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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
February 18, 2012

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Cefpodoxime (Vantin®) Flunks as a First-Line UTI Drug
Amoxicillin Has No Effect on Acute, Uncomplicated Bacterial Rhinosinusitis
Healthy Nutrients in the Blood Help the Aging Brain
Chipping Away at Bone: Proton-Pump Inhibitors and Smoking
Can Exercise Prevent Gestational Diabetes?
Calcium-Channel Blockers and Losartan Are Associated with Lower Risk for Gout
   in Hypertensive Patients
Tai Chi vs. Other Exercises for Parkinson Disease
Male Fertility Tied to a Key Omega-3

MM: Strong antibiotics and antibiotics in general should be reserved for times that less aggressive options won’t work. Mild UTI’s are an example of when products such as D-Mannose should be tried as a first line therapy. It tends to be quite quick and effective for E. coli UTI’s that historically make up over 80% of all UTI’s. One of the outstanding attributes of D-Mannose is that it doesn’t create super-infections that antibiotics may create. Mark Drugs has this product available in capsule or bulk powder with a scoop. We provide detailed recommendations how to use it for UTI’s.
JAMA 2012 Feb 8; 307:583
Cefpodoxime (Vantin®) Flunks as a First-Line UTI Drug
Response rates were clearly inferior to those achieved with short-course ciprofloxacin.
Uncomplicated urinary tract infection (UTI) in women is easy to treat — so easy that guidelines advise reserving fluoroquinolones like ciprofloxacin for more-serious infections (Clin Infect Dis 2011; 52:e103). However, without the quinolones, the list of first-line drugs for a standard-issue Escherichia coli UTI is quite short.
In a recent, double-blind, randomized trial, researchers compared the oral fourth-generation cephalosporin cefpodoxime (Vantin) with ciprofloxacin in 300 young, healthy women with uncomplicated UTI. Treatment lasted for 3 days in each group.
Compared with women who received ciprofloxacin, those who received cefpodoxime were significantly less likely to sustain a microbiologic cure within 1 week after treatment (81% vs. 96%) and were also less likely to report complete clinical cure 1 month later (82% vs. 93%). Analyses of various subgroups (women with no prior UTI during the past year, women with strains susceptible to the study antibiotic) yielded similar results. Drug-related side effects were similar in both groups.
Comment: These results are sufficient to eliminate cefpodoxime from the list of first-line oral drugs for uncomplicated urinary tract infection. In fact, the official prescribing information for this drug acknowledges its "lower bacterial eradication rates" compared with those of other drug classes. Clinicians are left with trimethoprim-sulfamethoxazole, nitrofurantoin, fosfomycin, and — for those who choose to ignore rising concerns about drug resistance — the ever-tempting and convenient ciprofloxacin.
Abigail Zuger, MD Published in Journal Watch General Medicine February 16, 2012
Citation(s):Hooton TM et al. Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: A randomized trial. JAMA 2012 Feb 8; 307:583.
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Amoxicillin Has No Effect on Acute, Uncomplicated Bacterial Rhinosinusitis
Amoxicillin Has No Effect on Acute, Uncomplicated Bacterial Rhinosinusitis
Amoxicillin doesn't ameliorate the severity of acute, uncomplicated bacterial rhinosinusitis any better than placebo, according to a JAMA study.
Some 160 patients with clinically confirmed disease (purulent nasal discharge and maxillary pain or facial tenderness) were randomized to receive either 1500 mg/day of amoxicillin or placebo for 10 days. In addition, all received a supply of symptomatic treatments (e.g., acetaminophen) for use as needed.
Patients' assessment of improvement in 16 sinus-related symptoms did not differ between groups at day 3 or at day 10. (While symptom scores did favor antibiotics at day 7, the authors judge the difference to be "too small to represent any clinically important change.")
In his Journal Watch HIV and ID Observations blog, Dr. Paul Sax says the study reminds us that "most of the common community-acquired infections resolve spontaneously."
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MM: Functional Medicine is when a clinician gives a particular herbal or nutritional supplement or combination and looks for a specific outcome. An example of this would be giving Saccharomyces Boulardii for diarrhea or using a combination or Red Yeast Rice, Fish oil, Policosanols, probiotics and Phytosterols for cholesterol and seeing the cholesterol numbers improve. This is a mainstay of how we help patients at Mark Drugs. This article is an example of Functional Medicine and nutrients and how they work.
Neurology 2012 Jan 24; 78:241
Healthy Nutrients in the Blood Help the Aging Brain
A study of nutrient biomarker levels in plasma confirms the usual suspects that help or hurt our cognition.
Many studies have suggested that dietary factors, including specific nutrients, the Mediterranean diet, and obesity, are important in cognition. However, the data obtained are usually from questionnaires that rely on recall of food intake. These investigators examined plasma nutrient biomarkers of diet in 104 participants in a brain aging study (mean age, 87; 62% women).
The investigators constructed several nutrient biomarker patterns (NBPs) and assessed the relationships of NBPs to findings from neuropsychological tests and volumetric magnetic resonance imaging (in 42 patients). Of the group, 10% were carriers of the APOE4 gene, 21% had depression, and 44% had hypertension.
Several NBPs were associated with outcomes. A profile high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E was associated with better global cognitive function, especially executive and visuospatial functions and attention. A profile high in plasma trans fat was associated with worse cognitive function. A profile high in plasma marine omega-3 fatty acids was associated with better executive function. Total cerebral brain volume was greater in participants with the plasma vitamin NBP and smaller in those with the trans fat NBP. The omega-3 NBP was associated with significantly fewer white-matter hyperintensities, but only in individuals without depression.
Comment: This study confirms what we have previously gleaned from dietary studies: Plasma vitamins found in green, leafy vegetables and fatty acids found in some fish are good for your brain; trans fats found in bakery items, fried foods, etc., are not. We should not interpret these findings, however, as recommending vitamin supplements. Taking supplemental vitamins is not the same as obtaining nutrients through real food.
Jonathan Silver, MD Published in Journal Watch Psychiatry February 6, 2012
Citation(s):Bowman GL et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology 2012 Jan 24; 78:241.
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BMJ 2012 Jan 31; 344:e372
Chipping Away at Bone: Proton-Pump Inhibitors and Smoking!
Long-term PPI use was associated with excess risk for postmenopausal hip fractures, especially in smokers.
Proton-pump inhibitors (PPIs) suppress gastric acid production and, consequently, calcium absorption. Thus, long-term PPI use may reduce bone density and raise fracture risk. Using data from the Nurses' Health Study (NHS) and prior studies, investigators assessed the association between long-term PPI use and risk for hip fracture in postmenopausal women.
Among 80,000 women in the NHS (age range at entry, 30–55), PPI use rose from 7% in 2000 to 19% in 2008. Absolute risk for hip fracture was 2.0 events per 1000 person-years among regular PPI users and 1.5 events per 1000 person-years among nonusers. Adjusted for multiple factors (e.g., body-mass index, calcium intake, osteoporosis history, use of hormone therapy), risk for hip fracture among women who used PPIs regularly for ≥2 years was 40% higher than among nonusers and rose with duration of PPI use. Among previous or current smokers, PPI use was associated with a 50% increased risk for hip fracture, whereas among never-smokers, PPI use was not associated with excess risk. In a meta-analysis involving 11 studies and 1.5 million participants, PPI use was associated with a 30% increased risk for hip fracture.
Comment: Notably, proton-pump inhibitor use also has been associated with excess risks for vertebral, forearm, and wrist fractures (JW Gen Med Jun 8 2010). The finding that chronic PPI use is associated with excess risk for hip fracture, especially in women with histories of smoking, suggests that long-term PPI use in women should be critically evaluated.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine February 14, 2012
Citation(s): Khalili H et al. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: A prospective cohort study. BMJ 2012 Jan 31; 344:e372. (http://dx.doi.org/10.1136/bmj.e372)
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Obstet Gynecol 2012 Jan; 119:29
Can Exercise Prevent Gestational Diabetes?
Trial results do not provide a clear answer.
Regular exercise helps prevent type 2 diabetes, but whether similar benefits apply to physical activity and gestational diabetes (GD) is not definitively known. To assess whether exercise during pregnancy can lower risk for insulin resistance and GD, Norwegian investigators randomized 855 pregnant women to a 12-week structured exercise program (weekly supervised sessions with encouragement to follow a home exercise program twice weekly) or to standard prenatal care. Women in the control group were not discouraged from exercising independently. Adherence was defined as exercising at least 3 days per week at moderate to high intensity. All participants underwent oral glucose tolerance testing at study entry (18–22 weeks' gestation) and completion (32–36 weeks' gestation).
Incidence of GD was similar in the exercise and control groups (7% and 6%, respectively). Levels of insulin resistance also showed no difference between groups, regardless of adjustment for factors such as baseline fasting insulin levels. Of note, only 55% of women in the exercise group met the definition of adherence; 10% of women in the control group exercised at least 3 days per week. An exploratory analysis in which adherent women in the exercise group were compared with women in the control group showed no difference in incidence of GD (7% and 6%), but fasting insulin was lower in the adherent women.
Comment: These results might not be generally applicable given that 100% of the study participants were white and only 10% had body mass indexes above 27. Also, the apparent lack of benefit from exercise is questionable, given that almost half of the women in the exercise group did not adhere to the protocol (whereas 10% of the control group exercised regularly). Given that the trial was not powered to compare adherent and nonadherent women, results of the exploratory analysis should be interpreted with caution. The authors point out the need for research on exercise in pregnant women with risk factors for gestational diabetes (e.g., obesity); however, a pressing priority is effective promotion of physical activity in such women.
Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health January 26, 2012
Citation(s):Stafne SN et al. Regular exercise during pregnancy to prevent gestational diabetes: A randomized controlled trial. Obstet Gynecol 2012 Jan; 119:29.
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BMJ 2012 Jan 12; 344:d8190
Calcium-Channel Blockers and Losartan Are Associated with Lower Risk for Gout in Hypertensive Patients
Diuretics, β-blockers, angiotensin-converting–enzyme inhibitors, and non-losartan angiotensin-receptor blockers are associated with increased risk.
Antihypertensive drugs either increase serum uric acid levels (e.g., diuretics, β-blockers) or decrease serum uric acid levels (e.g., calcium-channel blockers, losartan). An association between thiazide diuretics and gout is widely accepted, but whether other drug classes raise or lower risk for gout is unclear. In this case-control study, investigators determined the association between use of antihypertensive drugs and risk for incident gout in patients with hypertension.
Nearly 25,000 adults (age range, 20–79) with incident gout were matched with 50,000 controls. After adjustments for multiple potential confounders (e.g., age, sex, body-mass index, alcohol intake), risk for incident gout was significantly lower among hypertensive patients who were using calcium-channel blockers (relative risk, 0.9) and losartan (RR, 0.8) but elevated among those taking diuretics (RR, 2.4), β-blockers (RR, 1.5), angiotensin-converting–enzyme (ACE) inhibitors (RR, 1.2), and non-losartan angiotensin-receptor blockers (ARBs; RR, 1.3). Similar results were obtained for people without hypertension who took these drugs. Notably, longer use of calcium-channel blockers and losartan was associated with progressively lower risk for gout.
Comment: Consistent with their effects on serum uric acid levels, calcium-channel blockers and losartan are associated with lower risk for incident gout, whereas diuretics, β-blockers, ACE inhibitors, and non-losartan ARBs are associated with higher risk for gout. These results are relevant given that hypertension itself is a risk factor for gout, and many patients with gout have hypertension.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine February 7, 2012
Citation(s):Choi HK et al. Antihypertensive drugs and risk of incident gout among patients with hypertension: Population based case-control study. BMJ 2012 Jan 12; 344:d8190. (http://dx.doi.org/10.1136/bmj.d8190)
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N Engl J Med 2012 Feb 9; 366:511
Tai Chi vs. Other Exercises for Parkinson Disease
A randomized comparison suggests potential benefits from both tai chi and resistance training.
Aiming to assess whether practicing tai chi improves measures of postural stability in patients with Parkinson disease (PD), researchers randomized 185 patients with PD ranging from early to late disease stages to be trained in tai chi, resistance training, or stretching. Training consisted of 60-minute sessions twice weekly for 24 weeks. In the resistance-training group, resistance was added at week 10 and gradually increased from 1% to 5% of body weight. The primary outcome was postural stability at 6 months, measured by maximum excursion and directional control on the limits-of-stability test. Secondary outcomes included measures of gait and knee strength, scores on the functional-reach and timed up-and-go tests, motor scores on the Unified Parkinson's Disease Rating Scale, and number of falls recorded in patient diaries.
At 6 months, the tai chi group performed significantly better than the other two groups on the primary outcome measures (vs. resistance training: maximum excursion, 5.55 percentage points better; directional control, 10.45 percentage points better; vs. stretching: 11.98 and 11.38 percentage points better, respectively). Compared with the resistance-training group, the tai chi group had similar performance on many of the secondary measures and reported nonsignificantly fewer falls. (They reported significantly fewer falls than the stretching group.)
Comment: Because much of the disability in PD arises from gait, balance, and motor dysfunction, and because many experts now prescribe exercise as an intervention, this study provides important insights. The findings add to the growing body of evidence suggesting benefits of various activities in patients with PD. However, it is important not to overinterpret the results. Patients at a wide range of disease stages were included, making generalization and interpretation of effects tricky. Better characterization of pre- and posttreatment falling in the advanced-stage patients, especially those with preexisting fall-related issues, would have been more relevant. Also, medications were quantitated by number, not dose.
Tai chi incorporates movements that enhance balance control through practicing volitional destabilization of the center of mass. Therefore, the tai chi group's better performance on balance measures makes sense. Resistance training prioritizes muscle strengthening and force development and has potential benefits that are distinct from those of tai chi. The resistance training in this study was not particularly intense, especially compared with previous studies (Parkinsonism Relat Disord 2009; 15:752 and Gait Posture 2012 Jan 20; e-pub ahead of print). Similarly, stretching is a very important part of the daily regimen for the PD patient. Therefore, modalities should be selected and tailored to meet the needs of the individual patient.
Michael S. Okun, MD Published in Journal Watch Neurology February 8, 2012
Citation(s): Li F et al. Tai chi and postural stability in patients with Parkinson's disease.
N Engl J Med 2012 Feb 9; 366:511.
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Male Fertility Tied to a Key Omega-3
Finding holds implications for eye and brain health as well; clinical trials suggest that America’s "omega imbalance" enfeebles fertility
by Craig Weatherby
Some 15 percent of American couples fail to conceive within a year, despite frequent attempts to conceive. Male infertility plays a role in about half of all cases, and the immediate causes include low sperm production, misshapen or immobile sperm, or blockages that prevent its delivery.  Reports of a steady fall in human sperm quality and quantity, and a rise in testicular abnormalities, arose in the 1990's and continue to generate debate over the quality of the evidence (Carlsen E et al. 1993; Merzenich H et al. 2010). The controversy continues, but rising rates of reproductive problems suggest a generally negative trend ... one in which male infertility, more than female failures, is implicated.

Omega-3 intake is an often-overlooked factor in male fertility. And a new study from the University of Illinois shows one previously unknown reason why. In addition to low omega-3 intakes, the average American’s diet also features an extreme “omega imbalance” in favor of omega-6 fatty acids. As we’ll explain, the results of a clinical trial suggest that this dietary imbalance may be responsible for some cases of male infertility. First, let’s look at the new study in mice, and its implications for reproductive, brain, and eye health.

Novel studies detects critical role for DHA
Dozens of animal studies suggest that omega-3s are essential to fertility in male rodents, horses, pigs, and poultry. And most of these studies indicate that DHA – one of the two major omega-3s found in human cells and in fish fat – enhances sperm quality and motility. Over the past two years, researchers at the University of Illinois published studies that highlighted the importance of omega-3s … especially DHA. In addition to getting it from fish or fish oil, people can make small amounts of DHA from the short-chain omega-3 found in certain plant foods, known as ALA.  To test the effects of DHA on the formation of sperm cells, the University of Illinois team bred groups of mice to lack the gene necessary for the conversion of ALA to DHA (Roqueta-Rivera M et al. 2010).

The sperm of mice that were unable to make DHA from ALA were less mobile and lacked the properties necessary for penetrating an egg cell.

“We looked at sperm count, shape, and motility, and tested the breeding success rate. The male mice that lacked DHA were basically infertile,” said lead author Manabu Nakamura, DVM, Ph.D. (UI 2012) But when DHA was introduced into the mice's diet, fertility was completely restored. “It was very striking. When we fed the mice DHA, all these abnormalities were prevented,” he said (UI 2012).

Illinois study illuminates unrealized role of DHA in fertility … and beyond
The scientists used 3D microscopy to look at thin slices of tissue in progressive stages of a sperm cell’s development (Roqueta-Rivera M et al. 2011). As Professor Nakamura explained, “Normal sperm cells contain an arc-like structure called the acrosome that is critical in fertilization because it houses, organizes, and concentrates a variety of enzymes that sperm use to penetrate an egg.” (UI 2012) The study shows for the first time that omega-3 DHA is essential in fusing the building blocks of the acrosome together. In the absence of DHA, the vesicles were formed but they didn’t come together to make the arch critical to proper sperm cell structure. “We could see that the acrosome is constructed when small vesicles containing enzymes fuse together in an arc. But that fusion doesn't happen without DHA,” Nakamura said (UI 2012).

In short, it’s now clear that omega-3 DHA is necessary to construct the arch that turns a round, immature sperm cell into a strong, pointy-headed swimmer with an extra long tail. In light of their results and the many prior animal studies concerning DHA and male fertility, the researchers concluded that DHA plays a critical role in fertility of all mammals … including humans. But the implications of their findings extend far beyond fertility.

Sperm findings hold implications for brain and eye health
Because DHA is abundant in the brain and the retina as well as the testes, Nakamura’s team believes that their research findings hold implications for mental and visual health. As Dr. Nakamura said, “It's logical to hypothesize that DHA is involved in vesicle fusion elsewhere in the body, and because the brain contains so much of it, we wonder if deficiencies could play a role, for example, in the development of dementia. Any communication between neurons in the brain involves vesicle fusion.” (UI 2012) The Illinois scientists will continue to study sperm. Meanwhile, Nakamura has sent some of his DHA-deficient knockout mice to laboratories where scientists are studying DHA function in the brain and the retina.

Omega-3s improve men’s sperm quality in clinical trial
Last year, Iranian scientists published the results of a clinical trial testing the effects of omega-3 supplements on men’s sperm health (Safarinejad MR 2011). They recruited 238 infertile men and randomly assigned them to take 1.84 grams of supplemental omega-3s (EPA + DHA), per day, or a placebo, for 32 weeks. They found significant improvements in sperm count and concentration among men in the omega-3 group. And they also reported a significant correlation between higher levels of EPA and DHA in seminal fluid, greater antioxidant activity in the fluid, and better scores on key measures of sperm quality. Interestingly, the higher omega-3-related antioxidant activity seen in the omega-3 group’s seminal fluid was linked to enhanced sperm count, sperm motility, and sperm morphology. (The biomedical term “morphology” refers to the form and structure of organisms or cells and their specific structural features.) The Iranians came to an obvious conclusion: “[infertile] men with low levels of EPA and DHA may benefit from omega-3 supplementation.” (Safarinejad MR 2011)

Omega-3 imbalance implicated in male infertility
Two years ago, the same Iranian team published a study that linked the balance between omega-3 and omega-6 fatty acids to male infertility (Safarinejad MR et al. 2010). They recruited 82 infertile men with abnormal sperm density, movement, morphology, or shape, and 78 fertile men. The Iranians measured the levels of three major omega-3s (ALA, EPA and DHA) and two major omega-6 fatty acids (LA and AA) in the men’s blood and sperm.

Compared with the infertile men, the fertile volunteers had higher blood and sperm levels of omega-3s. And compared to the fertile men, the infertile recruits had significantly higher ratios of omega-6 to omega-3 fatty acids. Additionally, the blood and sperm levels of omega-6 AA in infertile subjects were higher and levels of omega-3 EPA and DHA were lower, compared with the fertile men. The infertile men also had higher average AA:DHA ratios and AA:EPA ratios, compared with the fertile men. Last, the Iranian team found a strong link between high AA:DHA and AA:EPA ratios and low sperm counts and motility, as well as abnormal sperm morphologies.

As they wrote, “Infertile men had lower concentrations of omega-3s in spermatozoa than fertile men. These results suggest that research should be performed to assess the potential benefits of omega-3 supplementation as a therapeutic approach in infertile men ...” (Safarinejad MR et al. 2010)

Sources:  Am-in N, Kirkwood RN, Techakumphu M, Tantasuparuk W. Lipid profiles of sperm and seminal plasma from boars having normal or low sperm motility. Theriogenology. 2011 Mar 15;75(5):897-903. Epub 2010 Dec 17.; Andersson AM, Jørgensen N, Main KM, Toppari J, Rajpert-De Meyts E, Leffers H, Juul A, Jensen TK, Skakkebaek NE.Adverse trends in male reproductive health: we may have reached a crucial 'tipping point'. Int J Androl. 2008 Apr;31(2):74-80. Epub 2008 Jan 10.; Blum R, Kiy T, Waalkens-Berendsen I, Wong AW, Roberts A. One-generation reproductive toxicity study of DHA-rich oil in rats. Regul Toxicol Pharmacol. 2007 Dec;49(3):260-70. Epub 2007 Aug 25. Brinsko SP, Varner DD, Love CC, Blanchard TL, Day BC, Wilson ME. Effect of feeding a DHA-enriched nutriceutical on the quality of fresh, cooled and frozen stallion semen. Theriogenology. 2005 Mar 15;63(5):1519-27. Carlsen E, Giwercman AJ, Keiding N, Skakkebaek NE. Evidence for increasing incidence of abnormalities of the human testis: a review. Environ Health Perspect. 1993 Jul;101 Suppl 2:65-71. Review. Castellano CA, Audet I, Bailey JL, Chouinard PY, Laforest JP, Matte JJ. Effect of dietary n-3 fatty acids (fish oils) on boar reproduction and semen quality. J Anim Sci. 2010 Jul;88(7):2346-55. Epub 2010 Mar 26. Conquer JA, Martin JB, Tummon I, Watson L, Tekpetey F. Effect of DHA supplementation on DHA status and sperm motility in asthenozoospermic males. Lipids. 2000 Feb;35(2):149-54. Conquer JA, Martin JB, Tummon I, Watson L, Tekpetey F. Fatty acid analysis of blood serum, seminal plasma, and spermatozoa of normozoospermic vs. asthenozoospermic males. Lipids. 1999 Aug;34(8):793-9. Giwercman A, Carlsen E, Keiding N, Skakkebaek NE. [Decline in semen quality from 1930 to 1991]. Ugeskr Laeger. 1993 Aug 16;155(33):2530-5. Review. Danish. Jouannet P, Wang C, Eustache F, Kold-Jensen T, Auger J.Semen quality and male reproductive health: the controversy about human sperm concentration decline. APMIS. 2001 May;109(5):333-44. Review. Merzenich H, Zeeb H, Blettner M. Decreasing sperm quality: a global problem? BMC Public Health. 2010 Jan 19;10:24. Review. Oborna I, Wojewodka G, De Sanctis JB, Fingerova H, Svobodova M, Brezinova J, Hajduch M, Novotny J, Radova L, Radzioch D. Increased lipid peroxidation and abnormal fatty acid profiles in seminal and blood plasma of normozoospermic males from infertile couples. Hum Reprod. 2010 Feb;25(2):308-16. Epub 2009 Nov 25. Roqueta-Rivera M, Abbott TL, Sivaguru M, Hess RA, Nakamura MT. Deficiency in the omega-3 fatty acid pathway results in failure of acrosome biogenesis in mice. Biol Reprod. 2011 Oct;85(4):721-32. Epub 2011 Jun 8. Roqueta-Rivera M, Stroud CK, Haschek WM, Akare SJ, Segre M, Brush RS, Agbaga MP, Anderson RE, Hess RA, Nakamura MT. Docosahexaenoic acid supplementation fully restores fertility and spermatogenesis in male delta-6 desaturase-null mice. J Lipid Res. 2010 Feb;51(2):360-7. Epub 2009 Aug 18. Safarinejad MR, Hosseini SY, Dadkhah F, Asgari MA. Relationship of omega-3 and omega-6 fatty acids with semen characteristics, and anti-oxidant status of seminal plasma: a comparison between fertile and infertile men. Clin Nutr. 2010 Feb;29(1):100-5. Epub 2009 Aug 8. Safarinejad MR, Hosseini SY, Dadkhah F, Asgari MA. Relationship of omega-3 and omega-6 fatty acids with semen characteristics, and anti-oxidant status of seminal plasma: a comparison between fertile and infertile men. Clin Nutr. 2010 Feb;29(1):100-5. Epub 2009 Aug 8. Safarinejad MR. Effect of omega-3 polyunsaturated fatty acid supplementation on semen profile and enzymatic anti-oxidant capacity of seminal plasma in infertile men with idiopathic oligoasthenoteratospermia: a double-blind, placebo-controlled, randomised study. Andrologia. 2011 Feb;43(1):38-47. doi: 10.1111/j.1439-0272.2009.01013.x. Epub 2010 Dec 19. Suh M, Merrells KJ, Dick A, Taylor CG. Testes of obese rats are highly responsive to n-3 long-chain fatty acids. Br J Nutr. 2011 Oct;106(7):1005-12. Epub 2011 Apr 13.,te Velde E, Burdorf A, Nieschlag E, Eijkemans R, Kremer JA, Roeleveld N, Habbema D.Is human fecundity declining in Western countries? Hum Reprod. 2010 Jun;25(6):1348-53. Epub 2010 Apr 14. University of Illinois at Urbana-Champaign (UIUC). Illinois Scientists Link Dietary DHA to Male Fertility. January 9, 2012. Accessed at http://fshn.illinois.edu/Illinois+Scientists+Link+Dietary+DHA+to+Male+Fertility. Wathes DC, Abayasekara DR, Aitken RJ. Polyunsaturated fatty acids in male and female reproduction. Biol Reprod. 2007 Aug;77(2):190-201. Epub 2007 Apr 18. Review.

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