Vitamin D supplementation to palliative cancer patients: protocol of a double-blind, randomised controlled trial ‘Palliative-D’

Björkhem‐Bergman

2017

IJMS

Self Cite

Vitamin D is a hormone synthesized in the skin in the presence of sunlight. Like other hormones, vitamin D plays a role in a wide range of processes in the body. Here we review the possible role of vitamin D in nociceptive and inflammatory pain. In observational studies, low vitamin D levels have been associated with increased pain and higher opioid doses. Recent interventional studies have shown promising effects of vitamin D supplementation on cancer pain and muscular pain—but only in patients with insufficient levels of vitamin D when starting intervention. Possible mechanisms for vitamin D in pain management are the anti-inflammatory effects mediated by reduced cytokine and prostaglandin release and effects on T-cell responses. The recent finding of vitamin D-mediated inhibition of Prostaglandin E2 (PGE2) is especially interesting and exhibits a credible mechanistic explanation. Having reviewed current literature, we suggest that patients with deficient levels defined as 25-hydroxyvitamin D (25-OHD) levels <30 nmol/L are most likely to benefit from supplementation, while individuals with 25-OHD >50 nmol/L probably have little benefit from supplementation. Our conclusion is that vitamin D may constitute a safe, simple and potentially beneficial way to reduce pain among patients with vitamin D deficiency, but that more randomized and placebo-controlled studies are needed before any firm conclusions can be drawn.

Section: Vitamin D In Cancer Painmentioning

confidence: 99%

Vitamin D in Pain Management

Björkhem‐Bergman

2017

IJMS

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“…The first study was a randomized, placebo-controlled, double-blind study on vitamin D in palliative care, “The Palliative-D study” performed during 2017–2020 [ 17 , 18 , 19 ]. Serum samples from the screening visit were used, i.e., before any study drug had been given.…”

Section: Methodsmentioning

confidence: 99%

CYP3A Activity in End-of-Life Cancer Patients Measured by 4β-Hydroxycholesterol/cholesterol Ratio, in Men and Women

Bergström

Klasson

et al. 2021

Cancers

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More than 50% of all drugs are metabolized by the cytochrome P450 3A enzyme (CYP3A). The aim of this study was to investigate if the CYP3A activity, measured by the endogenous marker 4β-hydroxycholesterol/cholesterol ratio (4β-OHC/C), is changed during the last weeks and days of life in men and women. To this end, serum samples from 137 deceased patients (median age 70 years) collected at a single time point 1–60 days before death, were analyzed and compared to 280 young (median 27 years), and 30 elderly (median age 70 years) non-cancer controls. There were no significant differences in the 4β-OHC/C ratio between men and women in end-of-life patients (p < 0.25). The median 4β-OHC/C was significantly higher in end-of-life male patients compared to both young (p < 0.0001) and elderly (p < 0.05) male controls. In a similar manner, 4β-OHC/C in end-of-life female patients was significantly higher compared to young and elderly female controls, p < 0.0001 and p < 0.001, respectively. There was no significant correlation between 4β-OHC/C and survival time. The results from this study suggest maintained CYP3A activity to the very last days of life and even a capacity of induction of the enzyme in end-of-life cancer patients.

“…It has been suggested that correction of vitamin D deficiency may have a positive effect on fatigue in palliative cancer patients [ 52 , 53 , 54 ]. This is currently investigated in a large ongoing randomized, placebo-controlled, double-blind study, “Palliative-D” [ 55 ]. The results from this study are still not published but in the baseline data from the study cohort ( n = 530) there was a significant association between low vitamin D levels and severe fatigue in men but not in women [ 56 ].…”

Section: Dietary Supplements and Complementary Medicinementioning

confidence: 99%

Fatigue in Cancer Patients in Palliative Care—A Review on Pharmacological Interventions

Klasson

Hagelin

et al. 2021

Cancers

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Fatigue is one of the most distressing symptoms experienced by cancer patients. The suggested biological mechanism for cancer related fatigue (CRF) includes immune activation triggered by tumor tissue or by anticancer treatment but other mechanisms have also been proposed. Previous large meta-analysis of interventions on fatigue focuses mostly on patients early in the disease trajectory, with only one tenth of included studies performed in palliative cohorts. The aim of this narrative review is therefore to present a background on CRF with focus on the palliative setting. A summary of recent randomized, controlled trials on pharmacological interventions on CRF in palliative care is presented, including studies on psychostimulants, corticosteroids, testosterone and melatonin. Interestingly, in several of these studies there was a positive and similar effect on fatigue in both the intervention and the placebo arm—indicating an important placebo effect for any pharmacological treatment. In addition, studies on dietary supplements and on pharmacological complementary medicines are discussed. To conclude, the evidence is still weak for using pharmacological treatments on CRF in palliative care patients—although methylphenidate and corticosteroids might be considered.