ACUTE SELENIUM TOXICITY OUTBREAK ASSOCIATED WITH LIQUID SUPPLEMENT USE
MacFarquhar JK, Broussard DL, Melstrom P, Hutchinson R, Wolkin A, Martin C, Burk RF, Dunn JR, Green AL, Hammond R, Schaffner W, and Jones TF. Acute selenium toxicity associated with a dietary supplement. Arch Intern Med. 2010;170:256–261.
Selenium is a trace mineral required in very small amounts. It is incorporated into the antioxidant enzymes selenoproteins. Selenoproteins may be important for regulating thyroid and immune function and protecting against chronic diseases such as cancer or heart disease. In the United States, selenium deficiency is rare; it is seen most commonly in association with malabsorptive conditions or in individuals receiving total parenteral nutrition. The recommended dietary allowance for selenium is 55 µg/d for individuals 14 years of age and older, and the tolerable upper intake limit is 400 µg/d. Selenium toxicity occurs with excess intake of selenium and is characterized by nausea, vomiting, nail discoloration, hair loss, fatigue and irritability, and a foul “garlic” breath odor. The report by MacFarquhar et al. describes cases from an outbreak of acute selenium toxicity following ingestion of a liquid dietary supplement that contained 200 times the labeled concentration of selenium.
The first cases were identified in March 2008 by a chiropractor who observed symptoms of selenium toxicity, including hair loss and gastrointestinal illness in several patients. The patients had been ingesting a liquid dietary supplement available at the practitioner's office, and they had increased their intake at the onset of symptoms. Patients then noted worsening symptoms and notified the local health department. During this time period, the Food and Drug Administration (FDA), state health departments, and poison control centers investigated similar complaints, and the supplement was identified as the common factor among affected individuals. Case finding was conducted at a national level using a list of all retail locations vending the supplement and a list of individuals who placed Internet or telephone orders for the supplement. The product was voluntarily recalled, and press releases from the FDA and state health departments stimulated self-reporting about consumption of the supplement and illness. A total of 227 affected individuals were identified and given questionnaires assessing demographics, amount of product consumed, symptoms, and resolution of symptoms. In total, 201 cases were identified in 10 states, with one individual requiring hospitalization. The median estimated intake of selenium in these individuals was 41,749 µg/d, and frequently reported symptoms included diarrhea, fatigue, hair loss, joint pain, nail brittleness or discoloration, and nausea. Symptoms persisting for at least 90 days included fingernail discoloration or loss, fatigue, and hair loss.
The product contained a blend of vitamins, trace elements, amino acids, and other nutritional compounds. The label listed a selenium content of 200 µg/30 mL, and label instructions directed adults to take 30 mL of the supplement daily, which reflects a nearly fourfold higher daily intake of selenium than the current RDA. Subsequent FDA analysis showed that the selenium concentration in the misformulated batch of the supplement was 40,800 µg/30 mL. Human error during manufacturing was identified as the cause of the of the product's misformulation. The authors argue that if dietary supplement manufacturers were subject to the same oversight and standards as the pharmaceutical industry, the outbreak could have been avoided.
Comment: In an invited commentary, Dr. Ashar describes the implementation of the Dietary Supplement Health and Education Act (DSHEA), which allowed manufacturers of dietary supplements to market products without providing proof of safety or efficacy to the FDA. Adverse events linked to the use of some supplements led to subsequent legislation to ensure good manufacturing practices, although problems still exist with respect to labeling, advertising, and medical claims. Dr. Ashar emphasizes that under the current regulations, there are limited data on the premarket evaluation of the efficacy and safety of dietary supplements, and, although the majority of supplement users do not report serious adverse events, more reliable and stringent evaluation of supplements should be implemented.
Comment: Ashar BH. The Dietary Supplement Health and Education Act: time for a reassessment. Arch Intern Med. 2010;170:261–263.
HIGHER DOSES OF DOCOSAHEXAENOIC ACID DO NOT IMPROVE BEHAVIORAL OUTCOME IN PRETERM INFANTS
Smithers LG, Collins CT, Simmonds LA, Gibson RA, McPhee A, and Makrides M. Feeding preterm infants milk with a higher dose of docosahexaenoic acid than that used in current practice does not influence language or behavior in early childhood: a follow-up study of a randomized controlled trial. Am J Clin Nutr. 2010;91:628–634.
Infants born preterm (<33 weeks) are at risk for later deficits in language development and increased behavioral problems relative to infants born at full term. One factor in these developmental impairments is the reduced gestational transfer of docosahexaenoic acid (DHA) in preterm infants. DHA is critical to proper neural development, and provision of 0.2–0.4% DHA (% of total fat) in formula improves brain development in preterm infants relative to those given non-supplemented formula. Limited evidence is available, however, on DHA supplementation and language development in preterm infants. The present study by Smithers et al. examined global development in children born preterm who were breastfed or formula-fed with either standard formula or a formula with higher levels of DHA than currently available formulas.
The children examined in this study represent a subgroup of participants enrolled in the Docosahexaenoic acid for the Improvement in Neurodevelopmental Outcome (DINO) trial. This follow-up study included behavioral and language assessments in children up to 5 years of age. At the time of enrollment, infants born prior to week 33 of gestation were randomly assigned to either the control condition (0.3% DHA) or the higher-DHA condition (1.0% DHA). Women who were breastfeeding in addition to formula-feeding were given soy oil capsules (controls received capsules containing no additional DHA) or tuna oil capsules (900 mg/d DHA). DHA supplementation continued until infants reached the full-term age. The higher dose of DHA was chosen to match the levels of intrauterine accumulation of DHA during development. Primary outcome measures included scores on the MacArthur Communicative Development Inventory (MCDI), the Strengths and Difficulties Questionnaire, which assesses child behavior, and the Short Temperament Scale for Children. Data were available for 128 children at 26-month follow-up, and for 125 children at 3–5-year follow-up. Language and behavior assessments did not differ between preterm children fed the current standard of 0.3% DHA and preterm children fed 1.0% DHA. Previous work by this group of researchers showed improvements in visual acuity and in global mental development scores in this population of children given higher-dose DHA. Although the trial was designed to determine whether providing DHA in the amounts seen during normal development would improve outcomes in preterm infants, there were no clinically relevant benefits of administering a higher percentage of DHA in terms of language or behavior.
SUPPLEMENTATION OF CONCORD GRAPE JUICE AIDS MEMORY IN INDIVIDUALS WITH MILD COGNITIVE IMPAIRMENT
Krikorian R, Nash TA, Shidler MD, Shukitt-Hale B, and Joseph JA. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010;103:730–734.
As the global population ages, age-related disorders of memory and brain function are of increasing concern. Mild cognitive impairment may render individuals at increased risk for dementia and may be indicative of early neurodegeneration. Interventions during the early stages of mental decline may slow or prevent progression to a more serious state of impairment. Some research shows that nutritional interventions with dietary compounds that are high in antioxidant and anti-inflammatory activity, such as berry fruits, are beneficial for modifying the neuronal signaling involved in memory function. Concord grape juice is relatively high in total phenolics, anthocyanins, and proanthocyanidins. In humans, supplementation with grape juice improves biochemical markers of cardiovascular disease including endothelial function, serum antioxidant capacity, and reduced platelet aggregation. Given the established link between cardiovascular disease and neurodegeneration, Concord grape juice holds potential as a nutritional intervention in individuals with early mild cognitive impairment.
Twelve participants (4 women; mean age, 78.2 years) with signs of early-stage memory decline were randomly assigned to receive either a placebo beverage (n = 7) or 100% Concord grape juice (n = 5). Participants consumed the beverages for 12 weeks. Total volume consumed each day was targeted at between 6 and 9 ml/kg/d. For example, individuals weighing between 54 and 64 kg were given 444 ml/d. Primary cognitive outcome assessments included the California Verbal Learning Test (list learning and recall) and the Spatial Paired Associate Learning Test (non-verbal memory). Additionally, mood was assessed using the Geriatric Depression Scale, and fasting insulin and blood glucose values were collected. There were no effects of beverage type on mood or blood glucose. An increase in fasting insulin levels was observed in the grape juice condition, but not the placebo condition. Word-list learning was significantly improved following intake of grape juice compared to placebo. Delayed recall for both verbal and spatial material was also improved following intakes of grape juice relative to placebo, although these differences were not statistically significant. The authors acknowledge the limitations of the study's small sample size, but propose that the observed moderate-to-large effect sizes suggest that larger intervention trials would be worthwhile.
DIETARY PROTEIN INTAKE AND BONE MASS ACCRUAL IN GIRLS WITH LOW CALCIUM INTAKE
Zhang Q, Ma G, Greenfield H, Zhu K, Du X, Foo LH, Hu X, and Fraser DR. The association between dietary protein intake and bone mass accretion in pubertal girls with low calcium intakes. Br J Nutr. 2010;103:714–723.
Childhood and adolescence are critical periods for bone mass accrual, and low bone mass accretion during this time period is associated with ongoing risk of fractures and increased risk for osteoporosis in later life. Some 60–80% of bone mass accrual is genetically determined, but environmental factors such as diet, including calcium intake, and activity levels determine maximum bone mass. Dietary intake of calcium is low in a number of countries, including China, where intakes can be below 500 mg/d. Dietary protein intake also affects bone mass accrual, but there is little information on the impact of protein on bone development in children with chronically low calcium intakes. The present study reported by Zhang et al. describes the relationship between protein intake and bone mass accretion in Chinese girls with low calcium intakes.
Prepubertal girls (mean age, 10.1 years) in the urban region of Beijing, China, were recruited into a trial investigating milk supplementation and bone development. Participants were followed for 2 years of milk supplementation and 3 years of follow-up with no further supplementation. The present analysis includes data from 757 girls for whom up to 60 months of bone mass data and dietary intake data were available. In the girls who had been in the control condition of the milk supplementation study, the average intake of calcium was 454 mg/d, and average protein intake was 56 g/d. For girls in the milk-supplemented conditions, calcium intakes averaged 774 mg/d during the 2-year supplementation period; they fell to 454 mg/d during the 3-year follow-up phase and protein intakes ranged from 61 g/d during supplementation to 55 g/d post-supplementation. The average total bone mass accrual over the 5-year study was 958 g for all groups. Bone mass accrual was positively associated with calcium intake and protein intake was negatively associated with bone mass accrual. When protein was categorized according to animal or plant source, protein from animal sources had significantly negative effects on bone mineral content, bone mineral density, and bone area. It is proposed that excretion of calcium may be increased with protein intake, and that approximately 6 mg of additional calcium is needed to compensate for the loss of calcium related to 1 g of protein intake. Using the present data, the authors indicate that in girls between 10 and 15 years of age with an average intake of 55 g/d protein, the girls would theoretically require an additional 330 mg/d calcium to compensate for calcium loss. In the case of girls with low calcium intake and relatively higher protein intake, less calcium would be retained for bone mass accretion. The authors indicate that the low intake of calcium in the study participants is reflective of calcium intake in general in China and in other regions where milk intake is low. They suggest that improvements in protein intakes in these regions may have a negative impact on calcium status, and that intake of calcium-rich foods should be encouraged.