High-Dose Folic Acid plus Vitamin B12 Supplements Linked to Cancer

Folic acid supplementation is associated with increased risk for cancer, according to a Norwegian study in JAMA. However, an editorial gives reassurance on the implications for the U.S.

Researchers examined cancer rates and mortality in some 6800 patients with ischemic heart disease who were randomized to receive various combinations of folic acid (0.8 mg/day), vitamin B12 (0.4 mg), or vitamin B6 (40 mg) — or placebo — for 3 years in an attempt to lower cardiovascular risks.

After a total follow-up of 6.5 years, risks for cancer diagnoses, cancer mortality, and all-cause mortality were higher in patients taking folic acid plus vitamin B12 than in those not taking the supplements (relative risk range, 1.18–1.38).

Editorialists note that cancer rates have dropped since the U.S. began fortifying grains with folic acid to prevent neural tube defects. In addition, the doses of folic acid used in the trial were about five times higher than the usual U.S. intake

http://jama.ama-assn.org/cgi/content/short/302/19/2119

Folic Acid and Cancer

Cancer incidence and mortality rose with vitamin use.

Since 1998, when the U.S. mandated folic acid (FA) fortification of flour and other grain foods to lower risk for neural tube defects, FA intake has risen dramatically. Supplementation with FA and other B vitamins also has been proposed to prevent cardiovascular disease (by lowering homocysteine levels), although no studies yet have shown such benefit. To examine a possible association between FA treatment and cancer risk, researchers combined the results of two Norwegian trials of vitamin B supplementation in nearly 7000 patients with ischemic heart disease. More than 70% of patients were current or former smokers. Norway does not mandate FA fortification of foods.

Patients were randomized to one of four daily regimens: FA (0.8 mg) plus vitamin B₁₂ (0.4 mg) plus vitamin B₆ (40 mg); FA plus vitamin B₁₂; vitamin B₆ alone; or placebo. After a median of 78 months of treatment and follow-up, risk for developing cancer in groups that were taking FA compared with those that were not taking FA was 21% higher (number needed to harm [NNH], about 63). Risk for dying from cancer was 38% higher in the FA groups (NNH, 91), and, for all-cause mortality, risk was 18% higher (NNH, 43). Lung cancer incidence accounted for much of the risk for developing or dying from cancer.

Comment: Because folic acid impairs immune surveillance of cancer cells and might stimulate the growth of established cancers, these findings have a biological basis; indeed, in another 2009 trial, folic acid supplementation was associated with excess risk for prostate cancer (JW Gen Med Mar 26 2009). Differences in baseline FA intake and smoking history might account for the results of earlier studies that did not show elevated risk for cancer. In any case, these results provide further reason not to recommend FA supplements for most middle-aged or older adults. The issue of what to do about FA fortification of foods is much more complicated, but editorialists believe that U.S. fortification places the population well within safe limits.

ACOG Releases New Cervical Screening Guidelines into Politically Charged Environment

New clinical management guidelines for cervical cytology screening advise that screening should begin at age 21, not at the age of first sexual intercourse.

The guidelines, released in the American College of Obstetricians and Gynecologists' ACOG Practice Bulletin, say the change is "based on the potential for adverse effects associated with follow-up of young women."

Initially, screening is recommended every 2 years. For women over 30 who have had three consecutive negative screenings, screening may occur at 3-year intervals. Women with certain risk factors may require more frequent screenings: those infected with HIV, the immunosuppressed, those with in utero exposure to DES, women with a history of cancer or cervical intraepithelial neoplasia.

Screening can be discontinued for most women between 65 and 70, or who have had a hysterectomy for benign indications and no history of high-grade CIN.

The guidelines also give recommendations on HPV screening.

http://journals.lww.com/greenjournal/documents/PB109_Cervical_Cytology_Screening.pdf.

USPSTF Recommends Against Routine Mammography for Women in Their 40s

The U.S. Preventive Services Task Force now recommends against routine screening mammography for average-risk women aged 40 to 49. This represents a change from the USPSTF's 2002 recommendation statement, which advocated for routine screening starting at age 40.

Among the task force's other updates, published in Annals of Internal Medicine:

Screening mammography should be performed every 2 years for average-risk women aged 50 to 74.

Evidence is insufficient to recommend for or against screening in women 75 or older.

Clinicians should not teach women how to perform breast self-exams.

Evidence is insufficient to make recommendations on using clinical breast exams in addition to mammography.

Evidence is insufficient to recommend for or against using digital mammography or MRI instead of film mammography.

In Journal Watch Women's Health, Dr. Andrew Kaunitz says that because the updated guidelines recommend less screening, women may be confused or even outraged. He calls for consistent "frank discussions" with patients about the benefits and risks of screening mammography.

(The American College of Radiology has spoken out against these guideline changes.)

http://www.annals.org/content/151/10/716.full

Yes, hormone therapy reduces mortality for some
The synthesis of data using Bayesian meta-analysis indicates a reduction in mortality in younger postmenopausal women taking hormone therapy compared with no treatment. This finding should be interpreted taking into account the potential benefits and harms of hormone therapy. The American Journal of Medicine

http://www.amjmed.com/article/S0002-9343(09)00666-4/fulltext

What lifestyle interventions can do in diabetes

During follow-up after the Diabetes Prevention Program, incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group, but the cumulative incidence of diabetes remained lowest in the lifestyle group. Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61457-4/abstract

Moderate-to-High Alcohol Intake Linked to Reduced CHD Risk in Men

Men who drink moderate to very high amounts of alcohol may have a reduced risk for coronary heart disease, according to an observational study in Heart.

Over 40,000 Spanish men and women completed questionnaires about their lifestyles, including alcohol intake, and were followed for a median of 10 years. During that time, 1.5% developed CHD.

After adjustment for lifestyle factors and comorbid conditions, men who regularly consumed moderate to very high amounts of alcohol (range: 5 to at least 90 g/day — the equivalent of roughly one to six standard drinks) had about half the risk for CHD as those who never drank. Findings were similar for all kinds of beverages consumed.

Among women, alcohol intake was not significantly associated with CHD.

Conclusions: In men aged 29-69 years, alcohol intake was associated with a more than 30% lower CHD incidence. Our study is based on a large prospective cohort study and is free of the abstainer error.

http://heart.bmj.com/cgi/content/abstract/hrt.2009.173419v1

Low-Fat Diet Associated with Improved Mood After 1 Year

Patients may ask about a small study suggesting that a low-fat diet, compared with a low-carbohydrate one, is associated with improved mood despite similar weight loss.

Reporting in Archives of Internal Medicine, researchers describe randomizing some 100 obese adults to either a low-carb or low-fat diet. After 1 year, participants lost an average of 14 kg, with no significant weight-loss difference between the diets.

Both groups saw initial improvements in mood scores as assessed by questionnaires. But by 1 year, the low-carb group saw its scores return to unfavorable baseline levels, while the low-fat group had sustained improvements in depression, anger, and confusion.

The authors note that average mood scores throughout the study were within the normal range, so their findings "are limited to healthy, obese, young to middle-aged adults with normal mood state and cannot be generalized to clinical populations."

Conclusions  Over 1 year, there was a favorable effect of an energy-restricted LF diet compared with an isocaloric LC diet on mood state and affect in overweight and obese individuals. Both diets had similar effects on working memory and speed of processing.

http://archinte.ama-assn.org/cgi/content/full/169/20/1873?home

Chronic stress is linked to consumption of high-fat foods
Researchers who interviewed more than 600 overweight or obese women found that those with chronic stress are more likely to eat high-fat foods and feel they lack control over their eating and hunger. The chronically stressed were also more likely to try to control their weight through "rigid restraint" techniques such as vowing to avoid certain foods or skipping meals -- strategies that often backfire. The study was presented at an Obesity Society meeting. USA TODAY

http://www.usatoday.com/news/health/weightloss/2009-11-02-stresseating02_ST_N.htm

Fifty Years of Thiazide Diuretic Therapy for Hypertension

Conclusion  We conclude that these agents are safe, effective, and well tolerated and should continue to be used either as monotherapy or with other medications in the management of hypertension.

http://archinte.ama-assn.org/cgi/content/abstract/169/20/1851?ct

Comparison of Three Insulin Regimens

Adding once-daily basal insulin to oral therapy conferred some advantages over alternate regimens.

The industry-sponsored "4-T" study was designed to examine various insulin regimens in patients with type 2 diabetes. Researchers randomized 708 patients with type 2 diabetes who were taking metformin and a sulfonylurea (glycosylated hemoglobin [HbA_1c] level, 7%–10%) to receive one of three insulin regimens, added to their oral drugs:

Once-daily basal insulin detemir (Levemir)

Twice-daily biphasic insulin aspart (NovoMix 30)

Thrice-daily prandial insulin aspart (NovoRapid)

During the trial, if HbA_1c levels remained higher than 6.5% despite insulin titration, sulfonylurea was stopped and a second insulin was added (3 prandial injections added in the basal group; 1 lunchtime prandial injection added in the biphasic group; or 1 basal insulin injection added in the prandial group). One-year outcomes were reported in 2007 (JW Gen Med Oct 23 2007).

The researchers now report 3-year findings: HbA_1c levels were similar in the three groups — about 7%. Mean weight gain was lower in the basal group (3.6 kg) than in the other two groups (about 6 kg). Hypoglycemia was least common in the basal group and most common in the prandial group.

Comment: The authors conclude that addition of once-daily basal insulin to oral therapy, with later addition of prandial insulin if needed, is preferred when one wishes to improve glycemic control in patients with type 2 diabetes. This conclusion is reasonable, given equivalent glycemic control and modestly less weight gain and hypoglycemia in the basal group compared with the other groups. However, these results should be viewed in the context of recent trials that failed to show improved outcomes with intensive glycemic control in similar patients (JW Gen Med Jun 6 2008 and JW Gen Med Dec 24 2008).

CONCLUSIONS: Patients who added a basal or prandial insulin-based regimen to oral therapy had better glycated hemoglobin control than patients who added a biphasic insulin-based regimen. Fewer hypoglycemic episodes and less weight gain occurred in patients adding basal insulin.

http://www.ncbi.nlm.nih.gov/pubmed/19850703?dopt=Abstract

Even Very Low Levels of Cardiac Troponin T Linked to Heart Failure, Cardiovascular Death

Even very low levels of cardiac troponin T are associated with increased risk for heart failure and cardiovascular death among patients with stable heart disease, according to an industry-funded study in the New England Journal of Medicine.

Using a highly sensitive assay, researchers tested for troponin T in nearly 3700 adults with stable coronary artery disease and preserved left ventricular function, and then followed them for roughly 5 years. (The assay is not commercially available.)

The test detected very low troponin T levels in nearly all subjects — levels that would have gone undetected using conventional assays, the researchers write. Even at these low concentrations, increasing troponin T was associated with elevated risk for cardiovascular death or heart failure (but not MI).

Conclusions After adjustment for other independent prognostic indicators, cardiac troponin T concentrations as measured with a highly sensitive assay were significantly associated with the incidence of cardiovascular death and heart failure but not with myocardial infarction in patients with stable coronary artery disease.

http://content.nejm.org/cgi/content/full/NEJMoa0805299