BACKGROUND: Adverse events associated with dietary supplements are difficult to monitor in the USA, because such products are not registered before sale, and there is little information about their content and safety. METHODS: In 1998, 11 poison control centres in the USA recorded details of 2332 telephone calls about 1466 ingestions of dietary supplements, in 784 of which patients had symptoms. We used a multitiered review process (kappa 0.42) to select 489 cases for whom we were at least 50% certain that their negative events were associated with dietary supplements. We aimed to assess the effects of multiple ingredients and long-term use, and collated data for patterns of use and information resources. FINDINGS: A third of events were of greater than mild severity. We noted both new and previously reported associations that included myocardial infarction, liver failure, bleeding, seizures, and death. Increased symptom severity was associated with use of several ingredients, long-term use, and age. Paediatric exposures were more often unintentional than were adult ingestions, and treatment of disease was the reason for supplement use in at least 28% of reports. Most products and ingredients were not identified in the information database (Poisindex) used by poison control centres, and specific adverse events were reported variably among five additional sources. INTERPRETATION: Dietary supplements are associated with adverse events that include all levels of severity, organ systems, and age groups. Associations between adverse events and ingredients are difficult to verify if a product has more than one ingredient, and because of incomplete information systems. Research into hazards and risks of dietary supplements should be a priority.
Comment In: Lancet. 2003 May 3;361(9368):156612737905
The Danish Fitness and Nutrition Council has evaluated the basis for recommendations on the intake of antioxidants and has found limited basis for increasing the recommended intake levels for the antioxidants vitamin C and E. Evidence was insufficient to support recommendations for polyphenol or carotenoid supplementation. Supplementation with high doses of vitamin E and beta-carotene may present a health risk. A high intake of fruit and vegetables is associated with a reduced risk of lifestyle diseases, but there is no evidence that this association is due to an antioxidant effect.
Comment In: Ugeskr Laeger. 2006 Oct 9;168(41):3537; author reply 353717066533
The sale of nonprescription weight-loss products accounts for millions of dollars spent by Americans trying to lose weight, yet there is little evidence for effectiveness and there are multiple safety concerns. The purpose of this study was to determine what products, and ingredients within products, were available at retail outlets in a metropolitan area. A purposive sampling strategy identified 73 retail outlets. An audit form was used to collect information from product labels. The audit identified 402 products containing 4,053 separate ingredients. The mean number of ingredients per product was 9.9+/-8.96 (range = 1 to 96). A database search was conducted regarding evidence for effectiveness, safety precautions, and side effects for the 10 ingredients that appeared most often across products. Modest evidence of effectiveness exists for green tea (Camellia sinensis), chromium picolinate, and ma huang (Ephedra major). For the remaining seven (ginger root [Zingiber officinale], guarana [Paullinia cupana], hydroxycitric acid [Garcinia cambogia], white willow [Salix alba], Siberian ginseng [Eleutherococcus senticosus], cayenne [Capsicum annuum], and bitter orange/zhi shi [Citrus aurantium]), inadequate or negative evidence exists. Although precautions and contraindications were found for all 10 ingredients, the strongest concerns in the literature appear for ma huang, bitter orange, and guarana. Our audit revealed numerous weight-loss products available to consumers, yet there is little evidence to support the effectiveness of the top 10 ingredients identified and many potential adverse reactions; therefore, food and nutrition professionals should discuss dietary supplement use with their clients.
Affiliations of authors: Cancer Prevention Program (ARK) and SWOG Statistical Center (AKD, CMT, PJG), Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Epidemiology (ARK, GEG) and Department of Environmental Health (GEG), University of Washington, Seattle, WA; University of Missouri, Research Reactor Center, Columbia, MO (JSM); Harry S. Truman Memorial Veterans Hospital, Columbia, MO (JSM); Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX (IMT); Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA (FLM); Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (LMM, HLP); Moores Cancer Center, University of California San Diego, San Diego, CA (SML); Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH (EAK).
The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case-cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status.
There were 1739 total and 489 high-grade (Gleason 7-10) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided.
Toenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium + vitamin E arms) had no effect among men with low selenium status (
Comment In: J Natl Cancer Inst. 2014 Mar;106(3):dju00524563520
Calcium and vitamin D are recommended for bone health, but there are concerns about adverse risks. Some clinical studies suggest that calcium intake may be cardioprotective, whereas others report increased risk associated with calcium supplements. Both low and high serum levels of 25-hydroxyvitamin D have been associated with increased mortality.
The purpose of this study was to determine the association between total calcium and vitamin D intake and mortality and heterogeneity by source of intake.
The Canadian Multicentre Osteoporosis Study cohort is a population-based longitudinal cohort with a 10-year follow-up (1995-2007).
This study included randomly selected community-dwelling men and women.
A total of 9033 participants with nonmissing calcium and vitamin D intake data and follow-up were studied.
Total calcium intake (dairy, nondairy food, and supplements) and total vitamin D intake (milk, yogurt, and supplements) were recorded.
The outcome variable was all-cause mortality.
There were 1160 deaths during the 10-year period. For women only, we found a possible benefit of higher total calcium intake, with a hazard ratio of 0.95 (95% confidence interval, 0.89-1.01) per 500-mg increase in daily calcium intake and no evidence of heterogeneity by source; use of calcium supplements was also associated with reduced mortality, with hazard ratio of 0.78 (95% confidence interval, 0.66-0.92) for users vs nonusers with statistically significant reductions remaining among those with doses up to 1000 mg/d. These associations were not modified by levels of concurrent vitamin D intake. No definitive associations were found among men.
Calcium supplements, up to 1000 mg/d, and increased dietary intake of calcium may be associated with reduced risk of mortality in women. We found no evidence of mortality benefit or harm associated with vitamin D intake.
Marine oils are rich in polyunsaturated fatty acids (PUFAs), including docosahexaenoic and eicosapentaenoic acid. These PUFAs are associated with health benefits and additional sustainable sources of marine oils are desirable. One of the source organisms is Calanus finmarchicus, a copepod endemic to the North Atlantic. PUFAs in the lipid fraction of this organism are largely in the form of wax esters. To assess the safety of these wax esters as a source of PUFAs, a randomized, double-blinded, placebo-controlled clinical trial was conducted whereby 64 subjects consumed 2 g Calanus oil in capsule form daily for a period of one year. A group of 53 subjects consumed placebo capsules. At baseline, 6-, and 12-months, series of evaluations were conducted, including: vital signs, clinical chemistry and hematological evaluations, and adverse event reporting. Food intake and physical exercise were controlled by means of a questionnaire. There were no effects on Calanus oil treatment on any of the safety parameters measured. A slight increase in the incidence of eczema was reported in the Calanus oil group, but the response was minor in nature, not statistically significant after controlling for multiple comparisons, and could not be attributed to treatment.
Cod liver oil is an important source of vitamin D, but also contains other fat-soluble components such as vitamin A. Before 1999, the cod liver oil formula in Norway contained a high concentration of vitamin A (1000 µg per 5 ml). High vitamin A status is associated with increased risks of several chronic diseases.
To investigate the association between cod liver oil intake and asthma development.
In the Nord-Trøndelag Health Study, a total of 25 616 Norwegian adults aged 19-55 years were followed up from 1995-1997 to 2006-2008. Current analysis based on 17 528 subjects who were free of asthma and had complete information on cod liver oil intake at baseline. Cod liver oil intake was defined as daily intake = 1 month during the year prior to baseline. Incident asthma was reported as new-onset asthma during the 11-year follow-up.
Of the 17 528 subjects, 18% (n=3076) consumed cod liver oil daily for = 1 month over the past year. Cod liver oil intake was significantly associated with incident asthma with an OR of 1.62 (95% CI 1.32 to 1.98) after adjustment for age, sex, daily smoking, physical activity, education, socio-economic status, family history of asthma, and body mass index (BMI). The positive association was consistent across age (
Although supplement use is prevalent in North America, there is little information on how supplements affect the prevalence of nutrient adequacy or risk of intakes greater than the tolerable upper intake level (UL). The objectives of this study were to compare the prevalence of nutrient adequacy and percent of intakes greater than the UL from diet alone between supplement users and nonusers and determine the contribution of supplements to nutrient intakes. Dietary intakes (24-h recall) and supplement use (previous 30 d) from respondents =1 y in the Canadian Community Health Survey 2.2 (n = 34,381) were used to estimate the prevalence of nutrient adequacy and intakes greater than the UL. Software for Intake Distribution Evaluation was used to estimate usual intakes. The prevalence of nutrient adequacy from diet alone was not significantly higher among supplement users than nonusers for any nutrient. Based on diet alone, children 1-13 y had a low prevalence of nutrient adequacy (30%. For other nutrients, there was a low prevalence of nutrient adequacy. There were no nutrient intakes greater than the UL from diet alone, except zinc in children. When supplements were included, =10% of users in some age/sex groups had intakes of vitamins A and C, niacin, folic acid, iron, zinc, and magnesium greater than the UL, reaching >80% for vitamin A and niacin in children. In conclusion, from diet alone, the prevalence of nutrient adequacy was low for most nutrients except for calcium, magnesium, and vitamins A and D. For most nutrients, supplement users were not at greater risk of inadequacy than nonusers; supplement use sometimes led to intakes greater than the UL.
OBJECTIVES: The objectives of this study were to report on the prevalence of enamel opacities from seven European study sites using a standardized photographic method, and to investigate the importance of variables responsible for enamel fluorosis. METHODS: The sample comprised a randomly selected group of 300 8-year-old children in each of the study areas. One examiner from each area was trained and calibrated in the use of a standardized photographic technique. Two transparencies were taken of each child's permanent maxillary central incisor teeth; one to represent the teeth 'wet' and one when the teeth had been allowed to dry out naturally for 105 s. The transparencies were viewed 'blind' by the author (JAC) and scored using the DDE and TF indices. Data relating to variables considered to be associated with enamel fluorosis were also collected. RESULTS: The prevalence of diffuse opacities ranged from 61% in fluoridated Cork (Ireland) to 28% in Athens (Greece). The percentage of subjects with a TF score of three or more ranged from 4% in Cork and nonfluoridated Haarlem (the Netherlands) to zero in Oulu (Finland) and Athens. Fluoridated water and the prolonged use of fluoride tablets were found to be significant contributory factors to fluorosis. CONCLUSIONS: The prevalence of fluorosis was found to be highest in fluoridated Cork. The prolonged use of fluoride supplements was also found to be a significant risk indicator associated with fluorosis.