To access the Libraries please log in:

VitaminD_pillsMany people are not aware that vitamin D is not a vitamin. This secosteroid hormone has many important functions and there are several metabolites (forms) of vitamin D. There is no Recommended Daily Allowance (RDA) for vitamin D, because it's endogenously produced by humans in the presence of a few minutes of sunlight. See Vitamin D.

Abnormally high vitamin D (1,25-D) is known as hypervitaminosis-D and it may cause a variety of symptoms such as constipation, anorexia, dehydration, fatigue, irritability, vomiting, headache, weight loss, polyuria, polydipsia and hypercalcemia.

Elevated 1,25-D also stimulates bone osteoclasts, causing bone to be resorbed (dissolved) back into the bloodstream. Not only does this lead to osteoporosis, but also to calcium being deposited into soft tissue of the body, including the lungs, breasts, and the kidneys (where it forms kidney stones).

It's interesting to note that vitamin D3 (cholecalciferol) is used as a toxicant in rat and mouse poisons. The excessive vitamin D mobilizes calcium from the rodent's bones into its bloodstream, producing hypercalcemia and heart failure. See Rodenticide.

Levels of 25-D above 50ng/ml have been correlated with an increased level of mortality. See study1 and study2.

It's trendy to supplement with vitamin D but too much can cause problems.  In this study from the general practice sector, a reverse J-shaped relation between the serum level of 25(OH)D and all-cause mortality was observed, indicating not only a lower limit but also an upper limit. The lowest mortality risk was at 50-60 nmol/liter (20-24 ng/ml).  

August 4, 2015 Study: Hi-Dose Vitamin D Shows No Benefit for Postmenopausal Women
"Study results do not justify the common and frequently touted practice of administering high-dose cholecalciferol to older adults to maintain serum 25 (OH) D levels of 30 ng/mL or greater," the team concluded, "Rather, study results support the Institute of Medicine's conclusion that vitamin D repletion is a serum 25(OH)D level of 20 ng/mL or greater."

Alarming trend

Supplementation with vitamin D to prevent diseases is an alarming trend based on faulty studies or faulty conclusions of clinical studies.

Epidemiological studies touting the benefits of supplemental vitamin D, and declaring that low vitamin D causes disease, are flawed because they only measure 25-D. Doctors and scientists have misinterpreted the results because they fail to understand that levels of 25-D are probably suppressed by elevated 1,25-D due to the disease process.

In other words, disease causes low 25-D; low 25-D does not cause disease. Only studies that measure both 25-D and 1,25-D and are analyzed with an understanding of their relationship to each other in health and disease will yield valid, pertinent results.

Dysregulated vitamin D metabolism


Normally, production of 1,25-D is tightly controlled by the kidneys in response to a complex system of hormonal regulation. But when nucleated cells are infected with bacterial pathogens, 1,25-D is generated by the inflammatory response. This causes the level of 1,25-D to exceed the upper limit normally controlled by the kidneys.

Elevations in 1,25-D are created by immune system (macrophages) attempts to activate the Vitamin D Receptor (VDR) in order to transcribe anti-microbial peptides. But this action is blocked by proteins secreted by the L-form bacteria as a strategy to avoid destruction.

The result is dysregulated vitamin D metabolism caused by the disease process.

Assessing vitamin D

It's essential to measure both vitamin D metabolites (25-D and 1,25-D) to determine the relevance of the results. The level of 25-D doesn’t directly reflect the level of 1,25-D. The low 25-D often found in sick patients does not mean their 1,25-D (the active metabolite) is also decreased. In fact, the opposite (high 1,25-D) is usually true.

Patients with chronic Th1/Th17 inflammation (who have not been supplementing with vitamin D) often have a low level of 25-D while the level of 1,25-D is high. Testing only 25-D, as is usually done, may result in the erroneous conclusion that the patient in 'deficient' in vitamin D. The key result is the level of 1,25-D because it is the active metabolite; 25-D function primarily as an inert precursor. See Diagnostic Tests.

Vitamin D supplementation

We recommend avoiding vitamin D supplementation (in all forms) in order to reduce the level of 25-D. This recommendation is made, not because vitamin D is immuno-suppressive (there's insufficient scientific evidence to make this claim) but because lowering 25-D to a reasonable level can help decrease elevations in 1,25-D and thus reduce inflammatory symptoms.

In most, or many, a 25-D level of 10-20ng/ml appears to be enough to maintain a normal 1,25-D (and not promote excessive production of 1,25-D which may cause inflammatory symptoms).

This study of 25-hydroxyvitamin-D (25-D), published August 2012 in the Journal of Endocrinology Metabolism, found "if blood contains less than 2.5 ng/mL of 25-D (6.24 nmol/L), mortality is 2.31 times higher. However, if the blood contains more than 56 ng/mL of 25-D (139.7 nmol/L), mortality is higher by a factor of 1.42. Both values were compared to 20 ng/mL of 25-D (49.9 nmol/L), where the scientists saw the lowest mortality rate."
A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study.

On Oct. 24, 2012 the journal PLOS ONE published new guidelines regarding vitamin D supplementation from the Institute of Medicine, based on this study by Loyola University Chicago Stritch School of Medicine researchers.
Mortality Rates Across 25-Hydroxyvitamin D (25[OH]D) Levels among Adults with and without Estimated Glomerular Filtration Rate <60 ml/min/1.73 m2: The Third National Health and Nutrition Examination Survey

The new guidelines advise that almost all people get sufficient vitamin D when their blood levels are at or above 20 nanograms per milliliter (ng/ml). Older guidelines said people needed vitamin D levels above 30 ng/ml.

This is not much higher than our recommended range of 10-20ng/ml which we believe is adequate to ensure production of enough 1,25-D (the active metabolite) that is essential for many metabolic functions. We advise 25-D not go too high because that encourages elevation of 1,25-D in people with chronic inflammation and dysregulated vitamin D metabolism, which may increase inflammatory symptoms. The symptom relief some experience with higher levels of 25-D likely happens because 25-D increases production of 1,25-D which can suppress immune system function and reduce inflammatory symptoms related to the immune system's efforts to eliminate intracellular pathogens.

If your doctor wants to see your 25-D higher than the IT recommendation, it's fine to increase it to 20ng/ml. There is NO evidence that 25-D suppresses the immune system, but a higher level than that could increase inflammatory symptoms.

The Mayo Clinic has published a long list of side effects of vitamin D supplementation.

If needed, it's best to increase 25-D by increasing your intake of foods high in vitamin D, rather than supplementation or sunlight exposure. Then recheck your 25-D level in a couple months to make sure it's not too high or too low.

Experts are becoming alarmed

A "father" of 1,25-D and VDR research is Anthony Norman; once a proponent of vitamin D supplementation he now says:

"The nutritional guidelines for vitamin D3 intake must be carefully reevaluated to determine the adequate intake. Supplementing the entire population with vitamin D may seem attractive, but there are some reasons to move slowly. The purpose of the adequate intake recommendations for vitamin D put forth by the Food and Nutrition Board of the Institute of Medicine in 1999 was to provide guidelines of vitamin D3 intake to achieve normal serum levels of 25(OH)D. This was a very difficult goal to achieve, however, given that a quantitative relation of vitamin D's (ie, operation of the vitamin D endocrine system) contribution to good health was not clearly appreciated by 1997."

"Vitamin D is not technically a vitamin, ie, it is not an essential dietary factor; rather, it is a prohormone produced photochemically in the skin from 7-dehydrocholesterol. Frequent errors occur in research studies when authors use vitamin D as a synonym for 1α,25(OH)2D3, sometimes even in the methods sections of articles. There are very significant structural and biological differences between 1α,25(OH)2D3 and vitamin D3. For example, a reader sees the following statement in the results or discussion section of an article, "the animals or subjects received a standard vitamin D dose that would not cause hypercalcemia," he or she would make a serious error of interpretation if he or she had not carefully read the methods section to learn that "all subjects received a dose of 1.5 micrograms of 1α,25(OH)2vitamin D3."

Dr. JoAnn Manson, who is overseeing the largest vitamin D preventive study (VITAL). says doctors and patients should follow the Institute of Medicine and USPSTF guidelines: doctors should not order vitamin D blood tests for all of their patients, and people shouldn't take more than 600 IU of the vitamin if they are otherwise healthy.
Manson JE, Bassuk, SS. Vitamin D Research and Clinical Practice At a Crossroads. JAMA. Published online February 19, 2015.

The rush to increase vitamin D consumption among the general population is reminiscent of the precipitous advice to menopausal women a few decades ago to adopt hormone supplementation, which was based on faulty study conclusions. The current advice to supplement vitamin D is tantamount to a mass experiment without giving the participants informed consent. The results could be catastrophic, considering the reality of the underlying science, with an eventual explosion of chronic inflammatory disease.

Thankfully, experts are expressing alarm about the blanket recommendation to supplement with vitamin D. Although this article doesn't correctly identify dysregulated vitamin D, the author states that Skepticism Grows Regarding Widespread Vitamin D Supplementation.

Despite the scientific attention being paid to vitamin D, experts caution that claims of wide-ranging health benefits are not yet supported by clinical evidence. Vitamin D shows promise but research still lagging

Although their rationale is wrong these doctors are also questioning vitamin D supplementation:
Are We Overselling The Sunshine Vitamin?

This article is from the 2010 Spring edition of American Journal of Kidney Diseases: Pitfalls of Vitamin D Replacement Therapy

From Forbes online, here is a blog posted August 18, 2010, which summarizes some of the problems with drawing conclusions about vitamin D. It's called "Vitamin D: Still More Questions Than Answers."

"Unfortunately, vitamin D information has become something of a shell game, with positions that overstate the strength of the evidence. As dermatologists, for example, we know the carcinogenic potential of sunlight, but there are now opposing groups that advocate health by increasing vitamin D through sun exposure." See Vitamin D- Myths or Truths?

Studies

Dr. Michael Kleerekoper in Ann Arbor says "There remain questions of causality, with the bulk of literature taking the form of observational, correlative studies. "

This report from the Institute of Medicine concludes: Scientific evidence indicates that calcium and vitamin D play key roles in bone health. The current evidence, however, does not support other benefits for vitamin D or calcium intake. More targeted research should continue. However, the committee emphasizes that, with a few exceptions, all North Americans are receiving enough calcium and vitamin D. Higher levels have not been shown to confer greater benefits, and in fact, they have been linked to other health problems, challenging the concept that "more is better."

This recent review of the literature, Vitamin D and Calcium: Systematic Review of Health Outcomes, concluded:

"The majority of the findings concerning vitamin D, calcium, or a combination of both nutrients on the different health outcomes were inconsistent. Synthesizing a dose-response relation between intake of either vitamin D, calcium, or both nutrients and health outcomes in this heterogeneous body of literature proved challenging."

Please access this link for a list of recent studies that challenge the assumption of the benefits of vitamin D supplementation.

Solution

The so-called vitamin D experts who are pushing supplementation (some have a worrisome conflict of interest) need to be called to account for their interpretation of the science of vitamin D metabolism. Studies need to be conducted that measure both vitamin D metabolites to learn the effect of each on the disease process. Long-term studies of vitamin D supplementation need to be conducted before the general population is given any more advice about increasing vitamin D intake.

Discussing this issue with your doctor

Doctors who advise vitamin D supplementation mean well but may not understand the science of dysregulated vitamin D metabolism in chronic disease. If your doctor wants you to supplement with vitamin D, tell him/her that you’re alarmed by the growing concern about vitamin D supplementation, and that you prefer to wait for definitive research because you’re not willing to be a research subject in a poorly designed mass experiment. Keep in mind that patients refuse their doctor’s instructions all the time - you may have to agree to disagree – it’s your body and your decision.