benefits of vitamin d for cancer and pregnancy/birth … f036...benefits of vitamin d for cancer and...
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Benefits of Vitamin D for Cancer and Pregnancy/Birth Outcomes
William B. Grant, PhDSunlight, Nutrition and Health Research
Center, San Francisco
Disclosure• I receive funding from Bio‐Tech Pharmacal, Inc. (Fayetteville, AR)
• I serve on the board of directors of VitaminDCouncil.org (San Luis Obispo, CA)
• I am a scientific advisor to GrassrootsHealth.net (Encinitas, CA)
Outline• Vitamin D pathways• Cancer: UVB exposure and vitamin D
– Geographical ecological studies– Observational studies– Studies of mechanisms– Clinical trials
• Pregnancy/birth outcomes and vitamin D– Beneficial outcomes found– Observational studies– Clinical trial demonstrating beneficial effect
Colon Cancer Mortality Rates, White Males 1970‐94
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0Garland et al.,Am J Public Health. 2006
The brothers Cedric and Frank Garland published their seminal paper in 1980
High doses in SW due to thinner stratospheric ozone layer and higher surface elevation.
Data from the NASA Total Ozone Mapping Spectrometer (TOMS)
Breast Cancer Mortality Rates, White Females, 2000‐04
Less pronounced geographicalvariation with respect to solar UVB doses due to less time in the sun, use of sunscreen,increased risk from other factors such as obesity, and improved survival rates.
All less Lung Cancer vs. UVB Index by Occupation in Nordic Countries
28% higher incidence rate for most indoor vs. most outdoor work. For men, the UVB index (lip cancer less lung cancer) was significantly inversely correlated with 14 types of internal cancer.Grant WB. Role of solar UV irradiance and smoking in cancer as inferred from cancer incidence rates by occupation in Nordic countries. Dermatoendocrinol. 2012;4(2):203‐11.
16 UVB/Vitamin D‐Sensitive Cancers from Ecological Studies
• Vitamin D‐sensitive cancers with strong support from ecological studies in six mid‐latitude plus Nordic countries after accounting for other factors:– Gastrointestinal: colon, esophageal, gallbladder, gastric, intestinal, rectal
– Urinary tract: bladder, kidney– Female: breast, cervical, endometrial, ovarian, vulvar– Blood: non‐Hodgkin’s lymphoma– Miscellaneous: laryngeal, lung
Graph of odds ratio for breast cancer incidence vs. 25(OH)D concentration from 11 case‐control studies.
Grant WB, Boucher BJ (2017) PLOS ONE 12(5): e0176448.
All‐Cancer Mortality Rate vs. Serum 25(OH)D Concentration
The cancer mortality rate for 8 ng/ml is 36% (95% CI, 6%, 74%) higher than for 50 ng/ml.
Gaksch M, et al. Vitamin D and mortality: Individual participant data meta‐analysis of standardized 25‐hydroxyvitamin D in 26916 individuals from a European consortium. PLoS One. 2017 Feb 16;12(2):e01707910.6
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25(OH)D (ng/ml)
All‐cause and Cancer Survival vs. Baseline 25(OH)D ‐ Norway
Results of a 9‐yr study. Significantly reduced cancer‐specific mortality rate for 25OHD trend for breast and lung cancer, and lymphoma.Tretli S, et al.Cancer Causes Control. 2012;23(2):363‐70.
Mechanisms• Mechanisms whereby vitamin D reduces risk are based on genetic actions of 1,25(OH)2D and include: – Cellular – effects on differentiation, proliferation and apoptosis
– Reduced inflammation– Reduced angiogenesis around tumors– Reduced metastasis
Creighton University Clinical Trial• Trial with 2303 postmenopausal women in Nebraska with mean BMI = 30 kg/m2, baseline 25(OH)D of 33 ng/ml, given 2000 IU/d vitamin D3 plus 1.5 g/d calcium or placebo, and followed for 4 yrs.
• By intention to treat, HR = 0.70 (95% CI, 0.47, 1.02, P = 0.06). (one extra case in treatment arm)
• Lappe et al., Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA 2017
All‐Cause Mortality Rate vs. 25(OH)D Meta‐analysis
Results from 32 studies were included.All‐cause mortality rate rose nearly linearly below 38 ng/ml.Garland et al., Am J Pub Health, 2014
Pregnancy and Birth Outcomes• Maternal vitamin D deficiency is linked to increased risk of gestational diabetes, pre‐eclampsia, primary C‐section, preterm birth.
• For the offspring, increased risk of asthma, autism, other neurological disorders, rickets.
Skin Pigmentation• Skin pigmentation has adapted to where people live for
many generations.• The driving factors are vitamin D production,
protection against DNA damage and folate production.• Jablonski NG. Human skin pigmentation as an example of adaptive
evolution. Proc Am Philos Soc. 2012 Mar;156(1):45‐57. • Grant WB. The UVB‐vitamin D3‐skin pigmentation is alive and well.
Am J Phys Anthro. 2016 Dec; 61(4):752‐755.
Primary Cesarean‐Section DeliveryMerewood A, et al. Association between vitamin D deficiency and primary cesarean section. J Clin Endocrinol Metab. 2009 Mar;94(3):940‐5.
Development of Asthma/Recurrent Wheeze vs. Vitamin D Treatment
Kaplan–Meier survival estimates for the effect of vitamin D treatment during pregnancy on the development of asthma/recurrent wheeze by age 3 year analyzed in an intent‐to‐treat format. Hollis & Wagner, 2017.
Reduced Risk of Preterm BirthOver 1000 women were enrolled and given free vitamin D supplements with the goal of achieving >40 ng/ml 25(OH)D.
McDonnell SL, et al. Maternal 25(OH)D concentrations ≥40 ng/mLassociated with 60% lower preterm birth risk among general obstetrical patients at an urban medical center. PLoS One. 2017 Jul 24;12(7): e0180483.
Trial involving women in South Carolina given 400, 2000, or 4000 IU/d vitamin D3 starting at 12th week of pregnancy.Hollis BW, et al. Vitamin Dsupplementation duringpregnancy: double‐blind, randomized clinical trial of safety and effectiveness.J Bone Miner Res. 2011 Oct;26(10):2341‐57.