Ian Clements’ Vitamin D research
Posted by Jonathan Chamberlain on April 21, 2011
YouTube presentations: 2
Vitamin D Prevents Cancer: Is It True?. 2
Gabriele Stähler on Vitamin D3. 2
Most Americans Seem to Have Healthy Levels of Vitamin D.. 3
Vitamin D Linked to Lung Cancer Survival, Study Suggests. 3
Higher Vitamin D Intake Could Cut Cancer Risk. 4
Associations of circulating and dietary vitamin D with prostate cancer risk. 4
Tanned women live longer (as long as you sunbathe sensibly), say scientists. 5
Taking Vitamin D, Calcium Supplements Not Necessary. 6
Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology 7
Serum vitamin D and risk of bladder cancer in smokers. 8
Insufficient Vitamin D Levels in Chronic Lymphocytic Leukemia Patients Linked to Cancer Progression and Death 9
Vit D and Bladder Cancer 11
Vitamin D Levels Confusion. 11
Vitamin D Deficiency Confirmed as Common Across a Range of Rheumatic Conditions 12
Vitamin D: With Meals, or Without?. 12
“Researchers at the Cleveland Clinic discovered that taking vitamin D with large meals boosts its absorption dramatically. 12
Vit D Research Video. 12
Vitamin D deficiency linked to more aggressive lymphoma. 12
Peter Granger’s Views. 13
Jan Alexander’s Views. 15
Vitamin A Reduces Vitamin D’s Effectiveness. 15
Vitamin D and Calcium Interplay Explored. 16
Recommended Level of Vit D.. 17
ask for the 25-Hydroxy Vitamin D test 18
Vitamin D Crucial to Activating Immune Defenses. 18
Chemical Reaction that Enables Activation. 19
Activating and Deactivating the Immune System.. 20
Vitamin D, Miracle Drug: Is It Science, or Just Talk?. 20
The Roles of Vitamin D Binding Protein in Human Immune Function. 23
From: Peter Granger (pete.granger@GMAIL.COM) 26
The Anticancer Effects Of Vitamin D3. 27
Vitamin D Levels Associated With Survival in Lymphoma Patients. 27
Meta-analysis of longitudinal studies: Serum vitamin D and prostate cancer risk. 29
Does Vitamin D Treat Cancer?. 29
It’s not that simple… 29
Summer diagnosis prolongs life. Why?. 30
Sunlight’s robust treatment effect 31
So, how much vitamin D does one need?. 31
Vitamin D’s unique behavior 32
25(OH)D level should be greater than 60 ng/mL.. 33
Little to no risk. 33
The real risk: waiting for further studies. 34
Vitamin D Can Alter Colon Cancer Cells In Many Ways, Through One Pathway. 34
Macrophage Activation May Suppress Breast Cancer Metastasis. 35
Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, Gc-MAF. 36
Colon cancer: prognosis for different latitudes, age groups and seasons in Norway. 37
Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans: An Important Tool to Define Adequate Nutritional Vitamin D Status. 37
Materials and Methods. 38
Women With Breast Cancer Have Low Vitamin D Levels. 43
Real Help for Cancer?. 44
High Levels of Vitamin D in Older People Can Reduce Heart Disease and Diabetes. 47
VITAMIN D TESTING 48
Inadequate Levels of Vitamin D May Significantly Increase Risk of Stroke, Heart Disease and Death 49
Heart and Bone Damage from Low Vitamin D Tied to Declines in Sex Hormones. 50
Vitamin D linked to lower heart disease risk. 52
Rheumatoid Arthritis Linked to Vitamin D Deficiency, Study Suggests. 54
Low Vitamin D Levels Associated With More Asthma Symptoms and Medication Use. 55
Researchers Recommend Pregnant Women Take 4,000 IU Vitamin D a Day. 56
Low Vitamin D Levels Are Related to MS Brain Atrophy, Cognitive Function, Studies Show 57
Vitamin D Deficiency Associated With Chronic Fatigue in Brain Injured Patients. 59
Better Vitamin D Status Could Mean Better Quality of Life for Seniors. 60
Effect of 25-hydroxyvitamin D status on serological response to influenza vaccine in prostate cancer patients 61
Vitamin D Prevents Cancer: Is It True?[i]
Gabriele Stähler on Vitamin D3[ii]
Most Americans Seem to Have Healthy Levels of Vitamin D[iii]
WEDNESDAY, March 30 (HealthDay News) — Nearly two-thirds of U.S. residents have sufficient levels of vitamin D levels, but about a fourth of the population is at risk for vitamin D inadequacy and 8 percent are at risk for vitamin D deficiency, a new federal government study indicates.
An additional 1 percent of Americans have vitamin D levels high enough that could be harmful, according to the report, released Wednesday by researchers at the U.S. National Center for Health Statistics, part of the U.S. Centers for Disease Control and Prevention.
The body needs vitamin D to help it absorb calcium, which is a requisite for healthy bones. Muscles and nerves need vitamin D to function properly, and it helps the immune system fight off disease. Too little can lead to thin, brittle bones; extremely high levels can be toxic.
Vitamin D can be absorbed naturally from sunlight or obtained through foods or dietary supplements.
The National Institute of Medicine defines sufficient vitamin D by the amount registered in the blood: as a serum 25-hydroxyvitamin D value of 50-125 nmol/L. A value of 30-49 nmol/L is defined as inadequacy and less than 30 nmol/L is considered a deficiency.
For their report, the researchers analyzed data from 2001 to 2006 from the National Health and Nutrition Examination Survey. It included people aged 1 and older.
The analysis showed that the risk for vitamin D deficiency differed by age, sex and race or ethnicity.
By age, the risk for deficiency ranged from 1 percent to 8 percent among males and from 1 percent to 12 percent among females. For both sexes, the risk was lowest among children aged 1 to 8 and increased significantly until age 30 in men and age 18 in women. After that, the risk changed little as people aged, the study found.
Whites were less likely to be at risk for vitamin D deficiency than blacks or Mexican-Americans.
Among women of childbearing age, those who were pregnant or lactating were less likely to be at risk for vitamin D deficiency than those who weren’t pregnant or lactating.
Though vitamin D deficiency became more common in the United States between 1988-1994 and 2001-2002, the study found, risk for the deficiency did not change between 2001-02 and 2005-06.
About 4 percent of males 12 years and older had vitamin D levels that put them at risk for deficiency in 1988-1994, and 17 percent were at risk for inadequacy. Those numbers had risen to 7 percent and 22 percent, respectively, by 2001-2002, according to the study.
Among females 12 and older, vitamin D deficiency rose from 7 percent in 1988-1994 to 11 percent in 2001-2002. However, the proportion of females with inadequate levels of vitamin D dropped from 30 percent to 25 percent in that time.
Vitamin D Linked to Lung Cancer Survival, Study Suggests[iv]
ScienceDaily (Mar. 1, 2011) — Recent research suggests vitamin D may be able to stop or prevent cancer. Now, a new study finds an enzyme that plays a role in metabolizing vitamin D can predict lung cancer survival.
The study, from researchers at the University of Michigan Comprehensive Cancer Center, suggests that this enzyme stops the anti-cancer effects of vitamin D.
Levels of the enzyme, called CYP24A1, were elevated as much as 50 times in lung adenocarcinoma compared with normal lung tissue. The higher the level of CYP24A1, the more likely tumors were to be aggressive. About a third of lung cancer patients had high levels of the enzyme. After five years, those patients had nearly half the survival rate as patients with low levels of the enzyme.
Researchers then linked this to how CYP24A1 interacts with calcitriol, the active form of vitamin D. CYP24A1 breaks down calcitriol, which has a normal and crucial role when kept in check. But when levels of CYP24A1 climb, the enzyme begins to hinder the positive anti-cancer effects of vitamin D.
Results of the study appear in Clinical Cancer Research.
Previous studies have linked low levels of vitamin D to a higher incidence of cancer and worse survival. Researchers are looking at using vitamin D to help prevent lung cancer from returning and spreading after surgery. This new study suggests the possibility of using CYP24A1 levels to personalize this approach to those likely to benefit most.
“Half of lung cancers will recur after surgery, so it’s important to find a way to prevent or delay this recurrence. A natural compound like vitamin D is attractive because it has few side effects, but it’s even better if we can determine exactly who would benefit from receiving vitamin D,” says study author Nithya Ramnath, M.D., associate professor of internal medicine at the U-M Medical School.
Researchers also are working to identify drugs that block CYP24A1. Blocking the enzyme would reinstate the positive anti-cancer effects of vitamin D, suggesting that this inhibitor could potentially be combined with vitamin D treatments.
Note: Current recommendations call for 600-800 IU of vitamin D daily, depending on age. Studies looking at vitamin D in lung cancer are testing medically administered doses 200 times what could be taken by mouth naturally. Taking large amounts of vitamin D supplements is not currently recommended to prevent or treat lung cancer.
Lung cancer statistics: 222,520 Americans will be diagnosed with lung cancer this year and 157,300 will die from the disease, making it the biggest cancer killer, according to the American Cancer Society
Additional U-M authors: Guoan Chen, So Hee Kim, Amanda N. King, Lili Zhao, Robert U. Simpson, Paul J. Christensen, Zhuwen Wang, Dafydd G. Thomas, Thomas J. Giordano, Lin Lin, Dean E. Brenner, David G. Beer
Funding was provided by the National Institutes of Health.
Journal Reference: H. Meng, G. Chen, X. Zhang, Z. Wang, D. G. Thomas, T. J. Giordano, D. G. Beer, M. M. Wang. Stromal LRP1 in lung adenocarcinoma predicts clinical outcome. Clinical Cancer Research, 2011; DOI: 10.1158/1078-0432.CCR-10-2385
Higher Vitamin D Intake Could Cut Cancer Risk[v]
SUNDAY, Feb. 27 (HealthDay News) — A new study says it takes far more vitamin D than initially thought to dramatically cut the risk of several major diseases, including breast cancer.
“We found that daily intakes of vitamin D by adults in the range of 4,000-8,000 IU are needed to maintain blood levels of vitamin D metabolites in the range needed to reduce by about half the risk of several diseases — breast cancer, colon cancer, multiple sclerosis and type 1 diabetes,” study co-author Dr. Cedric Garland, a professor of family and preventive medicine at the University of California at San Diego, said in a university news release.
Garland admitted that he was surprised that the levels required were so much higher than the 400 IU a day needed to vanquish rickets in the 20th century.
Vitamin D supplements often come in pills or capsules containing 1,000 or 2,000 international units. But 4,000 to 8,000 IU a day is still much lower than the range considered safe by the National Academy of Science’s Institute of Medicine, the researchers noted.
The study — which also involved the Creighton University School of Medicine in Omaha — was based on a survey of several thousand people who took supplements ranging from 1,000 to 10,000 IU per day. The volunteers also underwent blood tests to determine the levels of vitamin D metabolites circulating in their blood.
Some studies suggest that only 10 percent of people in the United States have the appropriate level of the vitamin D-related form in their blood to prevent disease linked to a deficiency of the vitamin. These people tend to work outdoors, where their vitamin D levels are boosted through sun exposure.
Last year, a National Academy of Sciences Institute of Medicine (IOM) committee announced that 4,000 IU a day of vitamin D appears safe for adults and kids aged 9 and up.
The IOM’s recommended minimum daily level is 600 IU, however, and the Institute noted there were preliminary signals that there might be some harms associated with consuming high levels of vitamin D daily, even at amounts under the recommended upper safe limit.
Garland and his colleagues suggested that 4,000 IU a day is a safe level.
“Now that the results of this study are in, it will become common for almost every adult to take 4000 IU/day,” Garland predicted in the news release. “This is comfortably under the 10,000 IU/day that the IOM Committee Report considers as the lower limit of risk, and the benefits are substantial.”
The findings appear in the journal Anticancer Research.
Associations of circulating and dietary vitamin D with prostate cancer risk[vi]
a systematic review and dose–response meta-analysis Cancer Causes and Control, 01/17/2011 Evidence Based Medicine Gilbert R et al. – Published literature provides little evidence to support a major role of vitamin D in preventing prostate cancer or its progression. Authors searched over 24,000 papers from seven electronic databases (to October 2010) for exposures related to vitamin D
Tanned women live longer (as long as you sunbathe sensibly), say scientists[vii]
By Sophie Borland
Last updated at 1:51 AM on 4th December 2010
Women who regularly sunbathe live longer, a leading cancer specialist has claimed.
Hakan Olsson says his research shows the health benefits of exposure to sunlight ‘far outweigh’ the danger of skin cancer.
He said vitamin D produced by the body when tanning gives vital protection against blood clots, diabetes and some tumours.
But the professor’s claims, based on a study of 40,000 women, sharply contradict warnings that sun exposure is behind soaring levels of skin cancer.
Dr Ollson said catching the sun had more health benefits than costs, as long as you don’t burn
Rates of malignant melanoma, the deadliest form of the disease, have quadrupled since 1980. Experts blame the rise on sunbeds and the increasing numbers of Britons going abroad on cheap package holidays.
But Professor Olsson, who works in the oncology unit at Lund University in Sweden, believes the benefits of the sun ‘far outweigh the negatives’.
He said there was overwhelming evidence that exposure to the sun helps protect against blood clots in the leg, which claim the lives of 25,000 Britons a year.
These clots, known as deep vein thromboses, have been shown to be far more prevalent in winter than summer.
Professor Olsson, who was presenting his research at the Swedish Society of Medicine, cited other studies showing that more patients are diagnosed with diabetes in the colder months, a phenomenon attributed to a lack of vitamin D.
For his study, he examined tanning habits and the incidence of illnesses such as heart disease, diabetes or malignant melanoma.
‘Our studies show that women with active sunbathing habits live longer,’ he said.
Professor Olsson also suggested that skin cancer was not caused by sunbathing alone.
‘I and many others believe that there may be factors other than the sun that influence the risk of malignant melanoma,’ he said.
‘The burning of the skin in the sun is not enough to explain this.’
But Ed Yong, of Cancer Research UK, said: ‘While some sunshine is good for us and vitamin D is important for good bone health, there’s inconclusive evidence to suggest that vitamin D protects against other disease such as cancer or heart disease.
‘Not burning is the most important thing people can do to protect themselves against developing skin cancer. Sunburn is a clear sign that skin cells have been damaged and increases the risk of the disease.
‘Everyone is different and you’re most at risk from skin cancer if you have fair skin, red hair, lots of freckles, moles, or a family history of the disease. These people should take extra care in the sun.’
Experts warn that most Britons lack vitamin D, which is found in oily fish, eggs and butter. Ninety per cent of our supply of it comes from the action of sunlight on the skin.
Taking Vitamin D, Calcium Supplements Not Necessary[viii]
Posted on: Tuesday, 30 November 2010, 09:21 CST
Most people get enough vitamin D from the sun, and there’s no evidence that taking supplements of the so-called sunshine vitamin will fight off cancer, prevent diabetes, or strengthen a person’s immune system, a panel of U.S. and Canadian doctors said on Tuesday.
The announcement comes as part of a new set of dietary intake guidelines for both calcium and vitamin D, released this week by the Institute of Medicine (IOM), an independent American health agency established in 1863.
Using expert testimony and nearly 1,000 published studies analyzing the two nutrients, the IOM discerned that most North Americans 70 years of age or under need just 600 international units (IUs) of vitamin D per day, and those over the age of 71 need 800 IUs. Calcium intake, on the other hand, can vary from 700 to 1,300 milligrams daily.
“The committee that wrote the report also reviewed hundreds of studies and reports on other possible health effects of vitamin D, such as protection against cancer, heart disease, autoimmune diseases, and diabetes,” the IOM said in a Tuesday press release. “While these studies point to possibilities that warrant further investigation, they have yielded conflicting and mixed results and do not offer the evidence needed to confirm that vitamin D has these effects.”
However, both calcium and vitamin D were proven to have positive effects when it comes to bone health and skeletal growth and maintenance, the researchers noted.
“There is abundant science to confidently state how much vitamin D and calcium people need,” Committee Chairperson Catharine Ross, a professor with the Pennsylvania State University Department of Nutritional Sciences, said in a statement. “We scrutinized the evidence, looking for indications of beneficial effects at all levels of intake. Amounts higher than those specified in this report are not necessary to maintain bone health.”
Children between the ages of 1 and 3 should consume 700mg of calcium per day, while kids between the ages of 4 and 8 should up their intake to 1,000mg, the IOM said. Individuals between the ages of 9 and 18 need no more than 1,300mg of calcium daily, while most adults between the ages of 19 and 50 can reduce their calcium intake back down to 1,000mg. Men over the age of 50 and under the age of 71 can maintain that level, while women are advised to up their consumption to 1,200mg daily.
“The majority of Americans and Canadians are getting enough vitamin D and calcium, the committee determined from reviewing national surveys of blood levels,” the IOM reported. “Some adolescent girls may not get quite enough calcium, and there is a greater chance that elderly individuals may fall short of the necessary amounts of calcium and vitamin D. These individuals should increase their intake of foods containing these nutrients and possibly take a supplement.”
Overdosing on either nutrient can be dangerous, the researchers reported. Consuming high levels of vitamin D (at least 10,000 IUs daily) are known to cause kidney and tissue damage, they claim, and even taking 4,000 IUs daily could be risky. In terms of calcium, the IOM says that taking more than 2,000mg each day could lead to kidney stones, especially in post-menopausal women.
Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology[ix]
Nutrition Journal 2010, 9:60doi:10.1186/1475-2891-9-60
Published: 23 November 2010
Serum 25-hydroxyvitamin D [25(OH)D] is the major circulating form of vitamin D and a standard indicator of vitamin D status. Emerging evidence in the literature suggests a high prevalence of suboptimal vitamin D (as defined by serum 25(OH)D levels of <32 ng/ml) as well as an association between lower serum levels and higher mortality in cancer. We investigated the effect of oral vitamin D supplementation as a means for restoring suboptimal levels to optimal levels in cancer.
This is a retrospective observational study of 2198 cancer patients who had a baseline test prior to initiation of cancer therapy at our hospital to evaluate serum 25(OH)D levels between Jan 08 and Dec 09 as part of their initial nutritional evaluation. Patients with baseline levels of <= 32 ng/ml (n=1651) were considered to have suboptimal serum 25(OH)D levels and were supplemented with 8000 IU of Vitamin D3 (four 2000 IU D3 capsules) daily as part of their nutritional care plan. The patients were retested at their first follow-up visit. Of 1651 patients, 799 were available for follow up assessment. The mean serum 25(OH)D levels were compared in these 799 patients across the 2 time points (baseline and first follow-up) using paired sample t-test. We also investigated the factors associated with response to vitamin D supplementation.
Of 2198 patients, 814 were males and 1384 females. 1051 were newly diagnosed and treated at our hospital while 1147 were diagnosed and treated elsewhere. The mean age at presentation was 55.4 years. The most common cancer types were breast (500, 22.7%), lung (328, 14.9%), pancreas (214, 9.7%), colorectal (204, 9.3%) and prostate (185, 8.4%). The mean time duration between baseline and first follow-up assessment was 14.7 weeks (median 10.9 weeks and range 4 weeks to 97.1 weeks). The mean serum 25(OH)D levels were 19.1 ng/ml (SD = 7.5) and 36.2 ng/ml (SD = 17.1) at baseline and first follow-up respectively; p <0.001. Patients with prostate and lung cancer had the highest percentage of responders (70% and 69.2% respectively) while those with colorectal and pancreas had the lowest (46.7% each). Similarly, patients with serum levels 20-32 ng/ml at baseline were most likely to attain levels >32 ng/ml compared to patients with baseline levels <20 ng/ml.
The response to supplementation from suboptimal to optimal levels was greatest in patients with prostate and lung cancer as well as those with baseline levels between 20-32 ng/ml. Characteristics of non-responders as well as those who take longer to respond to supplementation need to be further studied and defined. Additionally, the impact of improved serum 25(OH)D levels on patient survival and quality of life needs to be investigated.
Serum vitamin D and risk of bladder cancer in smokers[x]
Tuesday, 16 November 2010
Vitamin D may protect against several cancers, but data about the association between circulating vitamin D and bladder cancer are limited. Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a randomized controlled trial conducted to determine the effects of α-tocopherol and β-carotene supplements on cancer incidence in male smokers, 250 bladder cancer cases were randomly sampled by month of blood collection. Controls were matched 1:1 to cases on age at randomization and date of blood collection. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer by a priori categories of baseline serum 25-hydroxyvitamin D [25(OH)D; i.e., < 25, 25 to < 37.5, 37.5 to < 50, ≥50 nmol/L] and by season-specific quartiles. After multivariable adjustment, we found that lower 25(OH)D was associated with a statistically significantly increased risk of bladder cancer (versus ≥50 nmol/L; < 25 nmol/L: OR, 1.73; 95% CI, 1.03-2.91; 25 to < 37.5 nmol/L: OR, 1.81; 95% CI, 1.05-3.14; 37.5 to < 50 nmol/L: OR, 1.76; 95% CI, 1.02-3.02; P trend = 0.04). Similarly, increased risks for the lowest vitamin D category were observed when season-specific quartiles were used (Q1 versus Q4: OR, 1.63; 95% CI, 0.96-2.75; P trend = 0.03). In this prospective study of male smokers, lower serum 25(OH)D was associated with an increased risk of bladder cancer. Future studies should examine the association in other populations, especially nonsmokers and women.
Written by: Mondul AM, Weinstein SJ, Männistö S, Snyder K, Horst RL, Virtamo J, Albanes D
Reference: Cancer Res. 2010 Oct 26. doi: 10.1158/0008-5472.CAN-10-0985
PubMed Abstract PMID: 20978193
Insufficient Vitamin D Levels in Chronic Lymphocytic Leukemia Patients Linked to Cancer Progression and Death[xi]
ScienceDaily (Nov. 4, 2010) — Researchers at Mayo Clinic have found a significant difference in cancer progression and death in chronic lymphocytic leukemia (CLL) patients who had sufficient vitamin D levels in their blood compared to those who didn’t.
In the Mayo Clinic study, published online in the journal Blood, the researchers found that patients with insufficient levels of vitamin D when their leukemia was diagnosed progressed much faster and were about twice as likely to die as were patients with adequate levels of vitamin D.
They also found solid trends: increasing vitamin D levels across patients matched longer survival times and decreasing levels matched shortening intervals between diagnosis and cancer progression. The association also remained after controlling for other prognostic factors associated with leukemia progression.
The finding is significant in a number of ways. For the first time, it potentially offers patients with this typically slower growing form of leukemia a way to slow progression, says the study’s lead author, Tait Shanafelt, M.D., a hematologist at Mayo Clinic in Rochester, Minn.
“This finding may be particularly relevant for this kind of leukemia because although we often identify it at an early stage, the standard approach is to wait until symptoms develop before treating patients with chemotherapy,” Dr. Shanafelt says. “This watch and wait approach is difficult for patients because they feel there is nothing they can do to help themselves.”
“It appears vitamin D levels may be a modifiable risk factor for leukemia progression. It is simple for patients to have their vitamin D levels checked by their physicians with a blood test,” he says. “And if they are deficient, vitamin D supplements are widely available and have minimal side effects.”
While the researchers have not yet determined if vitamin D replacement in patients with initially low levels will reverse the more rapid progression associated with insufficiency, they are planning a study to explore that hypothesis.
This research adds to the growing body of evidence that vitamin D deficiency is a risk factor for development and/or progression of a number of cancers, the researchers say. Studies have suggested that low blood vitamin D levels may be associated with increased incidence of colorectal, breast and other solid cancers. Other studies have suggested that low vitamin D levels at diagnosis may be associated with poorer outcomes in colorectal, breast, melanoma and lung cancers, as well as lymphoma.
Replacing vitamin D in some patients has proven to be beneficial, the researchers say. For example, they cite a placebo-controlled clinical trial that found women who increased their vitamin D intake reduced their risk of cancer development.
Vitamin D insufficiency, in general, is widespread, Dr. Shanafelt says. “Between one-fourth and one-half of patients seen in routine clinical practice have vitamin D levels below the optimal range, and it is estimated that up to 1 billion people worldwide have vitamin D insufficiency,” he says.
Vitamin D is obtained from skin exposure to sunlight, from certain foods (fatty fish and eggs) and from supplements.
In this study, the research team, including physicians at the University of Iowa, enrolled 390 CLL patients into a prospective, observational study. They tested the blood of these newly diagnosed patients for plasma concentration of 25-hydroxyl-vitamin D and found that 30 percent of these CLL patients were considered to have insufficient vitamin D levels, which is classified as a level less than 25 nanograms per milliliter.
After a median follow-up of three years, CLL patients deficient in vitamin D were 66 percent more likely to progress and require chemotherapy; deficient patients also had a two-fold increased risk of death.
To confirm these findings, they then studied a different group of 153 untreated CLL patients who had been followed for an average of 10 years. The researchers found that about 40 percent of these 153 CLL patients were vitamin D deficient at the time of their diagnosis. Patients with vitamin D deficiency were again significantly more likely to have had their leukemia progress and to have died, Dr. Shanafelt says.
“This tells us that vitamin D insufficiency may be the first potentially modifiable risk factor associated with prognosis in newly diagnosed CLL,” he says.
The study was funded by the National Institutes of Health (http://www.nih.gov/), Gabrielle’s Angel Foundation for Cancer Research, the Henry J. Predolin Foundation, Vysis, Inc., and the Mayo Hematologic Malignancies Fund. The authors declare no conflicts of interest.
Vit D and Bladder Cancer
Reported by Crilly 4 Nov ‘11
Higher vitamin D levels associated with lower risk of bladder cancer An article published online on October 26, 2010 in the journal Cancer Research reveals an association between higher levels of serum vitamin D and a lower risk of bladder cancer in men. The finding adds another cancer to the list of those for which vitamin D appears to have a protective benefit. The current study involved 500 participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a randomized, double-blinded trial of Finnish male smokers conducted to determine the effects of alpha-tocopherol and beta-carotene supplementation on cancer risk. Participants were cancer-free at the beginning of the study. Blood samples drawn upon enrollment between 1985 and 1988 were analyzed for serum 25-hydroxyvitamin D levels and other factors. The National Cancer Institute researchers compared 250 subjects who were diagnosed with bladder cancer through April, 2005 and an equal number of participants who did not have the disease. Cases and controls were matched for age and date of blood draw. A low level of vitamin D was associated with a significantly greater risk of bladder cancer. Men whose vitamin D level was less than 25 nanomoles per liter experienced a 73 percent greater adjusted risk of the disease than those whose levels were at least 50 nanomoles per liter. Similar risks were observed for those whose levels fell between 25 and less than 37.5, and from 37.5 to less than 50 nanomoles per liter. "These findings are consistent with previous cell culture, in vivo, and genetic evidence suggesting that greater exposure to vitamin D could have a role in protecting against bladder cancer," Alison M. Mondul and co-authors write. "Higher serum 25-hydroxyvitamin D may be associated with greater urinary excretion and concentration of free and conjugated vitamin D metabolites. Increased exposure of the bladder mucosa to these metabolites could promote transitional cell differentiation and apoptosis and, thus, reduce epithelial proliferation and neoplasia." "Future studies should examine the association in other populations, especially nonsmokers and women, and evaluate possible effect modification by season of blood draw, physical activity, and intake of other nutrients, including vitamin E," they recommend.
Vitamin D Levels Confusion
From: Crilly Butler (crilly@DCN.ORG)
Sent: 01 July 2010 01:46:54
Remember--when Vit D levels are tested, the BLOOD levels are being tested, not the fat levels. Seems to me that the more Vit D stored in the fat, the less is available to the cells that need it as fed through the circulatory system. Also remember that Vit D is only stored in the fat, or made available to the cells that need it, when it is absorbed during digestion. That requires a complex interplay between GI transit time, condition of the GI tract, other foods with which the Vit D is taken, the amount of water consumed, and the interaction between Vit D, Calcium, Magnesium and probably other vitamins and minerals as well, not to mention your amount of sun exposure. Why some people seem to absorb Vit D and/or utilize it more effectively than others is difficult to pin down. That's why it's a good idea to slowly up your intake of the vitamin over time while regularly checking your blood levels until you reach the correct dosage.
Vitamin D Deficiency Confirmed as Common Across a Range of Rheumatic Conditions[xii]
ScienceDaily (June 19, 2010) — Two separate studies have shown that vitamin D deficiency is common in patients with a range of rheumatic diseases, with over half of all patients having below the ‘normal’ healthy levels of vitamin D (48-145 nmol/L) in their bodies. A further study assessing response to vitamin D supplementation found that taking the recommended daily dose did not normalise vitamin D levels in rheumatic disease patients.
Researchers found that, regardless of supplementation, levels of 25-hydroxyvitamin D (25(OH)D), (a standard clinical measure of vitamin D in the blood), were lower than healthy levels (<50 nmol/L) in 85% of the patients not taking a vitamin D supplement and in 60% of those taking 800 IU or more vitamin D daily as a supplement.
“The results of our study show that daily 800-1,000 IU supplementation is not sufficient to normalise vitamin D levels in patients with rheumatologic or bone conditions. What is unclear is whether a higher dose would be more effective.”
“Researchers at the Cleveland Clinic discovered that taking vitamin D with large meals boosts its absorption dramatically.
Vit D Research Video
Vitamin D deficiency linked to more aggressive lymphoma[xiii]
(NaturalNews) Lymphoma patients with vitamin D deficiency are twice as likely to die from their cancer than patients with sufficient blood levels of the vitamin, according to a study conducted by researchers from the Mayo Clinic and presented at a meeting of the American Society of Hematology.
Researchers took blood samples from 374 patients between 2002 and 2008 who had been recently diagnosed with a cancer of the white blood cells known as diffuse large B-cell lymphoma. The average participant age was 62.
Approximately 40 percent of all lymphomas are of the diffuse large-B cell type. The disease mainly affects people over the age of 50.
The researchers found that roughly 50 percent of all participants suffered from vitamin D deficiency at the beginning of the study, defined as having blood levels below 25 nanograms per liter. Over an average of three years of follow-up, patients with vitamin D deficiency were 50 percent more likely to have their cancer worsen and twice as likely to die as patients with vitamin levels above 25 nanograms per liter.
Researchers have known for a long time that vitamin D helps regulate calcium absorption and thus plays a crucial role in bone and dental health. Recent research suggests that the vitamin may also help regulate the immune system, and that higher levels can help prevent against chronic diseases such as Alzheimer’s, cancer, diabetes and dementia. Some researchers are making the case that for these benefits, vitamin D levels must be maintained at a level closer to 40 nanograms per liter.
The Mayo Clinic researchers used the 25 nanogram per liter cutoff because that is the level at which the body begins to leach calcium from its own bones, and is therefore a well-defined deficiency threshold.
Prior research has suggested that vitamin D deficiency may worsen the prognosis for patients with breast, colon and throat cancers.
Sources for this story include: www.sciencenews.org.
Peter Granger’s Views
From: Peter Granger (pete.granger@GMAIL.COM) Sent: 07 April 2010 21:31:07 & 16 May 2010 00:14:44 Most people are vitamin D deficient. I have been taking 4,000 - 8,000 IU/day (divide by 40 for conversion to mcg) for several years now, and my vitamin D [(25(OH)D] levels are at the maximum desirable range - which is about 56 ng/ml, or 140 nmol/L. [The recommended maximum levels vary considerably - http://www.easy-immune-health.com/Normal-Vitamin-D-level.html I wont be increasing this level, in fact, I may try and reduce it fractionally to be on the safe side. Those taking Oncovite may have lower vitamin D levels, and may need to increase their vitamin D intake until it gets into the preferred range. I am not a medical practitioner, but I believe the research is suggesting an increased intake of vitamin D and vitamin K (spinach, greens), in combination with modest dietary intake of calcium (dairy foods), is a more desirable option than supplementing with high doses of calcium. A daily 'dose' of spinach and ricotta pie is looking more and more attractive. Actually, to reach the calcium rda, you will need (say) 1 cup of ricotta, plus one cup of yoghurt, plus a little cheese or milk. http://www.dentalgentlecare.com/Calcontfood. I have serious concerns about calcium supplementation in the absence of adequate vitamin D and vitamin K levels. It seems much preferable to get adequate calcium from dairy foods, and vitamin K from greens - esp, spinach and parsely), plus some vitamin D supplementation. I believe treating calcium, vitamin D and vitamin K as separate entities has been a big mistake. Time will tell. & Its unlikely you will get vitamin D toxicity unless you start getting up to the 300 level (much less if pregnant). Nonetheless, both too much or too little vitamin D might increase the risk of atherosclerosis, so its better to keep vitamin D levels in moderation. Between 40 - 100 is recommended for cancer patients. Mine are are currently at 150 (excessive supplementation), which I am cutting back to below 100. 'vitamin D intoxication will not occur until a person (an adult) is taking more than 10,000 IU of vitamin D/d for more than six months'. 'my preference is to recommend that you take no more than 3,000 IU of vitamin D/d.' You can get more detail from: http://www.vitamindhealth.org/?p=63#more-63 Pete (and his quote from Wikipedia below)
'A concentration of over 15 ng/ml (>37.5 nmol/L) is recommended. Higher levels (>30 ng/ml or >75 nmol/L) are proposed by some as desirable for achieving optimum health but there is not enough evidence to support them.' 'Vitamin D toxicity is usually the result of taking supplements in excess, when toxic symptoms occur the serum 25(OH)D levels are usually found to be elevated >150 ng/mL (>375 nmol/L). 'full body exposure to sunlight (produces) approximately 250 µg (10,000 IU) per day'. 'The U.S. Dietary Reference Intake Tolerable Upper Intake Level (upper limit) of vitamin D for children and adults is set at 50 micrograms/day (2,000 IU)'. 'prompted a researcher  to suggest that 250 micrograms/day (10,000 IU) in healthy adults should be adopted as the tolerable upper limit' One study found a possible negative link between excessive vitamin D supplementation and calcification/atherosclerosis, however this risk may be confined to African-Americans (it is quite possible African Americans require much lower levels of vitamin D, and excessive supplementation may be harmful) - 'dietary vitamin D may be carried by lipoprotein particles into cells of the artery wall and atherosclerotic plaque, where it may be converted to active form by monocyte-macrophages'. A 2007 study reports that vitamin D supplementation (1,100 international units (IU)/day) resulted in a 60% reduction in cancer incidence, during a four-year clinical trial, rising to a 77% reduction for cancers diagnosed after the first year (and therefore excluding those cancers more likely to have originated prior to the vitamin D intervention). However, smokers who supplement with vitamin D may be at an additional risk of cancer.
Jan Alexander’s Views
From: Jan Alexander (jea1013@YAHOO.COM)
Sent: 16 May 2010 00:22:21
seems like we are all different–I have to take 8000/day just to maintain my level at 70. there is some thought that taking cod liver oil may interfere with the absorption of vit. d. i guess there is a lot we don’t know about this. but it is being researched more and more because it seems implicated in so many diseases, or rather, the lack of it seems implicated.
From: Jan Alexander (jea1013@YAHOO.COM)
Sent: 29 June 2010 15:27:14
My oncologist feels that anyone with cancer needs to have Vitamin D levels definitely above 60, and closer to 80 is better. At 50,000 IU/week my level will not budge above 60, so now I am at 72,000 IU/week, and will get my levels tested again next month. This is VERY important, she feels, for people with cancer, to keep those levels up. 30 is considered "normal" but is NOT enough for us. -Jan
Vitamin A Reduces Vitamin D’s Effectiveness[xv]
Posted by Dr. Mercola | March 16 2010
The British Medical Journal has published a remarkable paper confirming that low vitamin D levels obtained in the past are a risk factor for developing colon cancer in the future.
But the study contained an even more significant finding — as Dr. Cannell’s site has reported before, vitamin A, even in relatively low amounts, can thwart vitamin D’s association with reduced rates of colon cancer.
This is the largest study to date showing vitamin A blocks vitamin D’s effect.
Hidden on page eight of the paper was one sentence and a small table, showing that the benefits of vitamin D are almost entirely negated in those with the highest vitamin A (retinol) intake.
And the retinol intake did not have to be that high — only about 3,000 IU/day. Young autistic children often take 3,500 IU of retinol a day in their powdered multivitamins, which doesn’t count any additional vitamin A given in high single doses.
The finding explains some of the anomalies in other papers on vitamin D and cancer — similar studies sometimes have widely different results. This may be because the effect of vitamin A was not taken into account. In some countries, cod liver oil, which contains vitamin A, is commonly used as a vitamin D supplement, and in others it is used more rarely, causing differences in the results.
Vitamin D and Calcium Interplay Explored[xvi]
ScienceDaily (Mar. 15, 2010) — Increasing calcium intake is a common — yet not always successful — strategy for reducing bone fractures. But a study supported in part by the Agricultural Research Service (ARS) underscores the importance of vitamin D and its ability to help the body utilize calcium. The study also may explain why increasing calcium alone isn’t always successful in dealing with this problem.
Currently, calcium intake recommendations are not tied to vitamin D status, which may explain why markedly different recommended calcium intakes exist among countries. In the United States, the recommended calcium intake is 1,200 milligrams (mg) daily for adults aged 50 and older.
The body’s skeleton needs adequate dietary calcium to reach its full potential in terms of bone mass. Still, many other factors affect bone mass, such as exercise, smoking and vitamin D — the latter through its effect on calcium absorption and direct effect on the skeleton.
The study involved a close look at about 10,000 men and women aged 20 and older participating in a nationally representative survey. Coauthors included nutrition specialist Bess Dawson Hughes with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston, Mass. Dawson Hughes is director of the HNRCA Bone Metabolism Laboratory.
Blood levels of 25-hydroxyvitamin D are used as the primary indicator of vitamin D adequacy. Within the study sample of U.S. adults, a large fraction of younger and older adults were below a suggested desirable serum vitamin D concentration of at least 75 nanomoles-per-liter (nmol/L).
The study supports the idea that correcting inadequate blood levels of vitamin D is more important than increasing dietary calcium intake beyond 566 mg a day among women and 626 mg a day among men for better bone mineral density. For example, a higher calcium intake beyond 566 mg a day may only be important among women whose vitamin D concentrations are low (less than 50 nmol/L), according to authors.
1. Heike A Bischoff-Ferrari, Douglas P Kiel, Bess Dawson-Hughes, John E Orav, Ruifeng Li, Donna Spiegelman, Thomas Dietrich, Walter C Willett. Dietary Calcium and Serum 25-Hydroxyvitamin D Status in Relation to BMD Among U.S. Adults. Journal of Bone and Mineral Research, 2009; 24 (5): 935 DOI: 10.1359/jbmr.081242
Recommended Level of Vit D
Re: [CAFE] Vitamin D and Cancer/Immune System Functioning
From: Jan Alexander (jea1013@YAHOO.COM)
Sent: 09 March 2010 14:27:05
my oncologist wants me at least at 80, since i have had cancer. she said some studies even show 100 is better.
Re: [CAFE] Vitamin D and Cancer/Immune System Functioning
From: Linda Weyand (lweyand@AOL.COM)
Sent: 09 March 2010 15:19:55
Hi, Puff and All, The lab that ran my vitamin D, 25-Hydroxy test listed the range of 32 to 100 and added a note with reference that stated "Recent studies consider the lower limit of 32.0 ng/mL to be a threshold for optimal health." This coincides with articles I have read that lists anything below 30 as being a deficiency and stresses that this level is a bare minimum. These articles recommend a level of 50 to 80. With the recent studies showing the importance of vitamin D, I am glad my primary care physician suggested I have my level checked during my annual exam, especially since my results showed a level of 8.1....a severe deficiency. I have been taking the 50,000 IU capsules and after the first 3 months, my level tested at 22. At that time, I expressed the desire to have my levels reach the 50 to 80 level, so my doctor told me to continue taking the 50,000 IU and we would recheck at my next annual exam. She said that she has never had any of her patients test over 80, even those that had been taking high dosages over long period of time. Today I read: "Since vitamin D is a fat-soluble vitamin and is absorbed from the intestine like a fat, vitamin D [test] is sometimes used to monitor individuals with diseases that interfere with fat absorption, such as cystic fibrosis and Chron's disease, and in patients who have had gastric bypass surgery and may not be able to absorb enough Vitamin D." http://www.labtestsonline.org/understanding/analytes/vitamin_d/test.html To me, this means that those of us whose ileum (small intestine) has been used to make our urinary diversions MIGHT have impaired Vitamin D absorption. It also explains why the capsules are to be taken with food. With recent research connecting vitamin D deficiency with cancer, I think all of us probably should ask that the 25-Hydroxy, Vitamin D test be included with our check-ups. For any of us that are taking bile sequestrants, we need to space a good bit of time between taking the bile sequestrant and the Vitamin D. The literature that came with my Vitamin D stated that it should be spaced at least 2 hours, longer if possible and suggested taking the Vit. D at bedtime if taking these other medicines (bile acid sequestrants such as cholestyramine/colestipol, mineral oil, orlistat). This literature also cautioned that this medication (Vit. D) "may interfere with certain laboratory tests (including cholesterol test)" so to let all your doctors know you are taking this medication. My best to all, Linda W neobladder 2/2002
ask for the 25-Hydroxy Vitamin D test
Vitamin D Crucial to Activating Immune Defenses[xvii]
ScienceDaily (Mar. 8, 2010) — Scientists at the University of Copenhagen have discovered that Vitamin D is crucial to activating our immune defenses and that without sufficient intake of the vitamin, the killer cells of the immune system — T cells — will not be able to react to and fight off serious infections in the body.
For T cells to detect and kill foreign pathogens such as clumps of bacteria or viruses, the cells must first be ‘triggered’ into action and ‘transform’ from inactive and harmless immune cells into killer cells that are primed to seek out and destroy all traces of a foreign pathogen.
The researchers found that the T cells rely on vitamin D in order to activate and they would remain dormant, ‘naïve’ to the possibility of threat if vitamin D is lacking in the blood.
When the naïve T cell recognizes foreign molecules with its T cell receptor (TCR) it sends activation signals (1) to the VDR gene. The VDR gene now starts the production of VDR (2). VDR binds vitamin D in the T cell (3) and becomes activated. Vitamin D bound to activated VDR goes back into the cell nucleus and activates the gene for PLC-gamma1 (5). PLC-gamma1 is produced (6) and the T cells can get started. (Credit: Professor of Immunology, Carsten Geisler)
Chemical Reaction that Enables Activation
In order for the specialized immune cells (T cells) to protect the body from dangerous viruses or bacteria, the T cells must first be exposed to traces of the foreign pathogen. This occurs when they are presented by other immune cells in the body (known as macrophages) with suspicious ‘cell fragments’ or ‘traces’ of the pathogen. The T cells then bind to the fragment and divide and multiply into hundreds of identical cells that are all focused on the same pathogen type. The sequence of chemical changes that the T cells undergo enables them to both be ‘sensitized to’ and able to deliver a targeted immune response.
Professor Carsten Geisler from the Department of International Health, Immunology and Microbiology explains that “when a T cell is exposed to a foreign pathogen, it extends a signaling device or ‘antenna’ known as a vitamin D receptor, with which it searches for vitamin D. This means that the T cell must have vitamin D or activation of the cell will cease. If the T cells cannot find enough vitamin D in the blood, they won’t even begin to mobilize. ”
T cells that are successfully activated transform into one of two types of immune cell. They either become killer cells that will attack and destroy all cells carrying traces of a foreign pathogen or they become helper cells that assist the immune system in acquiring “memory.” The helper cells send messages to the immune system, passing on knowledge about the pathogen so that the immune system can recognize and remember it at their next encounter. T cells form part of the adaptive immune system, which means that they function by teaching the immune system to recognize and adapt to constantly changing threats.
Activating and Deactivating the Immune System
For the research team, identifying the role of vitamin D in the activation of T cells has been a major breakthrough. “Scientists have known for a long time that vitamin D is important for calcium absorption and the vitamin has also been implicated in diseases such as cancer and multiple sclerosis, but what we didn’t realize is how crucial vitamin D is for actually activating the immune system — which we know now. ”
The discovery, the scientists believe, provides much needed information about the immune system and will help them regulate the immune response. This is important not only in fighting disease but also in dealing with anti-immune reactions of the body and the rejection of transplanted organs. Active T cells multiply at an explosive rate and can create an inflammatory environment with serious consequences for the body. After organ transplants, e.g. T cells can attack the donor organ as a “foreign invader.” In autoimmune disease, hypersensitive T cells mistake fragments of the body’s own cells for foreign pathogens, leading to the body launching an attack upon itself.
The research team was also able to track the biochemical sequence of the transformation of an inactive T cell to an active cell, and thus would be able to intervene at several points to modulate the immune response. Inactive or ‘naïve’ T cells crucially contain neither the vitamin D receptor nor a specific molecule (PLC-gamma1) that would enable the cell to deliver an antigen specific response.
The findings, continues Professor Geisler “could help us to combat infectious diseases and global epidemics. They will be of particular use when developing new vaccines, which work precisely on the basis of both training our immune systems to react and suppressing the body’s natural defenses in situations where this is important — as is the case with organ transplants and autoimmune disease.”
Most Vitamin D is produced as a natural byproduct of the skin’s exposure to sunlight. It can also be found in fish liver oil, eggs and fatty fish such as salmon, herring and mackerel or taken as a dietary supplement. No definitive studies have been carried out for the optimal daily dosage of vitamin D but as a large proportion of the population have very low concentrations of vitamin D in the blood, a number of experts recommend between 25-50mg micrograms a day.
1. von Essen et al. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nature Immunology, 2010; DOI: 10.1038/ni.1851
Vitamin D, Miracle Drug: Is It Science, or Just Talk?[xviii]
Some research suggests that such a wonder treatment already exists. It’s vitamin D, a nutrient that the body makes from sunlight and that is also found in fish and fortified milk.
Yet despite the health potential of vitamin D, as many as half of all adults and children are said to have less than optimum levels and as many as 10 percent of children are highly deficient, according to a 2008 report in The American Journal of Clinical Nutrition.
As a result, doctors are increasingly testing their patients’ vitamin D levels and prescribing daily supplements to raise them. According to the lab company Quest Diagnostics, orders for vitamin D tests surged more than 50 percent in the fourth quarter of 2009, up from the same quarter a year earlier. And in 2008, consumers bought $235 million worth of vitamin D supplements, up from $40 million in 2001, according to Nutrition Business Journal.
But don’t start gobbling down vitamin D supplements just yet. The excitement about their health potential is still far ahead of the science.
Although numerous studies have been promising, there are scant data from randomized clinical trials. Little is known about what the ideal level of vitamin D really is, whether raising it can improve health, and what potential side effects are caused by high doses.
And since most of the data on vitamin D comes from observational research, it may be that high doses of the nutrient don’t really make people healthier, but that healthy people simply do the sorts of things that happen to raise vitamin D.
“People may have high vitamin D levels because they exercise a lot and are getting ultraviolet-light exposure from exercising outdoors,” Dr. Manson said. “Or they may have high vitamin D because they are health-conscious and take supplements. But they also have a healthy diet, don’t smoke and do a lot of the other things that keep you healthy.”
Dr. Manson is leading a major study over the next five years that should provide answers to these questions and more. The nationwide clinical trial is recruiting 20,000 older adults, including men 60 and older and women 65 and older, to study whether high doses of vitamin D and omega-3 fatty acids from fish-oil supplements will lower risk for heart disease and cancer. (Learn about taking part in the study at www.vitalstudy.org.)
Dr. Manson said fish-oil supplements were included in the study because they are another promising treatment that suffers from a dearth of clinical trial evidence. In addition, both vitamin D and fish oil are known to have an anti-inflammatory effect, but each works through a different pathway in the body, so there may be an added health benefit in combining them.
Study participants will be divided into four groups. One will take both vitamin D and fish oil pills. Two will take either a vitamin D or a fish-oil supplement and a placebo. The fourth will take two placebo pills.
Vitamin D is found throughout the body and acts as a signaling mechanism to turn cells on and off. Right now, the recommended dose from food and supplements is about 400 international units a day for most people, but most experts agree that is probably too low. The Institute of Medicine is reviewing guidelines for vitamin D and is expected to raise the recommended daily dose.
Study participants will take 2,000 I.U.’s of vitamin D3, believed to be the form most easily used by the body. The study will use one-gram supplements of omega-3 fish oil, about 5 to 10 times the average daily intake.
The vitamin D dose is far higher than what has been used in other studies. The well-known Women’s Health Initiative study, for instance, tracked women taking 400 units of vitamin D and 1,000 milligrams of calcium. The study found no overall benefit from the supplements, although women who consistently took their pills had a lower risk of hip fracture. Even so, many experts think 400 units is far too low for any additional health benefits.
Another study, of 1,200 women, looked at the effects of 1,500 milligrams of calcium and 1,000 units of vitamin D. Women who took both supplements showed a lower risk for breast cancer over the next four years, but the numbers of actual cases — seven breast cancers in the placebo group and four in the supplement group — were too small to draw meaningful conclusions.
Although consumers may be tempted to rush out and start taking 2,000 I.U.’s of vitamin D a day, doctors warn against it. Several recent studies of nutrients, including vitamins E and B, selenium and beta carotene, have proved disappointing — even suggesting that high doses do more harm than good, increasing risk for heart problems, diabetes and cancer, depending on the supplement.
Despite the promise of vitamin D in observational studies, research into other supplements shows it’s difficult to document a benefit in otherwise healthy people, and virtually impossible to predict potential harms, notes Dr. Eric A. Klein, chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic. Dr. Klein recently worked as national coordinator for Select, a study of vitamin E and selenium for prostate cancer. The study seemed promising, but in the end it showed no benefit from the supplements and a potentially higher risk for diabetes in selenium users.
“My sentiment is that the lesson we have learned form large trials with other vitamin supplements, including Select, is that there is no proven health or preventative benefit for dietary supplements in nutritionally replete populations, which accounts for most of the people who enter this sort of clinical trial,” Dr. Klein said. “It makes more sense to me to study dietary supplements or vitamins in populations who are deficient.”
People most at risk for vitamin D deficiency are older, have diabetes or kidney disease, stay indoors or have darker skin. African-American teenagers are at particularly high risk, possibly because in addition to their dark skin, they are less likely at that stage in life to drink milk or play outside.
The scientific community continues to debate the optimum level of vitamin D. In general, people are considered to be deficient if they have blood levels below 15 or 20 nanograms per milliliter. But many doctors now believe vitamin D levels should be above 30. The ideal level isn’t known, nor is it known at what point a person is getting too much vitamin D, which can lead to kidney stones, calcification in blood vessels and other problems.
People’s vitamin D levels are influenced by whether they have light or dark skin, where they live, how much time they spend outdoors and by fish and milk consumption. To raise vitamin D without supplements, a person could increase sun exposure for 10 to 15 minutes a day. Eating more fish can help — a 3.5-ounce serving of wild fresh salmon has 600 to 1,000 I.U.’s of vitamin D — but it would take a quart of milk a day to get the recommended dose of vitamin D.
“What we know is that there are a lot of people who are vitamin D deficient based on estimates from national surveys,” said Dr. Michal L. Melamed, assistant professor of medicine at Albert Einstein College of Medicine in the Bronx. “But we don’t know what happens when the curve shifts to the other end. There probably is a risk to having too much vitamin D in the system.”
And see http://www.vitamindcouncil.org/
The Roles of Vitamin D Binding Protein in Human Immune Function[xix]
Sunday, January 24th, 2010 at 5:47 pm
The recent proliferation of published studies outlining the role of vitamin D in the prevention of many diseases associated with a weakened immune system has brought to light the importance of monitoring the serum levels of 25(OH) vitamin D. (1) Specifically, the direct correlation of vitamin D levels in the human serum with increased levels of cathelicidin and the potentiating role cathelicidin plays in the immune response to infections, cancer, autoimmune disease, and especially acute viral infections. (2) While research into vitamin D needs to continue, the importance of vitamin D binding protein (VDBP) has been demonstrated to have synergistic yet independent functions in the human immune system.(3) This article will outline the emerging role of VDBP in the field of immunology.
A review of the scientific literature pertaining to vitamin D binding protein and its derivatives identified in human serum and produced in the laboratory.
Vitamin D binding protein, also known as Gc-protein, is a group of isoform proteins with O-linked glycans. The dominant isoform of VDBP are non-glycosylated 656 Da proteins produced mainly in the liver.(4) Vitamin D binding protein participates in liver cell stability and regeneration through Calcium dependent interaction with the megalin/gp330 receptor.(5) There are 4 important roles VDBP has in humans. It binds circulating vitamin D for transport and storage, it is the most important scavenger of extracellular G-actin, it enhances the chemotactic activity of C5a for neutrophils in inflammation, and it activates macrophages thru GaINAc-modified Gc-protein. (6) Additionally, low levels of VDBP have been found to correlate with multiple organ failure sepsis, and non-survival in fulminant liver failure and traumatic liver failure.(7) The non-glycosylated isoform of VDBP is able to mask the presence of endotoxins by 20%.(7) Therapy with VDBP may increase survival in trauma, sepsis and fulminant liver failure.(7)
The function of VDBP is independent of the hormone actions of 1,25(2OH) vitamin D and it has limited impact on the extracellular pool of 1,25(OH) vitamin D.(8) Vitamin D binding protein has virtually no impact on the distribution, uptake, activation profile, or biological potency of the hormone vitamin D.(8) Vitamin D binding protein is not affected by race or adiposity the way vitamin D levels are affected.(9) The serum levels of VDBP are decreased by trauma, septic infections, and chronic or acute liver diseases.(10) The normal levels of serum VDBP are 350-50 mg/L and low levels below 80 mg/L yield a positive and negative mortality predictive value 85% and 43% respectively.(11)
While vitamin D binding protein is a primary macrophage activating factor, several glycosylated isoforms have more potent and specific macrophage activating properties.(12) The most potent serum macrophage activation factor (MAF) is produced by a series of glycosylation reactions performed by the B-cells and T-cells.(13) Vitamin D-MAF as a potent adjuvant activity for immunization and healthy serum levels of MAF prevent tumours from being able to transplant into mice.(14) Other roles for VDBP derived MAF have been described, including an anti-angiogenesis function through blocking VEGF-induced angiogenesis.(15)
Laboratory derived MAF from serum VDBP has the advantage of activating macrophages and not being deglycosylated by N-acetylgalactosaminidase enzymes (NaGaLase) produced by cancer cells and infectious bacteria, viruses and fungi.(16) The clinical dose required to have a sustained systemic activation of macrophages in 100 mcg injected weekly.(16) A novel MAF (Gc-MAF) can be produced in the lab with cancer specific activity that targets undifferentiated cancer cells better than well differentiated cancer cells.(17) Several prospective clinical trials of treatment of cancer and HIV with Gc-MAF have been reported and three trials with metastatic colon, breast and prostate cancer have provided 100% remission rate beyond the five years since Gc-MAF treatment.(16)(17)(18)
The scientific and clinical experience with VDBP and Gc-MAF are very encouraging. Several clinical trials are underway in the Bahamas at the Immune Augmentation Therapy Centre to reproduce and confirm the current clinic studies, as well as to answer several clinical questions that have not yet been reported in the scientific literature about VDBP and Gc-MAF. If you would like to enrol any clients with cancer or immune suppression in a trial with Gc-MAF, please contact the author of this review.
- Bikie DD, “Vitamin D and immune function: understanding common pathways” Curr Osteoporos Rep. 2009 Jul;7(2):58-63
- Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, Lee SH, Kim JM, Jo EK, “Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin” Cell Host Microbe. 2009 Sep 17;6(3):231-43
- Chkri M et al, “Production of human macrophages with potent antitumoral properties (MAK) by culture of monocytes in the presence of GM-CSF and 1,25-dihydroxy vitamin D3.” Anticancer Res. 1992 Nov-Dec;12(6B):2257-60
- Christiansen M et al, “Protein chemical characterization of Gc-gobulin (vitamin D-binding protein) isoforms; Gc-f1, Gc-s, and Gc-2.” Biochem Biophys Acta. 2007 Apr; 1774(4):481-92
- Gressner OA et al, “Gc-globulin (vitamin D binding protein) is synthesized and secreted by hepatocytes and internalized by hepatic stellate cells through Ca2+ dependent interaction with megalin/gp330 receptor.” Clinica ChimiceActa 2008 Apr 390;1-2:28-37
- Nagasawa H et al, “Gc-protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity.” Anticancer Res. 2005 Nov-Dec; 25(6A):3689-95
- Jorgensen CS et al, “Large-scale purification and characterization of non-glycosylated Gc-protein (vitamin D binding protein) from plasma fraction IV.” Biotechnol Appl Biochem. 2006 Apr;44(pt1):35-44
- Zella LA et al, “Vitamin D-binding protein influences total circulating levels of 1,25-dihydroxyvitamin D3 but does not directly modulate the bioactive levels of the hormone in vivo.” Endocrinology. 2008 Jul;149(7):3656-67
- Winters SJ et al, “Influence of obesity on vitamin D-binding protein and 25-hydroxy vitamin D levels in African and white women.” Metabolism. 2009 Apr;58(4):438-42
- Schiodt FV et al, “Increased turnover of Gc-protein in patients with hepatic encephalopathy.” Scand J Gastroenterol. 2001 Sep;36(9):998-1003
- Schiodt FV et al, “Gc-globulin and prognosis in acute liver failure.” Liver Transpl. 2005 Oct;11(10):1223-7
- Homma S et al, “Vitamin D-binding protein (group-specific component) is the sole serum protein required for macrophage activation after treatment of peritoneal cells with lyso-phosphatidylcholine.” Immunol Cel Biol. 1993 Aug;71(pt4):249-57
- Yamamoto N et al, “Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by stepwise action of beta-galactosidase of B-celss and sialidase of T-cells.” J Immunol. 1993 Sep 1;151(5):2794-802
- Yamamoto N et al, “Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization.” Immunol Cell Biol. 1998 Ju;76(3):237-44
- Kallunte S et al, “Inhibition of angiogenesis by vitamin D-binding protein: characterization of anti-endothelial activity of DBP-MAF.” Angiogenesis. 2005;8(4):349-60
- Yamamoto N et al, “Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein derived macrophage activating factor, Gc-MAF.” Cancer Immunol Immunotherapy 2008;57:1007-16
- Yamamoto N et al, “Immunotherapy of metastatic breast cancer patients with vitamin D-bindng protein-derived macrophage activating factor (GcMAF).” Int J Cancer. 2008;122:461-467
- Yamamoto N, Suyama H, Yamamoto N “Immunotherapy for prostate cancer with Gc protein-derived macrophage activating factor, GcMAF.” Transl Oncol.2008 Jul;1(2):65-72
Kevin Paul Bethel MD CM FAARM is the Research Director for the Immune Augmentation Therapy Centre (Freeport Bahamas), the Regenerative Medicine Consultant at Renaissance Medical Centre (Nassau Bahamas), and Medical Director for the Freeport Family Wellness Centre (Freeport Bahamas). Contact information: firstname.lastname@example.org, PO Box F42689, Freeport, GBI, Bahamas. 1-242-352-7455
Re: [CAFE] More on Vit D & cancer
From: Peter Granger (pete.granger@GMAIL.COM)
|Sent:||26 January 2010 02:08:07|
A weakened immune response contributes to the development of
infections, cancer, autoimmune disease, and acute viral infections. A
vitamin D deficiency (in fact, reduced levels of vitamin D binding
protein (VDBP) and its derivatives such as macrophage activation
factor (MAF) contribute to a weakened immune response by lowering
MAF has various anti-tumor effects, including as an angiogenesis
inhibitor (hindering metastasis by preventing cancer cells forming
their own blood supply).
Cancer cells, bacteria, viruses and fungi are able to block MAP. This
unfortunately leads to harmful immunosuppression – which is also
cyclical in nature. However, not so MAF developed in the laboratory,
and injected in patients at about 100 mcg/weekly for 30-50 weeks. In
trials, these injections have proved very effective in treating
metastatic cancer and HIV.
There has been 5 year, 100% remission in three trials with metastatic
colon, breast and prostate cancer following such treatment.
Several clinical trials are underway in the Bahamas at the Immune
Augmentation Therapy Centre. Clearly, it is a very promising
treatment, especially in metastatic cancer. However, the trials are
not being held at a major cancer centre. The question is, why? The
treatment has been patented by a Japanese/American researchers
(Yamamoto, Division of Cancer Immunology and Molecular Immunology,
Socrates Institute for Therapeutic Immunology, Philadelphia) which may account for its current lack of acceptance. Presumably, the treatment is also quite expensive.
In the interim, maintaining high serum levels of vitamin D may be
beneficial in protecting against viral infections and cancer.
Other immune boosting techniques include low-dose naltrexone,
melatonin, zinc, curcumin (which is also anti-inflammatory, but works
via a different pathway), vitamin K, probiotics, omega 3, calorie
restriction, green tea, oats, garlic, mushrooms, taurine, and Coley’s
The Anticancer Effects Of Vitamin D3[xx]
ScienceDaily (July 7, 2009) — The active form of vitamin D3 seems to have anticancer effects. To try and understand the mechanisms underlying these effects, researchers previously set out to identify genes whose expression in a human colon cancer cell line was altered by the active form of vitamin D3.
One gene identified in this previous study was CST5, which is responsible for making the protein cystatin D. Now, a team of researchers, at the Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Spain, and the Universidad de Oviedo, Spain, has studied this protein in detail and determined that it has tumor suppressor activity that likely accounts for some of the anticancer effects of the active form of vitamin D3.
The team, led by Alberto Muñoz and Carlos López-Otín, initially established that the active form of vitamin D3 directly activates the CST5 gene in human colon cancer cell lines, increasing levels of cystatin D protein. Functionally, cystatin D was shown to inhibit the growth of human colon cancer cells lines in vitro and when they were xenotransplanted into mice. As knocking down expression of cystatin D in human colon cancer cell lines rendered them unresponsive to the antiproliferative effects of the active form of vitamin D3, the authors conclude that CST5 is a candidate tumor suppressor gene and that it mediates a large proportion of the anticancer effects of the active form of vitamin D3. These data provide rationale for clinical trials examining the preventive and therapeutic potential of the active form of vitamin D3 in colon cancer.
Vitamin D Levels Associated With Survival in Lymphoma Patients[xxi]
ScienceDaily (Dec. 9, 2009) — A new study has found that the amount of vitamin D in patients being treated for diffuse large B-cell lymphoma was strongly associated with cancer progression and overall survival. The results will be presented at the annual meeting of the American Society of Hematology in New Orleans.
“These are some of the strongest findings yet between vitamin D and cancer outcome,” says the study’s lead investigator, Matthew Drake, M.D., Ph.D., an endocrinologist at Mayo Clinic in Rochester. “While these findings are very provocative, they are preliminary and need to be validated in other studies. However, they raise the issue of whether vitamin D supplementation might aid in treatment for this malignancy, and thus should stimulate much more research.”
The researchers’ study of 374 newly diagnosed diffuse large B-cell lymphoma patients found that 50 percent had deficient vitamin D levels based on the commonly used clinical value of total serum 25(OH)D less than 25 ng/mL. Patients with deficient vitamin D levels had a 1.5-fold greater risk of disease progression and a twofold greater risk of dying, compared to patients with optimal vitamin D levels after accounting for other patient factors associated with worse outcomes.
The study was conducted by a team of researchers from Mayo Clinic and the University of Iowa. These researchers participate in the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE), which is funded by the National Cancer Institute. The 374 patients were enrolled in an epidemiologic study designed to identify predictors of outcomes in lymphoma. Since this was not a clinical trial, patient management and treatments were not assigned, but rather followed standard of care for clinical practice.
The findings support the growing association between vitamin D and cancer risk and outcomes, and suggest that vitamin D supplements might help even those patients already diagnosed with some forms of cancer, says Dr. Drake. “The exact roles that vitamin D might play in the initiation or progression of cancer is unknown, but we do know that the vitamin plays a role in regulation of cell growth and death, among other processes important in limiting cancer,” he says.
The findings also reinforce research in other fields that suggest vitamin D is important to general health, Dr. Drake says. “It is fairly easy to maintain vitamin D levels through inexpensive daily supplements or 15 minutes in the sun three times a week in the summer, so that levels can be stored inside body fat,” he says. Many physicians recommend 800-1,200 International Units (IU) daily, he adds.
Vitamin D is a steroid hormone obtained from sunlight and converted by the skin into its active form. It also can come from food (naturally or fortified as in milk) or from supplements. It is known best for its role of increasing the flow of calcium into the blood. Because of that role, vitamin D deficiency has long been known to be a major risk factor for bone loss and bone fractures, particularly in elderly people whose skin is less efficient at converting sunlight into vitamin D. But recent research has found that many people suffer from the deficiency, and investigators are actively looking at whether low vitamin D promotes poorer health in general.
Cancer researchers have discovered that vitamin D regulates a number of genes in various cancers, including prostate, colon and breast cancers. Recent studies have suggested that vitamin D deficiency may play a role in causing certain cancers as well as impacting the outcome once someone is diagnosed with cancer.
Researchers looked at vitamin D levels in lymphoma patients because of the observation, culled from U.S. mortality maps issued by the National Cancer Institute, that both incidence and mortality rates of this cancer increase the farther north a person lives in the United States, where sunlight is limited in the winter. Also, several recent reports have concluded that vitamin D deficiency is associated with poor outcomes in other cancers, including breast, colon and head and neck cancer. This is the first study to look at lymphoma outcome.
The study was funded by the National Cancer Institute and the Mayo Hematologic Malignancies Lymphoma Fund.
Meta-analysis of longitudinal studies: Serum vitamin D and prostate cancer risk[xxii]
Aim: To review and summarize evidence from longitudinal studies on the association between serum 25-hydroxyvitamin D (25(OH)D) and the risk of prostate cancer (PC). Methods: Relevant prospective cohort studies and nested case-control studies published until July 2009 were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. The following data were extracted in a standardized manner from eligible studies: first author, publication year, country, study design, characteristics of the study population, duration of follow-up, PC incidence/PC mortality according to serum vitamin D status and the respective risk ratios, and covariates adjusted for in the analysis. Due to the heterogeneity of studies in categorizing serum vitamin D levels, all results were recalculated for an increase in serum 25(OH)D by 10ng/ml. Summary odds ratios (ORs) were calculated using meta-analysis methods. Results: Overall, eleven original articles were included, ten of which reported on the association between serum vitamin D levels and PC incidence and one article reported on the association with PC mortality. Meta-analysis of studies on PC incidence resulted in a summary OR (95% confidence interval, CI) of 1.03 (0.96–1.11) associated with an increase of 25(OH)D by 10ng/ml (P=0.362). No indication for heterogeneity and publication bias was found.
Conclusions: According to available evidence from longitudinal studies, serum 25(OH)D is not associated with PC incidence.
Does Vitamin D Treat Cancer?[xxiii]
As you may remember, the last newsletter was on preventing cancer, not treating it. Below is a small sampling of some of the questions contained in the tragic emails generated by last month’s newsletter:
Dr. Cannell, I was just diagnosed with breast cancer. How much vitamin D should I take?
My mother has colon cancer, how much vitamin D should she take?
I’ve had prostate cancer for four years, is there any reason to think vitamin D would help?
Dr. Cannell, my son has leukemia, should I give him vitamin D?
It’s not that simple…
It’s one thing to talk about evidence that vitamin D may prevent cancer but something quite different to discuss evidence that vitamin D might help treat cancer. I used to think the answers to all the above questions were the same. Like anyone else, people with cancer should be screened for vitamin D deficiency and be treated if deficiency is present. Simple. However, it’s not that simple. The real questions are:
- What are reasonable 25-hydroxy-vitamin D [25(OH)D] levels for someone with a life-threatening cancer?
- How much vitamin D do they need to take to obtain such levels?
- Is there any evidence, of any kind, that vitamin D will help treat cancer?
The risk/benefit analysis of taking vitamin D is quite different if you are in perfect health than if your life, or your child’s life, is on the line.
Remember, unlike cancer prevention, not one human randomized controlled trial exists showing vitamin D has a treatment effect on cancer. By treatment effect, I mean prolongs the lives of cancer patients. However, as I cited in my last newsletter, Dr. Philippe Autier of the International Agency for Research on Cancer, and Dr. Sara Gandini of the European Institute of Oncology, performed a meta-analysis of 14 randomized controlled trials showing even low doses of vitamin D extend life but they looked at all-cause mortality, not just cancer. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167(16):1730–1737.
Summer diagnosis prolongs life. Why?
However, some epidemiological studies indirectly address the treatment issue and are quite remarkable. The first are a series of discoveries by Professor Johan Moan, Department of Physics at the University of Oslo, with Dr. Alina Porojnicu as the lead author on most of the papers. Moan J, et al. Colon cancer: Prognosis for different latitudes, age groups and seasons in Norway. J Photochem Photobiol B. 2007 Sep 19. Lagunova Z, et al. Prostate cancer survival is dependent on season of diagnosis. Prostate. 2007 Sep 1;67(12):1362–70. Porojnicu AC, et al. Changes in risk of death from breast cancer with season and latitude: sun exposure and breast cancer survival in Norway. Breast Cancer Res Treat. 2007 May;102(3):323–8. Porojnicu AC, et al. Season of diagnosis is a predictor of cancer survival. Sun-induced vitamin D may be involved: a possible role of sun-induced Vitamin D. J Steroid Biochem Mol Biol. 2007 Mar;103(3–5):675–8. Porojnicu AC, et al. Season of diagnosis is a prognostic factor in Hodgkin’s lymphoma: a possible role of sun-induced vitamin D. Br J Cancer. 2005 Sep 5;93(5):571–4. Porojnicu AC, et al. Seasonal and geographical variations in lung cancer prognosis in Norway. Does Vitamin D from the sun play a role? Lung Cancer. 2007 Mar;55(3):263–70.
What Professor Moan’s group repeatedly discovered is quite simple—whether it be cancer of the breast, colon, prostate, lung, or a lymphoma: You live longer if your cancer is diagnosed in the summer. And it is not just Moan’s group who has found this. A huge English study recently confirmed Moan’s discovery. Lim HS, et al. Cancer survival is dependent on season of diagnosis and sunlight exposure. Int J Cancer. 2006 Oct 1;119(7):1530–6.
What do these studies mean? Something about summer has a treatment effect on cancer. Whatever it is, you live longer if you are diagnosed in the summer but die sooner if you are diagnosed in the winter. What could it be about summer? Exercise? Fresh air? Melatonin? Sunlight? Pretty girls? Remember, these patients already had cancer. Whatever it is about summer, it is not a preventative effect that Professor Moan discovered, it is a treatment effect. Something about summer prolongs the life of cancer patients.
Sunlight’s robust treatment effect
Dr. Ying Zhou, a research fellow, working with Professor David Christiani at the Harvard School of Public Health, went one step further. The stuffy Harvard researchers assumed summer worked its magic, not by pretty girls, but by summer sunlight making vitamin D. So they looked at total vitamin D input, from both sun and diet, to see if high vitamin D intake improved the survival of cancer patients. Yes, indeed, remarkably. They found that early stage lung cancer patients with the highest vitamin D input (from summer season and high intake from diet) lived almost three times longer than patients with the lowest input (winter season and low intake from diet). Three times longer is a huge treatment effect, a treatment effect that most conventional cancer treatment methods would die for. Zhou W. Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients. Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2303–9.
And that’s not all, Marianne Berwick and her colleagues, at the New Mexico Cancer Institute, found malignant melanoma patients with evidence of continued sun exposure had a 60% mortality reduction compared to patients who did not. That implies a robust treatment effect from sunlight. Berwick M, et al. Sun exposure and mortality from melanoma. J Natl Cancer Inst. 2005 Feb 2;97(3):195–9.
I will not list the thousands of animal studies that indicate vitamin D has a treatment effect on cancer as almost all of them studied activated vitamin D or its analogs—drugs that bypass normal regulatory mechanisms, cannot get autocrine quantities of the hormone into the cell, and that often cause hypercalcemia. However, Michael Holick’s group found that simple vitamin D deficiency made cancers grow faster in mice. That is, vitamin D has a cancer treatment effect in vitamin D-deficient mice. Professor Gary Schwartz, at Wake Forest, recently reviewed the reasons to think that vitamin D may have a treatment effect in cancer. Tangpricha V, et al. Vitamin D deficiency enhances the growth of MC-26 colon cancer xenografts in Balb/c mice. J Nutr. 2005 Oct;135(10):2350–4. Schwartz GG, Skinner HG. Vitamin D status and cancer: new insights. Curr Opin Clin Nutr Metab Care. 2007 Jan;10(1):6–11.
Finally, one human interventional study exists. In 2005, in an open trial, Professor Reinhold Vieth and his colleagues found just 2,000 IU of vitamin D per day had a positive effect on PSA levels in men with prostate cancer. Woo TC, et al. Pilot study: potential role of vitamin D (Cholecalciferol) in patients with PSA relapse after definitive therapy. Nutr Cancer. 2005;51(1):32–6.
So, how much vitamin D does one need?
So we come back to the crucial question. If you have cancer, how much vitamin D should you take, or, more precisely, what 25(OH)D level should you maintain? We don’t know. You can correctly say that definitive studies have not been done and incorrectly conclude physicians treating cancer patients should do nothing. I say incorrectly because standards of medical practice have always demanded that doctors make reasonable decisions as to what is best for their patients based on what is currently known—what is called a risk/benefit analysis. If a patient has a potentially fatal cancer, the doctor cannot dismiss a relatively benign potential treatment modality just because definitive studies have not been done, passively watching his or her patient die. Standards of care require doctors perform a risk/benefit analysis and then act in the best interest of their patient.
Luckily, such doctors recently obtained some guidance. In the first study of its kind, Professor Bruce Hollis of the Medical University of South Carolina gave all of us something to think about. He asked and answered a simple question: How much vitamin D do you have to take to normalize the metabolism of vitamin D?
Vitamin D’s unique behavior
Remember, unlike other steroid hormones, vitamin D has very unusual metabolism in most modern humans, called first-order, mass-action kinetics. What this means is that the more vitamin D you take, the higher the 25(OH)D level in your blood and the higher the 25(OH)D level in your blood, the higher the levels of activated vitamin D in your tissues. No other steroid hormone in the body behaves like this. Think about it, would you like your estrogen level to be dependent on how much cholesterol you ate? Or your cortisol level? (I’d ask the same about testosterone levels but I know men well enough not to ask.) No, the body must tightly regulate powerful steroid hormones through substrate inhibition, that is, if an enzyme turns A into B, when the body has enough B, B inhibits the enzyme and so limits its own production.
Not so with vitamin D, at least at modern, human vitamin D levels. Professor Reinhold Vieth was the first to write about this and Vieth’s Chapter 61 in Feldman, Pike, and Glorieux’s wonderful textbook, entitled Vitamin D (Elsevier, 2005, second edition), is a great reason to buy the textbook or have your library do so. I’m glad to see Amazon is out of stock of the new ones—someone must be reading about vitamin D!—but you can still buy used editions.
Why would the kinetics of vitamin D be different from all other steroids? Maybe they are not, Hollis reasoned like Vieth before him. Maybe vitamin D levels are so low in modern humans that its metabolic system is on full blast all the time in an attempt to give the body all the vitamin D metabolites it craves. So Hollis asked, Is vitamin D’s metabolism different in populations in the upper end of 25(OH)D levels (a population of sun-exposed people and a group of women prescribed 7,000 IU per day)? Note: the entire Hollis study is free to download on Medline. Hollis BW, et al. Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status. J Steroid Biochem Mol Biol. 2007 Mar;103(3–5):631–4.
If you look at the two graphs (Figures 1 and 2) of Hollis’ paper, you find vitamin D’s kinetics can be normalized, made just like all other steroid hormones in the body, but you have to get enough sunshine or take enough vitamin D to get your 25(OH)D level above 50 ng/mL—60 ng/mL would be even better. Then your body would start to store cholecalciferol without much further increase in 25(OH)D levels. The reaction becomes saturable. This is a remarkable discovery and it implies levels of 30 and 40 ng/mL are usually not sufficient. It also implies actual vitamin D levels (cholecalciferol levels), not just 25(OH)D levels, may be useful in diagnosing and treating deficiency. Note, that not all of the sun-exposed individuals or women prescribed 7,000 IU/day achieved such levels. That’s because the sun-exposed individuals were tested after an Hawaiian winter and because prescribing and taking are two different things.
25(OH)D level should be greater than 60 ng/mL
So my answer to “How much should I take if I have cancer?” is “Take enough to get your 25(OH)D level above 60 ng/mL, summer and winter.” In doing so, you will have normalized the kinetics of vitamin D and stored the parent compound, cholecalciferol, in your tissues. In the absence of sunshine, you need to take at least 5,000 IU/day to do this. And this may not be enough; cancer patients may use it up faster (increased metabolic clearance) and children may do the same due to their young and vital enzymes. Or you may need less, because you get more sun than you think, more from your diet, or because you are taking a modern medicine that interferes with the metabolism of vitamin D. An even easier way to do it is go to a sun tanning booth every day and obtain and keep a dark, full-body, tan. Then you don’t have to worry about blood levels but I’d get one anyway, just to be sure it was above 60 ng/mL.
Given what Hollis discovered, given the well-known potent anti-cancer properties of activated vitamin D, given epidemiological evidence that summer extends the life of cancer patients, given a meta-analysis of randomized controlled trials showed that vitamin D prolongs life, given animal data that simple vitamin D has a treatment effect on cancer, and given a patient with a life-threatening cancer, what would a reasonable physician do? Simply let their patient die while muttering something about the lack of randomized controlled trials?
No, they would simply check 25(OH)D levels every month and advise cancer patients to take enough vitamin D or to frequent sun tanning parlors enough to keep their level above 60 ng/mL. Toxicity does not start until levels reach 150 ng/mL but if you take more than 5,000 IU per day have your doctor order a blood calcium every month or two, along with the 25(OH)D. Both you and he will feel better and because, if you have cancer, you are probably taking lots of other drugs and little is known about how modern drugs interact with vitamin D metabolism. By getting your level above 60 ng/mL, all you are doing is getting your level to where most lifeguards’ levels are at the end of summer, to levels our ancestors had when they lived in the sun, to levels regular users of sun-tan parlors levels achieve, and most importantly, to levels where vitamin D’s pharmacokinetics are normalized.
Little to no risk
In the end, if you have cancer and your physician won’t do a risk/benefit analysis, do it yourself. The risk side of that equation is easy. Both Quest Diagnostics and Lab-Corp, the two largest reference labs in the United States, report the upper limit of 25(OH)D normal is 100 ng/mL and toxic is above 150 ng/mL, so 60 ng/mL is well below both. The reason levels up to 100 ng/mL are published normals is because there is no credible evidence in the literature that levels of 100 ng/mL do any harm and because sun worshipers often have such levels. (If you don’t believe me, go to the beach in the summer for one month, sunbath every day for 30 minutes on each side in your bathing suit, and go home and have a 25(OH)D level.) By getting your level above 60 ng/mL, all you are doing is getting your levels into the mid to upper range of laboratory reference normals. Little or no risk.
What are the potential benefits? It probably depends on a number of things. Did your cancer cells retain the enzyme that activates vitamin D? Many do. Did your cancer cells retain the vitamin D receptor? Many do. If your cancer cells get more substrate [25(OH)D], will that substrate induce the cancer cells to make more vitamin D receptors or more of the activating enzyme? Some cancer cells do both. In practical terms, vitamin D is theoretically more likely to help your cancer the earlier you start taking it. However, no one knows. Certainly there is no reason, other than bad medicine, for cancer patients to die vitamin D deficient. Unfortunately, most do. Tangpricha V, et al. Prevalence of vitamin D deficiency in patients attending an outpatient cancer care clinic in Boston. Endocr Pract. 2004 May–Jun;10(3):292–3. Plant AS, Tisman G. Frequency of combined deficiencies of vitamin D and holotranscobalamin in cancer patients. Nutr Cancer. 2006;56(2):143–8.
It is very important that readers understand I am not suggesting vitamin D cures cancer or that it should replace standard cancer treatment. Oncologists perform miracles every day so one should do what they say. The only exception is vitamin D. If your oncologist tells you not to take vitamin D, ask him three questions.
- How do you convert ng/mL to nmol/L?
- How many IU in a nanogram (ng)?
- How do you spell “cholecalciferol?”
If he doesn’t know how to measure it, weigh it, or spell it, chances are he doesn’t know much about it.
The real risk: waiting for further studies
All of the epidemiological and animal studies in the literature suggest cancer patients will prolong their lives if they take vitamin D. I can’t find any studies that indicate otherwise. However, none of the suggestive studies are randomized controlled interventional trials; they are all epidemiological or animal studies, or, in the case of Vieth’s, an open human study. However, if you have cancer, or your child does, do you want to wait the decades it will take for the American Cancer Society to fund randomized controlled trials using the proper dose of vitamin D? Chances are you, or your child, will not be around to see the results.
John Jacob Cannell MD Executive Director
Vitamin D Can Alter Colon Cancer Cells In Many Ways, Through One Pathway[xxiv]
ScienceDaily (Nov. 26, 2008) — A colon cancer cell isn’t a lost cause. Vitamin D can tame the rogue cell by adjusting everything from its gene expression to its cytoskeleton. In the Nov. 17 issue of the Journal of Cell Biology, Ordóñez-Morán et al. show that one pathway governs the vitamin’s diverse effects. The results help clarify the actions of a molecule that is undergoing clinical trials as a cancer therapy.
Vitamin D stymies colon cancer cells in two ways. It switches on genes such as the one that encodes E-cadherin, a component of the adherens junctions that anchor cells in epithelial layers. The vitamin also induces effects on the cytoskeleton that are required for gene regulation and short-circuiting the Wnt/b-catenin pathway, which is overactive in most colon tumors. The net result is to curb division and prod colon cancer cells to differentiate into epithelial cells that settle down instead of spreading.
To delve into the mechanism, the team dosed colon cancer cells with calcitriol, the metabolically active version of vitamin D. Calcitriol triggered a surge of calcium into the cells and the subsequent switching on of RhoA–RhoGTPases, which have been implicated in the cytoskeletal changes induced by vitamin D. The activated RhoA in turn switched on one of its targets, the rho-associated coiled kinase (ROCK), which then roused two other kinases. Each step in this nongenomic pathway was necessary to spur the genomic responses, the researchers showed. The team also nailed down the contribution of the vitamin D receptor (VDR). The receptor was crucial at the beginning of the pathway, where it permitted the calcium influx, and at the end, where it activated and repressed genes.
The study is the first to show that vitamin D’s genomic and nongenomic effects integrate to regulate cell physiology. One question the researchers now want to pursue is whether VDR from different locations—the nucleus, the cytosol, and possibly the cell membrane—has different functions in the pathway.
Reference: Ordóñez-Morán, P., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200803020.
Macrophage Activation May Suppress Breast Cancer Metastasis[xxv]
By David Douglas
NEW YORK FEB 20, 2008 (Reuters Health) – Vitamin D-binding protein-derived macrophage activating factor (Gc-MAF) appears to be an effective immunotherapeutic agent in patients with metastatic breast cancer, according to US and Japanese researchers.
“Serum vitamin D-binding protein – known as Gc protein – is the precursor of the principal macrophage activating factor,” lead investigator Dr. Nobuto Yamamoto told Reuters Health.
“Treatment of purified Gc protein with beta-galactosidase and sialidase generates Gc-MAF,” he added, “the most potent macrophage activating factor ever discovered, which produces no side effect in humans.”
Dr. Yamamoto of the Socrates Institute for Therapeutic Immunology, Philadelphia and colleagues note that in vitro studies show that macrophages treated with Gc-MAF have a highly tumoricidal effect in mammary adenocarcinomas.
To investigate whether the approach can be effective in humans, the researchers studied 16 non-anemic breast cancer patients who were given “a minute amount – 100 nanograms per week – of Gc-MAF,” Dr. Yamamoto said.
The researchers found that after 16 to 22 Gc-MAF doses, initially elevated nagalase levels, which reflect the tumor burden, fell to those found in healthy controls. Follow-up over 4 years showed that the level remained low and that there was no tumor recurrence, they report in the January 15th issue of The International Journal of Cancer.
The findings, the team concludes, clearly demonstrate “the importance of focusing cancer immunotherapy on macrophage activation.”
International Journal Cancer. 2008 Jan 15; 122(2):461-7.
Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, Gc-MAF
Nobuto Yamamoto, Hirofumi Suyama, Hiroaki Nakazato, Nobuyuki Yamamoto and Yoshihiko Koga
Abstract: Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent macrophage-activating factor (Gc-MAF) ever discovered, but it produces no side effect in humans. Macrophages treated with Gc-MAF (100 pg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng Gc-MAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As Gc-MAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of Gc-MAF therapy. After 32–50 weekly administrations of 100 ng Gc-MAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of Gc-MAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.
May 22, 2008
Colon cancer: prognosis for different latitudes, age groups and seasons in Norway.[xxvi]
Department of Radiation Biology, Institute for Cancer Research, Montebello, 0310 Oslo, Norway. email@example.com
The survival of colon cancer patients in Norway, as determined three years after diagnosis, is dependent on the season of diagnosis. This has been attributed to seasonal variations of the vitamin D status. Since solar radiation and food are the human sources of vitamin D, we divided Norway in three regions: The southeast region with a high annual dose of ultraviolet (UV) to the population, as evidenced by a high incidence rate of squamous cell carcinoma of the skin (SCC), the midwest region and the north region with low annual UV doses. The latter region is characterized by a high consumption of vitamin D, mainly through fish intake. Vacations to southern latitudes were equally frequent for all the three geographical regions. Two age groups were analyzed separately (< or =65 years and >65 years), since the photosynthesis of vitamin D(3) in skin decreases with age. In all three regions, and in both age groups, the survival was highest for summer and autumn diagnosis. The seasonal effect was slightly, but not significantly, better for the younger than for the older age group. The effect was similar for all three geographical regions, irrespective of SCC incidence.
PMID: 18029190 [PubMed – indexed for MEDLINE]
Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans: An Important Tool to Define Adequate Nutritional Vitamin D Status[xxvii]
Bruce W. Hollis, Carol L. Wagner, Mark K. Drezner, and Neil C. Binkley
Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D3 and its metabolic product—25(OH)D3 has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6,400 IU vitamin D3/day for six months.
Results: 1) The relationship between circulating vitamin D3 and 25(OH)D in both groups was not linear, but appeared saturable and controlled; 2) Optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D3 and 25(OH)D exceeded 0.3; at this point, the Vmax of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol.
We hypothesize that as humans live today, the 25-hydroxylase operates well below its Vmax because of chronic substrate deficiency, namely vitamin D3. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be.
Keywords: vitamin D, 25-hydroxyvitamin D, nutritional vitamin D status
What is a normal circulating level of 25(OH)D that is sufficient to meet all physiological needs, not simply skeletal requirements in humans? In the past, this was addressed by simply sampling a diverse population of subjects who were asymptomatic for disease, measuring circulating 25(OH)D, and plotting the data using a Gaussian distribution. This approach yields normative data that are used to assess circulating 25(OH)D in that population. This is how Haddad and Chyu (1) performed their assessment of 25(OH)D status more than thirty-five years ago. They referred to their normal, asymptomatic volunteers as the normal population for circulating 25(OH)D levels. Their study also presented a group of lifeguards that had circulating 25(OH)D levels 2.5 times that of the “normals.” Countless similar studies have been performed during the ensuing decades, reiterating the same conclusion. We, however, interpret the original Haddad data differently: we suggest that the 25(OH)D levels in the sun-replete lifeguards are normal and the “normals” actually exhibit varying degrees of vitamin D deficiency.
How nutritional vitamin D deficiency is defined is a key to developing a coherent supplement policy that meets the needs of all humans. Recently, inadequate circulating 25(OH)D levels have been linked to biomarkers, including skeletal density (2–4), intestinal calcium absorption (5), secondary hyperparathyroidism (6–10), insulin secretion (11, 12), and innate immune response (13). These markers all are useful in identifying nutritional vitamin D deficiency; however, the link between 25(OH)D and vitamin D—when available at adequate concentration, remains unknown and could prove to be another important piece in understanding vitamin D metabolism. We sought to investigate this question of how 25(OH)D would respond if adequate substrate, namely vitamin D3, was always present. Thus, for this project, we studied two groups of subjects, one from a sun-rich environment and the other from a high-dose vitamin D3 supplementation study, the results of which are presented here.
Materials and Methods
Part 1. Study of Sun-Exposed Subjects
Approval for this study was granted by the University of Wisconsin Health Sciences Institutional Review Board for Human Subjects and the Committee on Human Studies at the University of Hawaii at Manoa. All subjects provided written informed consent prior to the conduct of any study procedure.
Skin surface exposed to the sun in these subjects varied from almost total in surfers to head, arms and hands in skateboarders. Ninety-three subjects (63 males/30 females) participated in the study.
Subjects from a sun-rich climate were recruited from the University of Hawaii at Manoa, and from patrons of the A’ala Park Board shop, Honolulu, Hawaii (latitude 21°N), in late March 2005. In order to participate, volunteers had to have met the entrance criteria of the following: a self-reported sun exposure time of three or more hours per day on five or more days per week for at least the preceding three months. Those who met entrance criteria were enrolled in the study following written informed consent.
- Blood was collected for serum 25(OH)D and vitamin D3 measurement when they were interviewed.
- All participants completed a non-validated, self-administered questionnaire, which included questions about sun exposure, sunscreen use, and dietary vitamin D intake.
- To document sun exposure, skin color was measured by reflectance colorimetry (IMS SmartProbe, Millford, CT). A measurement was taken on the back of the hand and the front of the distal thigh for the darkest measurement and under the arm and at the self-reported least sun-exposed area—often the breast or buttock, to determine the lightest or natural skin color. A previously developed sun exposure index (14), which utilizes the rule of nines was used to estimate the amount and duration of skin sun exposure.
- Circulating 25(OH)D was measured on all 93 subjects using an RIA as previously reported (15).
- Data Analysis: The 10 highest and 10 lowest circulating 25(OH)D levels were selected to determine circulating vitamin D3 levels using direct ultraviolet (UV) detection following high performance liquid chromatography as previously described (16). The data were plotted using a best-fit regression analysis with vitamin D3 serving as the independent variable.
Part II. Study of High Dose Vitamin D3 Supplemented Subjects
Approval for this study was granted by the Medical University of South Carolina’s (MUSC) Institutional Review Board for Human Subjects, HR #11345 and the General Clinical Research Center (GCRC; Protocol #694). Fully lactating mothers (17) within one month postpartum were eligible for inclusion in the study if they planned to continue full breastfeeding for the next six months. The subjects were randomly divided into two groups. Exclusion criteria included preexisting type I or type II diabetes, hypertension, parathyroid disease, and uncontrolled thyroid disease. Subjects were compensated for their participation with gift cards given at the end of each visit.
Women in the high dose supplementation group of a larger randomized, double-blind, placebo-control trial were included in this study. Following written informed consent, mothers were randomized to one of two vitamin D supplementation regimens: Group 1: 400 IU vitamin D3/day (0 IU vitamin D3—placebo and 1 prenatal vitamin containing 400 IU vitamin D3), or Group 2: 6,400 IU vitamin D3/day (6,000 IU vitamin D3 and 1 prenatal vitamin containing 400 IU vitamin D3).
- Following written informed consent, each mother had baseline serum samples collected for measurement of circulating 25(OH)D and vitamin D3.
- The mothers were started on a total of 400 or 6,400 IU vitamin D3 tablets/day (Tishcon Corporation, Westberry, NY, a Good-Manufacturing-Practice (GMP) facility that met FDA production guidelines) for up to 6 months.
- Serum samples were collected at monthly intervals and analyzed for circulating 25(OH)D and vitamin D3 as described for the sun-rich population in Part I (Methods).
- Data Analysis: The data were plotted as in Part I of the study using a best-fit regression analysis with vitamin D3 serving as the independent variable.
Subjects from the sun-rich environment exhibited a wide range of circulating 25(OH)D levels (11–71 ng/mL). Similarly, the range of circulating 25(OH)D levels in women in the supplementation group was from 12–77 ng/mL. This wide range also was observed for the circulating vitamin D3 levels (<1–64 ng/mL in the sun-rich environment group and <1–75 in the supplementation group). When data from the 20 subjects in the lowest and highest quartiles, comparing circulating 25(OH)D and vitamin D3 were plotted, a significant second-order equation was generated (p<0.0001, Figure 1). Similarly, when the data from the supplementation group was plotted, a similar, significant second-order equation was observed (p<0.0001, Figure 2). These equations did not differ statistically (p>0.15).
Circulating 25(OH)D as a Function of Vitamin D3 Status in Subjects from a Sun-Rich Environment
Circulating 25(OH)D as a Function of Vitamin D3 Status in Supplemented Subjects
The question, what is a “normal” nutritional vitamin D status, is currently a hotly debated topic. Historically, a “normal” nutritional vitamin D status has been defined as just about any circulating level of 25(OH)D in asymptomatic subjects (1, 18). Recently, attempts have been made to reevaluate this “normal” circulating level of 25(OH)D using biomarkers such as parathyroid hormone (6–10), intestinal calcium absorption (5), skeletal density (2–4), glucose clearance (12), and innate immune function (13). Generally, these studies suggest that a minimum circulating level of 25(OH)D should be >80 nmol (32 ng/mL) (18).
In the present study, we sought to investigate what circulating 25(OH)D levels would result in populations exhibiting no substrate limitations to the vitamin D-25-hydroxylase. To perform this, we chose two distinct populations. The first were individuals from a year-found sunny environment who spent a good deal of time outdoors. The second were a group of lactating women receiving a substantial daily oral dose of vitamin D3. Surprisingly, a study such as this previously had not been undertaken. There are several reasons for this. First, finding a group of sun-exposed individuals is not an easy task; in fact, we had to go to Hawaii to find them. Secondly, very few studies have been performed where subjects actually received adequate vitamin D3 supplementation to make them replete. Finally, it is very difficult and costly to measure circulating vitamin D3 and relate it to circulating 25(OH)D. The results of our study are far-reaching.
At a maternal intake of 6,400 IU vitamin D3/day, circulating vitamin D3 increased dramatically. Maternal circulating 25(OH)D also increase; however, the increase appeared to be limited and controlled (Figure 2). A similar relationship was observed in the sun-exposed individuals (Figure 1). In these individuals, sun exposure was greater than fifteen hours/week—although not all had total body exposure, some only hands, arms, and head. The data from our study suggests the following: The relationship between circulating vitamin D3 and 25(OH)D is not linear in either case; rather it appears saturable and controlled. This suggest either/or product-substrate inhibition of the vitamin D-25-hydroxylase. Optimal nutritional vitamin D status may occur when approaching equimolar concentrations of circulating vitamin D3 and 25(OH)D (>100 nmol). At this point, the Vmax of the enzyme appears to be achieved. It is important to note that as humans live today, the vitamin D-25-hydroxylase operates well below its Vmax because of chronic substrate (vitamin D) deficiency. Not a single other steroidal hormone system in the body is limited in this fashion since their starting point is cholesterol. When humans are sun- (or dietary-) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate availability.
This study also demonstrates that individuals can be vitamin D deficient with significant sun exposure if the skin area exposed is limited as was suggested several years ago (19). Finally, whether one receives their vitamin D3 orally or through UV exposure, the vitamin D-25-hydroxylase appears to handle it in an equivalent fashion with respect to maintaining circulating 25(OH)D levels. Thus, we believe that the relationship between circulating vitamin D and 25(OH)D may define adequate nutritional vitamin D status.
1. Haddad JG, Chyu K. Competitive protein-binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinal Metab. 1971;33:992–995.
2. Bischoff-Ferrari H, Dietrich T, Orav E, Dawson-Hughes B. Positive association between 25(OH)D levels and bone mineral density: A population-based study of younger and older adults. Amer J Med. 2004;116:634–639. [PubMed]
3. Fuleihan E, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H, et al. Effect of vitamin D replacement on musculoskeletal parameters in school children: A randomized controlled trial. J Clin Endocrinal Metab. 2006;91:405–412.
4. Javaid M, Crozier S, Harvey N, Gale C, Dennison E, Boucher B, et al. Maternal vitamin D status during pregancy and childhood bone mass at 9 years: A longitudinal study. Lancet. 2006;367:36–43. [PubMed]
5. Heaney R, Dowell M, Hale C, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Amer College Nutr. 2003;22(2):142–146.
6. Lips P, Wiersinga A, Van Ginkel FC, Jongen MJ, Netelenbos JC, Hackeng WH, et al. The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab. 1988;67:644–650. [PubMed]
7. Gloth FM, Gundberg CM, Holllis BW, Haddad JG, Tobin JD. Vitamin D deficiency in homebound elderly persons. JAMA. 1995;274:1683–1686. [PubMed]
8. Visser M, Deeg D, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): The longitudinal aging study Amsterdam. J Clin Endocrinal Metab. 2003;88:5766–5772.
9. Vieth R, Ladak Y, Walfish P. Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. J Clin Endocrinal Metab. 2003;88:185–191.
10. Chel VG, Ooms ME, Popp-Snijders C, Pavel S, Schothorst AA, Meulemans CCE, et al. Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly. J Bone Mineral Res. 1998;13:1238–1242.
11. Lee S, Clark S, Gill R, Christakos S. 1,25-Dihydroxyvitamin D3 and pancreatic beta-cell function: vitamin D receptors, gene expression, and insulin secretion. Endocrinology. 1994;134(4):1602–1610. [PubMed]
12. Chiu K, Chu A, Go V, Soad M. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Amer J Clin Nutr. 2004;79:820–825. [PubMed]
13. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik S, et al. Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response. Science. 2006:1770–1773. doi: 10.1126/science.1123933. [PubMed]
14. Barger-Lux MJ, Heaney RP. Effects of Above Average Summer Sun Exposure on Serum 25-Hydroxyvitamin D and Calcium Absorption. J Clin Endocrinol Metab. 2002;87(11):4952–4956. doi: 10.1210/jc2002-020636. [PubMed]
15. Hollis BW, Kamerud JQ, Selvaag SR, Lorenz JD. Determination of vitamin D status by radioimmunoassay with a 125I-labeled tracer. Clin Chem. 1993;39:529–533. [PubMed]
16. Hollis BW. Detection of vitamin D and its major metabolites. In: Feldman D, Glorieux F, Pike J, editors. Vitamin D. New York, N.Y.: Academic Press; 2005. pp. 932–950.
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18. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin sufficiency: Implications for establishing a new effective DRI for vitamin D. J Nutr. 2005;135:317–322. [PubMed]
19. Matsuoka LY, Wortsman J, Hollis BW. Use of topical sunscreen for the evaluation of regional synthesis of vitamin D3. J Amer Acad Dermatol. 1990;22:772–775. [PubMed]
Women With Breast Cancer Have Low Vitamin D Levels[xxviii]
ScienceDaily (Oct. 10, 2009) — Women with breast cancer should be given high doses of vitamin D because a majority of them are likely to have low levels of vitamin D, which could contribute to decreased bone mass and greater risk of fractures, according to scientists at the University of Rochester Medical Center.
In a study of 166 women undergoing treatment for breast cancer, nearly 70 percent had low levels of vitamin D in their blood, according to a study being presented Thursday, Oct. 8, at the American Society of Clinical Oncology’s Breast Cancer Symposium in San Francisco. The analysis showed women with late-stage disease and non-Caucasian women had even lower levels.
“Vitamin D is essential to maintaining bone health, and women with breast cancer have accelerated bone loss due to the nature of hormone therapy and chemotherapy. It’s important for women and their doctors to work together to boost their vitamin D intake,” said Luke Peppone, Ph.D., research assistant professor of Radiation Oncology, at Rochester’s James P. Wilmot Cancer Center. He is a member of the National Cancer Institute’s Community Clinical Oncology Program research base in Rochester.
Scientists funded by the NCI analyzed vitamin D levels in each woman, and the average level was 27 nanograms per milliliter; more than two-thirds of the women had vitamin deficiency. Weekly supplementation with high doses of vitamin D — 50,000 international units or more — improved the levels, according to Peppone’s study.
The U.S. Institute of Medicine suggests that blood levels nearing 32 nanograms per milliliter are adequate.
This problem is not unexpected, Peppone said, because previous studies have shown that nearly half of all men and women are deficient in the nutrient, with vitamin D levels below 32 nanograms per milliliter. Vitamin D, obtained from milk, fortified cereals and exposure to sunlight, is well known to play an essential role in cell growth, in boosting the body’s immune system and in strengthening bones.
Symptoms of Vitamin D deficiency include muscle pain, weak bones/fractures, low energy and fatigue, lowered immunity, symptoms of depression and mood swings, and sleep irregularities, many of which are common for women undergoing breast cancer treatment.
Adapted from materials provided by University of Rochester Medical Center.
Real Help for Cancer?
by Bill Sardi and Timothy Hubbell
The weekly injection of just 100 billionths of a gram of a harmless glyco-protein (a naturally-produced molecule with a sugar component and a protein component) activates the human immune system and cures cancer for good, according to human studies among breast cancer and colon cancer patients, producing complete remissions lasting 4 and 7 years respectively. This glyco-protein cure is totally without side effect but currently goes unused by cancer doctors.
Normal Gc protein (also called vitamin D binding protein), an abundant glyco-protein found in human blood serum, becomes the molecular switch to activate macrophages when it is converted to its active form, called Gc macrophage activating factor (Gc-MAF). Gc protein is normally activated by conversion to Gc-MAF with the help of the B and T cells (bone marrow-made and thymus gland-made white blood cells). But, as researchers explain it themselves, cancer cells secrete an enzyme known as alpha-N-acetylgalactosaminidase (also called Nagalase) that completely blocks conversion of Gc protein to Gc-MAF, preventing tumor-cell killing by the macrophages. This is the way cancer cells escape detection and destruction, by disengaging the human immune system. This also leaves cancer patients prone to infections and many then succumb to pneumonia or other infections.
The once-weekly injection of minute amounts of Gc-MAF, just 100 nanograms (billionths of a gram), activates macrophages and allows the immune system to pursue cancer cells with vigor, sufficient to produce total long-term cures in humans.
Nobuto Yamamoto, director of the Division of Cancer Immunology and Molecular Biology, Socrates Institute for Therapeutic Immunology, Philadelphia, Pennsylvania, says this is “probably the most potent macrophage activating factor ever discovered.”
A MACROPHAGE OVERCOMES AND EATS A CANCER CELL
FROM THE UPJOHN COMPANY, THE IMMUNE SYSTEM
Once a sufficient number of activated macrophages are produced, another Gc-MAF injection is not needed for a week because macrophages have a half-life of about six days. After 16-22 weekly doses of Gc-MAF the amount of Nagalase enzyme fell to levels found in healthy people, which serves as evidence tumors have been completely eliminated. The treatment was fool-proof – it worked in 100% of 16 breast cancer patients and there were no recurrent tumors over a period of 4 years, says a report in the January 15 issue of the International Journal of Cancer. [International Journal Cancer. 2008 January15; 122(2):461-7]
In another startling follow-up report by Dr. Yamamoto and colleagues, published in the upcoming July issue of Cancer Immunology Immunotherapy, Gc-MAF therapy totally abolished tumors in 8 colon cancer patients who had already undergone surgery but still exhibited circulating cancer cells (metastases). After 32-50 weekly injections, “all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells,” said researchers, an effect that lasted 7 years with no indication of cancer recurrence either by enzyme activity or CT scans, said researchers. [Cancer Immunology, Immunotherapy Volume 57, Number 7 / July, 2008] Published in an early online edition of this journal, this confirming report has received no attention by the new media so far, despite its striking importance.
Gc-MAF treatment for cancer has been agonizingly slow to develop. Dr. Yamamoto first described this immuno-therapy in 1993. [The Journal of Immunology, 1993 151 (5); 2794-2802]
● Untreated mice ○ Mice given macrophage activating factor
In a similar animal experiment published in 2003, researchers in Germany, Japan and the United States collaborated to successfully demonstrate that after they had injected macrophage activating factor (Gc-MAF) into tumor-bearing mice, it totally eradicated tumors (see the above chart). [Neoplasia 2003 January; 5(1): 32–40]
In 1997 Dr. Yamamoto injected Gc-MAF protein into tumor-bearing mice, with the same startling results. A single enzyme injection doubled the survival of these mice and just four enzyme injections increased survival by 6-fold. [Cancer Research 1997 Jun 1; 57(11):2187-92]
In 1996 Dr. Yamamoto reported that all 52 cancer patients he had studied carried elevated blood plasma levels of the immune inactivating alpha-N-acetylgalactosaminidase enzyme (Nagalase), whereas healthy humans had very low levels of this enzyme. [Cancer Research 1996 Jun 15; 56(12):2827-31]
In the early 1990s Dr. Yamamoto first described how the human immune system is disengaged by enzymes secreted from cancer cells, even filing a patent on the proposed therapy. [US Patent 5326749, July 1994; Cancer Research 1996 June 15; 56: 2827-31]
Activated Gc protein has been used in humans at much higher doses without side effect. This Gc macrophage activating factor (Gc-MAF) has been shown to be effective against a variety of cancers including breast, prostate, stomach, liver, lung, uterus, ovary, brain, skin, head/neck cancer and leukemia.
Although Gc-MAF is also called vitamin D binding protein, the activation of macrophages does not require vitamin D.
It cannot be said the Gc-MAF cancer cure has gone unheralded. Reuters News covered this developing story in January. But the news story still did not receive top billing nor did it fully elucidate the importance of the discovery, actually made years ago, that the human body is capable of abolishing cancer once its immune system is properly activated.
Gc-MAF is a naturally made molecule and is not patentable, though its manufacturing process is patent protected. There is no evidence of any current effort to commercialize this therapy or put it into practice. Should such an effective treatment for cancer come into common practice, the income stream from health insurance plans for every oncology office and cancer center in the world would likely be reduced to the point of financial insolvency and hundreds of thousands of jobs would be eliminated.
The National Cancer Institute estimates cancer care in the U.S. costs ~$72 billion annually (2004). Furthermore, about $55 billion of cancer drugs are used annually, none which have not significantly improved survival rates throughout the history of their use. If a typical cancer patient had to undergo 30 Gc-MAF injections at a cost of $150 per injection, that would cost ~$4500, not counting doctor’s office visits and follow-up testing. For comparison, gene-targeted cancer drugs range from $13,000 to $100,000 in cost per year and produce only marginal improvements in survival (weeks to months). [Targeted Oncology 2007 April, 2 (2); 113-19]
Up to this point, the National Cancer Institute is totally silent on this discovery and there is no evidence the cancer care industry plans to quickly mobilize to use this otherwise harmless treatment.
Timothy Hubbell, a biochemist from Cincinnati, first called attention to this discovery and provided consultation on the biochemistry.
High Levels of Vitamin D in Older People Can Reduce Heart Disease and Diabetes[xxix]
ScienceDaily (Feb. 22, 2010) — Middle aged and elderly people with high levels of vitamin D could reduce their chances of developing heart disease or diabetes by 43%, according to researchers at the University of Warwick.
A team of researchers at Warwick Medical School carried out a systematic literature review of studies examining vitamin D and cardiometabolic disorders. Cardiometabolic disorders include cardiovascular disease, type 2 diabetes mellitus and metabolic syndrome.
Vitamin D is a fat-soluble vitamin that is naturally present in some foods and is also produced when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis. Fish such as salmon, tuna and mackerel are good sources of vitamin D, and it is also available as a dietary supplement.
Researchers looked at 28 studies including 99,745 participants across a variety of ethnic groups including men and women. The studies revealed a significant association between high levels of vitamin D and a decreased risk of developing cardiovascular disease (33% compared to low levels of vitamin D), type 2 diabetes (55% reduction) and metabolic syndrome (51% reduction).
The literature review, published in the journal Maturitas, was led by Johanna Parker and Dr Oscar Franco, Assistant Professor in Public Health at Warwick Medical School.
Dr Franco said: “We found that high levels of vitamin D among middle age and elderly populations are associated with a substantial decrease in cardiovascular disease, type 2 diabetes and metabolic syndrome.
“Targeting vitamin D deficiency in adult populations could potentially slow the current epidemics of cardiometabolic disorders.”
All studies included were published between 1990 and 2009 with the majority published between 2004 and 2009. Half of the studies were conducted in the United States, eight were European, two studies were from Iran, three from Australasia and one from India.
Journal Reference: Parker et al. Levels of vitamin D and cardiometabolic disorders: Systematic review and meta-analysis. Maturitas, 2010; 65 (3): 225 DOI: 10.1016/j.maturitas.2009.12.013
“ …. studies have shown a link between low vitamin D status and heart disease.”[xxx]
VITAMIN D TESTING [xxxi]
I hope you are convinced by the information I’ve given you that Vitamin D3 is a vital part of your recovery (or prevention) regimen for cancer. It also is vital for preventing or treating virtually all other degenerative conditions. Studies have shown that over 95% of the population of all civilized countries are deficient in this vital substance.
When I interviewed Dr. William Grant a few weeks ago on my Web Talk Radio show, he stressed the importance of cancer patients taking enough of Vitamin D3. This is significant because Dr. Grant is one of the world’s most informed scientists about this subject. He has published at least three dozen studies of the effects of Vitamin D and cancer. He is a Ph.D., not a medical doctor, and this is his primary field of study.
Dr. Grant told me about a wonderful service where you can get your Vitamin D level tested every 6 months for the next 5 years for the very reasonable price of $40 every six months. This is part of a five-year study being done by Carole Baggerly, another Vitamin D expert, on the long term effects of Vitamin D on your health. When you go to the website below and sign up for this study, you’ll be asked to fill out a short health questionnaire. When you pay your $40, you’ll be sent a kit and instructions for drawing a couple of drops of blood from your finger at home. You send the packet back to them. A week or so later, you’ll receive an e-mail with your Vitamin D level. Here’s the website for getting started:
My first test came back at 94. That’s in the top 3% of all the tests they have done so far of these levels. Most cancer patients, according to Dr. Grant and others I have talked to about this, are in the low 20’s. The “healthy level” is defined as 40-60 on this test, but Dr. Grant assured me that even higher levels are healthy. Dr. Grant recommended that all cancer patients begin taking 30,000 to 40,000 I.U. of Vitamin D3 every day immediately. Then, he said you should adjust this dosage up or down after you get your test results. There is no toxicity at these levels — or much higher levels. The easy way to take this amount is to buy the 5,000 I.U gelcaps. They are very small and easy to swallow. They are also very inexpensive. I get mine at www.PuritansPride.com. I take one or two of these a day for prevention.
Inadequate Levels of Vitamin D May Significantly Increase Risk of Stroke, Heart Disease and Death[xxxii]
ScienceDaily (Nov. 16, 2009) — While mothers have known that feeding their kids milk builds strong bones, a new study by researchers at the Heart Institute at Intermountain Medical Center in Salt Lake City suggests that Vitamin D contributes to a strong and healthy heart as well — and that inadequate levels of the vitamin may significantly increase a person’s risk of stroke, heart disease, and death, even among people who’ve never had heart disease.
For more than a year, the Intermountain Medical Center research team followed 27,686 patients who were 50 years of age or older with no prior history of cardiovascular disease. The participants had their blood Vitamin D levels tested during routine clinical care. The patients were divided into three groups based on their Vitamin D levels — normal (over 30 nanograms per milliliter), low (15-30 ng/ml), or very low (less than 15 ng/ml). The patients were then followed to see if they developed some form of heart disease.
Researchers found that patients with very low levels of Vitamin D were 77 percent more likely to die, 45 percent more likely to develop coronary artery disease, and 78 percent were more likely to have a stroke than patients with normal levels. Patients with very low levels of Vitamin D were also twice as likely to develop heart failure than those with normal Vitamin D levels.
Findings from the study will be presented at the American Heart Association’s Scientific Conference on Nov. 16 in Orlando, Florida.
“This was a unique study because the association between Vitamin D deficiency and cardiovascular disease has not been well-established,” says Brent Muhlestein, MD, director of cardiovascular research of the Heart Institute at Intermountain Medical Center and one of the authors of the new study. “Its conclusions about how we can prevent disease and provide treatment may ultimately help us save more lives.”
A wealth of research has already shown that Vitamin D is involved in the body’s regulation of calcium, which strengthens bones — and as a result, its deficiency is associated with musculoskeletal disorders. Recently, studies have also linked Vitamin D to the regulation of many other bodily functions including blood pressure, glucose control, and inflammation, all of which are important risk factors related to heart disease. From these results, scientists have postulated that Vitamin D deficiency may also be linked to heart disease itself.
“Utah’s population gave us a unique pool of patients whose health histories are different than patients in previous studies,” Dr. Muhlestein says. “For example, because of Utah’s low use of tobacco and alcohol, we were able to narrow the focus of the study to the effects of Vitamin D on the cardiovascular system.”
The results were quite surprising and very important, says Heidi May, PhD, MS, an epidemiologist with the Intermountain Medical Center research team and one of the study authors.
“We concluded that among patients 50 years of age or older, even a moderate deficiency of Vitamin D levels was associated with developing coronary artery disease, heart failure, stroke, and death,” she says. “This is important because Vitamin D deficiency is easily treated. If increasing levels of Vitamin D can decrease some risk associated with these cardiovascular diseases, it could have a significant public health impact. When you consider that cardiovascular disease is the leading cause of death in America, you understand how this research can help improve the length and quality of people’s lives.”
Because the study was only observational, definitive links between Vitamin D deficiency and heart disease could not be assigned — but the findings create an impetus for further study, says Dr. Muhlestein.
“We believe the findings are important enough to now justify randomized treatment trials of supplementation in patients with Vitamin D deficiency to determine for sure whether it can reduce the risk of heart disease,” he says.
Heart and Bone Damage from Low Vitamin D Tied to Declines in Sex Hormones[xxxiii]
ScienceDaily (Nov. 16, 2009) — Researchers at Johns Hopkins are reporting what is believed to be the first conclusive evidence in men that the long-term ill effects of vitamin D deficiency are amplified by lower levels of the key sex hormone estrogen, but not testosterone.
In a national study in 1010 men, to be presented Nov. 15 at the American Heart Association’s (AHA) annual Scientific Sessions in Orlando, researchers say the new findings build on previous studies showing that deficiencies in vitamin D and low levels of estrogen, found naturally in differing amounts in men and women, were independent risk factors for hardened and narrowed arteries and weakened bones. Vitamin D is an essential part to keeping the body healthy, and can be obtained from fortified foods, such as milk and cereals, and by exposure to sunlight.
“Our results confirm a long-suspected link and suggest that vitamin D supplements, which are already prescribed to treat osteoporosis, may also be useful in preventing heart disease,” says lead study investigator and cardiologist Erin Michos, M.D., M.H.S.
“All three steroid hormones — vitamin D, estrogen and testosterone — are produced from cholesterol, whose blood levels are known to influence arterial and bone health,” says Michos, an assistant professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute. “Our study gives us a much better understanding of how the three work in concert to affect cardiovascular and bone health.”
Michos says the overall biological relationship continues to puzzle scientists because studies of the long-term effects of adding estrogen in the form of hormone replacement therapy in women failed to show fewer deaths from heart disease. Indeed, results showed that in some women, an actual increase in heart disease and stroke rates occurred, although, bone fractures declined.
The Hopkins team’s latest data were provided by analyzing blood samples from a subset of men participating in a study on cancer. That study was part of a larger, ongoing national health survey involving both men and women and was designed to compare the risk of diseases between those with the lowest blood levels of vitamin D to those with higher amounts. An unhealthy deficiency, experts say, is considered blood levels of 20 nanograms per milliliter or lower.
The men in the study had their hormone levels measured for both chemical forms of testosterone and estrogen found in blood, when each is either unattached or circulating freely, and when each is attached to a separate protein, known as sex hormone binding globulin, or SHBG for short.
Initial results showed no link between vitamin D deficiency and depressed blood levels of either hormone. And despite finding a harmful relationship between depressed testosterone levels and rates of heart disease, stroke, and high blood pressure, as well as osteopenia in men, researchers found that it was independent of deficiencies in vitamin D.
However, when researchers compared ratios of estrogen to SHBG levels, they found that rates of both diseases, especially osteopenia, the early stage of osteoporosis, were higher when both estrogen and vitamin D levels were depressed.
For every single unit decrease in ratios of estrogen to SHBG (both in nanomoles per liter), men low in vitamin D showed an 89 percent increase in osteopenia, but men with sufficient vitamin D levels had a less worrisome 64 percent jump.
Using the same measure of estrogen levels, men low in vitamin D were also at heightened risk of cardiovascular diseases, at 12 percent, compared to men with adequate levels of the vitamin, at 1 percent, numbers that researchers say are still statistically significant.
“These results reinforce the message of how important proper quantities of vitamin D are to good bone health, and that a man’s risk of developing osteoporosis and heart disease is heavily weighted on the complex and combined interaction of how any such vitamin deficits interact with both their sex hormones, in particular, estrogen,” Michos says.
Michos and her team next plan to analyze blood samples from women to see if the same results from men hold true.
Michos recommends that men and women boost their vitamin D levels by eating diets rich in fatty fish, such as cod, sardines and mackerel, consuming fortified dairy products, taking vitamin supplements, and in warmer weather briefly exposing skin to the sun’s vitamin-D producing ultraviolet light.
She points out that clinical trials are under way to determine whether or not vitamin D supplements can prevent incidents of or deaths from heart attack, stroke and other signs of cardiovascular disease.
The U.S. Institute of Medicine suggests that an adequate daily intake of vitamin D is between 200 and 400 international units, but Michos feels this is inadequate to achieve optimal nutrient blood levels (above 30 nanograms per milliliter). Previous results from the same nationwide survey showed that 41 percent of men and 53 percent of women are technically deficient in the nutrient, with vitamin D levels below 28 nanograms per milliliter.
Funding for this study was provided by the Hormone Demonstration Project, a part of the Maryland Cigarette Restitution Fund Research Grant Program at the Johns Hopkins University. Additional support was provided by the American College of Cardiology Foundation and a Clinician Scientist Award at the Johns Hopkins University.
Besides Michos, other researchers at Johns Hopkins involved in this study were Jared Reis, Ph.D.; and Meredith Shields and Elizabeth Platz, Ph.D., Sc.D., at the University’s School of Public Health; and Sabine Rohrmann, now at the German Cancer Research Center in Heidelberg. Another investigator in this research was Nader Rifai, Ph.D., at Children’s Hospital Boston and Harvard Medical School.
Vitamin D linked to lower heart disease risk[xxxiv]
By raising low levels of the vitamin to normal levels, patients reduce their risk of heart disease by about 30%, an observational study finds.
March 15, 2010|By Shari Roan
Raising the amount of vitamin D in the blood appears to help some people — at least those deficient in the vitamin — reduce their risk of heart disease by about 30%, researchers announced Monday. The findings, though preliminary, support further investigation of the interplay between vitamin D and heart health.
Observational studies have linked heart disease with low vitamin D levels in the blood. In recent years, studies have shown that as many as three-quarters of Americans have a concentration in their blood that is under the normal level of 30 nanograms per milliliter.
But it has been unclear if people with low vitamin D have more heart disease because of the vitamin deficiency or for other reasons, such as lack of exercise, said Dr. J. Brent Muhlestein, the lead author of the new study and director of cardiovascular research at Intermountain Medical Center Heart Institute in Salt Lake City.
He announced the findings at the American College of Cardiology annual meeting in Atlanta. “The question we looked at is, if you do something about it, like taking vitamin D supplements, does that reduce the risk?” he said.
Researchers have been uncomfortable randomizing people with low vitamin D into a group that receives supplements and a group that does not because, in theory, every vitamin D deficiency should be treated. Low vitamin D levels can contribute to weaker bones and have been associated with increased risks of several diseases, including several types of cancer.
Instead, Muhlestein’s group examined data from more than 9,000 people who had been diagnosed with low vitamin D and who had a blood sample taken at a later date.
About half of the people had normalized their vitamin D levels by the time of the second blood sample, and they showed much less heart disease compared to people whose levels were still below normal.
“What we did was observational and not definitive, but we think it adds significantly to the story,” Muhlestein said. “It’s at least a reasonable piece of evidence to add to the hypothesis that low vitamin D is causative of cardiovascular risk and treatment can reduce cardiovascular disease risk.”
It’s not clear, however, whether the people who improved their vitamin D levels did other things to benefit their health, such as lowering their cholesterol or blood pressure, that might account for the lower risk of heart disease. Moreover, the pages of science journals are littered with now-disproved studies suggesting that various nutrients, such as vitamins E, C and folic acid, might prevent or treat heart disease.
“It turned out those things didn’t help. The low levels seem to be just markers for people who are less healthy,” said Dr. Douglas Weaver, immediate past president of the American College of Cardiology and chief of cardiology at the Henry Ford Health System in Detroit. “But I think these studies that show a relationship between heart attack and vitamin D are going to provoke a lot more research to understand what is going on.”
Vitamin D is synthesized in the skin from exposure to sunlight. It’s also found in a limited number of foods, including salmon and fortified milk. Adequate levels may strengthen the immune system and reduce inflammation, Muhlestein said.
Rheumatoid Arthritis Linked to Vitamin D Deficiency, Study Suggests[xxxv]
ScienceDaily (Apr. 10, 2010) — Women living in the northeastern United States are more likely to develop rheumatoid arthritis (RA), suggesting a link between the autoimmune disease and vitamin D deficiency, says a new study led by a Boston University School of Public Health researcher.
In the paper, which appears online in the journal Environmental Health Perspectives, a spatial analysis led by Dr. Verónica Vieira, MS, DSc, associate professor of environmental health, found that women in states like Vermont, New Hampshire and southern Maine were more likely to report being diagnosed with RA.
“There’s higher risk in the northern latitudes,” Dr. Vieira said. “This might be related to the fact that there’s less sunlight in these areas, which results in a vitamin D deficiency.”
The study looked at data from the Nurses’ Health Study, a long-term cohort study of U.S. female nurses. Looking at the residential addresses, health outcomes and behavioral risk factors for participants between 1988 and 2002, researchers based their findings on 461 women who had RA, compared to a large control group of 9,220.
RA is a chronic inflammatory disease that affects the lining of the joints, mostly in the hands and knees. This chronic arthritis is characterized by swelling and redness and can wear down the cartilage between bones. RA is two to three times more common in women than in men.
Although the cause of RA is unknown, the researchers wrote, earlier studies have shown that vitamin D deficiency, which can be caused by a lack of sunlight, has already been associated with a variety of other autoimmune diseases.
“A geographic association with northern latitudes has also been observed for multiple sclerosis and Crohn’s disease, other autoimmune diseases that may be mediated by reduced vitamin D from decreased solar exposure and the immune effects of vitamin D deficiency,” the authors wrote.
The authors said further research is needed to look into the relationship between vitamin D exposure and RA.
Dr. Vieira said she and her co-authors were somewhat surprised by the findings. A previous geographic study of RA had suggested an ecologic association with air pollution, she said.
“The results were unexpected,” Dr. Vieira said. “Prior to the analysis, we were more interested in the relationship with air pollution. I hadn’t given latitudes much thought.”
In addition to the geographic variation, the study suggested that the timing of residency may influence RA risk. “Slightly higher odds ratios were observed for the 1988 analysis suggesting that long term exposure may be more important than recent exposure,” the study said.
Dr. Vieira and other BUSPH researchers previously have used innovative spatial-temporal analyses to study the incidence of breast cancer, specifically focused on Cape Cod.
In addition to Dr. Vieira, co-authors of the article are Dr. Jaime Hart, MS, ScD, research fellow, Department of Epidemiology, Harvard School of Public Health; Dr. Thomas Webster, DSc, professor and associate chair, Department of Environmental Health, Boston University School of Public Health; Dr. Janice Weinberg, ScD, MS, associate professor, Department of Biostatistics, Boston University School of Public Health; Dr. Robin Puett, PhD, MPH, research assistant professor, Environmental Health Sciences, University of South Carolina; Dr. Francine Laden, ScD, MS, associate professor, Department of Epidemiology, Harvard School of Public Health; Dr. Karen Costenbader, MD, assistant professor of medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Harvard Medical School; and Dr. Elizabeth Karlson, MD, associate professor of medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Harvard Medical School.
The research was funded by grants from the National Institutes of Health.
Vieira et al. Association between Residences in U.S. Northern Latitudes and Rheumatoid Arthritis: A Spatial Analysis of the Nurses’ Health Study. Environmental Health Perspectives, 2010; DOI: 10.1289/ehp.0901861
Low Vitamin D Levels Associated With More Asthma Symptoms and Medication Use[xxxvi]
ScienceDaily (Apr. 20, 2010) — Low levels of vitamin D are associated with lower lung function and greater medication use in children with asthma, according to researchers at National Jewish Health. In a paper published online this week in the Journal of Allergy & Clinical Immunology, Daniel Searing, MD, and his colleagues also reported that vitamin D enhances the activity of corticosteroids, the most effective controller medication for asthma.
“Asthmatic children in our study who had low levels of vitamin D were more allergic, had poorer lung function and used more medications,” said Dr. Searing. “Conversely, our findings suggest that vitamin D supplementation may help reverse steroid resistance in asthmatic children and reduce the effective dose of steroids needed for our patients.”
The researchers examined electronic medical records of 100 pediatric asthma patients referred to National Jewish Health. Overall, 47 percent of them had vitamin D levels considered insufficient, below 30 nanograms per milliliter of blood (ng/mL). Seventeen percent of the patients had levels below 20 ng/mL, which is considered deficient. These levels were similar to vitamin D levels found in the general population.
Patients low in vitamin D generally had higher levels of IgE, a marker of allergy, and responded positively to more allergens in a skin prick test. Allergies to the specific indoor allergens, dog and house dust mite, were higher in patients with low vitamin D levels. Low vitamin D also correlated with low FEV1, the amount of air a person can exhale in one second, and lower FEV1/FVC, another measure of lung function. Use of inhaled steroids, oral steroids and long-acting beta agonists were all higher in patients low in vitamin D.
“Our findings suggest two possible explanations,” said senior author Donald Leung, MD, PhD. “It could be that lower vitamin D levels contribute to increasing asthma severity, which requires more corticosteroid therapy. Or, it may be that vitamin D directly affects steroid activity, and that low levels of vitamin D make the steroids less effective, thus requiring more medication for the same effect.”
The researchers performed a series of laboratory experiments that indicated vitamin D enhances the action of corticosteroids. They cultured some immune cells with the corticosteroid dexamethasone alone and others with vitamin D first, then dexamethasone. The vitamin D significantly increased the effectiveness of dexamethasone. In one experiment vitamin D and dexamethasone together were more effective than 10 times as much dexamethasone alone.
The researchers also incubated immune-system cells for 72 hours with a staphylococcal toxin to induce corticosteroid resistance. Vitamin D restored the activity of dexamethasone.
“Our work suggests that vitamin D enhances the anti-inflammatory function of corticosteroids,’ said Dr. Leung. “If future studies confirm these findings vitamin D may help asthma patients achieve better control of their respiratory symptoms with less medication.”
This study comes on the heels of another paper by National Jewish Health faculty, which showed that low levels of vitamin D in adult asthma patients are associated with lower lung function and reduced responsiveness to corticosteroids.
Journal Reference: Searing et al. Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use. The Journal of Allergy and Clinical Immunology, 2010; DOI: 10.1016/j.jaci.2010.03.008
Researchers Recommend Pregnant Women Take 4,000 IU Vitamin D a Day[xxxvii]
ScienceDaily (May 1, 2010) — Taking vitamin D supplements during pregnancy is not only safe for mother and baby, but also can prevent preterm labor/births and infections, according to results of a randomized controlled study to be presented at the Pediatric Academic Societies (PAS) annual meeting in Vancouver, British Columbia, Canada.
In the 1950s and ’60s, people were concerned that vitamin D could cause birth defects, according to Carol L. Wagner, MD, lead author of the study and a pediatric researcher at Medical University of South Carolina. It now is known that vitamin D is important for maternal and infant health, including bone health and immune function.
Recent studies have shown that vitamin D deficiency during pregnancy is a serious public health issue.
“Diet doesn’t provide enough vitamin D, and we don’t go in the sun as much as we need,” Dr. Wagner said.
Therefore, she and her colleagues, including Bruce W. Hollis, PhD, who has worked in the field of vitamin D research for the last 30 years, set out to determine the optimal dose of vitamin D supplements for pregnant women without doing harm.
Researchers randomized 494 pregnant women at 12-16 weeks’ gestation into three treatment groups. Group one received 400 International Units (IU) of vitamin D a day until delivery; group two received 2,000 IU and group three received 4,000 IU. The women were evaluated monthly to ensure safety.
“No adverse events related to vitamin D dosing were found in any of the three arms of the study,” Dr. Wagner said.
Investigators also looked at the effects of vitamin D supplementation on complications during pregnancy, including preeclampsia, gestational diabetes, infections, and preterm labor and birth.
“The spectacular part of the study was it showed women replete in vitamin D had lower rates of preterm labor and preterm birth, and lower rates of infection,” Dr. Wagner said.
The greatest effects were seen among women taking 4,000 IU of vitamin D per day. Therefore, the researchers recommend this daily regimen for all pregnant women.
Low Vitamin D Levels Are Related to MS Brain Atrophy, Cognitive Function, Studies Show[xxxviii]
ScienceDaily (Apr. 30, 2010) — Low vitamin D levels may be associated with more advanced physical disability and cognitive impairment in persons with multiple sclerosis, studies conducted by neurologists at the University at Buffalo have shown.
Their results, reported at the American Academy of Neurology meeting, held earlier this month, indicated that:
- The majority of MS patients and healthy controls had insufficient vitamin D levels.
- Clinical evaluation and magnetic resonance imaging (MRI) images show low blood levels of total vitamin D and certain active vitamin D byproducts are associated with increased disability, brain atrophy and brain lesion load in MS patients.
- A potential association exists between cognitive impairment in MS patients and low vitamin D levels.
The MRI study involved 236 MS patients — 208 diagnosed with the relapsing-remitting type and 28 with secondary progressive, a more destructive form of MS — and 22 persons without MS.
All participants provided blood serum samples, which were analyzed for total vitamin D (D2 and D3) levels as well as levels of active vitamin D byproducts. MRI scans performed within three months of blood sampling were available for 163 of the MS patients.
Results showed that only seven percent of persons with secondary-progressive MS showed sufficient vitamin D, compared to 18.3 percent of patients with the less severe relapsing-remitting type.
Higher levels of vitamin D3 and vitamin D3 metabolism byproducts (analyzed as a ratio) also were associated with better scores on disability tests, results showed, and with less brain atrophy and fewer lesions on MRI scans.
Bianca Weinstock-Guttman, MD, UB associate professor of neurology/Jacobs Neurological Institute and director of the Baird Multiple Sclerosis Center, is first author on the study. Commenting on these results, Weinstock-Guttman said: “Clinical studies are necessary to assess vitamin D supplementation and the underlying mechanism that contributes to MS disease progression.”
While lower-than-normal vitamin D status is known to be associated with a higher risk of developing MS, little is known about its relationship to cognitive impairment.
Sarah A. Morrow, MD, UB assistant research professor of neurology/Jacobs Neurological Institute and lead author on the cognitive-impairment study, compared vitamin D levels in blood samples of 136 MS patients with the results of their neuropsychological assessments that tested multiple types of cognition affected by MS.
“Results showed that MS patients who were impaired on tests of executive function — critical reasoning and abstract thinking — and the ability to plan and organize, were more likely to be deficient in vitamin D,” said Morrow.
“This relationship held true when controlling for the season during which vitamin D was measured, as well as depression, which is known to be associated with lower vitamin D levels.” Morrow noted there also was a suggestion that verbal fluency (word generation) and visual-spatial memory (learning and memory of shapes and figures) is more likely to be affected when vitamin D levels are not sufficient.
Morrow is continuing her research to clarify these relationships.
Vitamin D Deficiency Associated With Chronic Fatigue in Brain Injured Patients[xxxix]
ScienceDaily (Apr. 28, 2010) — New evidence presented at the European Congress of Endocrinology has shown that vitamin D deficiency is closely associated with the chronic fatigue that often follows post traumatic brain injury (TBI).
TBI is a major cause of death and disability worldwide. In the European Union the annual incidence of TBI hospitalizations and fatalities is estimated at 235 per 100,000 people. This means that on average a large European state such as the UK, France or Germany, will have around 140,000 new traumatic brain injuries every year (national figures vary). Around two-thirds of post TBI patients go on to suffer chronic fatigue. Now a group of researchers in the Netherlands have linked vitamin D deficiency to chronic fatigue in post-TBI sufferers.
The group, led by Dr Jessica Schnieders from Rijnstate Hospital in Arnham, The Netherlands, looked at vitamin D and hormone levels in 90 fatigued and non-fatigued subjects. They also systematically evaluated pituitary hormones and factors such as sleep, attention, emotional well-being, quality of life, coping style, and daily activity. They found that 51% of TBI patients were severely fatigued 10 years after the trauma. Vitamin D deficiency was present in 65% of post TBI patients and significantly related with fatigue (P<0.05), with patients who suffered from fatigue more likely to be vitamin D deficient. The group also found a higher incidence of growth hormone and sex hormone deficiency in the fatigued group, but they found no evidence that these deficiencies contributed to the fatigue.
This work opens the possibility that correcting the vitamin D deficiency might help to reduce some of the chronic fatigue in TBI patients. However, as vitamin D levels in the body are affected by diet and time spent in the sunshine, further studies are now needed to confirm whether low vitamin D levels are a cause of the fatigue or whether they are a consequence of altered lifestyle led due to suffering from fatigue.
Lead researcher, Dr Jessica Schnieders said: “In the Netherlands we have 30,000 people every year who suffer a traumatic brain injury and many of these go on to suffer from chronic fatigue. This is early work, so we need to confirm that vitamin D is the cause of this fatigue, and if so to see if taking vitamin D, perhaps coupled with improved sleep patterns, can alleviate some of the symptoms.
“We looked at patients around 10 years after their trauma. Fatigued post traumatic brain injury patients are less active, and generally experience a reduced quality of life. They have difficulties in maintaining relationships and keeping jobs, and are less independent than people who have not had to cope with such trauma.”
Better Vitamin D Status Could Mean Better Quality of Life for Seniors[xl]
ScienceDaily (Apr. 26, 2010) — According to legend, it was The Fountain of Youth that the famed Spanish explorer Ponce de Leon was seeking when he landed on the Floridian coast in 1513. It has long been said that he who drinks from the Fountain will have his youth restored. Without a doubt, the quest for eternal youth is as ancient as any pursuit. However, although we are now living longer than ever, there is now growing concern that quantity of years is not nearly as important as quality of those years. Indeed, as we experience the many joys of living longer, we also must deal with myriad consequences accompanying this aging trend.
For instance, osteoporosis, arthritis, and other serious and often painful bone and joint diseases are much more common as we get older. And, not surprisingly, seniors often struggle daily with what was once the simple task of getting around. Hence, the obvious question in today’s society concerning our longevity is “What choices can we make to help ease these inconveniences of aging?”
One area of particular interest is the role that diet plays in keeping bones and muscles strong from infancy to old age. For instance, a limited number of studies point to the possibility that optimal intake of vitamin D (the “sunshine” vitamin) might help keep our muscles strong and preserve physical function. Although there are only few longitudinal studies investigating this relationship, their findings have been mixed. To help understand this diet-health association, Dr. Denise Houston from the Sticht Center on Aging at Wake Forest University and her collaborators studied the relationship between vitamin D status and physical function in a group of relatively healthy seniors living in Memphis, TN and Pittsburgh, PA. Their results will be presented on April 25 as part of the scientific program of the American Society for Nutrition, composed of the world’s leading nutrition researchers, at the Experimental Biology 2010 meeting in Anaheim, California.
This study was part of the Health, Aging, and Body Composition (Health ABC) study initially designed to assess the associations among body composition, long-term health conditions, and mobility in older adults. For Houston’s segment of the investigation, she studied 2788 seniors (mean age: ~75 years) for 4 years. At the beginning of the study, they assessed vitamin D status by analyzing each person’s blood for 25-hydroxyvitamin D, a precursor for activated vitamin D. At baseline and then 2 and 4 years later, the research team then determined whether circulating 25-hydroxyvitamin D was related to the participants’ physical function. Specifically, they looked at how quickly each participant could walk a short distance (6 meters) and rise from a chair five times as well as maintain his or her balance in progressively more challenging positions. Each participant was also put through a battery of tests assessing endurance and strength.
When the results were tabulated, participants with the highest levels of 25-hydroxyvitamin D had better physical function. And, although physical function declined over the course of the study, it remained significantly higher among those with the highest vitamin D levels at the beginning of the study compared to those with the lowest vitamin D levels. The scientists were not surprised to learn that, in general, vitamin D consumption was very low in this group of otherwise healthy seniors. In fact, more than 90% of them consumed less vitamin D than currently recommended, and many were relying on dietary supplements.
The good news: higher circulating 25-hydroxyvitamin D is related to better physical function in seniors. But it’s impossible to tell from this type of research whether increasing vitamin D intake will actually lead to stronger muscles and preserve physical function. This is partly due to the fact that our bodies can make vitamin D if they get enough sunlight. So, it is possible that the participants with better physical function had higher vitamin D status simply because they were able to go outside more often. Indeed, the ominous “chicken-or-the-egg” question can only be answered by carefully controlled clinical intervention trials. Nonetheless, it is possible that getting more vitamin D from foods (like fortified milk and oily fish) or supplements will help maintain youth and vitality as we enjoy longer lifespans. As Houston points out: “Current dietary recommendations are based primarily on vitamin D’s effects on bone health. It is possible that higher amounts of vitamin D are needed for the preservation of muscle strength and physical function as well as other health conditions. However, clinical trials are needed to definitively determine whether increasing 25-hydroxyvitamin D concentrations through diet or supplements has an effect on these non-traditional outcomes.”
Will vitamin D research lead us to The Fountain of Youth? Probably not. But paying attention to how much vitamin D we get is likely important at every age and will help enhance the “quality” component of life as we enter our senior years.
Dr. Denise Houston (Wake Forest University, Winston Salem, NC); Dr. Janet Tooze (Wake Forest University); Rebecca Neiberg (Wake Forest University), Dr. Kyla Shea (Wake Forest University), Dr. Dorothy Hausman (University of Georgia, Athens, GA), Dr. Mary Ann Johnson (University of Georgia), Dr. Jane Cauley (University of Pittsburgh, Pittsburgh, PA), Dr. Doug Bauer (University of California, San Francisco, CA), Dr. Frances Tylavsky (University of Tennessee, Memphis, TN), Dr. Marjolein Visser (VU University, Amsterdam, Netherlands), Dr. Eleanor Simonsick (National Institute on Aging, Baltimore, MD), Dr. Tamara Harris (National Institute on Aging), and Dr. Stephen Kritchevsky (Wake Forest University) were coauthors on this paper.
Adapted from materials provided by Federation of American Societies for Experimental Biology, via EurekAlert!, a service of AAAS.
Effect of 25-hydroxyvitamin D status on serological response to influenza vaccine in prostate cancer patients[xli]
The Prostate, 09/08/2010
Chadha MK et al. – Epidemiologic data suggest that there is an association between vitamin D deficiency and influenza infection. The authors conducted a prospective influenza vaccination study to determine the influence of vitamin D status on serological response to influenza vaccine in prostate cancer (CaP) patients. In this study in CaP patients, a replete vitamin D status was associated with more frequent serological response to influenza vaccine.