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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
January 14, 2012

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More Evidence That Commensal Gut Bacteria Might Affect Autoimmune Disease
Zohydro, ("Vicodin times 10") May Soon Be on the Market
Drug Shortages Dominate 2011 Headlines
Subclinical Atrial Fibrillation Seems Associated with Increased Stroke Risk
Meta-Analysis: Exenatide(Byetta®) and Liraglutide(Victoza®) Promote Weight Loss,
   but Caution Advised
Homicide No Longer One of Top 15 Causes of Death in U.S.
Cure: No Longer a Four-Letter Word in HIV Research
When Parents Request Alternative Childhood Immunization Schedules:
  What's Your Comfort Level?
Excedrin, Bufferin, NoDoz, and Gas-X Prevention Recalled
More Evidence That Combined Tacrolimus and Narrowband UVB Are Useful for Vitiligo
PHARMA Buybacks, Spinoffs Cater to Investors
Brain Decline Deterred by Omega-3s & Vitamins
Low Vitamin D Linked to Depression

MM: Bacteria in general and probiotics specifically have an intense effect on health and the human condition. It is imperative that we have a healthy balance of gut organisms to not just ward off disease but maintain health. Placing these friendly microorganisms in close proximity to nutritional products seems to potentiate their positive effects. This is one of the reasons that we add probiotics to so many of the nutritional products and other compounds that we make at Mark Drugs. All too often we see that the “inactive” ingredients in a product may have a definitive effect on the patient. We strive to make that affect a positive one.
Nature 2011 Nov 24; 479:538
More Evidence That Commensal Gut Bacteria Might Affect Autoimmune Disease
In a mouse model of multiple sclerosis, absence of gut bacteria prevented the disease from developing.
The guts of all mammals are colonized by nonpathogenic commensal bacteria. We have long known that this "human microbiome" produces various beneficial molecules (JW Gen Med Jul 1 2010). However, evidence is accumulating to show that these nonpathogenic bacteria can influence mammalian diseases, such as inflammatory bowel disease (JW Gen Med Jun 19 2008), and even obesity (JW Gen Med Jan 2 2007).
A team in Germany adds to the evidence that commensal gut bacteria influence the development and severity of some autoimmune diseases. The researchers used a strain of transgenic mice that spontaneously develops a multiple-sclerosis–like disease. When these mice were raised in an entirely germ-free environment, none developed the disease. When these germ-free mice then were colonized with gut commensal bacteria, they promptly developed the disease. The investigators showed that colonization with gut commensal bacteria increased the number of interleukin-17–producing helper T (TH17) cells. An increased ratio of TH17 cells to regulatory T (Treg) cells enhances several autoimmune diseases (JW Gen Med Jun 12 2008).
Comment: This report reflects two important new themes in mammalian (and possibly human) biology. First, gut commensal bacteria might influence development of diseases that affect organs other than the gut. Second, gut bacteria that increase the proportion of TH17 cells or decrease the proportion of Treg cells might encourage autoimmune diseases.
Anthony L. Komaroff, MD Published in Journal Watch General Medicine January 12, 2012
Citation(s): Berer K et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 2011 Nov 24; 479:538.
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Zohydro, ("Vicodin times 10") May Soon Be on the Market
A pure, more powerful version of the nation's second most-abused drug, which has addiction experts worried that it could spur a new wave of abuse, may be on the market soon. The new product will contain pure hydrocodone. Four companies have begun patient testing, and one of them-Zogenix of San Diego-plans to apply early next year to begin marketing its product, Zohydro.
If approved, this will be the first time patients could legally buy pure hydrocodone. Existing products combine the drug with other analgesics, such as acetaminophen.
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MM: Mark Drugs continually addresses this problem and we are able to satisfy many of the needs that arise when there are drug manufacturer shortages. From re-packaging existing supplies to formulating products from the raw ingredients, Mark Drugs may be able to help your practice or institution in their time of need. Please call us to see how we may be able to help you.
Drug Shortages Dominate 2011 Headlines
There were more drug shortages in 2011 than ever before, thanks to a variety of manufacturing problems, financial challenges, and drug plants running afoul of FDA manufacturing practices resulting in lowered production. The number of companies supplying certain low-margin generics dwindled, sometimes to a single manufacturer. Raw materials for some drug ingredients ran short and competitors tried to fill the gap but couldn't boost production overnight. The GAO concluded that the only way to address the problem is to grant the FDA more power and require drugmakers to report potential upcoming shortages.
For about half of shortages, companies will not reveal the reason; however, the reason is important in helping to manage the shortfall. The most common reasons for drug shortages are increased demand, shortages of active ingredients, and manufacturing delays, whether brought on by corporate production upgrades or FDA-mandated remediation.
The drugs mostly on the shortage list include oncology, antibiotics, analgesics, anesthetics, dietary supplements, and antiinflammatories.
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Subclinical Atrial Fibrillation Seems Associated with Increased Stroke Risk
Subclinical episodes of atrial fibrillation (AF) predict a significantly increased risk for stroke, according to an international study in the New England Journal of Medicine.
Researchers recruited some 2600 patients aged 65 and over who'd just received a pacemaker or an implantable cardioverter-defibrillator. None had previous episodes of clinical AF. By 3 months, the devices detected subclinical episodes of AF (a heart rate of 190 or more per minute and lasting longer than 6 minutes) in about 10% of patients. Over a mean follow-up of 2.5 years, those with subclinical AF had more than twice the risk for ischemic stroke or systemic embolism as those without subclinical AF.
Asked to comment, Journal Watch Cardiology's Dr. Mark Link writes: "Although the current findings are by no means definitive for guiding anticoagulation decisions, they do support taking device-documented subclinical AF seriously. If an asymptomatic patient's CHADS2 score is high and subclinical episodes are frequent or prolonged, I would consider anticoagulation."

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Meta-Analysis: Exenatide(Byetta®) and Liraglutide(Victoza®) Promote Weight Loss, but Caution Advised
In trials involving the glucagon-like peptide-1 receptor (GLP-1R) agonists exenatide (Byetta) and liraglutide (Victoza), the drugs led to greater weight loss than other diabetes treatments. However, an editorialist in BMJ urges caution.
A meta-analysis of some 25 randomized trials examined weight loss resulting from GLP-1R agonist use among more than 6400 overweight patients with or without type 2 diabetes. Those on GLP-1R agonists lost an average 3 kg more than those on control treatments. The authors conclude that these drugs "should be considered in patients with diabetes who are obese or overweight."
An editorialist calls the results "modest" and the drugs costly. He concludes that, given the lack of prospective data on cardiovascular events and mortality, off-label use of the drugs for weight loss in patients without diabetes should not be recommended.
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Homicide No Longer One of Top 15 Causes of Death in U.S.
Homicide has fallen out of the top 15 causes of death in the U.S., according to preliminary mortality data for 2010 compiled by the CDC.
Also of note, the report states that from 2009 to 2010:

The authors note that enterocolitis due to Clostridium difficile has become a growing concern, with deaths increasing nearly 10-fold since 1999. In 2010, C. difficile was the 18th leading cause of death for people aged 65 and older.
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Cure: No Longer a Four-Letter Word in HIV Research
Inspired by a singular case of apparent cure, researchers are energetically pursuing new eradication strategies.
In 2009, researchers published a case report of an HIV-infected man with leukemia who had maintained drug-free virologic control for at least 20 months after receiving a stem-cell transplant from a donor who was homozygous for the CCR5{Delta}32 allele. In 2011, the patient was still free of HIV, more than 3.5 years after stopping antiretroviral therapy (ART; JW AIDS Clin Care Jan 10 2011). This singular case has prompted new efforts to cure HIV infection.
One major barrier to achieving a cure is the persistence of residual viremia in almost all patients on suppressive ART. Not only does ART fail to eradicate HIV from circulating CD4 cells, but it might not prevent cell-to-cell spread of the virus either (JW Infect Dis Sep 21 2011), for example in tissue reservoirs. Moreover, HIV reservoirs are established so soon after infection that even patients who initiate ART early — and thus have smaller reservoirs (JW AIDS Clin Care Oct 7 2011) — experience viral rebound when therapy is stopped (JW AIDS Clin Care Nov 8 2010).
For some time, researchers speculated that intensifying ART with an additional antiretroviral agent, such as raltegravir, would reduce residual viremia, but recent studies do not support this approach (JW AIDS Clin Care Apr 4 2011 and Apr 11 2011). Another potential strategy is to use drugs that have been shown to activate expression of latent HIV in vitro. Examples include disulfiram (an anti-alcoholism drug), vorinostat (a cancer-fighting agent), and interleukin-7, all of which are now being tested in clinical trials.
Finally, a truly novel approach to eradication is the use of zinc finger nuclease (ZFN) technology to disrupt the CCR5 coreceptor on CD4 cells, thereby making them less susceptible to infection. Phase I study data were presented at CROI, showing that the ZFN-modified CD4 cells engraft in both blood and rectal mucosa (JW AIDS Clin Care Apr 4 2011), and then a small clinical study was described at ICAAC (Abstract H2-794a). In that study, six patients on ART received a single infusion of ZFN-modified cells and then underwent a 12-week treatment interruption. All the patients experienced viral rebound during the interruption, but one returned to undetectable levels before restarting therapy. Notably, he was the only patient in the group who was CCR5{Delta}32 heterozygous at baseline, which resulted in him having a higher percentage of cells with both CCR5 gene copies disrupted after ZFN therapy than other patients did.
Although these various new approaches are in early phases of testing, the field of HIV eradication has clearly been revitalized. New basic-science investigations must be fast-tracked to inform novel translational trials, and a new funding opportunity created by the NIH this summer (the Martin Delaney Collaboratory) should help with this. Eventually, 2011 could well be recognized as the year that our efforts to cure HIV infection really took off.
Rajesh T. Gandhi, MD Published in Journal Watch HIV/AIDS Clinical Care December 30, 2011
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Pediatrics 2011 Dec; 128:1094
When Parents Request Alternative Childhood Immunization Schedules: What's Your Comfort Level?
In a survey of pediatricians, 60% were comfortable honoring such requests by parents.
Researchers surveyed primary care pediatricians about alternative childhood immunization schedules (ACISs) to find out how frequently parents requested ACISs, how comfortable pediatricians were with ACISs, and how willing pediatricians were to comply with parents' requests.
Of 475 primary care pediatricians in the Washington Chapter of the American Academy of Pediatrics, 311 (65%) completed the Internet-based survey, and 209 met eligibility criteria for the analysis (≥20 patients aged <2 years weekly). Most respondents (77%) reported that parents frequently or sometimes requested ACISs. Overall, 60% of respondents reported that they were comfortable using ACISs when requested by parents. Many pediatricians were comfortable delaying the following three vaccines for >4 months: hepatitis B (69%), varicella (53%), and inactivated poliovirus vaccine (45%). Few respondents were comfortable delaying Haemophilus influenzae type b vaccine (7%), pneumococcal conjugate vaccine (8%), and diphtheria-tetanus toxoids-acellular pertussis vaccine (9%). Parents with college degrees were more likely to request ACISs. Pediatricians in neighborhood or community clinic practice settings were significantly less comfortable using ACISs than those in small (≤2 physicians) practices.
Comment: The pediatrician's strong and definitive voice is the most effective tool that can be used against the practice of allowing alternative childhood immunization schedules. Delaying vaccination — any vaccination — tacitly gives credence to false notions about vaccines and threatens the child's health. I favor striking a balance by providing a definitive written statement against ACISs and creating a practice culture in which providers welcome questions, allow time to listen to concerns, and provide clear answers about the importance of vaccinations. A special article published in Pediatrics offers a concise discourse about the fallacies of the alternative approach and misconceptions of families and physicians who opt for alternative schedules.
Louis M. Bell, MD Published in Journal Watch Pediatrics and Adolescent Medicine January 4, 2012
Citation(s): Wightman A et al. Washington state pediatricians' attitudes toward alternative childhood immunization schedules. Pediatrics 2011 Dec; 128:1094.
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Excedrin, Bufferin, NoDoz, and Gas-X Prevention Recalled
Novartis announced on Sunday a voluntary recall of Excedrin, Bufferin, NoDoz, and Gas-X Prevention in the U.S. because the packages may contain stray tablets, capsules, or caplets from other Novartis products, as well as broken tablets.
The recall includes all lots of certain Excedrin and NoDoz products with expiration dates of December 20, 2014, or earlier, plus Bufferin and Gas-X Prevention products with expiration dates of December 20, 2013, or earlier. A link to the list of affected products is provided below.
List of Affected Products: http://www.novartis-otc.com/otc/index.html
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J Eur Acad Dermatol Venereol 2011 Dec; 25:1440
More Evidence That Combined Tacrolimus and Narrowband UVB Are Useful for Vitiligo
Combined treatment was better than ultraviolet treatment alone, and the effects were tacrolimus dose-dependent.
With few therapeutic options, vitiligo can be frustrating for both patients and physicians. Narrowband ultraviolet B (UVB) phototherapy and tacrolimus ointment have each been shown effective in some patients. These investigators evaluated a combination of both treatments in a double-blind trial in 46 patients with stable, symmetrical vitiligo. All subjects received total-body narrowband UVB two or three times per week (mean number of phototherapy treatments, 46; range, 17–68). Subjects were instructed to apply a formulation containing tacrolimus ointment 0.1% once daily to lesions on one side of the body and a formulation containing vehicle alone to the other side (average number of topical treatments, 148; range, 33–221).
The target lesion area was reduced a median of 42.1% on the tacrolimus side and 29.0% on the vehicle side, a statistically significant difference (P=0.005). Nine of the 40 patients who completed the trial were considered to be high responders, 19 were low responders, and 12 were nonresponders to the combined regimen. The reduction in target lesion area correlated with the number of tacrolimus applications but not with the number of narrowband UVB treatments. Treatment response did not correlate with Fitzpatrick sun-reactive skin type. Participants were followed for 3 months after therapy completion. No major relapses were observed in this period, and no phototoxic reactions occurred.
Comment: This large, systematic trial supports previous findings of efficacy with combined narrowband ultraviolet B and calcineurin inhibitors for vitiligo. Theoretical concerns about the long-term effects of this treatment and the possibility of increased skin cancer incidence may be somewhat allayed by observations that vitiligo patients seem to be resistant to nonmelanoma skin cancers. No evidence to date has demonstrated increased susceptibility to skin cancer in calcineurin inhibitor recipients. Nevertheless, this combination should probably be reserved for patients with vitiligo who fail to benefit from other forms of therapy.
Craig A. Elmets, MD Dr. Elmets has served on a Data Safety Monitoring Board for a manufacturer of topical tacrolimus regarding its safety in patients with atopic dermatitis.
Published in Journal Watch Dermatology January 6, 2012
Citation(s): Nordal EJ et al. Treatment of vitiligo with narrowband-UVB (TL01) combined with tacrolimus ointment (0.1%) vs. placebo ointment, a randomized right/left double-blind comparative study. J Eur Acad Dermatol Venereol 2011 Dec; 25:1440.
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PHARMA Buybacks, Spinoffs Cater to Investors
What can PHARMA do when R&D productivity is in the tank? Generally, the approach is to create a diversion to look at something else. For example, if PHARMA companies weren't buying back shares by the million this year, they were raising dividends or spinning off units.
Two big actions this year came from Pfizer and Abbott Laboratories. Pfizer announced a company-wide asset review, stirring up talk of a breakup, and announcing plans to shed its $1.9 billion nutritionals unit and $3.6 billion animal health business, but keep its generics unit. It also sold off its Capsugel business for $2.4 billion. How do they use the cash these deals generate…stock buybacks and dividends…at least partly.
Abbott also unveiled its breakup plans by announcing that it would split into two companies: A diversified medical products firm under the Abbott name and an as-yet-unnamed drugmaker.
Also, AstraZeneca and GlaxoSmithKline continued with their multibillion-dollar stock repurchasing plans. Amgen announced a $5 billion buyback plan. Teva joined in just before the holidays with a $3 billion plan. Merck raised its dividend 11%. Pfizer hiked its payout 10% and announced a $10 billion buyback plan. Shareholders may be able to expect the red-carpet treatment to continue since the companies need some investor loyalty to carry them through the patent-cliff years.
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vitalchoiceseafood&show_ issue_date=F&issue_id=000565932&lid=bks07Vd&uid=b1h1R7NC

Brain Decline Deterred by Omega-3s & Vitamins
Key nutrients linked to better thinking and less brain shrinkage among elders in a novel blood-based study
by Craig Weatherby
News from Oregon adds valuable evidence to a growing set of research suggesting that key nutrients can help keep aging brains healthy. The study is among the first to measure people’s blood levels of dozens of nutrients and compare those levels to participants’ cognitive health and brain volume. The Oregon study links higher blood levels of omega-3s from fish (EPA and DHA) and vitamins B, C, D, and E to better performance on tests of mental acuity (thinking and memory).  
Higher blood levels of omega-3s and vitamins B, C, D, and E were also linked to having less brain shrinkage.

(Brain shrinkage both promotes and characterizes Alzheimer’s disease and other forms of dementia.)

In contrast, the participants who had the lowest blood levels of nutrients did the worst on mental acuity tests and showed the most brain shrinkage. Low blood levels of the key nutrients in question suggest that a person is eating lots of “empty-calorie” foods … such as the processed, refined foods that predominate in the standard American diet. The results of prior studies comparing people’s diets to their brain health – most of which used nutrient-intake estimates based on diet surveys – have been mixed and inconclusive.But researchers are now using better methods to look for such links, with encouraging results. For example, see “Brain Benefits of Fish Bolstered by MRI Study”, “Fish Oil Aided Size and Health of Aging Brains”, “Fish Oil Lowers Cortisol and Body Fat Levels”, “Omega-3s Display More Brain-Mood Benefits”, and “Brain Aging: Vitamin B12 May Deter Shrinkage and Dementia”.

The new investigation from Oregon is more reliable than studies that only estimate participants’ nutrient intakes – very roughly – based on their responses to diet questionnaires. According to co-author Maret Traber, Ph.D., “The vitamins and nutrients you get from eating a wide range of fruits, vegetables and fish can be measured in blood biomarkers. I’m a firm believer these nutrients have strong potential to protect your brain and make it work better.” (OSU 2011) Professor Traber went on to make a timely point: “These findings are based on average people eating average American diets. If anyone right now is considering a New Year’s resolution to improve their diet, this would certainly give them another reason to eat more fruits and vegetables.” (OSU 2011)

Blood-brain study affirms value of omega-3s and key vitamins
The research was performed by scientists from Oregon Health and Science University and Oregon State University, and was funded by the U.S. National Institutes of Health (Bowman GL et al. 2011). Their novel study involved 104 elders with no strong risk factors for poor memory or mental acuity, whose average age was 87. The Oregon team measured blood levels of 30 different nutrients, and 42 participants also underwent MRI scans to measure their brain volume. The use of blood analysis avoided the problems inherent in relying on people’s flawed recollection of what they ate.

The best cognitive performance and biggest brain volumes were associated with two dietary patterns:

The Oregon group’s analysis took into account other factors that affect brain health and volume, such as lifestyle, age, gender, education, smoking, drinking, blood pressure, cardiovascular health, body mass index, and many others. As expected, much of the variation in the participants’ mental performance depended on these factors … but the levels of these key nutrients measured in participants’ blood accounted for 17 percent of the thinking and memory scores and 37 percent of the variation in brain size. And poor cognitive performance on the mental tests was associated with a higher intake of omega-6 fats – regular or “trans” form – which mostly come from certain common vegetable oils (corn, soy, safflower, sunflower, cottonseed), and the fried foods, margarine, fast foods, and the many nutrient-poor packaged or prepared foods made with them. That link fits with other evidence that the excess of omega-6 fatty acids in the standard American diet – which abound in certain common vegetable oils (corn, soy, safflower, sunflower, cottonseed) and the foods made with them – undermines brain health and volume.

The American diet’s characteristic “omega  imbalance” – far too much omega-6 fat, and not enough omega-3 fat – reduces the body’s absorption of omega-3s from plant foods (leafy greens, canola oil, flaxseed), seafood, and fish oil (Conklin SM, Manuck SB, Yao JK et al. 2007; Conklin SM et al. 2010) Most foods offered at VitalChoice.com bear the innovative Omega 3/6 Balance Scores developed by leading fatty acids researcher Professor William E. Lands, Ph.D.

These scores reflect the proportion of omega-3 to omega-6 fats each food contains, with positive numbers (e.g., +30) indicating that a food has more omega-3s than omega-6s. For more information on this health issue and our Balance Scores, click here.
Sources: Ahmad A, Momenan R, van Gelderen P, Moriguchi T, Greiner RS, Salem N Jr. Gray and white matter brain volume in aged rats raised on n-3 fatty acid deficient diets. Nutr Neurosci. 2004 Feb;7(1):13-20. Bowman GL et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology WNL.0b013e3182436598; published ahead of print December 28, 2011. Conklin SM, Runyan CA, Leonard S, Reddy RD, Muldoon MF, Yao JK. Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the anterior cingulate cortex of individuals with major depressive disorder. Prostaglandins Leukot Essent Fatty Acids. 2010 Feb-Mar;82(2-3):111-9. Epub 2010 Jan 8. Conklin SM, Manuck SB, Yao JK, Flory JD, Hibbeln JR, Muldoon MF. High omega-6 and low omega-3 fatty acids are associated with depressive symptoms and neuroticism. Psychosom Med. 2007 Dec;69(9):932-4. Epub 2007 Nov 8. Conklin SM, Gianaros PJ, Brown SM, Yao JK, Hariri AR, Manuck SB, Muldoon MF. Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults. Neurosci Lett. 2007 Jun 29;421(3):209-12. Epub 2007 Jun 2. Conklin SM, Gianaros PJ, Hariri AR et al. Dietary intake of the long-chain omega-3 fatty acids is associated with increased grey matter volume in the perigenual cingulated cortex. Abstract 1669. American Psychosomatic Society 65th Annual Meeting. Budapest, Hungary – March 7-10, 2007. Erickson KI, Suever BL, Prakash RS, Colcombe SJ, McAuley E, Kramer AF. Greater intake of vitamins B6 and B12 spares gray matter in healthy elderly: a voxel-based morphometry study. Brain Res. 2008 Mar 14;1199:20-6. Epub 2008 Jan 26. Oregon State University (OSU). Diet, nutrient levels linked to cognitive ability, brain shrinkage. December 28, 2011. Accessed at:
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Low Vitamin D Linked to Depression
Texas study affirms findings of most population studies and two of three clinical trials; Findings add another reason to monitor your levels
by Craig Weatherby
One in 10 Americans suffers from major depressive disorder. Aside from the harm depression causes patients and their families, this epidemic places an enormous burden on public and private health budgets and the overall economy. Most, though not all, of the many epidemiological studies published to date link low omega-3 blood levels to increased risk of depression. (See “Top Psych Panel Says Omega-3s Deter Depression, Bipolar Disorder” from the Omega-3s & Brain Health section of our news archive.)
 There’s less evidence concerning vitamin D and the incidence of depression … but most of the half-dozen or so existing epidemiological studies link low vitamin D levels to mood disorders. And two out of the three published clinical studies found that vitamin supplements improved mood (Jorde R et al. 2008; Shipowick CD et al. 2010; Dean AJ et al. 2011). Now, the results of the largest epidemiological investigation ever undertaken support the idea that low levels of vitamin D promote depression. 
Sizeable Texas study links low vitamin D to depression
University of Texas (UT) Southwestern Medical Center psychiatrists compared the vitamin D blood levels of 12,549 people to their history of depression, or lack of it. The data came from the Cooper Aerobics Center, which has worked with UT on a joint medical research program aimed at improving health and preventing a wide range of chronic diseases. The institute’s databases – known as the Cooper Center Longitudinal Study – contains detailed information from more than 250,000 clinic visits since Dr. Kenneth Cooper founded the center and its associated Cooper Institute in 1970.
 According to senior study author E. Sherwood Brown, M.D., “Our findings suggest that screening for vitamin D levels in depressed patients – and perhaps screening for depression in people with low vitamin D levels – might be useful. But we don’t have enough information yet to recommend going out and taking supplements.” Dr. Brown and his colleagues from The Cooper Institute linked higher vitamin D levels to a significantly decreased risk of depression … particularly among people with a prior history of depression. The study did not address whether increasing vitamin D levels reduced depressive symptoms.The scientists have not determined the exact relationship – whether low vitamin D contributes to symptoms of depression, whether depression itself contributes to lower vitamin D levels, or chemically how that happens.
 Dr. Brown – who leads the psycho-neuro-endocrine research program at UT Southwestern – noted that vitamin D affects neurotransmitters, inflammation, and other relevant factors, which could help explain the relationship with depression. As the UT press release noted, vitamin D levels are “… accepted as risk factors for a number of other medical problems: autoimmune diseases, heart and vascular disease, infectious diseases, osteoporosis, obesity, diabetes, certain cancers, and neurological disorders such as Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and general cognitive decline.” (UT 2012)
 How much vitamin D is enough?
Last year, the U.S. Institute of Medicine raised the recommended daily allowance (RDA) for vitamin D, suggesting that instead of just 200 IU per day, people aged one to 70 should take 600 international units (IUs) of vitamin D per day, and people older than 71 should aim for 800 IUs. For more on this, and the reasons why leading researchers welcomed that rise but wanted a bigger increase in the RDAs, see “Vitamin D RDAs Raised Substantially”, from the Vitamin D Sources and Doses section of our news archive. This was part of the response to the IOM action from leading researcher Michael F. Holick, Ph.D., M.D., Professor of Medicine, Physiology and Biophysics at Boston University Medical Center:
“… the [IOM’s recommended blood level minimum] of 20 ng/mL in my opinion is the barely adequate level of vitamin D, and to ensure vitamin D's maximum effect on bone health and overall health and well-being I encourage physicians to [advise their patients to] maintain blood levels of vitamin D above 30 ng/mL and up to 100 ng/mL, [which] is perfectly safe unless you have sarcoidosis.”
 How much do you need to reach that level? As Dr. Holick wrote, “We published a paper in Archives of Internal Medicine in December last year [2009] reporting that [among] my patients who have been taking the equivalent of 3000 IU of vitamin D a day for up to six years [that dose] was safe and effective in maintaining their blood levels of vitamin D between 40-60 ng/mL.”
Dr. Holick's expert advice is based on the well-documented safety of vitamin D intakes substantially above the new RDA levels, so it would seem to make sense to follow his guidance.
 Sources: Bertone-Johnson ER, Powers SI, Spangler L, Brunner RL, Michael YL, Larson JC, Millen AE, Bueche MN, Salmoirago-Blotcher E, Liu S, Wassertheil-Smoller S, Ockene JK, Ockene I, Manson JE. Vitamin D intake from foods and supplements and depressive symptoms in a diverse population of older women. Am J Clin Nutr. 2011 Oct;94(4):1104-12. Epub 2011 Aug 24. Dean AJ, Bellgrove MA, Hall T, Phan WM, Eyles DW, Kvaskoff D, McGrath JJ. Effects of vitamin D supplementation on cognitive and emotional functioning in young adults--a randomised controlled trial. PLoS One. 2011;6(11):e25966. Epub 2011 Nov 4. Ganji V, Milone C, Cody MM, McCarty F, Wang YT. Serum vitamin D concentrations are related to depression in young adult US population: the Third National Health and Nutrition Examination Survey. Int Arch Med. 2010 Nov 11;3:29. Hoang MT, Defina LF, Willis BL, Leonard DS, Weiner MF, Brown ES. Association between low serum 25-hydroxyvitamin D and depression in a large sample of healthy adults: the Cooper Center longitudinal study. Mayo Clin Proc. 2011 Nov;86(11):1050-5. Hoogendijk WJ, Lips P, Dik MG, Deeg DJ, Beekman AT, Penninx BW. Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch Gen Psychiatry. 2008 May;65(5):508-12. Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med. 2008 Dec;264(6):599-609. Epub 2008 Sep 10. Nanri A, Mizoue T, Matsushita Y, Poudel-Tandukar K, Sato M, Ohta M, Mishima N. Association between serum 25-hydroxyvitamin D and depressive symptoms in Japanese: analysis by survey season. Eur J Clin Nutr. 2009 Dec;63(12):1444-7. Epub 2009 Aug 19. Pan A, Lu L, Franco OH, Yu Z, Li H, Lin X. Association between depressive symptoms and 25-hydroxyvitamin D in middle-aged and elderly Chinese. J Affect Disord. 2009 Nov;118(1-3):240-3. Epub 2009 Feb 27. Shipowick CD, Moore CB, Corbett C, Bindler R. Vitamin D and depressive symptoms in women during the winter: a pilot study. Appl Nurs Res. 2009 Aug;22(3):221-5. UT Southwestern Medical Center (UT). Low vitamin D levels linked to depression, UT Southwestern psychiatrists report. January 5, 2012. Accessed at: http://www.utsouthwestern.edu/newsroom/news-releases/year-2012/vitamin-d-brown.html

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