Clinical Briefs
With Comments from John La Puma, MD, FACP
Fish Oil Supplements for Bipolar Disorder
July 1999; Volume 2: 82-83
Source: Stoll AL, et al. Omega 3 fatty acids in bipolar disorder: A preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999;56:407-412.
Omega-3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate, two effective treatments for bipolar disorder. The present study examined whether omega-3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder.
Researchers conducted a four-month, double-blind, placebo-controlled study, comparing omega-3 fatty acids (9.6 g/d) with placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder. Using a Kaplan-Meier survival analysis of the cohort, researchers found that the omega-3 fatty acid patient group had a significantly longer period of remission than the placebo group (P = 0.002; Mantel-Cox). In addition, for nearly every other outcome measure, the omega-3 fatty acid group performed better than the placebo group.
Omega-3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder.
Comment
These Harvard, Baylor, and Berlin investigators noted laboratory and animal data which suggest that omega-3 fatty acids dampen "signal transduction pathways associated with phosphatidylinositol, arachidonic acid, and other systems." They tested menhaden fish oil concentrate (a total of 6.2 g of eicosapentaenoic acid and 3.4 g of docosahexanoic daily, in 14 capsules taken in a divided dose daily) against an olive oil placebo. The chief outcome measure was duration of time to exit the trial. The investigators equated exit with treatment failure and worsening of a baseline clinical state.
Forty-four patients with mixed bipolar diseases, varied mood states, and varying medications were randomized; only 30 had evaluable data. Of these, 14 received omega-3s and 16 received placebo. Most of both groups were women; the mean ages were 41 and 45 years respectively. Unfortunately, four dropouts left before the first month was up; 10 more patients did not receive the intervention for the needed four months and were excluded from the final analysis. Eleven fish oil subjects completed the study, but only six placebo did. The discrepancy of an "extra patient" in these latter numbers was not accounted for.
The research, unfortunately, was nearly sunk from the start. A fish oil shortage was documented. Relatively few variables were stratified. The "fishy" aftertaste of fish oil was more often reported in the omega-3 group than the olive oil group. No effort was made to standardize for disease or treatment stage.
Recommendation
It’s too early to know whether to recommend fish oil supplements, along with lithium and other medication, to your patients with affective disorders, but if they do take it in this dosage, make sure they subtract 180 calories daily from their diet—14 capsules of oil add up to at least 1.5 tablespoons of liquid fat. In the meantime, fish oil should come from tuna, salmon, mackerel, and herring—fish—instead of capsules.
Anthroposophic Lifestyle and Atopic Disorders
July 1999; Volume 2: 83-84
Source: Alm JS, et al. Atopy in children of families with an anthroposophic lifestyle. Lancet 1999;353:1485-1488.
Increased prevalence of atopic disorders in children may be associated with changes in types of childhood infections, vaccination programs, and intestinal microflora. People who follow an anthroposophic way of life use antibiotics restrictively, have few vaccinations, and consume many live lactobacilli, which may affect the intestinal microflora.
In a cross-sectional study, 295 children aged 5-13 years at two anthroposophic (or Steiner) schools near Stockholm, Sweden, were compared with 380 children of the same age at two neighboring schools. History of atopic and infectious diseases, use of antibiotics and vaccinations, and social and environmental variables were assessed. Skin prick tests were done for 13 common allergens, and blood samples from children and their parents were analyzed for allergen-specific serum IgE antibodies.
At the Steiner schools, 52% of the children had taken antibiotics in the past, compared with 90% in the control schools. Eighteen percent and 93% of children, respectively, had had combined immunization against measles, mumps, and rubella, and 61% of the children at the Steiner schools had had measles. Fermented vegetables containing live lactobacilli were consumed by 63% of the children at Steiner schools, compared with 4.5% at the control schools.
Skin-prick and blood tests showed that the children from Steiner schools had lower prevalence of atopy than controls (odds ratio 0.62 [95% CI 0.43-0.91]). There was an inverse relation between the number of characteristic features of an anthroposophic lifestyle and risk of atopy (P for trend = 0.01).
Prevalence of atopy is lower in children from anthroposophic families than in children from other families. Lifestyle factors associated with anthroposophy may lessen the risk of atopy in childhood.
Comment
Anthroposophy literally translated means wisdom and humanity of man. Promulgated by Rudolph Steiner in the early 20th century, anthroposophy is a phenomenological approach to the spirit, and holds a spiritual view of the world beginning with a capacity for thinking. This philosophy has been applied to education, architecture, art, agriculture, and medicine. In medicine, illness is regarded "as something intimately connected to the biography of the human being not as a chance occurrence or mechanical breakdown."
In this study of medical outcomes, "Steiner units" were defined as no MMR vaccination; none of seven other vaccinations before age six months; antibiotics not more than twice and not before age two years; antipyretics not more than twice and not before age six months; consumption of fermented vegetables at least for a year, and consumption of mainly organic or biodynamically produced food in early childhood.
Children were evenly matched in baseline demographics, except that breast feeding in infancy was longer in Steiner children (5.7 months) than controls (4.3 months). Signs of atopy were assessed according to clinical exam (asthma, allergic rhinoconjunctivitis, atopic dermatitis, food allergy, and allergic urticaria), skin prick, and blood samples. The prevalence of wheeze in the last six months was 3.1% among Steiner children and 7.6% among controls; reported asthma diagnosed by a physician was 2.7% and 9.5%, and wheeze "ever" was 7.1% and 17.1%. Positive skin pricks prevalence was 7% and 13%; positive blood tests were 24% and 33% respectively. All these relationships were statistically significant.
The authors, largely from the Karolinska Institute in Stockholm, are quick to point out that infectious diseases other than measles could also have been more frequent among the Steiner kids, and that a 1995 measles epidemic could have lowered the prevalence of atopy in Steiner kids. They could not identify a single specific factor responsible for the lower atopy.
Overuse of antibiotics in childhood is well-documented, and underuse of fruits and vegetables, fermented or not, is also well-documented among children and their parents. Avoiding MMR and other vaccinations, however, appears to be a different discussion.
Recommendation
Be open to patients who want to explore an anthroposophic approach—certainly to farming, which can yield delicious produce. The children of parents who elect to follow an anthroposophic medical lifestyle merit monitoring, as they may avoid common atopic and allergic diseases, now often treated with prescription medication.
Well-done Red Meat and Breast Cancer Risk
July 1999; Volume 2: 84
Source: Zheng W, et al. Well-done meat intake and the risk of breast cancer. J Natl Cancer Inst 1998;90:1724-1729.
Heterocyclic amines, mutagens formed in meats cooked at high temperatures, have been demonstrated as mammary carcinogens in animals. A nested, case-control study among 41,386 cohort members of the Iowa Women’s Health Study evaluated the potential role of heterocyclic amines and intake of well-done meat in the risk for human breast cancer.
A questionnaire was mailed to individuals who had breast cancer diagnosed during the period from 1992 through 1994 and a random sample of cancer-free cohort members to obtain information on usual intake of meats and on meat preparation practices. Color photographs showing various doneness levels of hamburger, beef steak, and bacon were included. Multivariate analysis was performed on data from 273 case subjects and 657 control subjects who completed the survey.
A dose-response relationship was found between doneness of meat consumed and breast cancer risk. The adjusted odds ratios (ORs) for very well-done meat vs. rare or medium-done meat were 1.54 (95% confidence interval [CI] 0.96-2.47) for hamburger; 2.21 (95% CI 1.30-3.77) for beef steak; and 1.64 (95% CI 0.92-2.93) for bacon. Women who consumed these three meats consistently very well-done had a 4.62 times higher risk (95% CI 1.36-15.70) than that of women who consumed the meats rare or medium. Risk of breast cancer was also elevated with increasing intake of well-done to very well-done meat.
Consumption of well-done meats and thus exposure to heterocyclic amines (or other compounds) formed during high temperature meat cooking may play an important role in the risk of breast cancer.
Comment
Put another brat on the fire! Here in Chicago, you can hear the backyard grillmeister next door man the tongs, shift the coals, and swear at the cat nearly every weekend and most weeknights. The grill is the one part of the kitchen in which most men feel truly at home, as it is usually not in the kitchen, but on the deck, in the backyard, by the shore, at the beach.
But what to do about the well-done crust, where evil lies? In this study, although frying, grilling, and barbecuing were only weakly correlated with the risk of breast cancer, well-doneness was highly correlated. And well-doneness can come from any of these cooking methods—plus roasting, deep frying, even sautéing.
This is strong, comprehensive, epidemiological case-control data. More than 41,000 Iowa women, aged 55-69, have been assessed for cancer risk and prevalence since they returned a mailed questionnaire in January 1986. No information was collected then about meat or its usual doneness, so the investigators performed a case-control study from 1995-1996. The investigators, from the Universities of Minnesota and Iowa and the National Cancer Institute, included chicken and fish with the definition of meat, but the correlation was with red meat.
Recommendations
Tell your patients who want to reduce their risk for breast cancer to cook or order their burgers and steak medium or rare, and to send them back or do it over if overdone. This is even more important than reducing red meat intake. If patients or the grillmeister want a good crust, use cracked spices (e.g., peppercorns or cumin seeds) and whole seeds (e.g., sesame or pumpkin) pressed into the meat. These will add extra flavor, so much so that you won’t miss the nearly burned char.
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