Patients on steroids must have Vit D levels checked

Posted on October 5, 2011 by Dr. Jonathan

A study just published in The Journal of Clinical Endocrinology & Metabolism alerts clinicians to the need for vigilance in attending to vitamin D levels for patients on chronic steroid medication. The authors state:

“In many disorders requiring steroid therapy, there is substantial decrease in bone mineral density. The association between steroid use and 25-hydroxyvitamin D [25(OH)D] deficiency has not been confirmed in large population-based studies, and currently there are no specific vitamin D recommendations for steroid users…The aim of the study was to evaluate the association of serum 25(OH)D deficiency [defined as 25(OH)D <10 ng/ml] with oral steroid use.”

They performed a cross-sectional analysis on a nationally representative sample of 22,650 U.S. children and adults from the NHANES study. (This is considered representative of 286 million U.S. residents.) It’s not clear why they set the bar so high, but their main outcome measure was serum 25(OH)D levels below 10 ng/ml which is a severe deficiency. What did the data show?

“A total of 181 individuals (0.9% of the population) used steroids within the past 30 d. Overall, 5% of the population had 25(OH)D levels below 10 ng/ml. Among steroid users, 11% had 25(OH)D levels below 10 ng/ml, compared to 5% among steroid nonusers. The odds of having 25(OH)D deficiency were 2-fold higher in those who reported steroid use compared to those without steroid use. This association remained after multivariable adjustment and in a multivariable model using NHANES III data.”

It’s a bit of a jolt to know that as many as 5% of the US population has 25(OH)D levels below 10 ng/ml. The risk is doubled for those on chronic steroids. The authors conclude:

“Steroid use is independently associated with 25(OH)D deficiency in this nationally representative cohort limited by cross-sectional data. It suggests the need for screening and repletion in patients on chronic steroids.”

Vitamin D status is linked to vascular health

Posted on September 19, 2011 by Dr. Jonathan

It’s become well known that an optimal level of vitamin D is important for systems throughout the body. A study just published in the Journal of the American College of Cardiology illuminates in greater detail how vitamin D is necessary for blood vessels to relax and expand properly. The authors state:

“The primary objective of this study was to elucidate mechanisms underlying the link between vitamin D status and cardiovascular disease by exploring the relationship between 25-hydroxyvitamin D (25-OH D), an established marker of vitamin D status, and vascular function in healthy adults.”

Moreover…

“Vitamin D influences endothelial and smooth muscle cell function, mediates inflammation, and modulates the renin-angiotensin-aldosterone axis. We investigated the relationship between vitamin D status and vascular function in humans, with the hypothesis that vitamin D insufficiency will be associated with increased arterial stiffness and abnormal vascular function.”

They measured serum 25-OH D in 554 subjects and assessed endothelial (blood vessel lining) function by the ability to dilate the flow of blood in the brachial artery. Microvascular function was determined by the digital reactive hyperemia index (how readily blood flows into small surface capillaries). Carotid-femoral pulse wave velocity, the radial tonometry-derived central augmentation index and the subendocardial viability ratio were used to assess arterial stiffness. Vitamin D showed effects throughout these parameters:

“…25-OH D remained independently associated with flow-mediated vasodilation, reactive hyperemia index, pulse wave velocity, augmentation index, and subendocardial viability ratio. In 42 subjects with vitamin D insufficiency, normalization of 25-OH D at 6 months was associated with increases in reactive hyperemia index and subendocardial viability ratio, and a decrease in mean arterial pressure.”

I think it is fair to assert that no cardiovascular workup is complete without measuring 25-OH vitamin D. For optimal function in most cases my preference is at least 50 ng/ml (with the usual care for rare signs of intolerance—hypercalcemia, etc.). The authors conclude:

“Vitamin D insufficiency is associated with increased arterial stiffness and endothelial dysfunction in the conductance and resistance blood vessels in humans, irrespective of traditional risk burden.”

Vitamin D is an independent risk factor for multiple sclerosis

Posted on February 14, 2011 by Dr. Jonathan

Yet more evidence for the importance of immune regulation by vitamin D is presented in a paper just published in the journal Neurology. This study investigates the association between vitamin D and central nervous system (CNS) demyelination, the pathological process by which the fatty conductive nerve ‘insulation’ is damaged in disorders like multiple sclerosis. The authors set out to…

“…examine whether past and recent sun exposure and vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] levels) are associated with risk of first demyelinating events (FDEs) and to evaluate the contribution of these factors to the latitudinal gradient in FDE incidence in Australia.”

Over a period of three years they compared 216 subjects aged 18–59 years with a FDE to 395 controls matched for age, sex, and study region who had no CNS demyelination. Besides self-reported sun exposure by life stage the gathered objective measures of skin type and sun related damage, along with vitamin D status. Not surprisingly…

“Higher levels of past, recent, and accumulated leisure-time sun exposure were each associated with reduced risk of FDE… Higher actinic skin damage and higher serum vitamin D status were independently associated with decreased FDE risk. Differences in leisure-time sun exposure, serum 25(OH)D level, and skin type additively accounted for a 32.4% increase in FDE incidence from the low to high latitude regions.”

There was a 93% decrease in first demyelinating events for every 10 nmol/L increase in serum 25(OH)D). The authors conclude:

“Sun exposure and vitamin D status may have independent roles in the risk of CNS demyelination. Both will need to be evaluated in clinical trials for multiple sclerosis prevention.”

Osteoporosis and autoimmune inflammation

Posted on January 11, 2011 by Dr. Jonathan

Most readers here are well aware that osteoporosis results from a failure to maintain the resilient protein matrix (web, or ‘scaffolding’) of bone tissue, and that chronic inflammation is a prime contributor. A paper just published in Current Opinion in Endocrinology, Diabetes and Obesity examines the role of autoimmunity, now so widespread, in skeletal disease in general and osteoporosis in particular. The authors state:

“There is an increased risk of osteoporotic fractures and osteonecrosis often at a young age among patients with certain systemic autoimmune diseases. The loss of bone mineral density and bone integrity seen with these diseases often cannot be explained by traditional risk factors alone…”

The review studies that document that in rheumatoid arthritis the risk of osteoporosis is doubled, the risk for hip fracture is doubled or tripled, and there is a two to six-fold risk of vertebral fracture.

“Reduction in bone mineral density in RA may be influenced by immobility, inflammation associated with osteoclast activation, and medications used to treat the disease such as corticosteroids.”

In the case of lupus…

“Risk factors for osteoporosis in patients with SLE include high disease activity, vitamin D deficiency, renal disease, corticosteroid use, and premature ovarian failure from cytotoxic medications…”

The include a review of vitamin D in skeletal health and note that besides its well-known role in bone metabolism…

“…vitamin D is thought to have an immunomodulatory function, with deficient levels associated with impaired innate immune function and overexuberant adaptive immune function. Markers of inflammation have been associated with increased bone turnover and bone loss, a factor that is thought to be particularly at play among patients with inflammatory diseases. Consequently, low vitamin D levels can lead to accelerated bone loss among patients with inflammatory diseases. Put together, these observations move us beyond the calcitropic effects of vitamin D deficiency among patients with inflammatory diseases, and argue in favor of higher serum levels than are currently accepted.“

Importantly, the mechanisms by which inflammation disrupts skeletal are becoming known:

“Several studies have found an association between pro-inflammatory cytokines which play a role in bone resorption, such as TNF-α, IL-1 and IL-6, and the development of osteoporosis. Epidemiologic studies have shown levels of systemic inflammation to predict bone loss and future fracture. It is becoming clear that T cells play a pivotal role in regulating bone homeostasis through direct interactions with bone marrow, stromal cells and osteoblasts. Once activated, these T cells release osteoclastogenic cytokines and Wnt ligands.”

And it appears that steroid treatment does not undo the skeletal effects of inflammation:

“Among a cohort of 20 patients with SLE who had never been on steroids, osteocalcin levels were significantly lower, the urinary excretion of cross-links were significantly higher than in a non-SLE cohort, suggesting that there is decreased bone formation and increased bone resorption among steroid-naive SLE patients. Although these findings were attributed to the underlying disease, comparable results were detected among a steroid-treated cohort implying that steroid treatment does not undo the skeletal effects of inflammation in SLE as was speculated by some researchers.”

Summing up the studies linking osteoporosis to SLE, the authors state:

“These findings suggest that patients with more active inflammation are at greater risk for bone loss.“

Concerning the importance of vitamin D and autoimmunity, they comment:

“In light of the alarming prevalence of vitamin D deficiency seen worldwide, all patients with autoimmune disease should have at least a baseline screening 25-hydroxyvitamin level to screen for vitamin D deficiency. The only laboratory test usually required to ascertain the patient’s status is the 25-hydroxyvitamin D level with a goal of at least greater than 30 ng/ml.”

Their conclusion is heightened in significance by the sharp increase in autoimmune disorders in recent years:

“Bone loss and damage commonly occurs in patients with systemic autoimmune diseases. We are improving in our ability to diagnose and treat autoimmune diseases and their complications; yet osteoporosis and osteonecrosis remain growing comorbid conditions.”

Vitamin D considerations for childhood disorders of learning, behavior and development

Posted on October 13, 2010 by Dr. Jonathan

Evidence continues to accumulate regarding the important role of vitamin D in brain development and immune regulation. As such vitamin D is considered a neurosteroid. The authors of a paper published recently in the journal Psychoneuroendocrinology state:

“There is now clear evidence that vitamin D is involved in brain development.“

The specific focus of their study is schizophrenia as a developmental disorder. This is of interest to all parents and clinicians because the same mechanisms may be involved for neurodevelopmental disorders on a lower end of the spectrum of intensity including problems of learning and behavior.

“The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia…”

The authors developed an animal model to study the effects of vitamin D deficiency on brain development that included removing vitamin D from the diet during gestation while being sure to maintain normal calcium levels. The effects were dramatic:

“The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing.”

The summarize their findings by stating:

“Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that vitamin D acts as a neurosteroid with direct effects on brain development.“

The authors of a paper published in the FASEB Journal (The Journal of the Federation of American Societies for Experimental Biology) report their review of the scientific evidence for the link between vitamin D and brain dysfunction. The examination included:

“1) biological functions of vitamin D relevant to cognition and behavior; 2) studies in humans and rodents that directly examine effects of vitamin D inadequacy on cognition or behavior; and 3) immunomodulatory activity of vitamin D relative to the proinflammatory cytokine theory of cognitive/behavioral dysfunction.”

The data over a wide range of topics was mixed, but the overall weight of evidence significant:

“We conclude there is ample biological evidence to suggest an important role for vitamin D in brain development and function…While mechanistic and biological evidence strongly suggests that calcitriol is involved in brain development and critical brain functions, it has proved more difficult experimentally to demonstrate obvious effects of vitamin D inadequacy on cognitive or behavioral endpoints…Despite residual uncertainty, we believe the evidence overall suggests that supplementation to ensure adequacy is prudent…”

Consider also a paper published a few months ago in Acta Neurologica Scandinavica that further examines the role of vitamin D in the central nervous system:

“Epidemiological and experimental evidence suggest that vitamin D deficiency is a risk factor for multiple sclerosis and other autoimmune diseases…Hypovitaminosis D is also associated with several other neurological diseases that is less likely mediated by dysregulated immune responses, including Parkinson’s disease and Alzheimer’s disease, schizophrenia and affective disorders, suggesting a more diverse role for vitamin D in the maintenance of brain health.”

Moreover…

“…both the vitamin D receptor and the enzymes necessary to synthesize bioactive 1,25-dihydroxyvitamin D are expressed in the brain, and hypovitaminosis D is associated with abnormal development and function of the brain.”

They offer insight into why studying the effects of vitamin D in the brain may not be as simple as presumed—specifically the difference between the levels in peripheral blood and intrathecal levels (in the cerebrospinal fluid around the spinal cord and brain):

“We here review current knowledge on the intrathecal vitamin D homeostasis in heath and disease, highlighting the need to assess vitamin D in the intrathecal compartment.”

What other evidence is there for a link between low levels of vitamin D and psychiatric diagnoses? A recent paper published in The Journal of Steroid Biochemistry and Molecular Biology examines the association between low vitamin D and psychiatric diagnoses in a group of Swedish patients. For 117 subjects serum 25-hydroxy-vitamin D (25-OHD) and plasma intact parathyroid hormone (iPTH) was collected, together with demographic data and psychiatric diagnoses.

“Their median 25-OHD was considerably lower than published reports on Swedish healthy populations. Only 14.5% had recommended levels…Patients with ADHD had unexpectedly low iPTH levels…having a diagnosis of autism spectrum disorder or schizophrenia predicted low 25-OHD levels. Hence, the diagnoses that have been hypothetically linked to developmental (prenatal) vitamin D deficiency, schizophrenia and autism, had the lowest 25-OHD levels in this adult sample, supporting the notion that vitamin D deficiency may not only be a predisposing developmental factor but also relate to the adult patients’ psychiatric state.”

And their data yielded another very relevant observation:

“This is further supported by the considerable psychiatric improvement that coincided with vitamin D treatment in some of the patients whose deficiency was treated.”

But how prevalent is vitamin D deficiency among American children? A paper published in the journal Pediatrics last year should serve as a reminder to both parents and doctors. The authors set out to…

“…determine the prevalence of 25-hydroxyvitamin D (25[OH]D) deficiency and associations between 25(OH)D deficiency and cardiovascular risk factors in children and adolescents.”

What did the data show? Even using a low reference range thatand is presently considered too low by most labs and has been updated:

“Overall, 9% of the pediatric population, representing 7.6 million US children and adolescents, were 25(OH)D deficient and 61%, representing 50.8 million US children and adolescents, were 25(OH)D insufficient.”

Even by outdated standards that amounts to 70% of the pediatric population in the US. Hence their conclusion:

“25(OH)D deficiency is common in the general US pediatric population and is associated with adverse cardiovascular risks.”

We can see from the above that the risks include brain health and development as well. How do you find out if your child’s (and your) vitamin D level is sufficient? Since individual genetic and circumstantial needs can vary so greatly, taking out the guesswork with a serum 25(OH)D (25-hydroxy vitamin D) test is best.

Facial skin aging and vitamin D

Posted on October 12, 2010 by Dr. Jonathan

A study just published in the journal Cancer Causes & Control throws light on the link between skin aging and vitamin D levels. The authors set out to investigate…

“…whether individuals with less facial aging due to photoprotection are more likely to have low vitamin D as measured by 25(OH) vitamin D levels.”

They examined 45 females over age 40 taking into consideration menopausal and smoking status, history of skin cancer, use of supplements, and when the blood draws were done according to season. Then…

“A single-blinded, dermatologist evaluated standardized digital facial images for overall photodamage, erythema/telangiectasias, hyperpigmentation, number of lentigines, and wrinkling.”

The data painted a striking picture:

“…women with lower photodamage scores were associated with a 5-fold increased odds of being vitamin D insufficient. Low scores for specific photodamage parameters including erythema/telangiectasias, hyperpigmentation, and wrinkling were also significantly associated with vitamin D insufficiency.”

What does this mean in practical terms? As previous studies have reported, it is usually not possible to optimize vitamin D levels by sun exposure only without an undesirable price to pay in skin damage. As other investigators have asserted, supplementation of vitamin D according to your specific needs as determined by the 25(OH)D (25-hydroxy vitamin D) blood test is best evidence-based method.

More evidence to give your children vitamin D to prevent flu

Posted on October 7, 2010 by Dr. Jonathan

You’re probably aware of the profound importance of vitamin D for immune system regulation, and some of the earlier science that supports its use to prevent opportunistic infections. Now research just published in the American Journal of Nutrition adds more evidence for the use of vitamin D supplementation to prevent flu in kids attending school.

“From December 2008 through March 2009, we conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D3 supplements (1200 IU/d) with placebo in schoolchildren. The primary outcome was the incidence of influenza A, diagnosed with influenza antigen testing with a nasopharyngeal swab specimen.”

The data showed that while 18.6% of the children in the placebo group came down with influenza A, only 10.8% in the vitamin D3 group did. Naturally…

“The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements…”

Their data yielded another interesting finding:

“In children with a previous diagnosis of asthma, asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D3 compared with 12 children receiving placebo.”

That’s an 83% reduction in the relative risk of having an asthma attack. This is biologically plausible considering the importance of vitamin D for immune inflammatory disorders. The authors conclude by stating:

“This study suggests that vitamin D3 supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren.”

Bear in mind, however, that individual needs vary greatly. The best way to objectively know that your child’s vitamin D needs are being met (or your own) is with a blood test for 25-hydroxy vitamin D.

Breast cancer risk decreased with higher vitamin D

Posted on September 21, 2010 by Dr. Jonathan

A study just published in the journal Cancer Epidemiology, Biomarkers & Prevention increases the weight of evidence for the importance of vitamin D in breast cancer prevention. The authors state:

“High 25-hydroxyvitamin D [25(OH)D] serum concentrations have been found to be associated with reduced breast cancer risk. However, few studies have further investigated this relationship according to menopausal status, nor have they taken into account factors known to influence vitamin D status, such as dietary and serum calcium, parathyroid hormone, and estradiol serum levels.”

The authors investigated the connection in 636 French women diagnosed with breast cancer compared with 1,272 controls with considerations for age, menopausal status, and other variables. What did the data show?

“We found a decreased risk of breast cancer with increasing 25(OH) vitamin D3 serum concentrations among women in the highest tertile. We also observed a significant inverse association restricted to women under 53 years of age at blood sampling.”

They concluded from their evidence:

“Our findings support a decreased risk of breast cancer associated with high 25(OH) vitamin D3 serum concentrations, especially in younger women, although we were unable to confirm a direct influence of age or menopausal status… the maintenance of adequate vitamin D levels should be encouraged by public health policy.”

In other words, vitamin D concentrations were found to be a significant influence regardless of age or menopausal status. How do you find out how you’re doing with vitamin D? Ask your doctor for a 25-hydroxyvitamin D [25(OH)D] blood test.

Vitamin D for mold allergies

Posted on August 19, 2010 by Dr. Jonathan

Mold allergies are a vexing problem for many whose immune system is compromised, especially when exposure at home or work is unavoidable. Research just published in The Journal of Clinical Investigation provides welcome evidence that Vitamin D substantially reduces the allergic response to mold and promotes tolerance.

“The development of Th2 responses, as in asthma and allergic bronchopulmonary aspergillosis (ABPA), is driven by both genetic and environmental factors. Mechanistically, inhaled allergens are presented by lung DCs [dendritic cells] to naive T cells, which leads to induction of allergen-specific Th2 cells…In patients with ABPA, immunological responses to a variety of A. fumigatus [mold] antigens result in a heightened Th2 response and an elevated IgE level.”

To determine what determines a Th2 allergic response as opposed to Treg (regulatory T cell) tolerance the authors compared a groups of cystic fibrosis patients suffering from ABPA and and another group without it by measuring several key immune factors. Their findings have great practical significance:

“Furthermore, we discovered that ABPA correlated with vitamin D deficiency, and supplementation with vitamin D potentiated Treg-mediated regulation of Th2 reactivity…Patients with ABPA had significantly lower 25-OH vitamin D (the major circulating form of vitamin D3) levels compared with non-ABPA controls, and the mean level was significantly below the recommended level of 30 ng/ml in CF.”

Any doctor who is diligently testing their patients for Vitamin D insufficiency knows that suboptimal levels are surprisingly common. Could this have something to do with relative malnutrition, time of year or geographic location? The authors’ data says “no”:

“Notably, there was no significant difference in BMI or vitamin A and E levels between ABPA and non-ABPA patients, suggesting that the relative vitamin D deficiency was not associated with relative malnutrition… To exclude potential environmental/geographical differences in our cohort, we used geographical information systems (GIS) mapping to determine whether there was geographical clustering of ABPA patients versus non-ABPA patients; however, this analysis did not identify significant clustering… Finally, there was no significant difference in terms of month of accrual in the study between the ABPA or non-ABPA cohort… Taken together, these findings strongly suggest that the relative 25-OH vitamin D deficiency observed in ABPA patients was not a surrogate marker of another variable…”

This research adds to the immense body of evidence regarding the importance of Vitamin D for immune regulati0n and the treatment of allergies and autoimmune diseases (along with a host of other conditions). How can you reliably know your Vitamin D status? Ask your doctor for a 25-hydroxy vitamin D blood test, and look for a level closer to the middle of the typical lab’s reference range rather than toward the bottom.

Supplementation is the safest way to get Vitamin D

Posted on July 29, 2010 by Dr. Jonathan

A study published just last month in the Journal of the American Academy of Dermatology addresses the question: “isn’t sun exposure (cutaneous photosynthesis) sufficient for satisfying my needs for Vitamin D?”

“We sought to provide estimates of the equivalency of vitamin D production from natural sun exposure versus oral supplementation.”

The authors went about determining the sun exposure times needed to achieve serum vitamin D3 concentrations equivalent to 400 or 1000 IU vitamin D for people with different skin types living in Miami, FL, and Boston, MA, during the months of January, April, July, and October. What did they conclude from their data?

“Although it may be tempting to recommend intentional sun exposure based on our findings, it is difficult, if not impossible to titrate [calibrate the dose of] one’s exposure. There are well-known detrimental side effects of ultraviolet irradiation. Therefore, oral supplementation remains the safest way for increasing vitamin D status.”