Vitamin D has been in the news quite frequently over the past decade and for good reason: It has numerous health enhancing benefits. In short, Vitamin D deficiency has been linked to far more than rickets, which, of course, represents the most extreme manifestation of a vitamin D deficiency. Before such an extreme deficiency presents itself, here are some illnesses linked to or exacerbated by a vitamin D deficiency, according to Dr. Michael Holick and other vitamin researchers. Dr. Holick, has been researching Vitamin D for forty years and wrote the excellent book, “The UV Advantage.”[iii]
Infections Hypertension (High Blood Pressure)
Diabetes Rheumatoid Arthritis
Multiple Sclerosis Cardiovascular Disease
Now when juxtaposing these major illnesses with recent claims that vitamin D is of very little benefit, one begins to see the disconnect between vitamin research and mass media coverage. Now the mainstream media is doing the same hatchet job on vitamin D. Are they that contemptuous of healthy people that they just can’t stand folks sitting out in the sun to enhance their health and vitality while helping to prevent future degenerative diseases? It would seem this way.
Well, it isn’t just Dr. Holick who has been educating people about the wide scale benefits of a diet rich in vitamin D or a lifestyle with adequate sunshine exposure. Researchers around the world have been announcing the benefits of this fat-soluble vitamin for decades.
THE TOP 100 MEDICAL BREAKTHROUGHS OF ALL TIME!
Back in 2007, Discover Magazine listed the top 100 medical breakthroughs of all time, and vitamin D (“Can Vitamin D Save Your Life,” December issue) came in at number seven! In that same year, Time magazine listed vitamin D as one of the “Top 10 Medical Breakthroughs.” (December, 2007) Teen Vogue, Fitness and other popular magazines have all covered this topic in major articles over the past few years.
Now phytoplankton have been making vitamin D-2 from U.V. radiation from the sun for over 500 million years. That makes vitamin D the earliest hormone ever produced. Now individuals are finally having “respect” for evolutionary science. Why is this? It is because 25 hydroxy-vitamin D (the immediate precursor to the active form of vitamin D in the body), is the most ordered assay in America! USA Today might not recognize the health benefits of vitamin D (nor do most physicians for that matter), but this hasn’t stopped thinking Americans who care about their health, to demand that their doctors check their vitamin D status.
It’s a good thing they’re asking their doctors since 30 percent of white and 42 percent of Hispanics and 84 percent of blacks are deficient in vitamin D. This writer feels the figures are higher, but the “normal” blood levels for vitamin D, keep decreasing which, of course, makes people more “secure” in their “vitamin D status.” Such manipulation of “normal figures” goes on for many nutrients AND it also occurs for “normal” levels of cholesterol—which keep going down. This later example explains why more people “need” statins to lower their cholesterol. “Gosh, you’re above normal,” “better take this medication.” (See our concluding chapter for more on this topic.)
This chapter will now address the history of vitamin D, some health benefits and review evidence of widespread vitamin D deficiency across America. It will also discuss sensible vitamin D recommendations. When you’re through, I hope you at least know that recommendations to “avoid” vitamin D (because it has “no health benefits” according to much of the mainstream media), are pure nonsense.
A LITTLE HISTORY ON VITAMIN D
The link between sunshine exposure and prevention of vitamin D deficiency was recognized by a Polish physician, Dr. Sniadecki, in 1822. Let’s quote Dr. S directly:
“Strong and obvious is the influence of sun on the cure of rickets and the frequent occurrence of the disease in densely populated towns where the streets are narrow and poorly lit.”
Are doctors stubburn? Yes they are and they were just as stubborn 192 years ago as they are today. It would take ninety-seven years before lack of adequate sunshine exposure was firmly linked to rickets in children. This fact was again addressed in 1890 by English physician Dr. Palm, who observed that poor children in Asia and India did not develop rickets like their equally poor counterparts in England and attributed rickets in this later group to be due to lack of sunshine exposure. Twenty-nine years later, in 1919 Viennese physician, Dr. Huldschinsky, began shining U.V. radiation from a mercury arc lamp on his rickets patients as a potent and effective therapy. X-rays would soon show marked improve-ments in mineral bone density from these treatments. A few years in 1922, after Dr. Huldschinsky’s observations, Hess and Unger placed children with rickets on the roof of various New York Apartment buildings and were able to illustrate, once again, the U.V. radiation cured rickets.
So you should therefore NOT be shocked to learn that in 1931, the U.S. Government started recommending “sensible sun exposure” for children to prevent rickets! Now, over 80 years later, some school districts have “sun avoidance policies” in place for children! How contemptuous we are for “basic sciences” when it comes to enhancing the health and well-being of our children! While we “should” be teaching children of the amazing health benefits of UV-B radiation, instead, we’re busy scaring them inside or to use “sunscreens” to protect their health. I would argue that one of the major reasons the health of our children is so darned awful is because of insufficient sunshine exposure.
So what of avoiding the sun to protect our health? What are the health consequences? It turns out, lack of adequate sunshine AND the resulting vitamin D deficiency can contribute to or even cause many diseases. Let’s review the major ones and give some cogent reasons that “USA Today” and the rest of the “mainstream media” is wrong on this front. These were listed earlier, now it’s time to give a little more details. First, let’s cover some misconceptions about vitamin D.
The term vitamin D actually refers to a group of chemicals called steroids. Vitamin D3, also known as cholecalciferol is generated in the skin of humans and other animals when sunlight is absorbed by a molecule, 7-dehydrocholesterol. Technically, Vitamin D is thus not really a vitamin because it does NOT have to come from the diet—indeed, the diet is a poor source of this ‘vitamin.’ There are dietary sources of vitamin D, including fish, cod liver oil, egg yolks, fortified dairy products and, most recently, some specially grown mushrooms—that’s about it! The plant form of vitamin D is called vitamin D2 or ergosterol is found in very small quantities in some plants. Typical American diets do not contain adequate quantities of vitamin D. This is why sunshine exposure is so important in order to prevent vitamin D deficiencies. Fortunately, your body stores vitamin D so that during the winter months when there is much less of the requisite sunshine and UV radiation, the vitamin D can do its job, PROVIDING YOU GOT YOUR REGULAR SUNSHINE DURING THOSE DAYS BETWEEN APRIL AND AUGUST! After all, you can’t store what ain’t there!
OSTEOMALACIA, OSTEOPOROSIS AND VITAMIN D DEFICIENCY
Both osteomalacia and osteoporosis are linked to a vitamin D deficiency. The difference between the two is significant, however. Osteomalacia is an end-stage bone disease of chronic and severe vitamin D or phosphate depletion. It can have a variety of possible causes such as vitamin D deficiency, malabsorption syndromes and drug interactions. Most cases of osteomalacia are cured by vitamin D replacement, but not all. Also, despite widespread vitamin D deficiency across our nation, osteomalacia is rare—it “only” afflicts approximately 200,000 Americans.
Recent literature suggests that osteomalacia can follow bariatric surgeries for morbid obesity due to lack of vitamin D absorption. (Gastric bypass surgery—all variations—causes significant calorie AND nutrient malabsorption and vitamin D would not likely be an exception.) Such surgeries do NOT affect one’s ability to produce vitamin D in skin from UV-B radiation exposure. Common clinical manifestations of osteomalacia include bone pain or tenderness, muscle weakness, and difficulty walking. These symptoms could be compared to the way more popular “osteoporosis,” which presents with zero symptoms typically until a fall fractures a wrist, a hip or a leg bone. Diagnostic work-up for both types of bone disease usually involves assessment of vitamin D status and may also include a transiliac bone biopsy, although a simple scan for mineral bone density is far more likely to be done. I once had a patient, Geraldine, whose vitamin D levels of 9.0 were considered “a little low,” but no supplemental vitamin D was recommend! Due to this extreme (and neglected), vitamin D deficiency, both ankles collapsed, and she now has to wear cumbersome ankle braces. And yes, her weight was around 290 pounds and this added to the stress on her ankles. So is vitamin D deficiency ignored—even in extreme cases in this country? I can say “yes it is,” because I’ve seen it for myself. It’s an embarrassment and indicates the utter ignorance of some doctors in this country on “basic” nutrition issues. Instead of studying potentially dangerous vaccines, they should be studying things like vitamin D (and the other nutrients discussed throughout this book).
So while osteomalacia is primarily a vitamin D deficiency problem, osteoporosis, is a combination of lack of calcium, phosphorus, silica, boron, vitamin C, vitamin K, AND vitamin D, coupled often with hormonal imbalances and insufficient exercise. Wow—that’s a lot of influences, isn’t it? In other words, osteoporosis, is partly due to vitamin D deficiency and osteomalacia is primarily a vitamin D deficiency disease. Vitamin D, therefore, plays a role in both bone diseases, but its overall impact varies depending upon the diagnosis. In both bone diseases, vitamin D status is very important.
According to the National Osteoporosis Foundation, in 2010, about 52.4 million Americans over the age of 50 had low bone density or osteoporosis. That’s approximately two in thirteen Americans! While only about 12 million of them have osteoporosis now, an estimated 13.9 million people will have osteoporosis in another ten years and the majority of these cases (about 80 percent of those affected) are women.
Now I am not of the belief that there is nothing you can do about prevention of osteoporosis, so let’s not think “gosh, the incidence of osteoporosis will keep going up, “oh well.” That’s ‘fatalistic thinking,’ and this kind of thinking is antithetical to ‘positive thinkers,’ isn’t it?
These numbers are slowly, but steadily, increasing. In 2002, 43.6 million Americans over 50 had osteoporosis or low bone mass. That means, in the past eight years, the number of affected Americans has increased by over 20 percent.
VITAMIN D AND HEALTH IMMUNE SYSTEM FUNCTIONING
Vitamin D is a critical nutrient for a healthy immune system, although sadly, few Americans know this and doctors rarely discuss this.
One vitamin D researcher, a Dr. Joe Prendergast, has found that vitamin D is likely more powerful than any vaccine you could take and substantially increases the production of anti-microbial peptides. German researchers have found it increases your immune system by a factor of three to five times. Don’t you think the readers of USA Today might benefit from this kind of information? According to the popular Mercola website,[iv]
“Vitamin D could rightly be described as a ‘miracle nutrient’ for your immune system, as it enables your body to produce well over 200 antimicrobial peptides, which are indispensable in fighting off a wide range of infections.”
Let’s quote further from this same article:
The conventional medical community, with the pharmaceutical industry at the helm, is hard at work creating a vaccine for any and every health condition they can – and then passing them off as the “solution” for disease prevention. Of course, there has never been a disease that is caused by a “vaccine deficiency,” but there absolutely are diseases that are caused by vitamin D deficiency — many of them, ranging from cancer to depression!
You may find it surprising that vitamin D is so important for your health, especially if you’re still under the impression that it’s mostly a nutrient for your bones. Most people also think that vitamin D is really a vitamin, but in reality, the active form of vitamin D is one of the most potent hormones in your body, and regulates more genes and bodily functions than any other hormone yet discovered. Vitamin D is produced as a pro-hormone in your skin after sunlight exposure, and is then converted to the potent hormone form.
Without this hormone, you could die, and indeed, many do die from vitamin D deficiency-related causes.
Let’s quote from a recent Oregon State University press release:[v]
A new study has concluded that one key part of the immune system, the ability of vitamin D to regulate anti-bactericidal proteins, is so important that it has been conserved through almost 60 million years of evolution and is shared only by primates, including humans – but no other known animal species.
The fact that this vitamin-D mediated immune response has been retained through millions of years of evolutionary selection, and is still found in species ranging from squirrel monkeys to baboons and humans, suggests that it must be critical to their survival, researchers say.
Even though the “cathelicidin antimicrobial peptide” has several different biological activities in addition to killing pathogens, it’s not clear which one, or combination of them, makes vitamin D so essential to its regulation.
The research also provides further evidence of the biological importance of adequate levels of vitamin D in humans and other primates, even as some studies and experts suggest that more than 50 percent of the children and adults in the U.S. are deficient in “the sunshine vitamin.”
“The existence and importance of this part of our immune response makes it clear that humans and other primates need to maintain sufficient levels of vitamin D,” said Adrian Gombart, an associate professor of biochemistry and a principal investigator with the Linus Pauling Institute at Oregon State University.
It would therefore appear that the author of the USA Today article noted earlier, had not done her homework. Or, perhaps, the writer of that ridiculous and irresponsible article skipped her classes on “investigative journalism,” you know, the kind that actually investigates before they put pen to paper!
Now keep in mind, this writer doesn’t just recommend you start taking vitamin D unless you know your blood levels AND are aware of some important interactions between vitamin D and other nutrients, such as vitamin A. Yes, they work together and one should not supplement with one without the other. Perhaps you remember your childhood days, when your mom maybe forced you to take cod liver oil? Perhaps you also remember that it was rich in vitamin A and vitamin D. Meanwhile, your holistically-educated health care practitioner should be able to advise you properly on how to get your vitamin D level (25 hydroxy-D), to the ideal level of 80-100 ng/ml. This writer doubts it’s there now, but you’ll only know by having an easy blood test taken.
In short, the role that vitamin D plays in healthy immune functioning is impressive and I would encourage the interested reader to do further research on this topic. It is, after all very substantial and maybe right up there in importance to a healthy immune system as is vitamin C.
Now let’s look into the role that vitamin D plays in cardiovascular health.
VITAMIN D DECREASES HEART DISEASE DEATH RATE BY ABOUT ONE-THIRD!
A recent study has shown that women, who take vitamin D supplements, lower their risk of death from heart disease by one-third. While previous studies correlated a higher risk with reduced blood levels of the vitamin, this study looked at the effects of taking a supplement of vitamin D.
Dr. Paul D. Varosy and his team analyzed data from nearly 10,000 women over the age of 65 who were enrolled in a study to learn more about osteoporosis and how this can lead to broken bones. Of these, more than 4,200 women reported that they took vitamin D supplements at the time of the study, and another 733 reported a prior history of supplement use.
The women were followed for nearly eleven years and those taking supplemental vitamin D were found to have a 31 percent lower death rate from heart disease. It should be noted that studies have indicated that sunshine raises vitamin D levels much more effectively than supplements. This is probably because the form of vitamin D made from sunshine is immediately bioavailable (after a few quick conversions in the machine shop of the liver and the kidneys). Also, about twenty minutes in bright sunshine will allow for the production of about 20,000 I.U. of 1, 25 OH-D, (vitamin D) about the amount that most supplement users would receive from FIFTY DAYS worth of supplementation with the standard 400 I.U. dose and this assumes the natural variety of supplement, not the synthetic version which studies show does not appreciably affect vitamin D blood levels.
One risk factor for heart disease and many other chronic and degenerative diseases is inflammation. It turns out that vitamin D status is strongly linked to anti-inflammatory effects! Low serum vitamin D is associated with inflammation, using such indicators as high-sensitivity C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α).[vi]
The researchers note that calcium supplements, education, self-reported health status or health-related behaviors had no effect on the protection afforded by vitamin D.[vii]
New research from the University of Copenhagen and Copenhagen University Hospital also shows that low levels of vitamin D are associated with a markedly higher risk of heart attack and early death. The study involved 10,170 Danish men and women and was published in the journal Arteriosclerosis, Thrombosis and Vascular Biology.[viii] Vitamin D deficiency has traditionally been linked with poor bone health. However, the results from several population studies indicate that a low level of this important vitamin may also be linked to a higher risk of ischemic heart disease, a designation that covers heart attack, coronary arteriosclerosis and angina. Other studies show that vitamin D deficiency may increase blood pressure, and it is well known that high blood pressure increases the risk of heart attack.
VITAMIN D TOXICITY AND SUNSHINE DANGERS
As regards frequent claims of vitamin D toxicity and sunshine dangers—these have been widely exaggerated and a cause of much ill health, especially with Americans in the Northern latitudes.[ix] Supplements of vitamin D are typically 400 or 1,000 I.U., yet you’ll make 20,000 I.U. of vitamin D in your body from 20 minutes of full sunshine exposure! No lifeguard has ever been diagnosed with vitamin D toxicity because the body cuts off production when it has enough. Therefore, the conception that a few thousand IU can be an overdose is absolutely wrong and very much ill-serves the public.
Vitamin D, as either D3 or D2, does not have significant biological activity. Rather, it must be metabolized within the body to the hormonally-active form. In fact, an adequate intake of vitamin D can help prevent up to twelve different forms of cancer, including breast, prostate and colon cancer. By how much can this prevention be? Up to FIFTY percent! Is it any wonder why the cancer industry doesn’t want Americans to know of the tremendous health benefits of sunshine—they can’t package it and make money from it. Indeed, proper sun exposure would cost the cancer industry (and several others that profit from ill-health) billions of dollars in unearned profits. So they exaggerate this ‘skin cancer’ connection and people are now afraid to go in the sun.
Unfortunately, many scientists and health professionals who should know better, keep parroting the same nonsense about sunshine and vitamin D toxicity and more often than not, the public buys it! This is not to say one should sunbathe for hours on end—just that the dangers for normal exposure are simply non-existent to folks following the lifestyle guidelines in this book (e.g., getting sufficient beta-carotene and other anti-oxidants to repair any skin damage caused by UV radiation). Remember, we’ve evolved over millions of years under full sunshine—not wearing sunscreen and apparently not suffering from epidemics of skin cancer along the way.
Here is a brief summary from the abstract of this study:
Comparing individuals with plasma 25-hydroxyvitamin D levels at the 1st to 4th percentile with individuals with levels at the 50th to 100th percentile, the multivariable adjusted risk was increased by 40% (95% CI, 14%–72%) for ischemic heart disease, by 64% (25%–114%) for myocardial infarction, by 57% (38%–78%) for early death, and by 81% (40%–135%) for fatal ischemic heart disease/myocardial infarction. In the meta-analyses of 18 and 17 studies, risk of ischemic heart disease and early death were increased by 39% (25%–54%) and 46% (31%–64%) for lowest versus highest quartile of 25-hydroxyvitamin D level.
In other words, low levels of vitamin D was associated with:
- An Ischemic heart disease increase of 40 percent
- Heart attacks going up by 64 percent
- An early death increase of 81 percent from low levels of vitamin D compared to higher levels.
These are not insignificant numbers!
One risk factor associated with so many ailments is diabetes, linked as it is to the “metabolic syndrome,” obesity, heart disease, elevated blood pressure, stroke, neurological conditions and early disability and death. Sixteen million Americans have Diabetes and another 17 million are pre-diabetic and on their way to developing diabetes if they don’t do something…fast!
Certainly if there were a vitamin that could play a role in reducing this major scourge to our nation’s health AND our national “health care burden,” we’d want to know of it, right? Well, let’s then address the role that one particular vitamin can play in the prevention of Diabetes, namely, vitamin D.
Recent studies have demonstrated correlations between low vitamin D levels and the development of type II diabetes while others correlate higher levels of vitamin D to a decreased incidence of this disease. Also, it is worth noting that previous research identified vitamin D receptors in the beta cells of the pancreas where vitamin D appears to be linked to healthy regulation of insulin secretion.
The reader may recall that the pancreas produces digestive enzymes to help us digest our food AND it produces insulin to help our bodies store fat. The purpose of insulin is NOT to “lower blood sugar,” but to gather ‘excess calories’ and store them for rainy days, e.g., food scarcity! Imagine that. So insulin production is part of an ‘ancient’ survival mechanism that our modern high carbohydrate/high sugar diets have totally messed up.
When blood sugar levels rise to high levels on a consistent basis, sugar becomes attached to hemoglobin—our oxygen carrying protein in the body. Over time, this hemoglobin can be tested in what’s called the HbA1C test—reflecting as it does, blood sugar ‘control’ over the previous three months. It’s not the one jelly donut you had for breakfast that will ‘mess up’ this test, but those that you have every day for three months! THIS is what HbA1C looks at. Normal is below 6.0 and diabetics (properly controlled), should aim for below 7.0.
A recent study has aimed to show a correlation between glycemic control (blood sugar control), and levels of vitamin D (25-hydroxy vitamin D3) in type II diabetic patients. This study looked at 25(OH) D3 and HbA1C levels of 120 persons with type II diabetes between the ages of 25 and 82. They then compared them to 120 similarly aged non-diabetic control subjects. A1C levels were higher in the diabetes group as expected (7.2 ± 0.18% versus 5.1 ± 0.05%) and the vitamin D3 levels were significantly lower in the diabetes group as compared to the control group (19.26 ± 0.94 ng/ml and 25.48 ± 1.02 ng/ml; p<0.001). The researchers further analyzed vitamin D levels in the diabetes versus the healthy control group and found that 17.5% (21/120) and 63.3% (76/120) of the persons in the diabetes group were vitamin D deficient and insufficient, respectively, as compared to 5.8% (7/120) and 23.3% (28/120) of the control group participants. In short, HbA1C levels showed an inverse relationship between vitamin D levels and this important measure of “long-term blood sugar control.”
This study shows a fairly strong correlation between vitamin D deficiency/insufficiency and type II diabetes and also demonstrates a negative correlation between vitamin D levels and HbA1C levels. Findings from this study suggest we should be monitoring vitamin D levels in persons with type II diabetes and providing vitamin supplementation to those in which it is clinically warranted.
More recently, a paper published in 2013 by Dr. Wang Song and associates[x] presented a large-scale analysis of numerous studies on this topic (called a “meta-analysis”). In this case, they reviewed 21 prospective studies of type II diabetes mellitus incidence with respect to serum 25(OH)D levels at the time of enrollment in the studies. The studies involved a total of 76,220 participants and 4,996 type II diabetes cases. The risk of diabetes, type II went down 55 percent when blood levels of vitamin D increased from a low of 14 ng/ml to 60 ng/ml! This analysis provides additional strong support for the role of vitamin D in reducing the risk of type 2 diabetes mellitus.
The reader should remember that reducing one’s risk of developing diabetes also means a reduced risk for heart disease, hypertension and stroke—all good things, of course! So cut out the sugar and refined carbohydrates AND get your vitamin D level checked!
AUTO-IMMUNE DISORDERS AND VITAMIN D
Auto-immune disorders are disorders of the immune system in which the body starts attacking its own tissues. Some examples (and the organs they attack) include Chronn’s Disease (intestinal tract), Hashimoto’s Disease (thyroid gland), Rheumatoid Arthritis (small joints in the hands) and Multiple Sclerosis (nervous system). Immunosuppressive drugs are commonly used to address these diseases. Auto-immune disorders are at epidemic levels in America today.
Before discussing the role of vitamin D in the development/prevention of these types of diseases, let’s first discuss auto-immune disorders in general. I hope this discussion proves beneficial!
A good way of thinking on these types of diseases is to address why the immune system has become disregulated and why it finds itself attacking its own tissues! Thus, holistic physicians treating such disorders will want to ask why is the body attacking itself! A good review on some of the basics of this subject can be found in the following three articles:
- The first is from Scientific American, June of 2012: “Your Inner Ecosystem,” by Jennifer Ackerman.” This article explains the extreme importance of ‘gut flora’ (healthy intestinal bacteria) for keeping our immune systems healthy. This is important because 70 percent of our immune system resides in the gut AND if you neglect gut (intestinal) health, you’re missing the whole boat AND—believe it or not, autoimmune problems can result!
- Another excellent article was written by Naturopathic Physician and teacher at the School of Naturopathic Medicine in Bridgeport, Connecticut, David Brady, N.D. This article discussed the role of healthy gut function to a smartly regulated immune system and was published in the June, 2012 issue of the Townsend Health Letter and I highly recommend it. (I have heard this doctor speak on this topic in June of 2012 in Bridgeport.)
- One widely ignored environmental cause of auto-immune disorders is the overuse of vaccines across America. This topic was the subject of an excellent article “Self-Organized Criticality Theory of Autoimmunity” by three Japanese researchers.[xi] According to this paper, “Systemic autoimmunity appears to be the inevitable consequence of over-stimulating the host’s immune ‘system’ by repeated immunization with antigen, to the levels that surpass the system’s self-organized criticality.” They went on to say that: “Autoimmune diseases are a modern plague, causing untold suffering and early, painful death. This study clearly documents that vaccinations are a primary cause.”
Now before the reader jump to any conclusions on the aforementioned items, it should be noted that the medical profession and the mainstream media barely give any attention to gut health or the overuse of vaccinations when discussing autoimmune disorders. So we should NOT call these topics controversial, as they’re not. They’re simply not in any kind of regular discussion of these issues. In other words, they’re ignored.
In studying this material, one would likely conclude that it is actually better to make the gut healthier (e.g., better ‘gut flora,’) than to simply start taking powerful medications that might cause a 50 pound weight gain and other side effects! Healthier gut health and function, is accomplished through a healthy diet. To make one’s immune system ‘smarter’ is accomplished by minimizing vaccine use and also by a smartly chosen supplement program that likely includes vitamin D.
There is a great deal of research pointing to lack of vitamin D as having a significant role to play in the development of a variety of auto-immune disorders. One paper had this to say: A study has linked vitamin D deficiency with an increased risk for cancer and autoimmune diseases, such as rheumatoid arthritis, MS, and lupus. Researchers found, through mapping vitamin D receptors binding throughout the human genome, that vitamin D deficiency is a major environmental factor in increasing the risk of developing these disorders.[xii]
A study has linked vitamin D deficiency with an increased risk for cancer and autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus. Researchers found, through mapping vitamin D receptors binding throughout the human genome, that vitamin D deficiency is a major environmental factor in increasing the risk of developing these disorders.
The role that Vitamin D plays in M.S. was first suggested by Dr. Goldberg in 1974 [xiii] He felt that getting insufficient sunlight to form vitamin D could be the trigger for MS in genetically susceptible people. He calculated, in relation to vitamin D and MS, on the basis of amount of sunshine in areas with little MS, and the rate at which vitamin D is formed in the body, that it would take 3,800 international units of vitamin D daily to prevent the onset of MS. Incredibly, exactly this dose has recently been calculated to be the amount of vitamin D required to maintain a steady reasonable vitamin D level. (It has not been proven that M.S. is an “autoimmune disorder,” but it may be.)
“Health Central,” an internet health newsletter, has recently published an excellent summary of the role that vitamin D plays in preventing R.A. and other auto-immune disorders.[xiv] Let’s quote directly from this article: From this same article comes this information about drugs and malabsorption of vitamin D:
Hydroxychloroquine, or Plaquenil, and corticosteroids, which both can be prescribed for the treatment of rheumatoid arthritis, are among these that can cause malabsorption of vitamin D! Even if you are taking one of these drugs, your doctor can adjust your vitamin D dose to correct the malabsorption.
MULTIPLE SCLEROSIS AND VITAMIN D STATUS
Approximately 500,000 Americans—about one in 640 persons, have M.S. today. Studies have indicated that adequate vitamin D status can substantially reduce the incidence of this neurological disorder. This is not to say the link between vitamin D status and M.S. is proven beyond any doubt as some studies—we’ll discuss shortly—show no association.
Here are some of the reasons we can associate insufficient vitamin D status to the risk of developing M.S.:
Inadequate exposure to sunshine and insufficient vitamin D intake during childhood might result in defective formation of the myelin which would be susceptible to breakdown in later life.[xv] Another study around the same time, indicated that the greatest benefits of sunlight in prevention of M.S., may accrue to migrating youngers, less than fourteen or fifteen years of age.[xvi]
In an excellent review article in Lancet Neurology, entitled Vitamin D and Multiple Sclerosis, Dr. Asherlo and colleagues demonstrate how geographical distribution of M.S. is very much related to sunshine exposure.[xvii] Let’s quote from the introduction of this important and recent, review article:
The risk of developing multiple sclerosis (MS), a relatively common cause of disability among young adults, is determined by a combination of genetic and environmental factors. The latter include Epstein-Barr virus (EBV) infection, cigarette smoking, and inadequate serum concentrations of vitamin D. Although EBV is nearly ubiquitous, there are no effective vaccines or treatments for EBV infection, leaving smoking cessation and vitamin D supplementation as the only available interventions that might result in a reduction in the global burden of MS. Because vitamin D deficiency is endemic worldwide, the potential impact of vitamin D supplementation on MS incidence is profound.
The hypothesis that vitamin D deficiency is a risk factor for MS was first proposed over 30 years ago, and gained credibility after the discovery of the immunomodulatory effects of vitamin D. However, over the past few years, the epidemiological evidence of an increased MS risk among individuals with low vitamin D concentra-tions has achieved substantial strength, thus approaching a threshold that calls for important decision-making in terms of experimental investigations or public-health interventions. In this Review, we will provide a critical analysis of the epidemiological studies on vitamin D and MS risk or severity, and their implications for M.S. prevention and treatment.
Within areas of low sunlight (e.g. Norway), differences in MS prevalence could be explained by dietary factors which affect vitamin D production. Such factors include the amount of fish eaten (increases vitamin D) and the amount of grains consumed (reduces vitamin D levels due to the action of phytates).9
In Switzerland, districts at low altitudes (<1000 m) have high MS rates, whereas districts at high altitudes (>2000 m) have low MS rates, despite the relative genetic similarity of the two populations. Increased short-wavelength ultraviolet radiation (increased vitamin D) received at high altitudes compared to low altitudes, may explain this anomaly.[xviii]
Within genetically similar migrating populations, those migrating to regions with increased solar radiation had reduced MS rates, whereas those migrating to regions with decreased solar radiation had increased MS rates.
One study published in a recent issue of Neurology showed that vitamin D was not effective in controlling relapses in multiple sclerosis patients.[xix] While this study appeared to be well-designed the researchers used vitamin D2, NOT the more recommended form, vitamin D3. The study was also small, with only 23 participants and study participants were on powerful medications that may affect nerve function, including interferon or glatiramer acetate (Copaxone) treatment. Finally, vitamin A was not given, nor were other nutrients that impact on nerve function. However, this later criticism is true for many vitamin studies, as these often follow the ‘drug model’ in which ONLY one drug is used at the same time.
It must be stressed that adequate calcium and magnesium intake must accompany vitamin D supplementation as discussed by Goldberg and associates in the International Journal of Environmental Studies.[xx] Cantorna and colleagues demonstrated in 1999 that calcium levels strongly affect the action of vitamin D for suppressing EAE (experimental autoimmune encephalomyelitis) in mice.[xxi] Calcium intake should be in the range of 600-900 mg/day with magnesium intake being about the same as this. (The EAE model in experimental animals is used because we can’t go around inducing auto-immune disorders in people!)
Vitamin D deficiency afflicts most MS patients, as demonstrated by their low bone mass and high fracture rates.[xxii]
The well established reduction of MS attacks during pregnancy and their increased occurrence following pregnancy is due in part or whole to the natural large increases in production of vitamin D hormone during pregnancy and its rapid decline afterwards.
Finally, Researchers from Norway and Italy undertook a classic case controlled study, that is comparing people with an illness to “control people” without the illness, and looked at particular risk factors and how much more or less common they were in the group with the illness. After filling out questionnaires, those with the least sun exposure in Norway had an 82 percent higher risk of developing MS compared with those with the most sun exposure, and 49 percent greater risk in Italy. In Norway where there was frequent sunscreen use up to the age of six a 44 percent greater risk of developing MS was seen![xxiii]
It seems likely that the greater risk modification from frequent sun exposure was seen in Norway because in summer, it was much more common for people to get frequent sun, and there was a much bigger difference between summer and winter in amount of sun exposure. The greatest effect of infrequent sun exposure was seen in early childhood in Italy and in late adolescence in Norway.
Adults living or working in sunny environments, where MS prevalence is lowest, have circulating vitamin D3 levels between 42 and 65 ng/ml. Thus, a 25(OH)D3 concentration greater than 40 ng/ml may be optimal to prevent MS.[xxiv] (1999)
Wow—that’s a lot of neurological system benefits for a vitamin. On this note, now would be a good time to give a summary of the evidence on the neurological health benefits to vitamin D from the DeLuca study.[xxv]
“Vitamin D and its metabolites have pleomorphic roles in both nervous system health and disease. Animal models have been paramount in contributing to our knowledge and understanding of the consequences of vitamin D deficiency on brain development and its implications for adult psychiatric and neurological diseases. The conflation of in vitro, ex vivo, and animal model data provide compelling evidence that vitamin D has a crucial role in proliferation, differentiation, neurotrophism, neuroprotection, neurotransmission, and neuroplasticity. Vitamin D exerts its biological function not only by influencing cellular processes directly, but also by influencing gene expression through vitamin D response elements. This review highlights the epidemiological, neuropathological, experimental and molecular genetic evidence implicating vitamin D as a candidate in influencing susceptibility to a number of psychiatric and neurological diseases. The strength of evidence varies for schizophrenia, autism, Parkinson’s disease, amyotrophic lateral sclerosis, Alzheimer’s disease, and is especially strong for multiple sclerosis.”
Each year over two million Americans will get cancer and 576,000 will die from it. Many of these cases could have been prevented had these individuals (and their doctors!), paid more attention to their vitamin D status. This is because it turns out that there is a link between cancer prevention and vitamin D status. In other words, the better your vitamin D status, the less likely you are to develop cancer. Vitamin D also appears to play an important role as part of a comprehensive immune-system enhancing protocol, as well.
The role that vitamin D plays in preventing cancer is an enormously popular area of research, yet it still has not percolated through the mainstream media’s anti-vitamin atmosphere. Since a healthy immune system is critical to the prevention of cancer and vitamin D is crucial for a healthy immune system, it is NOT much of a stretch to imagine that vitamin D, therefore, can play a role in the prevention of cancer.
One article on the popular Joseph Mercola website (Mercola.com), of May 12, 2013, had the following headline: Vitamin D Might Be Able to Slash Your Breast Cancer Risk by 90 Percent. Can you imagine if a drug could do this, what uproar the mainstream media would have over this? But the mainstream media is mainly silent on this topic of vitamin D and cancer, as are most physicians for that matter. Occasionally, it’ll get a passing mention–like washing your hands to not catch a cold!
A good way to appreciate the role that vitamin D plays in cancer prevention is offered by vitamin D researcher Carole Baggerly. Carole, the founder and director of GrassrootsHealth has a mission to increase awareness about vitamin D and the crucial role it plays in many aspects of your health, including the prevention of so many forms of cancer. Carole has been following the latest research on this topic, and I highly recommend her informative 44 minute video on this topic.[xxvi]
According to Mercola, optimizing your vitamin D levels may help you prevent more than 16 different types of cancer including pancreatic, lung, ovarian, breast, prostate, and skin cancers.
Mercola makes note of a study completed by Joan Lappe and Robert Heaney in 2007. In this study, a group of menopausal women were given enough vitamin D to raise their serum levels to 40 ng/ml. After just four years, these women experienced a 77 percent reduction in the incidence of all cancers, across the board. I do not consider 40 ng/ml a significant level and at the medical center where I work, we prefer 80-100 for optimum health benefits. This 40 ng/ml was, therefore, half what I and other researchers, consider ideal. Still, a 77 percent reduction in all cancers! This is absolutely amazing but I wonder if any of you reading this book, read of these results in your local paper or heard about them on your local 6 or 11 pm news!
If these studies indicating a significant reduction of cancer by adequate vitamin D were just one-third as good—e.g., 30 percent, not 90 percent, this would still mean that 30 percent of one million Americans who get cancer every year, NOT getting it! That’s 300,000 Americans each year. I contend it would be much higher, easily half a million Americans would NOT get cancer that otherwise will, were their vitamin D status to improve to a reasonable level of say 80 ng/ml to 100 ng/ml.
A Natural News article of February 25, 2012 about cancer, authored by Aurora Gibb, had this to say about the medical establishment, cancer and vitamin D[xxvii]:
The medical establishment’s dismissive take on vitamin D and its effects on cancer cannot seriously be taken in the light of new research supporting the effect of vitamin D on cancer. One cannot help but be suspicious of this rather cold shoulder treatment, especially when non-profit organizations that supposedly support the active search for a cure have financial ties with pharmaceutical companies, mammography equipment companies and other organizations that profit from cancer. Moreover, research on vitamin D is a threat to the cancer industry because it shows a way of dealing with cancer for free.
The reader should note that this is only a very brief review of the role that vitamin D plays in cancer prevention as hundreds of articles have been published on this topic over the past decade. Thus, it is imperative that YOU further study this issue to determine whether you should increase your sunshine exposure and/or supplement your diet with vitamin D(3)!
Vitamin D deficiency linked to poor health in our pet iguanas, and is also associated with infertility, low birth weights and poor birth outcomes. Your pet iguana however, gets respect! Your pet store will recommend reptisun, a fluorescent light for these unique pets. But we’re more concerned about people, aren’t we? We should hope, but just the same, one in eight children born in the United States are born premature with low-birth weights and I content that this is largely due to a lack of sunshine exposure in women before and during their pregnancies. So why aren’t doctors recommending UV lights (or sunshine) for people when they can make proper (vitamin D enhancing steps), for our pet iguanas? Why indeed.
Now let’s look at a recent study reported by Dr. Michael Holick in one of his recent lectures.[xxviii] In this lecture, he reported that in one study, with Dr. Bodner of Pittsburgh, 76 percent of mothers and 81 percent of newborns were deficient in vitamin D. He also noted that pre-eclampsia of pregnancy is associated with a vitamin D deficiency. Please note that the standard used was below 20 nanograms per mililiter—way less than the standard of 50-100 ng/ml that we prefer to use in our offices.
A reduction of MS attacks during pregnancy has become well-established and their increased occurrence following pregnancy is likely due in part or whole to the natural large increases in production of vitamin D hormone during pregnancy and its rapid decline afterwards.[xxix]
Now Hollis and Wanger (AJCN, 2004) showed that if you give pregnant women 4,000 I.U. of vitamin D per day, they’ll put enough vitamin D in their breast milk to satisfy the requirements of their children who are breast feeding.
It should also be noted that adequate vitamin D status in pregnant women reduced their require-ments for “C-section” by 400 percent!
HEALTHY DIETS TO ENHANCE VITAMIN D STATUS IN PEOPLE
So do you want to avert vitamin D deficiencies by eating a healthy diet? Sorry, but this is very difficult to do, as vitamin D is rare in regular foods. There is some in regular fortified cow’s milk, but there are reasons we might want to consider NOT drinking commercial cow’s milk, because of how it’s raised, the food it is fed and the hormones they might be given.[xxx] Some growers are exposing their mushrooms to U.V. radiation such that their finished product contains 387 I.U. per serving of mushrooms, but these mushrooms are not easy to come by. As for fish providing vitamin D, it’s only fatty fish that contains it and wild Alaskan salmon contains 500 to 600 I.U. per 3.5 ounces whereas farmed salmon contains a paltry 100 to 150 I.U. per serving.
As for making vitamin D in your skin, it needs to be from April through October AND between 10 and 3 AND you can’t be inside your office, at your desk, on your job! A LOT has to “come together” in order for you to make vitamin D in your skin. And by the way, you have to have skin exposure for this to work! How much does one half hour of sunshine exposure make in your skin? A minimum of 20,000 I.U.!
Research by Dr. Holick and others indicates that dark skinned individuals (blacks), in American need 5 to 10 times more vitamin D than their white skinned counterparts. It is this huge discrepancy in vitamin D status that may account for the often quoted differences in health outcomes in whites versus dark-skinned individuals. Turns out that 30 to 50 percent of African Americans are vitamin deficient. Hollick showed that in individuals over 50 years of age, 30 percent of whites, 42 percent of Hispanics and 84 percent of blacks were vitamin D deficient AND at the end of the summer! Why the media seems never to discuss this fact, is beyond the understanding of this writer, UNLESS “promotion of vibrant health” is of no interest to various disease-related business interests in America.
The optimum blood level for vitamin D is between 80 and 100 ng/ml. IF you decide to practice a healthy sunshine routine (during the useful months of April through August), AND if decide to supplement your diet with Vitamin D3, it would be useful to have your vitamin D status checked from time to time to make sure you’re NOT above say 125 ng/ml. In addition, it is important that you also watch your intake of other nutrients that work with Vitamin D, such as vitamin A and K2. Do NOT take vitamin D, without also paying attention to your vitamin A intake. My recommendation is that your vitamin A be half your vitamin D intake. A safe way to approach this subject is to ALSO check your vitamin A status from time to time.
VITAMIN D FROM SUNSHINE VERSUS VITAMIN D FROM FOODS
It turns out that the vitamin D you get from sunshine lasts twice as long as the vitamin D you get from foods. However the bad news about sunshine and vitamin D is that in northern climates, you’re not getting very much vitamin D from sunshine between November and April of any year. While you keep in mind the much greater benefit to one’s “vitamin D status” from sunshine versus vitamin D pills, it could prove useful to review some history of the discovery of this amazing vitamin.
THAT MAJOR STUDY QUESTIONING THE HEALTH BENEFITS OF VITAMIN D
One paper that has gotten considerable publicity is one calling into question the health benefits of vitamin D. Autier and colleagues published a paper comparing vitamin D randomized controlled trials to prospective studies based on health outcomes with respect to serum 25(OH)D levels[xxxi]. While they found good evidence from the observational studies that lower disease and mortality rates were correla-ted with higher serum 25(OH)D levels, they noted that few randomized controlled trials agreed with the observational studies.
I would contend that the failure of Autier and associates to recognize substantial benefits to vitamin D in randomized controlled trials (RCT’s) is due to following a pharmaceutical model when studying vitamin D effects. Vitamin D works in conjunction with many other nutrients—vitamin A, C, K2, magnesium, calcium and many others, and IF one is studying vitamin D, by itself one should not always expect miraculous results. After all, while the drug companies want ONE pill that does amazing things, (to be sold as a prescription), vitamins don’t work like this, they work as part of a team. Another failure of the Autier study is that they failed to recognize the importance of low initial blood levels of vitamin D at the start of the trial and that there should be have been a substantial increase of blood levels during a trial in order to gauge potential favorable effects. Their trial did not do this.
According to a critique of RCT’s, the vitamin D RCTs conducted to-date have for the most part been poorly designed and conducted. It is beyond the scope of this book to describe these in detail, so the interested reader is encouraged to seek out the Heaney report.[xxxii] Let’s quote directly from his report:
These criteria appropriate for vitamin D include strength of association, consistent findings in different populations, temporality, biological gradient, plausibility (e.g., mechanisms), coherence, experiment (e.g., RCT), and analogy. Not all criteria need be satisfied, but the more that are, the stronger the case. A number of health outcomes have been found to satisfy Hill’s criteria for causality for vitamin D including many types of cancer. Unfortunately, the paper by Autier and colleagues will likely dissuade many from recommending vitamin D in their practice or using it personally.
Dr. Pawel Pludowski, MD, (Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children’s Memorial Health Institute in Warsaw, Poland), and many colleagues, reviewed the evidence of health benefits of vitamin D at a major “Vitamin D Conference” attended by over 500 people in Warsaw, Poland in October of 2012.[xxxiii] The evidence reviewed was primarily from observational studies. They found:
“Adequate vitamin D status seems to be protective against musculoskeletal disorders (muscle weakness, falls, fractures), infectious diseases, autoimmune diseases, cardiovascular disease, type 1 and type 2 diabetes mellitus, several types of cancer, neurocognitive dysfunction and mental illness, and other diseases, as well as infertility and adverse pregnancy and birth outcomes. Vitamin D deficiency/insufficiency is associated with all-cause mortality.”
This paper provided the basis for recommending serum 25(OH)D levels of at least 30 ng/ml (75 nmol/l) for Central and Eastern Europe.
I hope this overview about vitamin D has convinced you to look further into the potential health benefits of regular sunshine, exposure, and perhaps to vitamin D supplementation for your family. With literally thousands of positive studies of all kinds on the health benefits of healthy sunshine exposure and vitamin D supplementation, at least we can feel positive about its potential benefits!
We now know that optimal vitamin D status is closely related to our resistance to developing cancer, neurological conditions, immune system dysfunction and many other health challenges and may prove beneficial if we should be suffering from some health challenges at the present time. It is important, of course, to work with your doctor closely to work out a plan that just may include a prescription for healthy sunshine exposure and maybe…two weeks in Bermuda! Meanwhile, just remember that good health must include many things and that vitamin D is just one of them, although an apparently, very important one!
[ii] Maybe that 50,000 I.U. of vitamin D I took back in Sept. of 2013, (every few days), during a battle with Lyme disease was a waste of my time? Maybe I got rid of my 105.8 fever in a few days by “luck”? Maybe the fact that I was back to running five miles per day less than two weeks later had nothing to do with the 30 – 50,000 units of vitamin D, 25,000 units of vitamin A and 15,000 milligrams vitamin C (on non-IV vitamin C days), I took each day?? Speaking of Intravenous Vitamin C, this was 50,000 milligrams /day, two to three days per week for two weeks and I also took other nutrients, as well. I have had no further symptoms since September 18, 2013. (My illness began on September 3, 2013. I also took antibiotics for six weeks. How many patients with severe Lyme disease can say they got better in two weeks? It’s only ridiculous for folks to claim that vitamins don’t work and you shouldn’t “bother” taking them. And if YOU don’t want to bother taking them…don’t.
[iii] Holick, Michael, Chapman, Mark, The UV Advantage, Truth Publishing, 2006.
[iv] http://mercola.com: Why this Vitamin is Better than ANY Vaccine and Improves Your Immune System by 3-5 Times, Jan. 12, 2012, website article.
[v] Gombart, Adrian, Key feature of immune system survived in humans, other primates for 60 million years; Oregon St. Un, Press Release, Aug. 18, 2009.
[vi] Bellia A, Garcovich C, et. al., Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects. Intern Emerg Med. Feb;8(1):33-40, 2013.
[vii] 42nd annual conference on Cardiovascular Disease and Epidemiology Prevention in Honolulu, Hawaii. April 23, 2002
[viii] Brøndum-Jacobsen, Peter, et. al. 25-Hydroxyvitamin D Levels and Risk of Ischemic Heart Disease, Myocardial Infarction, and Early Death, Arteriosclerosis, Thrombosis, and Vascular Biology, online edition,. Aug., 30, 2012
[ix] Holick, Michael, The UV Advantage, Truth Publishing, 256. p.
[x] Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, Hu FB. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care. 2013 May;36(5):1422-8
[xi] Tsumiyama, Ken, Miyazaki, Yuma, Shiozawa, Shunichi, Self-Organized Criticality Theory of Autoimmunity, Dec., 31, 2009, PLOS online, http://www.plosone.org
[xii] Andersen, Lene, Eight facts about Vitamin D and Rheumatoid Arthritis, Health Central, online newsletter, Aug. 15, 2013, updated, Jan. 3, 2014.
[xiii] Goldberg P. Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence (a viewpoint). Part 1: sunlight, dietary factors and epidemiology., Int J Environ Studies 1974; 6:19-27
[xiv] Andersen, Lene, 8 Facts About Vitamin D and Rheumatoid Arthritis; http://healthcentral.com; August 15, 2013;
[xv] Goldberg, Peter, M.D., Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence; International Journal of Environmental Studies; Volume 6, Issue 1, 1974.
[xvii] Ascherio, Alberto, Munger, Kassandra L, et. al., Vitamin D and Multiple Sclerosis, Lancet Neur, Vol. 9, 599-612, 2010.
[xviii] Geiger, R., The Climate Near the Ground, Harvard Univ. Press, 442-446, 1965.
[xix] Stein MS, Liu Y, Gray OM, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology, Vol 77, no 17, pp 1611-8, 2011.
[xx] Goldberg, Peter, Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence, International Journal of Environmental Studies, Volume 6, Issue 1, 1974
[xxi] Cantorna MT, Humpal-Winter J, DeLuca HF.; Dietary calcium is a major factor in 1,25-dihydroxycholecalciferol suppression of experimental autoimmune encephalomyelitis in mice; J Nutr. Nov;129(11):1966-71, 1999.
[xxii] Hayes, Colleen, Vitamin D: a natural inhibitor of multiple sclerosis, Department of Biochemistry, Un of Wisconsin, Proceedings of the Nutrition Society, Vol. 59, pp 531-535., 2000.
[xxiii] Yet another study showing sun exposure reduces the risk of M.S. http://overcomingmultiplesclerosis.org., Jan., 2014
[xxiv] Vieth, Reinhold, Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety, Am. J. Clin. Nutr., Vol 69, no. 5, pp 842-856, May, 1999.
[xxv] DeLuca GC, Kimball SM, et. al.; Review: the role of vitamin D in nervous system health and disease. Neuropathol Appl Neurobiol, Aug;39(5):458-84, 2013.
[xxvii] Geib, Aurora, Vitamin D and cancer – nine facts “they” won’t tell you, 2, 25, 2012 newsletter, Natural News, online.
[xxix] Schwartz, 1993, M.S. and pregnancy
[xxx] Epstein, Samuel S., M.D., What’s In Your Milk? An Expose of Industry and Government Cover-up on the Dangers of the Genetically Engineered (rBGH) Milk You’re Drinking; Trafford Pub, 2007
[xxxi] Autier P, Boniol M, Pizot C, Mullie, P. Vitamin D status and ill health: a systematic review. Lancet Diabetes & Endocrinology, Early Online Publication, 6 December, 2013.
[xxxii] Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev. January 2014;72(1):48-54.
[xxxiii] Pludowski P, Holick MF, Pilz S, et al.; Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev. Aug;12(10):976-89., 2013.