Vitamin D for the prevention and treatment of pancreatic cancer.
Pancreatic cancer is ranked fifth among cancer-related deaths worldwide with a 5-year survival rate of less than 5%.
Currently, surgery is the only effective therapy.
However, most patients are diagnosed in the late stage and are not suitable for receiving curative surgery.
Moreover, pancreatic cancer doesn't respond well to traditional chemotherapy and radiotherapy, leaving little effective treatment for advanced pancreatic cancer cases.
1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], the biologically active form of vitamin D(3), was originally identified during studies of calcium and bone metabolism, though it is now recognized that it exerts biological effects in almost every tissue in the body.
Abundant evidence has shown that 1alpha,25(OH)(2)D(3) has antiproliferative, apoptotic, pro-differentiation and antiangiogensis effects in many types of cancer cells in vivo and in vitro, including breast, prostate, and colon.
Similarly, the antitumor growth effect of 1alpha,25(OH)(2)D(3) on pancreatic cells has been demonstrated.
The clinical use of 1alpha,25(OH)(2)D(3) is impeded by the lethal side effects of hypercalcemia and hypercalciuria.
Therefore, 1alpha,25(OH)(2)D(3) analogs, which are either equipotent or more potent than 1alpha,25(OH)(2)D(3) in inhibiting tumor cell growth but with fewer hypercalcemic and hypercalciuric side effects, have been developed for the treatment of different cancers.
Recently, a pre-clinical study demonstrated that a less calcemic analog of 1alpha,25(OH)(2)D(3), 19-nor-1alpha,25(OH)(2)D(2) (Paricalcitol), is effective in inhibiting tumor growth in vitro and in vivo, via upregulation of p21 and p27 tumor suppressor genes.
Studies on the anti-tumor effects of a more potent analog of Paricalcitol are underway. 1alpha,25(OH)(2)D(3) and its analogs are potentially attractive novel therapies for pancreatic cancer.
It may be helpful to for those who are concerned about the possibility of the hypercalcemic and hypercalciuric adverse potential to read Vieth Paper Vitamin D and cancer mini-symposium: the risk of additional vitamin D. the abstract of which states
Any benefit of vitamin D needs to be balanced against the risk of toxicity, which is characterized by hypercalcemia.
Daily brief, suberythemal exposure of a substantial area of the skin to ultraviolet light, climate allowing, provides adults with a safe, physiologic amount of vitamin D, equivalent to an oral intake of about 10,000 IU vitamin D(3) per day, with the plasma 25-hydroxyvitamin D (25(OH)D) concentration potentially reaching 220 nmol/L (88 ng/mL).
The incremental consumption of 40 IU/d of vitamin D(3) raises plasma 25(OH)D by about 1 nmol/L (0.4 ng/mL).
High doses of vitamin D may cause hypercalcemia once the 25(OH)D concentration is well above the top of the physiologic range.
The physiological buffer for vitamin D safety is the capacity of plasma vitamin D-binding protein to bind the total of circulating 25(OH)D, vitamin D, and 1,25-dihydroxyvitamin D [1,25(OH)2D].
Hypercalcemia occurs when the free concentration is inappropriately high because vitamin D and its other metabolites have displaced 1,25(OH)2D from vitamin D-binding protein.
Evidence from clinical trials shows, with a wide margin of confidence, that a prolonged intake of 10,000 IU/d of vitamin D(3) poses no risk of adverse effects for adults, even if this is added to a rather high physiologic background level of vitamin D.
For anyone with a cancer diagnosis Dr Cannell of The Vitamin D Council has an interesting newsletter on the subject Does Vitamin D Treat Cancer.
Far better though is prevention and this is covered in this newsletter from the same source.