• Challenges in Glycemic Control for Adolescents with Type 2 Diabetes
• FDA: Teething Pain Remedies Dangerous
• FDA to Let Women Try New Breast Drugs Earlier
• Elimination Diet Works for Eosinophilic Esophagitis in Adults
• Dietary Fats Are Associated with Cognition
• CDC Reports 2012 Was Among Mildest Flu Seasons on Record
• Chill Out and Live Longer
• Alcohol Sensitivity and Mood Disorder
• FDA Warns Against Pain Relief Supplement
• Treatment of Subclinical Hypothyroidism Is Associated with Fewer Ischemic Cardiac Events
• HDL Cholesterol: Causal or Just a Marker for Coronary Risk?
• Computers Can Help Treat Adolescent Depression
• New Eye Benefit Seen in Omega-3s
• Interaction Between SSRIs and NSAIDs? Now It's Missing
MM: As I see it, the issue remains that drug treatment of type 2 diabetes remains a reactive rather than a pro-active approach to the problem. Long term lifestyle changes are necessary to get long term benefits. This must include weight loss, exercise and appropriate nutritional education. It is also interesting to note that the group with the highest failure rate was non-hispanic blacks, which would likely correlate with decreased systemic vitamin D levels. Vitamin D helps cellular function throughout the body including the pancreas and has a definitive potential impact on diabetes.
N Engl J Med 2012 Apr 29
Challenges in Glycemic Control for Adolescents with Type 2 Diabetes
Metformin plus rosiglitazone bested metformin monotherapy, but failure rates for all tested regimens were disappointingly high.
To address the persistent challenge of maintaining glycemic control in adolescents with type 2 diabetes, researchers compared three treatment options. The participants were 699 teenagers (age range, 10–17 years) with type 2 diabetes, body-mass index (BMI) in the 85th percentile, a negative test for diabetes-related autoantibodies, and a fasting C-peptide level >0.6 ng/mL.
After maintaining a glycated hemoglobin level <8% for 
2 months on metformin monotherapy, participants were randomized to continue receiving metformin alone, to receive metformin plus rosiglitazone (a thiazolidinedione that increases fat cells' sensitivity to insulin), or to receive metformin plus a lifestyle intervention. Mean follow-up was about 4 years.
Treatment failure — defined as a persistently elevated glycated hemoglobin level (
8%) for at least 6 months — occurred in 52% of the metformin-alone group, 39% of the metformin–rosiglitazone group, and 47% of the metformin–lifestyle group. Only the difference between the rosiglitazone group and the monotherapy group was statistically significant. The change in BMI over time differed significantly among the groups but was not a significant determinant of treatment failure.
The overall failure rate was somewhat higher in boys than girls (48% vs. 44%), and metformin plus rosiglitazone was significantly more effective in girls than boys. Non-Hispanic blacks had the highest failure rate overall (53%) and, in particular, with metformin monotherapy (66%).
Comment: Metformin plus rosiglitazone was superior to metformin monotherapy for achieving glycemic control in teenagers with type 2 diabetes. Rosiglitazone has been shown to be associated with myocardial infarction and heart disease in adults (JW Gen Med Apr 7 2011). Regardless of the therapy protocols used in this trial, the lack of success in maintaining glycemic control (an overall failure rate of 46%) is nonetheless disappointing.
— F. Bruder Stapleton, MD Published in Journal Watch Pediatrics and Adolescent Medicine May 23, 2012
Citation(s): TODAY Study Group. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med 2012 Apr 29; [e-pub ahead of print].
(http://dx.doi.org/10.1056/NEJMoa1109333)
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FDA: Teething Pain Remedies Dangerous
The FDA has warned that rubbing topical anesthetics such as Anbesol or Orajel on the throbbing gums of a teething baby can lead to methemoglobinemia and—in extreme cases—death. These OTC products contain benzocaine, and that is the source of the FDA's concern. The risk appears greatest among children less than 2 years old, the age range at which most children experience teething pain.
http://www.medpagetoday.com/Pediatrics/GeneralPediatrics/33006
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FDA to Let Women Try New Breast Drugs Earlier
A new FDA guidance document will allow drug companies to test their medications for a few months on women with highly aggressive breast cancers before they have surgery, instead of waiting until the drug has been proven first in gravely ill patients.
The aim of this therapy would be to cure the woman of breast cancer by moving a very promising drug into an early stage of the disease with a curative intent. This is a significant change from the current approach, in which promising drugs only are tested in earlier stage cancers after they have first proven to be safe and effective in advanced, metastatic cancer.
http://www.reuters.com/article/2012/06/03/us-cancer-trials-fda-idUSBRE85208720120603
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MM: I love the premise of this study. I have long postulated that many people have food sensitivities that are otherwise not seen with conventional allergy testing. Following the HCG Metabolic Syndrome and Weight Loss Protocol, we have experienced hundreds of patients who have discovered that certain foods – many that they love and desire – are triggers of intestinal inflammation, water retention and subsequent weight re-gain. Some of the most common of these foods are wheat/gluten and corn. This is consistent with the results of this study.
Gastroenterology 2012 Jun; 142:1451
Elimination Diet Works for Eosinophilic Esophagitis in Adults
A six-food elimination diet led to symptom improvement in 94% of patients and complete histologic improvement in 64%.
Eosinophilic esophagitis (EoE) is increasingly recognized as a cause of dysphagia, food impaction, and heartburn. In children, a true elemental diet seems to be effective but is too unpalatable for routine use. A six-food elimination diet (milk, soy, egg, wheat, peanuts/tree nuts, and shellfish/fish) has shown moderate effectiveness in treating children with EoE but has not been well studied in adults.
In a single-center, prospective study, researchers recruited 50 adult patients with symptoms of dysphagia, heartburn, or food impaction and 
15 eosinophils per high-power field (eos/hpf) to receive treatment with the six-food elimination diet instead of topical corticosteroids. The diet lasted 6 weeks, at which point endoscopy with esophageal biopsies was conducted to measure the primary endpoint of complete histologic improvement (
5 eos/hpf). Subsequently, one food was reintroduced every 2 weeks, and endoscopy with biopsy was repeated every 4 weeks during that process.
Of the 20 patients who completed the elimination diet, the mean esophageal eosinophil count decreased from 34 to 8 eos/hpf in the proximal esophagus and from 48 to 13 eos/hpf in the distal esophagus (P<0.0001 for both). At diet completion, eosinophil counts were 
5 eos/hpf in 64% of patients and 
10 eos/hpf in 70%; reduction in eosinophil count was 
50% in 78% of patients. Dysphagia symptom scores decreased in 94%, and endoscopic features improved in 78%. Response was greatest in those with initial complaints of heartburn. After reintroduction of trigger foods, all patients showed symptom recurrence within 5 days (median, 3 days) and histologic recurrence. The most common food triggers were wheat (60%) and milk (50%), followed by soy (10%), nuts (10%), and egg (5%). Fifteen percent of patients had 
1 trigger. Skin-prick testing predicted only 13% of these triggers.
Comment: This study is the first to demonstrate the effectiveness of a six-food elimination diet for eosinophilic esophagitis in adults. These results are similar to those found in children with EoE, supporting the hypothesis that food antigens play a role in susceptible individuals. Symptom recurrence after food reintroduction was rapid, which could be a useful marker for clinicians utilizing this approach. Unfortunately, skin-prick testing provided no guidance on dietary triggers for this disease. Also, about one third of patients did not achieve the benchmark for histologic improvement on this elimination diet, perhaps reflecting other potential allergens, dietary noncompliance, or cross-contamination. Patient adherence to the diet might necessitate the services of a dietician with expertise in food allergies. The long-term efficacy of this elimination diet is unknown.
— Chris E. Forsmark, MD Published in Journal Watch Gastroenterology June 8, 2012
Citation(s): Gonsalves N et al. Elimination diet effectively treats eosinophilic esophagitis in adults; Food reintroduction identifies causative factors. Gastroenterology 2012 Jun; 142:1451.
http://www.ncbi.nlm.nih.gov/pubmed/22391333?dopt=Abstract
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Ann Neurol 2012 May 17
Dietary Fats Are Associated with Cognition
In healthy older women, low saturated fat intake and high monounsaturated fat intake were beneficial.
"Unhealthy fats" — saturated fats and trans fats — promote cardiovascular disease, and "healthy fats" — monounsaturated and polyunsaturated fats — prevent cardiovascular disease. A new report from the Women's Health Study involved 6183 older women (mean age at study entry, 66) who provided detailed food-intake histories and underwent repeated cognitive testing (general cognition, verbal memory, and semantic fluency) during 4 years.
After adjusting for multiple confounding factors, higher saturated fat intake was associated significantly with worse global cognitive scores. In contrast, higher monosaturated fat intake was associated with better global cognitive scores. Researchers found a linear relation between the amount consumed of each fat consumed and the degree to which cognition changed. Women with the highest saturated fat intake were 60% to 70% more likely to develop poor cognition than were women with the lowest intake. In contrast, women with the highest monounsaturated fat intake had a 40% to 50% lower chance of poor cognition compared with those with the lowest intake. Contrary to the authors' hypothesis, neither trans fat nor polyunsaturated fat intake was associated with significantly worse or better cognition.
Comment: This large meticulously conducted observational study in older women shows a strong association between cognitive decline and both high saturated fat intake and low monounsaturated fat intake. In the absence of a randomized trial, the association cannot be considered causal; however, a randomized trial of this particular dietary pattern is unlikely to be conducted. The relatively low intake of trans fats in these generally healthy women might have led to the investigators' inability to establish an association with cognitive decline.
— Anthony L. Komaroff, MD Published in Journal Watch General Medicine June 5, 2012
Citation(s): Okereke OI et al. Dietary fat types and 4-year cognitive change in community-dwelling older women. Ann Neurol 2012 May 17; [e-pub ahead of print].
(http://dx.doi.org/10.1002/ana.23593)
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MM: Could this low incidence of flu be somehow related to the extraordinarily warm February/March we experienced in much of the country? We saw temperatures reaching into the 70’s and even the 80’s in much of the United States. The temperature alone would not have improved the lack of flu numbers but the skies were clear and I saw people out sunbathing on several days thereby possibly increasing their vitamin D levels. In late spring and summer, 20 minutes of sun exposure in the midwest for a fair complected person can yield as much as 20,000 IU of long-acting vitamin D. Perhaps this unseasonably warm weather and people’s ensuing activities inadvertently contributed to their improved immune status.
CDC Reports 2012 Was Among Mildest Flu Seasons on Record
The 2011–2012 influenza season turned out to be one of the mildest and latest on record in the United States, according to an article in MMWR.
Among the findings:
- The peak percentage of outpatient visits for influenza-like illness was 2.4% — the lowest since the surveillance program began in 1997.
- Hospitalization rates were also lower than in recent years, and there were fewer pneumonia and influenza deaths.
- The influenza A (H3N2) viruses were the most commonly reported, but the 2009 pandemic strain was also evident, particularly in the South. In addition, testing revealed 13 infections with H3N2v viruses, one with H1N1v, and one with H1N2v.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6122a4.htm?s_cid=mm6122a4_w
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Biol Psychiatry 2012 May 1; 71:767.
Chill Out and Live Longer
In men, but not in women, high levels of cynical hostility are linked to shorter telomeres and greater telomerase activity.
Hostility, a trait characterized by a global mistrustful attitude, has long been associated with elevated risks for illness and premature death. Recently, early mortality has been linked to shortened telomeres, resulting in genomic instability and early apoptosis (see JW Psychiatry Jan 12 2005). In the current study involving 434 British people without coronary heart disease (mean age, 63), researchers (two with proprietary interests in a telomere diagnostic company) examined the relationship of cynical hostility with two risk factors for early mortality — leukocyte telomere length (TL) and activity of telomerase (a telomere repair enzyme activated by telomere shortening).
Analyses adjusted for age, socioeconomic status, body-mass index, waist circumference, and sex. In men only, higher cynical hostility was associated with shorter TL, higher telomerase activity (TA), and the combination of shorter TL and higher TA. The association remained significant when other factors independently associated with short TL and TA were controlled for, such as plasma triglycerides, interleukin-6, salivary cortisol, and alcohol consumption.
Comment: Telomere shortening was not completely explained by other factors commonly associated with telomere length and telomerase activity. TA up-regulation may have most likely been an unsuccessful attempt to repair shortened telomeres. These authors did not study actual morbidity and mortality. Still, to the extent that short TL is a reliable marker of vulnerability to many illnesses, the results are consistent with others demonstrating that hostile men are prone to an exaggerated and prolonged stress response, poor self-care, and vulnerability to cardiovascular disease. Even though there is as yet no evidence that amelioration of hostility and its physiologic consequences reverses premature cellular aging, addressing hostility in patients is an appropriate health-maintenance intervention.
— Steven Dubovsky, MD Published in Journal Watch Psychiatry June 4, 2012
Citation(s): Brydon L et al. Hostility and cellular aging in men from the Whitehall II cohort. Biol Psychiatry 2012 May 1; 71:767.
http://www.ncbi.nlm.nih.gov/pubmed/21974787?dopt=Abstract
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Neuropsychopharmacology 2012 Apr 11
Alcohol Sensitivity and Mood Disorder
Young adults with bipolar features expect more pleasant effects from alcohol intake but have lower "highs" than controls.
High rates of alcohol use disorders (AUDs) among patients with bipolar disorders warrant examination of possible risk factors. These researchers conducted randomized, double-blind, cross-over trials of responses to a fruit drink plus alcohol or plus placebo (alcohol aroma was added to placebo). The participants were 20 young men (ages, 18–21) with broad bipolar phenotype (BBP) and 20 healthy controls matched for age and alcohol intake. BBP participants had scored 7 or higher on the Mood Disorders Questionnaire (3 people had bipolar disorder II or not otherwise specified), and controls had scored 0. The alcohol and placebo trials occurred separately, 1 week apart.
BBP participants had greater expectations (e.g., relaxation, arousal) than controls and, after alcohol (but not placebo), reported less intoxication. However, the two groups had equivalent breath alcohol levels and self-reported stimulant and sedative subscale scores. Greater expectancy was not significantly related to subjective drug effects that had between-group differences (e.g., getting high). This lack of correlation supports the hypothesis that the alcohol "high" was not due to expectancy.
Comment: Only longitudinal studies can address whether a low subjective response to alcohol predicts future alcohol use disorders. Nevertheless, it is reasonable to hypothesize that low response increases AUD risk because at-risk adolescents would likely increase intake to experience intoxication. How to clinically incorporate these findings is challenging, because of the easy availability of alcohol and social acceptance of intoxication among teenagers and young adults. Many people, however, may be unaware of differing responses to and sequelae of alcohol intake. Therefore, it may be useful to educate adolescents, families, and teachers about this phenomenon and the consequent need for individual choice between momentary intoxication and potential lifetime AUD.
— Barbara Geller, MD Published in Journal Watch Psychiatry May 14, 2012
Citation(s):Yip SW et al. Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype. Neuropsychopharmacology 2012 Apr 11; [e-pub ahead of print].
(http://dx.doi.org/10.1038/npp.2012.45)
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FDA Warns Against Pain Relief Supplement
The FDA cautioned late last week against using Reumofan Plus, a dietary supplement marketed as a "natural" pain reliever for arthritis, osteoporosis, and other conditions. The drug, which is made in Mexico but available online, contains unlabeled and potentially harmful pharmaceutical ingredients.
The warning follows reports of adrenal suppression, leg cramps, liver injury, and worsening glucose control associated with Reumofan Plus. FDA analysis revealed that it contains both diclofenac sodium, an NSAID that poses increased risk for serious cardiovascular and gastrointestinal events, and methocarbamol, a muscle relaxant that can cause dizziness, hypotension, and sedation. In addition, the Mexican government found that at least one lot contained the corticosteroid dexamethasone.
Patients who have used the supplement should be evaluated for disease and drug interactions.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/
SafetyAlertsforHumanMedicalProducts/ucm306360.htm
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Arch Intern Med 2012 Apr 23
Treatment of Subclinical Hypothyroidism Is Associated with Fewer Ischemic Cardiac Events
But only in patients younger than 70
Subclinical hypothyroidism (serum thyrotropin level, 5.01–10.0 mIU/L, and normal free thyroxine level) has been associated with elevated risk for adverse cardiac events and mortality in middle-aged, but not older, adults. Randomized trials of treating patients with subclinical hypothyroidism have been small and short term, and they have focused on subjective symptoms, not cardiac endpoints. Whether to treat patients with subclinical hypothyroidism has been controversial.
In this retrospective cohort study, U.K. researchers identified 3093 younger patients (age range, 40–70) and 1642 older patients (age, >70) with subclinical hypothyroidism; roughly 50% in each group were treated with levothyroxine (median dose, 75 µg daily). In analyses adjusted for baseline cardiovascular risk, the number of ischemic heart disease events in younger patients was 39% lower in those who were treated than in those who were not treated, during median follow-up of 7.6 years. No difference was found between treated and untreated older patients.
Comment: This retrospective study of patients with subclinical hypothyroidism cannot account for the many possible reasons that some patients were treated and others were not. Thus, no treatment recommendation can be made based on these results. The authors believe that a randomized controlled trial, focused on cardiac outcomes, is justified; however, a study that is adequately powered to show whether treatment improves cardiovascular outcomes or mortality would be very large and long term.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine May 8, 2012
Citation(s):Razvi S et al. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch Intern Med 2012 Apr 23; [e-pub ahead of print].
(http://dx.doi.org/10.1001/archinternmed.2012.1159)
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Lancet 2012 May 17
HDL Cholesterol: Causal or Just a Marker for Coronary Risk?
Genetically elevated HDL cholesterol level was not associated with lower risk for myocardial infarction.
Although randomized trials have established a causal relation between high LDL cholesterol levels and high cardiovascular risk, a similar causal association between high HDL cholesterol levels and low cardiovascular risk has not been proven. Moreover, if HDL cholesterol is merely a marker for some underlying factor that lowers cardiovascular risk, therapies designed to raise HDL cholesterol levels might not affect cardiovascular outcomes.
Investigators identified a genetic variant that is associated with substantially elevated HDL cholesterol levels but that does not affect other lipid or nonlipid cardiovascular risk factors. If high HDL cholesterol levels directly lower risk for myocardial infarction (MI), individuals with this genetic variant should suffer fewer MIs than those without it. Using the technique of "Mendelian randomization," the investigators determined the presence of this variant in more than 115,000 participants in 6 prospective cohort studies and in 14 case-control studies of cardiovascular risk factors. More than 20,000 participants suffered first MIs, and MIs occurred equally often in patients with and without the identified genetic variant in each study and in the entire group.
The researchers identified 13 single nucleotide polymorphisms (SNPs) that are associated exclusively with high LDL cholesterol levels and 14 SNPs that are associated exclusively with high HDL cholesterol levels; they assigned genetic LDL and HDL scores to more than 53,000 patients in a single case-control study. Risk for MI among these patients varied directly with LDL score but was unrelated to HDL score.
Comment: If genetically elevated HDL cholesterol levels are not associated with lower MI risk, medical interventions that increase HDL cholesterol levels might not be cardioprotective.
— Bruce Soloway, MD Published in Journal Watch General Medicine June 5, 2012
Citation(s): Voight BF et al. Plasma HDL cholesterol and risk of myocardial infarction: A mendelian randomisation study. Lancet 2012 May 17; [e-pub ahead of print].
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BMJ 2012 Apr 19; 344:e2598
Computers Can Help Treat Adolescent Depression
Cognitive behavioral therapy delivered to depressed adolescents by computer was at least as effective as usual treatment.
Fewer than 20% of adolescents with depression receive treatment, partly because of a shortage of qualified mental health providers. Could a computerized intervention fill this gap? To find out, investigators in New Zealand randomized 187 adolescents (60% female; mean age, 15.5 years) who sought help for clinically significant depression to receive usual treatment (face-to-face therapy provided by trained counselors or general practitioners) or a computerized cognitive behavioral therapy (CBT) intervention (SPARX).
Clinically significant depression was defined as a score of 10 to 19 on the Patient Health Questionnaire-9 or self-reported and clinician-verified depression troubling enough to require intervention. The computerized CBT intervention is an interactive fantasy game with seven modules delivered over 4 to 6 weeks and designed to cover core skills (e.g., finding hope, recognizing unhelpful thoughts). Participants choose an avatar and solve challenges to restore balance in a world dominated by gloomy negative automatic thoughts (GNATs). At the beginning and end of each level, participants interact with a guide who provides education about depression, gauges mood, and instructs and monitors real-life challenges. Sixty percent of participants completed all seven modules.
Reductions in raw scores on the Children's Depression Rating Scale-Revised (the primary outcome) were comparable in the two groups and rates of response to treatment were about 60% in both groups. Remission rates were significantly higher in the computer treatment group (44% vs. 26% in the usual-care group). Analysis of all other secondary measures confirmed noninferiority of the computer intervention. Improvements were maintained at follow-up 3 months after completion of the intervention.
Comment: These findings may not be applicable to all depressed adolescents because the study included only those seeking treatment and excluded those with severe depression or at major risk of self-harm. Nonetheless, the results are encouraging. The intervention shows promise as an alternative to address the shortage of mental health providers that will not disappear anytime soon. The authors note that an additional advantage of the computerized approach is that it might appeal to adolescents who are reluctant to seek traditional treatment.
— Alain Joffe, MD, MPH, FAAP Published in Journal Watch Pediatrics and Adolescent Medicine June 6, 2012
Citation(s):Merry SN et al. The effectiveness of SPARX, a computerized self help intervention for adolescents seeking help for depression: Randomised controlled non-inferiority trial. BMJ 2012 Apr 19; 344:e2598. (http://dx.doi.org/10.1136/bmj.e2598)
http://www.ncbi.nlm.nih.gov/pubmed/22517917?dopt=Abstract
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Article from Vital Choices Newsletter
(http://newsletter.vitalchoice.com/e_article002449110.cfm?x=blc47JJ,b1h1R7NC)
June 7, 2012
New Eye Benefit Seen in Omega-3s
DHA curbed buildup of a sludge that promotes the main cause of age-related vision loss and blindness; team plans tests in people
by Craig Weatherby
Omega-3 fatty acids from fish are proven essential to human eye health and function. Scientists at the National Eye Institute (NEI) within the National Institutes of Health say there’s “consistent evidence” that omega-3s protect against damage to the blood supply and nerves of the retina (SanGiovanni JP, Chew EY 2005).
These benefits are tied to both of the major omega-3s in fish fat – DHA and EPA – but it’s clear that DHA plays the most important role. Omega-3 DHA exerts anti-inflammatory and anti-oxidant influences on the genes in cells within the retina. The body makes omega-3 EPA from DHA, and EPA suppresses inflammation as well as the overgrowth of blood vessels that causes age-related macular degeneration (AMD). AMD results in loss of vision in the center of the visual field (so-called “central vision”) and is the main cause of blindness in people over 50.
The NEI team noted that omega-3s from fish are essential to vision: “… [omega-3] DHA insufficiency is associated with alterations in retinal function [and] visual processing deficits have been ameliorated with DHA supplementation ...” (SanGiovanni JP, Chew EY 2005). For example, see “Omega-3s Linked to Eye Health… Again” and related reports in the Omega-3s & Eye Health section of our news archive. And judging by the results of a mouse study from Canada’s University of Alberta, it appears we have more to learn about the importance of omega-3s – especially DHA – to eye health. Their study tested the effects of omega-3 DHA on a key player in the onset of macular degeneration.
Lipofuscin: The blinding result of declining waste-disposal in aging eye cells
The retina is a blood- and nerve-rich layer of tissue at the back of the eye, which receives light streaming through the lens. Nerve cells in the retina then transmit signals to the brain, which turns them into the miraculous phenomenon we experience as “vision”.
As people age, a substance called lipofuscin builds up in the eye’s retinal pigment epithelial (RPE) cells. Accumulation of lipofuscin – which consists of yellow-brown pigment granules – in these retinal cells is a major risk factor for macular degeneration. Lipofuscin is a byproduct of the breakdown of damaged blood cells, and is known as “the aging pigment”.
Buildup of lipofuscin implies declining performance by the lysosomes in retina cells. These tiny organelles serve as waste-disposal units for cells throughout the body. (Lipofuscin also accumulates in the liver, kidney, heart muscle, adrenal gland, and in nerve and brain cells as we age.)
Damage to lysosomes probably results from earlier damage to cell membranes (where omega-3s play essential structural and functional roles) and mitochondria (energy factories). Much of the retina damage associated with lipofuscin stems from accompanying buildup of a toxic component of lipofuscin called A2E, eye levels of which double as people age.
Canadian mouse study detects new anti-aging eye benefit from DHA
At the University of Alberta, a team of investigators led by Yves Sauve conducted an 18-month-long study in mice, to test whether supplemental omega-3 DHA would affect the buildup of lipofuscin and its A2E component in the animals’ eyes. They tested DHA in both “wild-type” mice and in transgenic mice bred to develop a genetic trait found in some humans (called E4), which causes massive A2E accumulation and related retina dysfunctions. No effect was seen from short-term feeding of DHA (one to three months), but when the vulnerable transgenic mice were fed DHA for six months, the function of their RPE cells was preserved. And when mice were fed DHA for 12 months, this led to preservation of full retina function in the transgenic mice, which were highly vulnerable to buildup of toxic AE2. After 12 to 18 months of eating DHA-fortified chow, eye levels of A2E dropped in all of the mice (wild-type and transgenic).
As the Canadian team concluded, “DHA supplementation was associated with: preserved retina function at mid-degenerative stages in E4 mice; prevention of age-related functional losses in WT mice; and reduced A2E levels in E4 and WT mice at the oldest age examined.” “These findings imply that dietary DHA could have broad preventative therapeutic applications … on pathologic and normal age-related ocular processes” (Dornstauder B et al. 2012).
As Dr. Sauve noted, “… there was no increase in this toxin whatsoever. This has never been demonstrated before – that supplementing the diet with DHA could make this kind of difference. This discovery could result in a very broad therapeutic use [of DHA]” (Dornstauder B et al. 2012). His team recently started another study, looking at people who have age-related macular degeneration. The researchers will look for DNA markers in study participants, to determine whether people with certain genetic markers will respond better to increased intake of DHA, and if so, why.
Most of the funds for the study came from the Canadian Institutes of Health Research, with added support from various vision-health foundations.
Sources: Dornstauder B, Suh M, Kuny S, Gaillard F, Macdonald IM, Clandinin MT, Sauvé Y. Dietary Docosahexaenoic Acid Supplementation Prevents Age-Related Functional Losses and A2E Accumulation in the Retina. Invest Ophthalmol Vis Sci. 2012 Apr 24;53(4):2256-65. Print 2012. Sparrow JR, Fishkin N, Zhou J, Cai B, Jang YP, Krane S, Itagaki Y, Nakanishi K. A2E, a byproduct of the visual cycle. Vision Res. 2003 Dec;43(28):2983-90. Review. Zhou J, Jang YP, Kim SR, Sparrow JR. Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16182-7. Epub 2006 Oct 23. SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res. 2005 Jan;24(1):87-138. Review. Wolf G. Lipofuscin and macular degeneration. Nutr Rev. 2003 Oct;61(10):342-6. Review. Maurier R. Discovery may help prevent vision loss with age. May 30, 2012. Accessed at:
http://www.news.ualberta.ca/article.aspx?id=81EE067D2D2848E3953ABF2117E95038
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Psychol Med 2012 Mar 6
Interaction Between SSRIs and NSAIDs? Now It's Missing
Unlike a previous study, this one shows that NSAID use does not affect antidepressant response.
In a 2011 examination of preclinical and clinical data (JW Psychiatry May 2 2011), researchers suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) interfere with the antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) through a specific interaction with the serotonin receptor. To further examine this interaction, the current researchers analyzed the effect of NSAIDs on the antidepressant efficacy of escitalopram (10–30 mg/day) and nortriptyline (50–200 mg/day) in 811 patients with major depression who were enrolled in a partially randomized clinical and pharmacogenetic study that had received some industry support.
Seventy-eight patients (10%) were taking NSAIDs, and 59 (7%) were taking analgesics. Use of analgesics was significantly associated with higher baseline depression scores. Multiple analyses of NSAID use revealed no significant effect on outcome of escitalopram treatment. For nortriptyline, only 1 of 18 analyses suggested a slightly better outcome with NSAIDs or analgesics. Remission rates were similar for both medications with or without NSAIDs or analgesics. In sensitivity analyses, findings were similar among the participants taking "clinically significant doses" of analgesics or NSAIDs (n=43 in each group).
Comment: This retrospective analysis suggests that the previously found effect of NSAIDs on response to SSRIs was due to other covariate conditions and was not a deleterious effect of NSAIDs. Unless the clinical situation warrants (e.g., a previously remitted depression recurs after an NSAID is started), clinicians and patients do not have to avoid the combination out of concern that the therapeutic effect would be blocked. These results are another example of the need for caution before making any definitive conclusions based on a single study.
— Jonathan Silver, MD Published in Journal Watch Psychiatry May 21, 2012
Citation(s): Uher R et al. Non-steroidal anti-inflammatory drugs and efficacy of antidepressants in major depressive disorder. Psychol Med 2012 Mar 6; [e-pub ahead of print].
(http://dx.doi.org/10.1017/S0033291712000190)
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