My favorite ways of keeping up to date are all available to you, or you can just read my notes on this website.  I use the National Institute of Health PubMed Medline search engine a lot.  Just click on PubMed to do it yourself.  I also like the free service of the British Medical Journal.  Science Daily and New Scientist are other favorites.  Of course, Google is a great search engine, but there is a huge amount of promotional fluff on the internet by people after your money or out to rip off the taxpayer.  There are many other good sites, but the above are the ones I visit the most.  I hope you enjoy my site.  The newest studies I have reviewed are below.  Older one's are listed above.  There are no November pages since I was too busy relocating offices.

Newest Studies: January-February, 2006

Blind People Helped by Melatonin: Melatonin 300 microg can entrain (synchronize) free-running circadian rhythms of 10 totally blind subjects that would otherwise drift later each day. Totally blind people will need to take melatonin daily over their entire lifetimes in order to remain entrained to the 24 h day. Left untreated, their free-running endocrine, metabolic, behavioral, and sleep/wake cycles can be almost as burdensome as not having vision. Melatonin Entrains Free-running Blind People According to a Physiological Dose-response Curve. Lewy AJ, et al. Oregon Health & Science University. Chronobiol Int 2005;22(6):1093-106.

Eye: Age-related Macular Degeneration Halted by Melatonin: Melatonin has been shown to have the capacity to control eye pigmentation and thereby regulate the amount of light reaching the photoreceptors, to scavenge hydroxyradicals and to protect retinal pigment epithelium (RPE) cells from oxidative damage. The physiological decrease of melatonin in aged people may be an important factor in RPE dysfunction, which is a well known cause for initiation of AMD. In a case-control study with a follow-up of 6-24 months, 100 patients with AMD were given 3 mg melatonin at bedtime for at least 3 months with 55 patients followed for more than 6 months. At 6 months, the visual acuity had been kept stable in general. This result is better than the otherwise estimated natural course. Only 8 eyes showed more retinal bleeding and 6 eyes more retinal exudates. The majority had reduced pathologic macular changes. We conclude that the daily use of 3 mg melatonin seems to protect the retina and to delay macular degeneration. No significant side effects were observed. Effects of melatonin in age-related macular degeneration. Yi C, et al. Sun Yat-Sen University, Guangzhou, China. . Ann NY Acad Sci 2005 Dec;1057:384-92. Ed: Melatonin is my candidate for the fountain of youth. After age 50, all of us should probably take it. For more see Melatonin.

ALS Helped Considerably in Mice by Carnitine: A mutation of the gene encoding Cu,Zn-superoxide dismutase (SOD1) has been reported in 20% of familial cases of ALS (FALS). Transgenic mice that overexpress a mutated human SOD1 exhibit a phenotype and pathology similar to those observed in patients with FALS. Mitochondrial abnormality has been reported in patients with ALS and in animal models of FALS. L-carnitine, an essential cofactor for the beta-oxidation of long-chain fatty acids, effectively inhibits various types of mitochondrial injury and apoptosis both in vitro and in vivo. Oral l-carnitine prior to disease onset significantly delayed the onset of signs of disease (P = 0.0008), delayed deterioration of motor activity, and extended life span (P = 0.0001) in transgenic mice carrying a human SOD1 gene with a G93A mutation (Tg). Subcutaneous injection of l-carnitine increased the life span of Tg mice (46% increase in male, 60% increase in female) even when given after the appearance of signs of disease. l-Carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis. Kira Y, et al. Osaka City University Medical School, Japan. Brain Res 2006 Jan 11. 

Sickle Cell Disease Appears to be Helped by Carnitine: L-carnitine was given to randomly selected 37 Sickle Cell Disease (SCD) children for 6 months. Weight, height, serum ferritin levels, units of blood transfused and the number of veno-occlusive crises all showed significant improvement. Cardiac diastolic function and pulmonary hypertention showed some improvement after L-carnitine administration. Diastolic dysfunction and pulmonary hypertension in sickle cell anemia: is there a role for L-carnitine treatment? El-Beshlawy A, et al. Cairo University, Egypt. Acta Haematol 2006;115(1-2):91-6. Double-blind research is needed. For more, see The Carnitines.

ADHD Youth Often Grow Up Developing Many Problems: In a case-control, 10-year prospective study of 140 ADHD youth vs. 120 without ADHD, many psychiatric disorders were more common in the grown up ADHD youth: Major Psychopathology (mood disorders and psychosis) up 510%, Anxiety Disorders 120%, Antisocial Disorders (conduct, oppositional-defiant, and antisocial personality disorder) 490%, Developmental Disorders (elimination, language, and tics disorder) 150%, and Substance Dependence Disorders (alcohol, drug, and nicotine dependence) 100%, as measured by blinded structured diagnostic interview. Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study. Biederman J, et al. Massachusetts General Hospital, Boston. Psychol Med 2006 Feb;36(2):167-79. For more, see ADHD.

Alcoholism Risk May be Lowered by Vitamin K at Birth: Taking advantage of a serendipitous event in the history of treating newborns, two thirds of the original 330 subjects in this study were high-risk sons of alcoholic fathers. Of 238 completing the 30-year follow-up, 44 received vitamin K supplementation at birth; 161 were considered high risk, and 66 were categorized as having lower birth weight (<6 lbs). Vitamin K treatment, inherited risk and low birth weight each independently predicted alcohol dependence and problem drinking. Vitamin K treatment was associated with significantly lower rates of alcohol dependence and fewer symptoms of problem drinking. Vitamin K might reduce early postnatal hemorrhage and oxidative brain damage, and thus lower the risk of alcoholism. Neonatal vitamin K might reduce vulnerability to alcohol dependence in Danish men. Manzarda AM, et al. University of Kansas. . J Stud Alcohol 2005 Sep;66(5):586-92. v

EPS, Akathesia, and Tardive Dyskinesia Common with Atypicals: Of 51 individual patient trials of atypical neuroleptic agents (17 risperidone, 13 olanzapine, 11 quetiapine, 8 ziprasidone, and 2 aripiprazole) in 37 bipolar patients (type I or type II) with an average duration of treatment was 25.5 weeks, 63% of trials resulted in moderate to severe EPS. EPS and discontinuation frequencies were similar between specific neuroleptic agents or between high potency (risperidone/ziprasidone/aripiprazole; 53%, 27/51 trials) and low potency (quetiapine/olanzapine; 47%, 24/51 trials) agents. Akathisia was less common with low potency agents. Younger age was associated with more akathisia. 31% discontinued due to side effects. 8% (4/51) of trials led to mild de novo tardive dyskinesia. Extrapyramidal side effects with atypical neuroleptics in bipolar disorder. Ghaemi SN, et al. Emory University. Prog Neuropsychopharm Biol Psychiatry 2006 Jan 10. v

Curcumin/Quercetin Reduce Kidney Rejection: In a 6-month DB PC study of 43 dialysis dependent cadaveric kidney, those given 480 mg of curcumin and 20 mg of quercetin, started after surgery and taken for 1 month, those given low dose (one capsule, one placebo) and high dose (two capsules). Delayed graft function occurred in 14% of controls, but none on curcumin/quercetin. Early graft function was controls 43%, low dose 71% and high dose 93% (P=0.013). Serum creatinine was significantly lower at 2 days (control 7.6, low 5.4, high 4.0; P=0.0001) and 30 days (control 1.82, low 1.65, high 1.33, P=0.03). Acute rejection incidence within 6 months was control 14.3%, low dose 14.3% and high dose 0%. Tremor was detected in 13% of high dose patients vs. 46% of others. Beneficial effects of the bioflavonoids curcumin and quercetin on early function in cadaveric renal transplantation: a randomized placebo controlled trial. Shoskes D, et al. Cleveland Clinic, Florida. Transplantation 2005 Dec 15;80(11):1556-9. Ed: Curcumin is promising for many disorders, but has little human research. For more, see Curcumin.

Added Risperidone No Help For Clozapine-Treated Schizophrenics: In an 8-week DB PC study of 68 schizophrenic patients on clozapine, the addition of 3 mg of risperidone made no statistically significant difference: 9 of 34 patients receiving placebo and 6 of 34 receiving risperidone responded to treatment. Clozapine Alone versus Clozapine and Risperidone with Refractory Schizophrenia. Honer WG, et al. University of British Columbia. N Engl J Med 2006 Feb 2;354(5):472-482. v

10% Murderers Serious Mental Illness at the Time: In a national clinical survey of 1594 people convicted of homicide in England and Wales, 5% had schizophrenia; 10% had symptoms of mental illness at the time of the offence; 9% received a diminished responsibility verdict and 7% a hospital disposal - both were associated with severe mental illness and symptoms of psychosis. Some perpetrators receive prison sentences despite having severe mental illness. Rates of mental disorder in people convicted of homicide: National clinical survey. Shaw J, et al. University of Manchester, UK. . Brit J Psychiatry 2006 Feb;188:143-7. Ed: The U.S. legal system is one of the least humane in the world, both in sentencing and after incarceration with abuse of prisoners commonplace in states like Pennsylvania.  Pennsylvania's county jails appear much more humane than it's state prisons.  This British study allows a more objective look. v

Anti-Psychotics May Increase the Death Rate: In a 17-year follow-up study of a nationally representative sample of 7,217 Finns over age 29, 39 of the 99 people with schizophrenia died. Adjusted for age and gender, the relative mortality risk between those with schizophrenia and others was increased 184%, and was increased 125% after further adjusting for somatic diseases, blood pressure, cholesterol, body mass index, smoking, exercise, alcohol intake and education. The number of neuroleptics used at the time of the baseline survey showed a graded relation to mortality. Adjusted for age, gender, somatic diseases and other potential risk factors for premature death, the relative risk was increased 150% per increment of one neuroleptic. Schizophrenia, neuroleptic medication and mortality. Joukamaa M, et al. University of Tampere, Finland. . Brit J Psychiatry 2006 Feb;188:122-7. Ed: This is the reason I give all my patients of anti-psychotics magnesium, since cardiac arrhythmias are reduced with magnesium and most or all anti-psychotics cause an increase in arrhythmias. v

Schizophrenics Die 15 Years Early: From a review of published studies, the average life expectancy of the general population is 76 years (72 years in men, 80 years in women), whereas the corresponding figure is 61 years (57 years in men, 65 years in women) among patients with schizophrenia, i.e., a 20% reduced life expectancy. Although patients with schizophrenia are 10 to 20 times more likely than the general population to commit suicide, more than two thirds of patients with schizophrenia, compared with approximately one-half in the general population, die of coronary heart disease (CHD). The chief risk factors for this excess risk of death are cigarette smoking, obesity leading to dyslipidemia, insulin resistance and diabetes, and hypertension. Schizophrenia and increased risks of cardiovascular disease. Hennehens CH, et al. Florida Atlantic University. . Am Heart J 2005 Dec;150(6):1115-21. For more, see Schizophrenia and Death.

Psychiatric Medication Studies Strongly Rigged in Favor of the Sponsor: In an analysis of 42 head-to-head comparison studies of second-generation antipsychotics, 33 were sponsored by a pharmaceutical company. In 90% of the company studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared, e.g. Drug A did better than Drug B when the drug was sponsored by Company A, but worse when the study was funded by Company B. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings. Why Olanzapine Beats Risperidone, Risperidone Beats Quetiapine, and Quetiapine Beats Olanzapine: An Exploratory Analysis of Head-to-Head Comparison Studies of Second-Generation Antipsychotics. Heres S, et al. Technischen Universitat Munchen, Germany. . Am J Psychiatry 2006 Feb;163(2):185-94. Ed: Corruption is rampant in even prestigious academic centers. For more, see Medications for Schizophrenia.

QK1 Gene Variant May Cause Some Schizophrenia by Interfering with Myelination and Nerve Development: Chromosome 6q25-6q27 includes a susceptibility locus for schizophrenia in a large pedigree from northern Sweden. A 0.5 Mb haplotype, likely to be inherited identical by decent, within the large family that is shared among the majority of the patients (69%) was found. A gamete competition test of this haplotype in 176 unrelated nuclear families from the same geographical area as the large family showed association to schizophrenia (empirical P-value 0.041). The only gene located in the region, the quaking homolog, KH domain RNA binding (mouse) (QKI), was investigated in human brain autopsies from 55 cases and 55 controls using a high-resolution mRNA expression analysis. Relative mRNA expression levels of two QKI splice variants were clearly downregulated in schizophrenic patients (P-value 0.0004 and 0.03, respectively). The mouse homolog is involved in neural development and myelination. Human QKI, a new candidate gene for schizophrenia involved in myelination. Aberg K, et al. Uppsala University, Sweden. Am J Med Gen 2006 Jan 5;141(1):84-90. For more, see Schizophrenia Genetics.

Honey as Good as Mupirocin (Bactroban) for Hemodialysis Venous Catheters: In a DB study of 101 patients who were receiving hemodialysis via tunneled, cuffed central venous catheters, the incidences of catheter-associated bacteremias in 3 times/week at exit site honey-treated and mupirocin-treated patients were comparable (0.97 versus 0.85 episodes per 1000 catheter-days, respectively; NS). No exit-site infections occurred. During the study period, 2% of staphylococcal isolates within the hospital were mupirocin resistant. Randomized, controlled trial of topical exit-site application of honey (Medihoney) versus mupirocin for the prevention of catheter-associated infections in hemodialysis patients. Johnson DW, et al. University of Queensland, Australia. . J Am Soc Nephrol 2005 May;16(5):1456-62. For more, see Wound Care.

Epidural: Fentanyl Narcotic Added No Benefit to Bupivacaine Alone in Coronary Bypass Surgery: In a DB study of 60 patients undergoing off-pump coronary artery bypass grafting, thoracic epidural anesthesia with bupivacaine 0.125% alone, did just as well as bupivacaine 0.125% with fentanyl 3 microg/ml or bupivacaine 0.125% with clonidine 0.6 microg/ml. Pain control was very good and was not significantly different between the groups using similar infusion rates after surgery. Paraesthesia in dermatomes T1 or C8 occurred equally in all three groups. There was no neurological complication related to TEA in this study. Comparison of three different epidural solutions in off-pump cardiac surgery: pilot study. Olivier JF, et al. l'Universite de Montreal, Canada. Br J Anaesth 2005 Nov;95(5):685-91. Ed: Opiate narcotics have no place in the practice of evidence-based medicine. You will find 190 studies comparing opiates and non-opiate pain killers and opiates did better in only 4 studies and against only the very weakest pain killers, like gabapentin and nortriptyline.  They did worse in 139 studies! For more, see Opiates for Pain.

Cranial Electrotherapy Stimulation Might Help Aggression: Nine aggressive, retarded patients refractory to conventional care at a maximum security hospital were given a 3-month course of cranial electrotherapy stimulation, usually 45-60 minutes twice a day. Aggressive episodes declined 59% from baseline; seclusions were down 72%; restraints were down 58%; and use of prescribed-as-needed sedative medications decreased 53%. No patients discontinued cranial electrotherapy stimulation (CES) because of side effects. Cranial electrotherapy stimulation reduces aggression in a violent retarded population: a preliminary report. Childs A. North Texas State Hospital, Vernon, TX. . J Neuropsychiatry Clin NeuroSci 2005 Fall;17(4):548-51. Ed: This is a clinical, not a research report, since there were no controls, and no blinding. This therapy has been found useful for depression, but is rarely used.  The research looks quite good, but I am just beginning to use it on patients. For more, see Cranial Electrotherapy Stimulation. 

Heated Humidified CO2 Better in Laparoscopy: In a random assignment study of 89 women undergoing laparoscopy, heated 95% humidified CO(2) resulted in significantly less pain in the 48 hours following surgery vs. the standard of heated, dry CO(2). Subgroup analysis in patients without chronic pelvic pain revealed lower mean pain scores at 1, 2, 24, and 48 hours and decreases in postoperative and total morphine equivalents (directional P values < .05) in the study group. Humidified Compared With Dry, Heated Carbon Dioxide at Laparoscopy to Reduce Pain. Beste TM, et al. East Carolina University. Obstet Gyn 2006 Feb;107(2):263-268. v

Hyperparathyroidism Helped by Vitamin D: Vitamin D deficiency led to more severe bone disease, increased parathyroid tumor growth, and delayed postoperative recovery of parathyroid function in patients with primary hyperparathyroidism in an epidemiologic study. Correlations between Vitamin D Status and Biochemical/Clinical and Pathological Parameters in Primary Hyperparathyroidism. Ozbey N, et al. Istanbul University. World J Surg v

Lungs: Strong Relationship Vitamin D and Pulmonary Function: Using data from the Third National Health and Nutrition Examination Cross-sectional Survey of 14,091 American adults, after adjustment for age, gender, height, body mass index, ethnicity, and smoking history, the mean FEV1 was 126 mL, and the mean FVC was 172 mL greater for the highest quintile of serum 25-hydroxy vitamin D level (> 85.7 nmol/L) compared with the lowest quintile (< 40.4 nmol/L; p < 0.0001). With further adjustment for physical activity, the intake of vitamin D supplements, milk intake, and the level of serum antioxidants, the mean difference between the highest and lowest quintiles of 25-hydroxy vitamin D was 106 mL for FEV1, and 142 mL for FVC (p < 0.0001). Relationship between serum 25-hydroxyvitamin d and pulmonary function in the third national health and nutrition examination survey. Black PN, et al. University of Auckland, New Zealand. . Chest 2005 Dec;128(6):3792-8. v

Vitamin D: High Supplementation Needed After Bariatric Surgery: In a study of 116 obese women before and 5 and 10 years after biliopancreatic diversion (BPD), hypovitaminosis D was 76% in the obese status and 91% and 89% at 5 and 10 years after surgery, despite ergocalciferol supplementation. 25(OH)D concentration decreased from 39.2 in obesity (p = 0.0001) to 27.4 and 25.1 nM 5 and 10 years after BPD. Low 25-hydroxyvitamin D does not affect insulin sensitivity in obesity after bariatric surgery. Manco M, et al. Catholic University, Rome, Italy. . Obes Res 2005 Oct;13(10):1692-700. Ed: Obviously, the amount of vitamin D supplementation being used is grossly inadequate.  My recommendation is 2000 units per day, or 500% of the government's daily value.  This can be obtained from iherb.com for about 5 cents a day. v

Americans: Vitamin D Deficiency Common Nationwide Even in People on Multivitamins: Using data from the third National Health and Nutrition Examination Survey for 15,390 adults, vitamin supplements caused a higher serum level of 25 (OH) D3 (79.47 vs 74.38 nmol/L) and a lower prevalence of vitamin D deficiency (39% vs 48%). Vitamin D deficiency was higher among women, elderly, and minorities. The current dose of vitamin D in routine vitamin supplements is still insufficient. The impact of routine vitamin supplementation on serum levels of 25 (OH) D3 among the general adult population and patients with chronic kidney disease. Tareen N, et al. Charles R Drew University, Los Angeles. Ethn Dis 2005 Autumn;15(4 Suppl 5):S5-102-6. Ed: The government's guidelines of 400 units per day is clearly insufficient. A daily 1000 units with 2000 for the elderly, during the winter, and in individuals with darker skin would be better. v

Metabolic Syndrome Reduced with Higher Calcium Intake: Using data from 10,066 women over age 44 from the Women's Health Study who were free of cardiovascular disease, cancer, or diabetes and who never used postmenopausal hormones, in age- and calorie-adjusted analyses, higher intakes of total, dietary, and supplemental calcium were significantly and inversely associated with the prevalence of metabolic syndrome. After further adjusting for smoking status, exercise, alcohol intake, multivitamin use, and parental history of myocardial infarction before age 60 years, the ORs of having the metabolic syndrome for increasing quintiles of total calcium intake were 1.00 (reference), 0.82, 0.84, 0.70, and 0.64 (P for trend <0.0001). This association was not appreciably altered by additional adjustment for other dietary factors or total vitamin D intake. Neither total (P for trend = 0.13) nor supplemental (P = 0.45) vitamin D was significantly associated with metabolic syndrome. Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. Liu S, et al. Brigham and Women's-Harvard. . Diabetes Care 2005 Dec;28(12):2926-32. Ed: Vitamin D at higher doses, e.g. 1000-2000 units/day, does have a beneficial effect. For more, see Calcium.

Higher Body DHA From Fish Linked to Less Depression: In a cross-sectional study of 130 healthy adults from the island of Crete, fat tissue DHA was inversely related with depression. Multiple linear regression analysis taking into account the possible confounding effect of age, gender, body mass index, smoking and educational level confirmed this association. Higher long-term dietary intake of DHA from fish or fish oil is associated with a decreased risk for depression in adults. Depression and long chain n-3 fatty acids in adipose tissue in adults from Crete. Mamalakis G, et al. University of Crete, Iraklion, Crete, Greece. European Journal of Clinical Nutrition 8 February 2006. For more, see Omega-3 for Depression.

Two-Third Still Depressed Two Years Later: In a study of adults in a general population survey who were found to be depressed, 65% were still depressed after two years of follow-up. Negative life events had occurred more often in those who had remained depressed than in the others. High initial depression scores and a worsening of a subject's economic situation during the follow-up period were associated with failure to recover. Lack of use of health services was associated with non-recovery. Recovery from depression: a two-year follow-up study of general population subjects. Vlinamaki H, et al. University of Kuopio, Finland. . Int J Soc Psychiatry 2006 Jan;52(1):19-28. For more, see Depression.

Alzheimer's with Depression More Brain Damage: The brains of 52 deceased patients with Alzheimer's disease without a lifetime history of major depression were compared with the brains of 50 patients with AD with a lifetime history of major depression. Brains of patients with AD with a lifetime history of depression showed much higher levels of both plaque (P<.005) and tangle (P<.002) formation within the hippocampus than brains of patients with AD without a history of depression. Those with a history of depression had more rapid cognitive decline than patients without a history of depression (P<.004). Within the group of patients with AD with a history of depression, those who had depression at the time of first diagnosis of AD had more pronounced neuropathological changes in the hippocampus (P<.006). Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression. Rapp MA, et al.  Mount Sinai School of Medicine. . Arch Gen Psychiatry 2006 Feb;63(2):161-7. v

Depression Not Linked to Alzheimer's Decline: In a 12-year prospective epidemiological study of 1265 adults over age 66 without dementia at baseline, 171 developed dementia. Depressive symptoms were not associated with rate of cognitive decline over time in either group. Depressive symptoms are cross-sectionally associated with cognitive impairment but not subsequent cognitive decline. Depressive symptoms and cognitive decline in late life: a prospective epidemiological study. Ganguli M, et al. University of Pittsburgh. . Arch Gen Psychiatry 2006 Feb;63(2):153-60. For more, see Causes of Alzheimer's.

Exercise Helps Depression in Stroke Victim Study: In a 9-month study of 100 stroke victims, 7.5% of those assigned to the exercise group had significant depressive symptoms compared with 25% who received usual care (P=.07). Participants with and without baseline depressive symptoms had equivalent treatment-related gains in impairments and functional limitations, but only participants with depressive symptoms had improved quality of life. Exercise may contribute to improved quality of life in those with poststroke depressive symptoms. Therapeutic exercise and depressive symptoms after stroke. Lai SM, et al. University of Kansas. J Amer Geriatric Soc 2006 Feb;54(2):240-7. For more, see Exercise and Depression.

Bupropion Least Switching into Mania: In a 1-year study of 159 patients with bipolar I disorder or bipolar II disorder participated in a total of 228 acute (10-week) randomized trials of bupropion, sertraline, or venlafaxine as an adjunct to a mood stabilizer, full 7-day switches into hypomania and mania occurred in 11.4% and 7.9%, respectively, of the acute treatment trials and in 21.8% and 14.9%, respectively, of the continuation trials. The rate of threshold switches was higher in the 169 patients with bipolar I disorder (30.8%) than the 59 patients with bipolar II disorder (18.6%). Venlafaxine was associated with the highest relative risk of such switching and bupropion with the lowest. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Leverich GS, et al. NIMH, Bethesda, MD 20892-1272. . Am J Psychiatry 2006 Feb;163(2):232-9. Ed: Other studies have found bupropion least likely to induce switching.  Since there was no control group, it is unclear how many would have switched without any anti-depressant. v

Lamotrigine and Inositol Used for Treatment Resistant Bipolar Depression: In 66 patients with bipolar I or bipolar II disorder enrolled in the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), all were in a current major depressive episode that was nonresponsive to a combination of adequate doses of established mood stabilizers plus at least one antidepressant. Patients were randomly assigned to open-label adjunctive treatment with lamotrigine, inositol, or risperidone for up to 16 weeks. The recovery rate with lamotrigine was 24%, whereas the recovery rates with inositol and risperidone were 17% and 5%, respectively. Treatment-Resistant Bipolar Depression: A STEP-BD Equipoise Randomized Effectiveness Trial of Antidepressant Augmentation With Lamotrigine, Inositol, or Risperidone. Nierenberg AA, et al. MGH Bipolar Clinic-Harvard. . Am J Psychiatry 2006 Feb;163(2):210-6. Ed: This is a very small and poor quality study, so it proves very little. This study may have been published as a favor to the manufacturer of Lamictal, an advertising in the magazine.  For more, see Bipolar Depression.

Magnesium Supplementation Good for Heart Failure in Very Small Study: In a 3-month DB PC study of 22 chronic heart failure patients, 800 mg oral magnesium oxide (250 mg twice a day) resulted in improved small arterial compliance at 3 months. Acute and chronic oral magnesium supplementation: effects on endothelial function, exercise capacity, and quality of life in patients with symptomatic heart failure. Fuentes JC, et al. Oak Lawn, IL. Congest Heart Fail 2006 Jan-Feb;12(1):9-13. Ed: Magnesium is a supplement I recommend for everyone. For more, see Magnesium.

Menopause Earlier in Smokers and Depressed for Different Reasons: Women with depression have earlier menopause on average. In a study of women with major depression, serum FSH levels were higher in women with a history of depression, while inhibin B levels did not differ between groups. Body mass index and age were significantly and inversely related to serum inhibin B levels. Smoking history had a significant negative association with inhibin B levels. Thus, smoking has a direct negative effect on ovarian reserve, as suggested by decreased serum inhibin B levels. In contrast, effects of depression on the reproductive axis may occur at the level of the pituitary and/or hypothalamus rather than at the gonadal level, as suggested by increased serum FSH levels. The influence of depression, body mass index and smoking on serum inhibin B levels in late reproductive aged women. Lambert-Messerlian GM, et al. Brown Medical School, Providence, RI. J Clin endocrin Metab 2006 Jan 31. For more, see Harm of Depression.

Sleep Apnea: CPAP Little Value in Mild to Moderate Sleep Apnea: Obstructive Sleep Apnoea Syndrome (OSAS) affects 2-4% of the middle-aged population. Meta-analyses of randomised controlled trials show that the severe presentation of the syndrome (Apnoea Hypopnoea Index >30/hr) is effectively treated with Continuous Positive Airway Pressure (CPAP). However, this review of the treatment of mild-moderate OSAS (AHI 5-30/hr) found that CPAP significantly reduced subjective daytime sleepiness (Epworth Sleepiness Scale) by only 1.2 points (p=0.001), improved objective daytime wakefulness (Maintenance of Wakefulness Test) by 2.1 mins (p=0.011), and did not affect objective daytime sleepiness (Multiple Sleep Latency Test, mean benefit -0.2 mins, p=0.6). The two significant effects were small (Effect size <0.30). The effects on sleepiness are of limited clinical significance. Continuous positive airway pressure reduces daytime sleepiness in mild-moderate obstructive sleep apnoea: meta-analysis. Marshall NS, et al. Massey University, New Zealand. Thorax 2006 Feb 7. v

Mirtazapine as Good as Propranolol: Mirtazapine 15 jmg/d, an anti-depressant with marked 5-HT(2A) antagonism, did slightly better than propranolol 80 mg/d in a 7-day DB PC study of 90 antipsychotic-treated patients with akathesia. Both reduced AIA severity (-34% mirtazapine and -29% propranolol vs. placebo -11%; p = .012 and p = .023). Five (16.7%) of 30 propranolol patients and none of mirtazapine discontinued due to hypotension or bradycardia. However, 7 mirtazepine vs 8 propranolol discontinued in all. Low-Dose Mirtazapine: A New Option in the Treatment of Antipsychotic-Induced Akathisia. A Randomized, Double-Blind, Placebo- and Propranolol-Controlled Trial. Poyurovsky M et al. Biol Psychiatry 2006 Feb 20. For more, see Akathesia.

Nasal Dilator Strip Might Help: In a 4-week randomized study of 80 nonobese, adults with a primary chronic sleep-maintenance insomnia and mild to moderate sleep disordered breathing (SDB), the treatment group had (p=.0001) large improvements in insomnia and sleep quality, as well as some improvement in life satisfaction. Nasal dilator strip therapy for chronic sleep-maintenance insomnia and symptoms of sleep-disordered breathing: a randomized controlled trial. Krakow B, et al. Albuquerque, NM. Sleep Breath 2006 Feb 23. Strips cost $8-10 for one that lasts a month. For more, see Insomnia. 

Selenium No Benefit for the Heart: In a 7.6 year follow-up DB PC study of 1004 adults without heart disease at the start, selenium 200 mcg/d had no beneficial effect on heart disease: all cardiovascular disease: hazard ratio (HR) = 1.03; myocardial infarction: HR = 0.94; stroke: HR = 1.02; all cardiovascular disease mortality: HR = 1.22. Effects of Selenium Supplementation on Cardiovascular Disease Incidence and Mortality: Secondary Analyses in a Randomized Clinical Trial. Stranges S, et al. State University of New York at Buffalo. Am J Epidem 2006 Feb 22. Ed: This is a very good study. However, the benefit of selenium has always been considered against cancer, not heart disease.  I will be looking for that report of this study. For more, see Selenium.

Denosumab: Expensive Antibody Coming for Osteoporosis: Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. Monoclonal antibody denosumab binds RANKL and inhibits its action. In an industry-financed, random-assignment, open 12-month study of 412 postmenopausal women with low bone mineral density, patients received denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. Denosumab resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent vs. 4.6 percent with alendronate vs. -0.8 percent with placebo with similar changes elsewhere. Denosumab increased bone mineral density and decreased bone resorption. Denosumab in postmenopausal women with low bone mineral density. McClung MR, et al. Portland, Oreg. . N Eng J Med 2006 Feb 23;354(8):821-31. Ed: This is a new, unnecessary and expensive drug for osteoporosis.  The vast majority of osteoporosis cases can be treated very effectively for $3 per month with vitamin K and vitamin D, which also have many other valuable benefits. For more, see Osteoporosis.

Falls: Vitamin D Supplements and Calcium Reduce Risk in Women 46%, But Not in Men: In a DB PC 3-year supplementation with cholecalciferol-calcium of 199 men and 246 women age 65 or older and living at home, 55% of women and 45% of men reported at least 1 fall. Cholecalciferol 700 IU-calcium 500 mg/daily significantly reduced the risk of falling in women by 46%, but not in men (7%). Fall reduction was most pronounced in less active women (65%). Baseline 25-hydroxyvitamin D level did not modulate the treatment effect. Supplementation had a neutral effect in men independent of their physical activity level. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial. Bischoff-Ferrari HA, et al. University Hospital Zurich, Switzerland. . Arch Int Med 2006 Feb 27;166(4):424-30. 

Diabetes: Vitamin D and Calcium Lower the Risk: In the Nurses' Health Study of 83,779 women who had no history of diabetes, cardiovascular disease, or cancer at baseline for the development of type 2 diabetes, during 20 years of follow-up, there were 4,843 new cases of type 2 diabetes. The relative risk (RR) of type 2 diabetes was 0.87 (p = 0.04) comparing the highest with the lowest category of vitamin D intake from supplements. The multivariate RRs of type 2 diabetes were 0.79 (p <0.001) comparing the highest with the lowest category of calcium intake from all sources and 0.82 (p <0.001) comparing the highest with the lowest category of calcium intake from supplements. A combined daily intake of >1,200 mg calcium and >800 IU vitamin D was associated with a 33% lower risk of type 2 diabetes with RR of 0.67 compared with an intake of <600 mg and 400 IU calcium and vitamin D. Vitamin d and calcium intake in relation to type 2 diabetes in women. Pittas AG, et al. Tufts-New England Medical Center. . Diab Care 2006 Mar;29(3):650-6. For more, see the amazing Vitamin D. 

New England Journal of Medicine Makes Glucosamine/Chondroitin Look Bad for Arthritis: In a 24-week DB PC Veterans Administration study, 1229 mild and 354 moderate-severe osteoarthritis knee patients took 1500 mg of glucosamine, 1200 mg of chondroitin sulfate, both glucosamine and chondroitin sulfate, 200 mg of celecoxib (Celebrex), or placebo each day. Overall, it was reported that glucosamine and chondroitin sulfate did no better than placebo in reducing knee pain by 20 percent. The placebo response was a surprisingly high 60% and the data for mild arthritis was bizarre in that glucosamine (64%) and chondroitin (66%) did better than the combination (62%) vs. just 70% for celecoxib. However, for patients with moderate-to-severe pain, glucosamine with chondroitin did very well (79% vs. 54%, P=0.002) and clearly better than the dangerous arthritis drug celecoxib (69%). Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. Clegg DO, et al. University of Utah School of Medicine. . New Eng J Med 2006 Feb 23;354(8):795-808. Ed: As expected, the study led the news media to trash glucosamine-chondroitin while failing to point out that the combination did very well with those with moderate-to- serious pain, i.e., the most important patients.  They also failed to mentioned that Celebrex did worse in this important category.  Despite the study being totally funded by the public, it was published in the expensive NEJM which is a cash cow for the Massachusetts Medical Society.  Citizens and doctors without a subscription could not see the actual study.  Celebrex costs $128/mo vs. $12/mo for glucosamine/chondroitin.  According to this study, it would be necessary to treated 30 mild patients with Celebrex to help one more patient with mild pain than chondroitin at a cost of $40,000/year.  Celebrex more than in the death rate due to heart disease (129% increase) and causes many stomach bleeds, an additional cause of death vs. no side-effects for glucosamine/chondroitin.  In addition to this, glucosamine/chondroitin has repeatedly been shown in 1 to 4 year studies to slow joint space deterioration while Celebrex does not. The New England Journal of Medicine receives very large amounts of advertising income from pharmaceutical companies.  Researchers being paid by public monies should be required to publish their full reports on free, internet medical journals, not profit-oriented, industry-subsidized magazines like NEJM. A highly controversial meta-analysis by Lee Simon of Harvard, coincidentally funded by Celebrex manafacturer Pfizer, claims that Celebrex is harmless for the heart (Arthritis News 23 November 2005).  Meanwhile, an independent analysis found a 129% increase in heart attacks and death.

Comfrey Cream Helped Muscular Back Pain: In a randomized study of topical Symphytum product Traumaplant(R) (Harras Pharma Curarina, Munchen, Germany) (10% active ingredient of a 2.5:1 aqueous-ethanolic pressed concentrate of freshly harvested, cultivated comfrey herb [Symphytum uplandicum Nyman], corresponding to 25 g of fresh herb per 100 g of cream) of 215 patients with myalgia were tested against a 1% product. With high concentration, back pain on active motion improved (P<.001) and pain on palpation. The number needed to treat was 3.2. Topical symphytum herb concentrate cream against myalgia: a randomized controlled double-blind clinical study. Kucera M, et al. Adv Ther 2005 Nov-Dec;22(6):681-92. v. Ed: Comfrey tea or any oral preparation may cause liver failure.

OBJECTIVE: To investigate the efficacy of the fixed combination of black cohosh (Cimicifuga racemosa) and St. John's wort (Hypericum perforatum) extracts in women with climacteric complaints with a pronounced psychological component. METHODS: In this double-blind randomized placebo-control study, 301 women experiencing climacteric complaints with psychological symptoms were treated with ethanolic St. John's wort extract and isopropanolic black cohosh extract or a matched placebo for 16 weeks. Climacteric complaints were evaluated by means of the Menopause Rating Scale mean score, and psychological complaints were evaluated using the Hamilton Depression Rating Scale sum score. RESULTS: The mean (+/- standard deviation) Menopause Rating Scale score decreased 50% (0.46 +/- 0.13 to 0.23 +/- 0.13) in the treatment group and 19.6% (0.46 +/- 0.14 to 0.37 +/- 0.15) in the placebo group. The Hamilton Depression Rating Scale total score decreased 41.8% in the treatment group (18.9 +/- 2.2 to 11.0 +/- 3.8 points), and 12.7% in the placebo group (18.9 +/- 2.1 to 16.5 +/- 4.3). The treatment was significantly (P < .001) superior to placebo in both measures. There were no relevant group differences regarding adverse events, laboratory values, or tolerability. Black Cohosh and St. John's Wort for Climacteric Complaints: A Randomized Trial. Uebelhack R, et al. Humboldt-University, Berlin, Germany. Obstet Gynecol 2006 Feb;107(2):247-55.

OBJECTIVES: To examine whether regular exercise is associated with anxiety, depression and personality in a large population-based sample as a function of gender and age. METHODS: The sample consisted of adolescent and adult twins and their families (N = 19,288) who participated in the study on lifestyle and health from The Netherlands Twin Registry (1991-2002). Exercise participation, anxiety, depression and personality were assessed with self-report questionnaires. RESULTS: The overall prevalence of exercise participation (with a minimum of 60 min weekly at 4 METs (Metabolic Energy Expenditure Index)) in our sample was 51.4%. Exercise participation strongly declined with age from about 70% in young adolescents to 30% in older adults. Among adolescents, males exercised more, whereas, among older adults, females exercised more. Exercisers were on average less anxious (-0.18 SD), depressed (-0.29 SD) and neurotic (-0.14 SD), more extraverted (+0.32 SD) and were higher in dimensions of sensation seeking (from +0.25 SD to +0.47 SD) than non-exercisers. These differences were modest in size, but very consistent across gender and age. CONCLUSIONS: This study corroborates and extends previous findings: regular exercise is cross-sectionally associated with lower neuroticism, anxiety and depression and higher extraversion and sensation seeking in the population. Regular exercise, anxiety, depression and personality: A population-based study. De Moor MH, et al. Vrije Universiteit, Amsterdam, The Netherlands. Prev Med 2006 Jan 23.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is associated with substantial infant mortality and morbidity. A previous cohort study suggested a possible association between maternal use of the selective serotonin-reuptake inhibitor (SSRI) fluoxetine late in the third trimester of pregnancy and the risk of PPHN in the infant. We performed a case-control study to assess whether PPHN is associated with exposure to SSRIs during late pregnancy. METHODS: Between 1998 and 2003, we enrolled 377 women whose infants had PPHN and 836 matched control women and their infants. Maternal interviews were conducted by nurses, who were blinded to the study hypothesis, regarding medication use in pregnancy and potential confounders, including demographic variables and health history. RESULTS: Fourteen infants with PPHN had been exposed to an SSRI after the completion of the 20th week of gestation, as compared with six control infants (adjusted odds ratio, 6.1; 95 percent confidence interval, 2.2 to 16.8). In contrast, neither the use of SSRIs before the 20th week of gestation nor the use of non-SSRI antidepressant drugs at any time during pregnancy was associated with an increased risk of PPHN. CONCLUSIONS: These data support an association between the maternal use of SSRIs in late pregnancy and PPHN in the offspring; further study of this association is warranted. These findings should be taken into account in decisions as to whether to continue the use of SSRIs during pregnancy. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. Chambers CD, et al. University of California, San Diego. . New Eng J Med 2006 Feb 9;354(6):579-587.

Ritalin Associated Heart Deaths: In the U.S. since 1999, 51 children and adults with ADHD have died while on methylphenidate.  Another 9 have died in the United Kingdom.  The FDA is finally requiring a black box warning.  Adderall was briefly banned in Canada in 2005 for the same reason.  http://www.guardian.co.uk/frontpage/story/0,,1707535,00.html 

Coffee May Lower Risk of Type-2 Diabetes: In a study of more than 88,000 women, higher coffee consumption, both with and without caffeine, was found to be associated with a lower risk of type-2 diabetes. The reduction in risk was 13% with one cup of coffee per day, and as much as 47% with four or more cups. The reduced risk of type-2 diabetes was limited to filtered coffee and instant coffee whereas consumption of espresso or percolator coffee did not significantly reduce the risk. Harvard. Diabetes Care Feb. 2006.

BACKGROUND: Elevated blood pressure (BP) is a risk factor for cardiovascular disease (CVD), but it remains unclear which component-alone or in combination-is the best predictor. We sought to determine which BP parameters are important predictors of CVD death across a wide age range. METHODS: We used a prospective cohort study design with 53,163 men followed for cause-specific death during a median of 5.7 years in the Physicians' Health Study enrollment cohort. Baseline age, systolic BP and diastolic BP were collected. We calculated relative risks (RRs) and their 95% confidence intervals using Cox proportional hazard models adjusting for major risk factors for CVD, and then stratified by age (39 to 49, 50 to 59, 60 to 69, and 70 to 84 years). RESULTS: There were 459 CVD deaths during follow-up. For each 10 mm Hg increase in systolic BP, the multivariable RRs by ascending age group were 1.46, 1.43, 1.24, and 1.13. The multivariable RRs for each 10 mm Hg increase in diastolic BP were 1.25, 1.20, 1.28, and 1.07. Compared with systolic BP, pulse pressure and mean arterial pressure were not consistent predictors across age ranges, and combining systolic BP with another parameter did not improve the model compared with using systolic BP alone in any age group (all P > .05). CONCLUSIONS: In this large cohort of healthy men with no history of hypertension, systolic BP was the most consistent and significant predictor of CVD death across all ages. Diastolic BP was not as strongly associated with risk. Our results support the continuing emphasis on using systolic BP in predicting cardiovascular risk. Effect of age on blood pressure parameters and risk of cardiovascular death in men. Bowman TS, et al. Massachusetts Veterans Affairs Epidemiology. . Am J Hypertension 2006 Jan;19(1):47-52.

OBJECTIVES: We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease (CAD). BACKGROUND: Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood. The INternational VErapamil-trandolapril STudy (INVEST) compared outcomes in hypertensive patients with CAD that were assigned randomly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure (BP) control. Trandolapril and hydrochlorothiazide were used as added agents. During follow-up (61,835 patient-years), BP control and the primary outcome (death, nonfatal myocardial infarction, and nonfatal stroke) were not different between strategies. METHODS: We investigated risk for adverse outcome associated with baseline factors, follow-up BP, and drug treatments using Cox modeling. RESULTS: Previous heart failure (adjusted hazard ratio [HR] 1.96), as well as diabetes (HR 1.77), increased age (HR 1.63), U.S. residency (HR 1.61), renal impairment (HR 1.50), stroke/transient ischemic attack (HR 1.43), smoking (HR 1.41), myocardial infarction (HR 1.34), peripheral vascular disease (HR 1.27), and revascularization (HR 1.15) predicted increased risk. Follow-up systolic BP <140 mm Hg or diastolic BP <90 mm Hg (HRs 0.82 or 0.70, respectively) and trandolapril with verapamil SR (HRs 0.78 and 0.79) were associated with reduced risk. CONCLUSIONS: In hypertensive patients with CAD, increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function. Lower follow-up BP and addition of trandolapril to verapamil SR each were associated with reduced risk. Predictors of adverse outcome among patients with hypertension and coronary artery disease. Pepine CJ, et al. University of Florida, Gainesville. . J Am Coll Cardio 2006 Feb 7;47(3):547-51.

OBJECTIVE: Unexplained hepatic iron overload with increased serum ferritin (SF) values has been associated with the insulin resistance syndrome (IRS), defined by the presence of one or more of the following criteria: increased body mass index (BMI), diabetes, hyperlipidemia or hypertension. However, as yet the association between IRS and SF in a representative population has not been investigated. METHODS: The study subjects participated in a nationwide epidemiological survey on metabolic disorders in the adult German population. The 1200 probands included in this study are representative of the German population. To eliminate major causes of secondary iron overload, 114 (9.5%) subjects with excessive alcohol consumption and 16 (1.5%) subjects with serological evidence for hepatitis B or C were excluded. For all remaining 1070 probands, complete clinical data of SF, HbA1c, known diabetes, BMI, cholesterol, high-density lipoprotein-cholesterol and blood pressure were available. RESULTS: SF values were significantly increased in men and women with high BMI (> 25 kg/m(2)), increased cholesterol (> 200 mg/dl), and increased systolic (> 160 mmHg) blood pressure, in women with diabetes, and in men with increased diastolic (> 95 mmHg) blood pressure. Furthermore, there was a significant correlation between the number of IRS criteria and SF. CONCLUSIONS: This study shows a significant correlation between SF and the presence of IRS criteria in a large representative population. Interestingly, the severity of the IRS seems to be associated with increased SF levels suggesting a causal connection. Further studies are required to investigate the pathophysiological mechanism and consequences of increased SF levels in patients with IRS. Association between serum ferritin and the insulin resistance syndrome in a representative population. Wrede CE, et al. University of Regensburg, Germany. Eur J Endocrin 2006 Feb;154(2):333-40.

Pulse pressure has been more strongly associated with cardiovascular outcomes, especially myocardial infarction and heart failure, than has systolic, diastolic, or mean arterial pressure in a variety of populations. Little is known, however, of the comparative effects of various classes of antihypertensive agents on pulse pressure. In retrospective analyses of the Veterans Affairs Single-Drug Therapy for Hypertension Study, we compared changes in pulse pressure with 6 classes of antihypertensive agents: 1292 men with diastolic blood pressure of 95 to 109 mm Hg on placebo were randomized to receive hydrochlorothiazide (12.5-50), atenolol (25-100 mg), captopril, clonidine (0.1-0.3 bid), diltiazem, prazosin (2-10 mg bid), or placebo. Drug doses were titrated to achieve a goal diastolic blood pressure of <90 mm Hg during a 4- to 8-week medication titration phase. Pulse pressure change (placebo subtracted) was assessed from baseline to the end of the 3-month titration and 1-year maintenance. Mean baseline systolic, diastolic, and pulse pressures were 152, 99, and 53 mm Hg, respectively. Reductions in pulse pressure during titration were greater (P<0.001) with clonidine (6.7 mm Hg) and hydrochlorothiazide (6.2 mm Hg) than with captopril (2.5 mm Hg), diltiazem (1.6 mm Hg), and atenolol (1.4 mm Hg); reduction with prazosin (3.9 mm Hg) was similar to all but clonidine. After 1 year, pulse pressure was reduced significantly more (P<0.001) with hydrochlorothiazide (8.6 mm Hg) than with captopril and atenolol (4.1 mm Hg with both); clonidine (6.3 mm Hg), diltiazem (5.5 mm Hg), and prazosin (5.0 mm Hg) were intermediate. These data show that classes of antihypertensive agents differ in their ability to reduce pulse pressure. Whether these differences affect rates of cardiovascular events remains to be determined. Pulse pressure changes with six classes of antihypertensive agents in a randomized, controlled trial. Cushman WC, et al. Memphis, Tennessee. . Hypertension 2001 Oct;38(4):953-7.

Twin studies provide estimates of genetic and environmental contributions to cognitive ability differences, but could be based on biased samples. Here we report whole-population estimates using twins from unique mental surveys in Scotland. The Scottish Mental Surveys of 1st June 1932 (SMS1932) and 4th June 1947 (SMS1947), respectively, administered the same validated verbal reasoning test to almost everyone born in 1921 or 1936 and attending school in Scotland. There were 572 twin pairs from the SMS1932, and 517 pairs from the SMS1947. Information on zygosity was unavailable. A novel application of a mixture distribution was used to estimate genetic and environmental components of verbal reasoning variation by maximum likelihood. We found consistent heritability (approximately 0.70) and shared environment (approximately 0.21) estimates. The estimates did not change substantially when additional quantitative traits (height and weight) were added in a multivariate analysis. More generally for studies in genetics, the methodological innovation developed here implies that large (national) data collections can provide sufficient information on twin pairs to estimate genetic parameters, even without zygosity. Large, consistent estimates of the heritability of cognitive ability in two entire populations of 11-year-old twins from Scottish mental surveys of 1932 and 1947. Benyamin B, et al. University of Edinburgh, UK. Behav Genetics 2005 Sep;35(5):525-34.

There is an intense search for longevity genes in both animal models and humans. Human family studies have indicated that a modest amount of the overall variation in adult lifespan (approximately 20-30%) is accounted for by genetic factors. But it is not known if genetic factors become increasingly important for survival at the oldest ages. We study the genetic influence on human lifespan and how it varies with age using the almost extinct cohorts of Danish, Finnish and Swedish twins born between 1870 and 1910 comprising 20,502 individuals followed until 2003-2004. We first estimate mean lifespan of twins by lifespan of co-twin and then turn to the relative recurrence risk of surviving to a given age. Mean lifespan for male monozygotic (MZ) twins increases 0.39 [95% CI (0.28, 0.50)] years for every year his co-twin survives past age 60 years. This rate is significantly greater than the rate of 0.21 (0.11, 0.30) for dizygotic (DZ) males. Females and males have similar rates and these are negligible before age 60 for both MZ and DZ pairs. We moreover find that having a co-twin surviving to old ages substantially and significantly increases the chance of reaching the same old age and this chance is higher for MZ than for DZ twins. The relative recurrence risk of reaching age 92 is 4.8 (2.2, 7.5) for MZ males, which is significantly greater than the 1.8 (0.10, 3.4) for DZ males. The patterns for females and males are very similar, but with a shift of the female pattern with age that corresponds to the better female survival. Similar results arise when considering only those Nordic twins that survived past 75 years of age. The present large population based study shows genetic influence on human lifespan. While the estimated overall strength of genetic influence is compatible with previous studies, we find that genetic influences on lifespan are minimal prior to age 60 but increase thereafter. These findings provide a support for the search for genes affecting longevity in humans, especially at advanced ages. Genetic influence on human lifespan and longevity. Hjelmborg JV, et al. University of Southern Denmark, Odense C, Denmark, . Hum Genetics 2006 Feb 4;:1-10.

Resveratrol, a natural phytoalexin found in grapes and red wine , increases longevity in the short-lived invertebrates Caenorhabditis elegans and Drosophila and exerts a variety of biological effects in vertebrates, including protection from ischemia and neurotoxicity . Its effects on vertebrate lifespan were not yet known. The relatively long lifespan of mice, which live at least 2.5 years , is a hurdle for life-long pharmacological trials. Here, the authors used the short-lived seasonal fish Nothobranchius furzeri with a maximum recorded lifespan of 13 weeks in captivity . Short lifespan in this species is not the result of spontaneous or targeted genetic mutations , but a natural trait correlated with the necessity to breed in an ephemeral habitat and tied with accelerated development and expression of ageing biomarkers at a cellular level . Resveratrol was added to the food starting in early adulthood and caused a dose-dependent increase of median and maximum lifespan. In addition, resveratrol delays the age-dependent decay of locomotor activity and cognitive performances and reduces the expression of neurofibrillary degeneration in the brain. These results demonstrate that food supplementation with resveratrol prolongs lifespan and retards the expression of age-dependent traits in a short-lived vertebrate. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Valenzano DR, et al. Pisa, Italy. Curr Biol 2006 Feb 7;16(3):296-300.

Summary The beneficial effects of polyphenol compounds in fruits and vegetables are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary polyphenols are beneficial in whole animals, particularly with respect to aging. To address this question, we examined the effects of blueberry polyphenols on lifespan and aging of the nematode, Caenorhabditis elegans, a useful organism for such a study. We report that a complex mixture of blueberry polyphenols increased lifespan and slowed aging-related declines in C. elegans. We also found that these benefits did not just reflect antioxidant activity in these compounds. For instance, blueberry treatment increased survival during acute heat stress, but was not protective against acute oxidative stress. The blueberry extract consists of three major fractions that all contain antioxidant activity. However, only one fraction, enriched in proanthocyanidin compounds, increased C. elegans lifespan and thermotolerance. To further determine how polyphenols prolonged C. elegans lifespan, we analyzed the genetic requirements for these effects. Prolonged lifespan from this treatment required the presence of a CaMKII pathway that mediates osmotic stress resistance, though not other pathways that affect stress resistance and longevity. In conclusion, polyphenolic compounds in blueberries had robust and reproducible benefits during aging that were separable from antioxidant effects. Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Wilson MA, et al. National Institute on Aging, Baltimore. Aging Cell 2006 Feb;5(1):59-68.

Thomas E. Radecki, M.D., J.D.

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