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In palliative care, all treatment aims to relieve symptoms and to maintain as high quality of life (QoL) as possible despite an incurable cancer. Cancer related fatigue (CRF) is one of the most distressing symptoms for cancer patients that impair QoL the most. Today, there is a lack of effective and safe pharmacological treatment for CRF in palliative care. We recently conducted a large clinical study where we found that Vitamin D treatment reduced the need for opiod use in palliative cancer patients. In addition, we found that Vitamin D reduced CRF. To confirm these results, we are now planning a new clinical study that completely focuses on CRF where 200 patients will be randomized to low dose vitamin D (400 IU/day) or high dose (4000 IU/day) for 16 weeks. The mechanisms for how Vitamin D can affect CRF will be studied by measuring proinflammatory markers and levels of oxysterols in the blood, which in turn can affect brain functions and possibly CRF.We want to answer the following questions: 1) Can Vitamin D reduce CRF and what is the optimal dose and blood concentration of vitamin D? 2) Can Vitamin D reduce CRF by decreasing inflammation and affecting 27-OHcholesterol levels? 3) Are high vitamin D levels harmful to cancer patients due to elevated levels of fibroblast growth factor 23 (FGF23)?Both positive and negative results are important in this study as there is currently lack of evidence whether Vitamin D can be used against CRF in palliative cancer care.