ORLANDO, May 22 — The next generation of therapy for erectile dysfunction could include semiannual intracavernosal injections of a gene that improves smooth muscle function, preliminary clinical results suggest.

A single injection of hMaxi-K led to restoration of normal erectile function that lasted for six months in two men treated with the highest dose, Arnold Melman, M.D., of Albert Einstein College of Medicine in New York, reported here at the American Urological Association meeting.

“The results were exactly as we had predicted from our animal studies,” said Dr. Melman. “If these findings hold up in further clinical investigations, we think men will require two injections a year to maintain normal sexual function.”

Two-year follow-up of the first 11 men treated has raised no safety concerns related to the gene transfer therapy, he added, although one patient was lost to follow-up.

The therapy evolved from recognition that abnormal smooth muscle function plays a major role in erectile dysfunction.

Dr. Melman said hMaxi-K consists of a naked DNA plasmid vector carrying human cDNA encoding a subunit of the smooth muscle potassium ion channel. The therapy stimulates endogenous protein production to correct abnormalities in smooth muscle function.

“We’ve shown in other studies that there is either a reduction in the amount of potassium channel present on the cell membrane or splice variants that don’t work as effectively that are present in both aging and disease,” said Dr. Melman.

An initial phase I dose-escalation study of hMaxi-K involved 11 men with moderate to severe erectile dysfunction. The patients had shown no improvement with other therapies or had rejected other types of therapy.

Three men each received doses of 500, 1,000, and 5,000 ?µg of hMaxi-K, and two men received 7,500 ?µg, injected directly into the corpus cavernosum.

Pre- and posttreatment scores on the International Index of Erectile Function showed that the two men who received the highest dose of hMaxi-K had a return of normal erectile function for six months. At that point, erectile function regressed to pretreatment levels.

A companion study reported at the AUA meeting showed the gene therapy affects sexual behavior, as well as erectile function.

Male cynomolgus monkeys with atherosclerosis-related erectile dysfunction received the gene transfer therapy and then were placed with estrogen-implanted female monkeys.

Following treatment virtually every aspect of the male monkeys’ sexual function and behavior improved, said George Christ, Ph.D., of Wake Forest University in Winston-Salem, N.C., a co-developer of hMaxi-K.

The treatment influenced behaviors unrelated to erectile function, such as time spent grooming the female and decreased frequency of body contact, typical of the postmating period of most macaque species.

“The therapy seemed to improve the males’ overall sense of well being,” said Dr. Christ. “They felt better about themselves.”

A phase1b clinical evaluation of three higher doses of hMaxi-K is expected to end by early June.

The potassium ion channel gene therapy has potential application in a variety of conditions involving smooth muscle dysfunction, said Dr. Melman. An initial clinical trial of patients with overactive bladder has already begun.

Drs. Melman and Christ are founders and remain principals in Ion Channel Innovations, the company that is developing the gene-transfer therapy.

Primary source: Journal of Urology

Source reference:
Melman A, et al “Long-term safety follow-up of a phase 1 trial for gene transfer therapy of ED with hMaxi-K” J Urol 2008; 179(suppl): 426; Abstract 1241.

BOSTON, Nov. 8 – About half of all children who turn up in the doctor’s office with a sore throat are given antibiotics for it, although at least two-thirds of those cases are likely caused by viral rather than bacterial infections, researchers here reported.

Only about half of physicians do a throat culture before children are given antibiotics for a sore throat, despite strong recommendations that they be tested for group A ??-hemolytic streptococci, reported Jeffrey A. Linder, M.D., M.P.H., of Harvard Medical School and colleagues.

The American Academy of Pediatrics, CDC, and Infectious Disease Society of America all recommend testing for group A ??-hemolytic streptococci.

Drawing on data from national ambulatory care surveys conducted from 1995 to 2003, Dr. Linder and colleagues found that in an estimated 7.3 million annual visits for sore throat, doctors prescribed antibiotics about 53% of the time (95% confidence interval [CI], 49%-56%), the investigators reported in the Nov. 9 issue of Journal of the American Medical Association. This rate is considerably in excess of the expected 15% to 36% prevalence of strep throat.

In addition, about half the kids who got antibiotics got the wrong or non-recommended one. Non-recommended antibiotics were prescribed to 27% (95% CI, 24%-31%) of children who received an antibiotic. Recommended agents include amoxicillin, penicillin, first-generation cephalosporins, and erythromycin.

Antibiotics not recommended but still prescribed in a significant number of cases included other cephalosporins, extended spectrum macrolides (e.g., Zithromax (azithromycin), Biaxin (clarithromycin), Augmentin (amoxicillin-clavulanate), or other agents.

“Encouragingly, we found a significant decrease in the proportion of patients receiving antibiotics over the study period,” Dr. Linder and colleagues wrote. “However, even at the end of the study period, the proportion of children prescribed an antibiotic still exceeded the maximum expected prevalence of group A ??-hemolytic streptococci among children with sore throat.”

Moreover, they found that the decrease in prescriptions was actually due to a drop in the use of drugs recommended for group A ??-hemolytic streptococci (49% to 38%; P=.002), whereas the proportion of children who received non-recommended antibiotics remained the same.

Physicians performed a group A ??-hemolytic streptococci test in 53% (95% CI, 48%-57%) of visits and in 51% (95% CI, 45%-57%) of visits at which an antibiotic was prescribed. group A ??-hemolytic streptococci testing was not associated with a lower antibiotic prescribing rate overall (48% tested vs 51% not tested; P=.40), but testing was associated with a lower antibiotic prescribing rate for children with a diagnosis of pharyngitis, tonsillitis, and streptococcal sore throat (57% tested vs 73% not tested; P

WASHINGTON — The Centers for Medicare and Medicaid Services (CMS) has proposed paying for “high intensity” obesity counseling for seniors to help turn the tide on the obesity epidemic in the U.S.

According to a proposed decision memo posted on the CMS website Wednesday, the agency is proposing to pay for obese Medicare beneficiaries to undergo behavior modification and weight-loss counseling by a primary care practitioner.

The counseling would involve one office visit every week for a month; one office visit every other week for months two to six; and one office visit for every remaining month through one year.

At the six-month visit, the doctor or other healthcare provider would determine how much weight the patient had lost so far. To be eligible for the next six months of treatment, the patient must have lost at least 6.6 lbs.

The counseling would have to take place in a primary care setting, such as a family physician’s office, in order to be eligible for reimbursement from Medicare. Hospitals, surgery centers, diagnostic testing facilities, skilled nursing facilities, inpatient rehabilitation facilities, and hospices wouldn’t qualify for reimbursement.

CMS is authorized to add new preventive services to the list of what Medicare Parts A and B it will pay for if the service is determined to be reasonable and necessary for the prevention or early detection of illness or disability, and is recommended by the United States Preventive Services Task Force (USPSTF).

Since 2003, the USPSTF has recommended screening for obesity in all adults and then offering intensive counseling and behavioral interventions to promote sustained weight loss.

The USPSTF has concluded that there’s “fair to good evidence” that “high-intensity counseling” on diet and/or exercise, coupled with behavioral interventions aimed at skill development, motivation, and support strategies, lead to sustained weight loss of between 6.6 lbs and 11 lbs among people who are obese.

Obesity is defined by having a body mass index of more than 30. For instance, a person who is 5’8″ and weighs 200 lbs would have a BMI of just over 30. The USPSTF has found that obesity is a risk factor for major causes of death, including cardiovascular disease, a variety of cancers, and diabetes, and is also linked to diminished life expectancy.

One way to reduce BMI and those other related conditions is “high-intensity” weight loss interventions, defined as those that occur at least twice per month, CMS said.

The agency analyzed a number of studies to make its proposal, including a 2009 literature review of randomized, controlled studies on behavioral interventions for weight loss that found eleven of 39 interventions produced significant improvement in weight after two years or longer, compared to groups who didn’t have any intervention. That study concluded that diet with exercise and/or behavior therapy also reduced hypertension and lowered a person’s risk of metabolic syndrome and diabetes.

CMS also relied on the results of a 2006 review that concluded healthy older adults who are at increased risk for cardiovascular disorders or arthritis-related functional impairment are likely to benefit from being diagnosed as obese and starting intensive lifestyle interventions, including diet and exercise and “behavioral components.”

“We conclude that the evidence is sufficient to determine that screening for obesity in adults, along with high-intensity behavioral interventions, is reasonable and necessary for the prevention or early detection of illness or disability,” CMS said.

One such behavioral intervention called the “five A’s approach” is adapted from smoking cessation programs. Assess the patient’s risk for obesity Ask if the patient is ready to try losing weight Advise in developing a dietary program Assist in establishing the intervention Arrange for appropriate follow-up

CMS first proposed expanding coverage for obesity prevention services in March, and received 27 comments on the issue. With the exception of several, most commenters were supportive of CMS paying for behavioral weight loss therapy.

CMS has no plans to hold a Medicare Coverage Advisory Committee meeting on this topic, which the agency often does to hear the evidence paying for a new drug or device. It is accepting additional public comments and will eventually issue a final coverage decision.

CHICAGO, May 4 — Two-thirds of small renal tumors remained stable for three years after treatment with extracorporeal, high-intensity focused ultrasound (HIFU), according to data from a small British study.

Seven of 15 evaluable patients had radiologic evidence of tumor ablation, said Tom Leslie, M.D., of Churchill Hospital in Oxford, England. Tumors in three others did not grow, despite a lack of objective evidence of ablation.

“We probably won’t know for sure what is going on in these patients until we perform another biopsy, which probably won’t occur until they have been followed for five years,” Dr. Leslie told colleagues at a meeting of the American Urological Association here.

There is no consensus about management of small renal tumors. Partial nephrectomy can cure the disease with minimal impact on renal function, but complications occur in up to a fourth of patients, said Dr. Leslie.

Active surveillance may be appropriate for some patients, but biopsy studies have revealed high-grade tumors in as many as 25% of patients.

Ablative therapies have demonstrated the potential of less invasive treatment, and both radiofrequency ablation and cryoablation have achieved medium-term disease control, Dr. Leslie continued.

Though still experimental, HIFU would offer a truly noninvasive therapy for small renal tumors, but the small clinical series reported to date had not clearly demonstrated the procedure’s effectiveness.

Adding to the modest database for HIFU, Dr. Leslie reported long-term follow-up in 15 patients treated at his center. In the first six months, one patient required surgery for invasive renal cell cancer. Four others subsequently required additional treatment: surgery in three cases and radiofrequency ablation in one.

Adverse effects consisted of mild or moderate discomfort in 13 patients, mild skin toxicity in five, and mild or moderate edema in six.

In seven patients, tumors exhibited loss of central enhancement on imaging, which Dr. Leslie and colleagues interpreted as evidence of ablation. HIFU ablated an average of 88% of the target area in the seven patients, and the amount of ablation ranged from 21% to 160%.

Comparison of patients who had successful versus unsuccessful treatment showed no substantive differences in tumor size or location or body mass index.

Ten patients remain under surveillance with little or no growth of their tumors. However, all 10 have a rim of peripheral enhancement, which could indicate residual tumor.

The investigators have found no explanations for the three patients who have had stable disease but no radiologic evidence of ablation.

Dr. Leslie reported no competing interests.

Primary source: American Urological Association

Source reference:
Ritchie RW, et al “High intensity focused ultrasound ablation of small renal tumors with an extracorporeal device: 3 year outcome data” AUA 2009; Abstract 1311.

RIDGEWOOD, N.J., April 30 — Treatment with erythropoiesis-stimulating agents (ESAs) in patients with cancer was associated with worse mortality during active treatment and with poorer overall survival, a large meta-analysis revealed.

ESA-treated patients had an estimated 17% increased mortality (combined HR 1.17 95% CI 1.06 to 1.30, P=0.003) as well as worsened overall survival (combined HR 1.06; 95% CI 1.00 to 1.12, P=0.046), Julia Bohlius, M.D., M.Sc.P.H., of the University of Bern in Switzerland, and colleagues reported in the May 2 issue of The Lancet.

These agents, including epoetin alfa (Epogen, Procrit), epoetin beta (NeoRecormon), and darbepoetin alfa (Aranesp) are used to treat anemia in patients with cancer.

The drugs increase hemoglobin concentrations, reduce the need for red blood cell transfusions, and can potentially improve quality of life, but they also increase the risk of thromboembolic events and may stimulate tumor growth, the researchers noted.

Safety of the agents has been discussed in a number of hearings conducted by the Food and Drug Administration and the European Medicines Agency, and their effect on survival has been uncertain.

Previous studies that sought to address these concerns were literature-based meta-analyses of aggregated results with heterogeneous mortality endpoints.

In contrast, this meta-analysis was based on individual data from 13,933 patients in 53 randomized controlled trials, including those done by independent investigators and ESA manufacturers.

Analysis of individual patient data permitted consideration of prognostic factors at the patient level, and allowed investigation of subgroups of interest and modification of effects by patient and study characteristics, the researchers said.

It also allowed the definition of uniform survival endpoints and analyses of mortality during active study periods as well as of overall survival based on the longest available follow-up, they explained.

Mortality during the active study period was defined as death from any cause between the date of randomization and 28 days after the end of the study phase, and overall survival was defined as death from any cause between the date of randomization and the last available follow-up.

Median age at randomization was 61 years for patients receiving ESAs and 60 years for controls. Median hemoglobin concentrations at baseline were 106 g/L in ESA patients and 108 g/L in controls.

The planned epoetin doses ranged from 21,000 IU to 63,000 IU per week; planned doses for darbepoetin were from 100 mcg to 157.5 mcg per week.

In assessment of mortality during the active study period, median follow-up of ESA patients was 3.7 months and that of control patients was 3.9 months.

In assessment of overall patient survival, the median follow-up of ESA patients was 6.2 months and that of control patients was 8.3 months, for a combined hazard ratio of 1.06 (95% CI 1.00 to 1.12, P=0.046).

Patients were given chemotherapy in 38 of the trials, with 5,676 patients being randomized to ESA and 4,765 to control. A 10% increase in mortality was seen in ESA patients undergoing chemotherapy, the researchers reported.

In the chemotherapy trials, assessment of mortality during the active study period found that the median follow-up of ESA patients was 4.1 months and that of controls was 4.3 months, for a combined hazard ratio of 1.10 (95% CI 0.98 to 1.24, P=0.12).

Assessment of overall survival in the chemotherapy trials found a median follow-up of 6.7 months in the ESA arm and 8.4 months in the control arm, for a combined hazard ratio of 1.04 (95% CI 0.97 to 1.11, P=0.263).

The investigators noted that they found little evidence for an interaction between ESA treatment, baseline hemoglobin concentration, planned ESA doses, and mortality, although patients whose baseline hematocrit was low had an increased risk of death compared with other subgroups.

“Low hematocrits might be a marker for advanced cancer and increased vulnerability to the detrimental effects of erythropoiesis-stimulating drugs,” they suggested.

The investigators also observed that patients with previous thromboembolic events seemed to be protected from an ESA-associated increase in mortality, explaining that prophylactic anticoagulation during cancer treatment might have been protective against thrombogenic effects.

Debate continues as to whether these agents are safer in patients undergoing chemotherapy than in those undergoing other treatments such as radiation, the researchers said.

They suggested that patients not undergoing myelosuppressive anticancer treatment are more likely to achieve higher hemoglobin concentrations and might therefore be at greater risk of thromboembolic events and impairments in tumor control.

They concluded that in clinical practice the increased risks of these agents should be balanced against potential benefits and that consideration should be given to the individual patient’s clinical circumstances and preferences.

They also said that more data are needed on quality of life and tumor progression, and that further research should focus on the cellular and molecular mechanisms and pathways involved.

Several of the study investigators disclosed relationships with manufacturers of ESAs including Amgen, Johnson & Johnson, and Hoffmann-La Roche.

Primary source: The Lancet

Source reference:
Bohlius J, et al “Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials” Lancet 2009; 373: 1532-42.

WINSTON-SALEM, N.C., April 12 – Positron emission tomography (PET) scans can identify esophageal cancer patients who responded well to neoadjuvant chemoradiation, possibly sparing them from esophagectomy, a study here suggested.

Other imaging techniques, such as computed tomography and endoscopic ultrasound, have been unable to identify responders to chemoradiation accurately, said Edward A. Levine, M.D., and colleagues at Wake Forest University here.

PET scans before chemoradiation also identified a subgroup of patients likely to have a significant response to treatment, Dr. Levine and colleagues reported in April issue of Annals of Surgery.

The study involved 64 patients with esophageal cancer. The investigators used PET to gauge disease severity by measuring tissue uptake of injected 18-flouro-deoxy-glucose (18 FDG). Patients underwent PET scans before chemoradiation and then again four to six weeks afterward, before esophagectomy.

Nearly 78% of patients with an uptake value of 15 standard units or more before chemoradiation had a significant response to the treatment, compared with about 24% of patients with an uptake value of less than 15 (P=.005).

After chemoradiation, 71% patients whose uptake value decreased by 10 or more units had a significant response to the therapy, compared with 33% of those whose value decreased by less than 10 units (P=.004).

Surgical pathology reports were compared with the PET scan results, indicating that the PET measurements had a sensitivity of 83% and a specificity of 88% for detecting metastatic disease after chemoradiation treatment.

The positive predictive value of PET was 55.6% and the negative predictive value of 96.7%, the investigators reported.

“While additional multicenter prospective studies are needed, the research clearly shows that PET is a useful tool for identifying patients who respond well to chemoradiation,” Dr. Levine said.

These results also showed the predictive power of pre-treatment PET imaging for identifying patients likely to have a significant tumor response to chemoradiation, added Dr. Levine.

“The evidence suggests the potential for PET to change clinical practice, perhaps helping some patients avoid surgery,” he concluded.

Primary source: Annals of Surgery

Source reference:
Levine EA et al. Predictive value of 18-flouro-deoxy-glucose positron emission tomography in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer. Annals of Surgery. 2006; 243(4):472-479.

An investigational drug aimed at osteoporosis appears to be of benefit in treating a rare bone tumor, researchers said.

In a small, single-arm, open-label study, 86% of patients with giant-cell tumor of bone had a response to denosumab, a fully human monoclonal antibody, according to David Thomas, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues.

Currently, surgery is the definitive therapy, but the finding warrants more investigation of denosumab as a systemic treatment for the disease, Thomas and colleagues said online in The Lancet Oncology.

Indeed, the finding was described as a “breakthrough” by Maurice Balke, MD, of the University of Witten-Herdecke in Cologne, Germany, and Jendrik Hardes, MD, of University Hospital Muenster in Muenster, Germany.

“This is the first report that clearly shows a promising systemic treatment option for this rare type of tumor,” they wrote in an accompanying editorial in the journal.

More study is needed to tease out the mechanism involved, they said, as well as to see how long the effect lasts and whether the drug is effective in a broader population with the disease.

But the study “might change clinical practice” in the treatment of the disease, they concluded.

Giant-cell tumor of bone accounts for about 4% of primary bone tumors and about 18% of benign bone tumors. About 80% of patients with primary giant-cell tumors have disease that’s amenable to resection, the researchers noted in the journal.

The tumors consist of sheets of neoplastic ovoid mononuclear cells evenly interspersed with osteoclast-like giant cells. The giant cells and their precursors express the protein RANK, and some of the mononuclear cells express RANK ligand (or RANKL).

Since denosumab inhibits RANKL, the researchers hypothesized, it might block bone destruction and eliminate the giant cells.

To test the idea, they enrolled 37 patients with recurrent or unresectable disease and gave them subcutaneous denosumab (at 120 milligrams every 28 days, with loading doses on days eight and 15 of the first month).

The primary endpoint was tumor response, defined as either elimination of at least 90% of the giant cells or no radiological progression of the target lesion up to week 25.

After 25 weeks of treatment, two patients couldn’t be evaluated because they lacked adequate histologic or radiologic data, the researchers said, but 30 of the remaining 35 had a response.

Specifically, all of the 20 patients with histologic data showed at least a 90% reduction in giant cells from baseline. And 10 of the 15 patients assessed by radiology did not have progression of the lesion.

The most common adverse event was pain in an extremity, followed by back pain and headache, Thomas and colleagues said.

Five patients had grade three through five adverse events, but only one (a grade three increase in human chorionic gonadotropin concentration not related to pregnancy) was thought to be possibly associated with treatment.

As well, there were five serious adverse events but none was deemed to be related to the drug.

Thomas and colleagues said the study is limited by its small sample size (from a select population with recurrent or unresectable disease), the short study duration, and the single group study design.

The study was supported by Amgen. Thomas reported financial links with Amgen, Pfizer, and Novartis, as well as a fellowship from the Victorian Cancer Agency. Several authors reported being employees of or holding equity in Amgen.

The editorial authors said they had no conflicts.

WASHINGTON — The FDA has approved a new Haemophilus influenzae type b (Hib) vaccine — Hiberix — for use as a booster dose from ages 15 months through 4 years.

The vaccine, made by GlaxoSmithKline, will be used to complete the four-dose series recommended by the CDC following immunizations at 2, 4, and 6 months. It should be available within several weeks, according to the company.

It was approved using an accelerated process that operates under the condition that clinical trials will continue during the postapproval marketing to confirm a benefit, the FDA said.

The decision that Hiberix is safe and effective as a booster dose was based on data from seven clinical trials conducted in Europe, Latin America, and Canada in more than 1,000 children.

The vaccine will help ease the effects of a nationwide shortage of Hib vaccine following the 2007 recall of certain lots of two of the four vaccines licensed at that time — Merck’s and COMVAX.

The CDC originally recommended deferring the booster dose until the vaccine supply could be restored. But it rescinded that guidance in June on the recommendation of its Advisory Committee on Immunization Practices. The panel noted that two new vaccines — ActHIB and Pentacel by Sanofi Pasteur — were now available.

Although the CDC now recommends children get the full course of immunizations, there is still not enough vaccine to recall all children who deferred the booster dose in a mass effort. The agency said these children can receive the booster dose during routine office visits.

The most common side effects seen with the Hiberix booster are pain, redness at the injection site, fever, fussiness, loss of appetite and restlessness, according to the FDA.

SAN FRANCISCO, Sept. 11 — Joint or muscle pain or both prompted 13% of breast cancer patients enrolled in a trial comparing exemestane (Aromasin) with letrozole (Femara) to discontinue treatment, researchers reported here.

That dropout rate was higher than anticipated and suggests that “the aches and pains associated with aromatase inhibitors may be more important than previously believed,” Norah Lynn Henry, M.D., Ph.D., of the University of Michigan Cancer Center in Ann Arbor, told attendees at the American Society of Clinical Oncology’s Breast Cancer Symposium.

The results were culled from a substudy of an ongoing trial comparing the pharmacogenomics of the two aromatase inhibitors. Dr. Henry’s study was based on findings from 97 of the first 100 women enrolled in the trial.

Dr. Henry said symptoms usually began within “the first month and a half and typically presented as aching joints or sore muscles.” There was, she said, no “classic presentation as would be the case with fibromyalgia.”

Patients were asked to complete a health assessment questionnaire and visual analog scale to assess changes in pain and/or function at baseline, and at one, three, six, 12, and 24 months. Patients who exceeded a predefined threshold based on those assessment tools were referred to a rheumatologist for a complete evaluation.

Among the findings:

Forty-two women met the criteria for rheumatologic referral.
The median time to referral was 3.7 months.
The most common musculoskeletal findings based on clinical evaluation were rotator cuff tendonitis (eight women), carpal tunnel syndrome (nine women), and osteoarthritis (12 women).
Median time to discontinuation of the study drug was 6.2 months.

Dr. Henry said that although there was a high rate of musculoskeletal complaints, she and her colleagues were not able to identify any predictive factors.

“There was no relationship with a particular type or stage of breast cancer or to a particular treatment regimen,” she said. That observation differs from a published report by a team of Columbia University researchers who reported that treatment with taxanes was associated with an increased risk of musculoskeletal pain when women were subsequently treated with aromatase inhibitors.

Julie Gralow, M.D., of the University of Washington School of Medicine, noted “this is an ongoing study, and although we are all very anxious to have a comparison between the two regimens, I think it is also important to find out the mechanism behind a side effect that appears to affect a large number of our patients.”

Dr. Gralow, who was not involved in the study, moderated a press conference where the study was discussed.

The researchers disclosed conflicts of interest in the form of honoraria and research funding from Pfizer, maker of Aromasin, and consultant or advisory roles for Pfizer. Dr. Gralow disclosed honoraria from Genentech, Novartis, and Roche.

Primary source: ASCO Breast Cancer Symposium

Source reference:
Henry NL, et al “Aromatase inhibitor (AI)-induced musculoskeletal toxicity in a prospective clinical trial: A Consortium on Breast Cancer Pharmacogenomics (COBRA) study” ASCO Breast 2007; Abstract 227.

Higher intakes of two B vitamins — but not folate — may help ward off depression among older people, particularly if they take supplements, according to a large population study.

The prospective study, which followed more than 3,000 people ages 65 and older, found that higher intakes of vitamins B-12 and B-6 were both associated with a slightly reduced risk of depression (P=0.01 and P=0.05, respectively) for up to 12 years of follow-up, reported Kimberly A. Skarupski, MD, of Rush University in Chicago, and colleagues.

“In the assessment and treatment of depressive symptoms in older adults, clinicians and other healthcare professionals should be mindful of the patient’s nutritional status in general, and whether there are vitamin insufficiencies in these nutrients before treatment,” they wrote in the August issue of the American Journal of Clinical Nutrition.

Recent data show that 6% of older people are deficient in vitamin B-12, and 20% may have marginal depletion, according to background information supplied by the authors. Vitamin B insufficiency among individuals over 65 can be caused by reduced absorption and by medical conditions.

The prevalence of depression in later life ranges from 7% to 49%, they further noted. Depression among older people is associated with adverse health outcomes (including risk of mortality) and increased health costs.

While B-vitamin deficiencies have been associated with depression, there’s little prospective evidence on this association in population-based studies of older adults, the researchers added.

The researchers analyzed data from 3,503 participants in the ongoing Chicago Health and Aging Project. The average age of the study cohort was 73.5; 59% were African American, and 59% were female. One-third reported being widowed.

Diets (including intakes of vitamins B-6, B-12, and folate) were assessed via food-frequency questionnaire, and depression was measured by the Center for Epidemiologic Studies Depression scale, which has shown reasonable specificity and sensitivity for detecting major depression among older adults.

These instruments were used during four interview cycles. Around 13% of participants reported depressive symptoms during three of the four cycles.

Using logistic regression models, the researchers found that higher intakes of B-6 and B-12 that included supplementation were associated with a decreased likelihood of incident depression for up to 12 years of follow-up (average follow-up 7.2 years per participant).

Each additional 10 mg of vitamin B-6, and each additional 10 μg of B-12, from both food and supplements, were associated with 2% lower odds of depressive symptoms per year, they found.

These associations remained after adjusting for smoking, alcohol use, caregiving status, cognitive function, widowhood, physical disability, and medical conditions.

Folate intake, however, was not prospectively associated with reduced risk of depressive symptoms (P values ranged from 0.61 to 0.91).

Also, there was only a marginal association for intake of vitamin B-12 solely from dietary sources, not supplementation.

This “likely represents the poor bioavailability and absorption of vitamin B-12 from food sources, especially in older age,” the researchers wrote.

Intake of vitamin B-6 from dietary sources wasn’t significantly associated with depressive symptoms. Thus, the researchers wrote, “it is possible that the association with total intake is due to partial confounding by vitamin B12 contained in multivitamin supplements.”

African Americans were disproportionately represented in the lowest tertiles for vitamin B intakes.

Vitamin B-12 deficiency causes a neurologic syndrome that includes cognitive and depressive symptoms; the primary biologic form of vitamin B-6 is a cofactor in the synthesis of neurotransmitters, including serotonin.

The study was limited by its observational nature and by the use of self-reported data. It also may not apply to different ethnic groups with other patterns of diet and supplement use, the researchers cautioned.

They also warned that the findings may be “proxies for other unmeasured factors such as an overall healthy diet.”

In an accompanying editorial, Seren Haf Roberts, MD, of Bangor University in England, and colleagues wrote that the study “has made an important contribution to a long-running fascination with the associations between B vitamins and depression.”

But they noted that the associations “are not clear-cut.” For instance, they don’t support the association of folate intake with depressive symptoms, as previous research has shown.

Roberts and colleagues called for the need for further information on the role of dietary intake of these vitamins and the long-term mental health benefits.

Still, the findings “have taken us some way along the road to addressing some of these areas, but large-scale public health interventions, such as the fortification of flour, require us to travel much further,” they concluded. “The proof of the pudding, as they say, is in the eating.”

The researchers reported no conflicts of interest.

The editorialists are on the FolATED trial team, an NIH-funded trial.