ANTIOXIDANT SUPPLEMENTS AND CANCER PREVENTION
Gaziano JM, Glynn RJ, Christen WG, et al. Vitamins E and C in the prevention of prostate and total cancer in men: The Physicians' Health Study II randomized controlled trial. JAMA. 2008. Dec 9. doi:10.1001/jama.2008.862
Higher dietary intake of the antioxidant vitamins E and C has been associated with reduction of risk for some cancers. In trials designed to assess the ability of antioxidant supplements such as vitamin E to reduce the risk for developing cancer, the results have been mixed, with some research showing a reduced risk for prostate cancer, but not lung cancer, and others showing no effect on site-specific cancers. It has been argued that the conflicting findings may be due to differences in study design such as duration of treatment and insufficient power. The present study by Gaziano et al. reported on findings from the Physicians' Health Study II, a well-powered, long-term, randomized controlled trial designed to determine the effects of vitamins E and C on cancer.
Male physicians (N = 14,641) aged 50 years and above at the time of enrollment were randomized to receive vitamin E (400 IU every other day) or placebo or vitamin C (500 mg/d) or placebo. There was an additional arm receiving beta-carotene or placebo, but the data for the beta carotene arm are not reported in this analysis. Participants took the supplements for an average of eight years. During this time, there were 1008 incidents of prostate cancer and 1943 total cancers. Relative to placebo, supplementation with vitamin E alone had no effect on the development of prostate cancer or total cancer. Similarly, there was no effect of supplementation with vitamin C on cancer incidence. The present data do not support the use of these antioxidants for the prevention of cancer in older men.
Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2008. Dec 9. doi:10.1001/jama.2008.864
In the report described above, Gaziano et al. found no effect of long-term antioxidant supplementation on the prevention of prostate cancer in older men. In the same issue of JAMA, Lippman et al. present data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT). SELECT is a large, multicenter, randomized placebo-controlled trial to examine the effects of selenium alone (200 ug/d), vitamin E alone (400 IU/d), or a combination of the two to prevent prostate and other cancers in men. Participants (N = 35,533) include men over the age of 50 years without demonstrable prostate cancer receiving supplements or placebo for 7–12 years.
Over the study period, supplementation with selenium had no effect on the development of cancer, and the combination of selenium and vitamin E similarly had no effect on cancer incidence. Supplementation with vitamin E alone showed a non-significant trend towards an increased risk for prostate cancer. Due to recommendations from the data and safety monitoring committee, based on the seven-year interim analysis, trial supplementation was discontinued as there was no evidence of a beneficial effect of supplementation. Like the Physicians' Health Study II, described above, the present trial was well-powered to detect the effects of micronutrient supplementation on the risk for cancer. Additionally, the participant population in SELECT included individuals from the United States, Puerto Rico, and Canada, and represented a racially heterogeneous sample, thus increasing the generalizability of the findings.
Comment: In an accompanying editorial, Dr. Gann commends both trials for their high level of participant adherence, high levels of retention, and cost-effectiveness. Both trials will continue to contribute a wealth of data on the relationship of nutrient supplementation on health in middle-aged and older men. However, he raises the argument that the reductionist approach of supplementation with individual nutrients may be insufficient to truly examine the protective role of diet on risk for cancer.
Comment: Gann PH. Randomized trials of antioxidant supplementation for cancer prevention: first bias, now chance–next, cause. JAMA. 2008. Dec 9. doi:10.1001/jama.2008.863
TYPE 2 DIABETES AND COGNITIVE IMPAIRMENT
Saczynski JS, Jónsdóttir MK, Garcia ME, et al. Cognitive impairment: an increasingly important complication of type 2 diabetes: The Age, Gene/Environment Susceptibility–Reykjavik Study. Am J Epidemiol. 2008;168:1132–1139.
Type 2 diabetes is an increasing global public health concern, particularly in older individuals. Diabetes is a risk factor for cardiovascular pathology and cerebrovascular disease and some research shows that global cognitive impairment is seen in individuals with type 2 diabetes, but the influence of diabetes on specific cognitive domains has not been adequately described. The contributions of impaired fasting blood glucose, duration of diabetes, and glucose-lowering medications to cognitive impairments are less well understood. Saczynski et al. examined these questions in a subset of participants enrolled in the Age, Gene/Environment Susceptibility–Reykjavik Study (AGES–Reykjavik; N = 30,795).
A total of 1917 participants in AGES–Reykjavik were included in the present analysis and data included clinical exams, MRIs, and cognitive testing. A diagnosis of diabetes was based on self-report of a doctor's diagnosis and/or use of diabetic medication. Duration of disease was assessed using questionnaires. Undiagnosed diabetes was defined as no self-report of diabetes and a fasting blood glucose level ≥7.0 mmol/L. Cognitive testing assessed memory, processing speed, and executive function. Participants were categorized into normoglycemic (∼50%), impaired fasting blood glucose (∼39%), diagnosed type 2 diabetes (∼8%), and undiagnosed diabetes (∼3%). When compared with normoglycemic participants, individuals with type 2 diabetes had a significantly slower processing speed, but did not differ on memory or executive function tasks. Individuals with undiagnosed type 2 diabetes performed significantly worse on processing speed and memory tasks than normoglycemic individuals. Duration of disease for longer than 15 years was associated with significantly slower processing speed and poorer executive function in comparison to no disease. Within individuals with diabetes, there was no effect of diabetes-related medication on cognitive performance. The present study suggests that type 2 diabetes in older individuals affects memory and processing speed, and cognitive decrements in executive functioning are exacerbated by long experience with the disease. Undiagnosed diabetes was associated with the worst cognitive performance. The authors suggest that cognitive impairment seen with type 2 diabetes may negatively influence self-care and management of the disease, and treatment protocols should be designed with cognitive status in mind.
FOLIC ACID SUPPLEMENTS AND CHILD RESPIRATORY HEALTH
Håberg SE, London SJ Dr, Stigum H, Nafstad P, and Nystad W. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child. 2008. Dec 5. doi:10.1136/adc.2008.142448
In order to reduce the risk of neural tube defects, maintaining an adequate intake of folate or folic acid is recommended for all women planning to start a pregnancy. Some countries such as the United States and Canada have implemented mandatory fortification of foods with folic acid to ensure that at-risk populations reach an adequate intake of this nutrient. Other countries, including Norway, have not instituted fortification of the food supply, but do recommend supplements with folic acid for women before and during the first three months of pregnancy. High folate intakes, however, may adversely affect the developing immune system, perhaps through increased methylation reactions and altered gene expression. One potential outcome of increased global methylation would be the development of an allergic asthma phenotype. The data presented here by Håberg et al. examine the effect of folic acid supplements during pregnancy on the development of wheezing and respiratory tract infections (RTI) in offspring.
Data on maternal folic acid use and offspring wheeze and RTI were collected from the Norwegian Mother and Child Cohort Study (MoBa; N = 32,077). Respiratory outcomes were assessed using questionnaires and children were followed up to 18 months of age. Use of folic acid supplements was associated with higher levels of maternal education, lower parental smoking, and increased duration of breastfeeding. Exposure to folic acid during the first trimester was associated with increased risk for RTI and wheeze, although the effect was small. The authors stress that although persistent wheeze may be related to a predisposition for asthma, respiratory symptoms in these children may be transient and not indicative of chronic respiratory disease. Planned follow up of this cohort will continue to measure health status in comparison with maternal folic acid intake.
PLASMA SELENIUM CONCENTRATION AND PROSTATE CANCER RISK
Allen NE, Appleby PN, Roddam AW, et al.; European Prospective Investigation into Cancer and Nutrition. Plasma selenium concentration and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). Am J Clin Nutr. 2008;88:1567–1575.
Low dietary intake of selenium may be associated with an increased risk for prostate cancer, and selenium can inhibit carcinogenesis in tissue. Selenium levels in plant foods are largely dependent on selenium content of the soil, and selenium levels in Europe tend to be low. As described in the Lippman study above, intervention trials have attempted to demonstrate a protective influence of selenium on the risk for prostate cancer but have been unsuccessful; however, in the North American population, it is possible that selenium intakes were already sufficient. Allen et al. examine the association between plasma selenium concentrations, α- and γ-tocopherol levels, and prostate cancer risk in European men.
A subset of participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) trial with incident prostate cancer (n = 959) and matched controls (n = 1059) were evaluated. Diagnosis of cancer was subsequent to the initial enrollment and blood samples. Plasma selenium levels at baseline were compared with incidence of prostate cancer and stage of disease. Neither selenium nor α-tocopherol levels were associated with either incidence or severity of prostate cancer in this population. At the time that this analysis of the EPIC trial was defined, some research suggested that selenium in combination with vitamin E (α-tocopherol) may reduce the risk for cancer. However, neither the SELECT trial described earlier nor the present analysis lends support to the earlier observations regarding the protective role of selenium or α-tocopherol in the prevention of cancer.
VITAMIN D STATUS IN THE UNITED STATES
Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, and Yetley EA. Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004. Am J Clin Nutr. 2008;88:1519–1527.
Over the past several years, research on vitamin D and health has grown exponentially; however, the vitamin D status of the general population has not been estimated using recent data. Since the original estimates for vitamin D levels using data from the National Health and Nutrition Examination Survey obtained between 1988 and 1994 (NHANES III), significant changes that could affect vitamin D status may have occurred in the population. During the intervening time between the third NHANES and the most current assessments, prevalence of overweight and obesity has increased, milk consumption has decreased, and use of sunscreen is more common. Looker et al. compared 25-hydroxyvitamin D [25(OH)D] levels from NHANES III (n = 18,158) and those from the most current NHANES dataset (2000–2004; n = 20,289).
In addition to 25(OH) D levels, BMI was calculated from height and weight data, and milk intake and sun exposure were assessed using questionnaires. Additionally, to account for differences in assays over time, a sample of specimens from NHANES III were re-run with the current analysis. Mean serum levels of 25(OH)D were significantly lower in all population subgroups in the current NHANES group relative to NHANES III. After adjusting for assay shifts, mean serum concentrations were lower in most populations of males, but not in most populations of females. In adults, increases in BMI, decreased milk intake, and decreased sun exposure contributed to a decline in vitamin D status in the United States.
Comment: Dr. Norman highlights the importance of the data generated in the Looker et al. study. 25(OH)D data are reported for the first time for children between the ages of 1 and 11 years old, for pregnant women, and for Mexican Americans. The observation that vitamin D levels are declining is potentially troubling given the current body of research showing the importance of adequate vitamin D levels for immune, cardiovascular, bone, and brain health. Moreover, as more is understood about the need for vitamin D, many researchers judge the current recommendations for vitamin D intake to be too low, and the research presented here should be considered with regard to vitamin D nutritional policy.
Comment: Norman AW. A vitamin D nutritional cornucopia: new insights concerning the serum 25-hydroxyvitamin D status of the US population. Am J Clin Nutr. 2008 Dec;88:1455–1456.