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Content 7

 

The Doctor and the Pharmacist

Radio Show Articles:
December 10, 2011

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FDA Approves Hangover Medication
Scalping Cancer Drugs
More Bad News About Varenicline (Chantix®)
Exercise Referral Schemes Have Marginal Benefits for Sedentary Patients
Whole-Body Vibration: No Benefit for BMD
Could Iron-Fortified Formula Be Bad for Development?
Pediatric Antibiotic Prescribing in the U.S.: Frequent and Frequently Inappropriate
Can PTSD Be Prevented?
The Real Risk for Suicide in Mental Disorders
Meta-Analysis: Androgen Deprivation in Prostate Cancer Doesn't Increase
  Cardiovascular Death
Second-Generation Antidepressants Seem to Have Similar Efficacy
Autistic Children Have More Neurons
Omega-3s Score Again for Bones

FDA Approves Hangover Medication
The FDA has approved a new OTC hangover medication called Blowfish. It combines 1,000 milligrams of aspirin, 120 milligrams of caffeine and a "stomach-soothing agent" into two effervescent tablets taken the morning after a night of heavy drinking. The drug costs $2.99 for a single dose.
http://articles.nydailynews.com/2011-12-03/news/30473060_1_hangover-tablets-aspirin
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Scalping Cancer Drugs
Some companies are purchasing critical cancer medications in short supply and then attempting to resell them at inflated prices ranging from 650 percent to 4,000 percent over the usual cost. This "gray market" does not violate the law and could even be in a position to expand further following the presidential signing of an executive order that attempted to correct the problem. However, it may have only widened the loophole.
http://www.pharmacistelink.com/index.php/drugs-and-treatment/651-cancer-drug-scalpers-corner-us-market
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MM: Unfortunately the downside of Chantix® for smoking cessation is even worse than smoking. Mark Drugs has a better option. We have a prescription Nicotine lollipop available that provides a source of nicotine and merges the repetitious action of hand to mouth that is familiar and soothing to smokers. Please call us for more information.
  
PLoS ONE 2011 Nov 2; 6:e27016
More Bad News About Varenicline (Chantix®)
Compared with other smoking-cessation treatments, the risk for suicidal behavior or depression was markedly increased with varenicline.
The safety of varenicline for smoking cessation continues to generate controversy. In a recent systematic review and meta-analysis, investigators analyzed data from 14 trials and found a significantly increased risk for cardiovascular events with varenicline. Now, a group that includes some of the same authors has evaluated data from the FDA's Adverse Event Reporting System (AERS) to compare the neuropsychiatric safety profiles of three smoking-cessation treatments: varenicline, bupropion, and nicotine-replacement products.
 
The AERS consists of case reports about serious adverse events that are sent to drug manufacturers or directly to the FDA. From 13,243 case reports on the three products, the investigators identified 3249 events described as suicidal/self-injurious behavior or depression. Of these events, 90% were associated with varenicline, 7% with bupropion, and 3% with nicotine replacement. Of the 295 completed suicides, 92% were associated with varenicline. Headache and pain events, which are not surmised to be associated with these drugs but are common symptoms of nicotine withdrawal, did not differ in prevalence among the three interventions.
 
Comment: This study has many limitations and provides no information on absolute risk, but the findings raise further concerns about the adverse-event profile of varenicline. The challenge for clinicians is to balance these potential risks against the clear benefits of smoking cessation. These authors conclude that varenicline should not be used as a first-line agent for smoking cessation. Until more information on adverse-event incidence is available, the drug should at least be prescribed with caution and close surveillance.
Harlan M. Krumholz, MD, SM Published in Journal Watch Cardiology December 7, 2011
 
Citation(s): Moore TJ et al. Suicidal behavior and depression in smoking cessation treatments. PLoS ONE 2011 Nov 2; 6:e27016.
http://www.ncbi.nlm.nih.gov/pubmed/22073240?dopt=Abstract
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MM: This brings to mind the old adage, “Don’t throw out the baby with the bath water.” Exercise is certainly not the be all and end all to all metabolic syndrome issues but it should be a part of an overall health program. Benefits have been shown for improved mood, decreased pain and increased mobility. All of which are more difficult to measure than BMI, BP & lipids. BMI is an easy mathematical assessment but fat vs lean muscle changes are likely to be more meaningful and this is achieved with a proper diet and exercise. These Quality of Life (QOL) aspects should not be ignored.
  
BMJ 2011 Nov 6; 343:d6462
Exercise Referral Schemes Have Marginal Benefits for Sedentary Patients
Patients exercised more, but body-mass index, blood pressure, and lipid levels remained unchanged.
General practitioners are well-positioned to advise sedentary patients to exercise more and to refer them to exercise programs. In this meta-analysis, investigators assessed the effect of exercise referral schemes (the identification and referral of sedentary individuals to third-party providers who prescribe and monitor exercise programs tailored to individual needs) on physical activity and health
 
Eight randomized trials with 5200 sedentary primary care patients (follow-up range, 2–12 months) were included. Compared with usual care (simple exercise advice or no intervention), exercise referral schemes resulted in a 16% relative increase in the number of participants who achieved 90 to 150 minutes of moderately intense physical activity weekly but did not result in lower body-mass index (BMI) or body fat. No between-group differences were noted in blood pressure, lipid levels, or respiratory function. However, exercise referral schemes resulted in significantly fewer patients with depression.
 
Comment: In this meta-analysis, exercise referral schemes increased physical activity and lowered the incidence of depression, but did not affect BMI, blood pressure, or lipid levels in sedentary primary care patients. An editorialist points out that simple exercise advice, which control-group participants in these trials received, has a small salutary effect on increasing physical activity — "similar to advice to stop smoking." Therefore, we can reasonably continue to advise sedentary patients to increase their physical activity, bearing in mind that the benefits of referring such patients to exercise programs appear to be marginal.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine
December 6, 2011
 
Citation(s):Pavey TG et al. Effect of exercise referral schemes in primary care on physical activity and improving health outcomes: Systematic review and meta-analysis. BMJ 2011 Nov 6; 343:d6462. (http://dx.doi.org/10.1136/bmj.d6462)
http://www.ncbi.nlm.nih.gov/pubmed/22058134?dopt=Abstract
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MM: Unfortunately, “quackery” medical devices seem to constantly enter the market and have done so for hundreds if not thousands of years. Also, unfortunately, when a product that has true medicinal benefit fails to consistently be successful it may be withheld from the marketplace. This is a tight rope that we walk. One that tries to protect consumers while also trying to benefit those same consumers.
  
Ann Intern Med 2011 Nov 15; 155:668
Whole-Body Vibration: No Benefit for BMD
Daily use of devices for 1 year did not improve bone-mineral density.
Animal studies have suggested that whole-body vibration (WBV) –– delivered via platforms that vibrate while the user stands still –– can improve bone density; however, results from human studies have not been clear-cut. In this Canadian trial, researchers enrolled 202 postmenopausal women with bone-mineral density T-scores of –1.0 to –2.5; the participants were randomized to 90-Hz WBV, 30-Hz WBV (each for 20 minutes daily), or no WBV. All patients received calcium and vitamin D supplements.
 
After 12 months, no significant differences in bone-mineral density were found across groups.
 
Comment: Many WBV devices are marketed directly to patients. In a quick Google search, I found several websites that promote devices ranging in price from US$200 to $2000 with claims such as "researchers have found that rapid, whole-body vibration builds bone density." In this study, which by far is the largest to date, WBV use provided no benefits for bone health.
Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine December 6, 2011
 
Citation(s):Slatkovska L et al. Effect of 12 months of whole-body vibration therapy on bone density and structure in postmenopausal women: A randomized trial. Ann Intern Med 2011 Nov 15; 155:668. (http://www.annals.org/content/155/10/668.full)
http://www.ncbi.nlm.nih.gov/pubmed/22084333?dopt=Abstract
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Arch Pediatr Adolesc Med 2011 Nov 7
Could Iron-Fortified Formula Be Bad for Development?
Children given iron-fortified formula as infants scored lower on cognitive and visual-motor tests at age 10 years.
Most infant formula in the U.S. is fortified with iron (about 12 mg/L), and keeping infants iron replete is thought to be key to normal development. To examine long-term developmental effects of iron-fortified formula, researchers assessed measures of IQ, math skills, spatial memory, and visual and motor functioning in 473 10-year-olds in Chile who had participated in an anemia prevention trial as infants. Each child had been randomized to receive either iron-fortified formula (mean, 12.7 mg/L) or low-iron formula (2.3 mg/L) between ages 6 and 12 months. Infants with iron deficiency anemia were excluded. At age 12 months, iron deficiency without anemia was significantly more common in the low-iron group than the iron-fortified group (35% vs. 17%); at age 10 years, iron status did not differ between groups.
 
All developmental test scores were higher in the low-iron group than in the iron-fortified group, but scores were significantly higher only for spatial memory and visual-motor integration (mean differences, 4.6 and 2.6 points, respectively, on 100-point scales). Among a small subset of 26 children with high hemoglobin levels (>12.8 g/dL) at age 6 months, the low-iron group scored significantly better than the iron-fortified group on all tests but one, with mean differences ranging between 11 and 19 points.
 
Comment: It makes sense that we should not give infants too little or too much iron. But is iron-fortified formula itself detrimental to long-term development, especially in infants with relatively high hemoglobin levels (and presumably high iron stores)? An editorialist notes that findings from other studies of development and iron supplementation are inconsistent. These are provocative results and should be replicated before we start checking hemoglobin levels in young infants and stocking up on low-iron formula.
Cornelius W. Van Niel, MD Published in Journal Watch Pediatrics and Adolescent Medicine December 7, 2011
 
Citation(s):Lozoff B et al. Iron-fortified vs low-iron infant formula: Developmental outcome at 10 years. Arch Pediatr Adolesc Med 2011 Nov 7; [e-pub ahead of print], (http://dx.doi.org/10.1001/archpediatrics.2011.197)
Christian P. Iron in infancy and long-term development. Arch Pediatr Adolesc Med 2011 Nov 7; [e-pub ahead of print]. (http://dx.doi.org/10.1001/archpediatrics.2011.203)
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Pediatric Antibiotic Prescribing in the U.S.: Frequent and
Frequently Inappropriate

Pediatric ambulatory care visits in the U.S. frequently lead to antibiotic prescriptions for conditions in which they are not clearly indicated, according to a Pediatrics study.
 
Researchers examined nationally representative data from more than 60,000 pediatric ambulatory visits for the years 2006 through 2008. Among the findings:

http://pediatrics.aappublications.org/content/128/6/1053.abstract
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MM: I found it interesting that in many of the comments on this article by psychiatrists, they seemed to indicate that the most important treatment aspect to prevent PTSD is promptness. They also repeatedly mentioned the use of beta blockers such as Inderal® (propranolol).
  
Arch Gen Psychiatry 2011 Oct 3
Can PTSD Be Prevented?
Prolonged exposure or cognitive therapy seems very effective for patients who show PTSD symptoms soon after trauma.
Studies of the use of medications or debriefing to prevent post-traumatic stress disorder (PTSD) in traumatized people have had disappointing results, perhaps because of the intervention's timing or because participants were unlikely to develop PTSD (e.g., did not have acute stress disorder). Researchers in Israel randomized 296 adults who had been exposed to motor vehicle accidents, terrorist attacks, or other traumas to four treatment conditions for 12 weeks. Participants had PTSD symptoms but did not meet the duration criterion for formal diagnosis (82% met all symptomatic criteria).
 
Participants could decline one or two treatments. Treatments were prolonged exposure (PE; imaginal and in vivo exposure and breathing-control training [paced diaphragmatic breathing]); trauma-focused cognitive therapy (CT); double-blind drug therapy (20 mg/day escitalopram vs. pill placebo); or waiting list (WL). At 5 months, PE and CT recipients were significantly less likely to have PTSD (prevalence, 18%–21%) than those assigned to escitalopram, placebo, or WL (prevalence, 56%–62%).
 
Symptomatic WL patients were offered delayed PE after 5 months. At 9 months, PTSD prevalence remained significantly higher with escitalopram and placebo (42%–47%), but decreased in the WL group to that of the PE and CT groups (21%–23%). Patients with only some baseline PTSD symptoms did equally well regardless of assignment.
 
Comment: One could argue that these researchers were studying treatment of evolving PTSD, not prevention of PTSD in an at-risk group. Still, a moderate antidepressant dose seems to not alter the risk for full-blown PTSD and to produce worse outcomes at 9 months than prolonged exposure and cognitive therapy. PE and CT seem very effective for short-term PTSD symptoms, but people with few PTSD symptoms seem not to need these interventions. Soon after catastrophic events that affect a large number of people, those with PTSD symptoms should be offered PE or CT. If resources are limited, treatment can be deferred for some (e.g., those who do not yet want it), with the understanding that later treatment works but delays the start of recovery.
Steven Dubovsky, MD Published in Journal Watch Psychiatry November 21, 2011
 
Citation(s): Shalev AY et al. Prevention of posttraumatic stress disorder by early treatment: Results from the Jerusalem Trauma Outreach and Prevention study. Arch Gen Psychiatry 2011 Oct 3; [e-pub ahead of print]. (http://dx.doi.org/10.1001/archgenpsychiatry.2011.127)
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MM: Finally, we see that the world may be in a better state than previously reported. For those who have friends or family members with long time psychiatric disorders and were in fear for their well-being, it is a ray of sunshine to see that they may not be at the level of risk that was previously expected. However, it is still important to be vigilant and especially for newly diagnosed cases as these appear to be the patients most significantly at risk for self harm.
  
Arch Gen Psychiatry 2011 Oct; 68:1058.
The Real Risk for Suicide in Mental Disorders
New results suggest that the risk is lower than previously reported
Presence of a mental disorder increases the risk for suicide, but investigators typically have estimated risks in relatively brief, small studies, without adjusting for patients who are lost to follow-up or die of unclear causes. To avoid these limitations while ascertaining lifetime risks for suicide associated with specific disorders, researchers used Danish national registries to prospectively follow 176,347 people with a first psychiatric contact for a mental disorder after age 15 and 881,735 nonpsychiatric controls for up to 36 years (birth years, 1955–1991). Data included diagnoses of all treatment recipients; death from suicide or from other causes; emigration; and loss to follow-up.
 
Absolute risk (i.e., cumulative incidence) for suicide in nonpsychiatric controls was 0.72% in men and 0.26% in women. In patients with bipolar disorder, the risk was 7.77% in men and 4.78% in women; in those with unipolar depression, 6.67% and 3.77%; in those with schizophrenia, 6.55% and 4.91%; in those with "schizophrenia-like disorder," 5.90% and 4.07%; and in those with substance abuse treated in psychiatric settings, 4.71% and 3.34%. Suicide risk in women with anorexia nervosa was 2.62%. Independent of age at onset of the disorder, suicide risk increased the most in the early years after first psychiatric contact; cumulative incidence stabilized after 22 years. Lifetime suicide risk increased with comorbid substance abuse or unipolar depression and doubled with history of deliberate self-harm (e.g., overdose). Men with bipolar disorder and deliberate self-harm had the highest lifetime suicide risk (17.08%).
 
Comment: Although suicide risk is clearly elevated in people with psychiatric disorders, their suicide rates are lower in this comprehensive study than in other studies. The authors state that not accounting for emigration and death from other causes would have increased their estimates of risk by 10%. This study's most important clinical implications: Suicide risk increases sharply soon after diagnosis, and comorbidity and history of self-harm, especially in men with bipolar disorder, greatly increase suicide risk. Such individuals should be monitored closely for suicidality.
Steven Dubovsky, MD Published in Journal Watch Psychiatry November 21, 2011
 
Citation(s):Nordentoft M et al. Absolute risk of suicide after first hospital contact in mental disorder. Arch Gen Psychiatry 2011 Oct; 68:1058.
http://www.ncbi.nlm.nih.gov/pubmed/21969462?dopt=Abstract
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Meta-Analysis: Androgen Deprivation in Prostate Cancer Doesn't Increase Cardiovascular Death
Contrary to earlier findings, androgen-deprivation therapy for prostate cancer carries no apparent increased risk for cardiovascular mortality, according to a JAMA meta-analysis. Editorialists, however, express caution.
 
Researchers examined outcomes from eight randomized trials testing androgen deprivation against control therapy in some 4000 men with unfavorable-risk nonmetastatic prostate cancers.
 
Androgen deprivation was not associated with increased cardiovascular mortality during roughly 10 years' follow-up. In fact, both prostate cancer–specific mortality and all-cause mortality were lower with androgen deprivation.
 
The editorialists point out that the meta-analysis focuses on mortality and does not take into account the possible effects of deprivation on "development or acceleration of cardiovascular disease." They point to a Swedish registry study from 2010 that found elevated cardiovascular risks in all prostate cancers — and the risks increased with androgen deprivation. They recommend that men with cardiac disease undergoing androgen deprivation "should follow the appropriate secondary preventive measures."
http://jama.ama-assn.org/content/306/21/2359.short
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Second-Generation Antidepressants Seem to Have Similar Efficacy
All second-generation antidepressants have roughly the same therapeutic efficacy in adults with major depressive disorder, according to an Annals of Internal Medicine meta-analysis. Their differences lie mainly in their rapidity of action, side effects, and price.
 
The drugs under consideration were bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine. Studies that compared drugs head-to-head were used to assess relative efficacies, and when head-to-head studies were not available, indirect assessments were possible when two drugs were separately compared with placebos.
 
Although the drugs were all found to be about equally effective, they differed in their side effects, dosing convenience, onset of action, cost, and indications for use outside of depression. The authors counsel that "familiarity with a broad spectrum of antidepressants is prudent." They conclude that current evidence "does not warrant" choosing a particular drug as first-line therapy
http://www.annals.org/content/155/11/772.abstract
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JAMA 2011 Nov 9; 306:2001
Autistic Children Have More Neurons
These findings support the hypothesis that autism is present at birth, even if not yet clinically evident.
Autistic children have macrocephaly (e.g., Neurology 2002; 59:175), but whether neuron and glia cell counts correspond with that finding has not been known. These researchers conducted a postmortem study of seven autistic boys and six normal boys (age range, 2–16 years). Dorsolateral and mesial prefrontal cortical (DLPFC and mPFC, respectively) areas in the brain specimens were suitable for stereological cell counts. Causes of death could not include diseases or conditions associated with increased brain size or neuronal cell counts. Autism severity ranged from intellectual disability to having functional speech, ascertained by postmortem standardized parent interviews (1 child was diagnosed with autism when alive). Analyses compared neuron and glia cell counts and brain weights between groups.
 
Mean neuron cell counts in the DLPFC and mPFC were 67% higher in the autism group (DLPFC, 79%; mPFC, 29%) than in the healthy comparison group. Compared with mean normal brain weights for age, brain weights were 17.6% higher in the autism group (a significant difference) and 0.2% higher in the comparison group. Only in controls were cell counts linearly associated with brain weight. Glia cell counts did not differ significantly between groups.
 
Comment: Because neuronal development is ordinarily complete in the first half of gestation, these findings support the hypothesis that autism is present at birth, even if not yet clinically evident. Therefore, they reinforce the need for the earliest possible interventions that might mitigate later impairments (JW Psychiatry Jun 21 2010) and for preventive efforts as environmental risk factors become known (JW Psychiatry Aug 15 2011 and Aug 29 2011). Future researchers can address how these findings relate to different clinical trajectories (worsening, regression, lack of development; JW Psychiatry Jun 27 2011).
Barbara Geller, MD Published in Journal Watch Psychiatry December 5, 2011
 
Citation(s):Courchesne E et al. Neuron number and size in prefrontal cortex of children with autism. JAMA 2011 Nov 9; 306:2001.
http://www.ncbi.nlm.nih.gov/pubmed/22068992?dopt=Abstract
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http://www.imakenews.com/eletra/mod_print_view.cfm?this_id=2288246&u=
vitalchoiceseafood&show_issue_date=F&issue_id=000561093&lid=bklRCNc&uid=b1h1R7NC

Omega-3s Score Again for Bones
Omega-3 fish oil plus exercise bolstered women’s bones more effectively than either tactic could by itself
by Craig Weatherby
Many things remain uncertain about human bones, and how to keep them strong indefinitely. For certain, weight-bearing exercise and adequate intake of key nutrients are critical to bone strength and resiliency. The key bone minerals are calcium, magnesium, boron, copper, manganese, phosphorus, and zinc, while the critical vitamins are D, K, A, B6, B12, C, and folic acid. But another, long-overlooked factor in the bone-health equation is fatty acids … namely, the contrasting effects of omega-3 and omega-6 fatty acids.

As Dr. Bruce Watkins of Purdue University said in 2005, “Our lab and others have shown that omega-3 fatty acids help promote bone formation. We also have shown that higher intakes of omega-6 fatty acids lead to an increased production of compounds associated with bone loss.” Bone researchers suspect that some of the omega-3 fish fats’ apparent bone benefits flow from their tendency to curb production of pro-inflammatory messenger proteins (cytokines) … which also promote the breakdown of bone. For more on this, see “Omega-3s Seen as Stellar Bone-Builders” and other articles in the “Omega-3s & Bone Health” section of the Vital Choices archive.

Most recently, as we reported in “Fishy Diets May Bolster Hip Bones”, Tufts University researchers analyzed dietary habits and medical records from more than 600 older adults in the Boston area. Those who consumed the most long-chain omega-3 fatty acids (EPA and DHA) from fish and fish oil were more likely to have maintained adequate hip-bone density four years later. In contrast, low omega-3 intake combined with high intake of omega-6 fatty acids – whether from vegetable oils and plant or animal foods – was linked to developing dangerously porous hip bones.

Iranian trial finds omega-3s + exercise yield synergistic bone benefits
The results of a small clinical trial add valuable new information to the bone health picture, by testing omega-3s and exercise … alone and together. The trial was conducted by the same research team – from Iran’s Urmia University – that has performed three prior studies on the effects of supplemental omega-3s in people during exercise. We covered two of their studies in “Omega-3s for Exercise: Trials Find Muscle and Breathing Benefits”.

The purpose of their new study was to examine the effects of aerobic exercise and omega-3 supplementation on bone mineral density (BMD), and other markers of bone health, including inflammation, in post-menopausal women. They recruited 79 healthy, sedentary post-menopausal women aged 58 to 78 for this 6-month trial, and assigned them randomly to one of 4 groups:

  1. Exercise + Omega-3s (1000mg daily)
  2. Exercise only
  3. Omega-3s only
  4. Control (no exercise or fish oil)

The subjects in the E+O-3 and E groups performed aerobic exercise training (walking and jogging), three times a week for 24 weeks. The exercise was designed to cause the subjects to attain 65 percent of their safe maximum heart rate (HRmax), based on their age. The researchers measured key signs of bone health at the outset, and again after 12 and 24 weeks:

The results were surprisingly clear and dramatic, with only the Exercise + Omega-3s group showing desirable increases in blood levels of estrogen, calcitonin, vitamin D3, spine and pelvis BMD. Likewise, only the Exercise + Omega-3s group showed desirable drops in blood C-telopeptide, parathyroid hormone, TNF-alpha, IL-6, and PG-E2. Perhaps unsurprisingly, the women in the three other groups showed higher levels of inflammation and other markers for poor bone health. They also had lower levels of positive bone health markers. As the Iranian team wrote, “The present study demonstrates that long-term aerobic exercise training plus omega-3 supplementation [has] a synergistic effect in attenuating [lessening] inflammation and augmenting BMD in post-menopausal [women’s] osteoporosis.”

What’s the takeaway? Omega-3s and exercise are both proven beneficial to bone health, but seem to work better and faster when combined.
 
Sources: Tartibian B, Hajizadeh Maleki B, Kanaley J, Sadeghi K. Long-term aerobic exercise and omega-3 supplementation modulate osteoporosis through inflammatory mechanisms in post-menopausal women: a randomized, repeated measures study. Nutr Metab (Lond). 2011 Oct 15;8:71. Accessed at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212907. Tartibian B, Maleki BH, Abbasi A. Omega-3 fatty acids supplementation attenuates inflammatory markers after eccentric exercise in untrained men. Clin J Sport Med. 2011 Mar;21(2):131-7. Tartibian B, Maleki BH, Abbasi A. The effects of omega-3 supplementation on pulmonary function of young wrestlers during intensive training. J Sci Med Sport. 2010 Mar;13(2):281-6. Epub 2009 Jun 12. Tartibian B, Maleki BH, Abbasi A. The effects of ingestion of omega-3 fatty acids on perceived pain and external symptoms of delayed onset muscle soreness in untrained men. Clin J Sport Med. 2009 Mar;19(2):115-9.
 
 
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