Specialty Supplements Research Articles

Modulation of Gut Microbiota by Glucosamine and Chondroitin in a Randomized, Double-Blind Pilot Trial in Humans.

Glucosamine and chondroitin (G&C), typically taken for joint pain, are among the most frequently used specialty supplements by US adults. More recently, G&C have been associated with lower incidence of colorectal cancer in human observational studies and reduced severity of experimentally-induced ulcerative colitis in rodents. However, little is known about their effects on colon-related physiology. G&C are poorly absorbed and therefore metabolized by gut microbiota. G&C have been associated with changes in microbial structure, which may alter host response. We conducted a randomized, double-blind, placebo-controlled crossover trial in ten healthy adults to evaluate the effects of a common dose of G&C compared to placebo for 14 days on gut microbial community structure, measured by 16S rRNA gene sequencing. Linear mixed models were used to evaluate the effect of G&C compared to placebo on fecal microbial alpha and beta diversity, seven phyla, and 137 genera. Nine genera were significantly different between interventions (False Discovery Rate < 0.05). Abundances of four Lachnospiraceae genera, two Prevotellaceae genera, and Desulfovibrio were increased after G&C compared to placebo, while Bifidobacterium and a member of the Christensenellaceae family were decreased. Our results suggest that G&C affect the composition of the gut microbiome which may have implications for therapeutic efficacy.

Consumer Usage and Reasons for Using Dietary Supplements: Report of a Series of Surveys

Objective: Consumer usage of dietary supplements is prevalent in the United States, and total usage is higher than reported in recent National Health and Nutrition Examination Surveys (NHANES), because these surveys capture usage only in the 30 days prior to the respondent's interview and do not capture occasional and seasonal use throughout the year. We report data from a series of consumer surveys on the full extent of dietary supplement use, on the reasons for supplement use, and on the products most commonly taken, as well as other health habits of supplement users. Methods: The Council for Responsible Nutrition (CRN), a trade association of the dietary supplement industry, has contracted with Ipsos Public Affairs to conduct consumer surveys annually since 2000. The surveys have been administered online since 2007 to about 2000 subjects each year. We report 5 years of data (2007 to 2011) on the prevalence of dietary supplement use, as well as more detailed data from the 2011 survey on the products used, the reasons for using supplements, and other health habits of supplement users. Results: The prevalence of supplement use fluctuated within the range of 64% to 69% from 2007 to 2011, and the prevalence of regular supplement use ranged from 48% to 53%, with no statistically significant differences from year to year. Over the 5-year period, the percentage of respondents who said that they regularly used a variety of supplements increased from 28% to 36%, and the increase from 2010 to 2011 was statistically significant. The percentage of respondents who said that they regularly used only a multivitamin, as opposed to a variety of supplements, declined from 24% to 17%, and the decrease from 2007 to 2008 was statistically significant. Detailed results from the 2011 survey confirm that supplement use increases with age and is higher in women than in men. Vitamin or mineral supplements were used by 67% of all respondents in 2011, specialty supplements by 35%, botanicals by 23%, and sports supplements by 17%. Among supplement users, multivitamins were the most commonly used supplement (71%), followed by omega-3 or fish oil (33%), calcium (32%), vitamin D (32%), and vitamin C (32%). The reasons most often cited for supplement use were for overall health and wellness (58%) and to fill nutrient gaps in the diet (42%). Supplement users were significantly more likely than nonusers to say that they try to eat a balanced diet, visit their doctor regularly, get a good night's sleep, exercise regularly, and maintain a healthy weight. Conclusions: Annual consumer surveys over a period of 5 years show that dietary supplement use is somewhat more prevalent in the United States than has been reported in the NHANES surveys, when occasional and seasonal use are taken into account, in addition to regular use. Most dietary supplement users take a multivitamin, and many take a variety of products. The primary reasons given for supplement use are for overall health and wellness or to fill nutrient gaps. Users of dietary supplements are more likely than nonusers to adopt a variety of healthy habits, indicating that supplement use is part of an overall approach to living healthy.

Specialty Supplement Use and Biologic Measures of Oxidative Stress and DNA Damage

Oxidative stress and resulting cellular damage have been suggested to play a role in the etiology of several chronic diseases, including cancer and cardiovascular disease. Identifying factors associated with reduced oxidative stress and resulting damage may guide future disease-prevention strategies. In the VITamins And Lifestyle (VITAL) biomarker study of 209 persons living in the Seattle area, we examined the association between current use of several specialty supplements and oxidative stress, DNA damage, and DNA repair capacity. Use of glucosamine, chondroitin, fish oil, methylsulfonylmethane (MSM), coenzyme Q10 (CoQ10), ginseng, ginkgo, and saw palmetto was ascertained by a supplement inventory/interview, whereas the use of fiber supplements was ascertained by questionnaire. Supplements used by more than 30 persons (glucosamine and chondroitin) were evaluated as the trend across number of pills/week (non-use, <14 pills/week, 14+ pills/week), whereas less commonly used supplements were evaluated as use/non-use. Oxidative stress was measured by urinary 8-isoprostane and PGF2α concentrations using enzyme immunoassays (EIA), whereas lymphocyte DNA damage and DNA repair capacity were measured using the Comet assay. Multivariate-adjusted linear regression was used to model the associations between supplement use and oxidative stress/DNA damage. Use of glucosamine (Ptrend: 0.01), chondroitin (Ptrend: 0.003), and fiber supplements (P: 0.01) was associated with reduced PGF2α concentrations, whereas CoQ10 supplementation was associated with reduced baseline DNA damage (P: 0.003). Use of certain specialty supplements may be associated with reduced oxidative stress and DNA damage. Further research is needed to evaluate the association between specialty supplement use and markers of oxidative stress and DNA damage.

Association Between Use of Specialty Dietary Supplements and C-Reactive Protein Concentrations

Laboratory evidence suggests that certain specialty dietary supplements have antiinflammatory properties, though evidence in humans remains limited. Data on a nationally representative sample of 9,947 adults from the 1999-2004 cycles of the National Health and Nutrition Examination Survey were used to assess the associations between specialty supplement use and inflammation, as measured by serum high-sensitivity C-reactive protein (hs-CRP) concentration. Using survey-weighted multivariate linear regression, significant reductions in hs-CRP concentrations were associated with regular use of glucosamine (17%, 95% confidence interval (CI): 7, 26), chondroitin (22%, 95% CI: 8, 33), and fish oil (16%, 95% CI: 0.3, 29). No associations were observed between hs-CRP concentration and regular use of supplements containing methylsulfonylmethane, garlic, ginkgo biloba, saw palmetto, or pycnogenol. These results suggest that glucosamine and chondroitin supplements are associated with reduced inflammation in humans and provide further evidence to support an inverse association between use of fish oil supplements and inflammation. It is important to further investigate the potential antiinflammatory role of these supplements, as there is a need to identify safe and effective ways to reduce inflammation and the burden of inflammation-related diseases such as cancer and cardiovascular disease.

Vitamin, mineral, and specialty supplements and risk of hematologic malignancies in the prospective VITamins And Lifestyle (VITAL) study.

Increasing evidence suggests that nutrients from fruits and vegetables have chemoprotective effects on various cancers including hematologic malignancies, but the effects of nutritional supplements are poorly examined. Herein, we prospectively evaluated the association of vitamin, mineral, and specialty supplements with incident hematologic malignancies in 66,227 men and women aged 50 to 76 years from Washington State recruited from year 2000 to 2002 to the VITamins And Lifestyle (VITAL) cohort study. Hematologic malignancies cases (n = 588) were identified through December 2008 by linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry. HRs and 95% CIs associated with supplement use were estimated with Cox proportional hazards models. After adjustment, high use of garlic supplements [≥4 days per week for ≥3 years; HR = 0.55 (95% CI = 0.34-0.87); P(trend) = 0.028] and ever use of grape seed supplements [HR = 0.57 (95% CI = 0.37-0.88)] were inversely associated with hematologic malignancies in our models. In addition, high use (8-10 pill-years) of multivitamins was suggestive of an inverse association [HR = 0.80 (95% CI = 0.64-1.01)]. In contrast, no associations were observed for the remaining supplements. These data indicate that the use of garlic and grape seed may be associated with reduced risk of hematologic malignancies. This is the first cohort study to suggest a possible role of these supplements in the chemoprevention of hematologic malignancies.

Specialty Supplements and Prostate Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort

Although there is evidence from studies of prostate cancer cell lines and rodent models that several supplements may have antiinflammatory, antioxidant, or other anticancer properties, few epidemiologic studies have examined the association between nonvitamin, nonmineral, “specialty” supplement use and prostate cancer risk. Participants, 50–76 yr, were 35,239 male members of the VITamins and Lifestyle (VITAL) cohort who were residents of western Washington state, and who completed an extensive baseline questionnaire in 2000–2002. Participants responded about their frequency (days/wk) and duration (yr) of specialty supplement uses. 1,602 incident invasive prostate cancers were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariate-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models. Any use of grapeseed supplements was associated with a 41% (HR 0.59, 95% CI: 0.40–0.86) reduced risk of total prostate cancer. There were no associations for use of chondroitin, coenzyme Q10, fish oil, garlic, ginkgo biloba, ginseng, glucosamine, or saw palmetto. Grapeseed may be a potential chemopreventive agent; however, as current evidence is limited, it should not yet be promoted for prevention of prostate cancer.

Abstract 1912: Long-term use of glucosamine and chondroitin and lung cancer risk in the vitamins and lifestyle (VITAL) cohort

Abstract Glucosamine and chondroitin, typically taken to treat osteoarthritis and chronic joint pain, are among the most commonly used non-vitamin, non-mineral, specialty supplements in the United States. These supplements have been shown to exhibit anti-inflammatory and anti-cancer properties in vitro and in vivo. Inflammation is thought to play an important role in cancer etiology and progression at several anatomic sites, including the lung. Studies have reported inverse associations of non-steroidal anti-inflammatory drug (NSAID) use and lung cancer risk; however, none have examined long-term use of glucosamine and chondroitin with lung cancer risk. The VITamins And Lifestyle (VITAL) study is a large, prospective cohort study designed to investigate the association of vitamin, mineral, and specialty supplements with cancer risk. Previously in this cohort, we found that glucosamine and chondroitin were inversely associated with lung cancer risk. We now evaluate these specific associations in more detail (by amount of use, histological subtypes of cancer) with an additional year of follow-up. Participants included 76,904 adults, 50-76 years, with no history of lung cancer, who were living in the region of western Washington State included in the Surveillance, Epidemiology, and End Results (SEER) cancer registry, and who completed a baseline questionnaire in 2000-2002. After 6 years of follow-up, 807 lung cancer cases were accrued. We characterized glucosamine and chondroitin use in the 10 years before baseline as non-use; low: &amp;lt;4 days/week or &amp;lt;4 years; high: ≥3 days/week and ≥4 years. We used multivariable-adjusted Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of glucosamine and chondroitin with lung cancer risk. Compared to non-use, high use was associated with a linear 33% reduction in risk (HR 0.67, 95% CI: 0.56-1.07, P-trend=0.04). There was no clear trend with high chondroitin use (HR 0.96, 95% CI: 0.67-1.37, P-trend=0.21). When stratified by histologic type, high use of glucosamine (HR 0.49, 95% CI: 0.27-0.90, P-trend&amp;lt;0.01) or chondroitin (HR 0.69, 95% CI: 0.36-1.31, P-trend=0.03) was strongly and inversely associated with risk of adenocarcinoma but not small cell or other non-small cell lung cancers. Factors associated with inflammation, including smoking, chronic-obstructive pulmonary disease, osteoarthritis, and NSAID use, did not modify these associations. The strength of the associations we observed is similar to those reported from studies of NSAIDs and lung cancer risk. Unlike NSAIDs, glucosamine and chondroitin carry few known adverse effects. Although confirmatory studies are needed, glucosamine and chondroitin may be potential lung cancer chemopreventive agents. Supported by NCI grants R25-CA94880, R01-CA154512, and K05-CA154337 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1912. doi:10.1158/1538-7445.AM2011-1912

Abstract 1915: Specialty supplements and prostate cancer risk in the vitamins and lifestyle (VITAL) cohort

Abstract Although there is evidence from studies of prostate cancer cell lines and rodent models that several supplements may have anti-inflammatory, anti-oxidant, or other anti-cancer properties, few epidemiologic studies have examined the association between non-vitamin, non-mineral, specialty supplement use and prostate cancer risk. Participants, 50-76 years, were 35,239 male members of the VITamins And Lifestyle (VITAL) cohort who were residents of western Washington State, and who completed an extensive baseline questionnaire in 2000-2002. Participants responded about their frequency (days/week) and duration (years) of specialty supplement uses. 1,602 incident invasive prostate cancers were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariate-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models. Any use of grapeseed supplements was associated with a 41% (HR 0.59, 95% CI: 0.40-0.86) reduced risk of total prostate cancer. Although not statistically different, the association was somewhat stronger for low-grade (HR 0.58, 95% CI: 0.33-1.03) than high-grade tumors (HR 0.82, 95% CI: 0.34-2.00). There were no associations for use of chondroitin, co-enzyme Q10, fish oil, garlic, ginkgo biloba, ginseng, glucosamine, or saw palmetto. Grapeseed may be a potential chemopreventive agent, however as current evidence is limited, it should not yet be promoted for prevention of prostate cancer. This work is supported by NCI grants R25-CA94880, R01-CA142545, and K05-CA154337 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1915. doi:10.1158/1538-7445.AM2011-1915

Long-Term Use of Supplemental Vitamins and Minerals Does Not Reduce the Risk of Urothelial Cell Carcinoma of the Bladder in the VITamins And Lifestyle Study

Urothelial carcinoma has the highest lifetime treatment cost of any cancer, making it an ideal target for preventative therapies. Previous work has suggested that certain vitamin and mineral supplements may reduce the risk of urothelial carcinoma. We used the prospective VITamins And Lifestyle cohort to examine the association of all commonly taken vitamin and mineral supplements as well as 6 common anti-inflammatory supplements with incident urothelial carcinoma in a United States population. A total of 77,050 eligible VITAL participants completed a detailed questionnaire at baseline on supplement use and cancer risk factors. After 6 years of followup 330 incident urothelial carcinoma cases in the cohort were identified via linkage to the Seattle-Puget Sound SEER cancer registry. We analyzed use of supplemental vitamins (multivitamins, beta-carotene, retinol, folic acid, and vitamins B1, B3, B6, B12, C, D and E), minerals (calcium, iron, magnesium, zinc and selenium) and anti-inflammatory supplements (glucosamine, chondroitin, saw palmetto, ginkgo biloba, fish oil and garlic). For each supplement the hazard ratios (risk ratios) for urothelial carcinoma comparing each category of users to nonusers, and 95% CIs, were determined using Cox proportional hazards regression, adjusted for potential confounders. None of the vitamin, mineral or anti-inflammatory supplements was significantly associated with urothelial carcinoma risk in age adjusted or multivariate models. The results of this study do not support the use of commonly taken vitamin or mineral supplements or 6 common anti-inflammatory supplements for the chemoprevention of urothelial carcinoma.

Specialty Supplements and Breast Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort

Specialty Supplements and Breast Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort

Vitamins, Minerals, and Specialty Supplements and Risk of Hematological Malignancies In the VITamins and Lifestyle (VITAL) Cohort Study

AbstractAbstract 4143 Introduction:The use of vitamins and dietary supplements is a common health practice in many parts of the world, in part because of the belief that they will prevent diseases, including cancer. However, results of epidemiologic studies regarding their efficacy in reducing the risk of any cancer, particularly hematologic malignancies, are inconsistent and are mostly limited to case-control studies. Materials:Participants were male and female members of the VITamins And Lifestyle (VITAL) cohort. Between 2000 and 2002, 64,839 men and women, aged 50 to 76 years, who lived in the region of Washington State covered by the Surveillance, Epidemiology, and End Results (SEER) registry, were recruited. Participants were excluded if they had any cancer prior to baseline other than non-melanoma skin cancer and were censored at the time of diagnosis of a non-hematologic malignancy during follow-up; after exclusions, there were 64,839 participants available for study. Incident cases of hematologic malignancies were identified through December 2008 by linkage to the SEER registry. Participants answered questions on the frequency (days/week), duration (years), and dose per day of their supplemental use of vitamins, including A, B3, B6, B12, C, D, E, multivitamin compounds, and folic acid; minerals, including calcium, selenium, iron, magnesium, chrome, and zinc during the 10 years before baseline. For the non-vitamin, non-mineral “specialty” supplements, garlic, ginseng, and fish oil, only frequency and duration were ascertained. Use of vitamin and mineral supplements was categorized into non-users and tertiles of use, such that the highest category was greater than could be achieved only by use of a common multivitamin (Centrum Silver). 10-year average use of specialty supplements was categorized into: non-user; low use, <4 days/week or <3 years; and high use, ≥4 days/week and ≥3 years. Multivariable-adjusted Cox proportional hazards models were used to estimate hazards ratios (HR) and 95% confidence intervals (95% CI) of the use of dietary supplements with the risk of total hematologic malignancies. Models were adjusted for age, sex, race/ethnicity (white/hispanic/other), education, smoking, self-rated health, physical activity, history of anemia in the year before baseline, and family history of leukemia or lymphoma. Results:A total of 577 case of hematological malignancies were identified including MDS [n=54], AML [n=36], myeloproliferative disorders [n=46], CLL/SLL [n=88] and other non-Hodgkin lymphomas [n=235], Hodgkin lymphomas [n=22], plasma cell disorders [n=66], mature NK/T cell neoplasms [n=17], and other entities [n=13]). None of the vitamin 10-year average intakes were associated with decreased risk of incident hematologic malignancies There was no evidence that high use of vitamins A (HR=0.79, 95% CI: 0.58–1.08; p-trend=0.28), B12 (HR=0.98, 95%CI: 0.73–1.31; p-trend=0.26), C (HR=0.97, 95% CI: 0.77–1.22; p-trend=0.99), D (HR=0.90, 95% CI: 0.62–1.31; p-trend=0.45), or folic acid (HR=1.00, 95% CI: 0.73–1.39; p-trend=0.19) was associated with the risk of blood cancer. Among specialty supplements, only high 10-year average use of garlic was significantly associated with a reduced risk of development of blood cancers (HR=0.64,95% CI: 0.42–0.98); however the association was not linear (p-trend=0.14). Conclusions:We observed no reduction in the risk of incident hematologic malignancies with dietary supplement and vitamin use with the exception of garlic when used at a high amount (≥4 days/week for ≥ 3 years). Disclosures:No relevant conflicts of interest to declare.

Specialty Supplements and Breast Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort

Use of nonvitamin, nonmineral "specialty" supplements has increased substantially over recent decades. Several supplements may have anti-inflammatory or anticancer properties. Additionally, supplements taken for symptoms of menopause have been associated with reduced risk of breast cancer in two case-control studies. However, there have been no prospective studies of the association between the long-term use of these supplements and breast cancer risk. Participants were female members of the VITamins And Lifestyle (VITAL) Cohort. Postmenopausal women, ages 50 to 76 years, who were residents of western Washington State, completed a 24-page baseline questionnaire in 2000 to 2002 (n = 35,016). Participants were queried on their recency (current versus past), frequency (days/week), and duration (years) of specialty supplement use. Incident invasive breast cancers (n = 880) from 2000 to 2007 were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariable-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models. Current use of fish oil was associated with reduced risk of breast cancer (HR, 0.68; 95% CI, 0.50-0.92). Ten-year average use was suggestive of reduced risk (P trend = 0.09). These results held for ductal but not lobular cancers. The remaining specialty supplements were not associated with breast cancer risk: Specifically, use of supplements sometimes taken for menopausal symptoms (black cohosh, dong quai, soy, or St. John's wort) was not associated with risk. Fish oil may be inversely associated with breast cancer risk. Fish oil is a potential candidate for chemoprevention studies. Until that time, it is not recommended for individual use for breast cancer prevention.

Associations of Herbal and Specialty Supplements with Lung and Colorectal Cancer Risk in the VITamins And Lifestyle Study

Millions of Americans use dietary supplements with little knowledge about their benefits or risks. We examined associations of various herbal/specialty supplements with lung and colorectal cancer risk. Men and women, 50 to 76 years, in the VITamins And Lifestyle cohort completed a 24-page baseline questionnaire that captured duration (years) and frequency (days per week) of use of commonly used herbal/specialty supplements. Dose was not assessed due to the lack of accurate potency information. Supplement exposure was categorized as "no use" or "any use" over the previous 10 years. Hazard ratios (HR) were estimated by multivariate Cox regression models. Incident lung (n = 665) and colorectal cancers (n = 428) were obtained from the Surveillance, Epidemiology, and End Results cancer registry. Any use of glucosamine and chondroitin, which have anti-inflammatory properties, over the previous 10 years, was associated with significantly lower lung cancer risk: HR 0.74 [95% confidence interval (95% CI), 0.58-0.94] and HR 0.72 (95% CI, 0.54-0.96) and colorectal cancer risk: HR 0.73 (95% CI, 0.54-0.98) and HR 0.65 (95% CI, 0.45-0.93), respectively. There were also statistically significantly inverse associations of fish oil: HR 0.65 (95% CI, 0.42-0.99), methylsulfonylmethane: HR 0.46 (95% CI, 0.23-0.93), and St. John's wort: HR 0.35 (95% CI, 0.14-0.85) with colorectal cancer risk. In contrast, garlic pills were associated with a statistically significant 35% elevated colorectal cancer risk. These results suggest that some herbal/specialty supplements may be associated with lung and colorectal cancer risk; however, these products should be used with caution. Additional studies examining the effects of herbal/specialty supplements on risk for cancer and other diseases are needed.

Associations of Herbal and Specialty Supplements with Lung and Colorectal Cancer Risk in the VITamins And Lifestyle Study

Associations of Herbal and Specialty Supplements with Lung and Colorectal Cancer Risk in the VITamins And Lifestyle Study

Demographic and health-related correlates of herbal and specialty supplement use

Background By broadening the definition of a dietary supplement, the 1994 Dietary Supplements Health and Education Act opened the market to many herbals, botanicals, and other food ingredients that would have otherwise needed safety testing before being sold. Information regarding patterns and correlates of herbal and specialty supplement use can help nutritionists understand which compounds are most commonly used, who are likely to use these supplements, and whether the choice of herbal supplements appears motivated by specific health concerns. Methods Data are from 61,587 participants, aged 50 to 76 years, who completed a self-administered mailed questionnaire in 2000–2002 on current dietary supplement use (20 herbal/specialty supplements, multivitamins, and 17 individual vitamins or minerals), demographic and lifestyle characteristics, and medical history. Results When compared with no supplement use, herbal/specialty supplement use was significantly higher among respondents who were older, female, educated, had a normal body mass index, were nonsmokers, engaged in exercise, and ate a diet lower in fat and higher in fruits and vegetables (all P<.001). Similar trends were observed when herbal/specialty supplement users were compared with vitamin/mineral users. For specific supplements and medical conditions, the strongest associations were cranberry pills and multiple bladder infections (odds ratio [OR], 4.66; 95% confidence interval [CI], 4.03–5.38), acidophilus pills and lactose intolerance (OR, 3.37; 95% CI, 2.96–3.84), and saw palmetto and enlarged prostate (OR, 3.33; 95% CI, 3.00–3.72). Conclusions Odds of supplement use are high for certain demographic and lifestyle characteristics. Additionally, persons with specific medical conditions are using supplements promoted to reduce risk for their particular conditions.