Glucosamine/Chondroitin and Mortality in a US NHANES Cohort

Study Population

The National Health and Nutrition Examination Survey (NHANES) is a series nationally representative cross-sectional survey conducted by National Center for Health Statistics (NCHS). The purpose of the surveys was to assess the health and nutrition status among noninstitutionalized population in the United States using a complex, multistage probability design. Starting from 1999, the NHANES data are released on public-use data files in 2-year increments. Participants were interviewed at home followed by an examination in a mobile examination center for collection of various health and nutrition related data. Informed consents were obtained from all participants and the protocols for conducting the surveys were approved by the Center of Disease Control and Prevention Institutional Review Board. Details on survey design and response rate can be found on the NHANES Web site: NCHS. NHANES Survey methods and analytic guidelines. Available at: https://wwwn.cdc.gov/nchs/nhanes/analyticguidelines.aspx.

Study Participants

The present study used combined data from NHANES 1999 to 2010. We merged the baseline survey data with the 2015 Public-use Linked Mortality File, which provides mortality follow-up data from the date of survey participation through December 31, 2015. Information obtained from the mortality data included vital status, the number of person-months of followup from NHANES examination date and underlying leading cause of death, derived from the 10th revision of the International Statistical Classification of Diseases, Injuries, and Causes of Death (ICD-10) code (NCHS. Public-use Linked Mortality File. Available at: https://www.cdc.gov/nchs/data/datalinkage/public-use-2015-linked-mortality-file-description.pdf.) Participants with missing vital status or cardiovascular disease (CVD) at baseline were excluded from the study.

Mortality Outcomes

The primary outcomes in this study were all-cause and cardiovascular mortalities. To identify all-cause mortality, we used mortality status variable, which coded “0” if assumed “alive” and “1” if assumed deceased. Cardiovascular mortality was identified using variable for leading cause of death. For NHANES 1999 to 2006, there were 9 specific categories from the underlying cause-of-death: heart disease, cancer, chronic lower respiratory disease, cerebrovascular diseases, diabetes, pneumonia and influenza, Alzheimer disease, kidney disease, and unintentional injuries. For NHANES 2007 to 2010, there were only 2 specific cause-of-death groups, heart disease and cancer, due to the short follow-up time and small sample sizes for the other cause-specific death categories. All other causes of death were residual. In this study, we defined death resulting from heart disease or cerebrovascular diseases as cardiovascular mortality. The follow-up time was calculated using person months from the mobile examination center date to date of death or the end of the mortality period (December 31, 2015).

Glucosamine/Chondroitin Use

The continuous NHANES has been collecting data on participants’ use of dietary supplements. During the household interview using the Computer-Assisted Personal Interviewing system, participants were asked a series of questions related to use of dietary supplements for the past 30 days. For participants who indicated use of supplements in the past month, they were asked to list all supplements they had taken during this period; information on how long they have been taken and how much do they take daily were also collected for each supplement use. Each reported supplement was then linked to a dietary supplement database containing detailed ingredients information for each type of supplement. In this study, participants reporting use of glucosamine/chondroitin for 365 days or more before the interview date were identified as glucosamine/chondroitin users; participants reporting no use or use on fewer than 365 days were considered nonusers.

Covariates

Other demographic covariates extracted from the data included age, gender, race, Body Mass Index (BMI), smoking status, physical activity, and education. Participants were categorized into 4 age groups: 40 to 49 years, 50 to 59 years, 60 to 69 years, and 70 years or older. We combined 4 race categories of Non-Hispanic White, Non-Hispanic Black, Hispanic, and other race. BMI was classified as underweight (< 18.5 kg/m²), normal (≥ 18.5 kg/m² and < 25 kg/m²), overweight (≥ 25 kg/m² and < 30 kg/m²), and obese (≥30 kg/m²) based on the Center for Disease Control and Prevention breakdown. Smoking status was identified as current smoker and nonsmoker. We divided education into 2 levels of “≤ 11 years” and “> 11 years.” Physical activity was defined as “≥ 150 minutes” or “< 150 minutes” of moderate-intense recreational physical activity per week.

Statistical Analysis

All analyses in this study were conducted using SAS (version 9.4, 2013, SAS Institute Inc. Cary, NC). Accounting for the complex survey design (including oversampling, survey nonresponse, and post stratification), we used appropriate sampling weights and SAS survey analysis procedures following NHANES survey methods and analytic guidelines.

Demographic characteristics of the study sample were compared between glucosamine/chondroitin users and nonusers using χ² test. To estimate the association of glucosamine/chondroitin use with total mortality and cardiovascular mortality, Cox proportional hazards regression analysis was conducted; we analyzed unadjusted, age-adjusted, and multivariable-adjusted hazard ratio (HR). In the multivariable-adjusted model, age, gender, race, smoking status, education, and physical activity were included as covariates. All tests were 2 tailed, and P < .05 was considered statistical significance.