Vitamin D reduces fatigue in patients with advanced cancer, say researchers

Patients with lower vitamin D are more likely to suffer from fatigue and this is especially the case for men who are more prone to severe fatigue, they explain.

However, a recent trial indicates that supplementation to correct vitamin D deficiencies significantly reduced fatigue in men, but not women.

Analyses also suggest vitamin D helped manage pain relief among study participants, with opioid use significantly lower in the vitamin D group compared to the placebo.

“Since pharmacological treatment options for fatigue in palliative care are limited, and the evidence bases for these treatments are weak, the reported positive effect of vitamin D is highly interesting,”​ they authors write.

Limited evidence​

Fatigue is common in patients with advanced or metastatic cancer and has repercussions on quality of life (QoL), the authors write, with recent analysis showing as many as 60% of patients suffer from fatigue.

Cancer-related fatigue affects women more than men, especially at the end of life but treatment for fatigue in palliative cancer is challenging. Studies suggest it should focus on behavioural and psychological intervention since medication has shown limited success, they say.

A correlation between lower vitamin D and increased fatigue in cancer patients has been established in some cohort studies, but here is limited research into the etiology between sexes or on the treatment of fatigue.

Vitamin D is a steroid hormone important for regulating the immune system and has beneficial anti-inflammatory properties. Therefore, correcting deficiencies might reduce inflammation related to increased fatigue.

Supplementation has shown positive results for self-reported fatigue in health individuals and also been associated with higher health related QoL, the team says.

Benefits for men​

The aim of the present study was to investigate gender differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue.

There was no correlation between vitamin D levels and fatigue in women and no apparent mechanistic explanation for differences observed between men and women, the authors maintain.

Previous studies have shown an association between low vitamin D and hypogonadism in men, and this was posited as one potential theory.

In addition, vitamin D deficiency is linked to muscle mass in men but not women and other gender related risk factors for fatigue, such as physical, psychological, and social features, but a lack of information on how these factors are distributed between men and women, if they are interlinked, and the extent to which they effect vitamin D levels.

Study protocol​

The double-blind placebo-controlled trial was conducted in palliative care homes in the Stockholm region and involved 244 patients with advanced or metastatic cancer and with a predicted remaining lifespan of at least three months. Only patients with vitamin D deficiency were randomised to the treatment group.

Participants were randomised to the vitamin D3 group (123) and given a 4000 IU dose of cholecalciferol per day, or to the placebo (121) for 12 weeks. Of these, 67 in the treatment group and 83 in the placebo completed the full trial. The high dropout rate was due to clinical deterioration or death.

Study objectives were to assess the impact of supplementation on pain with opioid treatment (fentanyl) and the effects on infection, fatigue, quality of life, and plasma vitamin D (25-hydroxyvitamin D) .

Analysis of 25-OHD was conducted using a chemiluminescence immunoassay instrument and fatigue measured using the Edmonton Symptom Assessment scale (ESAS). Participants were also required to complete a QoL questionnaire.

A significant reduction in fatigue was observed in men. A borderline significant effect on improved QoL was also noted in men, but not women. There was no difference in self-assessed infections between the groups.

Explanations​

Results must be interpreted with caution given the additional variables mentioned that could impact the results. The researchers assert that the effect on fatigue could not be solely explained by the reduced opioid doses in the vitamin D group and other mechanisms independent of opioid-induced fatigue must be involved.

In addition, the small numbers of patients who completed the study demonstrates the difficulties in performing trials in a palliative cohort with a high attrition rate due to death.

They conclude that future research should be performed that is specially designed to study sex differences in the effects of vitamin D on fatigue in cancer patients before any firm conclusions can be drawn.

Source: Cancers​

Published online: doi.org/10.3390/cancers 14030746​​

‘Sex Differences in the Effect of Vitamin D on Fatigue in Palliative Cancer Care—A Post Hoc Analysis of the Randomized, Controlled Trial ‘Palliative-D’’​

Caritha Klasson, Maria Helde Frankling, Anna Warnqvist, Carina Sandberg, Marie Nordström, Carina Lundh-Hagelin and Linda Björkhem-Bergman