By Nita Sharma Das, PhD, Doctor of Naturopathy
This article discusses
- the way Vitamin D is formed in the body,
- a wide range of diseases and medical conditions associated with Vitamin D deficiency, and
- how these conditions may benefit from Vitamin D supplementation.
Vitamin D For Treating & Preventing DiseaseAvoiding the sun is not a good option for keeping you or your next generation healthy. Now that we’re encouraged to limit our sun exposure for health reasons, we see more frequent influenza epidemics, higher incidence of the common cold, and increased rates of autism, asthma and type 1-diabetes in early childhood, all of which are associated with a deficiency of Vitamin D.
Vitamin D is often referred to as a type of fat-soluble vitamin, but this is something of an over-simplification. It is in fact a component within a complex system that includes precursors, active metabolites, enzymes, and receptors.
Vitamin D has diverse functionality. Vitamin-D is primarily known for maintaining an appropriate balance of calcium and phosphorous level involved in the regulation of bone density. Its ‘non-calcemic’ effects include host defence, immunity, inflammation and cancer prevention and treatment, these effects noted in a number of clinical trials completed to date.,
The metabolic product of Vitamin-D acts as a potent substrate, as a pleiotropic nutrient involved in repair and maintenance, and formation of a secosteroid hormone that targets more than 200 human genes in a wide variety of tissues, thus having functions beyond those of a mere vitamin.
Vitamin D Synthesis
Vitamin D has two different forms: vitamin D3, or cholecalciferol, and vitamin D2, or ergocalciferol.
Vitamin D3 production in the human body starts in the skin or lymph after exposure to sunlight, or UVB radiation. Vitamin D2 is generated from various plant sources that include yeast and fungi when they are exposed to UVB radiation. It is possible for a combination of dietary sources of Vitamin D and exposure to UVB to provide an adequate supply of Vitamin D2 and Vitamin D3 in the human body.
After vitamin D enters into blood circulation, it reaches the liver within a few hours and accumulates there.
Hydroxylation of Vitamin D has two steps. First, hydroxylation is conducted in the liver where vitamin D converts to 25(OH)D or calcidiol by the action of cytochrome P450 enzyme CYP27A1 and, second, hydroxylation occurs within the kidneys by the mitochondrial 1α-hydroxylase enzyme CYP27B1. The majority of CYP27B1 enzyme is present in the kidney, although the colon, prostate, breast, lung and pancreas also possess CYP27B1 and thus can also synthesize and degrade calcitriol.
Endocrinal Activity Of Vitamin D Acts To Regulate Bone Density And Levels Of Calcium And Phosphorus
Vitamin D is effective in maintaining a healthy skeleton system development in a wide range of ways. First, it maintains blood serum concentrations of calcium and phosphorus within the normal range, by boosting the efficiency of the small intestine to absorb these minerals from the diet.
Second, an adequate supply of vitamin D prevents and cures rickets in children as well as osteomalacia and porotic bone (osteoporosis) in adults.
In the case of an inadequate supply of calcium from dietary sources, the body’s calcium requirement is fulfilled by 1,25-dihydroxyvitamin D (1,25(OH)2D) along with parathyroid hormone (PTH). 1,25-dihydroxy vitamin D (1,25(OH)2D) is a biologically active hormone which is formed by hydroxylation, as Vitamin D, either D2 (ergocalciferol) or D3 (cholecalciferol), or a combination of both, is biologically inert (ie has insignificant biological activity).
When the dietary intake of calcium is inadequate to satisfy the body’s calcium requirement, 1,25(OH)2D and parathyroid hormone (PTH) work together to mobilize monocytic stem cells in the bone marrow to become mature osteoclasts, thus able to utilize the calcium stored within the bone. The osteoclasts, in turn, are stimulated by a variety of cytokines and other factors to increase the mobilization of calcium stores from the bone. Thus, vitamin D maintains the blood calcium and phosphorus at supersaturating concentrations that are deposited in the bone as calcium hydroxyapatite.
These ‘calcemic’ actions of Vitamin D are well known. But during the end of 20th century, scientists discovered more information about Vitamin D’s efficacy and its role as a potent anti-proliferative and pro-differentiation hormone, as we’ll discuss below.
The Cell Signalling (Autocrine) Function Of Vitamin D Significantly Reduces All-Cause Of Death Rate
The action of vitamin D has previously been viewed as a single endocrinal activity that works in combination with Parathyroid hormone (PTH). However, more recent research reveals that vitamin D not only has a single action in maintaining haemostasis of calcium level, but that it also provides multiple autocrine functions as vitamin D and its analogues wield their effects through both genomic and non-genomic pathways. .
- Vitamin D receptors (VDR) are distributed in many organs and tissues associated with the epidermis and each of the Cardiovascular, Endocrine, Gastrointestinal, Immune, Renal, Respiratory, Osteomuscular, Reproductive, and central nervous systems. Thus Vitamin D deficiency is associated with cardiovascular disease, hypertension, stroke, diabetes, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, osteoporosis, periodontal disease, macular degeneration, mental illness, propensity to fall, and chronic pain. (1,2,3)
- One of the most important genes, cathelicidin, is a naturally occurring broad-spectrum antibiotic, and is up-regulated by vitamin D.
- In winter, when vitamin D levels are reduced, pneumococcal disease, meningococcal disease, and group A streptococcal disease are all more common. The three bacteria associated with these diseases are sensitive to antimicrobial peptides (AMP) as they have a broad spectrum antibiotic activity. Pharmacological doses of vitamin D would be an effective adjuvant treatment against these infections by augmenting the production of AMPs, although vitamin D has no direct antimicrobial activity itself.
- Vitamin D plays a role in HIV control as vitamin D-sensitive antimicrobial peptides (AMP) inhibit the HIV virus. (4,5,6,7)
- A randomized clinical trial conducted by Lappe et al (8) first reported that vitamin D is able to prevent internal cancers and found a 60-percent reduction in such cancers by increasing baseline 25(OH)D levels from 29 ng/mL to 38 ng/mL with 1,100 IU (28 mcg) per day.
- Cellular studies revealed that Vitamin D modulates the activity of various defense and immune cells including blood monocytes, macrophages, antigen-presenting cells and activated CD4 T cells, or epithelial cells (Bhalla et al.,1983; Manolagas et al., 1986; Veldman et al., 2000). It is well established that 1,25(OH)2D modulates T lymphocyte proliferation and function. (9)
Vitamin D: Effectiveness In Cancer Treatment and Prevention
Vitamin D, through its genetic mechanism of action can also be effective against cancer. Vitamin D is able to reduce cellular proliferation, induce cell differentiation and apoptosis, and prevent angioneogenesis, each an important goal in cancer treatment.
Furthermore, local production and degradation of calcitriol in the colon, prostate, breast, lung, and pancreas have been suggested to represent a key factors in several types of human cancer. (10) The vitamin D receptor (VDR) communicates with both benign and malignant proliferative cells. Epidemiologic and in vitro studies suggest that Vitamin D plays an important role in cancer development which can be demonstrated in the following ways:
- Low circulating levels of vitamin D are associated with increased risk of developing cancer,
- A high intake of vitamin D is associated with a reduced risk of cancer,
- The aggressiveness of a cancer is lower in summer when the production of vitamin D is higher, (11)
- Polymorphisms (different types) of encoding proteins of genes involved in the signal pathway of vitamin D affect the risk of developing cancer.
Vitamin D’s Role In Prostate Cancer
In 2012, the American Chemical Society (ACS) reported on a study in which men with low-grade prostate cancer took vitamin D supplements for a year, after which 55 percent of them showed decreased readings on the standard “Gleason” grading scale or even complete disappearance of their tumors compared to their biopsies a year before (J. Clin. Endocrinol. Metab., 2012, DOI: 10.1210/jc.2012-1451). This helped to explain that vitamin D caused dramatic changes in the expression levels of many cell lipids and proteins, particularly those involved in inflammation in the case of prostate gland cancer.
Vitamin D and Breast Cancer
Dr. Cedric F. Garland of the University of California’s San Diego Moores Cancer Center established a relationship between the development of breast cancer and vitamin D deficiency (4). Epithelial cells present in the breast are held together by a glue-like substance called E-cadherin which is composed mostly of vitamin D and calcium. This structure can come apart due to inadequate levels of vitamin D, and those cells do what they are programmed to do in order to survive — they go forth and multiply. If this growth process (cell proliferation) gets out of control, it can result in cancer. If breast cancer is in progress, the addition of vitamin D can help stop cancer cells in their tracks by replenishing E-cadherin.
Garland explained that Vitamin D can increase the survival rate in breast cancer patients as it both blocks aggressive cell division and additionally can stop tumour growth by limiting its blood supply in a process known as angiogenesis inhibition. If the formation of new blood vessels to a tumor (angiogenesis) can be stopped, the tumor is thus starved of blood and nutrients, leading to an improved outcome. In fact Vitamin D acts a selective angiogenesis inhibitor—it retards the growth of new, undesirable “feeder” blood vessels into cancer cells.
The Role of Vitamin D In Skin Cancer And Other Skin Diseases
By now, we’re all familiar with warnings about skin cancer and sun exposure, but perhaps we’re taking it too far. Vitamin D naturally synthesizes in the skin in presence of sunlight and in recent decades there has been some misconception that vitamin D may be harmful to the skin.
More recent studies show that Vitamin D acts as an “immunomodulator”, regulating and normalizing the immune system, and that this provides therapeutic effects in atopic dermatitis, psoriasis, and skin cancer. Non melanoma cutaneous carcinomas can develop due to exposure to ultraviolet (UV) radiation but, in the lab (in vitro), Vitamin D has been to shown to offer protection to keratinocytes (skin cells) against UV radiation. (13) Vitamin D production in the skin, in response to sunlight, is thus a major player in reducing the risk of melanoma. Enzymes in melanoma cells form active vitamin D, which in turn can lead to melanoma cell death, and in lab experiments, it’s been shown that active vitamin D can destroy melanoma cells. (14)
Vitamin D, Colon and Colorectal Cancer
Vitamin D3 comes in two forms: 25(OH)D3 (25-Hydroxycholecalciferol or Calcifediol) and 1,25 (OH)2D3 (Calcitriol). Of these, the most active form is Calcitriol, which acts as a potent steroid hormone, binding to VDR and thereby altering the expression of a variety of genes regulating growth, differentiation and survival of epithelial cells.
Epidemiological studies (15) suggest that deficiency of vitamin D increases the incidence of colon cancer and also has a negative impact on the survival of colon cancer patients.
A clinical trial conducted in 2011 shows that those with polyps in their colon or rectum and given vitamin D 800 IU had 77% lower rates of inflammation than the placebo group. A paper published in 2011 (16) reported that people with the highest levels of vitamin D in their body had a 50% lower chance of developing rectal cancer, and a 23% lower chance of developing colon cancer than people with the lowest levels of vitamin D.
Vitamin D in Endocrine cancer
A clinical trial conducted in 2015 by Jeffrey Drebin, MD, PhD, Chair of the Department of Surgery at the Perelman School of Medicine at the University of Pennsylvania reported that vitamin D makes cancer cells inactive in pancreatic cancer.
Furthermore, researchers have found that vitamin D stops the production of stromal cells, which fuel the tumor and feed it, and which create a physical barrier preventing chemo drugs from entering the cell.
Studies also point to the efficacy of vitamin D against thyroid gland carcinoma (17). The chemotherapy drug paclitaxel (Taxol) and suberoylanilide hydroxamic acid (SAHA, Vorinostat) provide additive and synergistic antiproliferative effects when used in a combination treatment with 1,25(OH)2D or its superagonistic analog .
The Role of Vitamin D in Lung Cancer
Vitamin D improves the survival rate in lung cancer. Preclinical trials indicate that vitamin D is able to inhibit lung cancer metastasis. The British Journal of Cancer reported as early as 2001 that cooked and raw fish, among the richest sources of Vitamin D, lowered the risk of lung adenocarcinoma among the Japanese. In a more recent study of Norwegian men and women, consumption of cod liver oil, another of the top Vitamin D sources, was also found to protect against lung cancer.
Role of Vitamin D in Ovarian cancer
There are no reported studies of using vitamin D to treat ovarian cancer. However, it has been noted that U.S.A.-based women with ovarian cancer were four times more likely to have low vitamin D blood levels than women without ovarian cancer. This study compared vitamin D levels greater than 23 ng/mL (58 nmol/L) to lower levels.
Natural Sources of Vitamin D
Very few foods in nature contain vitamin D. The flesh of fatty fish (such as salmon, tuna, and mackerel) and fish liver oils are among the best sources. Small amounts of vitamin D are also found in beef liver, cheese, and egg yolks.
Vitamin D in these foods is primarily in the form of vitamin D3 and its metabolite 25(OH)D3. Some mushrooms provide vitamin D2 in variable amounts. Mushrooms with enhanced levels of vitamin D2 are also available, having been exposed to ultraviolet light under controlled conditions. It is possible but difficult to obtain enough vitamin D from diet alone. Most people only get five to ten per cent of their vitamin D from food.
As discussed above, the body makes vitamin D when skin is directly exposed to the sun. A review of vitamin D production from sunlight recommended getting all over sun (such as swimming in swimwear) for about 10-15 minutes on a standard UV index (i.e 14) for seven days of the week. Skin exposed to sunshine indoors through a window will not produce vitamin D. Cloudy days, shade, and having dark-colored skin also reduce the amount of vitamin D the skin makes.
The UK’s National Diet and Nutrition Survey results from Years 1 to 4 (combined) of the rolling programme for 2008 and and 2009 – 2011 and 2012 (Public Health England and Food Standards Agency) shows that vitamin D levels are highest among all age groups in the summer months and lowest in the winter. For example, only 8% of adults aged 19–64 had a low vitamin D status in July to September, compared with 39% in January to March. Similarly, around 2% of children aged 4 to 10 years had a low vitamin D status in July to September, compared to 32% in January to March.
However, despite the importance of the sun to vitamin D synthesis, it is prudent to limit exposure of skin to sunlight in order to lower the risk for skin cancer. When out in the sun for more than a few minutes, it’s best to wear protective clothing and apply sunscreen with a SPF (sun protection factor) of 8 or more. Tanning beds also cause the skin to make vitamin D, but pose similar risks for skin cancer (Non melanoma cutaneous carcinomas).
How To Determine Vitamin D Deficiency
Serum concentration of 25(OH)D is the best indicator of vitamin D status. Levels are described in either nanomoles per liter (nmol/L) or nanograms per milliliter (ng/mL), where 1 nmol/L = 0.4 ng/mL. According to the USA’s NIH report of 2010, the Institute of MedicineFood and Nutrition Board, concluded that
- Levels below 30 nmol/L (12 ng/mL) are too low for bone or overall health,
- Levels above 125 nmol/L (50 ng/mL) are probably too high.
- Levels of 50 nmol/L or above (20 ng/mL or above) are sufficient for most people.
High Risk Groups
According to the UK’s National Institute for Health and Care Excellence (NICE) guidelines of 2014, the following groups are at risk for Vitamin D deficiency and may require vitamin D supplementation, particularly if they avoid nuts, are vegan or have a halal or kosher diet:
- Infants and children aged under 5
- Pregnant and breastfeeding women, particularly teenagers and young women
- People over 65
- People who have low or no exposure to the sun, for example, those who cover their skin for cultural reasons, who are housebound or confined indoors for long periods
- People with darker skin, for example, people of African, African-Caribbean or South Asian family origin.
Reference Nutrient Intake
According to the UK’s NICE guidelines of 2014, the current reference nutrient intakes (mcg/day) for vitamin D are:
- 5 for infants up to 6 months
- 7 for children between 6 months and 3 years
- 10 for women during pregnancy and lactation and adults over 65.
The UK’s Scientific Advisory Committee on Nutrition has not provided a reference nutrient intake for people aged between 4 and 65 years. In these cases it is assumed that the action of sunlight on skin will provide adequate vitamin D, except for specific at-risk groups, as listed above..
Vitamin D Supplementation and Cancer Prevention
Results of randomized clinical trials published in 2011 (18) suggest that an inadequate level of vitamin D in blood serum increases the risk factor for development of breast, colon, and rectal cancers. Compared to low levels of vitamin D (below 20 ng/mL [50 nmol/L]), high levels (above 40 ng/mL [100 nmol/L]) may reduce the risk of these cancers by 15% to 25%. High levels of vitamin D may also increase survival after cancer diagnosis. These findings may also apply to ovarian cancer. Taking 1000–4000 international units (IU) (25–100 mcg)/day of vitamin D is generally required to reach blood levels of 40 ng/mL (100 nmol/L). (19)
Dietary products and sunshine alone are not adequate to meet the needs of someone with vitamin D deficiency. As per Canadian guidelines, 1000 IU vitamin D is required to maintain the required serum concentration for those under the age of 50; for elderly patients over 50 years of age, they would need 2000 IU vitamin D.
The process of utilization and metabolism of vitamin-D is complex in certain disease states. It is reasonable to predict that vitamin D is utilized more rapidly in some disease states than others. For example, patients with diabetes, HIV, or cancer may rapidly use 25(OH)D as substrate (a molecule upon which an enzyme acts) to make large amounts of 1,25(OH)2 D to fight their disease. Therefore, a patient with cancer may require significantly higher doses of vitamin D to maintain 25(OH)D levels of 55-70 ng/mL than a healthy adult of similar weight and body fat.
A recent study appearing in the Anticancer Research Journal suggests that to be able to take advantage of cancer protection benefits, higher levels of Vitamin D are required, or as much as 4,000 to 8,000 IU for adults per day, depending upon the patient condition. Subject to the patient having no history of hypercalcemia, practitioners can extend the dose up to 10,000 IU or more per day with frequent monitoring of 25(OH)D and calcium levels. Oral vitamin D supplementation can be recommended to significantly reduce the cancer mortality from melanoma and other solid tumors without increasing the risk of non-melanoma cutaneous cancers inherent to increased ultraviolet light exposure.
As dietary products contain very low amounts of vitamin D, the chief source of vitamin D is normally sunlight. However, factors such as geographical location, race, culture and seasonal changes can limit the supply of vitamin D synthesized from sunlight. Studies show a high incidence of vitamin D deficiency in patients undergoing treatment for cancer (20). Thus there is significant scope to incorporate vitamin D supplements in the treatment of cancer. Other conditions that may benefit from Vitamin D, not covered in this article, include Multiple Sclerosis, HIV, and hepatitis B.
The breadth of results available from preclinical and clinical studies strongly suggest that vitamin D deficiency increases the risk of developing cancer and that avoiding deficiency and adding vitamin D supplements might be an economical and safe way to reduce cancer incidence and improve cancer prognosis and outcome.
A recent study published in 2015 by the journal Pharmacokinetics reported on older adults who frequently fall and sustain a related injury. The study concluded that Vitamin D supplementation with annual medication reviews was found to be a more effective and less costly treatment in comparison to no medical intervention other than the use of hip protectors.
According to an article in Journal of the American College of Nutrition of the 30 leading causes of death in the United States in 2010, 19 have been linked to low vitamin D status, including various forms of cardiovascular disease, various cancers, diabetes mellitus, Alzheimer’s disease, and falls and fractures in the elderly.(22) The study suggests that, if the population of the United States were to increase their vitamin D status to 40 ng/mL, this could potentially result in a reduction of as much as 336,000 deaths each year out of 2.1 million deaths attributed to the diseases concerned, or 16% (21) Included in these figures are estimated reductions of 180,000 deaths from cardiovascular disease, 20,000 from colorectal cancer, 12,000 from breast cancer, 70,000 from other cancers, and 15,000 from Alzheimer’s disease.
The study goes on to propose that, in addition to this annual reduction in deaths, the direct costs of care for the associated diseases could be reduced by roughly $130 billion each year. Thus raising 25(OH)D concentrations appears to be an efficient and cost-effective way to reduce the burden of disease and increase life expectancy.
Vitamin D Supplementation
Forms of Vitamin D Supplements
Vitamin D is a fat-soluble vitamin generally considered not to have a very pleasant taste. In the pharmaceutical market, vitamin D supplements are available in the form of powder capsules, softgels, chewable tablets, liquids, and drops.
Given the fat-soluble nature of Vitamin D, the use of an oil-based softgel as a delivery mechanism may result in increased absorption. The softgel format may further help to maintain patient compliance. The following points support this:
- Administration is easy; no difficulty swallowing
- No unpalatable taste, no need for the addition of any sweeteners or flavouring agents
- Patient compliance is high, as taste or smell does not create a barrier for administering the dose
- Allows for equal dosing
- Degradation is fast and the active ingredients easily absorbable
- Maintains stability of product in atmospheric conditions such as humidity and heat
- Protects against chemical reaction with air light or other substances.
Benefits of Vitamin D with Olive Oil
A study conducted by Dr. Sathit Niramitmahapanya at Tufts University in Boston concluded that Vitamin D administered with monounsaturated fats, like those found in beef and some oils, especially olive oil, was associated with better absorption than vitamin D given with fish oils. (23)
A recent preclinical trial conducted in 2014 by Tagliaferri C et al concluded that extra virgin olive oil fortified with vitamin D3 is able to counteract the bone loss induced by estrogen deprivation. (24) Such a bone sparing effect could be explained by an improvement of both inflammation status and oxidative stress.
Olive oil is graded by its level of acidity, or free oleic acid. The amount of free oleic acid in olive oil indicates the extent to which fat has broken down into fatty acids. Extra-virgin olive oil is unrefined oil and the highest-quality olive oil, as it has a lower level of oleic acid (no more than 1% oleic acid) and also contains more of the natural vitamins and minerals found in olives. Extra-virgin olive oil is considered an unrefined oil since it’s not treated with chemicals or altered by temperature.
Ideally the olive oil extracted from olives for the delivery of Vitamin D should be a non-GMO, organic product. Non-GMO means non-genetically modified. Genetically modified (GM) crops have increased overall pesticide use and have been associated with creating “superweeds”. The long-term health risks to humans of ingesting GM foods is as yet unknown.
Treatment with sunlight or artificial UVB radiation would be simple but increases the risk of non-melanoma skin cancers and ages the skin. Sunburn increases the risk of malignant melanoma. Thus adequate oral supplementation is required for treating vitamin D deficiency.
Treatment of vitamin D deficiency in otherwise healthy patients must be individualized due to the numerous factors affecting 25(OH)D levels, and doses should be adequate to maintain serum 25(OH)D levels between 40-70 ng/mL.
Patients with chronic diseases associated with vitamin D deficiency, especially internal cancers, should be supplemented with doses adequate to maintain 25(OH)D levels in the higher normal range, 55-70 ng/mL. Caution is required in any patient with hypercalcemia.
Toxicity Associated With Vitamin D
The only absolute contraindication to vitamin D supplementation is vitamin D toxicity or allergy to vitamin D, although at the time of writing no reports have been found of acute allergic reactions to vitamin D supplements. Oral treatment is recommended for patients who have had any type of skin cancer.
Vitamin D hypersensitivity syndromes – often confused with vitamin D toxicity – occur when extrarenal tissues produce 1,25(OH)2 D in an unregulated manner, causing hypercalcemia. These syndromes are diagnosed by measuring serum calcium (elevated), 25(OH)D (normal or low), and 1,25(OH)2 D (elevated).
Vitamin D hypersensitivity syndromes can occur in some of the granulomatous diseases (especially sarcoidosis and tuberculosis), and in some cancers (especially non-Hodgkin’s lymphoma and oat cell carcinoma of the lung). Such conditions may be unmasked by vitamin D treatment; for example, sarcoidosis may become clinically evident after summer sun exposure. Therefore, hypercalcemia is a relative contraindication to vitamin D, sunlight, and artificial UVB radiation.
The practitioner should carefully evaluate any hypercalcemic patient for the cause of hypercalcemia. Once the cause is clear, should the practitioner decide to treat concomitant vitamin D deficiency – despite the hypercalcemia – it should only be if the hypercalcemia is mild to moderate (<12mg/dL) and should proceed cautiously, with frequent monitoring of clinical condition, urine and serum calcium, 25(OH)D, and 1,25(OH)2 D. Vitamin D, especially in large doses, could theoretically precipitate a worsening clinical course in such patients.
- Villamor E. A potential role for vitamin D on HIV infection? Nutr Rev 2006;64:226-233.
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355893/#B106; (Haussler et al., 1998; Schwartz et al., 2004; Cross, 2007).
- http://ucsdnews.ucsd.edu/archive/newsrel/health/05-08VitaminDBreastCancer.asp; (2007; GLOBOCAN, developed by the World Health Organization’s International Agency for Research on Cancer revealed that an association between higher levels of vitamin D3 or markers of vitamin D status and lower risk of cancers of the breast, colon, ovary and kidney.)
- Hopkins MH, Owen J, Ahearn T, et al. Effects of supplemental vitamin D and calcium on biomarkers of inflammation in colorectal adenoma patients: a randomized, controlled clinical trial. Cancer Prev Res (Phila) 2011;4(10):1645-1654.
- http://www.moyak.com/papers/vitamin-D-sunshine.html (Morishita M, Ohtsuru A, Kumagai A, Namba H, Sato N, Hayashi T, Yamashita S. Vitamin D3 Treatment for Locally Advanced Thyroid Cancer: A Case Report. Endocr J. 2005 Oct;52(5):613-6.)
- William B. Grant, Ph.D. Sunlight, Nutrition, and Health Research Center (SUNARC)
- http://www.altmedrev.com/publications/13/1/6.pdf (Tangpricha V, Colon NA, Kaul H, et al. Prevalence of vitamin D deficiency in patients attending an outpatient cancer care clinic in Boston. Endocr Pract 2004;10:292-293.)
- Sunlight and Vitamin D: Necessary for Public Health, Published online: 22 Jun 2015; Journal of the American College of Nutrition Volume 34,Issue 4, 2015
- Niramitmahapanya S, Harris SS, Dawson-Hughes B. Type of dietary fat is associated with the 25-hydroxyvitamin d3 increment in response to vitamin d supplementation. J Clin Endocrinol Metab. 2011 Oct;96(10):3170-4.
- http://www.altmedrev.com/publications/13/1/6.pdf, Use of Vitamin D in Clinical Practice
- http://www.overcomingmultiplesclerosis.org/Recovery-Program/Sunlight-and-Vitamin-D/; (Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999; 69:842-856.)
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