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With Comments from Russell H. Greenfield, MD, Dr. Greenfield is Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC; and Visiting Assistant Professor, University of Arizona, College of Medicine, Tucson, AZ.
Pretzel Logic—Yoga for Migraines
Source: John PJ, et al. Effectiveness of yoga therapy in the treatment of migraine without aura: A randomized controlled trial. Headache 2007;47:654-661.
Goal: To assess effectiveness of a specific program of yoga therapy vs. self-care in the treatment of migraine.
Study design: Randomized, controlled clinical trial over three months.
Subjects: People with migraine without aura (n = 72).
Methods: Subjects were recruited from a multispecialty headache clinic with the understanding that a study was being performed to evaluate treatment for migraines "intended to reduce the negative effect on their personal, family, and social lives." A headache diary was maintained for four weeks prior to randomization to either yoga therapy or self-care. The yoga group was taught a set of practices by a trained yoga therapist, and given handouts on techniques to use during the prodromal stage of migraine. Yoga therapeutics included specific postures emphasizing neck, back, and shoulder stretching followed by relaxation, strengthening, and flexibility exercises. Vigorous bending exercises were excluded. Breathing exercises, relaxation, and meditation techniques were also employed. Yoga was to be practiced five days a week for one hour at a time. Deep cleansing (called kriya) was performed once a week in association with relaxation, and involved nasal douching followed by forced exhalations. Subjects were instructed not to perform the specific yoga practices during an acute headache, or during resolution or the postdromal stage. Those in the self-care group received an educational session once a month that addressed migraine types and triggers, as well as self-care preventive strategies. Primary outcomes of interest were headache frequency as determined through a headache diary, migraine severity as reported on a 0-10 numeric scale, and pain as measured via the McGill Pain Questionnaire. Secondary outcome measures included levels of anxiety and depression as determined via the Hospital Anxiety and Depression Scale, and medication usage.
Results: Participants in the yoga group reported significant improvements in headache intensity, frequency, duration and pain, and in symptoms of anxiety and depression as compared with the self-care group. In addition, subjects who used yoga required less medication over the study period than did people in the self-care group.
Conclusion: Specific yoga practices performed over three months can result in improvements in a variety of migraine parameters.
Study strengths: Diagnosis of migraine without aura was confirmed by a neurologist; three-month duration of trial.
Study weaknesses: Minimal and unclear description of exclusion criteria; no sham yoga group; unique and "special" attention paid to subjects in the yoga group; lack of objective assessment; and as an aside, there were multiple spelling errors present in the text.
Of note: A 2002 survey found that 85% of patients at an outpatient head/neck pain clinic had used some form of alternative medicine to address their headaches, and 60% felt they had received benefit from these therapies; generally positive results have been reported on specific types of yoga therapy against a number of clinical entities that include anxiety, depression, stress, asthma, and musculoskeletal disorders; participants in this trial were charged a registration fee for entrance into the study, and were asked to obtain their own yoga mat and a neti pot (for sinus irrigation); subjects were permitted to use rescue medications as prescribed by their neurologist but no other agents, including over the counter remedies; the study was performed under the auspices of the Department of Zoology (!), University of Rajasthan, India.
We knew that: The most commonly employed CAM therapies for headache include massage therapy, medicinal herbs, acupuncture, and chiropractic care; yoga breathing exercises (also referred to as pranayama) are often promoted as a means of balancing the autonomic nervous system and contributing to a sense of calm.
Comments: Few would argue that yoga, meditation, and other mind/body therapies can help ameliorate anxiety, stress, and perhaps even depression. In addition, specific yoga therapy may contribute to an improvement in symptoms with certain maladies, if not an improvement in the experience of those symptoms. The present study is intriguing but significantly flawed. Did migraineurs benefit due to the special attention paid them in the yoga group, or was it the specific interventions that created clinical improvement? Was there a sinus component to the headaches? Would an hour of relaxation and gentle stretching on most days of the week be as effective as a specific yoga practice? Many questions remain unanswered, and little from this trial's results can be applied clinically with any degree of authority. Yoga therapy may well be of help to some people with migraine headaches, but a paucity of sound clinical research assessing risks and benefits of yoga in this setting remains a serious obstacle to acceptance.
What to do with this article: Remember that you read the abstract.
Move the Cheese: Dairy and Prostate Cancer
Source: Mitrou PN, et al. A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland). Int J Cancer 2007;120:2466-2473.
Goal: To examine the association between dietary intakes of calcium and dairy products in relation to the risk of prostate cancer.
Study design: Prospective, randomized, double-blind, 2 × 2 factorial design, primary prevention trial.
Subjects: Cohort of 27,028 male smokers aged 50-69 years who smoked five or more cigarettes a day at study entry (data taken from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, also called ATBC).
Methods: Dietary intake was assessed at baseline using a validated 276-item food questionnaire that addressed food preferences over the prior year, and nutrient intakes were calculated using an accepted food composition database. Participants provided detailed information regarding medical history and demographics, as well as data on smoking. Cases of prostate cancer were identified through the Finnish Cancer Registry. Medical records were reviewed by two study oncologists, and cytology specimens were reviewed by 1-2 pathologists to confirm presence of cancer and histologic type.
Results: Over 17 years of follow-up, a total of 1,267 incident cases of prostate cancer were identified. A graded positive association was readily evident between calcium intake and total risk of prostate cancer. Across increasing categories of calcium intake there was an associated increase in the relative risk (RR) of prostate cancer as follows (mg/d, RR): < 1000 mg/d, 1.00; 1000-1,499 mg/d, 1.28; 1,500-1,999 mg/d, 1.38; and > 2,000 mg/d, 1.63. Similar results were found after analyzing data by quintiles of calcium intake. No association was found between stage or grade of prostate cancer and calcium from total dairy intake, and no clear association was found for any individual dairy food and prostate cancer risk. When dietary calcium or calcium from dairy products was controlled for, the association between total dairy intake and increased risk of prostate cancer became statistically nonsignificant.
Conclusion: High intakes of dietary calcium or some related component contained in dairy foods is associated with an increased risk for prostate cancer.
Study strengths: Long duration of follow-up (up to 17 years); detailed examination of total risk of prostate cancer and risk by stage and grade of disease; essentially complete identification of cases of prostate cancer; multivariate model that accounted for a multiplicity of potential confounding variables.
Study weaknesses: Problems inherent in the use of a food frequency questionnaire; issues of generalizability since population was limited to older male smokers (but other trials that included nonsmokers have suggested similar risk).
Of note: In a prior ATBC report based on eight years' follow-up, researchers suggested that men with low calcium and higher phosphorus intakes may be at decreased risk of prostate cancer; numerous potential mechanisms have been posited for the apparent association between dairy product intake and increased risk of prostate cancer, including the potential for dairy products to increase serum levels of insulin growth factor I, and especially due to the propensity for calcium intake to suppress the active form of vitamin D; the ATBC study was performed in Finland, a country where dairy intake is generally high; the researchers focused on dietary calcium because calcium intake in the Finnish population results mainly from dietary and not supplement intake; variables like total fat, dietary vitamin D intake, lycopene, alcohol, and red meat intake did not alter study results appreciably; in general, men in the trial with higher dietary calcium intakes were slightly older with higher BMIs, were more likely to have diabetes, lived in urban areas, were less highly educated, and less physically active than men with low calcium intakes; a large proportion of the cases of prostate cancer were detected as a result of clinical symptoms (population-based PSA screening programs are not widespread in Finland).
We knew that: The ATBC trial tested whether daily supplementation with 20 mg beta-carotene and/or 50 mg alpha-tocopherol reduced the incidence of lung cancer in male smokers from southwestern Finland, with the trial ending in 1993 (notable findings were that beta-carotene increased the incidence of lung cancer as well as mortality, and that vitamin E appeared to have a chemopreventive effect against prostate cancer, but was also associated with an increased incidence of death due to hemorrhagic stroke); epidemiologic data regarding an association between calcium intake and prostate cancer risk have yielded inconsistent data (several case control studies, specifically, have shown an increased risk with high calcium intake either from food or from supplements, especially in regard to advanced cancers); total dietary vitamin D intake is a poor correlate of total vitamin D because humans mainly derive vitamin D from sunlight; smoking decreases intestinal calcium absorption; calcium appears to offer chemopreventive effects against colon cancer, and offers benefit against osteoporosis, and possibly against hypertension and insulin resistance.
Comments: Results of this well-done study bring added concerns about high dairy intake to the fore. Calcium has an important role in health for men as in women, but dosage becomes the critical question, and may ultimately become gender-specific. To quote the authors, "Our data suggest that the current recommended dietary allowance (RDA) of 1,200 mg/d of calcium for men aged 50 or over (equivalent to 2-3 glasses of milk per day) may exceed the optimal amount needed to achieve a balance between the apparent health benefit and risks of calcium." For now, men without specific clinical indications (like osteoporosis) should shun calcium supplementation, especially older men with a predisposition towards prostate cancer, and consider moderating their intake of dairy products. Foods like kale, spinach, fortified cereals, and salmon provide calcium at lower levels as well as offering additional nutrients. Unfortunately, studies like this one turn a milk mustache into a frown.
What to do with this article: Keep a hard copy in your file cabinet.
Phooey on Folate? Colorectal Cancer Chemoprevention
Source: Cole BF, et al. Folic acid for the prevention of colorectal adenomas. JAMA 2007;297:2351-2359.
Goal: To evaluate safety and effectiveness of folic acid supplementation to prevent new colorectal adenomas in subjects with a history of same.
Study design: Double-blind, placebo-controlled, two-factor, phase 3, randomized clinical trial performed at nine clinical centers in 2004 (the Aspirin/Folate Polyp Prevention Study [AFPPS]).
Subjects: Patients with a history of colorectal adenomas but no invasive colorectal carcinoma (n = 1,021, aged 21-80 years).
Methods: Questionnaires were completed by participants that addressed personal characteristics, medical history, and lifestyle habits. Subjects were randomized to receive folic acid 1 mg/d (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin 81 mg or 325 mg, or placebo. Development of adenomas was determined by colonoscopic evaluation and pathology review. Follow-up colonoscopy was scheduled to take place after three years, and then again after another three or five years (the latter being offered as an invitation to participate and without mandatory use of aspirin). During the first follow-up interval, subjects received questionnaires regarding multiple parameters including symptoms and adherence to study protocol. During the second follow-up interval, questionnaires were again mailed every four months to participants who continued to take study tablets, and annually to all other subjects. Plasma folate levels were determined at the end of the first follow-up interval to gauge adherence to study protocol. The primary outcome measure of interest was development of at least one colorectal adenoma. Secondary outcome measures included occurrence of advanced lesions and presence of multiple adenomas.
Results: During the first surveillance cycle, the incidence of at least one colorectal adenoma was 44.1% in the folic acid group and 42.4% for the placebo group, while the incidence of at least a single advanced lesion was 11.4% and 8.6%, respectively. During the second surveillance cycle, incidence of at least one colorectal adenoma was 41.9% in the folic acid group and 37.2% for the placebo group, while the incidence of at least a single advanced lesion was 11.6% and 6.9%, respectively. For the 607 subjects with endpoint information on both follow-up intervals, the rate of any adenoma being identified in either interval was 71.3% in the folic acid group and 65.5% in the placebo group, and the overall rate of advanced lesions was 23.1% and 17.1%, respectively. Suggestion of an increased risk of colorectal adenomas with folic acid was confined to those subjects not randomized to receive aspirin. Use of folic acid was associated with a higher risk of multiple colorectal adenomas, as well as noncolorectal cancers (specifically due to an excess incidence of prostate cancer).
Conclusion: Folic acid taken at a daily dose of 1 mg/d for up to six years does not reduce the risk of colorectal adenomas in people with a history of adenomas, and may actually increase the risk of colorectal neoplasia.
Study strengths: Excellent follow-up for first colonoscopy cycle (96.7%); consideration of potential time constraints in showing a benefit for folate as compared with aspirin; excellent adherence to study protocol, especially during first follow-up cycle, including avoidance of nonstudy folic acid-containing supplements; intention-to-treat analysis.
Study weakness: Marked decrease in follow-up rate for second surveillance cycle.
Of note: The epidemiological data supporting the idea that a low-folate diet contributes to colorectal neoplasia is especially notable for people who regularly imbibe alcohol (which can antagonize folate metabolism); plasma vitamin B12 and, as necessary, methylmalonic acid levels, were obtained to avoid masking of vitamin B12 deficiency and to exclude those people with preexisting B12 deficiency; animal data exist suggesting a cancer-promoting effect of folate supplementation, and a protective effect of folate deficiency against experimental carcinogenesis (some data suggest a protective effect of folate on normal mucosa, but a cancer-promoting effect on early neoplasia); originally, the AFPPS was designed to investigate only aspirin, but it was quickly expanded to examine folic acid; participants had to have had removal of all known polyps within three months of study enrollment; allocation to the folic acid group resulted in a significant increase in plasma folate and a modest decrease in plasma homocysteine levels.
We knew that: Fortification of the food supply with folate began in 1996 and was made mandatory if 1998; adenomas are precursors of most colorectal cancers; folate is a derivative of folic acid; folic acid and its derivatives play an important role in nucleotide synthesis and methylation reactions; bench data and epidemiologic research both suggest chemopreventive effects for folic acid against colon cancer; folate supplementation lessens the risk for neural tube defects; folate deficiency leads to macrocytic anemia; the AFPPS data regarding aspirin showed that low-dose (81 mg/d) aspirin had a moderate chemopreventive effect against development of colorectal adenomas, whereas high-dose aspirin (325 mg/d) provided no clinical benefit; foods high in folic acid include fortified cereals, garbanzo beans, broccoli, lentils, and turkey.
Comments: A high-quality trial raising the specter of over-supplementation with specific nutrients leading to possible morbidity is important news, especially so in the case of folate, where mandatory fortification efforts have been in place since 1998. Results of this trial suggest an increased risk of colorectal adenomas in people with a history of adenomas even in subgroups where the benefits of folate supplementation would seem readily apparent (low folate levels or high alcohol intake, for example). There is also the suggestion of an increased risk of noncolorectal neoplasia. The trial does not, however, address primary prevention of colorectal adenomas.
Recent studies have caused some practitioners to question their enthusiasm for folate supplementation in the setting of cardiovascular disease. The findings of this trial further dampen hopes for folate being a panacea. Until further data become available, those with a history of colorectal adenomas should not use supplemental folic acid, but should continue to enjoy food sources of folate in moderation. Future studies need to focus on whether folate provides a chemoprotective effect for individuals with no history of colorectal adenomas.
What to do with this article: Keep a hard copy in your file cabinet.