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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
February 5, 2011

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Compounded Options - Could have a Positive Impact on the Treatment of MS
Depression and Diabetes — A Bad Combination
Polycystic Ovary Syndrome as a Risk Factor for Depression
Restricted Diet May Improve ADHD Symptoms, but Not Based on IgG Testing
A New Treatment for Insomnia?
Diabetes Adversely Affects Breast Cancer Outcomes
Weight Lifting: Safe in Breast Cancer Survivors Following Lymph Node Resection
Steroids for Children with Community-Acquired Pneumonia?
Use of Hemoglobin A1c to Diagnose Diabetes
Omega-3s Show New Benefit for Mood Health French study in mice
   Omega-3s’ link to mood health; lack of fish fats blunts cannabinoid receptors,
   new brain connections
Vitamin D and Frailty — A Not-So-Simple Relation

I was recently approached regarding compounded options that could have a positive impact on the treatment of MS:
Following is my response…
     Thank you for contacting me regarding this issue. MS and its treatment have been a passion of mine for many years. Most of the conventional meds on the market are outrageously expensive, have significant side effects and are only marginally effective. I have been networking and working with physicians and other clinicians throughout the chicagoland area and around the country to try to help patients achieve an improved quality of life (QOL) in a reasonable and economical fashion. Following are some of the things that we have found effective for many patients. Obviously not everything works for everyone but here are some things that are wonderfully effective and backed up by clinical studies published in the peer-reviewed literature. 
     Vitamin D3 50,000 IU PO daily (cost $45/35 days or $135/140 days) - Journal: Neurology - MS patients took 40000IU PO daily for 23 weeks and had a mean blood level of 250ng/ml (typical range: 30-100ng/ml). Patients showed no adverse effects and universally showed improvement in many MS parameters 
     HCG Low dose - Dr Anette Mnabhi, Montgomery IL - MS and FMS Patients using HCG in low doses (125IU) intranasally or IM exhibited improved mobility, energy and decreased pain and no significant adverse reactions. Activity levels (number of steps taken daily) increased 700 - 1500%. This was initially associated with the very low calorie HCG diet (VLCD) protocol that we have been working with for the past year but the activity levels were so remarkable that Dr Mnabhi decided to continue the treatment after weight loss goals were reached and had continued success.
     Probiotics with FOS and Saccharomyces Boulardii (SB)- both the immune systen and the inflammatory system are highly affected and even modulated by the gut. Probiotics normalize gut function and will often repair tissue in the colon and ileum. the Probiotic, Saccharomyces Boulardii (SB) is a non-commensal fungal probiotic that releases short chain fatty acids such as propionic, acetic and butyric acids that modulate and promote healthy gut flora. What is really great is that once the SB hasa been discontinued it will predominantly leave the environment within 10 days thereby not establishing an artificial flora and subsequent dysbiosis. Probiotics with FOS 20-40 billion units of probiotic ans 1-2 grams of FOS (fructooligosaccharides) divided into 2 daily doses has been useful to restore and maintain appropriate gut flora, provide bowel regularity and reduce many of the inflammatory aspects of MS
     Low Dose Naltrexone (LDN 3-4.5mg HS) - a compounded product that has been very useful in alleviating pain & discomfort associated with MS. It allows improved mobility and at this dose has yet to show any adverse effects on our patients. It is inexpensive and typically very effective. 
     Aminopyridine Sustained Release capsules - aminopyridine (4-AP) has recently become commercially available in a 10mg sustained release product. Many people are unable to tolerate this new pill and for many it does not seen to be as weffective as the compounded product. Additionally, people who have been on the compounded product have not experienced the same frequency of dose related seixures that have been occurring with the commercial product. we have been compounding 4-AP for many years and have seen remarkable responses tomany patiens without adverse reactions. Additionally, the compounded product has historically been a fraction of ther price of the commercially available product. 
     Procarin Cream - Procarin is a Histamine and caffeine cream that was developed by a RN in Utah about a decade ago. It enjoyed marginal success for several years and only a few pharmacies were licensed by its creator to prepare the product. Mark Drugs was and still is one of those compounding pharmacies. It costs the consumer about $249/month and only about 20-30% of people who use it see significant improvement. The improvement in mobility tends to last for about a year but then tends to diminish. We had one woman -who is still a patient or ours but not using Procarin any longer- who was able to leave her wheelchair and walker ah mome for 6 months and go to the mall, grocery shopping and a variety of "normal" activities for about 6 months then started to regress. 
     We have had other successes with a variety of nutritional and dietary approaches that seem to solve parts of the puzzle. I would be happy to discuss these and other options at greater length.
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Arch Gen Psychiatry 2011 Jan; 68:42.
Depression and Diabetes — A Bad Combination
In the Nurses' Health Study, both conditions increased all-cause and cardiovascular mortality, and the combination was worse than either condition alone.
     Both depression and diabetes increase the risk for cardiovascular disease (CVD), and depression is more common in patients with diabetes than in the general population. For this report from the longitudinal Nurses' Health Study, investigators used repeated structured questionnaires to examine the impact of diabetes and depression on CVD-related and all-cause mortality during 6 years of follow-up in 78,282 women aged 54 to 79 at baseline.
     Depression was defined as having a diagnosis of depression, taking antidepressants, and/or reporting severe depressive symptoms. Type 2 diabetes was identified by reports of typical symptoms plus an elevated blood glucose level, of two or more elevated glucose levels, or of treatment with hypoglycemic agents. Compared with women who had neither condition, those who had depression only, diabetes only, and both conditions had age-adjusted risks of 1.76, 1.71, and 3.11, respectively, for all-cause mortality and 1.81, 2.67, and 5.38 for CVD mortality. Correcting for other risk factors (including BMI, smoking, alcohol intake, physical activity, hypertension, hypercholesterolemia, heart disease, stroke, and cancer), participants with both depression and diabetes still had the highest risks for all-cause and CVD mortality (relative risks, 2.07 and 2.72, respectively).
     Comment: Clearly, depression can exacerbate both diabetes mellitus and CVD by encouraging poor diet, inactivity, smoking, alcohol use, and nonadherence to medication regimens. In addition, both disorders have been linked to activation of proinflammatory cytokines (see JW Psychiatry Mar 29 2010 and Nov 27 2006), which can contribute to CVD. Whether amelioration of depression directly improves cardiovascular risk factors is unknown, but it seems likely to enhance patients' active involvement in treatment of both diabetes and CVD.
Steven Dubovsky, MD Published in Journal Watch Psychiatry January 31, 2011
Citation(s): Pan A et al. Increased mortality risk in women with depression and diabetes mellitus. Arch Gen Psychiatry 2011 Jan; 68:42.PMID: 21199964
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Obstet Gynecol 2011 Jan; 117:145
Polycystic Ovary Syndrome as a Risk Factor for Depression
Psychological distress should be considered in all women with PCOS.

     Previous studies have suggested that women with polycystic ovary syndrome (PCOS) are at excess risk for abnormal depression scores on screening. But is the pattern sufficiently clear to warrant screening of all women with PCOS? Investigators conducted a systematic review and meta-analysis that included 10 cross-sectional studies that involved 522 women with well-documented PCOS and 475 women without PCOS who were screened for depression. The psychological instruments varied among studies, but the Beck Depression Inventory was used most commonly.
     Women with PCOS were fourfold more likely to have abnormal depression scores than were women without PCOS (odds ratio, 4.03; 95% confidence interval, 2.96–5.50). Subanalysis indicated that odds of having abnormal scores were independent of body-mass index.
     Comment: These findings should be viewed with caution because appropriate psychological screening instruments and interventions remain to be developed for women with PCOS. Still, the data are sufficiently compelling (along with a growing body of evidence suggesting that PCOS is a risk factor for psychological dysfunction) to indicate that psychological distress, not just depression, should be considered in all women with PCOS. Whether this distress is related directly to PCOS itself or to its manifestations (e.g., obesity, hirsutism, infertility, glucose intolerance) is unknown.
Robert W. Rebar, MD Published in Journal Watch Women's Health January 27, 2011
Citation(s): Dokras AS et al. Increased risk for abnormal depression scores in women with polycystic ovary syndrome: A systematic review and meta-analysis. Obstet Gynecol 2011 Jan; 117:145.PMID: 21173657
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The Lancet, Volume 377, Issue 9764, Pages 494 - 503, 5 February 2011
Restricted Diet May Improve ADHD Symptoms, but Not Based on IgG Testing
A restricted diet may help reduce symptoms of attention-deficit hyperactivity disorder in children, according to a study in the Lancet.
     Hypothesizing that ADHD might be a hypersensitivity disorder, researchers randomized 100 children aged 4 to 8 years with ADHD to a diet or control group. The intervention group ate an individually designed restricted diet consisting of rice, meat, vegetables, pears, water, potatoes, fruits, and wheat. After 5 weeks, 64% of children in the restricted diet group showed a clinical improvement of at least 40% on ADHD scores.
     The 30 children with clinical improvement moved on to the challenge phase — having either three high-IgG or three low-IgG foods (based on individual blood tests) reintroduced into their diet for 2 weeks before switching to the other IgG group. Most children (63%) experienced a relapse of ADHD behavior during this phase, regardless of whether they were receiving high- or low-IgG food components.
     A commentator says that the results provide "evidence against the benefit of using IgG blood levels (a common practice in complementary medicine) to determine which foods are triggering ADHD symptoms." She says that children with ADHD may go on a restricted diet for 2 to 5 weeks, and then reintroduce one food per week.
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J Am Geriatr Soc 2011 Jan; 59:82
A New Treatment for Insomnia?
A combination of melatonin, zinc, and magnesium was safe and effective,
but the results are preliminary.

     Insomnia is an extremely frustrating problem for many older patients and their clinicians. In this randomized double-blind trial from Italy, researchers enrolled 43 residents (mean age, 78) of a long-term care facility; all met criteria for primary insomnia, and none had psychiatric diagnoses or dementia. Participants received either placebo or a nightly supplement that consisted of melatonin (5 mg), zinc (11.25 mg), and magnesium (225 mg). The authors' stated rationale for including zinc and magnesium was that previous research suggested these substances improve mood and enhance endogenous synthesis of melatonin. Previous clinical trials of melatonin alone for insomnia have yielded mixed results (JW Gen Med Feb 17 2004).
     After 60 days of treatment, the supplement group exhibited highly significant improvement on a validated sleep quality index (mean change, 7 points on a 21-point scale), compared with no change in the control group. Significant changes on secondary measures (other sleep scales, a quality-of-life survey, and a depression scale) also favored the supplement group. No adverse effects were recorded.
     Comment: These results are almost too good to be true — an apparently safe and highly effective treatment for primary insomnia. Additional research to replicate these findings in other populations and to assess longer-term safety and efficacy is essential. But, in the meantime, the intervention might be worth a try in selected patients for whom standard sleep hygiene measures have been unsuccessful.
Allan S. Brett, MD Published in Journal Watch General Medicine February 3, 2011
(s):Rondanelli M et al. The effect of melatonin, magnesium, and zinc on primary insomnia in long-term care facility residents in Italy: A double-blind, placebo-controlled clinical trial. J Am Geriatr Soc 2011 Jan; 59:82. (http://dx.doi.org/10.1111/j.1532-5415.2010.03232.x) PMID: 21226679
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J Clin Oncol 2011 Jan 1; 29:54
Diabetes Adversely Affects Breast Cancer Outcomes
All-cause mortality was higher among women with diabetes and breast cancer than among their nondiabetic counterparts; breast cancer diagnosis and treatment differed for women with versus without diabetes.
     Women with diabetes have higher breast-cancer–related mortality than do women without diabetes, possibly because of delays in diagnosis, less-common use of adjuvant therapy, and diabetes-related comorbidities. Now, researchers have conducted a prospective cohort study and a meta-analysis to distinguish among these and other factors that influence breast cancer outcomes in women with diabetes.
     In the first report, investigators assessed baseline blood samples from the Women's Healthy Eating and Living Study, in which breast cancer survivors were followed. Among 3003 women whose glycosylated hemoglobin (HbA1c) levels were measured, 6% had levels ≥6.5% (diagnostic for chronic hyperglycemia). At a median follow-up of 7.3 years, 503 women experienced distant or locoregional recurrences or new breast primary tumors. Of 414 deaths at a median follow-up of 10.3 years, 372 were caused by breast or other cancers, 22 were from other causes, and 11 were caused by heart disease. In adjusted analysis, HbA1c levels ›7.0% compared with levels <6.5% were associated with more than twofold higher risk for all-cause mortality, although not with higher risk for breast cancer recurrence.
     The meta-analysis included eight breast cancer outcome studies in women with preexisting diabetes. Pooled results during 1- to 12-year follow-up showed that women with breast cancer and diabetes had higher all-cause mortality risk than did women with breast cancer but no diabetes (hazard ratio, 1.5). In two studies, researchers addressed breast-cancer–specific mortality; in one, among women who received chemotherapy, those with diabetes had slightly higher mortality than did those without diabetes (odds ratio, 1.2; 95% confidence interval, 1.07–1.35). Of four studies in which breast cancer stage at diagnosis was reported, three showed positive associations between preexisting diabetes and excess risk for late-stage breast cancer diagnoses. Three studies identified treatment differences for women with diabetes versus those without diabetes. One study showed that diabetes adversely affected disease-free survival.
     Comment: Although all-cause mortality was consistently higher among women with diabetes and breast cancer than among their nondiabetic counterparts, whether and how this relation is causal remain unknown. The authors of the cohort study suggest that altered levels of insulin, insulin-like growth factors, sex hormones, and inflammatory markers might directly affect breast cancer progression in women with diabetes. We need more studies designed to determine whether both expedited diagnosis and better control of diabetes will improve breast cancer outcomes.
Diane E. Judge, APN/CNP Published in Journal Watch Women's Health February 3, 2011
Citation(s): Erickson K et al. Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast cancer. J Clin Oncol 2011 Jan 1; 29:54.PMID: 21115861
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JAMA 2010 Dec 22; 304:2699
Weight Lifting: Safe in Breast Cancer Survivors Following Lymph Node Resection
Upper-body exercise did not raise risk for lymphedema.
    Lymphedema is an uncomfortable, disfiguring, and potentially disabling complication of breast cancer surgery. The condition occurs in as many as 7% of women who undergo sentinel node biopsy and as many as 47% who undergo complete axillary dissection. Although conventional advice is to avoid lifting heavy objects with the affected arm following breast cancer surgery, weight training has been shown to be safe in breast cancer survivors with known lymphedema (JW Womens Health Aug 13 2009). Now, the same researchers have investigated weight lifting in women with breast cancer (diagnosed 1–5 years previously) who had undergone removal of 2 axillary lymph nodes and who were free of lymphedema. A total of 154 participants were randomized to a 1-year membership in a local community fitness center where they were instructed twice-weekly in progressive weight lifting or to no intervention (control). Participants in the control group were asked not to change their exercise levels and were offered supervised weight training after study completion.
     Overall, among 134 women who completed follow-up assessments at 1 year, incidence of lymphedema was 11% in the intervention group and 17% in the control group (P=0.04). Among women who had 5 nodes removed, lymphedema rates were 7% and 22% in the intervention and control groups, respectively (P=0.003).
     Comment: Taken together with the authors' previous findings, these results provide reassurance that women who have undergone surgery for breast cancer should not be discouraged from using their arms and upper bodies much as they did before surgery — or from participating in weight training. The results show that weight lifting in such women is not associated with excess risk for lymphedema. Perhaps the next step will be to see whether weight lifting might prevent lymphedema associated with breast cancer surgery.
Andrew M. Kaunitz, MD Published in Journal Watch Women's Health January 6, 2011
     Citation(s): Schmitz KH et al. Weight lifting for women at risk for breast cancer–related lymphedema: A randomized trial. JAMA 2010 Dec 22; 304:2699.PMID: 21148134
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Pediatrics 2011 Feb; 127:e255
Steroids for Children with Community-Acquired Pneumonia?
Hospital length of stay was shorter in children who received corticosteroids — but only in those with wheezing.
    Some data suggest that corticosteroids have an ameliorative effect in adults with community-acquired pneumonia (CAP), presumably because these agents downregulate inflammatory cytokines, resulting in quicker resolution of disease. In a recent retrospective cohort study, researchers examined whether corticosteroids might benefit children with CAP. They analyzed data for 20,703 CAP patients aged 1 to 18 years who were discharged from any of 38 hospitals in 2006 or 2007.
     A total of 7234 (35%) patients received adjunctive corticosteroids, but the proportion varied greatly among centers (1%–51%). Across all age groups, length of stay (LOS) was shorter for children who received steroids than for those who did not. The median LOS was 3 days for all children; 10% of steroid recipients and 20% of nonrecipients had an LOS ≥7 days. Among the children who received β-agonists (presumably an indicator of wheezing), LOS was shorter for steroid recipients than for nonrecipients. However, among those who did not receive β-agonists, the LOS was slightly longer for steroid recipients than for nonrecipients.
     Comment: These data suggest that steroids benefit children with CAP — but only those who have wheezing. The study suffers from several limitations, however. For example, there was no information about the causative organisms, no validation of the pneumonia diagnosis, and no apparent protocol for deciding when to discharge. Furthermore, institutions varied in their use of adjunctive corticosteroids from 1% to 51%, so the indications for corticosteroids were inconsistent. The question of which children with CAP might benefit from corticosteroids should be addressed in a protocol-driven, prospective, randomized trial.
Robert S. Baltimore, MD Published in Journal Watch Infectious Diseases February 2, 2011
(s): Weiss AK et al. Adjunct corticosteroids in children hospitalized with community-acquired pneumonia. Pediatrics 2011 Feb; 127:e255.
(http://dx.doi.org/10.1542/peds.2010-0983) PMID: 21220397
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J Clin Endocrinol Metab 2010 Dec; 95:5289
Use of Hemoglobin A1c to Diagnose Diabetes
Cutoffs for glycosylated hemoglobin and fasting glucose levels don't identify the same people as having diabetes.
    In 2010, the American Diabetes Association (ADA) endorsed glycosylated hemoglobin (HbA1c) level as an acceptable method for diagnosing diabetes mellitus (Diabetes Care 2010; 33[Suppl 1]:S62). According to the ADA, diabetes should be diagnosed when HbA1c level is ≥6.5% or fasting plasma glucose (FPG) level is ≥126 mg/dL; prediabetes is diagnosed when HbA1c level is 5.7% to 6.4%, or FPG level is 100 to 125 mg/dL.
     Researchers measured both HbA1c and FPG in 1865 community-dwelling older adults (age range, 70–79) without diabetes. Eighty people (4.3%) met either the HbA1c or the FPG criterion for diabetes; about one third had elevated HbA1c only, one third had elevated FPG only, and one third had both. In addition, 596 people (32%) met one or both prediabetes criteria; again, about one third fell into each diagnostic group. In an analysis that reached borderline statistical significance, black participants were more likely to receive diagnoses of diabetes or prediabetes based on elevated HbA1c than based on elevated FPG; the reverse was true for white participants.
    Comment: Hemoglobin A1c measurement varies across assays. Moreover, genetic differences in hemoglobin glycation and heterogeneity in red cell life span could explain why correlations between HbA1c and plasma glucose differ across populations. The authors of the current study worry that clinicians will screen many patients with both HbA1c and FPG, which could result in overdiagnosis of diabetes. Along the same lines, editorialists suggest that the HbA1c cutoff for diagnosing diabetes should be raised to 7.0%.
Allan S. Brett, MD Published in Journal Watch General Medicine February 1, 2011
     Citation(s): Lipska KJ et al. Identifying dysglycemic states in older adults: Implications of the emerging use of hemoglobin A1c. J Clin Endocrinol Metab 2010 Dec; 95:5289. (http://dx.doi.org/10.1210/jc.2010-1171)PMID: 20861123
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February 3, 2011
Omega-3s Show New Benefit for Mood Health French study in mice adds another reason for omega-3s’ link to mood health; lack of fish fats blunts cannabinoid receptors and new brain connections
by Craig Weatherby
Encouraging animal research from France supports evidence that omega-3 fatty acids play a key role in mood health … and expands our grasp on how they work in the brain.

    Encouraging animal research from France supports evidence that omega-3 fatty acids play a key role in mood health … and expands our grasp on how they work in the brain.
    French scientists tested the effects of feeding mice a diet that was relatively low in omega-3 fatty acids and high in the omega-6 fatty acids that predominate in most  vegetable oils (Lafourcade M et al. 2011).
     As they said in a press release, this imbalanced fat intake “had deleterious consequences on synaptic functions and emotional behaviors.”  (INSERM 2011)
     In other words, it messed with brain systems and chemicals that maintain mood.
     As our readers know, the average American’s diet suffers from the same kind of “omega-imbalance”, which is associated with major health conditions from cardiovascular disease and osteoporosis to depression and dementia.
     For our past coverage of this topic, see the “Omega-3 / Omega-6 Balance” section of our news archive, and for an overview, see “Report Finds Americans Need More Omega-3s ... and Far Fewer Omega-6 Fats”.
     The average American’s diet is grossly imbalanced in favor of omega-6 fats, primarily from the vegetable oils most commonly used in homes and in packaged or prepared foods (corn, canola, soy, safflower, sunflower). Omega-6s also abound in soy milk, poultry, and red meats
     Olive oil, macadamia nut oil, and special “hi-oleic” safflower and sunflower oils are the only oils low in omega-6s.
     Most researchers estimate that Americans consume 20 to 40 times as much omega-6 as omega-3 fatty acids … when we should be eating the two types in roughly equal amounts, consuming no more than three grams of omega-6 fats for every gram of omega-3 fats.
     This extreme imbalance reduces the amounts of omega-3s that can get into our cells … a “blocking” effect that has broad, deep health implications for brain and overall health.
     French study finds omega-3s affect key mood-related systems
     Prior animal research showed that omega-3s foster growth of cells in the brain’s hippocampus region and promote connections between those cells … an effect associated with reduced depression risk and symptom severity (Venna VR et al. 2008).
     And clinical findings by NIH psychiatrist Joe Hibbeln, M.D., show that people with higher blood levels of omega-3 fatty acids have more serotonin and dopamine – two key mood-related neurotransmitters – in their spinal fluid (Hibbeln JR et al. 1998).
     Now, findings from INSERM – France’s equivalent to the U.S. National Institutes of Health – add another reason why omega-3s and the omega balance matter to mood (Lafourcade M et al. 2011).
     A team led by Drs. Olivier Manzoni and Sophie Layé wanted to test the idea that feeding mice an omega-imbalanced diet starting before birth would influence brain systems involved in depression and anxiety.
     The INSERM team fed mice a life-long diet imbalanced in omega-3 and omega-6 fatty acids.
     They found that the resulting shortage of omega-3s and overload of omega-6 fats disturbed communication between brain cells (neurons).
     Critically, this was the first research to show the omega-imbalanced diet virtually shut down their brain cells’ CB1R cannabinoid receptors, which play a key role in between-cell communications (i.e., neurotransmission).
     And the “neuronal dysfunction” induced by an omega-imbalanced diet was accompanied by depressive behaviors among the mice.
     Among omega-3 deficient mice, the usual effects produced by cannabinoid receptor activation disappeared, along with the critical antioxidant effects exerted by the brain’s cannabinoid compounds.
     The researchers discovered that the omega-3 deficient diet impaired synaptic plasticity – the ability to form new connections in the brain – in at least two areas (prefrontal cortex and nucleus accumbens) involved in reward, motivation, and emotional regulation.
     These parts of the brain contain a large number of CB1R cannabinoid receptors and have important functional connections with each other.
     Drs. Manzoni and Layé noted that their results “… corroborate clinical and epidemiological studies which have revealed associations between an omega-3/omega-6 imbalance and mood disorders.” (INSERM 2011)
     Critically, these findings provide another biological explanation for the statistical associations repeatedly found between diets low in omega-3s – which are now common, worldwide – and mood disorders such as depression.
     Human evidence supports omega-3s’ hypothetical mood-regulation role
Five years ago, the American Psychiatric Association concluded that people who consume higher amounts of omega-3s from fish (EPA and DHA) enjoy lower risks of depression and related mood disorders (Freeman MP et al. 2006).
     For that story, see “Top Psych Panel Says Omega-3s Deter Depression, Bipolar Disorder”.
     Then, two years ago, the results of the largest-ever clinical trial found that omega-3 fish oil significantly benefited the half of clinically depressed participants who did not also have a diagnosed anxiety disorder (Lesperance F et al 2009).
     In fact, fish oil appeared to help these people about as much as the leading class of antidepressant drugs ... selective serotonin re-uptake inhibitors (SSRIs) such as Prozac and Paxil. (See “Fish Oil Rivals Antidepressants in Clinical Trial.”)
     For more research on omega-3s and mood, see the “Omega-3s & Brain Health” section of our news archive.
     Sources: Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, Keck PE Jr, Marangell LB, Richardson AJ, Lake J, Stoll AL. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry. 2006 Dec;67(12):1954-67. Review. Hibbeln JR, Linnoila M, Umhau JC, Rawlings R, George DT, Salem N Jr. Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. Biol Psychiatry 1998; 44: 235-242. INSERM (Institut National de la Santé et de la Recherche Médicale). A deficiency of dietary omega-3 may explain depressive behaviors. January 30, 2011. Accessed at   http://www.eurekalert.org/pub_releases/2011-01/ind-ado012811.php Lafourcade M, Larrieu T, Mato S, Duffaud A, Sepers M, Matias I, De Smedt-Peyrusse V, Labrousse VF, Bretillon L, Matute C, Rodríguez-Puertas R, Layé S, Manzoni OJ. Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. Nat Neurosci. 2011 Jan 30. [Epub ahead of print] Lesperance F et al. The efficacy of eicosapentaenoic acid for major depression: Results of the OMEGA-3D trial. 9th World Congress of Biological Psychiatry: Abstract FC-25-005. Presented July 1, 2009. Accessed at:http://www.wfsbp-congress.org/fileadmin/user_upload/WFSBP_Final_Programme_090625.pdf Nemets B, Stahl Z, Belmaker RH. Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry. 2002; 159(3): 477-479. Owen C, Rees AM, Parker G. The role of fatty acids in the development and treatment of mood disorders. Curr Opin Psychiatry. 2008 Jan; 21(1): 19-24. Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry. 2002; 59(10): 913-919. Sahay A, Hen R. Hippocampal neurogenesis and depression. Novartis Found Symp. 2008; 289: 152-60; discussion 160-4, 193-5. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003 Aug 8; 301(5634): 805-9. Venna VR, Deplanque D, Allet C, Belarbi K, Hamdane M, Bordet R. PUFA induce antidepressant-like effects in parallel to structural and molecular changes in the hippocampus. Psychoneuroendocrinology. 2009 Feb; 34(2): 199-211. Epub 2008 Oct 10.
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J Clin Endocrinol Metab 2010 Dec; 95:5266
Vitamin D and Frailty — A Not-So-Simple Relation
Both low and high vitamin D levels were associated with frailty in older women.
    Frailty is one postulated result of inadequate vitamin D status in older populations. In this observational study, researchers assessed cross-sectional and longitudinal relations between vitamin D levels and a five-item measure of frailty.
     In a cohort of about 6300 older white women (mean age, 77), the relation between baseline serum 25-hydroxyvitamin D (25[OH]D) level and frailty was "U-shaped": Compared with women who had serum 25(OH)D levels between 20 and 30 ng/mL, women with levels <15 ng/mL were significantly more likely to be frail (odds ratio, 1.47), but the same was true for women with levels ≥30 ng/mL (OR, 1.32). The U-shaped relation also existed in the subgroup of women who took no vitamin D supplements. During 5 years of follow-up, 16% of initially non-frail women became frail; no statistically significant association was noted between baseline vitamin D level and incident frailty.
     Comment: This observational study obviously doesn't prove that high vitamin D levels cause frailty. Rather, its value is to remind us that the relation between vitamin D status and health (outside of "bone health") remains controversial and that no evidence yet exists to support vitamin D supplementation with target levels higher than 30 ng/mL. The Institute of Medicine's recent widely publicized report, entitled Dietary Reference Intakes for Calcium and Vitamin D, makes exactly this point.
Allan S. Brett, MD Published in Journal Watch General Medicine February 1, 2011
     Citation(s): Ensrud KE et al. Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab 2010 Dec; 95:5266. (http://dx.doi.org/10.1210/jc.2010-2317) PMID: 21131545

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