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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
December 22, 2012

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Rudolph's Red Nose
Painful Diabetic Neuropathy: A Three-Drug Comparison
'Z' Drugs May Help Insomniacs Fall Asleep, but Effect Is Small
ACOG Offers Updated Guidelines on Weight Gain During Pregnancy
Alzheimer Disease Risk Variant Discovered
Man's Best Friend Sniffs Out C. difficile
Nasal Gel Recalled Due to Burkholderia cepacia Contamination
Amoxicillin Offers Little Benefit for Uncomplicated Lower Respiratory Tract Infection
Whiplash: Active Intervention Shows No Lasting Benefit
Long-Term Aspirin Use Associated with Small Increased Risk for Macular Degeneration
Diabetes and Weight-Loss Results Found Modest with Intensive Lifestyle Intervention
Thyroid Function and Risk for AF: A Linear Relation
Cases of Gonorrhea and Chlamydia on the Rise
Fish Fraud Marches On
Are Stinky Cheeses Heart-Healthy?

BMJ 2012 Dec 17; 345:e8311
Rudolph's Red Nose
Rudolph, Santa's lead reindeer, has a red nose. But why? Finally, investigators have forensic tools to answer this age-old question.
New, hand-held, intravital video microscopes allow direct visualization of blood vessels. These authors compared the functional morphology of nasal microcirculation in humans and in reindeer to test the hypothesis that Rudolph's luminous red nose is caused by a highly dense and rich nasal microcirculature.
High-quality images were captured of the nasal septum and inferior turbinate of two adult reindeer subjects and five human controls. Mean perfused vessel density in humans was 15 mm/mm2. Reindeer nasal mucosa had abundant microcirculation, with a mean perfused density of 20 mm/mm2. The flow index was similar in reindeers and humans. Reindeer blood was pumped in pulses; no blood cells were seen in the vascular lumens during diastole. The investigators conclude that Rudolph's nose is red because it is richly supplied with red blood cells, because it has a highly dense microvasculature, and because the reindeer's nose is physiologically adapted to avoid freezing while flying and to regulate brain temperature while pulling a sled under extreme temperatures.
Comment: An accompanying figure shows a distinct pink color at the tip of a Norwegian reindeer in arctic weather — perhaps the legend of Rudolph is based on fact. Rudolph and other arctic reindeer have red noses because their noses are richly vascularized. They need high vascularity to dissipate heat while panting through their noses and mouths. The relevance to red human noses remains speculative.
Mark V. Dahl, MD Published in Journal Watch Dermatology December 21, 2012
Citation(s): Ince C et al. Why Rudolph's nose is red: Observational study. BMJ 2012 Dec 17; 345:e8311.
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MM: Diabetic neuropathy and other neuropathic pain are examples of conditions that are typically not life-threatening but are certainly life tormenting. Although the oral medications discussed in this article show some efficacy, the potential for adverse reactions is quite significant. For many years the staff at Mark Drugs has researched and worked with physicians to treat these painful conditions by using prescription transdermal creams and gels that are applied to the local site of discomfort, to localized trigger points that affect specific painful areas and/or to dermatomes located along the spine. The creams and gels contain a combination of medications that complement each other and block local pain receptors thereby preventing the "message of pain" from being transmitted to the brain. These application sites and practices have shown to be extremely effective and have demonstrated very few side effects or adverse reactions. Please contact Mark Drugs for more information or visit our website at markdrugs.com.
Diabetes Care 2012 Dec; 35:2451
Painful Diabetic Neuropathy: A Three-Drug Comparison
Amitriptyline, duloxetine, and pregabalin reduced pain to a similar extent.
Head-to-head comparisons of drugs commonly prescribed for painful diabetic neuropathy are scarce. In this double-blind trial, funded by a maker of pregabalin (an anticonvulsant; Lyrica), 83 patients (mean age, 65) with painful diabetic neuropathy were randomized to receive amitriptyline (a tricyclic antidepressant), duloxetine (a serotonin-norepinephrine reuptake inhibitor; Cymbalta), or pregabalin. Patients were treated for 4 weeks; total daily doses were titrated to a maximum of 75 mg of amitriptyline, 120 mg of duloxetine, and 600 mg of pregabalin.
At 4 weeks, mean pain scores had improved in all three groups, with no significant differences among groups. Duloxetine lessened sleep efficiency compared with the other two drugs, whereas pregabalin was associated with slightly worse cognitive function than the other two drugs. Adverse effects (particularly fatigue, dizziness, and somnolence) were most common with pregabalin. Premature withdrawal from the study due to adverse events occurred in six pregabalin recipients, three duloxetine recipients, and one amitriptyline recipient.
Comment: These three drugs had similar effects on painful diabetic neuropathy. Pregabalin was the least well tolerated, perhaps because of the high dose (note that target doses for duloxetine and pregabalin in this study were twice that of the FDA-approved maximal doses for diabetic neuropathy). Amitriptyline — by far the least expensive alternative — seems to be the winner here; however, many patients can't tolerate its anticholinergic side effects, and tricyclics are contraindicated in some patients with cardiac disease.
Allan S. Brett, MD Published in Journal Watch General Medicine December 20, 2012
Citation(s): Boyle J et al. Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain: Impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes Care 2012 Dec; 35:2451.
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MM: I agree with the authors that psychological interventions should be examined in lieu of sleep drugs for long term benefits but unfortunately those take time and effort and our current thought process is that we have neither of those available to us whereas a pill will do the job for us easily and immediately. Couple this attitude with the simple fact that drug companies will make nothing unless drugs are sold and it is doubtful that we will see any significant change in the paradigm any time soon.
'Z' Drugs May Help Insomniacs Fall Asleep, but Effect Is Small
Nonbenzodiazepine hypnotics, the so-called "Z" drugs (eszopiclone, zaleplon, and zolpidem), are associated with only slight improvements in sleep latency, according to a meta-analysis in BMJ.
Researchers analyzed 13 trials submitted to the FDA in which 4400 patients with insomnia were randomized to a Z drug or placebo.
Relative to placebo, Z drugs decreased the amount of time it took participants to fall asleep by a mean of 22 minutes, judged by polysomnography. The subjective time it took participants to fall asleep was also lower in the drug group, but only by 7 minutes. Larger doses were associated with greater improvements.
The authors conclude that the size of this effect is small and "needs to be balanced with concerns about adverse effects, tolerance, and potential addiction. The placebo response accounted for about half of the drug response. This suggests that increased attention should be directed at psychological interventions for insomnia."
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ACOG Offers Updated Guidelines on Weight Gain During Pregnancy
The American College of Obstetricians and Gynecologists supports the Institute of Medicine's guidelines on weight gain during pregnancy. The committee opinion appears in Obstetrics & Gynecology.
In brief:

ACOG has also issued a separate committee opinion on obesity in pregnancy. That document, noting that more than half of pregnant women in the U.S. are overweight or obese, offers recommendations including anesthesiology consultation early in labor and possible thromboprophylaxis for those undergoing cesarean section.


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N Engl J Med 2012 Nov 14
Alzheimer Disease Risk Variant Discovered
An anti-inflammatory gene is linked to increased risk for Alzheimer disease.
Most cases of Alzheimer disease (AD) affect people after age 65 and do not involve clear autosomal-dominant genetics. Clinicians are generally aware of the increased risk for late-onset AD conferred by the {varepsilon}4 allele of apolipoprotein E (APOE {varepsilon}4). Now, two groups report a new, rare variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) that results in an odds ratio for AD that is similar to the odds with APOE {varepsilon}4. TREM2 is expressed throughout the central nervous system, particularly in the white matter. Its protein is related to immunoglobulin and acts as a phagocytic receptor for bacteria and as a control of the inflammatory response. On microglia, the protein is important for the clearance of neural debris.
The two research teams each used a complicated series of genetics methods, including direct sequencing of DNA from AD patients and controls, genome-wide association studies with imputation, and assays of gene expression across regions of the human brain and in mouse models. Jonsson and colleagues found that the R47H variant of TREM2 was associated with a significantly increased risk for AD in a relatively homogenous Icelandic group (odds ratio, 2.92), and in other, more heterogenous, populations. Similarly, among people of European and North American ancestry, Guerreiro and colleagues found a significantly increased risk for AD associated with the R47H variant (OR, 4.5).
Comment: Because the R47H variant is rare, these findings are unlikely to affect current clinical care. However, the further implication of neuroinflammation in the pathogenesis of AD supports rapid and extensive exploration of therapeutics in this domain. Likewise, as editorialists note, the associations of the TREM2 gene with other neurodegenerative illnesses that lead to leukoencephalopathy (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, and hereditary diffuse leukoencephalopathy with spheroids) provide a unique opportunity to explore overlap in the pathophysiology of different forms of neurodegeneration and the potential treatment implications therein.
Brandy R. Matthews, MD Published in Journal Watch Neurology December 18, 2012
Citation(s): Jonsson T et al. Variant of TREM2 associated with the risk of Alzheimer's disease. N Engl J Med 2012 Nov 14; [e-pub ahead of print].
Guerreiro R et al. TREM2 variants in Alzheimer's disease. N Engl J Med 2012 Nov 14; [e-pub ahead of print].
Neumann H and Daly MJ. Variant TREM2 as risk factor for Alzheimer's disease. N Engl J Med 2012 Nov 14; [e-pub ahead of print].
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BMJ 2012 Dec 13; 345:e7396
Man's Best Friend Sniffs Out C. difficile
A trained dog identified toxigenic strains of Clostridium difficile with 100% accuracy in stool and 83% sensitivity and 98% specificity when near patients.
Infection with toxigenic strains of Clostridium difficile (CD) causes significant morbidity and mortality and is a large and growing problem in hospitalized patients. The available tests to reveal the presence of these strains require several days to complete, increasing the likelihood of nosocomial spread.
Noting the characteristic "horse manure–like" odor of diarrheic stool from patients infected with toxigenic CD, researchers in the Netherlands postulated that dogs — whose sense of smell is far superior to that of humans — might be able to detect this odor with great sensitivity and specificity. (One of the researchers is owner and chair of Scent Detection Academy and Research, Animal Behaviour and Cognition, HL&HONDEN, Edam, Netherlands.)
A 2-year-old male beagle was trained to identify the odor of toxin-producing CD and to sit or lie down on detection of this scent. In preliminary testing involving 50 CD-positive and 50 CD-negative stools, the dog's sensitivity and specificity were 100%. Using a case-control method, the dog was then put in proximity to one CD-positive and nine CD-negative patients on detection rounds in two hospitals. This process was repeated 29 times so the dog was exposed to a total of 30 CD-positive and 270 CD-negative inpatients. The dog correctly identified 25 of the 30 case-patients (sensitivity, 83%; 95% confidence interval, 65%–94%) and 265 of the 270 controls (specificity 98%; 95% CI, 95%–99%).
Comment: The authors note several limitations of this proof-of-principle study, including the variability of both trainers and dogs and, more importantly, the fact that many of the CD-positive patients had been moved to a single room (which could have influenced the trainer — and thus the dog's response). Further experience in this method is warranted and may prove very rewarding.
Stephen G. Baum, MD Published in Journal Watch Infectious Diseases December 19, 2012
Citation(s): Bomers MK et al. Using a dog's superior olfactory sensitivity to identify Clostridium difficile in stools and patients: Proof of principle study. BMJ 2012 Dec 13; 345:e7396.
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Nasal Gel Recalled Due to Burkholderia cepacia Contamination
One lot of Zicam Extreme Congestion Relief liquid nasal gel has been recalled by Matrixx Initiatives because Burkholderia cepacia was found in a sample during a routine review, the FDA announced on Wednesday.
Exposure to B. cepacia, which is resistant to many common antibiotics, could lead to serious respiratory infections in patients with cystic fibrosis or other chronic lung conditions, or in those with compromised immune systems.
There is little risk for healthy people, says the manufacturer, but all consumers should stop using the affected product. The half-ounce spray bottle is packaged in a carton displaying the lot number 2J23 and expiration date 09/15.
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Amoxicillin Offers Little Benefit for Uncomplicated Lower Respiratory Tract Infection
For patients with uncomplicated lower respiratory tract infection, amoxicillin does not reduce symptoms — and might cause "slight harms" — according to a study in the Lancet Infectious Diseases.
Researchers randomized some 2000 adults with acute lower respiratory tract infection and without suspected pneumonia to receive amoxicillin (1 g three times daily) or placebo for 7 days. Patients were enrolled at primary care practices in 12 European countries.
Duration of symptoms rated "moderately bad" or worse and severity of symptoms within the first few days were similar with amoxicillin and placebo, both overall and among patients aged 60 and older. Compared with controls, the amoxicillin group reported fewer new or worsening symptoms. Adverse effects, including nausea, rash, and diarrhea, were more common with amoxicillin. One patient in the amoxicillin group had anaphylaxis.
The authors conclude that "unless pneumonia is suspected, antibiotics should not be prescribed for patients with lower respiratory tract infection."
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Whiplash: Active Intervention Shows No Lasting Benefit
Neither active management consultations nor added physiotherapy sessions provide lasting benefit for whiplash injury, a Lancet study finds.
In the two-step study, 15 emergency departments in the U.K. were randomized to provide active management consultations or usual care consultations to nearly 4000 patients with acute whiplash. Active management included advice about prognosis, return to normal activities, neck exercises, and pain treatment. There was no difference in Neck Disability Index scores between the two groups at 4, 8, or 12 months.
Then, some 600 patients with persistent symptoms after 3 weeks were randomized to receive either a single physiotherapy session or a package of up to six sessions. A modest but significant benefit was seen in the package group at 4 months, but not at 8 or 12.
Asked to comment, Journal Watch Emergency Medicine's Kristi Koenig said: "Even for patients with only minor whiplash injuries, the psychological trauma of experiencing a car crash and going to the emergency department can be significant. This study supports our current approach of providing patient education and reassurance."
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MM: I find it interesting that the debate over the benefits and hazards of aspirin use rages on. Over time this is a product that has been considered virtually innocuous while also being elevated to the status of the perfect drug. It stands to reason that any product that has the potential to have an effect or change on the body has the same potential for harm as it does for benefit.
Long-Term Aspirin Use Associated with Small Increased Risk for Macular Degeneration
Regular use of aspirin is associated with a "small but statistically significant" increase in the risk for neovascular age-related macular degeneration (AMD), according to a JAMA study.
Nearly 5000 people in a single Wisconsin community were followed for 20 years, with retinal photographs and questions about their use of aspirin. (Regular aspirin use was defined as occurring at least twice a week for more than 3 months.)
Regular aspirin use for 10 years was associated with an increased risk for late AMD (incidence, 1.76% vs. 1.03% in nonusers). That association was stronger for the neovascular type of late AMD. Regular aspirin use was not associated with early AMD.
The authors speculate that the increased risk may be driven by aspirin's tendency, in the presence of injury, to increase the surrounding vascular density and the growth of aberrant vessels.
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Diabetes and Weight-Loss Results Found Modest with Intensive Lifestyle Intervention
An intensive lifestyle intervention was associated with more weight loss and remission of diabetes than one based on education and support, according to a study in JAMA.
Some 4500 adults with BMIs of 25 or more and type 2 diabetes were randomized to one of two 4-year regimens: intensive lifestyle intervention (including frequent group counseling and liquid meal replacements) or the control intervention.
The intensive lifestyle intervention group lost a greater percentage of weight by year 1 (net difference, −7.9%) and year 4 (−3.9%). Partial or complete remission of diabetes (defined as the transition to prediabetic or nondiabetic glucose levels) was also more prevalent in the intervention group in year 1 (11.5% vs. 2.0%) and year 4 (7.3% vs. 2.0%).
Editorialists call the results "disappointing" and point to the success (and potential disadvantages) of bariatric surgery. Prevention, they conclude, should be the rallying cry.
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BMJ 2012 Nov 27; 345:e7895
Thyroid Function and Risk for AF: A Linear Relation
Patients with even subclinical hyperthyroidism had excess risk for atrial fibrillation.
Patients with overt hyperthyroidism (suppressed thyroid-stimulating hormone [TSH] and elevated free thyroxine [T4] levels) have excess risk for developing atrial fibrillation (AF). However, the relations between subclinical hyperthyroidism (suppressed TSH and normal T4), overt hypothyroidism (elevated TSH and low T4), and subclinical hypothyroidism (elevated TSH and normal T4) are unclear.
In a population-based cohort study, nearly 590,000 primary care patients (mean age, 50; 39% men) underwent thyroid function blood testing from 2000 through 2010. Overall, 0.3% of patients had overt hypothyroidism, 2.0% had subclinical hypothyroidism, 96.0% were euthyroid, 1.0% had subclinical hyperthyroidism, and 0.7% had overt hyperthyroidism. During a median follow-up of 5.5 years, >17,000 participants received first diagnoses of AF. Compared with euthyroid patients, patients with overt hypothyroidism had less risk for AF (incidence rate ratio, 0.67), as did those with subclinical hypothyroidism (IRR, 0.87); risk for AF was higher in patients with subclinical hyperthyroidism (IRR, 1.31) or overt hyperthyroidism (IRR, 1.42) than for euthyroid patients. Stratifying data by age, sex, or both did not change the associations.
Comment: In this large prospective study, a linear relation was observed between thyroid function and risk for AF: hypothyroid patients had lower risk and hyperthyroid patients had excess risk. The authors suggest that patients with overt and subclinical hyperthyroidism should be screened routinely for AF.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine December 18, 2012
Citation(s): Selmer C et al. The spectrum of thyroid disease and risk of new onset atrial fibrillation: A large population cohort study. BMJ 2012 Nov 27; 345:e7895.
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Cases of Gonorrhea and Chlamydia on the Rise
The CDC has updated its report of sexually transmitted disease trends with data from 2011. Notable changes include:

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Fish Fraud Marches On
Two investigations find continuing bait-and-switch problem  By Craig Weatherby
It says something that our news archive features a section titled “Seafood Labeling & Fraud Issues”.
Now, two new investigations have found that fraud remains rampant in restaurants and supermarkets.  Imported fish – which constitutes about 91 percent of the seafood sold in America – accounts for much of the substitution. According to the Centers for Disease Control and Prevention, disease outbreaks linked to imported fish have risen in recent years.
Oceana probed New York seafood ... with sorry results
In one probe, the conservation group Oceana conducted genetic analyses on seafood bought in New York City … mostly in Manhattan. (Last year, Oceana launched a new “Stop Seafood Fraud” campaign based on its report, “Bait and Switch: How Seafood Fraud Hurts Our Oceans, Our Wallets and Our Health” … see “Fish Fraud Remains Rampant”.) Sadly, 39 percent of nearly 150 samples of fresh seafood collected from 81 restaurants and stores were mislabeled:

Surprisingly, compared with regional chains or small specialty markets, national chain supermarkets sold less mislabeled seafood.
Boston Globe finds fraud for a second year running
Last year, the Boston Globe reported that restaurants and stores in Massachusetts were routinely substituting cheaper, lower-quality fish for higher-quality fish. And a new round of DNA testing shows that most are still mislabeling seafood. The Globe tested 76 seafood samples from 58 restaurants and markets that sold mislabeled fish in 2011, and found that more than three in four were mislabeled. The testing focused on species that are most likely to be mislabeled, such as red snapper and cod. After the Globe’s 2011 report, state and federal lawmakers pledged to strengthen oversight of the seafood industry.  The Food and Drug Administration has focused efforts on food safety, rather than economic fraud such as seafood substitution.  The agency began conducting its own DNA testing recently, but hasn’t pinpointed where mislabeling typically occurs in the supply chain.
Why trust Vital Choice?
Thanks to decades of fishing northwest and Alaskan waters, we know our seafood very well. During those decades, we built a network of superior suppliers, so we know where all of our seafood comes from ... and how it gets to us. For example, Vital Choice North Pacific albacore tuna comes from nearby neighbor Paul Hill ... while our Alaskan seafood comes either from folks we’ve known for many years or from fishing co-ops and other suppliers we’ve visited and carefully vetted. And when we decided to offer premium European sardines and mackerel, we went to Portugal to find our current partner … a venerable, family-run business renowned for integrity and superior quality. Not surprisingly, our rigorous, highly personal and reliable purchasing practices remain rare among markets and restaurants. Very few seafood sellers spend the time and focus required to ensure the identity and source of their fish … and in many cases sellers deliberately mislabel seafood to boost profits.

Sources: Abelson J, Daley B. New round of DNA tests finds dozens of repeat offenders in fish mislabeling. December 10, 2012.;  Accessed at http://www.boston.com/ news/local/massachusetts/2012/12/01/dnasidebar/mao PlTvCRdnKmzKdmhHxpO/story.html.;
  Oceana. Widespread Seafood Fraud Found in New York City. December 11, 2012. Accessed at http://oceana.org/en/news-media/publications/reports/ widespread-seafood-fraud-found-in-new-york-city,; Rosenthal E. Tests Say Mislabeled Fish Is a Widespread Problem. The New York Times. December 11, 2012. Accessed at http://www.nytimes.com/2012/12/11/science/earth/ tests-call-mislabeled-fish-a-widespread-problem-in-new-york.html

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Are Stinky Cheeses Heart-Healthy?
Bleu cheese and other pungent types may lower blood pressure and inflammation
By Craig Weatherby
Could cheese be the missing piece in the “French paradox” puzzle? That’s the provocative title of a paper published by researchers from a UK-based lab. Judging by their findings, the answer may be a qualified “yes” … but it’s likely that pungent cheeses are just one piece, not “the” missing piece.
The French paradox
Despite French people’s tendency to eat foods high in saturated fats – such as cheese, foie gras, and butter – and to drink wine daily, they have low rates of cardiovascular disease (CVD).  This so-called “French paradox” has puzzled researchers for decades. The French habit of relaxed, slow meals and modest portions – plus their liking for vegetables, olive oil, and red wine – may explain the paradox. Light-to-moderate wine consumption has been linked to lower risk of chronic inflammation, heart disease, and certain cancers … likely due to red wine’s polyphenols, including resveratrol. The average French citizen drank 46 liters (49 quarts) of wine in 2010, while Americans drank only 9.42 liters (10 quarts) in the same year.
Stinky cheese may play a paradoxical part
An examination of three pungent, fermented cheeses favored in France – Roquefort, Bleu, and Camembert – suggests that they may account for part of the French paradox.  UK-based researchers found that these cheeses contain peptides (bio-active protein fragments) that reduce blood pressure and key markers of inflammation such as C-reactive protein (CRP). The new findings apply only to these three rich, stinky cheeses. It remains to be seen whether they might apply to milder kinds like cheddar, Swiss, and American.
For millennia, global cultures hailed fermented foods as healthful and tasty, and found that fermentation kept foods edible longer … although they didn’t know why. And we’re still a very long way from knowing the myriad ways in which bacterial cultures in fermented foods – and their metabolic byproducts, such as the peptides in cheese – affect human health.
The stinky cheese paradox: Rich, but healthful (in moderation) For decades, cheese has been seen as a heart-attacker, because of its relatively high saturated fat and cholesterol content.
And high calorie intake – made more likely by a yen for fatty (hence, calorie-dense) foods such as cheese – can easily lead to obesity, which promotes diabetes, heart disease, and high blood pressure.  But even the rich, stinky cheeses in the new study don’t contribute an excess of calories, saturated fat, or cholesterol … if you limit consumption to an ounce or so per day.
The official 2010 Dietary Guidelines for Americans recommend these daily limits for moderately active people aged 30-50 years:

We should note that the evidence does not support undue fear of saturated fats, which vary widely in structure and in their impact on blood fat-cholesterol profiles. For example, the predominant saturated fat in chocolate and coconut (stearic acid) is very benign. Also, moderate cholesterol intake is clearly not a heart risk … unless you are among the very few who cannot process dietary cholesterol properly.
By comparison, these are the amounts of calories, sodium, cholesterol, and saturated fat per oz of Roquefort, Bleu, and Camembert:

These rich, stinky cheeses are fairly high in calories and fat ... but it appears that they can be healthful if you limit them to an ounce or two per day.

Sources: Colquhoun DM, Somerset S, Irish K, Leontjew LM. Cheese added to a low fat diet does not affect serum lipids. Asia Pac J Clin Nutr. 2003;12 Suppl:S65. ; Dietary Guidelines for Americans 2010. Accessed at: http://health.gov/dietaryguidelines/dga2010/DietaryGuidelines2010.pdf ; Lippi G, Franchini M, Favaloro EJ, Targher G. Moderate red wine consumption and cardiovascular disease risk: beyond the "French paradox". Semin Thromb Hemost. 2010 Feb;36(1):59-70. doi: 10.1055/s-0030-1248725. Epub 2010 Apr 13. Review. ; Petyaev IM, Bashmakov YK. Could cheese be the missing piece in the French paradox puzzle? Med Hypotheses. 2012 Dec;79(6):746-9. doi: 10.1016/j.mehy.2012.08.018. Epub 2012 Sep 13. ; Soriguer F, García-Escobar E, Morcillo S, García-Fuentes E, Rodríguez de Fonseca F, Olveira G, Rojo-Martínez G. Mediterranean diet and the Spanish paradox. A hypothesis. Med Hypotheses. 2012 Dec 7. doi:pii: S0306-9877(12)00496-3. 10.1016/j.mehy.2012.11.015. [Epub ahead of print] ; Wu JM, Wang ZR, Hsieh TC, Bruder JL, Zou JG, Huang YZ. Mechanism of cardioprotection by resveratrol, a phenolic antioxidant present in red wine (Review). Int J Mol Med. 2001 Jul;8(1):3-17. Review.


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