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Diseases associated with low levels of 25-D

Related articles: Mistaking correlation for causation in vitamin D studies, Incidence and prevalence of chronic disease

According to the Marshall Pathogenesis, chronic inflammatory disease is caused by a microbiota of pathogens which interfere with proper functioning of the innate immune system. Patients suffering from inflammatory diseases have been shown to have lower than normal levels of 25-hydroxyvitamin D, and there are at least several reasons why bacterial pathogens generate this response.

  • When the immune system is challenged by pathogens, the body activates CYP27B1, causing more 25-D to be converted to 1,25-D.
  • When bacterial ligands block the Vitamin D Receptor, the Receptor is prevented from transcribing CYP24A1, a well-studied enzyme which breaks down excess 1,25-D.

A full understanding of vitamin D metabolism supports the conclusion that elevated 1,25-D and depressed 25-D are a result rather than a cause of the inflammatory process.

Lower than normal levels of 25-D have been independently associated both with all-cause mortality1 2 and a number of chronic inflammatory diseases. The following selection of diseases (and patient groups) have been observed to display the hallmarks of this kind of dysregulated vitamin D metabolism.

Anomalies

  • risk of breast cancer – In a 2011 study of nurses who were predominantly premenopausal, circulating 25-D levels were not significantly associated with breast cancer risk.
  • risk of prostate cancer – In a 2008 nested case-control study appearing in Journal of the National Cancer Institute, Ahn et al. found that patients with the lowest levels of 25-D also had the lowest risk of prostate cancer.68
  • risk of pancreatic cancer – Patients with the highest levels of 25-D were at greatest risk of pancreatic cancer.69
  • some rarer cancers70 – non-Hodgkin lymphoma or cancers of the endometrium, esophagus, stomach, kidney, ovary and pancreas
  • cancer mortality – A 2010 longitudinal study found that both high and low concentrations of plasma 25(OH)D were associated with elevated risks of overall and cancer mortality, and low concentrations are associated with cardiovascular mortality.71
  • neonatal vitamin D status and risk of schizophrenia – Danish neonates with the highest measurable levels of 25-D had a two-fold elevated risk of developing schizoprhenia. Based on this analysis, the population-attributable fraction associated with neonatal vitamin D status was 44%. The relationship was not explained by a wide range of potential confounding or interacting variables.72 This study is consistent with the explanation that higher rates of disease were caused by the immunosuppressive effects of heavy supplementation with vitamin D.
  • atherosclerosis in African Americans – Vitamin D is widely used to treat patients with osteoporosis and/or low vitamin D levels based on a medically accepted normal range. This “normal” range is typically applied to all race groups, although it was established predominantly in whites. It is thought that as low vitamin D levels rise to the normal range with supplementation, protection from bone and heart disease (atherosclerosis) may increase, as well. Blacks generally have lower vitamin D levels than whites, partly because their darker skin pigmentation limits the amount of the vitamin produced by sunlight. “Despite” these lower vitamin D levels and dietary calcium ingestion, blacks naturally experience lower rates of osteoporosis and have far less calcium in their arteries. Studies further reveal that black patients with diabetes have half the rate of heart attack as whites, when provided equal access to health care. A 2010 study (explained here) determined the relationship between circulating vitamin D levels and arterial calcium in 340 black men and women with type 2 diabetes.73 The team concluded that higher circulating levels of 25-D in blacks were associated with higher levels of calcified atherosclerotic plaque.

Notes and comments

Here's another study that is consistent with the new science of vitamin D: http://www.sciencedaily.com/releases/2010/12/101208083047.htm

A recent study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM) found that lower AND higher vitamin D levels were associated with an increased likelihood of frailty in older women. Women with vitamin D levels between 20.0 and 29.9 ng/ml were at the lowest risk of frailty.

This new study however found a U-SHAPED RELATIOSHIP between vitamin D levels and frailty; older women with vitamin D levels higher than 30 ng/ml and those with levels lower than 20 ng/ml were more likely to be frail.

“Vitamin D supplementation has grown in popularity, yet the association between vitamin D status and risk of adverse health outcomes in older adults is uncertain,” said Kristine Ensrud, MD, professor of medicine and epidemiology, Minneapolis VA Medical Center and the University of Minnesota and lead author of the study. “Our study did not find that higher vitamin D status was associated with lower subsequent risks of frailty or death. In fact, higher levels of vitamin D were associated with increased likelihood of frailty.”

“Evidence is lacking to support use of vitamin D supplementation for prevention of frailty and other outcomes including cancer or all-cause mortality,” said Ensrud.

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