients with brain malignancies

Clinical Nutrition ESPEN Vol 55, June 2023, Pages 428-433 https://doi.org/10.1016/j.clnesp.2023.04.009 $25 paywall
Mohammadreza Shahmohammadi a,
Melika Hajimohammadebrahim-Ketabforoush b,
Zahra Vahdat Shariatpanahi b

• a Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran
• b Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Background and aims
Survival from diagnosis of brain malignancies is often very short. Craniotomy in turn may be associated with morbidity and even post-operative mortality. Vitamin D and calcium were known as protective factors on all-cause mortality. However, their role is not well-understood in post-surgery survival of brain malignant patients.

Methods
Totally, 56 patients completed the present quasi-experimental study, comprising the intervention group (n = 19) under intramuscular administration of 300 000 IU vitamin D3, the control group (n = 21), and the group of patients with optimal vitamin D status at admission (n = 16).

Results
The mean ± SD of preoperative 25(OH)D levels in the control, intervention, and optimal vitamin D status groups were 15.15 ± 3.63 ng/mL, 16.61 ± 2.56 ng/mL, and 40.03 ± 10.56 ng/mL, respectively (P < 0.001).
Crude survival was significantly greater in the optimal vitamin D status group than those in another two groups (P = 0.005).
Also, Cox proportional hazard model showed that the risk of mortality was higher in the control group and the intervention group than in the group of patients with optimal vitamin D status at admission (P-trend = 0.03).
However, this correlation weakened in the full-adjusted models. Preoperative total calcium had an inverse significant correlation with mortality risk [HR value 0.25, (95%, CI: 0.09–0.66), P = 0.005], and age had a positive correlation [HR value 1.07, (95%, CI: 1.02–1.11), P = 0.001].

Conclusion
Total calcium and age were predictive factors in six-month mortality and optimal vitamin D status appears to improve the survival in these patients, which should be examined more closely in future studies.

Introduction
Surgical intervention, traditionally known as a craniotomy, is a gold standard in clinical management of brain malignancies, though the largest volume of tumor removal in this route is just an opportunity for treatment [1,2]. Brain malignancies, most of which include high-grade glioma, grade III and IV according to the World Health Organization (WHO) classification, and metastatic brain tumors, have a low life expectancy since diagnosis [3]. The median of survival from diagnosis of high grade gliomas and brain metastases have been shown to be 12–15 months [4] and 3.9 months [5], respectively. On the other hand, craniotomy may be associated with neurological deficit and even post-operative mortality [1]. Although there is limited investigation concerning post-operative complications and mortality and its predictive risk factors in malignant brain tumors, it was suggested that age, smoking, medical comorbidities, location of lesions, preoperative ASA, and KPS scores, and intraoperative bleeding could be related to post-craniotomy morbidity and mortality [1,2,4,6,7]. To date, however, the role of nutritional factors as an important part of a patient's lifestyle in these neurosurgery studies is largely unknown. Vitamin D and calcium have recently been gaining enormous attention in critically-ill settings. Studies have shown that low vitamin D concentrations are associated with inflammation, increased risk of cardiovascular disease (CVD), and higher insulin resistance and all-cause mortality in critically ill patients [8,9]. Moreover, vitamin D status correction substantially improves outcomes and decrease risk in other disorders such as CVD, diabetes, cancers, and overall survival in cancer patients [[[10], [11], [12], [[13]]. According to a meta-analysis of trials in general population, vitamin D with calcium, not vitamin D alone, could reduce mortality [14]. In this regard, an extensive study on 1360 critically ill patients with serum 25(OH)D levels <20 ng/mL could not find any meaningful effects of early administration of high-dose enteral vitamin D3 compared with placebo on three-month mortality [15]. One study among colorectal cancer patients indicated that higher prediagnosis intakes of total calcium and milk could be associated with lower risk of death [16]. Another study on patients with early stage lung adenocarcinoma with serum 25(OH)D levels <20 ng/mL indicated that vitamin D supplements for one year after surgery which could improve the survival compared with placebo [17]. This effectiveness has also been reported on patients with glioblastoma [18,19]. Moreover, in the surgical setting, a systematic review article supported this hypothesis that hypovitaminosis D is associated with postoperative adverse outcomes following the variety of surgical procedures [20].

Interestingly, only a few study reported that brain tumor surgeries conducted in summer season associated with lower death rate during post-surgery follow up [21]. Therefore, given the lack of enough relative studies and importance of survival in patients with brain malignancies, the present study was conducted in the quasi-experimental design aiming to compare the effects of single high dose vitamin D3 in patients with serum 25(OH)D levels ≤20 ng/mL, with the control group and patients that had optimal vitamin D status at admission (25(OH)D levels >30 ng/mL) on survival after craniotomy for brain malignancies during six-month from surgery.

Section snippets

Study design and participations
A total of 56 patients completed the present quasi-experimental study, comprising the intervention group (n = 19) under intramuscular (IM) administration of 300 000 IU vitamin D3, the control group (n = 21), and the group of patients with optimal vitamin D status at admission (n = 16). The present study used a part of patients from our previous randomized clinical trial (N = 27; intervention = 14, control = 13), and patient recruitment continued to December 2019. For a detailed study of the . . . .

Results
71.4% of patients with malignant brain tumors had the serum 25(OH)D levels ≤20 ng/mL at the admission. They were known as insufficient patients in terms of vitamin D status, and randomly included in the control and the intervention groups. Only 28.6% of our patients had the serum 25(OH)D levels >30 ng/mL, and they were considered as optimal vitamin D status group (normal patients in terms of this vitamin). The mean ± SD of preoperative serum 25(OH)D levels in the control, intervention, and . . . .

Discussions
We conducted the present study to compare the effect of single high dose vitamin D3 in patients with serum 25(OH)D levels ≤20 ng/mL, with the control group and also patients that had optimal vitamin D status at admission (25(OH)D levels >30 ng/mL) on survival after craniotomy for brain malignancies during six-month from surgery. According to our results, 71.4% of patients with malignant brain tumors were insufficient in terms of vitamin D status. The crude survival has not statistically . . . .

Conclusions
In conclusion, vitamin D insufficiency was common in patients with malignant brain tumors. Among these insufficient patients, the crude survival does not have any statistically significant difference between the patients under administration of single intramuscular 300 000 IU dose of vitamin D3 compared with the control group, while in comparison with these two patients groups, patients with optimal vitamin D status at admission had longer survival time, although this correlation weakened in . . .

Acknowledgements
This study did not receive any grants and funding. The authors declare that they have no competing interests. The authors' contributions are as follows: M.H, M.S. and Z.V. conceptualized and designed the study; M.H. and Z.V. analyzed data; M.H. and M.S. wrote the manuscript; M.H. and M.S. collected data; M.H. and M.S. interpreted the data; Z.V provided professional comments; M.S. critically revised the manuscript for intellectual content and data accuracy; M.H. and M.S. had responsibility for

References include:

• F.L. Ataide et al. Safety and effectiveness of vitamin D mega-dose: a systematic review Clin Nutr ESPEN (2021) doi: 10.1016/j.clnesp.2021.09.010 No comment on outcome – PDF is behind paywall
• Q.Y. Chen et al. Post-diagnosis vitamin D supplement use and survival among cancer patients: a meta-analysis Nutrients (2022)
• L. Rejnmark et al. Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials J Clin Endocrinol Metab (2012)
• A.A. Ginde et al. Early high-dose vitamin D 3 for critically ill, vitamin D-deficient patients N Engl J Med (2019)

Vitamin D Life - 35 studies in both categories Surgery and Loading Dose

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