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Wetherington reports no relevant disclosures.
Complementary and alternative medicine is a multibillion-dollar industry made popular by people looking for improved well-being. This effort can be done with or without guidance from a health care provider.
Many people look to dietary and herbal supplements for a healthier lifestyle. There is a perception that herbals, vitamins and minerals are harmless or safer than pharmaceuticals because these are “natural.”
The recent recall by TruVision Health LLC of various nutritional supplements brings into question the safety of these products for patients with kidney disease. The supplements contained unapproved ingredients hordenine and/or octodrine dimethylhexylamine, which behave as stimulants, and are possibly unsafe and are not permitted to be sold.
Unseen harm
Patients with kidney disease are more vulnerable to the unseen harm of supplements, which can contribute to kidney damage (see Table 1). A published review by Gabardi and colleagues examined reported cases of dietary supplement-induced renal dysfunction in humans. They found 17 dietary supplements associated with complementary and alternative medicine (CAM)-induced immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with AKI and hepatorenal syndrome. In some cases, the renal dysfunction was diagnosed either through renal biopsy or clinical observation.
Creatine may be the most controversial of these offenders as there are several small-scale trials that argue against nephrotoxicity of creatine supplementation. However, there have been at least two reported cases in which the consumer acquired renal dysfunction from acute focal interstitial nephritis and tubular injury with a 2 g to 5 g per day dose of creatine. One patient had a previous existing condition of focal segmental glomerulosclerosis. It is important to assess for CAM in patients at higher risk for renal injury from common supplements used for exercise performance.
Vitamins
There have been cases in which chromium picolinate supplementation dosing and product purity may have played a role in kidney injury.
Renal dysfunction has been reported due to kidney stones/oxalate formation with ascorbic acid (vitamin C) and vaccinium macrocarpon (cranberry). Vitamin C supplementation is commonly used to enhance wound healing or iron absorption and for benefiting immune system resiliency. Cranberry tablets are commonly used to prevent or treat bladder and urinary tract infections. A 450 mg concentrated cranberry tablet contains approximately 180 mg of oxalate.
In a study by Terris and colleagues, an analysis of urine samples saw an increase of oxalate excretion by 43.3% after cranberry tablet ingestion. Cranberry and vitamin C supplements may increase risk for calcium-oxalate stone formation.
Supplements like licorice, that have diuretic properties, have been associated with severe hypokalemia. Others include kava, aloe vera, creatine, ephedra, gingko, green tea, L-arginine, juniper berries and uva ursi. These agents should be used with caution in patients with underlying renal dysfunction or those who take prescription diuretics.
Renal dysfunction may also be induced by hepatorenal syndrome through supplementation of herbal substances that can cause hepatotoxicity; common ones include echinacea, yellow oleander, valerian, kava and pennyroyal.
Herbal medicine
A review on nephrotoxicity and Chinese herbal medicine by Yang and colleagues examined reported cases of renal dysfunction caused by traditional herbal medicines. The evidence reviewed came from case reports in which a kidney biopsy confirmed diagnoses or clinical observation substantiated mechanism of injury. However, in many patients the exact pathology of AKI was unknown. The most common causes of AKI were acute tubular necrosis and acute interstitial nephritis. A number of herbal substances were shown to cause AKI (see Table 2).
Mineral imbalance
In kidney disease, vitamin and mineral imbalances commonly occur. Supplements can be hidden sources of both potassium and phosphorus, and due to limited regulation on supplement content, the consumer may not know how much the product contains.
The National Kidney Foundation provides a list of herbal supplements with potassium and phosphorus, such as stinging nettle (leaf), turmeric (rhizome), bitter melon, evening primrose, coriander (leaf), American ginseng, flaxseed (seed) and water lotus among others.
Additionally, some herbal supplements may interfere with medication metabolism such as St. Johns Wort, echinacea, ginseng and ginkgo.
Herbal products, such as uva ursi, cat’s claw, java tea leaf, nettle and stinging nettle, are risky for consumers with any stage of kidney disease and for patients who have had a transplant.
Anti-inflammatory and analgesic
Dietary supplements are rarely taken in pure form and instead are in mixtures of a variety of compounds, which could have interactions and make it difficult to isolate the offending nephrotoxin. Unless a company voluntarily undergoes third-party testing for purity it can be difficult to know with certainty what is in supplement products. NSAIDs have been found in CAM products intended to provide an anti-inflammatory or analgesic benefit. Patients with CKD should avoid NSAIDs, and it is concerning that patients may unknowingly be exposed through concomitant medication or impurities in adulterated supplements, such as glucosamine, advertising pain relief, according to Gabardi and colleagues.
Heavy metal contamination is also a common concern. Common heavy metals that can cause renal dysfunction include arsenic, lead and mercury. Inappropriate processing techniques can also result in toxicity due to industrial dyes.
Yang and colleagues reported Carthamus tinctorius (safflower), used for various medical conditions as an anti-inflammatory and analgesic, was found to be contaminated with Auramine O, a known carcinogenic industrial dye that can cause kidney and liver toxicity.
Errors in the manufacturing of herbal remedies can increase exposure to high-risk toxic herbal compounds. An example of this is the plant Asarum, which is commonly used as an herbal analgesic to treat headaches, toothaches and other inflammatory conditions. The root of Asarum has a low concentration of aristolochic acid. However, if the whole plant is used in the manufacturing process, then it yields an herbal product with high risk of nephrotoxicity.
There are examples of manufacturing errors and mistakenly using incorrect plants in the development of remedies. Yang and colleagues found more than 100 women in Belgium and France who reported extensive renal interstitial fibrosis from 1990 to 1992 after ingesting a weight loss compound that contained Aristolochia fanchi, which contains high levels of aristolochic acid, instead of the intended herb Stephania tetrandra.
Oversight
Herbal medicine is growing in popularity. Consumers can easily purchase enticing herbal teas that claim “kidney cleanses” or “kidney support” yet contain herbal substances with potential nephrotoxic effects. The immediate risk with supplements is little oversight and regulation.
Taking supplements will always be a risk to the consumer because the FDA does not regulate dose, ingredients or purity. Few studies show the real benefits of herbal supplements to consumers, and there are even fewer studies for the CKD population. Due to the potential harm, it is important to increase awareness among health care professionals about the indications and potential consequences so patients with CKD and consumers can be appropriately educated.
- References:
- Delshad E, et al. Electron Physician.2018;doi:10.19082/6672.
- Gabardi, S, et al. CJASN. 2007;doi:10.2215/CJN.00500107.
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Herbal supplements and kidney disease. National Kidney Foundation. (2023) www.kidney.org/atoz/content/herbalsupp?next=%2Fanswers%2Fcan-taking-a-lot-of-supplements-really-damage-the-kidneys%2Fsupplements-kidney-disease%2F.
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Terris MK, et al. Urology. 2001 doi: 10.1016/s0090-4295(00)00884-0.
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TruVision Health recalls dietary supplement products because of possible health risk. www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/truvision-health-recalls-dietary-supplement-products-because-possible-health-risk. Published April 27, 2023. Accessed June 12, 2023.
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Yang B, et al. CJASN. 2018; doi:10.2215/CJN.11571017.
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For more information:
- Amanda C. Wetherington, RD, LD, is a virtual dietitian for DaVita Integrated Kidney Care based in New Bern, North Carolina. She can be reached at [email protected].
