Table of contents
- Serum 25-Hydroxyvitamin D Concentrations >40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study
295 Cancer articles - More Cancers if poor Vitamin D Receptor
- Extrapolation to ZERO incidence of 3 types of Cancer at 104 nanograms
- Description in newsletter from Grassroots Health
- 159 citations of this study as of Dec 2022
Serum 25-Hydroxyvitamin D Concentrations >40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study
Sharon L. McDonnell1 sharon at grassrootshealth.org, Carole Baggerly1, Christine B. French1, Leo L. Baggerly1, Cedric F. Garland2, Edward D. Gorham2, Joan M. Lappe3, Robert P. Heaney3
1 GrassrootsHealth, Encinitas, California, United States of America,
2 Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California, United States of America,
3 Department of Medicine, Creighton University, Omaha, Nebraska, United States of AmericaVitaminDWikiNice integration of data from two data sources
Considers many non-skin cancers - mainly Breast CancerVitaminDWiki observation - Many possible problems with this study
The Grassroots cohert is expected to have a healthy lifestyle, which will tend to include
- Supplementing with vitamin D or getting lots of sunshine
- Paying about $100/year to monitor just the vitamin D portion of their health
Thus they have higher income level, live near green area, and probably better eduction - Probably also taking cofactors such as Magnesium, Omega-3, Vitamin K2, etc
Each of these cofactors increase vitamin D benefits to cells - sometimes in ways that cannot be mearued by Vitamin D tests - Less obese than the general population? (Less obesity is associated with less risk of cancerf
- Smoke far less that the average (3% vs 30% globally)
less smoke ==> less cancers, not just less lung cancer
_Note: Smoking reduces vitamin D - many studies
Grassootshealth was also probably unaware of many cancers in their cohort
- Because the participants were embarresed about getting the Cancer
- Participants were too distracted by the Cancer so failed to report
- Participants quickly died of the Cancer/ Fast cancers include; Merkel cell, pancreatic
VitaminDWiki opinion: More likely a 30% reduction in real-world cancers for 40 ng
Note should it be > 60 ng rather than just 40ng?
- The study appears to consider 40 nanograms to be a good level
- The data shows ZERO cancers for vitamin D levels above 60 nanograms
- Wonder if the target level should be > 60 nanograms rather than 40 nanograms
- The curve which shows increasing risk of cancer for > 60 nanograms appears to be just due to the matching of the data to a constant +expodent. Matching the curve using more than 2 variables would not show an increase of cancer with higher levels of vitamin D
Figure F1Al
See also VitaminDWiki- 'Cancer Screening Has Never Saved Lives' (but Vitamin D supplementation does) - Jan 2016
- Off topic – More money to be made in TREATING cancer than PREVENTING it – NYT Dec 2015
- Vitamin D does not improve cancer survival much – when dose size, etc. is ignored – Oct 2015
- Cancer deaths of senior women 60 percent more likely if low Vitamin D – March 2015
Similar to conclusion of the study on this page - Cancer incidence in 87 countries is related to food, smoking, alcohol, GDP, and UVB - Jan 2014
- Cancer Survival is poor if vitamin D is less than 20ng (every study showed benefit)– review Nov 2013
Vitamin D both PREVENTS and TREATS many cancers - Vitamin d - pivotal nutraceutical in the regulation of cancer metastasis and angiogenesis. – 2013
Vitamin D also reduces the spread of cancer - 6X less Breast Cancer if have even minimal vitamin D – July 2013
- Children with Cancer were 3X more likely to be vitamin D deficient – July 2013
Vitamin D even helps even non- adults - 85 percent less risk of death from Breast Cancer when vitamin D levels higher than 30 ng – May 2012
Note - this is death, not just incidence - Hypothesis – anticancer benefits from synergy of omega-3 and vitamin D – May 2011
- Breast cancer – reduced proliferation with Vitamin K2 in lab – May 2015
- Cancer risk and survival improved by increasing vitamin D or UVB – April 2016 Grant
- Is 50 ng of vitamin D too high, just right, or not enough
- Vitamin D and Cancer – Special issue Jan 2013
Some influences of Omega-3 and Magnesium ARE NOT SEEN by Vitamin D tests
click on chart for details
Cancer category in VitaminDWiki starts with the following- Cancer
295 items Overview Cancer and vitamin D - Cancer and Vitamin D - many studies
- After Cancer Diagnosis
114 items - Bladder Cancer
28 items - Breast Cancer
259 items Overview Breast Cancer and Vitamin D - Colon Cancer
145 items Overview Cancer-Colon and vitamin D - Leukemia
19 items - Liver Cancer
17 items - Lung Cancer
55 items Overview Lung cancer and vitamin D - Lymphoma Cancer
26 items - Other Cancer
66 items - Ovarian Cancer
26 items - Pancreatic Cancer
58 items - Prostate Cancer
103 items Overview Prostate Cancer and Vitamin D - Skin Cancer
121 items Overview Suntan, melanoma and vitamin D - Childhood Cancers - Vitamin D can help - many studies
- Easiest way to treat cancer – take Vitamin D – Nov 2022
- 13 Cancers are helped by Vitamin D – Biobank July 2023
- 2X increase of 14 cancers in non-seniors in 20 years (low vitamin D) – Sept 2022
- Vitamin D prevents and treats cancer in many ways – May 2021
- Those with recent cancer diagnosis had 7X increased risk of COVID-19 (more if A-A )- Dec 2020
- Deaths from many types of Cancer associated with low vitamin D- review of meta-analyses Sept 2020
- Cancer incidence and mortality is decreased if 40-60 ng of Vitamin D – April 2019
- 8 ways that Cancer might be prevented by Vitamin D - June 2019
- Cancer stem cells and Vitamin D - many studies
- Vitamin D Reduces Cancer Risk - Why Scientists Accept It but Physicians Do Not - Feb 2019
- Overview of Vitamin D Actions in Cancer – 31 page chapter in a book – 2018
- Vitamin D prevents breast cancer, reduces BC mortality, and reduces BC chemotherapy problems – Sept 2018
- Diagnosed with breast cancer – take vitamin D to cut chance of death by half – July 2018
- Melanoma 25 X more likely if low vitamin D – Feb 2018
- Better Cancer survival if higher vitamin D a decade earlier (esp. Melanoma, Kidney, Prostate)– Aug 2018
295 Cancer articles - wiki page:
- Vitamins fight cancer: 9 of the 10 most cited studies were for Vitamin D - Dec 2024
- Vitamin D Roles - more than just help the immune system
- Vitamin D for all senior Germans would cost-effectively prevent 30,000 cancer deaths annually - March 2021
- Obese person with a cancer is 1.7 X higher risk of subsequent Kidney Cancer (low vitamin D) - Oct 2024
- Cancer prevention starts with 30 ng of Vitamin D – Sept 2024
- Incidence of many cancers increased 1.5 X in a generation – June 2024
- Vitamin D might be fighting some cancers by increasing good microbiota – May 2024
- Cancers take years to develop, but already have 36 COVID vaccination suspected cancers - May 2024
- Cancers are prevented by Vitamins D etc (Gynecological Cancer in this case) – May 2024
- Fewer deaths (All-cause, Cardiovascular, Cancer) when Vitamin D levels are above 36 ng – April 2024
- More Evidence Showing Vitamin D Combats Cancer - Mercola May 2024
- 23 Cancers in the US are associated with low UVB - Grant April 2024
- Vitamin D can be inside of a “trojan horse” nanoball made of folate, Cancer cells attrack folate – April 2024
- Keytruda (175,000 dollars per year) fights some cancers, Vitamin D reduces how much Keytruda is needed
- Magnesium and Cancer - many studies
- The Science of Magnesium and Its Role in Aging and Disease - Patrick March 2024
- Most Common Cancers per country
- Increased risk of early-onset Solid Cancer if family member had one: 7.3X if black, 3 X if white – June 2021
- 30% increase in early-onset cancers expected in a decade – March 2023
- Calcium often reduces the risk of health problems such as Colorectal Cancer – March 2024
- Vitamin D: Viral infections, Infectious diseases, EBV and MS, Virus and Cancers – Grant March 2024
- Predicted US Cancer statistics for 2024 - Feb 2024
- Vitamin D and Cancer - Jan 2024
- Vitamin D and Cancer (portions of a book chapter) - Jan 2024
- Childhood Cancers - Vitamin D can help - many studies
- 79% increase in cancer under age 50 in 3 decades - Sept 2023
- People with Cancer having more than 30 ng of Vitamin D are 40% less likely to die (of any cause) – Nov 2023
- Cancers reduced after 2 years of 2000 IU Vitamin D daily (2nd RCT) – RCT Aug
- Much more likely to survive cancer if more than 20 ng of Vitamin D - Oct 2023
- Cancer Metabolism might be fought by many things – such as vitamin D – Oct 2023
- Multiple COVID vaccinations might increase Cancer Incidence - many studies
- Vitamin D fortification in Europe preventing 27,000 Cancer deaths, could prevent 129,000 – May 2022
- Vitamin D restricts new capillary growth (angiogenesis) in fat and cancers
- 13 Cancers are helped by Vitamin D – Biobank July 2023
- Global burden of brain disorders surpasses cardiovascular disease and cancer - July 2023
- Cancer Treatments - vitamin D is one of the 30 alternatives - June 2023
- Inflammation associated with Cancer reduced by Vitamin D – meta-analysis May 2023
- 11 cancers fought by Vitamin D - mini review April 2023
- Vitamin K2 fights Breast and some other cancers - many studies
- 100 years since the discovery of Vitamin D - 23 studies - 2022, 2023
- Restore your Vitamin D levels before surgery (Gastric Cancer in this case) - Jan 2023
- Only 1 in 7 cancers are found by screening (but 2 in 7 are prevented by Vitamin D) – Dec 2022
- Cancers fought by Garlic, Onion, and Sulfur - several studies
- Cancer incidence or mortality not changed by small Vitamin D doses: 2021-2023
- Cancer and Vitamin D - many studies
- 3,200 IU of daily not help much in population already having 30 ng of Vitamin D – RCT Jan 2022
- 2X increase of 14 cancers in non-seniors in 20 years (low vitamin D) – Sept 2022
- USPSTF says no evidence that Vitamins prevent CVD or Cancer (data disagrees) Aug 2022
- Cancers are associated with low vitamin D, poor vaccination response and perhaps poor VDR – July 2022
- Poor prognosis of solid childhood cancers 14.7 X more likely with a poor Vitamin D Receptor – July 2022
- 500 IU of vitamin D does not reduce the risk of Obesity-related Cancers – June 2022
- COVID, Cancer, etc. are Vitamin D low-hanging-fruit – Editorial June 2022
- Cancer mortality reduced 40 pcnt by 2000 IU Vitamin D daily if normal weight – Meta-analysis June 2022
- Vitamin K2-7 helps bone, blood vessels, cancer, diabetes, etc. – June 2022
- Interview with transcript of Dr. Grant on Vitamin D and Cancer by Dr. Moss - June 2022
- Newly diagnosed Children with Cancer have low vitamin D, especially if black - May 2022
- Changes in CYP3A4 gene affects Vitamin D, health, reactions to some drugs, etc - June 2022
- Vitamin D fortification could eliminate 1 in 10 Cancer deaths in the EU – May 2022
- Many cancers reduce oxygen to protect themselves in 6 ways. Vitamin D stops all 6 ways – March 2022
- 23 Cancers if little sun, 12 of which have been associated with low vitamin D – March 2022
- Cancer of the eye in children: most of the risk factors are associated with low vitamin D – July 2021
- Vitamin D probably has a Role in Cancer, CVD, and COVID - video and transcript Dec 1, 2021
- Cancers and Vitamin D Receptors, including change with race – Feb 2021
- Needing a high level of vitamin D is a good clue that the Vitamin D Receptor is deactivated
- Cancer incidence and death reduced by both Vitamin D and UVB – Grant Oct 2021
- Cancer mortality not reduced by small vitamin D doses - Sept 2021
- Virus cause some cancers
- Cancer death (non-skin) 2.3 X more likely if low Vitamin D – Aug 2021
- Children's Cancer hospital now testing vitamin D frequently and supplementing weekly – July 2021
- Consensus recommends at least 20 ng of Vitamin D for childhood cancer (not nearly enough) – June 2021
- Cancer during childhood - many studies
- Vitamin D prevents and treats cancer in many ways – May 2021
- Increased cancer risk from night shift (and many others- low vitamin D) - April 2021
- Some cancer rates are reduced when live at high altitude, but other cancers increase after a few generations – March 2021
- 2,000 IU of Vitamin D daily to German Seniors would save 30,000 lives a year – March 2021
- Vitamin D appears to reduce energy to cancer cells in several ways – March 2021
- 26 health factors increase the risk of COVID-19 – all are proxies for low vitamin D
- Those with recent cancer diagnosis had 7X increased risk of COVID-19 (more if A-A )- Dec 2020
- Vitamin D Receptor (Cancers OR Viruses) - many studies
- Book: Sunlight, UV, Vitamin D and Receptor, Skin and other Cancers - Dec 2020
- 2,000 IU of vitamin D and Omega-3 reduced Cancer death rate bv 40% (normal weight) – VITAL RCT Nov 2020
- Deaths from many types of Cancer associated with low vitamin D- review of meta-analyses Sept 2020
- Vitamin D fights 13 cancers – review of 35 meta-analyses – Oct 2020
- Live 7 years longer free of major disease if eat well, not smoke, not obese, moderate drink and exercise (100,000 people) – Jan 2020
- How cancer is fought by Vitamin D (Ovarian this time) – Feb 2020
- More Cancer if less sun – model adding climate helps (need additional factors) – Nov 2019
- 8 ways that Cancer might be prevented by Vitamin D - June 2019
- Cancer is leading cause of death - Vitamin D and Receptor activators help
- Childhood Cancer survivors – only 1 in 25 had consumed Vitamin D RDA – Oct 2019
- Vitamin D Supplements Reduce Cancer Mortality – Greger Sept 2019
- Exercise reduces cancer deaths, Magnesium RDA reduces deaths even more – Aug 2019
- The Vitamin That Cuts Cancer Risk 13 Percent - July 2019
- Children with cancer were deficient in Vitamin D, Vitamin C, and Zinc – July 2019
- Mortality increased: 4X Cancer, 5X Diabetes if eat a lot of meat protein – March 2014
- People supplemented with Vitamin D had 13 percent fewer Cancer deaths – Meta-analysis of RCT June 2019
- Women with diabetes 60 percent more likely to get Cancer (perhaps low vitamin D) – May 2019
- Cancer incidence and mortality is decreased if 40-60 ng of Vitamin D – April 2019
- The sun appears to generate Co-Q10 in our bodies when we eat our greens – Greger April 2016
- Omega-3 reduces side effects of Cancer treatments – April 2019
- Non-Hodgkin Lymphoma 20 percent more likely if low UV – meta-analysis April 2019
- The Role of Resveratrol in Cancer Therapy – Dec 2017
- Cancer stem cells and Vitamin D - many studies
- A poor Vitamin D Receptor is associated with many cancers (oral cancer in this case) – Jan 2019
- Overview of Vitamin D Actions in Cancer – 31 page chapter in a book – 2018
- Increased incidence of 7 cancers if live far from equator (if not take vitamin D) – March 2019
- Cancer with low Vitamin D increases Mortality by 13 percent – meta-analysis Feb 2019
- Vitamin D Reduces Cancer Risk - Why Scientists Accept It but Physicians Do Not - Feb 2019
- Rates of some newly diagnosed Cancers increased with higher Vitamin D (217,000 Danes) – Jan 2019
- Better Cancer survival if higher vitamin D a decade earlier (esp. Melanoma, Kidney, Prostate)– Aug 2018
- Cancer treatment by Vitamin D sometimes is restricted by genes – Oct 2018
- Fight Cancer with more than cut, burn, and poison – Nobel prize for T-Cell – Oct 2018
- Importance of Vitamin K – Pizzorno – July 2018
- Active Vitamin D level should not be used for Prospective Studies of Cancer – Aug 2018
- Both Vitamin D and Vitamin C fight cancers and aid anticancer drugs – May 2018
- Embrace the Sun – benefits of the sun (Nitric Oxide etc.) – book June 2018
- Active vitamin D appears to treat cancer – more studies needed – June 2018
- Vitamin D receptor is essential for both normal and cancerous cells in the lab – June 2018
- Vitamin K2 appears to treat some cancers – April 2018
- Muscle pain (Low Magnesium) plus Low Vitamin D associated with 10X more Cancer, etc (San Francisco) – Aug 2017
- Cancer not treated by Vitamin D when ignore dose size, type, and length of trial – meta-analysis April 2018
- Active Vitamin D reduces Ovarian Cancer stem cells growth by 4X (via Vitamin D receptor in lab rat) – March 2018
- Half of dogs now get cancer, it used to be just 1 percent (probably low Vitamin D)
- Evidence that Vitamin D prevents Cancer – Grant Feb 2018
- Oral Contraceptives (which increase Vitamin D) reduce the risk of some cancers – Jan 2018
- Bone fractures 2.8 X more likely among cancer survivors (perhaps low vitamin D) – Dec 2017
- Childhood cancer survivors have increased chronic health problems as adults – Sept 2017
- Cancer and the Vitamin D Receptor, a primer – Sept 2017
- Magnesium in Healthcare (Rickets, Stones, Pregnancy, Depression, etc.) with level of evidence – Sept 2017
- Prostate Cancer treatment (Vitamin D, Omega-3, Tumeric) RCT ending Dec 2018
- Dogs with Cancer have low vitamin D, same as humans – Sept 2017
- Omega-3 prevents and treats several cancers – Sept 2017
- Cancer risks and Vitamin D Receptors – association is unclear – 2017
- Modeling Cancer RCTs – including Breast Cancer – April 2017
- Cancer 4 times more likely if low vitamin D (in dogs) – 2016
- Ethical challenge – giving vitamin D to only half of Cancer (etc) patients – Jan 2017
- Vitamin D, Vitamin D Receptor and Cancer – Nov 2016
- Hypothesis: Vitamin D treating of breast and other cancers may be via CCN genes – Oct 2016
- Cancer risk in older women reduced 32 percent by 2,000 IU of Vitamin D plus Calcium – 4 year RCT Oct 2016
- Risk of Cancer increased if poor Vitamin D Receptor – meta-analysis of 73 studies Jan 2016
- Obesity linked to 13 cancers, the linkage is probably vitamin D – Aug 2016
- Cancer and Vitamin D – PhD dissertation 2015
- Vitamin D and cancer – epidemiological association with colon and breast – Sept 2014
- Adaptive immunity (cancer, viruses, autoimmune) and vitamin D – April 2016
- If you were born after 1960 your risk of getting cancer is 1 in 2 if you do not get a lot of vitamin D
- Cancer risk and survival improved by increasing vitamin D or UVB – April 2016
- Cancer risk reduced 65 percent by vitamin D levels greater than 40 nanograms – April 2016
- 'Cancer Screening Has Never Saved Lives' (but Vitamin D supplementation does) - Jan 2016
- Off topic – More money to be made in TREATING cancer than PREVENTING it – NYT Dec 2015
- Dog Cancer 4X more likely if low Vitamin D – Nov 2015
- Vitamin D does not improve cancer survival much – when dose size, etc. is ignored – Oct 2015
- The health benefits of vitamin K – Oct 2015
- Cancer risk weakly associated with vitamin D-binding protein – meta-analysis Sept 2015
- Vitamin D and receptor reduce carcinogenic effects of pollutants – July 2015
- Cancer treated better when active vitamin d (calcitriol) is inside of PLGA nanoparticles – June 2015
- How active vitamin D (Calcitriol) deals with cancer – June 2015
- Cancer - far less for outdoor workers
- Obesity causes 20 percent of all cancer, low vitamin D may be the connection – meta-analysis - Sept 2014
- Opioid use in palliative cancer patients far less if high level of vitamin D – May 2015
- Cancer deaths strongly related to low vitamin D if sampled near time of diagnosis – Feb 2012
- Cancer deaths of senior women 60 percent more likely if low Vitamin D – March 2015
- Photodynamic Therapy used to kill cancer in mice was improved 4X by Vitamin D – Feb 2015
- Cancer – will 4,000 IU of vitamin D daily help in one month (no) – VIDAFACT Dec 2014
- Cancer and active Vitamin D – in Spanish – Nov 2014
- Cancer, Sunlight, and Vitamin D - Holick Oct 2014
- Off Topic: Cannabinoids as Cancer chemotherapy – Sept 2014
- Obesity increases Cancer - perhaps due to low vitamin D - many articles
- Off topic: Oncologists paid 350 dollars per patient-month to use less effective and more toxic cancer drugs – Oct 2014
- More vegetables or fish, less Cancer – June 2014
- Dog Cancer (hemangiosarcoma) is rare if more than 100 ng of vitamin D – July 2014
- Role of Vitamin D in human Diseases and Disorders – An Overview – DBP, VDR June 2014
- Cancer incidence not reduced by 1100 IU of vitamin D (proven again) but mortality decreased – June 2014
- Less intestinal cancer in mice if add vitamin D, but even less with ultraviolet light – June 2014
- Cancer Council of Australia recommends 30 minutes of daily sunshine – June 2014
- Cancer survival 4 percent more likely with just a little more vitamin D (4 ng) - meta-analysis July 2014
- Vitamin D Receptor role in Autoimmune Diseases and or cancers – Nov 2013
- Vitamin D receptor polymorphisms are risk factors for various cancers – meta-analysis Jan 2014
- Vitamin D and Cancer at NIH - Oct 2013
- Vitamin D proven to treat or prevent many cancers in animals, but only breast cancer in humans so far – Jan 2014
- Cancer and low vitamin D – which causes which – Nov 2013
- Cancer incidence in 87 countries is related to food, smoking, alcohol, GDP, and UVB - Jan 2014
- Skin cancer increases other cancers (low-vitamin D) – Dec 2013
- Cancer Survival is poor if vitamin D is less than 20ng (every study showed benefit)– review Nov 2013
- People more likely to freckle are more likely to get prostate cancer (low vitamin D) – April 2013
- National Cancer Institute noticing Vitamin D - Oct 2013
- Appears that IBD lowers vitamin D, which increases risk of cancer by 80 percent – Oct 2013
- 4 uses of tanning beds per year did not reduce rate of internal cancers – Oct 2013
- Vitamin d - pivotal nutraceutical in the regulation of cancer metastasis and angiogenesis. – 2013
- Molecular Link between Vitamin D and Cancer Prevention – Oct 2013
- Review of cancer and supplements includes vitamin D – Sept 2013
- Death of women from cancer 24% less likely if 20 ng more vitamin D – meta-analysis Sept 2013
- Probably need more than 1000 IU of vitamin D to prevent cancer – meta-analysis Aug 2013
- Mayo clinic starting Cancer RCT using grossly inadequate 2,000 IU of vitamin D – Sept 2013
- Children with Cancer were 3X more likely to be vitamin D deficient – July 2013
- Vitamin D protects against many types of health problems – review May 2013
- Less Solar Radiation was associated with more Cancer - 1941
- Some childhood cancer 30% less likely in parts of California with more UVB – April 2013
- Cancer associations, including problems with too much vitamin D – March 2013
- Low vitamin D strongly related to death due to tobacco cancer, but not others – March 2013
- Vitamin D increasingly associated with inflammation such as RA, TB, Lupus, and cancer – March 2013
- The sun appears better at reducing incidence of some cancers than vitamin D – Dec 2012
- Solar UVB reduces Cancer Risk – Grant, Jan 2013
- The Anti-cancer Actions of Vitamin D – Jan 2013
- Vitamin D Supplementation and Cancer - Review of RCT Jan 2013
- Vitamin D and Cancer Mortality – review Jan 2013
- Vitamin D, Sunlight and Cancer Connection – Holick Jan 2013
- Relevance of Vitamin D in Bone and Muscle Health of Cancer Patients - Jan 2013
- How Vitamin D prevents many cancers (c-MYC) – Nov 2012
- Cancer
- Big Pharma continues to seek a patentable form of vitamin D for Breast Cancer – Nov 2012
- A review of the evidence regarding the solar ultraviolet-B-vitamin D-cancer hypothesis - Oct 2012
- Vitamin D still appears to reduce Cancer Mortality – Systematic Review Oct 2012
- CYP24A1 gene in cancer cells may actually remove vitamin D from the blood – Oct 2012
- Vitamin D levels very low for some childhood cancers, then got lower – Sept 2012
- More US deaths due to cancer than heart if dark skinned – Sept 2012
- Vitamin D and cancer: a view based of all models – April 2012
- Review of Cancer and Vitamin D – April 2012
- Photodynamic therapy for Cancer might be helped by vitamin D – July 2012
- Vitamin D in Cancer Patients: Above All, Do No Harm – 2009
- Not enough women willing to stop taking vitamin D to permit breast cancer clinical trial – June 2012
- More UVB is associated with less cancer – study of 450,000 people – April 2012
- Hypothesis: Blacks get more cancer than whites due to lower levels of vitamin D – June 2012
- 2000 IU of vitamin D reduced fatigue of advanced cancer – RCT May 2012
- The role of vitamins in cancer: a review – 2011
- Vitamin D3 analog, 20-hydroxyvitamin D, inhibits cancer cells and is non-toxic – March 2012
- Advanced stage cancer 3X more likely if low level of vitamin D – March 2012
- Getting little UV is associated with 15 types of Cancer – Jan 2012
- Lack of solar UVB in US is associated with some Cancers - 2006
- Possible ways that vitamin D does its magic
- 800 IU Vitamin D doesn't prevent heart attack or cancer – Dec 2011
- The lower the vitamin D the sooner a blood cancer needed to be treated – Nov 2011
- Use of tanning beds would reduce associated deaths by 10X – Oct 2011
- Cancer in children 6X more likely if very low vitamin D – Oct 2011
- Breast and other Cancer prevention - Dr. Wascher 2011
- Vitamin D has a complex relationship with Cancer – meta-analysis July 2011
- Cancers and Vitamin D Council
- Sun exposure is associated with increased survival from melanoma – 2005
- Excessive sun increases cancer all around the body – July 2011
- Some cancer due to low UV – Grant – April 2010
- Hypothesis – anticancer benefits from synergy of omega-3 and vitamin D – May 2011
- Vitamin D and Cancer Treatment and Prevention – presentations May 2011
- Mortality and Cancer varies with latitude in France too – 2010
- Video on how Vitamin D reduces Cancer – Feb 2011
- Vitamin D and Prevention of Cancer — Is it ready for Prime Time – March 2011
- Vitamin D appears to both prevent and treat various cancers – Mar 2011
- Children with Cancer were 6X more likely to have less than 10ng of vitamin D – Feb 2011
- Large Healthcare Org: 1500-2000 IU vitamin D to reduce cancer - Dec 2009
- Increase in some childhood cancers with latitude – Nov 2010
- How active vitamin D stops various cancers – abstract Oct 2010
- Is there an optimal level of vitamin D to prevent cancer – Sept 2010
- Less cancer if had more physical activity – perhaps due to the sun – Sept 2010
- Overview Cancer and vitamin D
- Active form of vitamin D appears to help prevent and treat some cancers – Feb 2011
- How I Treat Vitamin D Deficiency - for Cancer Mar 2010
- Anticancer Vitamins du Jour—The ABCED's So Far – July 2010
- Dr Frank Garland who researched vitamin D and cancer died - Aug 2010
- Cancer meeting discussion of Nov 2009 mentioned vitamin D
- Impediments to UV Vitamin D Cancer hypothesis – Sept 2009
- 18 Quotes on Vitamin D and Cancer – Feb 2010
- Meta-analysis of 3 cancers - 10 ng more vitamin D decrease colorectal by 15 percent– May 2010
- Vitamin D and Cancer from Health Book Summaries – Feb 2010
- 30 to 40 ng of vitamin D did not reduce some Cancers - no surprise - June 2010
- China has documented that less UV results in more cancer – June 2010
- Why clinical trials are not finding benefits of vitamin D on cancer prevention and treatment – June 2010
- Lack of vitamin D may account for increased rate of some cancers in obese persons – May 2010
- Grassroots PDF and video updates May and June 2010
- Hypercalcemia overview
- Vitamin D Shows Potential in Natural Chemotherapy April 2010
- Solar radiation, vitamin D and cancer incidence and mortality in Norway
- Vitamin D decreases incidence of disease
- file:
- Vitamin D and Calcium reduces risk of cancer - Lappe 2007
- Vitamin D and Cancer - Dalgleish May 2011.pdf
- Vitamin D and Cancer - GrassRoots May 2011.pdf
- Vitamin D and Calcium reduce Cancer - RCT trial - Lappe - May 2011.pdf
- Vitamin D and UVB reduce Cancer - Grant May 2011.pdf
- Cancer cells and vitamin D - Kallay May 2011.jpg
- Cancer cells and Calcium - Kallay May 2011.jpg
- U shaped risk curves happen where UV varies a lot - Vieth 2011.jpg
- Vitamin D Cancer - Garland 2009.pdf
- 8000 IU raised vitamin D for many Cancer patients - 2010.pdf
- vitamin D and cancer condundrum - 2010.pdf
- Mechanisms of the Anti-Cancer and Anti-Inflammatory - 2011.PDF
- Vitamin D in combination cancer treatment - 2010.PDF
- Letter to editor on errors in rare cancers study - Sept 2010
- Cancer incidence with vitamin D supplements- CDC Aug 2010 - GIF
- Vitamin D for prevention and treatment of Cancer - technical July 2010
- Vitamin D prevent 25% cancers - 2009
- Promise of vitamin D analogues in the treatment of Cancer -2006
- meta analysis vitamin D and cancers - prepub 2010
- Role of vitamin D in cancer treatment and prevention - June 2010
- Many cancers increase in Japan during past 50 years
- Chart All Cancers reduced by 68 percent if > 29ng/ml Heaney - May 2010
- Vitamin D Cancer and latitude 2008 PNAS
- Vitamin D prevent Cancer - 2009
- file gallery:
More Cancers if poor Vitamin D Receptor
Cancers get less Vitamin D when there is a poor Vitamin D Receptor- Vitamin D Receptor pages in VitaminDWiki with CANCER in title 86 as of July 2023
- Cancer and the Vitamin D Receptor, a primer – Sept 2017
- Vitamin D Receptor (Cancers OR Viruses) - many studies
- Risk of Cancer increased if poor Vitamin D Receptor – meta-analysis of 73 studies Jan 2016
- Cancer (general) and VDR
23 articles - Breast Cancer and VDR
24 articles - Colon Cancer and VDR
13 articles - Prostate Cancer and VDR
7 articles - Skin Cancer and VDR
10 articles - Note some Health problems, such as some Cancers, protect themselves
by actively reducing Receptor activation
Overview Cancer and vitamin D has a summary of the Lappe cohort))
Extrapolation to ZERO incidence of 3 types of Cancer at 104 nanograms
http://www.vitamindinfo.net/: Extrapolation
No Colon Cancer: 46 ng, No Ovarian Cancer: 60 ng, No Breast Cancer:104 ngNote also
- 150 ng of Vitamin D CURES Mulitple Sclerosis
- One doctor went out of business after patients average # of visits dropped from 4/year to 1/year
After he got their vitamin D levels to 80 nanograms - Video
Description in newsletter from Grassroots Health
Summary chart from Grassroots Health
Note: The shaded area does NOT represent any existing data.
It is just an extrapolation from due to using just 2 variables to match the existing data. Download the PDF from VitaminDWiki
Abstract
Background
Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with a lower risk of multiple cancer types across a range of 25(OH)D concentrations.
Objectives
To investigate whether the previously reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women aged 55 years and older across a broad range of 25(OH)D concentrations.
Methods
Data from two cohorts representing different median 25(OH)D concentrations were pooled to afford a broader range of 25(OH)D concentrations than either cohort alone: the Lappe cohort (N = 1,169), a randomized clinical trial cohort (median 25(OH)D = 30 ng/ml) and the GrassrootsHealth cohort (N = 1,135), a prospective cohort (median 25(OH)D = 48 ng/ml). Cancer incidence over a multi-year period (median: 3.9 years) was compared according to 25(OH)D concentration. Kaplan-Meier plots were developed and the association between 25(OH)D and cancer risk was examined with multivariate Cox regression using multiple 25 (OH)D measurements and spline functions. The study included all invasive cancers excluding skin cancer.
Results
Age-adjusted cancer incidence across the combined cohort (N = 2,304) was 840 cases per 100,0 person-years (1,020 per 100,000 person-years in the Lappe cohort and 722 per 100,0 person-years in the GrassrootsHealth cohort). Incidence was lower at higher concentrations of 25(OH)D. Women with 25(OH)D concentrations >40 ng/ml had a 67% lower risk of cancer than women with concentrations <20 ng/ml (HR = 0.33, 95% CI =0.12- 0.90).
Conclusions
25(OH)D concentrations >40 ng/ml were associated with substantial reduction in risk of all invasive cancers combined.Introduction
There were 14 million new cases of cancer worldwide in 2012 and 8.2 million cancer-related deaths [1]. Looking ahead, the annual number of new cases is projected to increase to 22 million within the next two decades [1]. In the United States, it is estimated that over 1.68 million new cases of cancer will be diagnosed in 2016 and almost 600,000 deaths due to cancer will occur [1]. A total of $125 billion was spent on cancer care in the United States in 2010, and is expected to grow to over $150 billion in 2020 [1]. A focus on primary prevention is imperative to slow or reverse these upward trends in cancer incidence, treatment burden, mortality, and associated costs.
Thirty-five years ago, Garland and Garland first proposed a link between cancer and vitamin D from observations of higher colon cancer mortality in higher latitudes and areas with less solar radiation [2]. Since then, multiple epidemiologic studies have found an inverse association between serum 25-hydroxyvitamin D [25(OH)D] concentration and the risk of many types of cancer including breast [3-10], colorectal [11-12], and prostate [13]. In a randomized controlled trial by Lappe et al. [14], it was found that women assigned to a vitamin D and calcium treatment group had a 60% reduction in incidence of all non-skin cancers compared to women in the placebo group (RR = 0.40, 95% CI: 0.20-0.82, P = 0.01). For women free of cancer at one year into the trial, the reduction in incidence was 77% (RR = 0.23, 95% CI: 0.090.60, P<0.005).
The objective of this analysis was to quantify more precisely the association between 25 (OH)D concentration and risk of non-skin cancer among women aged 55 years and older, and to do so across a broader range of 25(OH)D concentrations than had been previously analyzed. The present study used data from two cohorts representing different median 25(OH)D concentrations. The first was a cohort from a randomized controlled clinical trial performed by Lappe et al. [14,15] in Nebraska (N = 1,169), with a median 25(OH)D of 30 ng/ml (Interquartile Range (IQR): 25-37). The Lappe et al. cohort (hereafter termed Lappe cohort) provided a majority of the data for the lower 25(OH)D concentrations. The second was a cohort from a prospective cohort study consisting of volunteer participants residing in 52 countries worldwide (90% in the United States or Canada) recruited by a non-profit public health research organization, GrassrootsHealth of San Diego, California (N = 1,135), with a median 25(OH)D of 48 ng/ml (IQR: 39-61). The GrassrootsHealth cohort provided a majority of the data for the higher 25(OH)D concentrations. Because of the larger sample size, this pooled cohort has improved statistical power. It also provided a broader range of 25(OH)D concentrations than either cohort alone. This novel approach allowed for analysis of results across a wide range of 25(OH)D concentrations. This would otherwise not have been possible due to the paucity of data in the higher concentrations of 25(OH)D in the Lappe and other similar treatment cohorts. Serum 25(OH)D concentration was selected as the independent variable rather thantreatment assignment or reported intake because it is a better indicator of vitamin D status, capturing the effect of multiple input sources and making provision for inter-individual variability in dose response [16].Materials and Methods
Lappe Cohort
The Lappe cohort participated in a four year, double-blind, placebo-controlled trial of vitamin D and calcium supplementation. A detailed description of the participants and study design can be found elsewhere [14,15]. Briefly, participants were recruited via random digit dialing within a 9-county area in Eastern Nebraska as a population-based sample. Inclusion criteria included women aged 55 years and older without known cancer at enrollment or within 10 years prior. All participants were non-Hispanic white. Participants who were lost to follow-up before their second visit were excluded because of lack of prospective data for this analysis. All participants provided written informed consent and this research study was approved by the Creighton University Institutional Review Board (Omaha, NE).
Participants were randomly assigned to one of three groups: calcium (either 1400 mg/day of calcium citrate or 1500 mg/day of calcium carbonate, plus vitamin D placebo), calcium plus vitamin D (calcium as mentioned previously plus 1000 IU/day of vitamin D3), or control (calcium and vitamin D placebos). The calcium group and the calcium plus vitamin D group each comprised 40% of the total cohort, with 20% serving as the control group. Health status and supplement intake according to bottle weight were assessed at 6-month interval visits. When a diagnosis of cancer was reported, medical records were examined to confirm diagnosis and ascertain diagnosis date. Serum 25(OH)D concentrations were measured at baseline and annually thereafter using radioimmunoassay after extraction with the use of the IDS Radioimmunoassay kit (Foundation Hills, AZ) at the Creighton University Osteoporosis Research Center Laboratory (Omaha, NE). The laboratory participates in the Vitamin D Quality Assessment Scheme (DEQAS), whose objective is to ensure the analytical reliability of 25(OH)D assays, with findings on test samples collected during the course of the study regularly close to the international mean.
GrassrootsHealth Cohort
GrassrootsHealth, a non-profit public health research organization, has been running a large prospective population-based study allowing voluntary participants to reach and sustain a serum 25(OH)D concentration of their choice, and tracking self-reported health status measures through a questionnaire. Participants were individuals who responded to an invitation to attendees at a GrassrootsHealth seminar in 2008 and others recruited via internet. There were no exclusion criteria for enrollment. Participation required submission of a home blood spot 25(OH)D test kit and completion of an online health questionnaire. All participants provided informed consent and this research study was approved by the Western Institutional Review Board (Olympia, WA).
This current analysis included all non-Hispanic white female participants aged 55 years and older without known cancer at enrollment or within 10 years prior who completed at least two health assessments and 25(OH)D measurements. These inclusion criteria were chosen to match GrassrootsHealth members to features of the Lappe cohort. Between January 2009 and December 2014, participants completed health questionnaires and home blood spot test kits at approximately 6 month intervals. Cancer diagnosis dates and types were reported as well as average daily calcium supplement intake, smoking status, and height and weight for calculation of body mass index (BMI). Serum 25(OH)D concentrations were determined by blood spot test kits analyzed using liquid chromatography-mass spectroscopy (LC-MS/MS) by ZRT Laboratory (Beaverton, OR) or Purity Laboratory (Lake Oswego, OR). Both the ZRT and Purity assays had been validated against the LC-MS/MS consensus group reporting to DEQAS, with R2 values of 0.998 and 0.994 respectively. LC-MS/MS has been validated against the radioimmunoassay method, with an R2 value of 0.91 and with a slope not different from 1.0 [17].
Overall, this analysis included 1,169 women from the Lappe cohort (median follow-up time, 4.0 years) and 1,135 women from the GrassrootsHealth cohort (median follow-up time, 1.2 years) (pooled cohort N = 2,304; median follow-up time, 3.9 years). The total person-time was 4,239 person-years in the Lappe cohort and 2,175 person-years in the GrassrootsHealth cohort (6,414 person-years in the pooled cohort). The most common type of cancer diagnosed during the study was breast cancer (43% of all cancers in the pooled cohort).
Statistical Methods
Demographic characteristics for the Lappe and GrassrootsHealth cohorts were summarized and compared using Mann-Whitney tests for age, BMI, and baseline 25(OH)D, and the chi- square test was used to compare smoking status. Mean 25(OH)D concentration was calculated for each participant by taking the mean of all 25(OH)D measurements during the observation period (for cases, only measurements before the date of diagnosis were used). The outcome of interest was the diagnosis of any non-skin cancer during the period of observation. A previous analysis of the Lappe cohort [14] included 2 cases of melanoma but these were considered skin cancer and not identified as cases for this analysis. Age-adjusted incidence rates (standardized to the 2010 US population) of non-skin cancer (hereafter termed cancer) were calculated for the Lappe and GrassrootsHealth cohorts.
Cancer incidence rates and 95% confidence intervals were calculated for successive 20 ng/ ml groups of 25(OH)D concentration, using a moving average method [18-20] to assess incidence trends across the range of 25(OH)D for both baseline 25(OH)D and mean 25(OH)D (mean of all measurements for a given individual during the observation period as a single measure of overall vitamin D status during the study). Using the curve fitting routine of Sigma- Plot 12.3 (Systat Software Inc., San Jose, CA, USA), the relationship of serum 25(OH)D concentration to cancer incidence was fitted to an exponential equation (Y = A + B-X/C, where Y = cancer incidence rate, X = serum 25(OH)D).
To estimate cancer-free survival over time and account for varying lengths of follow-up, Kaplan-Meier cancer-free survival curves were developed (allowing for participants switching groups). The proportion of cancer-free participants for 25(OH)D concentrations of <20 ng/ ml, 20-39 ng/ml, and >40 ng/ml were computed.
Multivariate Cox regression was used to determine the association between serum 25(OH) D and the risk of developing cancer, adjusting for age, BMI, smoking status, and calcium supplement intake. Hazard ratio (HR) estimates and 95% confidence intervals (CIs) were calculated for 25(OH)D concentration as a categorical variable divided into three a priori categories: <20 ng/ml, 20-39 ng/ml, >40 ng/ml (the 20 ng/ml cut point is from the Institute of Medicine (IOM) recommendation for bone health [21] and the 40 ng/ml cut point is from literature recommending at least this concentration for cancer prevention [22-26]). Calcium supplement intake was also assessed as a categorical variable (<1000 mg/day vs. >1000 mg/day) based on the IOM recommendation for bone health [21]. Since 25(OH)D concentration and calcium supplement intake changed over the course of the study for most participants, multiple values for each participant were entered in the model as time varying, with their mean values for the prior year. Age and BMI were entered as baseline continuous variables and smoking status was entered as a categorical variable (yes/no) for “current smoker” at baseline. The proportional hazards assumption was tested by assessing the interaction of each variable with log of time. Effect modification was tested by including pair-wise product interaction terms. Modeling was confined to participants with valid values for all of the involved variables.
The association between 25(OH)D concentration and cancer risk was assumed to be nonlinear, based on the typical nutrient physiological response which consists of a response region where improved nutrient status produces significantly lower risk, and an upper region where less benefit is observed with increasing status [27]. A multivariate Cox regression model with restricted cubic splines with 3 knots in default locations was used to identify the nature of the non-linear association between 25(OH)D and cancer risk. Analyses were performed using the R software (www.r-project.org).
Results
The median baseline serum 25(OH)D concentration in the Lappe cohort was 28 ng/ml (IQR: 23-34) and in the GrassrootsHealth cohort was 43 ng/ml (IQR: 34-58) (P<0.0001). The baseline characteristics of the Lappe and GrassrootsHealth cohorts are shown in Table 1. The Lappe cohort had a higher median age and BMI and a higher proportion of participants who were current smokers.
Mean 25(OH)D concentration was computed for each participant as the mean of all 25 (OH)D measurements during the observation period as a single measure of overall 25(OH)D concentration status during the study. The median of the within-subject mean 25(OH)D values, calculated for each cohort, was 30 ng/ml (IQR: 25-37) in the Lappe cohort and 48 ng/ml (IQR: 39-61) in the GrassrootsHealth cohort (P<0.0001). Corresponding values for the pooled cohort were 37 ng/ml (IQR: 29-49). 55% of women in the Lappe cohort and 17% in the GrassrootsHealth cohort had a mean calcium supplement intake of >1000 mg/day (P<0.0001) (36% in the pooled cohort). Those in the Lappe cohort with a mean calcium supplement intake of < 1000 mg/day were either assigned to the control group or took <70% of assigned calcium doses.
Fifty-eight women in the pooled cohort were diagnosed with cancer during the observation periods (48 from the Lappe cohort and 10 from the GrassrootsHealth cohort). The age- adjusted incidence rate of cancer was 840 cases per 100,000 person-years in the pooled cohort, 1020 cases per 100,000 person-years in the Lappe cohort and 722 cases per 100,000 person- years in the GrassrootsHealth cohort. Cancer types for each cohort are shown in S1 Table.To assess cancer incidence trends across the range of 25(OH)D in the pooled cohort, incidence rates were calculated according to categories of 25(OH)D for both baseline 25(OH)D and mean 25(OH)D (mean of all measurements during the observation period as a measure of overall 25(OH)D concentration during the study) (Fig 1). For both baseline and mean 25(OH) D, when 25(OH)D was higher, incidence rates were lower. Specifically, there was a 77% lower incidence rate of cancer for >40 ng/ml vs. <20 ng/ml for baseline 25(OH)D (Rate Ratio = 0.23, 95% CI: 0.09-0.59, P = 0.002) and a 71% lower incidence rate for mean 25(OH)D (Rate Ratio = 0.29, 95% CI: 0.11-0.77, P = 0.02). Fig 2 shows plots of cancer incidence rates by baseline and mean serum 25(OH)D with fitted exponential curves. Rates were lower in higher 25 (OH)D categories (>40 ng/ml). There was continued gradual decline with higher concentrations.
To estimate cancer-free survival over time and account for varying lengths of follow-up, Kaplan-Meier curves comparing the proportion of cancer-free participants for <20 ng/ml, 2039 ng/ml, and >40 ng/ml (allowing for participants switching groups) were computed for the pooled cohort (Fig 3). These curves were significantly different, with the highest proportion cancer-free at 4 years in the >40 ng/ml group (98%) and the lowest proportion cancer-free in the <20 ng/ml group (93%) (proportion with cancer was 71% lower for >40 ng/ml vs. <20 ng/ ml, P = 0.02). The >40 ng/ml group diverged early from the other groups and the 20-39 ng/ml diverged from the <20 ng/ml group at approximately 2 years.
Table 1. Demographic characteristics of the pooled, Lappe, and GrassrootsHealth cohorts.
Statistical comparison of characteristics between Lappe and GrassrootsHealth cohorts. Age, BMI, baseline 25(OH)D, and mean 25(OH)D were compared using Mann-Whitney tests. Smoking status was compared using chi-square test.
bMean 25(OH)D concentration was computed for each participant as the mean of all 25(OH)D measurements during the observation period as a single measure of overall 25(OH)D concentration status during the study.Multivariate Cox regression was used to quantify the association between 25(OH)D and cancer risk, adjusting for other risk factors (allowing multiple 25(OH)D values per participant to accommodate changes over the course of the study). Women in the pooled cohort with 25 (OH)D concentrations >40 ng/ml had a 67% lower risk of cancer compared to women with concentrations <20 ng/ml, adjusting for age, BMI, smoking status, and calcium supplement intake (HR = 0.33, 95% CI: 0.12-0.90, P = 0.03) (Table 2). Those with concentrations of 20-39 ng/ml had 43% lower risk of cancer compared to those with concentrations <20 ng/ml (HR = 0.57, 95% CI: 0.25-1.30, P = 0.18). Women taking >1000 mg/day of calcium supplements had a 19% lower risk of cancer, but this association was not significant (HR = 0.81, 95% CI: 0.47-1.40, P = 0.45); also, the association of 25(OH)D with cancer risk did not vary based on the level of calcium supplement intake. Age, BMI, and smoking status were also not significant predictors of cancer risk.
Multivariate Cox regression with spline terms was used to identify the nature of the non-linear association between 25(OH)D and cancer risk. Spline regression revealed a sharp decrease in the risk of cancer with increased 25(OH)D concentration in the lower range of 25(OH)D and a gradual decline as serum concentrations neared 40 ng/ml and above, with no evidence of increased risk in the upper 25(OH)D concentrations (Fig 4). The reduction in risk from 20 ng/ ml to 40 ng/ml was approximately 70%.
Findings were similar when we limited the analysis to just the Lappe cohort (S1-S3 Figs and S2 Table) and when we excluded non-US residents in the GrassrootsHealth cohort. Additionally, we conducted multivariate Cox regression analysis using tertiles of 25(OH)D concentration and the results were also similar. Specifically, women with 25(OH)D concentrations in the highest tertile (>40 ng/ml) had a 65% lower risk of cancer compared to women with concentrations in the lowest tertile (<28 ng/ml) (HR = 0.35, 95% CI: 0.17-0.75, P = 0.007). In the Lappe cohort, women in the highest tertile (>32 ng/ml) had a 61% lower risk of cancer compared to women with concentrations in the lowest tertile (<25 ng/ml) (HR = 0.39, 95% CI: 0.18-0.84, P = 0.02).
Figure F1A
Fig 1. Frequency distribution and cancer incidence rates by 25(OH)D concentration, pooled cohort (N = 2304). The bars represent the number of noncases by groupings of 10 ng/ml, white dots represent the 25(OH)D concentration for each cancer case, black dots represent cancer incidence rates per person-years for indicated 25(OH)D groupings (plotted at the median 25(OH)D value for each grouping: baseline 25(OH)D groups at 17, 25, 30, 37, 46, and 63 ng/ml; mean 25(OH)D groups at 17, 25, 31,38, 47, 58, and 69 ng/ml). Vertical error bars indicate the 95% confidence intervals.Fig 2. Cancer incidence rates by 25(OH)D concentration with fitted curves, pooled cohort (N = 2304). Black dots represent cancer incidence rates per person-years for indicated 25(OH)D groupings (rates are displayed at the median value for each grouping: baseline 25(OH)D groups at 17, 25, 30, 37, 46, and 63 ng/ml; mean 25(OH)D groups at 17, 25, 31,38, 47, 58, 69 ng/ml), as seen in Fig 1. Solid black lines represent the best fit line to the exponential equation: Y = A + B(e ( -X/C), where Y = cancer incidence rate, X = serum 25(OH)D (dashed lines represent the 95% confidence intervals).
Fig 3. Kaplan-Meier plot comparing the proportion of cancer-free participants by 25(OH)D concentration (allowing for participants switching groups), pooled cohort (N = 2304). Four-year cumulative cancer-free proportion was 98% among participants with 25(OH)D concentrations >40 ng/ml compared to 93% for those with 25(OH)D concentrations <20 ng/ml (proportion with cancer was 71% lower for >40 ng/ml vs. <20 ng/ml, P = 0.02).
Table 2. Association between serum 25(OH)D and risk of cancer, pooled cohort (N = 2304).
Serum 25(OH)D (ng/ml)
Bold values signify significant hazard ratios.
aAdjusted for age, BMI, smoking status, and calcium supplement intake.
Fig 4. Association between serum 25(OH)D and risk of cancer adjusted for age, BMI, smoking status, and calcium supplement intake in the range of 100 ng/ml, pooled cohort (N = 2304). Solid black line represents the estimated hazard ratio for the Cox regression model with restricted cubic splines with 3 knots and dashed lines represent the 95% confidence interval of the estimate. The reduction in risk from 20 ng/ml to 40 ng/ml was approximately 70%.Discussion
We found a clear association between 25(OH)D serum concentration and cancer risk, according to multiple types of analyses. These results suggest the importance of vitamin D for theprevention of cancer. Women with 25(OH)D concentrations >40 ng/ml had a significantly lower risk of cancer (~70%) compared to women with concentrations <20 ng/ml. When looking at the risk of cancer across the 25(OH)D continuum available in the pooled cohort, we observed the greatest decrease in risk occurring between ~10-40 ng/ml, with additional benefit also observed at >40 ng/ml. We would have preferred to have randomized clinical trial data in the higher 25(OH)D ranges, but since these do not currently exist, using the GrassrootsHealth prospective cohort data allowed us to observe results across a wider range of 25(OH)D concentrations than using the Lappe cohort alone.
Other studies have found a similar reduction in risk for individual cancers [3-13]. Lowe et al. demonstrated in a hospital-based case control study that women with serum concentrations of >60 ng/ml had an 83% reduction in breast cancer risk compared to women with concentrations <20 ng/ml (P<0.001) [3]. A population-based case control study found a 63% lower risk of breast cancer for women with 25(OH)D concentrations >30 ng/ml compared to women with concentrations <20 ng/ml (OR = 0.37, 95% CI: 0.27-0.51), with a 71% lower risk among post-menopausal women (OR = 0.29, 95% CI: 0.19-0.45) [6]. A recent nested case-control study found a 55% lower risk of colorectal cancer in women with 25(OH)D concentrations >29 ng/ml compared to women with concentrations <18 ng/ml (OR = 0.45, 95% CI: 0.25 0.81) [12].
Two previous studies of the Women’s Health Initiative (WHI) randomized trial did not find an association between vitamin D treatment group and colorectal or breast cancer risk [28,29]. That trial used vitamin D doses of 400 IU/day, an intake amount that is unlikely to raise basal concentrations to a sufficient status, and experienced poor compliance (approximately 50%). When the WHI data were analyzed by baseline 25(OH)D concentration, higher 25(OH)D was associated with lower cancer risk (60% lower risk of colorectal cancer for >23 ng/ml vs. <12 [28] and 78% lower risk of colorectal cancer for >26 ng/ml vs. <13 ng/ml [29]). Also, studies of other cancers from this trial found significant inverse relationships between vitamin D status and lung and pancreatic cancer risk [30,31].
Future studies should base their study design on nutrient physiology, taking into account the sigmoidal nature of nutrient response by assessing participants whose basal status was deficient (<20 ng/ml) and using a vitamin D dose sufficient to raise 25(OH)D concentrations to above the response range (~40 ng/ml as seen in Fig 4) [27]. Comparing 25(OH)D concentration groups outside of this response range or treating the relationship as linear, spread across the entire 25(OH)D range instead of a sigmoidal response would dilute the effect. Further, comparing 25(OH)D concentration groups over too narrow a region of the response range may also yield non-significant results. Note in Fig 4 the smallness in the reduction in risk as 25 (OH)D exposure increases from 25 to 35 ng/ml. To the extent that Fig 4 adequately represents the association of risk and vitamin D status, this small effect size in the mid exposure range may explain why many treatment studies, particularly those that did not raise mean 25(OH)D concentration into the range above 40 ng/ml, failed to detect an association of serum 25(OH)D with cancer. This illustrates the importance of dosing in a manner calculated to span an appreciable portion of the sigmoid response curve [27].
Of interest, several newly-identified, naturally occurring vitamin D3 metabolites have been detected in human epidermis and serum that are products of CYP11A1-mediated metabolism of vitamin D [32]. These vitamin D metabolites exert anti-proliferative, pro-differentiation, and anti-inflammatory effects that are similar to, or greater than, the effects of 1,25(OH)2D3 [33,34]. Also, the major vitamin D metabolite from this pathway, 20(OH)D3, occurs in much higher concentrations in human serum than 1,25(OH)2D3 (~60 times) [34]. This new research shows that there are many active metabolites of vitamin D that may be contributing to the influence of solar UVB and serum 25(OH)D3. These newly-identified metabolites should be considered for inclusion in future studies of cancer prevention since their spectrum of action may extend beyond that of 25(OH)D3 and 1,25(OH)2D3.
Calcium supplement intake was not a significant independent predictor of cancer risk in this analysis. This finding is similar to the results of the previous analysis based on assigned treatment group by Lappe et al., that found that women assigned to the calcium treatment group did not have a significant reduction in cancer risk compared to women in the control group (RR = 0.53, 95% CI: 0.27-1.03), including among the subgroup of women who were free of cancer at one year (RR = 0.59, 95% CI: 0.29-1.21) [14]. Since information on dietary calcium intake was unavailable, the present analysis was limited to the assessment of supplemental calcium intake. It is possible that dietary calcium intake (or total calcium intake) may play a role in cancer risk.
The median follow-up time for the Lappe cohort was 4.0 years, compared to 1.2 years for the GrassrootsHealth cohort. All rates were calculated using person-time denominators, so the difference in length of follow-up did not affect the rates. Also, Kaplan-Meier plots and Cox regression were used because these analyses account for varying lengths of follow-up. Still, there could be a difference between the two cohorts if a certain amount of time must pass for the serum 25(OH)D to exert its influence. For example, in the original analysis of the Lappe cohort [14], the effect of vitamin D on risk of all invasive cancers was greater if one year was allowed to pass before starting the counting of cases. If we assume that participants of the GrassrootsHealth cohort had started their self-intervention less than a year before follow-up began, the true association might have been stronger if a longer time interval was available. The impact of vitamin D on risk of cancer could be greater than the hazard ratio we report here (HR = 0.33, 95% CI = 0.12-0.90) (Table 2). The GrassrootsHealth cohort is still under active surveillance, and a future article will report on the effect of longer follow-up.
There were three times as many cases of breast cancer in the Lappe cohort than in the Grass- rootsHealth cohort; however, median follow-up time for the Lappe cohort was 3.3 times longer than for the GrassrootsHealth cohort. Also, the GrassrootsHealth cohort had higher 25(OH)D concentrations than the Lappe cohort, which has been associated with lower risk of breast cancer [3-10]. It is of some interest that there were seven cases of lung cancer in the Lappe cohort compared to zero cases in the GrassrootsHealth cohort. Although the difference was only statistically significant at P = 0.11, and could be explained by alternative explanations, it is consistent with the existence of an inverse relationship between vitamin D status and risk of lung cancer [30,35]. Some of the differences may also have been due to the median age of the Lappe cohort being 4 years older than that of the GrassrootsHealth cohort, the BMI of the Lappe cohort being 28 compared to 24 in the GrassrootsHealth cohort, and the proportion of current smokers in the Lappe cohort being 9% compared to 3% in the GrassrootsHealth cohort. However, this analysis took into account these cohort differences when assessing the association between 25(OH)D and cancer risk by adjusting for these factors in multivariate Cox regression analyses (Table 2). Further follow-up of the GrassrootsHealth cohort may result in larger numbers of cases for particular cancer types, allowing analysis for individual cancer types.
The strengths of this analysis include using serum 25(OH)D concentration, which is the physiological measure of vitamin D status accounting for all input sources including cutaneous, supplementation, and food. Using serum 25(OH)D concentration also overcomes the inherent bias of treatment compliance and inter-individual variability in dose response which are features of analyses based on assignment to treatment groups. Also, entering 25(OH)D concentration and calcium supplement intake as separate covariates allowed us to assess the independent roles of vitamin D and calcium on cancer risk. This analysis also used multiple analysis techniques, including comparing cancer incidence across 25(OH)D groups, computing Kapan- Meier plots, and conducting adjusted Cox regression analyses with multiple 25(OH)D measurements per participant to account for changes in vitamin D status, all of which found a >65% lower risk or rate of cancer for those with 25(OH)D concentrations >40 ng/ml compared to those with concentrations <20 ng/ml. Additionally, this analysis included individuals with a wider range of serum 25(OH)D concentrations than other studies and identified the response region of cancer risk related to 25(OH)D.
Limitations of this study include the use of self-report data for certain variables where recall bias may have occurred. This analysis also was not able to control for some covariates related to cancer risk such as family history of cancer, diet, physical activity, or alcohol use. Differences in methods and demographics between the Lappe and GrassrootsHealth cohorts may have affected pooled analyses, which is why results for the Lappe cohort were also presented separately. The small proportion of current smokers in the study population did not allow for an adequate assessment of the association between smoking status and cancer risk, a known risk factor for cancer. However, this provided a unique opportunity to assess other risk factors without the potentially overpowering influence of smoking. An additional limitation is that we did not have sufficient power to assess associations for individual cancer types. While this analysis did show a significant inverse association of 25(OH)D concentration and risk of cancer for non-Hispanic white women aged 55 years and older, results may not be generalizable to other ethnicities, age groups, or to males.
The findings from this analysis support the inverse association between 25(OH)D and risk of cancer and highlight the importance for cancer prevention of achieving a concentration substantially above 20 ng/ml, the concentration recommended by the IOM for bone health [21]. Increasing 25(OH)D concentrations to a minimum of 40 ng/ml could substantially reduce cancer incidence and associated mortality in the population based on these findings as well as other studies [22-26]. Primary prevention of cancer, rather than solely expanding early detection or improving treatment, will be essential for reversing the current upward trend of cancer incidence worldwide; this analysis suggests that improving vitamin D status is a key prevention tool.
Supporting Information
Fig. Frequency distribution and cancer incidence rates by 25(OH)D concentration, Lappe cohort (N = 1169). The bars represent the number of non-cases by groupings of 10 ng/ ml, white dots represent the 25(OH)D concentration for each cancer case, black dots represent cancer incidence rates per 100,000 person-years for indicated 25(OH)D groupings (plotted at the median 25(OH)D value for each grouping: baseline 25(OH)D groups at 17, 24,29, 35, and 43 ng/ml; mean 25(OH)D groups at 17, 25, 30, 36, and 43 ng/ml). Vertical error bars indicate the 95% confidence intervals. (EPS)
Fig. Kaplan-Meier plot comparing the proportion of cancer-free participants by 25(OH) D concentration (allowing for participants switching groups), Lappe cohort (N = 1169).
Four-year cumulative cancer-free proportion was 97% among participants with 25(OH)D concentrations >40 ng/ml compared to 93% for those with 25(OH)D concentrations <20 ng/ml (proportion with cancer was 57% lower for >40 ng/ml vs. <20 ng/ml, P =0.16). (EPS)
Fig. Association between serum 25(OH)D and risk of cancer adjusted for age, BMI, smoking status, and calcium supplement intake in the range of <50 ng/ml, Lappe cohort (N= 1169). Solid black line represents the estimated hazard ratio for the Cox regression model with restricted cubic splines with 3 knots and dashed lines represent the 95% confidence interval of the estimate. The reduction in risk from 20 ng/ml to 40 ng/ml was approximately 80%. (EPS)
Table. Cancer types for pooled, Lappe, and GrassrootsHealth cohorts. (DOCX)
Table. Association between serum 25(OH)D and risk of cancer, Lappe cohort (N= 1169). (DOCX)Acknowledgments
The authors wish to thank the participants who provided the information for this study.
Author Contributions
Conceived and designed the experiments: JML RPH CB LLB CBF CFG. Performed the experiments: JML RPH CB CBF. Analyzed the data: RPH SLM LLB. Wrote the paper: SLM CB CBF LLB CFG EDG RPH.References
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159 citations of this study as of Dec 2022
- Review of Recent Advances in Understanding the Role of Vitamin D in Reducing Cancer Risk: Breast, Colorectal, Prostate, and Overall Cancer - GRANT - Jan 2020 https://doi.org/10.21873/anticanres.13977
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