Deakin University Honours Project #2

Impact of vitamin D on outcomes in patients with colorectal cancer


Prof David Watters, Dr Eileen Moore




Department of Surgery, Deakin University; University Hospital Geelong, Barwon Health.



Project description

The purpose of this study is to determine whether vitamin D levels affect the short and long term outcomes of patients who are treated for colorectal cancers.  Around 150 patients with these cancers have had dietary assessments and measurement of bone density.  This project will involve assessing their long-term oncologic and other clinical outcomes.


Vitamin D is the name given to a group of lipid soluble molecules that enhance calcium absorption in the small intestine.  The well-known consequences of vitamin D deficiency (serum level <20ng/ml) include rickets in children, and osteomalacia and osteoporosis in adults.  Vitamin D increases in circulation primarily as a result of synthesis from cholesterol during dermal exposure to ultraviolet-B (UVB, as from sunlight).  Other forms of intake are from oily fish and through the use of supplements or fortified foods.  Sun avoidance has increased in recent years due to increased publicity relating sun exposure to skin cancer.[1] Consequently; health agencies have revised guidelines to include higher intakes from foods and supplements. 


Recommended dietary intakes (RDI) for Australia and New Zealand were published by the National Health and Medical Research Council in 2006.[2] A RDI of 5.0 micrograms was recommended for males and females from birth to age 50 years, including pregnant and lactating women.  Adults between 50-70 years were recommended to take 10.0 micrograms per day; whereas a RDI of 15.0 micrograms was recommended for adults over the age of 70 years.  Increased intake was recommended for older adults in part to mitigate decreased levels due to limited sun exposure, especially in institutionalised adults, and as previous studies had shown an inverse correlation between vitamin D levels and the rate of falls and fractures in these age groups.[3]  


Inactive forms of vitamin D are converted to the active form (calcitriol) after two hydroxylation reactions.  The first of these reactions occurs in the liver, and then the second reaction occurs in the kidneys.  A well-known action of calcitriol is to maintain calcium homeostasis by initiating bone resorption via osteoclasts[4] when serum calcium levels are low.  Potential extra-skeletal functions of vitamin D are ardently debated despite a surfeit of information from observational studies and randomised controlled interventional trials.  Low serum vitamin D levels have been linked to increased mortality[5], cardiovascular disease[5-6], hypertension[6], cancer[5-7], diabetes[6], infectious diseases[5], fractures[6], falls[6], cognitive decline[8], and mood disorders.[9]


Zhang and Giovanucci (2011) advocate that epidemiological studies support a 20-30% reduction in cancer risk when vitamin D levels are adequate.[10] The most frequently referred to mechanism is increased cell trafficking of calcium ions into cancer cells to levels that arrest cell proliferation and induce apoptosis.[11] Additionally, Fleet et al. (2012) suggest possible roles for vitamin D in enhancing DNA repair mechanisms, antioxidant protection, and in immunomodulation.[12] Alternately; Chlebowski (2011) argues that there is insufficient evidence to support the use of vitamin D supplements to prevent or treat cancer[13], and some researchers urge caution as high vitamin D levels have been associated with vascular calcifications[6], pancreatic cancer[6], and breast cancer.[14]


Low vitamin D levels were associated with increased rates of post-operative complications and adverse outcomes in 28 of 31 studies in a recent review.[15] Low vitamin D levels were associated with increased rates of graft and transplant rejections, decreased strength and joint mobility, hypertension, bacterial and viral infection, increased length of hospital stay, and mortality due to all-causes.  Low vitamin D levels have been associated with adverse post-operative outcomes in parathyroidectomy[16], hip and knee arthroplasty, gastric bypass, non-transplant cardiac surgery, and transplant cardiac, liver, kidney and lung surgeries.[15] A placebo controlled trial in 218 Australians aged 65 years and older reported that pain scores after hip fracture surgery were inversely associated with vitamin D levels.[17]


Previous studies of vitamin D levels and surgical outcomes have lacked sufficient controls for potential confounders.  Poor vitamin D status may be a surrogate marker for poor diet, seasonal variation, or sun avoidance habits.  Additionally; there is limited information currently available to inform the choice of supplementation (dietary intervention, supplements and/or sun exposure) or level of supplementation before and/or after surgery.  Thirdly, information for the Australian population has come from studies of older Australians and patients treated for hip fracture.  There is a need to study the impacts of vitamin D status on surgical outcomes in patients from the local region in all age groups, and especially those treated for bowel complaints where vitamin D intake from food and supplements may be compromised.






[1]  Holick MF.  Sunlight “D”ilemma: risk of skin cancer or bone disease and muscle weakness.  The Lancet.  2001; 357: 4-5.

[2]  National Health and Medical Research Council.  Nutrient Reference Values for Australia and New Zealand. 2006; 127-38.  ISBN Online 1864962437.

[3]  Pasco JA, Henry MJ, Kotowicz MA, Sanders KM, Seeman E, Pasco JR, Schneider HG, Nicholson GC. Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures: the Geelong Osteoporosis Study. J Bone Miner Res. 2004; 19: 752–8.

[4]  Hadjidakis DJ, Androulakis II.  Bone Remodeling.  Ann N Y Acad Sci.  2006; 1092: 385-96.

[5]  Perez-Lopez FR, Fernandez-Alonso AM, Mannella P, Chedraui P.  Vitamin D, sunlight and longevity.  Minerva Endocrinol.  2011; 36(3): 257-66.

[6]  Melamed ML, Manson JE.  Vitamin D and cardiovascular disease and cancer: not too much and not too little? The need for clinical trials.  Womens Health.  2011; 7(4): 419-24.

[7]  Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H.  Meta-analysis: Serum vitamin D and colorectal adenoma risk.  Prev Med. 2011; 53(1): 10-6.

[8]  Soni M, Kos K, Lang IA, Jones K, Melzer D, Llewellyn DJ.  Vitamin D and cognitive function.  Scand J Clin Lab Invest Suppl.  2012; 243: 79-82.

[9]  Tariq MM, Streeten EA, Smith HA, Sleemi A, Khabazghazvini B, Vaswani D, Postolache TT.  Vitamin D: a potential role in reducing suicide risk?  Int J Adolesc Med Health.  2011; 23(3): 157-65.

[10] Zhang X, Giovannucci E.  Calcium, vitamin D and colorectal cancer chemoprevention.  Best Pract Res Clin Gastroenterol. 2011; 25(4): 485-94.

[11] Sergeev IN.  Vitamin D and cellular Ca2+ signalling in breast cancer.  Anticancer Res. 2012; 32(1): 299-302.

[12] Fleet JC, DeSmet M, Johnson R, Li Y.  Vitamin D and cancer: a review of molecular mechanisms.  Biochem J.  2012; 441(1): 61-76.

[13] Chlebowski RT.  Vitamin D and breast cancer: interpreting current evidence.  Breast Cancer Res.  2011; 13(4): 217. 

[14] Lazzeroni M, Gandini S, Puntoni M, Bonanni B, Gennari A, DeCensi A.  The science behind vitamins and natural compounds for breast cancer prevention.  Getting the most prevention out of it.  Breast.  2011; 20(3): S36-41.

[15] Iglar PJ, Hogan KJ.  Vitamin D status and surgical outcomes: a systematic review.  Patient Safety in Surgery.  2015; 9: 14-23.

[16] Nuti R, Merlotti D, Gennari L.  Vitamin D deficiency and primary hyperparathyroidism.  J Endocrinol Invest.  2011; 34(7): 45-9.

[17] Mak JC, Klein LA, Finnegan T, Mason RS, Cameron ID.  An initial loading-dose vitamin D versus placebo after hip fracture surgery: baseline characteristics of a randomized controlled trial (REVITAHIP).  BMF Geriatr.  2014; 14: 101-8.

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