High level of circulating vitamin D during neoadjuvant therapy may lower risk of metastatic progression in high-risk rectal cancer.

BACKGROUND: Following curative-intent neoadjuvant therapy in locally advanced rectal cancer, metastatic progression is still dominant. We investigated if patients' circulating 25-hydroxyvitamin D [25(OH)D] levels were associated with outcome. METHODS: Serum 25(OH)D concentration was assessed by liquid chromatography-mass spectrometry in samples collected from 84 patients at baseline, completion of the neoadjuvant therapy, and treatment evaluation before surgery, and analyzed with respect to season, disease presentation, and treatment effects. RESULTS: In the cohort of patients residing at latitude 58-62°N, baseline 25(OH)D differed significantly over the seasons, with highest measures (mean of 71.2 ± 5.6 nmol/L) in summer and lowest (48.7 ± 4.5 nmol/L) in spring, and changed over the three-month neoadjuvant period till response evaluation solely owing to season. The patient subgroup with slightly reduced performance status, anemia, and T4 disease that did not respond to the neoadjuvant therapy (ypT4 cases), had significantly lower baseline 25(OH)D (below 50 nmol/L) than T4 cases with response (ypT0-3) and T2-3 cases (above 60 nmol/L). Compared to the T4 patients with levels above 50 nmol/L, regarded as sufficient for a healthy bone status, those presenting levels below had significantly heightened risk of disease progression (mainly metastasis) and death, with hazard ratio of 3 and 17, respectively, on adjustment for age, sex, body mass index, and season. CONCLUSION: Rectal cancer T4 cases had high risk of metastatic progression and death if circulating 25(OH)D levels were insufficient but obtained short-term and long-term outcome to neoadjuvant treatment no worse than patients with T2-3 disease when 25(OH)D was sufficient. TRIAL REGISTRATION: ClinicalTrials.gov NCT00278694 ; registration date: 16 January 2006, retrospective to enrollment of the first 10 patients of the current report.

Influence of multiple UV exposures on serum cobalamin and vitamin D levels in healthy females.

AIMS: Ultraviolet (UV) radiation is a major source for vitamin D production. Furthermore, UV destroys cobalamins (also called vitamin B12) in solution. However, data from humans are scarce. The aim of the present study was to clarify if UV exposure has any effect on serum cobalamins, as compared to vitamin D levels, in healthy volunteers. METHODS: This single-center, open observational study was conducted in a research institute: 23 non-pregnant, non-lactating, healthy, fair-skinned female subjects had their serum cobalamin and 25-hydroxyvitamin D (25(OH)D, the marker for vitamin D status) levels measured before and after exposure to UV. RESULTS: UV exposure increased serum 25(OH)D levels from 61.6 nmol/L to 88.5 nmol/L (44%; p < 0.001). A statistically insignificant decay in serum cobalamin levels from 300 pmol/L to 260 pmol/L (13%; p = 0.142) was observed in the volunteers after the first UV exposure; however, no additional decline of statistical significance was seen after subsequent exposures. CONCLUSIONS: Multiple exposure to UV radiation give a significant increase in 25(OH)D levels, but has no detrimental effect on cobalamin concentrations.

Vitamin D status in healthy Romanian caregivers and risk of respiratory infections.

OBJECTIVES: To investigate the vitamin D status during winter of a healthy population of hospital employees and to assess the correlation between vitamin D status and risk of infections in the upper respiratory tract. DESIGN: One hundred and ten healthy volunteers answered a questionnaire on their solar exposure habits and vitamin D intake and delivered one blood sample for quantification of vitamin D level (serum 25-hydroxyvitamin D (25(OH)D) concentration) during December 2007-January 2008. At the end of the winter we screened for the occurrence of respiratory infections and sought associations with vitamin D status. SETTING: Bucharest, Romania, 45°N. SUBJECTS: One hundred and ten healthy hospital employees. RESULTS: Eighty per cent of participants were vitamin D deficient (25(OH)D level below 50 nmol/l). The main determinant of serum 25(OH)D was sun exposure during the summer previous to the study (P = 0·02 in multivariate analysis). Intake of vitamin D, BMI and age played no significant role for the level of 25(OH)D. Overall we found a non-significant negative correlation between 25(OH)D level and new cases of infection (Spearman correlation coefficient of -0·12, P = 0·2). CONCLUSIONS: Vitamin D status is alarmingly poor in active, relatively young women residing in Romania. If our results are reproduced by other investigations, action to improve vitamin D status at the population level is necessary. We were not able to show a statistically significant relationship between vitamin D status and infection risk in our material.

Serum 25-hydroxyvitamin D is a predictor of serum 1,25-dihydroxyvitamin D in overweight and obese patients.

Recent research suggests that 1,25-dihydroxyvitamin D [1,25(OH)(2)D], a steroid hormone that regulates calcium homeostasis, may also play a role in the development and progression of cancer, multiple sclerosis, cardiovascular, and other diseases. Decreased serum 1,25(OH)(2)D concentrations are often observed in overweight and obese patients. However, little is known about the factors that may influence 1,25(OH)(2)D renal synthesis, because it is generally accepted that serum 1,25(OH)(2)D concentration is strictly regulated by parathyroid hormone and serum concentrations of calcium and phosphorus. In this study, the associations among serum 1,25(OH)(2)D, serum 25-hydroxyvitamin D [25(OH)D], and body composition were analyzed in 1779 patients with excess body weight registered in a Metabolic and Medical Lifestyle Management Clinic in Oslo, Norway. According to our results, serum 25(OH)D, adiposity, age, season of blood sampling, and gender directly influence serum 1,25(OH)(2)D (r = 0.33; P < 0.001), with serum 25(OH)D being the strongest predictor for serum 1,25(OH)(2)D. The 1,25(OH)(2)D concentrations were 25.4 pmol/L (95% Cl: 19.3-31.5; P < 0.001) lower in the lowest 25(OH)D quartile to compared with highest quartile. A seasonal variation was observed for both vitamin D metabolites. Thus, our results suggest that in patients with excess body weight, serum 1,25(OH)(2)D concentrations were associated with 25(OH)D and varied during the year. Therefore, it may also be valuable to measure both serum 25(OH)D and 1,25(OH)(2)D for the evaluation of vitamin D status in overweight and obese persons.

Vitamin D status in Norwegian children and adolescents with excess body weight.

OBJECTIVES: The prevalence of childhood and adolescent obesity has increased during the past decades. A high body mass index (BMI) is associated with a low vitamin D status. The purpose of this study was to determine the prevalence of vitamin D deficiency and insufficiency in Norwegian children and adolescents with excess body weight. METHODS: Vitamin D status and seasonal variations of 25(OH)D and 1,25(OH)(2)D were analyzed in 102 children and adolescents (70 girls and 32 boys), 8-19 yr of age, with overweight and obesity. RESULTS: Overall, 50% of the children and adolescents included in the study had a low vitamin D status (25(OH)D <75 nmol/L) and 19% had vitamin D deficiency (25(OH)D <50 nmol/L). This was most prevalent in adolescents. Only 42% of teenagers had 25(OH)D levels ≥75 nmol/L vs. 72% of preteens. Both 25(OH)D and 1,25(OH)(2)D showed seasonal variations. A peak in serum 25(OH)D concentrations was observed during the summer while the lowest values were seen during the spring. In contrast, serum 1,25(OH)(2)D had a peak during the spring and the lowest concentrations during the winter. CONCLUSIONS: The prevalence of vitamin D deficiency and insufficiency is higher in obese and overweight adolescents than in overweight children. This might be related to low outdoor activities and low vitamin D intake in teenagers. Seasonal variations of both the vitamin D metabolites were observed.

Latitude gradient for melanoma incidence by anatomic site and gender in Norway 1966-2007.

Latitude gradients and time trends for cutaneous malignant melanoma (CMM) were analyzed using incident cases from the Norwegian Cancer Registry for the period 1966-2007. Sex and various anatomic regions of the body were taken into account, for better understanding of the role of ultraviolet radiation in CMM etiology. There is a latitude gradient for CMM on all body sites included in the present study, with 2-2.5 times higher incidence rates in the south. The latitude gradients seem to be largest for the trunk. Melanomas on sites intermittently exposed to the sun (like the trunk) dominate both in the north and in the south and this distribution has not changed over the years. A leveling off of the incidence rates are observed for both sexes and for all sites studied, after 1985-1995, slightly more in the south than in the north, except for the head and neck where the incidence rates have continued to increase slowly in the north as well as in the south. The leveling off of melanoma trend is probably associated with melanoma prevention campaigns and with increasing awareness, although vitamin D could play a role.

Where the sun does not shine: is sunshine protective against melanoma of the vulva?

Intermittent sun exposure and sunburn are strong predictors of cutaneous malignant melanoma (CMM). On the other hand, melanomas may arise also in non-sun-exposed areas such as the vulva. However, little is known about a possible relationship between sun exposure and vulvar melanoma. Temporal and latitudinal dependencies of the incidence rates of vulvar melanoma were studied in comparison with those of CMM among Caucasians in Sweden, East Germany, USA and Victoria (Australia). The ratios of vulvar melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. The incidence rates of CMM have increased with time until recently, while those of vulvar melanoma have either decreased or remain constant. In USA vulvar melanoma incidence rates seem to increase from south to north, while for CMM incidence rates on sun exposed skin areas decrease from south to north. Comparison of latitudinal trends of the incidence rates of vulvar melanomas and CMM show opposite trends. Whenever CMM rates increase, either with time or with decreasing latitude (indicating increased sun exposure) the ratio of vulvar melanoma rates to CMM rates on exposed skin, seem to decrease. Thus, latitudinal trends seem to support the assumption that vulvar melanomas are not generated by UV radiation, and the possibility exists that solar UV radiation, probably via its role in vitamin D photosynthesis in exposed skin, may have a protective effect against vulvar melanoma and should be further investigated.

Time trends and latitude dependence of uveal and cutaneous malignant melanoma induced by solar radiation.

In order to evaluate the role of solar radiation in uveal melanoma etiology, the time and latitude dependency of the incidence rates of this melanoma type were studied in comparison with those of cutaneous malignant melanoma (CMM). Norway and several other countries with Caucasian populations were included. there is a marked north-south gradient of the incidence rates of CMM in Norway, with three times higher rates in the south than in the north. No such gradient is found for uveal melanoma. Similar findings have been published for CMM in other Caucasian populations, with the exception of Europe as a whole. In most populations the ratios of uveal melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. This is also true for Europe, in spite of the fact that in this region there is an inverse latitude gradient of CMM, with higher rates in the north than in the south.In Norway the incidence rates of CMM have increased until about 1990 but have been constant or even decreased (for young people) after that time, indicating constant or decreasing sun exposure. The uveal melanoma rates have been increasing after 1990. In most other populations the incidence rates of CMM have been increasing until recently while those of uveal melanoma have been decreasing. These data generally support the assumption that uveal melanomas are not generated by ultraviolet (UV) radiation and that solar UV, via its role in vitamin D photosynthesis, may have a protective effect.

Obesity and increased risk of cancer: does decrease of serum 25-hydroxyvitamin D level with increasing body mass index explain some of the association?

Low levels of vitamin D and excess body weight are both factors associated with increased risk of cancer. The increased risk seems to be proportional to the increase in BMI, and to decrease in serum 25-hydroxyvitamin D (25(OH)D) level. Our earlier investigations suggest that serum 25(OH)D levels decrease with increasing BMI. Although the connection between cancer risk, BMI and vitamin D status might be arbitrary, it has not been discussed in the literature so far. In this study, we analyze data published in current meta-analysis, prospective studies, and systematic reviews on cancer-specific risk attributed to high BMI and low vitamin D status. The contribution of low 25(OH)D levels associated with high BMI to increased cancer risk was calculated for 13 vitamin-D-sensitive cancers with a focus on colorectal and breast cancer as the most frequently studied vitamin-D-sensitive cancer types. Our study suggests that a low vitamin D status may explain at least 20% of the cancer risk attributable to high BMI. The contribution of low 25(OH)D to the increased cancer risk with increasing BMI may be different for different cancer types. Thus, we find 40% for breast cancer, and 26 and 75% for colorectal cancer in men and women, respectively.

Estimated benefit of increased vitamin D status in reducing the economic burden of disease in western Europe.

Vitamin D has important benefits in reducing the risk of many conditions and diseases. Those diseases for which the benefits are well supported and that have large economic effects include many types of cancer, cardiovascular diseases, diabetes mellitus, several bacterial and viral infections, and autoimmune diseases such as multiple sclerosis. Europeans generally have low serum 25-hydroxyvitamin D [25(OH)D] levels owing to the high latitudes, largely indoor living, low natural dietary sources of vitamin D such as cold-water ocean fish, and lack of effective vitamin D fortification of food in most countries. Vitamin D dose-disease response relations were estimated from observational studies and randomized controlled trials. The reduction in direct plus indirect economic burden of disease was based on increasing the mean serum 25(OH)D level to 40 ng/mL, which could be achieved by a daily intake of 2000-3000 IU of vitamin D. For 2007, the reduction is estimated at euro187,000 million/year. The estimated cost of 2000-3000 IU of vitamin D3/day along with ancillary costs such as education and testing might be about euro10,000 million/year. Sources of vitamin D could include a combination of food fortification, supplements, and natural and artificial UVB irradiation, if properly acquired. Additional randomized controlled trials are warranted to evaluate the benefits and risks of vitamin D supplementation. However, steps to increase serum 25(OH)D levels can be implemented now based on what is already known.