Vitamin D is fat-soluble vitamin requiring bile for absorption, and occurs naturally in animal foods such as salmon, sardines, egg yolks, cod liver oil and dairy. It can be acquired either by ingestion or by exposure to sunlight.
Vitamin D is found primarily in foods of animal origin, unless they are fortified. Vegetables are usually low in vitamin D, except mushrooms which are significant source of absorbable vitamin D.
Vitamin D2 (ergocalciferol) is obtained from plants. Vegetables are usually low in vitamin D, but leafy dark green vegetables and mushrooms are significant non-animal sources. Vitamin D3 (cholecalciferol) is stable to heat, light, and storage and is derived from animal products.
It is estimated that the RDA can be achieved through the exposure of 30% of a person’s skin surface to the sun for 30 minutes at moderate latitudes. The darker the skin, the less vitamin D will be produced (up to 95% of UV light is blocked). If longer exposure times are had, even with the darkest skin color, sufficient levels of vitamin D are produced. Glass blocks UV light, so indoor exposure does not help. The RDA for adults is 200 IU; for children, teens and pregnant or lactating women it is 400 IU; for the elderly or those with poor sunlight exposure or living in high northern or southern latitudes, it is 400 – 800 IU. During the winter months especially, it is advisable to supplement vitamin D if sun exposure is low and dietary sources are in question. The vitamin D in human breast milk varies with sun exposure and vitamin D intake.
Unusually high doses may be suggested in some autoimmune conditions. The “no observed adverse effect level” (NOAEL) for vitamin D appears to be at least 10,000IU per day. The lowest observed adverse effect level (LAOEL) is 40,000IU per day. Thus 10,000IU per day is definitely safe (assuming no hypersensitivity) and 40,000IU per day can be a problem. It would be next to impossible for anyone living in a northern area to get too much vitamin D from sunlight and a 4000IU per day supplement. Thus such a supplementation level is safe for anyone who is not hypersensitive to vitamin D.
Commentary by Alan R. Gaby, M.D.
Vitamin D3 is Preferable to Vitamin D2 as a Nutritional Supplement
Vitamin D3 (cholecalciferol) is the “natural” form of vitamin D for humans, since it is produced in the skin after sunlight exposure and is present in foods such as fish and eggs. However, prescription-strength vitamin D preparations available in North America are made exclusively with vitamin D2, a compound produced by irradiating yeast with ultraviolet light. Vitamin D2 is also the main form of vitamin D used in the fortification of milk and other foods. While vitamin D3 and vitamin D2 are both biologically active, there are important differences between them. A recent review article summarized these differences and concluded that vitamin D2 should no longer be used as a nutritional supplement or in food fortification.1
One of the differences between vitamin D3 and vitamin D2 is that the former is considerably more potent. These two forms of vitamin D have long been considered to be biologically equivalent and of equal potency, but that belief is based on an old and relatively insensitive measure of vitamin D activity: the capacity to prevent rickets in experimental animals. More recently, it has become clear that vitamin D3 is much more effective than vitamin D2 at raising the serum concentration of 25-hydroxyvitamin D (25-(OH)D) which is considered a reliable indicator of vitamin D status. In one study, while both types of vitamin D raised the serum 25-(OH)D concentration by the same amount initially, 25-(OH)D levels continued to rise for 14 days after vitamin D3 supplementation. In contrast, after vitamin D2 supplementation, initially elevated 25-(OH)D levels fell rapidly and were not different from baseline at 14 days. According to calculations based on the area under the serum 25-(OH)D concentration-time curve, vitamin D3 is at least 3.4 times as potent as vitamin D2, and may be as much as 9.4 times as potent. 2
A second difference between vitamin D3 and vitamin D2 is in their metabolism. Vitamin D2 is metabolized in large part to 25-(OH)D2, which does not bind as efficiently to vitamin D binding protein in plasma as does the respective vitamin D3 metabolite, 25-(OH)D3. Consequently, the availability of vitamin D2 to some tissues may be lower than that of vitamin D3. Moreover, because of its reduced affinity for vitamin D binding protein, 25-(OH)D2 has a shorter half-life than 25-(OH)D3 does, which might explain the greater potency of vitamin D3.
In addition to its lower bioactivity, vitamin D2 is less stable than vitamin D3, particularly on exposure to variations in temperature and humidity. Consequently, vitamin D2 has a shorter shelf life than vitamin D3. Because of its poor stability, vitamin D2 preparations might contain relatively high concentrations of toxic degradation products.
Another problem associated with use of vitamin D2 supplements is that commonly used laboratory tests do not detect 25-(OH)D2 in the blood as efficiently as they detect 25-(OH)D3. These laboratory tests may therefore underestimate vitamin D status in patients being treated with vitamin D2, potentially leading to an unwarranted increase in the dosage and subsequent vitamin D toxicity.
Because of the disadvantages associated with the use of vitamin D2, and considering that vitamin D3 is the form of vitamin D that occur naturally in humans, the authors of the review article argued that vitamin D3 should be used for routine vitamin D supplementation. They pointed out, however, that patients with hypoparathyroidism or other vitamin D-responsive conditions who are well controlled on high-dose vitamin D2 should probably not have their regimens changed.
When switching from high-dose vitamin D2 to vitamin D3, it is important to remember that vitamin D3 is considerably more potent than vitamin D2. A 50,000-IU dose of vitamin D2 is roughly equivalent to 5,000 to 15,000 IU of vitamin D3. Failure to consider this difference in potency when using vitamin D3 in place of vitamin D2 could place the patient at risk of developing vitamin D toxicity. Because the relative potency of these two forms of vitamin D may differ substantially from one person to the next, patients being switched from vitamin D2 to vitamin D3 should have their serum 25-(OH)D level monitored until their optimal dosage is determined. That caveat does not apply to vitamin D3 doses of 2,000 IU per day or less, which are considered safe for the general population.
Alternative Medicine Review March 2008
A meta-analysis of 18 randomized controlled trials has found that supplemental vitamin D significantly reduces mortality from all causes.
The analysis emphasizes the medical, ethical, and legal implications of promptly diagnosing and adequately treating vitamin D deficiency.
Not only are such deficiencies common, but vitamin D deficiency is implicated in most of the diseases of civilization. Vitamin D’s final metabolic product targets more than 200 human genes in a wide variety of tissues. One of the most important genes vitamin D up-regulates is for cathelicidin, a naturally occurring broad-spectrum antibiotic.
Since vitamin D deficiency is both endemic and is associated with numerous diseases, it is one of the most important medical problems in modern society. Treatment of vitamin D deficiency in otherwise healthy patients must be individualized due to the numerous factors affecting vitamin D levels. Steps should be taken to keep patients with chronic diseases associated with vitamin D deficiency, especially internal cancers, in the higher normal range of vitamin D blood levels.
References:
1 Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr 2006;84:694-7.
2 Armas LAG, et al. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 2004;89:5387-91.
Vitamin D can help with the following
Premature/Signs of Aging
A 2008 meta-analysis of 18 randomized controlled trials has found that supplemental vitamin D significantly reduces mortality from all causes. See the Treatment discussion of Vitamin D for further details. [Alternative Medicine Review March 2008]
Multiple Sclerosis / Risk
An abundance of scientific evidence indicates that vitamin D deficiency is associated with MS onset and progression. Small clinical trials have suggested that vitamin D has some efficacy in slowing autoimmune disease progression although no properly controlled trials have been conducted.
Vitamin D can be readily attained from exposure to sunlight and studies have shown that the optimal intake of vitamin D is about 4000 – 6000IU a day. This results in a circulation concentration of 25(OH)D of 100 – 125 nmol/litre and this level seems to be required for the proper functioning of all vitamin D-dependent systems. In colder, low sunlight areas such an intake from the sun is impossible for most of the year and it is important to use supplements to makeup the shortfall in vitamin D supply. A daily supplement of 4000IU of vitamin D3 seems warranted for people who do not get a lot of exposure to sunlight throughout the year.
Researchers have found women who eat a diet rich in vitamin D may reduce their chances of developing rheumatoid arthritis (RA) and multiple sclerosis (MS). Two studies involving women have shown proof of the vitamin’s benefits.
The RA study followed 29,368 women aged 55 to 69 years, and the MS study looked at more than 185,000 women. The participants were given questionnaires to fill out about their dietary habits and vitamin D intake at the beginning of each study, and researchers followed up with the women every four years for up to 20 years. They discovered that women were 30 percent less likely to develop RA, and 40 percent less likely to develop MS, when taking the recommended daily amount or more of vitamin D.
Out of 100 people worldwide, one or two will develop RA and around 0.04 percent have MS. Both of these conditions are thought to occur when the body’s immune system turns against itself. Researchers suggest that vitamin D may work by calming overactive immune cells.
Responding to this study, vitamin D experts advise future researchers studying vitamin D levels to administer a blood test to read the levels more accurately, and cautioned that this study did not use the best way to determine vitamin D levels in the participants. [Neurology January, 2004 13;62(1):60-5, Arthritis & Rheumatism January, 2004;50(1):72-7]
Please see the link between MS and vitamin D deficiency for a 2006 study supporting this connection.
Chronic Thyroiditis
Vitamin D is an important vitamin for calming the immune system. Vitamin D stimulates the T-regulatory cells of the immune system.
Autoimmune Tendency
A variety of data, from epidemiology, animal experiments, immunological investigations, genetics and small clinical trials indicates that vitamin D can have a suppressant effect on autoimmune reactions and help to slow autoimmune disease. In recent years there has been an effort to understand possible noncalcemic roles of vitamin D, including its role in the immune system and, in particular, on T cell-medicated immunity. The vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. However, its highest concentration is in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. The significant role of vitamin D compounds as selective immunosuppressants is illustrated by their ability to either prevent or markedly suppress animal models of autoimmune disease. Results show that 1,25-dihydroxyvitamin D3 can either prevent or markedly suppress experimental autoimmune encephalomyelitis, rheumatoid arthritis, systemic lupus erythematosus, type I diabetes, and inflammatory bowel disease. In almost every case, the action of the vitamin D hormone requires that the animals be maintained on a normal or high calcium diet.
It must be stressed that adequate calcium and magnesium intake must accompany vitamin D supplementation. [Medical Hypotheses 1986 (21): pp. 193-200] Calcium levels strongly affect the action of vitamin D for suppressing EAE (animal MS) in mice. Calcium intake should be in the range of 600-900mg per day with magnesium intake being about the same as this. [Journal of Nutrition, 1999 (129): pp. 1966-1971]
Although the use of vitamin D and vitamin D analogs in the therapy of certain autoimmune diseases holds promise, further research is required before their safety and efficacy can be determined.
Ulcerative Colitis
See the link between Autoimmune Tendency and Vitamin D.
Crohn's Disease
See the link between Autoimmune Tendency and Vitamin D.
Lupus, SLE (Systemic Lupus Erythromatosis) / Risk
See the link between Autoimmune Tendency and Vitamin D.
Diabetes Type I
See the link between Autoimmune Tendency and Vitamin D.
Sarcoidosis
There is a hormone which allows the sarcoid granuloma to flourish. It is called 1,25-dihydroxyvitamin D. It is formed in the kidneys from 25-hydroxyvitamin D, the metabolite formed when our bodies take in Vitamin D from sunlight or from food. Although the 1,25 D hormone is normally manufactured in the kidneys, it is also manufactured in the granulomatous inflammation of sarcoidosis.
Raised serum calcium levels occur in 2-63% of sarcoidosis patients due to overproduction of vitamin D by sarcoid granulomas. The concentration of this hormone in the blood of sarcoid patients can rise to quite high levels, and cause them to suffer from the symptoms of “Hypervitaminosis D”. These include fatigue, pins and needles, numbness, muscle pain, muscle cramps, dizzyness, loss of balance and even facial palsy.
IBS (Irritable Bowel Syndrome)
IBS (Irritable Bowel Syndrome) has been linked with a lack of vitamin D for the first time in a study published in the BMJ (British Medical Journal December 21, 2015). Of the 51 patients with IBS tested, 82% had insufficient vitamin D levels.
Seasonal Affective Disorder (SAD)
A 1998 study supports the vitamin D theory. During the Australian winter, researchers gave 44 healthy students either 400 IU, 800 IU, or no vitamin D3 for 5 days. Both dosages of vitamin D3 significantly enhanced mood (Lansdowne et al. 1998).
Ehlers Danlos Syndrome
If avoiding sun exposure, one should consider the use of supplemental vitamin D.
Hypoparathyroidism
See the link between Hypoparathyroidism and Calcium.
Elevated Insulin Levels
A 2004 study published in the American Journal of Clinical Nutrition determined that raising a person’s serum vitamin D levels (from 25 to 75 nmol/l) could improve insulin sensitivity by 60%!
Low Testosterone Level
Researchers at Stanford’s School of Medicine wanted to see what vitamin D’s active form, calcitriol, would do regarding breast cancer. What they found was that calcitriol reduced aromatase expression in two ways – firstly, by directly suppressing its transcription at the gene level i.e. reducing how much of it is produced by the body. And secondly, by suppressing Cyclooxygenase-2 (COX-2), a pro-inflammatory pathway, and increasing 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH), an anti-inflammatory pathway.
Combined, this effect reduces the levels of local prostaglandins including Prostaglandin E2 (PGE2), which is a major stimulator of aromatase transcription. They also found that calcitriol downregulates the expression of estrogen receptor alpha (Era) in breast cancer cells, therefore reducing the effects of estrogen signalling at the receptor level. [Krishnan AV, Swami S, Feldman D. Vitamin D and breast cancer: Inhibition of estrogen synthesis and signaling. J Steroid Biochem Mol Biol. 2010 Feb 13.]
Hyperparathyroidism
Hyperparathyroidism is caused by a malfunction of the parathyroid glands in the neck, which regulate calcium in the blood by parathyroid hormone (PTH). The disease most often strikes women, particularly older women. It can cause fatigue, disorientation, and depression, and can also lead to bone loss, kidney stones, and even coma.
A study published in the Journal of Clinical Endocrinology and Metabolism found an inverse relationship between the severity of the disease and patients’ intake of vitamin D through diet and supplements. Such a link has long been suspected, but hadn’t been shown until now, and the finding may affect the way some physicians treat the disease. Vitamin D hormone replacement reduces the production of PTH.
Dr. Rao says there is a myth among both doctors and patients that people with hyperthyroidism should avoid calcium and vitamin D, since they have too much calcium in their bloodstreams. But this is “biologically implausible,” he says, and the myth only aggravates the situation.
Dr. De Papp echoes his concern. “The fear is if they take supplements, they will make their blood calcium go higher,” de Papp says. “Although there is some truth to that, their blood calcium will be higher, it is at the expense of their bones, because if they don’t take calcium supplements they are much more likely to … end up with nutritional osteoporosis from vitamin D and calcium deficiency on top of the primary hyperparathyroid bone disease that they may have. So they get bad bones for two reasons.
“If you restrict vitamin D, PTH levels go up, which stimulates bone loss, specifically cortical bone, which is in your wrist and your hip,” she says. “Hip fractures are a tremendous cause of morbidity and mortality among postmenopausal women in this country.”
“In other words, people with hyperparathyroidism need as much vitamin D and calcium, and perhaps more, than the general public,” says Dr. Rao
Study Results:
Vitamin D -25 is suppressed and Vitamin D-1-25 is increased in patients with primary hyperparathyroidism in linear fashion as calcium levels increase, returning to normal within weeks of tumor removal. A protective mechanism is in play.
Overview: Vitamin D-25 is converted to Vitamin D-1-25 in patients with primary HPT in a linear fashion as calcium levels increase. Thus the vast majority of patients with primary HPT will have low Vit D-25 that normalizes by itself in most patients within several months.
Objective: Vitamin D-25 is often measured in patients with apparent primary HPT to rule out a possible secondary cause. This study was undertaken to examine if a relationship exists between Vit-D levels and parathyroid pathology in patients with elevated calcium levels.
Methods: A prospective, single institution study measured preoperative Vitamin D (25OH and 1-25OH) in 1,587 patients undergoing surgery for sporadic primary hyperparathyroidism (PHPT) over a 1-year period. All patients underwent curative parathyroidectomy with pathology noted. Patients were put on nominal doses of Vit-D postop contained within supplemental calcium tablets (Citracal+D; 250 IU cholecalciferol daily) for two months; none took additional Vit-D. Blood levels were measured at 1 and 2 months post-op.
Results: All patients had primary HPT with high serum calcium and PTH preop that normalized at all postop measures indicating cure. The average preop Vit-D25 was 25.8+10 ng/ml (range 4-65). 1039 patients (67%) had Vit-D25 levels below 30 ng/ml preop, while 594 patients (38%) had levels below 20 ng/ml preop (mean 14.6, range 4-19), No patient had high Vit-D25 preop. Vit-D25 levels decreased linearly as calcium levels increased such that 71% of those with levels above 12 mg/dl had Vit-D25 <20 (p<0.01, R=0.91).The levels of Vit-D1-25 were low in 0%, normal in 58.5%, and high in 41.5% (mean 56.2 + 14)(p<0.01). The findings at surgery were identical (p=0.98) for those with low vs. normal Vit-D25 (single adenoma=92%, double adenoma=6%, 4-gland hyperplasia=3%). 82% of patients with low preop Vit-D25 had increased levels at 1 month postop (mean 41.4+12, range 17-63, p<0.005), increasing to 91% at 2 months. All patients with normal Vit-D25 preop remained normal postop. 68% showed decreased Vit-D1-25 into the normal range (p<0.001) within 1 month of surgery.
Conclusion: Vit-D25 levels decrease in a linear fashion as calcium levels rise in patients with primary HPT. Overall, 38% will have Vit-D25 levels less than 20 ng/ml, increasing to 71% of those with calcium levels above 12mg/dl. Vit-D1-25 shows the opposite pattern suggesting a protective mechanism. The pathology found at surgery is identical in PHPT patients with low versus normal Vit-D25 indicating no causal relationship. Low Vit-D25 should not be interpreted as signaling secondary HPT in patients with elevated calcium levels. The vast majority of patients will normalize their low Vit-D25 and high Vit-D1-25 levels within 2 months of tumor removal.
Chronic Fatigue / Fibromyalgia Syndrome
A study from the Mayo Clinic in 2003 looked at the prevalence of vitamin D deficiency in people aged 10-65 with chronic pain syndromes like fibromyalgia and chronic fatigue. It was reported that 93% of these were found to be deficient in vitamin D.
A new study from the Orthopaedic Hospital Speising in Vienna, Austria, brings hope for those suffering from fibromyalgia, finding that vitamin D supplementation may ease the nerves, bringing down inflammation in the body. Study leader Florian Wepner was excited about the results, suggesting, “Vitamin D levels should be monitored regularly in FMS patients, especially in the winter season, and raised appropriately.”
Although the study was able to find an association between vitamin D supplementation and an easing of fibromyalgia pain, it did not prove a cause-and-effect link.
However, two experts on the illness said the findings make sense.
“Fibromyalgia patients and those with chronic pain should certainly have their vitamin D blood levels checked and, if low, consider supplementation under the guidance of a physician,” said Dr. Kiran Patel, a pain medicine specialist at Lenox Hill Hospital in New York City who often treats people with fibromyalgia.
Dr. Houman Danesh, director of integrative pain management at Mount Sinai Hospital in New York City, agreed. “Vitamin D deficiency has been linked to chronic pain, and this study further strengthens the argument to [replenish] vitamin D in deficient individuals,” he said. [ Kiran Patel, M.D, pain medicine specialist, Lenox Hill Hospital, New York City; Houman Danesh, M.D., director, integrative pain management, The Mount Sinai Hospital, New York City; Elsevier, press release, Jan. 17, 2014]
Rheumatoid Arthritis
A small clinical trial for RA and a vitamin D metabolite was conducted over a three-month time period. The results were positive: “Therapy showed a positive effect on disease activity in 89% of the patients (45% with complete remission and 45% with a satisfactory effect). Only two patients (11%) showed no improvement, but no new symptoms occurred”. [Clin. Exp. Rheumatol. 1999 (17): pp. 453-456] Also see the link between Autoimmune Tendency and Vitamin D.
Researchers have found women who eat a diet rich in vitamin D may reduce their chances of developing rheumatoid arthritis (RA) and multiple sclerosis (MS). Two studies involving women have shown proof of the vitamin’s benefits.
The RA study followed 29,368 women aged 55 to 69 years, and the MS study looked at more than 185,000 women. The participants were given questionnaires to fill out about their dietary habits and vitamin D intake at the beginning of each study, and researchers followed up with the women every four years for up to 20 years. They discovered that women were 30 percent less likely to develop RA, and 40 percent less likely to develop MS, when taking the recommended daily amount or more of vitamin D.
Out of 100 people worldwide, one or two will develop RA and around 0.04 percent have MS. Both of these conditions are thought to occur when the body’s immune system turns against itself. Researchers suggest that vitamin D may work by calming overactive immune cells.
Responding to this study, vitamin D experts advise future researchers studying vitamin D levels to administer a blood test to read the levels more accurately, and cautioned that this study did not use the best way to determine vitamin D levels in the participants. [Neurology January, 2004 13;62(1):60-5, Arthritis & Rheumatism January, 2004;50(1):72-7]
Dr. Joseph Mercola, D.O. reports that he has “seen several hundred patients with rheumatoid arthritis in the last two years, and I have measured their levels. I have yet to analyze the results, but I cannot recall any RA patients who had normal levels of vitamin D. In fact, it is so consistent that I immediately start any new patient who comes in with RA on supplemental vitamin D, in addition to vitamin D in cod liver oil.”
Osteoporosis / Risk
A study of elderly women found that receiving 1,200mg per day of calcium plus vitamin D at 800IU per day experienced less than one-half the falls of those taking calcium alone. [Family Practic News, December 15, 2001: p.6]
The recommended daily intake level for women and men (ages 19-50 years) and pregnant or lactating women is 400 IU (10 mcg) per day; women and men over 50 years, 800 IU (20 mcg) per day. [2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 2002;167(Suppl): pp.1-34]
Overdosing with vitamin D at a single session is difficult as can be seen in stoss therapy. Stoss therapy, which has been used in children, has also been used to reduce fracture rates in the elderly (100,000 IU of oral cholecalciferol every four months for five years). Average 25-hydroxyvitamin D levels in the subjects after this treatment period was only about 29 ng/ml, which is still mildly deficient. [BMJ Mar 1, 2003;326: p.469]
Oral vitamin D supplements at a dose of at least 400 international units per day are associated with a reduced risk of bone fractures in older adults, according to results of a meta-analysis published in the March 23, 2009 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
Leg Cramps At Night
Here is the story of one man’s journey to find an answer for his night time leg cramps:
‘I need to tell you about my quest for nocturnal leg cramp relief and how I achieved it. I am a healthy 60 year old male who five years ago, was being treated for hypertension. The doctors were giving me medicines to treat this and then a heart specialist put me on some kind of diuretic. I don’t remember the name of it but it was a small white pill.
I think this caused some type of electrolytic imbalance because not more than two weeks into this treatment I started being awakened in the early mornings (4AM) by painful calf cramping. I was also having cramps in the arch of my feet. It was so bad that I had to jump out of bed and walk around the bedroom for relief. Even quiting the treatment didn’t cure the cramping.
These are not the kind of fatigue cramps that I’ve had in my large muscles, such as thigh or hamstring which can be cured with quinine sulfate tablets, these come right out of the blue and are very strong. The GP doctors that I complained to kind of poo poo’ed my problem and told me I should get plenty of potassium and calcium etc. I loaded up on these minerals (calcium, magnesium, and potassium) and it reduced the problem by about 20%.
This went on for YEARS before I told a co-worker about this problem and he said “Oh, You need vitamin D”. I started taking a 400IU vitamin D pill daily along with a Calcium tablet and IMMEDIATELY stopped having these nightly cramps. I think this cure is remarkable and have never seen this reported in any article about leg cramps and hoping that I am telling the right people. Someone should launch a study on this.” Barry M.
Neuritis/Neuropathy
Increasingly, it appears that vitamin D plays a role in nerve growth and maintenance and may have important pharmaceutical applications for treatment of neurodegenerative conditions.
The therapeutic potential of ergocalciferol – the plant-derived form of vitamin D, named vitamin D2 – was assesed in a rat model of peripheral nerve injury and repair. The left peroneal nerve was cut out on a length of 10 mm and immediately autografted in an inverted position. After surgery, animals were treated with ergocalciferol (100 IU/kg/day) and compared to untreated animals. Functional recovery of hindlimb was measured weekly, during 10 weeks post-surgery, using a walking track apparatus and a numerical camcorder. At the end of this period, motor and sensitive responses of the regenerated axons were calculated and histological analysis was performed. We observed that vitamin D2 significantly (i) increased axogenesis and axon diameter; (ii) improved the responses of sensory neurons to metabolites such as KCl and lactic acid; and (iii) induced a fast-to-slow fiber type transition of the Tibialis anterior muscle. In addition, functional recovery was not impaired by vitamin D supplementation. Altogether, these data indicate that vitamin D potentiates axon regeneration. Pharmacological studies with various concentrations of the two forms of vitamin D (ergocalciferol vs. cholecalciferol) are now required before recommending this molecule as a potential supplemental therapeutic approach following nerve injury. [J Neurotrauma. 2008 Oct;25(10):1247-1256]
Previous research has found that vitamin D deficiency is common in patients with Type 2 diabetes, but its effect on neuropathic pain has not previously been tested, say study authors Drs Paul Lee and Roger Chen from Concord Repatriation General Hospital.
Their study, published in today’s Archives of Internal Medicine (168:771-772) involved 51 patients with Type 2 diabetes and typical neuropathic pain. All patients were vitamin D deficient with a mean serum 25D concentration of 18 ng/mL.
After three months, vitamin D repletion with cholecalciferol (vitamin D3) tablets resulted in a significant reduction in pain scores using two separate assessments, one suggesting the pain severity was reduced by 40% the other suggesting pain severity had been halved.
How vitamin D reduces the severity of diabetic neuropathic pain is uncertain, but the researchers suggest that vitamin D insufficiency may potentiate diabetic nerve damage and impair nociceptor function. The results could not be explained by a decrease in parathyroid hormone as testing did not show any statistically significant difference in hormone level following the vitamin D repletion, they say.
Macular Degeneration
Age-related vision changes result in large part from changes is the outer retina of the eye, which is subject to inflammation and cell loss. Glen Jeffery, from the Institute of Ophthalmology at University College London (United Kingdom), and colleagues fed old mice vitamin D for six weeks, observing that inflammation was reduced, the retinal debris partially removed, and tests showed that the animals’ vision was improved.
The researchers identified two changes taking place in the eyes of the mice that they posit that accounted for this improvement. Firstly, the number of potentially damaging cells, called macrophages, were reduced considerably in the eyes of the mice given vitamin D. Giving mice vitamin D not only led to reduced numbers of macrophages in the eye, but also triggered the remaining macrophages to change to a different configuration. Rather than damaging the eye the researchers think that in their new configuration macrophages actively worked to reduce inflammation and clear up debris.
The second change the researchers saw in the eyes of mice given vitamin D was a reduction in deposits of a toxic molecule called amyloid beta that accumulates with age. Inflammation and the accumulation of amyloid beta are known to contribute, in humans, to an increased risk of age-related macular degeneration (AMD), the largest cause of blindness in people over 50 in the developed world.
The researchers submit that, based on their findings in mice, giving vitamin D supplements to people who are at risk of AMD might be a simple way of helping to prevent the disease. [“Vitamin D rejuvenates aging eyes by reducing inflammation, clearing amyloid beta and improving visual function.” Neurobiology of Aging, 2 January 2012.]
Increased Risk of Breast Cancer
The breast cancer study, published online in the current issue of the Journal of Steroid Biochemistry and Molecular Biology (Article Date: 07 Feb 2007), pooled dose-response data from two earlier studies – the Harvard Nurses Health Study and the St. George’s Hospital Study – and found that individuals with the highest blood levels of 25-hydroxyvitamin D, or 25(OH)D, had the lowest risk of breast cancer.
“The data were very clear, showing that individuals in the group with the lowest blood levels had the highest rates of breast cancer, and the breast cancer rates dropped as the blood levels of 25-hydroxyvitamin D increased,” said study co-author Cedric Garland, Dr.P.H. “The serum level associated with a 50 percent reduction in risk could be maintained by taking 2,000 international units of vitamin D3 daily plus, when the weather permits, spending 10 to 15 minutes a day in the sun.”
And, in 2007, if vitamin D3 levels among populations worldwide were increased, 600,000 cases of breast and colorectal cancers could be prevented each year, according to researchers from the Moores Cancer Center at the University of California, San Diego (UCSD). This includes nearly 150,000 cases of cancer that could be prevented in the United States alone.
The researchers estimate that 250,000 cases of colorectal cancer and 350,000 cases of breast cancer could be prevented worldwide by increasing intake of vitamin D3, particularly in countries north of the equator.
The study examines the dose-response relationship between vitamin D and cancer, and is the first to use satellite measurements of sun and cloud cover in countries where blood serum levels of vitamin D3 were also taken.
Serum vitamin D levels during the winter from 15 countries were combined, then applied to 177 countries to estimate the average serum level of a vitamin D metabolite among the population.
An inverse association between serum vitamin D and the risk of colorectal and breast cancers was found.
Protective effects began when 25-hydroxyvitamin D levels (the main indicator of vitamin D status) ranged from 24 to 32 nanograms per milliliter (ng/ml). In the United States, late winter 25-hydroxyvitamin D levels ranged from 15 to 18 ng/ml.
Previous research has suggested that raising levels to 55 ng/ml was actually optimal to prevent cancer, the researchers said.
To increase your vitamin D3 levels, the researchers recommended a combination of dietary methods, supplements and sunlight exposure of about 10 to 15 minutes a day, with at least 40 percent of your skin exposed. [The Journal of Steroid Biochemistry and Molecular Biology March 2007; 103(3-5):708-11]
Increased Risk of Colon Cancer
The colorectal cancer study, published online February 6, 2006 in the American Journal of Preventive Medicine, is a meta-analysis of five studies that explored the association of blood levels of 25(OH)D with risk of colon cancer. All of the studies involved blood collected and tested for 25 (OH)D levels from healthy volunteer donors who were then followed for up to 25 years for development of colorectal cancer.
“Through this meta-analysis we found that raising the serum level of 25-hydroxyvitamin D to 34 ng/ml would reduce the incidence rates of colorectal cancer by half,” said co-author Edward D. Gorham, Ph.D. “We project a two-thirds reduction in incidence with serum levels of 46ng/ml, which corresponds to a daily intake of 2,000 IU of vitamin D3. This would be best achieved with a combination of diet, supplements and 10 to 15 minutes per day in the sun.”
Increased Risk of Melanoma
Dr. Dianne Godar of the U.S. Food and Drug Administration (FDA) has conducted a study indicating that UVA light — not the UVB light that causes suntans and allows your body to produce vitamin D — may be responsible for the melanoma epidemic.
What’s more, the UVA light, unlike UVB, can pass through window glass, meaning you can still be exposed to it while you are indoors or in your car.
UVB, on the other hand, appears to be protective against melanoma — or rather, the vitamin D your body produces in response to UVB radiation is protective. Dr. Godar points out that the melanoma epidemic began long before sunbeds, and that the dramatic melanoma increase occurs primarily in indoor workers, not outdoor workers.
Low vitamin D levels actually predict melanoma, and all-year tans protect against melanoma. Melanoma patients who expose themselves to the sun live longer than those who don’t. [Medical Hypotheses April 2009; 72 (4): pp.434-443]
Cancer / Risk - General Measures
Evidence of vitamin D’s protective effect against cancer is compelling. For more than 50 years, documentation in medical literature suggests regular sun exposure is associated with substantial decreases in death rates from certain cancers and a decrease in overall cancer death rates. Recent research suggests this is a causal relationship that acts through the body’s vitamin D metabolic pathways. For instance, some evidence points to a prostate, breast and colon cancer belt in the United States, which lies in northern latitudes under more cloud cover than other regions during the year. Rates for these cancers are two to three times higher than in sunnier regions.
Dark-skinned people require more sun exposure to make vitamin D. The thickness of the skin layer called the stratum corneum affects the absorption of UV radiation. Dark human skin is thicker than white skin and thus transmits only about 40% of the UV rays for vitamin D production. Darkly pigmented individuals who live in sunny equatorial climates experience a higher mortality (not incidence) rate from breast and prostate cancer when they move to geographic areas that are deprived of sunlight exposure in winter months. The rate of increase varies, and researchers hesitate to quote figures because many migrant black populations also have poor nutrition and deficient health care that confound statistics somewhat.
Although excessive sun exposure may give rise to skin cancer, researchers as early as 1936 were aware that skin cancer patients have reduced rates of other cancers. One researcher estimates moderate sunning would prevent 30,000 annual cancer deaths in the United States.
Vitamin D may also go beyond cancer prevention and provide tumor therapy. Much has been made of pharmaceutical angiogenesis inhibitors – agents that help inhibit the growth of new, undesirable blood vessels that tumors require for nutrient supply and growth. Laboratory tests have shown vitamin D to be a potent angiogenesis inhibitor.
Vitamin D also works at another stage of cancer development. Tumor cells are young, immortal cells that never grow up, mature and die off. Because vitamin D derivatives have been shown to promote normal cell growth and maturation, drug companies today are attempting to engineer patentable forms of vitamin D for anti-cancer therapy.
The first large-scale, randomized, placebo-controlled study on vitamin D and cancer has shown that vitamin D can cut cancer risks by as much as 60%. In response, the Canadian Cancer Society is now recommending vitamin D for all adults, the first time a major public-health organization has endorsed the vitamin as a cancer-prevention therapy.
The study looked at almost 1,200 women, aged 55 and older, over the course of four years. Those in a group that was given supplemental calcium and vitamin D had a 60 percent lower risk for all cancers than those who received a placebo. [American Journal of Clinical Nutrition, 85(6):1586-91 June 2007]
Increased Risk of Rectal Cancer
The rate of colorectal cancer is much higher in the United States, where a high-fat diet is common, than in Japan, where people don’t eat a lot of fat and colorectal cancer is almost nonexistent. But no one has understood why that is. At least part of the answer lies in lithocholic acid, a bile acid produced to help digest fat.
Lithocholic acid is probably the most toxic compound that your body naturally makes, so you have to have a way to get rid of it. Normally, bile acids are made in the liver and stored in the gallbladder. Bile acids solubilize foods. When you eat a high-fat diet, your body makes more bile acids. Usually they are efficiently recycled, with the exception of lithocholic acid. Lithocholic induces changes in DNA.
If you give animals high concentrations, just directly put it into the intestine, they get colon cancer. But laboratory animals given doses of vitamin D and then given lithocholic acid do not get colon cancer. Colon cancer patients also have high concentrations of lithocholic acid. Vitamin D has a role in detoxifying lithocholic acid.
A colorectal cancer study, published online February 6, 2006 in the American Journal of Preventive Medicine, is a meta-analysis of five studies that explored the association of blood levels of 25(OH)D with risk of colon cancer. All of the studies involved blood collected and tested for 25 (OH)D levels from healthy volunteer donors who were then followed for up to 25 years for development of colorectal cancer.
“Through this meta-analysis we found that raising the serum level of 25-hydroxyvitamin D to 34 ng/ml would reduce the incidence rates of colorectal cancer by half,” said co-author Edward D. Gorham, Ph.D. “We project a two-thirds reduction in incidence with serum levels of 46ng/ml, which corresponds to a daily intake of 2,000 IU of vitamin D3. This would be best achieved with a combination of diet, supplements and 10 to 15 minutes per day in the sun.”
And in another study, if vitamin D3 levels among populations worldwide were increased, 600,000 cases of breast and colorectal cancers could be prevented each year, according to researchers from the Moores Cancer Center at the University of California, San Diego (UCSD). This includes nearly 150,000 cases of cancer that could be prevented in the United States alone.
The researchers estimate that 250,000 cases of colorectal cancer and 350,000 cases of breast cancer could be prevented worldwide by increasing intake of vitamin D3, particularly in countries north of the equator.
The study examines the dose-response relationship between vitamin D and cancer, and is the first to use satellite measurements of sun and cloud cover in countries where blood serum levels of vitamin D3 were also taken.
Serum vitamin D levels during the winter from 15 countries were combined, then applied to 177 countries to estimate the average serum level of a vitamin D metabolite among the population.
An inverse association between serum vitamin D and the risk of colorectal and breast cancers was found.
Protective effects began when 25-hydroxyvitamin D levels (the main indicator of vitamin D status) ranged from 24 to 32 nanograms per milliliter (ng/ml). In the United States, late winter 25-hydroxyvitamin D levels ranged from 15 to 18 ng/ml.
Previous research has suggested that raising levels to 55 ng/ml was actually optimal to prevent cancer, the researchers said.
To increase your vitamin D3 levels, the researchers recommended a combination of dietary methods, supplements and sunlight exposure of about 10 to 15 minutes a day, with at least 40 percent of your skin exposed. [The Journal of Steroid Biochemistry and Molecular Biology March 2007; 103(3-5):708-11]
Increased Risk of Prostate Cancer
See the link between Vitamin D Deficiency and Cancer, Prostate, Increased Risk.
Increased Risk of Lymphoma
Administration of activated vitamin D (1,25 dihydroxycholecalciferol) may be beneficial in non-Hodgkin’s lymphoma. Experimental Study: In a small trial, patients with non-Hodgkin’s lymphoma who were found to have high levels of vitamin D receptors responded to activated vitamin D.
[Cunningham D, Gilcrist NL, Cowan RA, et al. Vitamin D as a modulator of tumour growth in low grade lymphomas. Abstract. Scot Med J 30: 193, 1985]
Psoriasis
Vitamin D has been recognised for many years to improve some of the important abnormalities present in psoriasis skin, but ingestion of even only slightly above the daily recommended amount of Vitamin D can lead to problems with calcium metabolism in the body (possible kidney stones and irregular heart beats).
For this reason calcipotriol, a synthetic form of vitamin D, is used instead in ointment form. Calcipotriol has been found to also have the ability to improve psoriasis, but with minimum effects on internal calcium metabolism. It is available in a very greasy, ointment base for twice daily application. There is a risk of facial dermatitis if the ointment is used on the face or neck, so application is only recommended for the trunk and limbs, and it is important that the hands are thoroughly washed after application to avoid inadvertent transfer to the skin of the face. Comparative studies have shown that calcipotriol ointment is at least as effective as topical cortisones and dithranol in the treatment of stable plaque psoriasis.
Breast Cancer
See the link between Breast Cancer and Vitamin A. High levels of oral D3 are needed to achieve the serum levels recommended for those with active breast cancer. Blood testing for vitamin D should be done routinely in anyone with breast cancer or increased risk of breast cancer. When treating cancer or heart disease, many recommend that levels should be in the 70-100 ng/ml range.
Prostate Cancer
In patients with advanced hormone refractory prostate cancer with bone metastases, 2000 IU of vitamin D with 500mg of calcium per day for three months was found to reduce bone pain, increase muscle strength, and improve the quality of life. [J. Urology 2000; 163: pp.187-190]
A study showed that combining high doses of the vitamin D analog, calcitriol, with chemotherapy (docetaxel) may improve the response in patients with prostate cancer who no longer are responding to hormonal therapy. [J Clin Oncol 2003;21(1): pp.123-8]
See the link between Vitamin D Deficiency and Prostate Cancer.
Polycystic Ovary Syndrome (PCOS)
Vitamin D deficiency appears to occur frequently in women with PCOS and may be a contributing factor to some ot the biochemical abnormalities seen in this condition. Vitamin D also improves glucose tolerance, insulin secretion, and insulin sensitivity in those with diabetes. This improved glucose tolerance may be the mechanism for producing benefits in PCOS. A reasonable dosage is 800 to 1,200 IU per day for several months.
Possible Pregnancy-Related Issues
The Children’s Memorial Hospital in Chicago studied five vitamin D-deficient infants; at least two cases were caused by low vitamin D levels during pregnancy. Health problems ranged from seizures and growth failure to rickets. [Daaboul J, et al. J of Perinat 1997;17(1): 104] Congenital cataracts have also been linked to low levels of vitamin D. [Blau EB. The Lancet 1996;347: p.626] Other research points to vitamin D as a possible adjunct therapy for premature babies with respiratory distress syndrome [Nguyen TM, et al. Am J of Physiol 1996; 271(3): L3929] and for women with gestational diabetes. [Rudnicki PM, Molsted-Pedersen L. Diabetologia 1997; 40(1): 404] The U.S. RDA is 400 IU or 10mg.
It would be wise to make sure you are getting some vitamin D in supplement form or adequate sun exposure during your pregnancy. In analyzing over a million records it was found that babies born in the autumn weighed more than those born at springtime. In later life, low birth weight was associated with increased blood pressure, cholesterol levels, some forms of obesity and a decrease in lung function. Babies born in autumn also lived 4-7 months longer. This is just one more reason to take care of yourself and your child during this time. It is also something you can tell your child you did with them in mind when they are older.
Key
| May do some good |
| Likely to help |
| Highly recommended |
| May have adverse consequences |
| Avoid absolutely |
Glossary
Vitamin D
A fat-soluble vitamin essential to one's health. Regulates the amount of calcium and phosphorus in the blood by improving their absorption and utilization. Necessary for normal growth and formation of bones and teeth. For Vitamin D only, 1mcg translates to 40 IU.
Bile
A bitter, yellow-green secretion of the liver. Bile is stored in the gallbladder and is released when fat enters the first part of the small intestine (duodenum) in order to aid digestion.
RDA
Recommended Daily Allowance of vitamins or other nutrients as determined by the FDA. U.S. RDAs are more widely used than RDAs, and focus on 3 age groups: Infants of 0-12 months; Children of 1-4 years; Adults and children of more than 4 years.
IU
International Units. One IU is 1/40th (0.025) of a microgram (mcg).
Autoimmune Disease
One of a large group of diseases in which the immune system turns against the body's own cells, tissues and organs, leading to chronic and often deadly conditions. Examples include multiple sclerosis, rheumatoid arthritis, systemic lupus, Bright's disease and diabetes.
Yeast
A single-cell organism that may cause infection in the mouth, vagina, gastrointestinal tract, and any or all bodily parts. Common yeast infections include candidiasis and thrush.
Rickets
Vitamin-D deficiency characterized by abnormal calcification of bone tissues.
Serum
The cell-free fluid of the bloodstream. It appears in a test tube after the blood clots and is often used in expressions relating to the levels of certain compounds in the blood stream.
Metabolism
The chemical processes of living cells in which energy is produced in order to replace and repair tissues and maintain a healthy body. Responsible for the production of energy, biosynthesis of important substances, and degradation of various compounds.
Protein
Compounds composed of hydrogen, oxygen, and nitrogen present in the body and in foods that form complex combinations of amino acids. Protein is essential for life and is used for growth and repair. Foods that supply the body with protein include animal products, grains, legumes, and vegetables. Proteins from animal sources contain the essential amino acids. Proteins are changed to amino acids in the body.
Metabolite
Any product (foodstuff, intermediate, waste product) of metabolism.
Endemic
Used to refer to a disease that constantly occurs in any particular geographical region.
Chronic
Usually Chronic illness: Illness extending over a long period of time.