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

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 diseasesHypovitaminosis 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.”


“…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

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

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

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

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 reactivityPatients 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

Journal of the American Academy of DermatologyA 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.”

Vitamin D for cognitive decline and Parkinson’s Disease

Archives of Internal MedicineTwo studies have just been published linking Vitamin D status to brain health. The authors of one paper appearing in Archives of Internal Medicine observe:

“To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia.”

They examined the correlation between low levels of serum 25-hydroxyvitamin D (25[OH]D) and the risk of serious loss of cognitive function in 858 adults over 8 years. What did the data show?

“…substantial cognitive decline on the MMSE [Mini-Mental State Examination] in participants who were severely serum 25(OH)D deficient (levels <25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (≥75 nmol/L)…the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D.”

Thus their conclusion:

Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.”

Archives of NeurologyThe same week a study was published in Archives of Neurology that examines the relation between Vitamin D and Parkinson Disease. The authors set out to:

“…investigate whether serum vitamin D level predicts the risk of Parkinson disease.”

They crunched the numbers for 3,173 men and women who were followed up over 29 years (the baseline serum 25-hydroxyvitamin D level was determined from frozen samples) for the relationship between serum vitamin D concentration and Parkinson disease. The data showed that:

Individuals with higher serum vitamin D concentrations showed a reduced risk of Parkinson disease. The relative risk between the highest and lowest quartiles was 0.33 [about a third less] after adjustment for sex, age, marital status, education, alcohol consumption, leisure-time physical activity, smoking, body mass index, and month of blood draw.”

Thus their conclusion:

“The results are consistent with the suggestion that high vitamin D status provides protection against Parkinson disease.”

The results of these studies are not surprising considering that Vitamin D is necessary for regulating the immune inflammatory response and both dementia and Parkinson’s involve chronic brain inflammation. By the way, as stated in Science Insider:

“Most Alzheimer’s disease (AD) researchers agree that the disease starts ravaging the brain years, if not decades, before the first symptoms of forgetfulness appear.”

New diagnostic criteria were just proposed at the International Conference on Alzheimer’s Disease in Honolulu.

Should you take Vitamin D for multiple sclerosis?

Current Neurology & Neuroscience ReportsThe ‘full-disclosure’ answer is that it depends upon what your lab tests reveal, taking into consideration that people with autoimmune disease may require higher amounts due to polymorphisms (genetic variants) of the vitamin D receptor. But as this paper published last month in Current Neurology & Neuroscience Reports begins:

“A relationship between vitamin D and several diseases, including multiple sclerosis (MS), has recently received interest in the scientific community. Vitamin D appears to have important actions beyond endocrine function, particularly for the immune system. Risk of development of MS, as well as disease severity, has been associated with vitamin D in a variety of studies.”

The authors conclude their review by stating:

“Given the current evidence of the potential benefits of vitamin D, it appears to be reasonable and safe to consider vitamin D supplementation at dosing adequate to achieve normal levels in patients with MS.”

Taking an aromatase inhibitor for early breast cancer? Check your vitamin D…

MaturitasA paper just published in the journal Maturitas (the journal of the European Menopause and Andropause Society) is a reminder the importance of vitamin D in breast cancer treatment. As the authors observe:

Aromatase inhibitors (AI) treatment leads to an increased risk of bone loss and fractures.

The authors examined a group of women with early breast cancer (EBC) and baseline Vitamin D deficiency (<30 ng/ml) who were treated with aromatase inhibitors. They followed serum levels of Vitamin D, bone mineral density (BMD), calcium intake, and the increase of serum 25(OH)D from 3 months of Vitamin D supplementation. What did their data show?

“At baseline [the beginning of AI therapy], 88.1% had 25(OH)D levels <30 ng/ml, 21.2% had severe deficiency (<10 ng/ml), and 25% of the participants had osteoporosis…We found a significant association between 25(OH)D levels and BMD…Plasma 25(OH)D levels improved significantly at 3 months follow-up in those treated with high dose Vitamin D supplements.”

This is only one aspect of the crucial role of Vitamin D in breast cancer prevention and treatment. The authors’ conclusion should be borne in mind by all those caring for or dealing with breast cancer:

“Our study suggests a high prevalence of commonly unrecognized Vitamin D deficiency in women with EBC treated with AI, a known osteopenic agent. Our results support the need for a routine assessment of 25(OH)D levels and, when necessary, supplementation in these patients.

For a discussion of aromatase inhibitors versus tamoxifen see this recent post.

Cholesterol crystals are a trigger for local and systemic inflammation. What then?

Journal of Clinical LipidologyThere is an evidence-based middle ground between the dogmas of those who assert that cholesterol is the main cause of cardiovascular disease and those who insist that its contribution is trivial. An interesting paper just published in the Journal of Clinical Lipidology illustrates an important mechanism by which cholesterol crystals trigger an inflammatory response.

“The response to arterial wall injury is an inflammatory process, which over time becomes integral to the development of atherosclerosis and subsequent plaque instability…In this review, a model of plaque rupture is hypothesized with two stages of inflammatory activity.”

In the first stage buildup of cholesterol crystals inside the “foam” cells that accumulate cholesterol induces their death (“apoptosis”); these dead cells elicit an inflammatory response that gathers more lipids into a vulnerable plaque. In stage two further expansion of crystals leads to intimal (blood vessel wall) injury…

“…which can manifest as a clinical syndrome with a systemic inflammation response…We recently demonstrated that when cholesterol crystallizes from a liquid to a solid state, it undergoes volume expansion, which can tear the plaque cap. This observation of cholesterol crystals perforating the cap and intimal surface was made in the plaques of patients who died with acute coronary syndrome.”

The authors refer to their previous work showing that alcohol, aspirin and statins can dissolve cholesterol crystals. Their conclusion:

“…we propose that cholesterol crystallization could help explain in part both local and systemic inflammation associated with atherosclerosis.”

American Journal of CardiologyOf course there are a number of other pathways to  inflammation in cardiovascular disease (please see related posts) but this is one of the reasons why I prefer that patients who have both high cholesterol and evidence of inflammation have the benefit of the natural statin derived from red rice yeast with the necessary supportive and protective cofactors including coenzyme Q10. This paper published recently in the American Journal of Cardiology provides evidence that red rice yeast is as effective and better tolerated than the commonly prescribed drug pravastatin:

“The present trial evaluated the tolerability of red yeast rice versus pravastatin in patients unable to tolerate other statins because of myalgia.”

The authors enrolled adults who had to discontinue statins due to muscle pain. Their findings are reassuring for those who prefer a natural alternative to pharma statins:

“The low-density lipoprotein cholesterol level decreased 30% in the red yeast rice group and 27% in the pravastatin group. In conclusion, red yeast rice was tolerated as well as pravastatin and achieved a comparable reduction of low-density lipoprotein cholesterol in a population previously intolerant to statins.”

This is a serious issue. Statin-associated myalgia or the diagnosis rhabdomyolysis does not do justice to the devastating side effects I recently observed in a patient who had a bad reaction to lovastatin.

AtherosclerosisBut how do we know when to intervene since high cholesterol alone is not a reliable risk factor and CRP (c-reactive protein) may not be elevated if the inflammation it is supposed to report is also preventing the liver from making it? One very helpful test for discriminating whether high cholesterol is contributing to vascular disease is the lipoprotein-associated phospholipase A2 (Lp-PLA2, PLAC) test, described here in an earlier post, that is associated specifically with inflammation in plaques. Another relies on the fact that it is cholesterol that has been damaged by oxidation that participates in the vascular lesion. To gauge this we can measure lipid peroxides. As this paper published in the journal Atherosclerosis documents, atherosclerosis is strongly associated with the presence of oxidized LDL:

“We investigated the relation between serum lipids including oxidized LDL and the severity of coronary atherosclerosis. Serum lipids and oxidized LDL was measured in 62 men (33–66 years), who underwent diagnostic coronary angiography and sonography to measure the carotid intima-media thickness…Regression analysis indicated that the carotid intima-media thickness and…the ox-LDL:LDL ratio…were the only factors associated independently with the severity of coronary atherosclerosis.”

Seminars in Thrombosis & HemostasisWe have also a fascinating study just published in the German medical journal Seminars in Thrombosis & Hemostasis that shows how oxidized LDL taken up by platelets induces inflammation in the blood vessel:

“Platelets are involved in the initiation of atherosclerosis by adherence to inflamed endothelium…In this study we investigated the functional consequences of oxidized low-density lipoprotein (oxLDL) uptake on platelet function and interaction with the endothelium.”

The authors were actually able to visualize the intracellular vesicles (microscopic sacs) containing the oxidized LDL using immunoflorescence microscopy. They made a fascinating observation: the platelets containing oxLDL provoked more cellular stickiness than regular LDL, oxLDL in the bloodstream or platelets without oxLDL.

“Furthermore, oxLDL-laden platelets induced foam cell development from CD34+ progenitor cells. On endothelial regeneration, oxLDL-laden platelets had the opposite effect: The number of CD34+ progenitor cells (colony-forming units) able to transform into endothelial cells was significantly reduced in the presence of oxLDL-platelets, whereas native LDL had no effect.”

This is a striking insight: it was only the oxidized LDL that prevented the endothelial cells (lining the blood vessel wall) from repairing, not the ‘native’ LDL.

Doctors and patients alike need to bear in mind the summary of their findings:

“Our results demonstrate that activated platelets internalize oxLDL and that oxLDL-laden platelets activate endothelium, inhibit endothelial regeneration, and promote foam cell development. Platelet oxLDL contributes significantly to vascular inflammation and is able to promote atherosclerosis.”

LipidsBut, you may ask, since diabetes and pre-diabetes (metabolic syndrome) are so strongly associated with cardiovascular disease shouldn’t there be some kind of connection here? This study published in the journal Lipids shows the evidence that there is.

Oxidized low-density lipoprotein (ox-LDL) plays a key role in the progression of atherosclerosis and diabetes complications. The aim of this study was first, to evaluate the association between ox-LDL and diabetes duration, and second, to examine serum level of ox-LDL in patients with prolonged diabetes and a desirable LDL-cholesterol level.”

It’s important to appreciate that the study group had ‘regular’ LDL in the desirable range, so a typical blood test would appear to be fine. Their very interesting observation is that the longer the person had diabetes (= the longer the risk factor for cardiovascular disease was building up) the more oxLDL they had in proportion to regular LDL:

“The ox-LDL-to-LDL ratio was dramatically higher in patients with diabetes duration >5 years in comparison to newly diagnosed patients and healthy participants. Ox-LDL was significantly associated with diabetes duration.”

Their final comments must be borne in mind by anyone caring for patients with both diabetes and a significant burden of insulin resistance:

“In conclusion, this study showed that the serum ox-LDL level increases with the length of diabetes, even though the patients’ LDL-cholesterol level is maintained at a desirable level. Our findings highlight that possibly more attention should be focused on markers of oxidative stress in the management of lipids in diabetic patients.”

Blood PressureCan we reliably measure oxidized LDL as implied by the lab test mentioned above? This study published in the journal Blood Pressure assure us that we can:

Cardiovascular diseases are accompanied by the presence of active oxygen species and organic free radical generation. The aim of this study was to examine the possibility of using malondialdehyde (MDA)-modified low-density lipoprotein (LDL) analyses as a diagnostic and prognostic biomarker.”

MDA-modified LDL is the same as oxLDL. What conclusion did they draw from their data?

“MDA-modified LDL estimation has a diagnostic accuracy and may be used as an independent biochemical marker for atherosclerosis.”

Truthfully, the functional approach to cardiovascular disease encompasses a number of other important aspects, but I’m wondering if you’ve gotten this far. As a reward for your diligence I’ll conclude this limited post with a few interesting items of satisfying practical significance. First we have a paper just published in The Journal of Steroid Biochemistry & Molecular Biology that reassures us of the benefit of vitamin D in the prevention and treatment of cardiovascular disease.

Journal of Steroid Biochem & Molec Bio“Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). In type 2 diabetics, the prevalence of vitamin D deficiency is 20% higher than in non-diabetics, and low vitamin D levels nearly double the relative risk of developing CVD compared to diabetic patients with normal vitamin D levels.”

The authors endeavored to uncover the mechanism behind vitamin D’s benefit:

“We found that 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] suppressed foam cell formation by reducing acetylated low density lipoprotein (AcLDL) and oxidized low density lipoprotein (oxLDL) cholesterol uptake in diabetics only. …In addition, 1,25(OH)2D3…improved insulin signaling, downregulated SR-A1 expression, and prevented oxLDL- and AcLDL-derived cholesterol uptake.”

You can remember their conclusion when getting your vitamin D level checked:

“The results of this research reveal novel insights into the mechanisms linking vitamin D signaling to foam cell formation in diabetics and suggest a potential new therapeutic target to reduce cardiovascular risk in this population.”

Anatolian Journal of CardiologyThrow some nuts in there too. A nice original study was published not long ago in The Anatolian Journal of Cardiology evaluated the benefit of hazelnuts (filberts) on atherosclerosis. The authors observed a number of interesting effects:

“Lag time for oxidation and α-tocopherol content of LDL were found to be increased while ox-LDL levels decreased during the study period. Total cholesterol, LDL-cholesterol, apolipoprotein (apo) B and apo B/apo AI ratio were found to be significantly lower while apo AI was higher. In respect to LDL subfraction, ratio of large/small LDL was significantly increased at the end of the study.”

They summed up their ‘take home’ message  on hazelnuts (which earlier posts suggest applies to most if not all nuts) accordingly:

“Hazelnut-enriched diet may play important role in decrease in atherogenic tendency of LDL by lowering the susceptibility of LDL to oxidation and plasma ox-LDL levels, and increasing the ratio of large/small LDL beyond its beneficial effect on lipid and lipoprotein levels.”

Digestive Diseases and SciencesHelicobacter pylori infection is, as you likely know, extremely common—according to WHO the most common infection in the world. It is a causative agent in almost all gastric ulcers. We see it here all the time. Finding out if you have it and getting it treated is another important therapeutic point for cardiovascular disease as this paper just published in the journal Digestive Diseases and Sciences reminds us. The authors investigated the impact of H. pylori infection on coronary atherosclerosis by examining the effects of infection on levels of serum lipid, high-sensitivity C-reactive protein (hsCRP) and oxidized low-density protein (oxLDL). What did their data show?

“The levels of total cholesterol, LDL, apolipoprotein B, serum hsCRP, oxLDL were significantly elevated and the severity of coronary atherosclerosis was significantly increased in H. pylorigroup.”

Their conclusion echoes the findings of other investigators:

“More serious coronary atherosclerosis was observed in CHD patients with H. pylori…infection. H. pylori…infection might be involved in coronary atherosclerosis by modifying serum lipids, enhancing LDL oxidation, and activating the inflammatory responses.”

Remember, the most reliable ways to diagnose H. pylori infection are by stool antigens, a provoked breath test, or PCR (DNA amplification). H. pylori antibodies are not dependable.

AngiologyAlthough it’s a major topic that deserves more space, mention at least much be made of the autoimmune aspect of cardiovascular disease as described in this recent paper published in the journal Angiology:

Atherosclerosis is now recognized as a chronic inflammatory disease and is characterized by features of inflammation at all stages of its development. It also appears to display elements of autoimmunity, and several autoantibodies including those directed against oxidized low-density lipoprotein (ox-LDL) and heat shock proteins (Hsps) have been identified in atherosclerosis.”

The authors then describe their investigation of immune complexes, antibodies and receptor signaling in this process. Certain cases demand a thorough evaluation of the autoimmune component of their CVD.

EndocrinologyIt would also not be appropriate to close without at least alluding to the influence of hormones on cardiovascular disease, a topic that has many aspects treated in other posts. This paper recently published in the journal Endocrinology makes a very important but little known point for men (for whom most everyone knows that too little testosterone or excess conversion to estrogen is a big risk factor for CVD). Testosterone is normally converted into its dihydrotestosterone form (DHT) which does a lot of the heavy lifting because it’s ten times stronger than the original. Men with prostate disease are commonly prescribed medications (including saw palmetto) that block the conversion of testosterone to DHT, but without first measuring the levels of the bioactive forms of these hormones. These medications don’t always help because not everyone with a prostate condition has too much DHT. Moreover, DHT is important for protection against cardiovascular disease. The authors…

“…investigated the effect of…dihydrotestosterone (DHT) on the rabbit atherogenesis in relation to…oxidized-low-density lipoprotein receptor-1 (LOX-1) and its downstream molecules.”

What did they find?

“…DHT significantly reduced HCD-induced [high cholesterol diet-induced] foam cell formation…DHT inhibited the formation of foam cells induced by oxidized low-density lipoprotein. Moreover, the expression of LOX-1 and inflammatory cytokines in the cultured macrophages was significantly suppressed by DHT.”

Inappropriately blocking the conversion of testosterone to DHT can thus open a door to cardiovascular disease. So remember, both gentlemen and ladies: no hormone interventions without measuring the free-fraction bioactive levels before and after!