Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors.

BACKGROUND & AIMS: Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age 50. METHODS: We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among women enrolled in the Nurses' Health Study II. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset CRC were estimated with Cox proportional hazards model. Multivariable-adjusted odds ratios (ORs) and 95% CIs for early-onset conventional adenoma and serrated polyp were estimated with logistic regression model. RESULTS: We documented 111 incident cases of early-onset CRC during 1,250,560 person-years of follow-up (1991 to 2015). Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC (HR for ≥450 IU/day vs <300 IU/day, 0.49; 95% CI, 0.26-0.93; P for trend = .01). The HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83). The inverse association was significant and appeared more evident for dietary sources of vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). For CRC precursors, the ORs per 400 IU/day increase were 0.76 (95% CI, 0.65-0.88) for conventional adenoma (n = 1,439) and 0.85 (95% CI, 0.75-0.97) for serrated polyp (n = 1,878). CONCLUSIONS: In a cohort of younger women, higher total vitamin D intake was associated with decreased risks of early-onset CRC and precursors.

Vitamin D Status and Cancer Incidence, Survival, and Mortality.

Over the last several decades, extensive research on vitamin D and its role on cancer incidence, cancer survival (survival or mortality from cancer among individuals diagnosed with cancer), and cancer mortality (fatal cases occurring during the study period in an initially cancer-free population) has been conducted. A variety of study designs were implemented to explore vitamin D status, assessed by measuring sun exposure, vitamin D intake, and circulating 25-hydroxyvitamin D (25(OH)D) concentration. Although not many randomized controlled trials have examined the relationship between vitamin D and cancer incidence, observational studies have consistently shown a protective association between vitamin D and cancer incidence, especially for colorectal cancer. In addition, randomized controlled trials and most observational studies suggested that vitamin D plays a role in reducing cancer mortality. The potential benefit of vitamin D on cancer mortality may operate during the pre-diagnostic stages by affecting late-stage tumor progression and metastatic seeding, during the treatment phase by complementing or enhancing effects of therapies, or during the post-diagnostic stages. However, further studies are needed to confirm these conclusions, establish the optimal dosage and timing of vitamin D intakes for the most benefit, find which cancer types are affected, and understand the underlying mechanisms.

Obesity and efficacy of vitamin D3 supplementation in healthy black adults.

PURPOSE: Results from recent clinical trials suggest that vitamin D efficacy against cancer may be influenced by body mass index. As suppression of parathyroid hormone (PTH) is one indicator of vitamin D efficacy, we examined to what extent doses of vitamin D3 supplementation suppress PTH levels in individuals with and without obesity. METHODS: A total of 328 healthy African Americans were randomized into the following four groups and treated for 3 months: placebo, 1,000, 2,000, or 4,000 IU/day of vitamin D3 supplementation. RESULTS: Among the participants, 250 individuals with PTH measurements were included in the analysis. Obese individuals (n = 141) experienced a steep reduction of 3-month PTH from placebo to 1,000 IU/day of vitamin D3 supplementation, but no further reduction at 2,000 or 4,000 IU/day. For non-obese individuals (n = 109), the reduction of 3-month PTH was approximately linear for increasing vitamin D3 doses. At supplementation of 2,000 to 4,000 IU/day, 3-month 25(OH)vitamin D levels were high in both non-obese and obese individuals, but the 3-month PTH levels remained about 10 pg/mL higher in individuals with obesity. CONCLUSION: Our findings suggest that excess adiposity confers resistance to vitamin D efficacy in suppressing PTH levels, even when given at high doses.

Garlic intake and gastric cancer risk: Results from two large prospective US cohort studies.

Although many case-control studies suggested that garlic intake may reduce gastric cancer risk, evidence from prospective cohort studies has been lacking. We examined the association between garlic intake and subsequent risk of gastric cancer among 77,086 women in the Nurses' Health Study (1984-2014) and 46,398 men in the Health Professionals Follow-Up Study (1986-2014). Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. We additionally examined garlic intake in relation to Helicobacter pylori (H. pylori) infection among 613 participants using logistic regression. During up to 30 years of follow-up, 292 participants were diagnosed with gastric cancer. The pooled multivariable RR of gastric cancer among participants who ate garlic, as compared to those who did not, were 1.11 (95% CI = 0.81-1.51) for the intake of garlic less than once per week, 0.98 (95% CI = 0.71-1.36) for one to four times per week and 1.39 (95% CI = 0.89-2.17) for five or more times per week (p for trend = 0.23). Similarly, no statistically significant association was observed cross-sectionally between garlic intake and H. pylori infection (comparing five or more times per week to never, pooled multivariable odds ratio = 1.66, 95% CI = 0.89-3.09; p for trend = 0.11). The findings from this large prospective study do not support the hypothesis that high garlic intake reduces risk of gastric cancer.

Antiobesity and Antidiabetes Effects of a Cudrania tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential.

Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate. Cudrania tricuspidata leaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity.