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Content 7

 

The Doctor and the Pharmacist

Radio Show Articles:
September 17, 2011

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Further Evidence That Route of Estrogen Administration Affects VTE Risk
Sodium Excretion of >7 g or <3 g Daily Is Associated with Elevated Cardiovascular Morbidity
Gray-Matter Lesions and Inflammation in MS
Hospitals Cut Doses as a Result of Drug Shortage
Looking Far Afield . . . THE SECRET LIFE OF BOTTLENOSE DOLPHINS
Safe Preparation and Administration of Intravitreal Bevacizumab Injections
FDA Approves Topical Oxybutynin 3% gel
CPAP Treatment Lowers BP in Hypertensive Patients with Sleep Apnea
For Losing Weight, Commercial Programs Are Better and Cheaper Than
  Noncommercial Programs
Does Stopping Hormone Therapy (HT) Mean the End of a Good Night's Sleep?
Omega-3 DHA Boosted Middle-Age Memory

MM: This is nothing new but its always nice to have more studies to support a premise of safety. We have felt for many years that Bio-identical HRT in a transdermal presentation is both superior and safer than oral, equin based and synthetic forms of estrogen
  
Menopause 2011 Oct; 18:1052.
Further Evidence That Route of Estrogen Administration Affects VTE Risk
Another retrospective study shows that risk for venous thromboembolism is lower with transdermal estrogen than with oral estrogen.
Use of oral estrogen by menopausal women raises risk for venous thromboembolism (VTE), and data suggest that risk is lower with transdermal preparations. To address this distinction in a real-world, commercially insured, North American population, investigators conducted a retrospective matched cohort study using health insurance claims data in new users (age, ≥35) of a transdermal estradiol system or oral estrogen therapy. A total of 27,018 transdermal users were matched with an equal number of oral estrogen users; the study was funded by the manufacturer of a transdermal system.
 
VTE developed in 115 transdermal estradiol users and in 164 oral estrogen users. Adjusted analysis showed that transdermal estradiol users  had significantly lower incidence of VTE than did oral estrogen users (adjusted incidence rate ratio, 0.67); for hospitalization-related VTE, adjusted IRR was 0.38.
 
Comment: Yet another retrospective study shows that venous thromboembolism risk is lower with transdermal estrogen than with oral estrogen. Editorialists note that this study is limited in that the authors did not take into account estrogen dose or type of oral estrogen. Whether a prospective study will ever be conducted is doubtful; however, in aggregate, existing data indicate that transdermal estradiol is the preferred route and formulation for women with VTE risk factors (e.g., obesity).
Robert W. Rebar, MD Published in Journal Watch Women's Health December 1, 2011
 
Citation(s):Laliberté F et al. Does the route of administration for estrogen hormone therapy impact the risk of venous thromboembolism? Estradiol transdermal system versus oral estrogen-only hormone therapy. Menopause 2011 Oct; 18:1052.
http://www.ncbi.nlm.nih.gov/pubmed/21775912?dopt=Abstract
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MM: Dr Peter Rosi along with other physicians and researchers have long stated that salt(sodium chloride (NaCl)) is not the evil culprit that it is claimed to be. In fact many clinicians state that sea salt is of significant benefit and should be the product of choice. Salt is necessary for maintaining blood volume and for producing stamach acid necessary to digest food and solubilize minerals and nutrients. More attention should be paid to obesity, diet and diabetes than to the NaCl issue.
  
JAMA 2011 Nov 23/30; 306:2229
Sodium Excretion of >7 g or <3 g Daily Is Associated with Elevated Cardiovascular Morbidity
By comparison, higher potassium excretion was associated with lower stroke risk.
The WHO recommends daily sodium intake of less than 2 g, based on relatively short trials in which the effect of sodium intake on blood pressure was assessed. In this study, researchers analyzed data for 28,880 patients in two international clinical trials of an angiotensin-receptor blocker; most patients (mean age, 67; 70% men) had histories of myocardial infarction, stroke, hypertension, or diabetes. People with congestive heart failure (CHF), decreased renal function, or uncontrolled hypertension were excluded. Mean daily sodium excretion (a surrogate for sodium intake) was 4.77 g, and daily potassium excretion was 2.19 g.
 
At 5 years, a composite outcome of cardiovascular mortality, myocardial infarction, stroke, and hospitalization for CHF occurred in 4729 patients. Patients with urinary sodium excretion of 4 to 6 g daily had the lowest risk for the composite outcome. Risk was higher by 21%, 16%, 15%, and 49% for patients with daily excretion of <2 g, 2–3 g, 7–8 g, and >8 g, respectively. Compared with patients who had daily potassium excretion of <1.5 g, risk for stroke was 32% lower in those with excretion of >3 g. These analyses were adjusted for numerous clinical and demographic factors.
 
Comment: This J-shaped relation between sodium intake and cardiovascular outcomes conflicts with current recommendations to limit daily sodium intake to 2 g. However, an editorialist is unconvinced and believes that randomized trials are needed to account for confounding caused by preexisting disease and risk factors. The small number of patients with low sodium intake — 3% of the total sample had urinary excretion <2 g daily — also tempers the results. Consuming a diet high in natural foods and low in processed foods would result in a lower sodium–potassium ratio –– which could be more important than the actual intake levels.
Thomas L. Schwenk, MD Published in Journal Watch General Medicine December 13, 2011
 
Citation(s):O'Donnell MJ et al. Urinary sodium and potassium excretion and risk of cardiovascular events. JAMA 2011 Nov 23/30; 306:2229.
(http://dx.doi.org/10.1001/jama.2011.1729)
http://www.ncbi.nlm.nih.gov/pubmed/22110105?dopt=Abstract
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N Engl J Med 2011 Dec 8; 365:2188
Gray-Matter Lesions and Inflammation in MS
MS cortical lesions can be inflammatory in nature, not just a result of neurodegeneration, new biopsy evidence shows.
Cortical lesions have been shown to be common and extensive among some patients with multiple sclerosis (MS) at autopsy. Prior case series of cortical lesions were based on autopsies of patients with long-standing and often progressive-stage MS, in whom significant cortical-based inflammatory infiltrates were not found. Now, researchers have evaluated brain biopsy specimens from patients who were suspected of having a tumor but were found to have had demyelinating disease instead.
 
Of 138 patients with early inflammatory demyelinating disease compatible with MS, cortical demyelination was present in 38%. In a subanalysis of 38 patients, T-cell infiltrates were found in most cortical lesions (82%). In 41 patients with cortical demyelination, nearly half (41%) of lesions had macrophages containing myelin debris. Of 104 studied lesions, 50% were leukocortical, 34% were subpial, and 16% were intracortical. Meningeal inflammation was observed adjacent to active cortical lesions. Some patients demonstrated diffuse meningeal inflammation, often associated with subpial lesions.
 
Comment: Cortical lesions have been a source of fascination in the MS community for at least a decade. Such lesions are present at the earliest stages of MS and have prompted much discussion about the substrates of neurodegeneration, cognitive dysfunction, and disease progression in MS.
 
The current findings clearly demonstrate, in an impressive number of brain biopsies, that cortical lesions can contain inflammatory cells. These regions of cortical inflammation are often associated with signs of focal and diffuse meningeal inflammation. This finding marks a major paradigm shift: Prior autopsy studies in patients with progressive MS did not find inflammatory cells within the cortex, only in the meninges, which we can now appreciate as a reflection of the stage of the disease at autopsy.
 
Cortical lesions remain a challenge to image. However, newer scanners and sequences are providing further insights. The inability to sufficiently image gray matter may contribute to the magnetic resonance imaging–clinical mismatch paradox of MS. Whether white-matter lesions are sufficient surrogates of gray-matter lesions at the individual level remains unclear. We also do not know whether all cortical lesions develop by the same mechanism, or whether MS treatments are as effective for gray-matter lesions as they are for white-matter lesions.
Robert T. Naismith, MD Published in Journal Watch Neurology December 7, 2011
 
Citation(s):Lucchinetti CF et al. Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 2011 Dec 8; 365:2188.
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Hospitals Cut Doses as a Result of Drug Shortage
Hospitals have had to cut doses and ration supplies of nutrition drugs and disinfectant products. The situation is part of a broader drug shortage that has federal health officials rethinking how they monitor the nation's pharmaceutical supply. While shortages of chemotherapy and anesthesia drugs have received much attention, now they are looking at the shortage of nutrition drugs and disinfectant products.
http://online.wsj.com/article/SB10001424052970204844504577098870278510832.html
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J Invest Dermatol 2011 Dec; 131:2503.
Looking Far Afield . . . THE SECRET LIFE OF BOTTLENOSE DOLPHINS
Dolphins demonstrate a remarkable wound-healing process.
The attraction between humans, especially children, and bottlenose dolphins is immediate. The animals are responsive, trainable, and smart, and have been helpful to mankind since antiquity. Study of remarkable wound-healing properties in dolphins may improve treatment of serious skin wounds in humans.
 
Zasloff and colleagues studied two severely wounded adult animals, Nari and Echo, in an Australian marine lab. The animals had sustained shark-inflicted wounds, 30 cm long and 4 cm deep, that seemed relatively painless and healed in several quick stages. Within a day, blubber migrated to the surface and formed a white "wound dressing." By day 2, "pink granulation tissue" gradually filled the wound upward from its base, eventually restoring the volume deficit with blubber. By 4 weeks, healing, including of the epidermis, was complete. Dolphin blubber has high levels of isovaleric acid, which reduces the freezing point of the tissue and has a role in the mechanism by which sound is transmitted through blubber. Isovaleric acid may also have antibacterial properties, as shown by the absence of infection in open wounds continuously exposed to seawater.
 
The use of dolphins to study wound healing may raise ethical and practical issues, and other matters complicate working with dolphins. These very social, physically frisky animals are prone to genital herpes infections in the wild and especially in zoos (J Wildlife Dis 2009; 405:895). Plaques containing gamma herpesvirus and serum anti-herpes antibodies are often found in male and female genital slits. After a day in the dolphin lab or swimming with these intriguing creatures, good hand washing and a body scrub are necessary. It would be embarrassing to try to explain that you got herpes from a dolphin at work.
Lowell A. Goldsmith, MD, MPH, Editor Emeritus, Journal Watch Dermatology Published in Journal Watch Dermatology December 16, 2011
 
Citation(s):Zasloff M. Observations on the remarkable (and mysterious) wound-healing process of the bottlenose dolphin. J Invest Dermatol 2011 Dec; 131:2503.
http://www.ncbi.nlm.nih.gov/pubmed/21776005?dopt=Abstract
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Safe Preparation and Administration of Intravitreal Bevacizumab Injections
The off-label use of bevacizumab (Avastin) for neovascular age-related macular degeneration makes a more affordable treatment than ranibizumab (Lucentis) for preventing blindness. Since bevacizumab is supplied in 100-mg and 400-mg vials, it is often compounded into individual doses for intravitreal injections. During this process, contamination can occur during preparation or administration.
 
In Tennessee, three recent clusters of endophthalmitis secondary to alpha-hemolytic streptococcus, after intravitreal injections of bevacizumab in nine patients occurred. Four patients lost eyesight and one also had meningitis and encephalitis. Two completed investigations have implicated the same compounding pharmacy. What was observed was a situation of noncompliance with face-mask usage as outlined in the standards for sterile compounding developed by the U.S. Pharmacopeia, known as USP <797>. Tennessee has rules that pertain to the compounding and dispensing of sterile preparations but does not require adherence to USP <797>. The rules of the Tennessee Board of Pharmacy require the wearing of a mask only if no laminar-flow hood is used or if the pharmacist or technician has a respiratory condition that may result in contamination of sterile products. The pharmacist at the implicated pharmacy compounded bevacizumab under a laminar-flow cabinet with no vertical barrier; the pharmacist wore no mask and spoke during the procedure. It was hypothesized that this resulted in contamination.
http://www.nejm.org/doi/full/10.1056/NEJMc1105759
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FDA Approves Topical Oxybutynin 3% gel
A topical oxybutynin 3% gel has been approved by the FDA for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. The gel is applied once daily, in 84 mg doses, to the thigh, abdomen, upper arm, or shoulder through a metered-dose pump.
 
Since the drug is applied topically, it is not metabolized in the liver and has a lower adverse event profile than oral formulations.
http://www.medpagetoday.com/Urology/UrinaryIncontinence/30104
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MM: This is another link in the chain of sleep apnea, causes and treatments. Unfortunately it is also a chicken-egg question but it seems that by helping sleep cycles, BP will also improve and if BP improves, sleep tends to improve as well.
  
BMJ 2010 Nov 24; 341:c5991
CPAP Treatment Lowers BP in Hypertensive Patients with Sleep Apnea
Blood pressure benefits of continuous positive airway pressure treatment
were significant but small.

Obstructive sleep apnea (OSA) is a risk factor for hypertension; prior studies suggest that treating OSA patients with continuous positive airway pressure (CPAP) lowers blood pressure (BP). In this multicenter, double-blind, randomized trial, Spanish investigators assessed the effect of CPAP on 24-hour ambulatory BP monitoring values in patients with newly diagnosed untreated systemic hypertension (systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or both) and OSA (apnea-hypopnea index per hour of sleep >15 events/hour).
 
For 3 months, 340 patients (mean age, 52) received either CPAP or sham CPAP (CPAP at <1 cm H2O). In the intent-to-treat analysis, patients randomized to CPAP experienced significant decreases in mean 24-hour ambulatory systolic and diastolic BP and mean nocturnal BP, but differences between the CPAP and sham groups were only 1 to 2 mm Hg for each of these measurements.
 
Comment: CPAP results in statistically significant, yet small, reductions in BP among patients with untreated hypertension and OSA. The clinical significance of these reductions is unclear. Aside from CPAP, standard treatment approaches likely apply to many, if not all, patients with OSA and hypertension: better diet, more exercise, weight loss, and medications, if necessary.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine January 20, 2011
 
Citation(s):Durán-Cantolla J et al. Continuous positive airway pressure as treatment for systemic hypertension in people with obstructive sleep apnoea: Randomised controlled trial. BMJ 2010 Nov 24; 341:c5991. (http://dx.doi.org/10.1136/bmj.c5991)
http://www.nejm.org/doi/full/10.1056/NEJMoa1103944
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BMJ 2011 Nov 3; 343:d6500
For Losing Weight, Commercial Programs Are Better and Cheaper Than Noncommercial Programs
The "power of the group" seems to sustain motivation.
How do noncommercial weight-loss programs compare with commercial weight-loss programs? In an eight-arm randomized trial that involved 740 overweight or obese adults in the U.K., researchers compared the relative effectiveness of various 12-week programs: general practice one-to-one counseling, pharmacy one-to-one counseling, a group-based dietetics program, and three commercial programs (Rosemary Conley, Slimming World, and Weight Watchers). Participants in another group were allowed to choose among these six programs. Each participant in the control group received 12 vouchers for free visits to a fitness center.
 
All programs resulted in significant mean weight loss at 12 weeks (range, 1.4 kg for general practice to 4.4 kg for Weight Watchers). All programs, except general practice and pharmacy one-to-one counseling, resulted in significant weight loss at 1 year (range, 0.7–3.5 kg). Only the Weight Watchers group, however, experienced significantly greater mean weight loss at 1 year (2.5 kg) than the control group. Costs were highest for general practice and pharmacy counseling programs and lowest for the commercial programs.
 
Comment: In this trial, commercial weight-loss programs were cheaper and more effective (Weight Watchers was particularly effective) than noncommercial weight-loss programs. Editorialists speculate that commercial programs are effective because they provide intensive support (e.g., "the power of the group" in weekly sessions) and incentives, which sustain motivation and behavioral change. Notably, these results are similar to those of another trial in which Weight Watchers was superior to weight-loss advice provided by primary care practices (JW Gen Med Sep 22 2011).
—  Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine December 15, 2011
 
Citation(s):Jolly K et al. Comparison of range of commercial or primary care led weight reduction programmes with minimal intervention control for weight loss in obesity: Lighten Up randomised controlled trial. BMJ 2011 Nov 3; 343:d6500.
(http://dx.doi.org/10.1136/bmj.d6500)
http://www.ncbi.nlm.nih.gov/pubmed/22053315?dopt=Abstract
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Menopause 2011 Nov; 18:1184
Does Stopping Hormone Therapy (HT) Mean the End of a Good Night's Sleep?
Women were more likely to report sleeping poorly after discontinuing hormone therapy.
Short-term postmenopausal hormone therapy (HT) relieves severe menopausal symptoms, but whether HT affects women's sleep remains unknown. Investigators randomized 1704 women (age range, 45–80) who had been using HT for ≥2 years to continue HT or discontinue use for 1 or 2 months.
 
Women who discontinued HT reported an average of 1 more day of poor sleep monthly than did ongoing HT users. Women were not asked to rate how bothersome they found changes in their sleep patterns. However, use of sleep aids did not differ significantly among groups.
 
Comment: Major limitations of this trial are that participants were not blinded and that women who were randomized to discontinue hormone therapy were more likely to withdraw from the study. In addition, the authors were unable to account for use of other medications (e.g., selective serotonin reuptake inhibitors) that might affect sleep. Although prior studies have suggested that both progesterone and estrogen can affect sleep positively, the present results are far from definitive.
 
Eleanor Bimla Schwarz, MD, MS Published in Journal Watch Women's Health December 15, 2011
 
Citation(s):Tom SE et al. Sleep problems after short-term hormone therapy suspension: Secondary analysis of a randomized trial. Menopause 2011 Nov; 18:1184.
 http://www.ncbi.nlm.nih.gov/pubmed/21785373?dopt=Abstract
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http://www.imakenews.com/eletra/mod_print_view.cfm?this_id=2295248&u=
vitalchoiceseafood&show_issue_date=F&issue_id=000562052&lid=bknqpkn&uid=b1h1R7NC

Omega-3 DHA Boosted Middle-Age Memory
Clinical trial affirms the idea that DHA supports optimal memory and thinking in young a … especially in those who eat little fish
by Craig Weatherby
Enjoying fatty fish every week – or taking omega-3 fish oil – may help delay or ameliorate Alzheimer’s and other dementias … and possibly enhance or extend mental performance in old age. For more on this topic, see the “Omega-3s & Brain Health” section of our news archive, where you’ll see reports on the mixed but mostly positive studies in older people. We know less the effects of omega-3s in young people (teenagers to age 35) ... or in people in the “young middle age” bracket (aged 36-55). Like the larger group of studies involving people 65 and older, the results of omega-3/brain investigations in younger adults have been mixed, though mostly positive. The mixed research record seen so far from studies in younger and older adults alike seems unsurprising, in light of the differences in participants’ genes, lifestyles, and diets, and the widely varying designs of studies … including the doses and composition of the fish oils tested in trials.

For example, the results of a small, short clinical trial published earlier this year showed no brain benefits in healthy young adults aged 18 to 35 who took either a DHA-heavy fish oil or an EPA-heavy fish oil for three months (Jackson PA, Deary ME, Reay JL, et al. 2011) But the same authors detected brain-oxygen-flow benefits in other young and middle-aged adults taking fish oil; see our sidebar, “Omega-3 DHA boosted younger brain’s oxygen supply”. And most other studies have detected brain benefits in young and middle-aged adults. These include clinical trials and “observational” studies, in which scientists compare people’s estimated omega-3 intakes from fish or their omega-3 blood levels to their brain performance. For example, see “Middle-Aged Brain Boost Linked to Omega-3s”, “Omega-3s Seen Boosting Performance of Healthy Young Brains”, “Omega-3s Enhance Mood and Brain Speed, and “Feel-Good Findings”. Let’s take a look at the new findings from New Zealand, which add force to the increasing calls for large, long-term clinical trials testing omega-3 fish oil in people aged 20 to 55.

New Zealand trial affirms benefits of omega-3 DHA in middle-aged brains
Of the two omega-3s from fish fat – DHA and EPA – omega-3 DHA is by far the most important for brain health. (See our sidebar, “DHA … the brains in the omega-3 family”.) As the author of a 2010 study wrote about the significance of their positive results in middle-aged adults: “These findings suggest that [omega-3] DHA is related to brain health throughout the lifespan...” (Muldoon MF et al. 2010). Researchers from Auckland’s Massey University report that healthy adults who took DHA-rich fish oil showed gains in memory and speed of memory recall. Professor Welma Stonehouse led the six month, randomized, placebo-controlled, double-blind trial (Stonehouse W et al. 2011).Her team recruited 176 healthy adults aged 18 to 45, selecting people who reported eating relatively little fish in their regular diets. Half were given a fish oil supplement providing 375mg of DHA, three times a day, and the other were given placebo capsules.
 
After six months, those in the fish oil group showed improvements in the ability to store and recall information over long periods. Perhaps more importantly, the women in the fish oil group showed statistically significant improvements in working memory and other aspects of memory, while the men posted gains in the speed of working memory.
 
As Professor Welma Stonehouse said, “This is the first robust study to show that a DHA-rich supplement can improve some aspects of memory functioning in young healthy adults that normally follow an omega-3 deficient diet. These findings contribute to the growing body of research showing that omega-3s play a very important role in brain function throughout the life cycle, even in healthy cognitively intact individuals.” (ScoopNZ 2011) Working memory holds information for a few seconds or minutes, and is among the first mental capacities affected by Alzheimer’s and milder forms of dementia. Loss of working memory makes it hard to complete tasks, sustain attention, follow directions, carry out multi-step instructions, remember things temporarily, and engage in complex reasoning. Or, as Stonehouse described the importance of working memory, “The cognitive functions shown to be affected by the DHA-rich fish oil, namely memory and working memory, are among the most important functions of our brains for numerous everyday activities, such as working, driving, shopping, studying, playing sports, etc.” (ScoopNZ 2011) Her team’s findings seem very encouraging in the context of other positive studies in young and middle-aged adults. However, they must be repeated in larger, longer trials so that we can see which people benefit from omega-3 DHA supplements, and exactly which mental capacities are improved.
 
When you put the results of this trial together with the negative trial published earlier this year, it seems that people who don’t eat much fatty fish – e.g., wild salmon, sardines, tuna, mackerel, sablefish – may be the biggest beneficiaries of fish oil pills.
 
Sources: Devore EE, Grodstein F, van Rooij FJ, Hofman A, Rosner B, Stampfer MJ, Witteman JC, Breteler MM. Dietary intake of fish and omega-3 fatty acids in relation to long-term dementia risk. Am J Clin Nutr. 2009 Jul;90(1):170-6. Epub 2009 May 27. Eskelinen MH, Ngandu T, Helkala EL, Tuomilehto J, Nissinen A, Soininen H, Kivipelto M. Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study. Int J Geriatr Psychiatry. 2008 Jul;23(7):741-7. Fontani G, Corradeschi F, Felici A, Alfatti F, Bugarini R, Fiaschi AI, Cerretani D, Montorfano G, Rizzo AM, Berra B. Blood profiles, body fat and mood state in healthy subjects on different diets supplemented with Omega-3 polyunsaturated fatty acids. Eur J Clin Invest. 2005 Aug;35(8):499-507. Jackson PA, Deary ME, Reay JL, Scholey AB, Kennedy DO. No effect of 12 weeks' supplementation with 1 g DHA-rich or EPA-rich fish oil on cognitive function or mood in healthy young adults aged 18-35 years. Br J Nutr. 2011 Aug 25:1-12. [Epub ahead of print] Jackson PA, Reay JL, Scholey AB, Kennedy DO. DHA-rich oil modulates the cerebral haemodynamic response to cognitive tasks in healthy young adults: a near IR spectroscopy pilot study. Br J Nutr. 2011 Oct 3:1-6. [Epub ahead of print] Kalmijn S, van Boxtel MP, Ocké M, Verschuren WM, Kromhout D, Launer LJ. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology. 2004 Jan 27;62(2):275-80. Meharban Singh (March 2005). "Essential Fatty Acids, DHA and the Human Brain from the Indian Journal of Pediatrics, Volume 72" (PDF). http://medind.nic.in/icb/t05/i3/icbt05i3p239.pdf. Retrieved October 8, 2007 Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Fish consumption and cognitive decline with age in a large community study. Arch Neurol. 2005 Dec;62(12):1849-53. Epub 2005 Oct 10. Muldoon MF, Ryan CM, Sheu L, Yao JK, Conklin SM, Manuck SB. Serum Phospholipid Docosahexaenonic Acid Is Associated with Cognitive Functioning during Middle Adulthood. J Nutr. 2010 Feb 24. [Epub ahead of print] doi:10.3945/jn.109.119578. ScoopNZ. High DHA Fish Oil Improves Memory in Healthy Adults. Wednesday, 30 November 2011. Accessed at http://www.scoop.co.nz/stories/BU1111/S01100/high-dha-fish-oil-improves-memory-in-healthy-adults.htm Stonehouse W et al. DHA supplementation influences cognitive performance in healthy young adults. Concurrent Session 1: Fatty Acids 1120 – 1130. Joint Annual Scientific Meeting of the Nutrition Society of New Zealand and the Nutrition Society of Australia. Wednesday 30th November 2011. Australia New Zealand Joint Nutrition Conference, Queenstown. Accessed at http://www.events4you.co.nz/; van de Rest O, Spiro A 3rd, Krall-Kaye E, Geleijnse JM, de Groot LC, Tucker KL. Intakes of (n-3) fatty acids and fatty fish are not associated with cognitive performance and 6-year cognitive change in men participating in the Veterans Affairs Normative Aging Study. J Nutr. 2009 Dec;139(12):2329-36. Epub 2009 Oct 14. van Gelder BM, Tijhuis M, Kalmijn S, Kromhout D. Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr. 2007 Apr;85(4):1142-7.

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