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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
May 19, 2012

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Lower-Risk People Should Be Treated with Statins, Meta-Analysis Suggests
Why Sleep Patterns Matter
Is Botulinum Toxin Type A Effective for Headache Prophylaxis?
Gender Bias
Azithromycin (Z-Pak®) Associated with Cardiovascular Death
FDA Responds to Study on Azithromycin and Cardiovascular Death
Clostridium difficile Infection — Treat Orally, if Possible
Does Drinking Coffee Lower Mortality?
Maternal Obesity May Increase Risk for Autism
Is Urine Odor Associated with UTI?
FDA Questions Whether Long-Term Use of Bisphosphonates Provides Fracture Benefit
Study Casts Doubt on Protective Effects of Raising HDL Cholesterol
Clean your hands!
Washington State Declares Whooping Cough Epidemic
The Incremental Relation Between Fasting Glucose and Glycosylated Hemoglobin
Sugary Brain Damage Blunted by Omega-3s
Fructose-heavy diet dulled rats’ brains, but omega-3 DHA from fish countered the disruption

Lower-Risk People Should Be Treated with Statins, Meta-Analysis Suggests
Even patients with a low 5-year risk for major vascular events may benefit from LDL-lowering statin therapy, according to a government-funded meta-analysis in the Lancet.
The study included 27 trials comparing statins with control therapy in nearly 175,000 participants. During 5 years' follow-up, statins lowered the risk for major vascular events by 21% per 1.0 mmol/L (39 mg/dL) reduction in LDL cholesterol. In particular, the lowest-risk patients (i.e., estimated 5-year risk for major vascular events <10%) had reductions in coronary events, revascularizations, and stroke that were similar to reductions in higher-risk patients.
Statins were not associated with cancer or nonvascular mortality.
The authors say statins' benefits in lower-risk patients greatly exceed "any known hazards." They continue: "Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. ... These guidelines might need to be reconsidered." They do, however, raise concerns about the costs of widespread treatment.
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Sci Transl Med 2012 April 11; 4:129ra43.
Why Sleep Patterns Matter
Prolonged experimental shortening or disruption of sleep led to a prediabetic condition.
Epidemiologic studies suggest that people who habitually sleep fewer than 6 hours nightly, or whose sleep patterns do not correspond to normal circadian rhythms, have excess risk for developing obesity and type 2 diabetes. Researchers conducted a controlled study to confirm and explain this observation. Twenty-one participants lived in individual quarters in a sleep laboratory for 6 weeks. They had no contact with the outside world (including cues about nighttime and daytime); timing of meals, caloric intake, and activity levels were experimentally controlled. For the first 3 weeks, 10 hours of darkness ("sleep opportunity") occurred during what was nighttime in the outside world. For the next 3 weeks, the amount and timing of darkness was experimentally manipulated to be shorter (providing the equivalent of a 5.6-hour sleep opportunity per 24 hours, the rest of which consisted of monitored wakefulness) and to start 4 hours later each night, until "nighttime" was beginning during what was actually daytime. A 9-day recovery period consisted of 10 hours of nightly sleep that always occurred at true nighttime.
Insulin sensitivity, pancreatic insulin secretion, and resting metabolic rates all dropped during sleep disruption, which raised blood glucose levels. These physiological changes reverted to or toward baseline during the recovery period.
Comment: This experimental study provides strong evidence to support the epidemiologic observations that sleep that is regularly short or out of phase with day–night cycles (situations typical of shift work) can cause physiological changes that predispose people to type 2 diabetes.
Anthony L. Komaroff, MD Published in Journal Watch General Medicine May 8, 2012
Citation(s):Buxton OM et al. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med 2012 April 11; 4:129ra43.
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JAMA 2012 Apr 25; 307:1736
Is Botulinum Toxin Type A Effective for Headache Prophylaxis?
A meta-analysis finds that it may be effective for chronic, but not episodic, migraine headache but not for any form of tension-type headache.
Headache is common in the community, with migraine and tension-type headache being the most common primary headache disorders to present to physicians (Headache 2004; 44:856). Frequent headache, called chronic daily headache, occurs on 15 or more days per month for 3 or more months (Curr Opin Neurol 2002; 15:287) and is the most challenging to treat. Chronic daily headache largely consists of chronic migraine (CM) and chronic tension-type headache (CTTH). Few controlled trials in these disorders have been conducted, largely because the definitions have been argued over for a long period and are only now standardized (Cephalalgia 2006; 26:742).
Botulinum toxin type A has been studied in both CM and CTTH and is the subject of a new meta-analysis of the evidence for its use in headaches in adults. The authors examined 27 placebo-controlled, randomized trials and 4 randomized studies comparing botulinum toxin type A with other medications. They demonstrate a reduction in headache days for CM and a less clear outcome for the umbrella diagnosis of chronic daily headache. There is no clear effect for either episodic migraine, defined as occurring on more than 15 days a month, or CTTH. As with any active treatment, there are adverse effects, such as blepharoptosis, skin tightness, and neck discomfort.
Comment: The results and conclusions in this meta-analysis are comparable to those of a pooled analysis of the chronic migraine studies (Headache 2010; 50:921) and recapitulate the rationale behind the U.S. Food and Drug Administration approval of botulinum toxin type A for the treatment of CM. Although one could quibble about the inclusion of studies that did not have a placebo injection arm in the CM analysis, since botulinum toxin type A administration would be completely unblinded, the overall outcome conclusions of the meta-analysis are not altered. The marginal effect in chronic daily headache illustrates, as the authors surmise, that the mixed population does less well. The meta-analysis underscores the importance of good medical history-taking and making a clear diagnosis to align patient presentation with the evidence. CM is a common, disabling, often life-ruining problem for patients, and a substantial public health problem. It requires more research into its pathophysiology and many more clinical trials to develop further evidence-based approaches.
Peter J. Goadsby, MD, PhD, DSc Dr. Goadsby is a consultant for the manufacturer of Botox (botulinum toxin type A).
Published in Journal Watch Neurology May 15, 2012
Citation(s):Jackson JL et al. Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: A meta-analysis. JAMA 2012 Apr 25; 307:1736.
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J Clin Oncol 2012 Apr 30
Gender Bias
Women have better postmelanoma survival than men — but why?
Disparity between men and women in survival after melanoma has been well documented; in numerous studies, women appear to fare better than men. The behavior hypothesis suggests that differences in self-awareness, appropriate seeking of medical care, and timely detection influence this observed trend. Alternatively, others propose that hidden biological differences between men and women may explain the difference in prognosis.
These authors conducted an aggregate analysis of data from four large, randomized trials conducted by the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group in 2672 patients (48% men) with stage I/II cutaneous disease. Women had a highly persistent and independent advantage in overall survival (adjusted hazard ratio, 0.70; 95% confidence interval, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). These trends remained consistent after subgroup analysis, except in patients with thin melanomas (0–2.00 mm) or head and neck melanomas, and in those who underwent sentinel lymph node biopsies.
Comment: Overall, research has shown an approximately 30% female advantage in postmelanoma survival across nearly every study that has examined this issue. Given this widespread observation, the explanation is more likely to be biological than behavioral, but what is this biological feature? The advantage persists beyond menopause, making a purely hormonal effect unlikely. It is possible that immunogenic effects are at work, given that autoimmune phenomena are more common among women than men. We hope that future studies will provide more insight into the etiological basis of this female advantage.
Hensin Tsao, MD, PhD Published in Journal Watch Dermatology May 18, 2012
Citation(s): Joosse A et al. Superior outcome of women with stage I/II cutaneous melanoma: Pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials. J Clin Oncol 2012 Apr 30; [e-pub ahead of print].
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Azithromycin (Z-Pak®) Associated with Cardiovascular Death
The antibiotic azithromycin — which may have proarrhythmic properties — is associated with increased risk for cardiovascular death, according to a retrospective cohort study in the New England Journal of Medicine.
The study, in a Medicaid population, included nearly 350,000 azithromycin prescriptions, 1.4 million control periods without antibiotic prescriptions, and 1.8 million prescriptions for other antibiotics, mostly amoxicillin.
Azithromycin conferred a nearly threefold increase in risk for CV death and a nearly twofold increase in all-cause mortality during the 5 days of therapy, relative to no treatment. When azithromycin and amoxicillin were compared, there were 47 excess CV deaths per 1 million courses of azithromycin. For patients with the highest CV risk at baseline, there were 245 excess deaths per 1 million azithromycin treatments, compared with amoxicillin.
Azithromycin also posed greater risk for CV mortality compared with ciprofloxacin, but not compared with levofloxacin.
In HIV and ID Observations, Dr. Paul Sax writes: "If there's a silver lining to this report ... it's that clinicians will stop prescribing azithromycin for conditions that clearly don't need it — which is just about every uncomplicated outpatient respiratory infection. ... Hey, we can dream, can't we?"
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FDA Responds to Study on Azithromycin and Cardiovascular Death
Patients should not stop taking the antibiotic azithromycin without first consulting with their physician, the FDA said in a statement following a study published in the New England Journal of Medicine — and covered here Thursday.
That study linked the drug with increased risk for cardiovascular death during short-term therapy. The FDA notes that other macrolide antibiotics also carry warnings about possible QT interval prolongation.
The agency says it's reviewing the work and that "healthcare professionals should be aware of the potential for QT interval prolongation and heart arrhythmias when prescribing or administering macrolides."

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Antimicrob Agents Chemother 2012 Apr; 56:1974
Clostridium difficile Infection — Treat Orally, if Possible
The risk for death was significantly higher with intravenous metronidazole than with oral metronidazole or oral vancomycin.
Clostridium difficile infection (CDI) is an urgent clinical problem with a rapidly rising prevalence. Guidelines recommend oral metronidazole as the treatment of choice for most patients and oral vancomycin for seriously ill individuals. For patients who cannot take oral medications, intravenous metronidazole is the only option — but is it equivalent to oral treatment?
To explore this issue, researchers in Austria conducted a hospital-based, prospective cohort study involving patients with mild CDI (i.e., without pseudomembranous colitis at onset, peritonitis, ileus, toxic megacolon, marked leukocytosis, rise in creatinine or lactate level, or other signs of severe colitis). All patients were able to take oral medication; choice of regimen was at the discretion of the treating physician. Of the 205 study participants, 121 received oral metronidazole, 42 received intravenous metronidazole, and 42 received oral vancomycin.
Mean patient age was 77, and more than half the patients suffered from moderate/severe comorbidity (Charlson comorbidity index >2 points). The all-cause 30-day mortality rate — 13% overall — was significantly higher in the intravenous metronidazole group (38%) than in the oral metronidazole or the oral vancomycin group (7% and 10%, respectively). After adjustment for sex, age >65, and severity of comorbidity, the risk for death within 30 days was ≥4-fold higher with intravenous metronidazole than with oral metronidazole or oral vancomycin.
Comment: This study is limited by its nonrandomized design. Nevertheless, the findings support current guidelines that advocate oral treatment for CDI, if possible. Confirmatory trials are definitely needed. The authors note that worse outcomes with intravenous metronidazole might be explained by insufficient gut drug levels after infusion. The possibility that patients who cannot take oral medication (usually the sicker ones) might be left with less-than-optimal treatment for CDI is disturbing.
Thomas Glück, MD Published in Journal Watch Infectious Diseases May 2, 2012
Citation(s):Wenisch JM et al. Prospective observational study comparing three different treatment regimes in patients with Clostridium difficile infection. Antimicrob Agents Chemother 2012 Apr; 56:1974
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N Engl J Med 2012 May 17; 366:1891
Does Drinking Coffee Lower Mortality?
Apparently so, according to results of the largest-ever study to examine the relation.
Many epidemiologic studies on the effects of coffee drinking on total mortality and disease-specific mortality have been small and underpowered and have produced conflicting results. In the mid-1990s, epidemiologists at the National Cancer Institute administered a detailed diet and lifestyle questionnaire to 402,260 members of the AARP. The participants (age range, 50–71), who were free of heart disease, stroke, and cancer at study onset, were followed for a decade — more than 5.1 million person-years of follow-up.
After adjusting for many potential confounders, a graded and inverse relation was found between the amount of coffee consumed and total mortality, as well as disease-specific mortality from heart disease, stroke, respiratory disease, diabetes, and infection, but not death from cancer. The results were similar in men and women, and for caffeinated and decaffeinated coffee.
Comment: In the largest study ever conducted on the health effects of coffee drinking, men and women who drank six or more cups of coffee daily had a mortality rate that was 10% and 15% lower, respectively, than people who did not drink coffee. Because this study was observational, it cannot be concluded that this association is causal. Yet the graded dose-response relation and the careful adjustment for potential confounders suggests that it may be. The authors speculate that the many antioxidants in coffee might explain the possible benefits of coffee consumption.
Anthony L. Komaroff, MD Published in Journal Watch General Medicine May 17, 2012
Citation(s): Freedman ND et al. Association of coffee drinking with total and cause-specific mortality. N Engl J Med 2012 May 17; 366:1891.
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Pediatrics 2012 May; 129:e1121
Maternal Obesity May Increase Risk for Autism
More evidence that maternal metabolic conditions during pregnancy are associated with neurodevelopmental disorders in children.
To examine whether metabolic conditions (diabetes, hypertension, and obesity) during pregnancy are associated with neurodevelopmental disorders in children, researchers in California performed a population-based, case-control study of children aged 2 to 5 years with autism spectrum disorder (ASD; 517 children), developmental delay without ASD (172 children), or with typical development (315 controls from the general population matched to the ASD group for age and sex). Maternal demographic and medical information was obtained from medical records, structured interviews, and an environmental exposure questionnaire. Validated instruments were used to diagnose ASD and developmental delay. Children with major motor and sensory impairments (blindness or deafness) were excluded.
All three metabolic conditions were more prevalent in case mothers than in control mothers. In analyses adjusted for covariates, mothers with diabetes were 2.3 times more likely than control mothers to have a child with developmental delay but were not significantly more likely to have a child with ASD. However, obese mothers (prepregnancy body-mass index >30 kg/m2) were 2 times more likely than control mothers to have a child with developmental delay and 1.7 times more likely to have a child with autism. Maternal diabetes was associated with greater deficits in expressive language among children with and without ASD.
Comment: This carefully executed study adds to increasing evidence indicating that maternal metabolic health during pregnancy affects neurodevelopmental health in children. The high prevalence of both obesity and diabetes among U.S. women of child-bearing age might contribute to increasing risk for autism, developmental delay, and other developmental impairments.
Louis M. Bell, MD Published in Journal Watch Pediatrics and Adolescent Medicine May 16, 2012
Citation(s):Krakowiak P et al. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 2012 May; 129:e1121.
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Pediatrics 2012 May; 129:885
Is Urine Odor Associated with UTI?
Parental report of malodorous urine was significantly associated with urinary tract infection in young febrile children.
Urine has an odor, but often parents describe the odor of their child's urine as stronger or more objectionable than usual. To determine whether parent report of urine odor is a reliable indicator of urinary tract infection (UTI), Canadian researchers analyzed symptom questionnaires for 331 children (age range, 1–36 months) who presented to an emergency department with symptoms suggestive of UTI (>90% had fever without source, others had unexplained vomiting or irritability without fever). Urine obtained for culture was collected by bladder catheterization (90%), midstream clean catch (9%), or suprapubic aspiration (1%). Questionnaires were completed before urinalysis results were known.
Fifteen percent of children had a UTI (defined as a positive urine culture). Urine that was stronger or more offensive than usual was reported by parents in 57% of children with UTI and 32% of children without UTI. In multiple regression, children with malodorous urine had significantly increased odds of UTI (odds ratio, 2.73), after adjustment for sex and the presence of vesicoureteral reflux. The sensitivity, specificity, and positive likelihood ratio of malodorous urine as an indicator of UTI were 57%, 68%, and 1.8, respectively. Urine odor was more strongly associated with UTI than vomiting, diarrhea, or dysuria.
Comment: It is tempting to discount parental reports of symptoms such as ear pulling, nasal discharge color, and urine odor as being too subjective and not reliably related to bacterial infections. But this study shows that, at least in children younger than 3 years with fever, malodorous urine is significantly associated with urinary tract infection. Children of parents who reported malodorous urine were 80% more likely to have a UTI than children of parents who did not. Urine odor is not sensitive or specific enough to be used alone to diagnose UTI or prompt bladder catheterization, but for clinical situations where the decision to collect urine from a febrile child is not obvious, asking the parents about urine odor might help with this judgment call.
Cornelius W. Van Niel, MD Published in Journal Watch Pediatrics and Adolescent Medicine May 16, 2012
Citation(s):Gauthier M et al. Association of malodorous urine with urinary tract infection in children aged 1 to 36 months. Pediatrics 2012 May; 129:885.
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FDA Questions Whether Long-Term Use of Bisphosphonates Provides
Fracture Benefit

An FDA analysis, published in the New England Journal of Medicine, calls into question the fracture-prevention benefits of long-term bisphosphonate use.
The FDA examined three randomized trials in which bisphosphonates were given initially for at least 3 years, and then extended for an additional 3 to 6 years (total duration, 6–10 years). Pooled data showed that women receiving bisphosphonates for at least 6 years had similar overall fracture rates as those who switched to placebo (roughly 10% and 8.5%, respectively).
The authors say there are not enough data to determine which subgroups of patients may benefit from use beyond 3 to 5 years. But commentators provide the following recommendations:

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Study Casts Doubt on Protective Effects of Raising HDL Cholesterol
A genetics-based analysis finds that raising HDL will not necessarily lower risk for myocardial infarction. Reporting in the Lancet, researchers describe a two-pronged approach.
First, they searched for the presence of a specific allele (LIPG Asn396Ser, associated with higher HDL levels in carriers) in a large cohort of subjects with and without MI. The allele's presence should have lowered MI risk by about 15%, but no such association was found.
Similarly, testing for the presence of an array of HDL-raising gene variants (and assigning a score on the basis of the number of variants in each subject) failed to find an association of lower risk with higher scores.
The authors conclude that raising HDL, whether with lifestyle interventions or drugs, "cannot be assumed ipso facto to lead to a corresponding benefit with respect to ... myocardial infarction."
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BMJ 2012 May 3; 344:e3005
Clean your hands!
Increased procurement of soap and alcohol-based hand cleansers was associated with decreased rates of MRSA and C. difficile infections in England and Wales.
Infection with methicillin-resistant Staphylococcus aureus (MRSA) or Clostridium difficile can be acquired in the community or in healthcare settings. To decrease the spread of infectious agents by healthcare workers, thorough hand-cleaning has been emphasized. Compliance with this recommendation varies and is hard to measure.
In a recent study, researchers drew on monthly procurement data for alcohol hand rub and liquid soap to circumvent the difficulties in monitoring hand-washing. Using information from 187 National Health Service hospital trusts in England and Wales, they compared figures for January 2005 through June 2008 with those from late 2004 — before the start of the national Cleanyourhands campaign.
Soap procurement was independently associated with C. difficile infection throughout the study: A 10-mL increase in soap procurement per patient bed-day was correlated with a 7.1% decrease in the C. difficile infection rate (95% confidence interval, 3.9% to 9.6%). The relation between alcohol-rub procurement and MRSA bacteremia changed over time and was significant only during the final year of the study. For every 10-mL increase in cleanser procurement per patient bed-day, MRSA bacteremia rates fell by 9.6% (95% CI, 4.9% to 14.3%). Alcohol-rub procurement was not associated with C. difficile infection. Paradoxically, increased soap procurement was significantly associated with an increase in the rate of bacteremia caused by methicillin-sensitive S. aureus.
Comment: This clever study would be possible only in a closed system of infection and procurement reporting. Although numerous confounding events and actions could have occurred simultaneously with the collection of these data, the association of C. difficile infection with the procurement of soap and not with that of alcohol-based cleansers (to which this organism is resistant) gives considerable validity to the findings.
Stephen G. Baum, MD Published in Journal Watch Infectious Diseases May 16, 2012
Citation(s): Stone SP et al. Evaluation of the national Cleanyourhands campaign to reduce Staphylococcus aureus bacteraemia and Clostridium difficile infection in hospitals in England and Wales by improved hand hygiene: Four year, prospective, ecological, interrupted time series study. BMJ 2012 May 3; 344:e3005.
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Washington State Declares Whooping Cough Epidemic
Washington state is experiencing a pertussis epidemic, with 1284 cases reported through early May, the New York Times reports. At this point last year, the state had only 128 cases. This is the most in at least 30 years, and state health officials suspect it represents only about a fifth of the true number of cases. Most victims are between age 8 and 12 years.
The top medical officer in one hard-hit county is urging doctors to stop testing to confirm a pertussis diagnosis if a patient has symptoms and has been in close contact with someone with pertussis. The test can cost $400 and take days to get a result.
Potentially compounding the outbreak, Washington has the highest exemption rate in the U.S. for childhood immunizations. Some 6.2% of kindergarteners last year had parent-signed exemptions for one or more vaccines, according to a CDC study. Most pertussis patients in the current outbreak had received early childhood immunizations.
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Diabetes Care 2 012 Apr; 35:749
The Incremental Relation Between Fasting Glucose and Glycosylated Hemoglobin
The relation is affected, in part, by the degree of fasting hyperglycemia and use of oral antidiabetes drugs.
Sometimes glycosylated hemoglobin (HbA1c) test results don't seem consistent with patients' reported blood glucose levels. In this study, researchers sought to determine whether ethnicity, geographic region, or oral antidiabetes drug use affects the relation between HbA1c and fasting plasma glucose (FPG) levels. The study involved 12,500 patients worldwide with type 2 diabetes, impaired glucose tolerance, or impaired fasting glucose; none were using insulin.
Results were as follows:

The above-noted results were not affected by type of oral antidiabetes drug (metformin or sulfonylurea), geographic location (North America, South America, Europe, or Pacific Rim) or ethnicity (white, Latino, Asian, or black)
Comment: We know that HbA1c can be affected by hemoglobin structure, erythrocyte lifespan, and lability of blood glucose levels (JW Gen Med Sep 13 2011). This study provides additional insights: (1) as FPG increases above 162 mg/dL, HbA1c does not rise as steeply as it does for FPG increments below that threshold; and (2) at any given level of FPG, HbA1c will likely be lower in patients who take oral antidiabetes drugs, compared with untreated patients. Finally, note that these findings apply to fasting glucose levels and not to 24-hour average glucose levels.
Allan S. Brett, MD Published in Journal Watch General Medicine April 26, 2012
Citation(s): Ramachandran A et al. Relationship between A1C and fasting plasma glucose in dysglycemia or type 2 diabetes: An analysis of baseline data from the ORIGIN trial. Diabetes Care 2012 Apr; 35:749.
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Sugary Brain Damage Blunted by Omega-3s
Fructose-heavy diet dulled rats’ brains, but omega-3 DHA from fish countered the disruption

by Craig Weatherby
Cramming for a work project or school exam?

Beware … it appears that sweet foods and drinks can give Jack (or Jill) a duller brain. If the results of a rat study apply to people – which seems likely – you’d be smart to go easy on sweet things and use omega-3s to shield your brain against the ones you can’t resist. The long-chain omega-3 fatty acids found in human cells and fish (DHA and EPA) are essential to our survival and to optimal health. And it’s increasingly clear that these omega-3s can also help reduce the damage caused by the standard American diet.

For several years, a California-based team’s been examining the effects of junky, American-style diets on rats’ brains. The group’s mission and main thesis are expressed on their UCLA NeuroLife Lab website:
“Our approach is to harness the power of diet and exercise to prevent or cure neurological and psychiatric disorders … the proper management of lifestyle habits can arm us with the brainpower necessary to fortify cognitive reserve and battle various brain and spinal cord diseases.”

Their prior findings in rats suggest that the standard American diet reduces the brain’s “plasticity” … the cluster of characteristics that support our capacity for learning, memory, and recovery. Loss of plasticity dulls the brain while making it more vulnerable to lifestyle-induced damage and less able to recover from injuries of physical or metabolic origin. These investigations have been led by Fernando Gomez-Pinilla, Ph.D., professor of neurosurgery, integrative biology, and physiology at UCLA.

As Gomez-Pinilla’s UCLA team wrote four years ago, “… [fast food] diet[s] impose a risk factor to the molecular machinery in charge of maintaining neuronal [brain] function ...” (Wu A et al. 2008). Fortunately, they’ve also found that the brain damage induced in rats by junky diets can be blunted by exercise, omega-3s, and vitamin E. The UCLA scientists hypothesize that exercise and diets high in omega-3s and food-borne antioxidants can also help people maintain brain plasticity. Now, they’ve published another encouraging rat study … one with implications for the opposite roles of dietary sugars and omega-3s in people.

UCLA study tests omega-3 DHA against sugary brain damage
The new rat study from UCLA is the first to show how a diet high in fructose slows the brain, hampering memory and learning … and that omega-3 DHA can counteract the disruption (Agrawal R, Gomez-Pinilla F 2012). The findings, albeit from research in animals, should be of interest to people, since they suggest that indulging in soda and sweets routinely for as little as six weeks may blunt your brain.  

“Our findings illustrate that what you eat affects how you think,” said Gomez-Pinilla. “Eating a high-fructose diet over the long term alters your brain's ability to learn and remember information. But adding omega-3 fatty acids to your meals can help minimize the damage.” (UCLA 2012)

“[Omega-3] DHA is essential for synaptic function — brain cells' ability to transmit signals to one another,” Gomez-Pinilla said. “This is the mechanism that makes learning and memory possible. Our bodies can't produce enough DHA, so it must be supplemented through our diet.” (UCLA 2012)

While earlier research has revealed how fructose harms the body through its role in diabetes, obesity and fatty liver, this study is the first to uncover how the sweetener influences the brain. The UCLA team focused on high-fructose corn syrup (HFCS), which is ubiquitous in processed foods, soft drinks, condiments, sauces, dressings, and even baby food ... which explains why the average American consumes more than 40 pounds of HFCS annually.
Note: Compared with HFCS, cane sugar and other natural sweeteners contain just as much fructose … see our sidebar, “All sweeteners are full of fructose”, which covers some of the unique adverse effects of HFCS.

Omega-3 DHA blunted sugar-induced brain damage
All of the animals were fed standard rat chow and trained on a maze twice daily for five days. Then the authors divided the rats into two groups – Control and Omega-3. For six weeks, both groups got fructose in their drinking water but were fed a different diet:

*The supplemented chow contained 0.5% flaxseed oil and 1.2% DHA. Flaxseed oil contains the short-chain omega-3 called ALA, very little of which gets converted to DHA, so it’s not clear why the researchers included it. The UCLA team tested how well the rats were able to navigate a maze that contained numerous holes and visual landmarks but only one exit. Six weeks later, the researchers tested the rats’ ability to recall the route and escape the maze. What they saw supported the hypothesis that omega-3 DHA may help reduce the brain-dulling effects of sugar.

The second [omega-3-supplemented] group of rats navigated the maze much faster than the rats that did not receive omega-3 fatty acids,” Gomez-Pinilla said. (UCLA 2012) He added, “The [omega-3] DHA-deprived animals were slower, and their brains showed a decline in synaptic activity. Their brain cells had trouble signaling each other, disrupting the rats' ability to think clearly and recall the route they'd learned six weeks earlier.” (UCLA 2012)

Fructose also raised rat’s insulin resistance
The DHA-deprived rats also developed signs of resistance to insulin, a hormone that controls blood sugar and regulates synaptic function in the brain. A closer look at the rats’ brain tissue suggested that insulin had lost much of its power to influence the brain cells.  “Because insulin can penetrate the blood–brain barrier, the hormone may signal neurons to trigger reactions that disrupt learning and cause memory loss,” Gomez-Pinilla said. (UCLA 2012). He suspects that this special effect of fructose was a key culprit behind the DHA-deficient rats’ brain dysfunctions and consequent problems remembering the maze pattern.

Eating too much fructose could block insulin's ability to regulate how cells use and store sugar for the energy required for processing thoughts and emotions. “Insulin is important in the body for controlling blood sugar, but it may play a different role in the brain, where insulin appears to disturb memory and learning,” he said. “Our study shows that a high-fructose diet harms the brain as well as the body. This is something new.” (UCLA 2012)

UCLA researchers offer brainy diet advice
Gomez-Pinilla advises people to keep fructose intake to a minimum and swap sugary desserts for fresh berries and Greek yogurt, which he keeps in a small refrigerator in his office. An occasional bar of dark chocolate that hasn't been made without a lot of sugar is fine too, he said. (Look for bars containing at least 70% cocoa solids … the more the better, to reduce the proportion of sugar and maximize the amount of antioxidant-rich cocoa.) To make it safer to enjoy sweets in moderation, Gomez-Pinilla urges people to routinely eat foods rich in omega-3 DHA, like salmon, or take a daily omega-3 fish oil capsule … he recommends getting enough fish oil to provide one gram of DHA per day.

“Our findings suggest that consuming DHA regularly protects the brain against fructose's harmful effects,” said Gomez-Pinilla. “It's like saving money in the bank. You want to build a reserve for your brain to tap ...”. (UCLA 2012)

The UCLA study was funded by the National Institute of Neurological Disorders and Stroke. Gomez-Pinilla's lab will next examine the role of diet in recovery from brain trauma.

Sources: Agrawal R, Gomez-Pinilla F. 'Metabolic syndrome' in the brain: deficiency in omega-3 fatty acid exacerbates dysfunctions in insulin receptor signalling and cognition. J Physiol. 2012 May 15;590(Pt 10):2485-99. Epub 2012 Apr 2. Accessed at http://jp.physoc.org/content/early/2012/03/31/jphysiol.2012.230078.abstract. Heinrichs SC. Dietary omega-3 fatty acid supplementation for optimizing neuronal structure and function. Mol Nutr Food Res. 2010 Apr;54(4):447-56. Review. Rayssiguier Y, Gueux E, Nowacki W, Rock E, Mazur A. High fructose consumption combined with low dietary magnesium intake may increase the incidence of the metabolic syndrome by inducing inflammation. Magnes Res. 2006 Dec;19(4):237-43. Review. University of California Los Angeles (UCLA). Sugar makes you stupid: UCLA study shows high-fructose diet sabotages learning, memory. May 15, 2012. Accessed at http://www.eurekalert.org/pub_releases/2012-05/uoc--smy051512.php. Wu A, Ying Z, Gomez-Pinilla F. Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience. 2008 Aug 26;155(3):751-9. Epub 2008 Jun 17. Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma. 2004 Oct;21(10):1457-67. Wu A, Ying Z, Gomez-Pinilla F. The salutary effects of DHA dietary supplementation on cognition, neuroplasticity, and membrane homeostasis after brain trauma. J Neurotrauma. 2011 Oct;28(10):2113-22. Epub 2011 Oct 4.

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