Dietary supplements are widely used in the United States, despite their potential for harmful effects.18
Individuals with or at risk for CKD may be particularly vulnerable to harmful effects of supplement use through direct nephrotoxicity and other renal complications, as well as decreased clearance of substances, resulting in adverse product accumulation. To our knowledge, our study is the first to describe the use of dietary supplements potentially harmful in persons with and at risk for CKD in a nationally representative sample. Similar to the findings in other studies,5,6
we found that more than half of U.S. adults (age ≥20 years) reported taking any supplement within the 30 days prior to the survey. We show that roughly 1 in 12 U.S. adults is taking at least one supplement that is potentially harmful in persons with kidney disease and that those with or at risk for CKD have a similar likelihood of taking such supplements when compared to those without CKD, after accounting for important confounders. Certainly, our findings that potentially harmful supplements are frequently marketed under seemingly benign product names (such as multivitamins) and by trusted manufacturers, as well as that most individuals report taking them nearly every day and for prolonged periods of time, underscore the scope of this issue.
The lack of variability by CKD status in taking potentially harmful supplements may in part be due to unawareness of CKD. An estimated 80%-90% of individuals with substantially decreased kidney function are unaware of their CKD.19,20
Further, most individuals with CKD may be unaware they are at increased risk of harm, given that consumers often assume “natural” products are safe and beneficial to health.21
Unawareness regarding potential harm of supplements may also be attributed to the lack of rigorous pre-marketing regulation and safety testing. With the passage of the Dietary Supplement Health and Education Act in 1994 (which classified supplements as a subcategory of food, rather than a drug) 22
manufacturers were permitted to market supplement products directly to consumers without submitting proof of safety or efficacy to the U.S. Food and Drug Administration. Consequently, marketing of these products often includes information that is inaccurate and possibly deceptive.23-25
Furthermore, products are often not available in reliable or consistent potencies and dosages, making research on safety or efficacy extremely difficult.26
While aristolochic acid nephropathy, a rapidly progressive interstitial fibrosis of the kidneys frequently leading to end-stage renal disease and urothelial carcinomas, is one of the most dramatic and highly cited examples of herb-induced nephrotoxicity,27,28
the ingestion of more common herbs contained in supplements may be an underappreciated source of nephrotoxicity or other adverse effects of particular concern in those at risk for or with advanced CKD. For example, dietary supplements containing herbs that increase blood pressure or worsen glycemic control may indirectly lead to or worsen existing CKD. Dietary supplements containing herbs that induce hypoglycemia or hyperkalemia may be of particular risk for those with advanced CKD. Older individuals and those with concomitant medication use may be particularly vulnerable.3
Similarly, dietary supplements containing herbs that lead to diarrhea and vomiting may cause decreased kidney perfusion that results in acute kidney injury, an established CKD risk factor.29,30
Since patients may be less likely to attribute harmful effects to dietary supplements,21
there may be delays in diagnosing the etiology of such complications.
Interestingly, we found that the prevalence of both potentially harmful and other supplement use was higher with higher number of healthcare visits. We expected that those with more healthcare visits would have a lower prevalence of potentially harmful supplement use because of more opportunities for healthcare providers to assess and advise against potentially harmful ingestions. This contradictory finding may be explained by people with chronic conditions having more frequent healthcare encounters and higher likelihood of complementary and alternative medicine use than those without a chronic condition15
but may also be a reflection of provider recommendations supporting the patient’s use of generally accepted supplements (e.g., vitamin D and calcium) but lack of awareness regarding the patient’s use of potentially harmful supplements or CKD status. Provider unawareness may be due to a failure to ascertain whether the patient is taking other supplements, coupled with provider unawareness of dietary supplement safety31
and purposeful patient non-disclosure. This assertion is supported by our finding that the number of healthcare visits did not affect the likelihood of taking a potentially harmful supplement but was an independent predictor for taking other dietary supplements (data not shown). In a national health survey of supplement users, only 33% of individuals---and 51% of individuals with chronic conditions---reported disclosing this use to their primary healthcare provider,32
possibly due to skepticism of provider knowledge and attitude toward supplements.21
Prior research has shown that those with higher educational attainment and income are more likely to use supplements, possibly because these individuals are more knowledgeable regarding purported supplement indications and have greater disposable income for such purchases than less well-educated or affluent Americans.33
In our study, the finding that prevalence of supplement use potentially harmful in kidney disease was also higher among adults with higher educational attainment and income may suggest a general lack of awareness of the risk these supplements may impose.
We recognize limitations of our study. First, because the NKF website is a prominent resource for public health education about kidney health, we chose to investigate only the herbs listed on the website as it may have served as a possible deterrent for potentially harmful supplement use for those with CKD. However, this list is unlikely to be exhaustive. For example, the list did not include acai berry, an herb touted for weight loss but has COX-1 and COX-2 inhibitory action34
like certain non-steroidal anti-inflammatory drugs, which are associated with acute kidney injury in the general population35
and with disease progression among those with CKD.36
Further, the NHANES question to ascertain supplement use does not specifically include teas, which may be important but under-recognized sources of potentially harmful herbs. Therefore, our finding that roughly 14% of reported supplements are potentially harmful in the setting of CKD is likely conservative. A more comprehensive list of herbs may have resulted in even higher estimates. On the other hand, of herbs included on the NKF list and reported among our study population, broom was the only herb for which we found no associated literature for adverse renal effects. Therefore, our estimate of prevalence is unlikely to be an underestimation of prevalent use of potentially harmful supplements.
Similarly, we acknowledge that some herbs included in the NKF list may have potential benefits. Senna, for example, is widely prescribed for constipation and a recent uncontrolled pilot trial found wormwood significantly reduced proteinuria in 10 patients with IgA nephropathy.37
However given the lack of consistency between products,26,38
the lack of rigorous safety or efficacy testing, and tendency for patients to believe people are rarely or never harmed by supplements,21
it is important to raise awareness of potential harm.
Moreover, we did not examine dosages of supplements taken and, therefore, cannot conclude that individuals taking potentially harmful supplements are taking enough to do significant harm. Given the wide variety of documented discrepancies in product label claims and actual content in addition to possible undisclosed contaminations,38,39
true quantitation and comparison of dosages would be impossible without direct product analysis. Regardless, it is important to note that a substantial proportion of our study population reported taking supplements over many years, possibly placing themselves at risk of cumulative effects. Consistent with this possibility, we found that individuals with CKD were more likely to report long-term supplement use than those with preserved kidney function. While we are unable to determine causality due to study design, this association highlights the need for further examination of the longitudinal relationship between supplement use and kidney function.
In conclusion, the use of dietary supplements potentially harmful in the setting of CKD is common regardless of CKD status, even after accounting for confounders. Further study of a more comprehensive list of potentially harmful herbs and repeated measures to determine the actual risk to kidney function or other organ systems resulting from supplement use is needed. Nevertheless, this study supports the recommendation that providers vigilantly ask patients about all ingestions and appropriately advise patients about potential risks within the context of their CKD status.